Sample records for involves multiple steps

  1. Semantic Structures of One-Step Word Problems Involving Multiplication or Division.

    ERIC Educational Resources Information Center

    Schmidt, Siegbert; Weiser, Werner

    1995-01-01

    Proposes a four-category classification of semantic structures of one-step word problems involving multiplication and division: forming the n-th multiple of measures, combinatorial multiplication, composition of operators, and multiplication by formula. This classification is compatible with semantic structures of addition and subtraction word…

  2. Measurements of gluconeogenesis and glycogenolysis: A methodological review

    USDA-ARS?s Scientific Manuscript database

    Gluconeogenesis is a complex metabolic process that involves multiple enzymatic steps regulated by myriad factors, including substrate concentrations, the redox state, activation and inhibition of specific enzyme steps, and hormonal modulation. At present, the most widely accepted technique to deter...

  3. Stepwise approach to establishing multiple outreach laboratory information system-electronic medical record interfaces.

    PubMed

    Pantanowitz, Liron; Labranche, Wayne; Lareau, William

    2010-05-26

    Clinical laboratory outreach business is changing as more physician practices adopt an electronic medical record (EMR). Physician connectivity with the laboratory information system (LIS) is consequently becoming more important. However, there are no reports available to assist the informatician with establishing and maintaining outreach LIS-EMR connectivity. A four-stage scheme is presented that was successfully employed to establish unidirectional and bidirectional interfaces with multiple physician EMRs. This approach involves planning (step 1), followed by interface building (step 2) with subsequent testing (step 3), and finally ongoing maintenance (step 4). The role of organized project management, software as a service (SAAS), and alternate solutions for outreach connectivity are discussed.

  4. Stepwise approach to establishing multiple outreach laboratory information system-electronic medical record interfaces

    PubMed Central

    Pantanowitz, Liron; LaBranche, Wayne; Lareau, William

    2010-01-01

    Clinical laboratory outreach business is changing as more physician practices adopt an electronic medical record (EMR). Physician connectivity with the laboratory information system (LIS) is consequently becoming more important. However, there are no reports available to assist the informatician with establishing and maintaining outreach LIS–EMR connectivity. A four-stage scheme is presented that was successfully employed to establish unidirectional and bidirectional interfaces with multiple physician EMRs. This approach involves planning (step 1), followed by interface building (step 2) with subsequent testing (step 3), and finally ongoing maintenance (step 4). The role of organized project management, software as a service (SAAS), and alternate solutions for outreach connectivity are discussed. PMID:20805958

  5. Parameter Estimation of Multiple Frequency-Hopping Signals with Two Sensors

    PubMed Central

    Pan, Jin; Ma, Boyuan

    2018-01-01

    This paper essentially focuses on parameter estimation of multiple wideband emitting sources with time-varying frequencies, such as two-dimensional (2-D) direction of arrival (DOA) and signal sorting, with a low-cost circular synthetic array (CSA) consisting of only two rotating sensors. Our basic idea is to decompose the received data, which is a superimposition of phase measurements from multiple sources into separated groups and separately estimate the DOA associated with each source. Motivated by joint parameter estimation, we propose to adopt the expectation maximization (EM) algorithm in this paper; our method involves two steps, namely, the expectation-step (E-step) and the maximization (M-step). In the E-step, the correspondence of each signal with its emitting source is found. Then, in the M-step, the maximum-likelihood (ML) estimates of the DOA parameters are obtained. These two steps are iteratively and alternatively executed to jointly determine the DOAs and sort multiple signals. Closed-form DOA estimation formulae are developed by ML estimation based on phase data, which also realize an optimal estimation. Directional ambiguity is also addressed by another ML estimation method based on received complex responses. The Cramer-Rao lower bound is derived for understanding the estimation accuracy and performance comparison. The verification of the proposed method is demonstrated with simulations. PMID:29617323

  6. Time-Accurate Local Time Stepping and High-Order Time CESE Methods for Multi-Dimensional Flows Using Unstructured Meshes

    NASA Technical Reports Server (NTRS)

    Chang, Chau-Lyan; Venkatachari, Balaji Shankar; Cheng, Gary

    2013-01-01

    With the wide availability of affordable multiple-core parallel supercomputers, next generation numerical simulations of flow physics are being focused on unsteady computations for problems involving multiple time scales and multiple physics. These simulations require higher solution accuracy than most algorithms and computational fluid dynamics codes currently available. This paper focuses on the developmental effort for high-fidelity multi-dimensional, unstructured-mesh flow solvers using the space-time conservation element, solution element (CESE) framework. Two approaches have been investigated in this research in order to provide high-accuracy, cross-cutting numerical simulations for a variety of flow regimes: 1) time-accurate local time stepping and 2) highorder CESE method. The first approach utilizes consistent numerical formulations in the space-time flux integration to preserve temporal conservation across the cells with different marching time steps. Such approach relieves the stringent time step constraint associated with the smallest time step in the computational domain while preserving temporal accuracy for all the cells. For flows involving multiple scales, both numerical accuracy and efficiency can be significantly enhanced. The second approach extends the current CESE solver to higher-order accuracy. Unlike other existing explicit high-order methods for unstructured meshes, the CESE framework maintains a CFL condition of one for arbitrarily high-order formulations while retaining the same compact stencil as its second-order counterpart. For large-scale unsteady computations, this feature substantially enhances numerical efficiency. Numerical formulations and validations using benchmark problems are discussed in this paper along with realistic examples.

  7. Novel Genome-Wide Screening Method Identifies Genes Important to Breast Cancer Metastasis | Center for Cancer Research

    Cancer.gov

    For patients with solid tumors, the primary cause of illness and death is metastasis, a complex process involving multiple steps and cooperation between cancerous and normal cells. Many genes must be involved, but few have been found and characterized.

  8. Efficient Control Law Simulation for Multiple Mobile Robots

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

    Driessen, B.J.; Feddema, J.T.; Kotulski, J.D.

    1998-10-06

    In this paper we consider the problem of simulating simple control laws involving large numbers of mobile robots. Such simulation can be computationally prohibitive if the number of robots is large enough, say 1 million, due to the 0(N2 ) cost of each time step. This work therefore uses hierarchical tree-based methods for calculating the control law. These tree-based approaches have O(NlogN) cost per time step, thus allowing for efficient simulation involving a large number of robots. For concreteness, a decentralized control law which involves only the distance and bearing to the closest neighbor robot will be considered. The timemore » to calculate the control law for each robot at each time step is demonstrated to be O(logN).« less

  9. Analytical Derivation: An Epistemic Game for Solving Mathematically Based Physics Problems

    ERIC Educational Resources Information Center

    Bajracharya, Rabindra R.; Thompson, John R.

    2016-01-01

    Problem solving, which often involves multiple steps, is an integral part of physics learning and teaching. Using the perspective of the epistemic game, we documented a specific game that is commonly pursued by students while solving mathematically based physics problems: the "analytical derivation" game. This game involves deriving an…

  10. Theoretical analysis of the effects of light intensity on the photocorrosion of semiconductor electrodes

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

    Benito, R.M.; Nozik, A.J.

    1985-07-18

    A kinetic model was developed to describe the effects of light intensity on the photocorrosion of n-type semiconductor electrodes. The model is an extension of previous work by Gomes and co-workers that includes the possibility of multiple steps for the oxidation reaction of the reducing agent in the electrolyte. Six cases are considered where the semiconductor decomposition reaction is multistep (each step involves a hole); the oxidation reaction of the reducing agent is multistep (each step after the first involves a hole or a chemical intermediate), and the first steps of the competing oxidation reactions are reversible or irreversible. Itmore » was found, contrary to previous results, that the photostability of semiconductor electrodes could increase with increased light intensity if the desired oxidation reaction of the reducing agent in the electrolyte was multistep with the first step being reversible. 14 references, 5 figures, 1 table.« less

  11. Comprehension of Multiple Documents with Conflicting Information: A Two-Step Model of Validation

    ERIC Educational Resources Information Center

    Richter, Tobias; Maier, Johanna

    2017-01-01

    In this article, we examine the cognitive processes that are involved when readers comprehend conflicting information in multiple texts. Starting from the notion of routine validation during comprehension, we argue that readers' prior beliefs may lead to a biased processing of conflicting information and a one-sided mental model of controversial…

  12. Multiple-step preparation and physicochemical characterization of crystalline α-germanium hydrogenphosphate

    NASA Astrophysics Data System (ADS)

    Romano, Ricardo; Ruiz, Ana I.; Alves, Oswaldo L.

    2004-04-01

    The reaction between germanium oxide and phosphoric acid has previously been described and led to impure germanium hydrogenphosphate samples with low crystallinity. A new multiple-step route involving the same reaction under refluxing and soft hydrothermal conditions is described for the preparation of pure and crystalline α-GeP. The physicochemical characterization of the samples allows accompaniment of the reaction evolution as well as determining short- and long-range structural organization. The phase purity of the α-GeP sample was confirmed by applying Rietveld's profile analysis, which also determined the cell parameters of its crystals.

  13. Metal-Free Multiple Carbon-Carbon and Carbon-Hydrogen Bond Activations via Charge-Switching Mechanism in Unstrained Diindolylmethanes.

    PubMed

    Challa, Chandrasekhar; Varughese, Sunil; Suresh, Cherumuttathu H; Lankalapalli, Ravi S

    2017-08-18

    A transformation of the unstrained phenol substituted 3,3'-diindolylmethanes (DIPMs) to 2,3'-diindolylketones (DIKs) by double C-C single bond cleavage with associated rearrangements, triggered by phenyliodine(III) diacetate (PIDA), is reported. Density functional theory studies reveal a mechanism involving multiple "charge-switching" steps by synergistic involvement of the two indole units with overall low activation energy. The indole 'charge-switching' mechanism in DIPMs was further extended toward synthesis of a natural product motif cyclohepta[b]indole from biaryl appended DIBM.

  14. Multiple Criteria Decision Analysis for Health Care Decision Making--Emerging Good Practices: Report 2 of the ISPOR MCDA Emerging Good Practices Task Force.

    PubMed

    Marsh, Kevin; IJzerman, Maarten; Thokala, Praveen; Baltussen, Rob; Boysen, Meindert; Kaló, Zoltán; Lönngren, Thomas; Mussen, Filip; Peacock, Stuart; Watkins, John; Devlin, Nancy

    2016-01-01

    Health care decisions are complex and involve confronting trade-offs between multiple, often conflicting objectives. Using structured, explicit approaches to decisions involving multiple criteria can improve the quality of decision making. A set of techniques, known under the collective heading, multiple criteria decision analysis (MCDA), are useful for this purpose. In 2014, ISPOR established an Emerging Good Practices Task Force. The task force's first report defined MCDA, provided examples of its use in health care, described the key steps, and provided an overview of the principal methods of MCDA. This second task force report provides emerging good-practice guidance on the implementation of MCDA to support health care decisions. The report includes: a checklist to support the design, implementation and review of an MCDA; guidance to support the implementation of the checklist; the order in which the steps should be implemented; illustrates how to incorporate budget constraints into an MCDA; provides an overview of the skills and resources, including available software, required to implement MCDA; and future research directions. Copyright © 2016 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  15. The Overgrid Interface for Computational Simulations on Overset Grids

    NASA Technical Reports Server (NTRS)

    Chan, William M.; Kwak, Dochan (Technical Monitor)

    2002-01-01

    Computational simulations using overset grids typically involve multiple steps and a variety of software modules. A graphical interface called OVERGRID has been specially designed for such purposes. Data required and created by the different steps include geometry, grids, domain connectivity information and flow solver input parameters. The interface provides a unified environment for the visualization, processing, generation and diagnosis of such data. General modules are available for the manipulation of structured grids and unstructured surface triangulations. Modules more specific for the overset approach include surface curve generators, hyperbolic and algebraic surface grid generators, a hyperbolic volume grid generator, Cartesian box grid generators, and domain connectivity: pre-processing tools. An interface provides automatic selection and viewing of flow solver boundary conditions, and various other flow solver inputs. For problems involving multiple components in relative motion, a module is available to build the component/grid relationships and to prescribe and animate the dynamics of the different components.

  16. Predicting falls in older adults using the four square step test.

    PubMed

    Cleary, Kimberly; Skornyakov, Elena

    2017-10-01

    The Four Square Step Test (FSST) is a performance-based balance tool involving stepping over four single-point canes placed on the floor in a cross configuration. The purpose of this study was to evaluate properties of the FSST in older adults who lived independently. Forty-five community dwelling older adults provided fall history and completed the FSST, Berg Balance Scale (BBS), Timed Up and Go (TUG), and Tinetti in random order. Future falls were recorded for 12 months following testing. The FSST accurately distinguished between non-fallers and multiple fallers, and the 15-second threshold score accurately distinguished multiple fallers from non-multiple fallers based on fall history. The FSST predicted future falls, and performance on the FSST was significantly correlated with performance on the BBS, TUG, and Tinetti. However, the test is not appropriate for older adults who use walkers. Overall, the FSST is a valid yet underutilized measure of balance performance and fall prediction tool that physical therapists should consider using in ambulatory community dwelling older adults.

  17. Multiple cis-acting signals, some weak by necessity, collectively direct robust transport of oskar mRNA to the oocyte.

    PubMed

    Ryu, Young Hee; Kenny, Andrew; Gim, Youme; Snee, Mark; Macdonald, Paul M

    2017-09-15

    Localization of mRNAs can involve multiple steps, each with its own cis -acting localization signals and transport factors. How is the transition between different steps orchestrated? We show that the initial step in localization of Drosophila oskar mRNA - transport from nurse cells to the oocyte - relies on multiple cis -acting signals. Some of these are binding sites for the translational control factor Bruno, suggesting that Bruno plays an additional role in mRNA transport. Although transport of oskar mRNA is essential and robust, the localization activity of individual transport signals is weak. Notably, increasing the strength of individual transport signals, or adding a strong transport signal, disrupts the later stages of oskar mRNA localization. We propose that the oskar transport signals are weak by necessity; their weakness facilitates transfer of the oskar mRNA from the oocyte transport machinery to the machinery for posterior localization. © 2017. Published by The Company of Biologists Ltd.

  18. Load forecasting via suboptimal seasonal autoregressive models and iteratively reweighted least squares estimation

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

    Mbamalu, G.A.N.; El-Hawary, M.E.

    The authors propose suboptimal least squares or IRWLS procedures for estimating the parameters of a seasonal multiplicative AR model encountered during power system load forecasting. The proposed method involves using an interactive computer environment to estimate the parameters of a seasonal multiplicative AR process. The method comprises five major computational steps. The first determines the order of the seasonal multiplicative AR process, and the second uses the least squares or the IRWLS to estimate the optimal nonseasonal AR model parameters. In the third step one obtains the intermediate series by back forecast, which is followed by using the least squaresmore » or the IRWLS to estimate the optimal season AR parameters. The final step uses the estimated parameters to forecast future load. The method is applied to predict the Nova Scotia Power Corporation's 168 lead time hourly load. The results obtained are documented and compared with results based on the Box and Jenkins method.« less

  19. Anisotropic Dispersion and Partial Localization of Acoustic Surface Plasmons on an Atomically Stepped Surface: Au(788)

    NASA Astrophysics Data System (ADS)

    Smerieri, M.; Vattuone, L.; Savio, L.; Langer, T.; Tegenkamp, C.; Pfnür, H.; Silkin, V. M.; Rocca, M.

    2014-10-01

    Understanding acoustic surface plasmons (ASPs) in the presence of nanosized gratings is necessary for the development of future devices that couple light with ASPs. We show here by experiment and theory that two ASPs exist on Au(788), a vicinal surface with an ordered array of monoatomic steps. The ASPs propagate across the steps as long as their wavelength exceeds the terrace width, thereafter becoming localized. Our investigation identifies, for the first time, ASPs coupled with intersubband transitions involving multiple surface-state subbands.

  20. Software forecasting as it is really done: A study of JPL software engineers

    NASA Technical Reports Server (NTRS)

    Griesel, Martha Ann; Hihn, Jairus M.; Bruno, Kristin J.; Fouser, Thomas J.; Tausworthe, Robert C.

    1993-01-01

    This paper presents a summary of the results to date of a Jet Propulsion Laboratory internally funded research task to study the costing process and parameters used by internally recognized software cost estimating experts. Protocol Analysis and Markov process modeling were used to capture software engineer's forecasting mental models. While there is significant variation between the mental models that were studied, it was nevertheless possible to identify a core set of cost forecasting activities, and it was also found that the mental models cluster around three forecasting techniques. Further partitioning of the mental models revealed clustering of activities, that is very suggestive of a forecasting lifecycle. The different forecasting methods identified were based on the use of multiple-decomposition steps or multiple forecasting steps. The multiple forecasting steps involved either forecasting software size or an additional effort forecast. Virtually no subject used risk reduction steps in combination. The results of the analysis include: the identification of a core set of well defined costing activities, a proposed software forecasting life cycle, and the identification of several basic software forecasting mental models. The paper concludes with a discussion of the implications of the results for current individual and institutional practices.

  1. Comparison of two stand-alone CADe systems at multiple operating points

    NASA Astrophysics Data System (ADS)

    Sahiner, Berkman; Chen, Weijie; Pezeshk, Aria; Petrick, Nicholas

    2015-03-01

    Computer-aided detection (CADe) systems are typically designed to work at a given operating point: The device displays a mark if and only if the level of suspiciousness of a region of interest is above a fixed threshold. To compare the standalone performances of two systems, one approach is to select the parameters of the systems to yield a target false-positive rate that defines the operating point, and to compare the sensitivities at that operating point. Increasingly, CADe developers offer multiple operating points, which necessitates the comparison of two CADe systems involving multiple comparisons. To control the Type I error, multiple-comparison correction is needed for keeping the family-wise error rate (FWER) less than a given alpha-level. The sensitivities of a single modality at different operating points are correlated. In addition, the sensitivities of the two modalities at the same or different operating points are also likely to be correlated. It has been shown in the literature that when test statistics are correlated, well-known methods for controlling the FWER are conservative. In this study, we compared the FWER and power of three methods, namely the Bonferroni, step-up, and adjusted step-up methods in comparing the sensitivities of two CADe systems at multiple operating points, where the adjusted step-up method uses the estimated correlations. Our results indicate that the adjusted step-up method has a substantial advantage over other the two methods both in terms of the FWER and power.

  2. Friction of atomically stepped surfaces

    NASA Astrophysics Data System (ADS)

    Dikken, R. J.; Thijsse, B. J.; Nicola, L.

    2017-03-01

    The friction behavior of atomically stepped metal surfaces under contact loading is studied using molecular dynamics simulations. While real rough metal surfaces involve roughness at multiple length scales, the focus of this paper is on understanding friction of the smallest scale of roughness: atomic steps. To this end, periodic stepped Al surfaces with different step geometry are brought into contact and sheared at room temperature. Contact stress that continuously tries to build up during loading, is released with fluctuating stress drops during sliding, according to the typical stick-slip behavior. Stress release occurs not only through local slip, but also by means of step motion. The steps move along the contact, concurrently resulting in normal migration of the contact. The direction of migration depends on the sign of the step, i.e., its orientation with respect to the shearing direction. If the steps are of equal sign, there is a net migration of the entire contact accompanied by significant vacancy generation at room temperature. The stick-slip behavior of the stepped contacts is found to have all the characteristic of a self-organized critical state, with statistics dictated by step density. For the studied step geometries, frictional sliding is found to involve significant atomic rearrangement through which the contact roughness is drastically changed. This leads for certain step configurations to a marked transition from jerky sliding motion to smooth sliding, making the final friction stress approximately similar to that of a flat contact.

  3. Process for removing an organic compound from water

    DOEpatents

    Baker, Richard W.; Kaschemekat, Jurgen; Wijmans, Johannes G.; Kamaruddin, Henky D.

    1993-12-28

    A process for removing organic compounds from water is disclosed. The process involves gas stripping followed by membrane separation treatment of the stripping gas. The stripping step can be carried out using one or multiple gas strippers and using air or any other gas as stripping gas. The membrane separation step can be carried out using a single-stage membrane unit or a multistage unit. Apparatus for carrying out the process is also disclosed. The process is particularly suited for treatment of contaminated groundwater or industrial wastewater.

  4. Validation of a One-Step Method for Extracting Fatty Acids from Salmon, Chicken and Beef Samples.

    PubMed

    Zhang, Zhichao; Richardson, Christine E; Hennebelle, Marie; Taha, Ameer Y

    2017-10-01

    Fatty acid extraction methods are time-consuming and expensive because they involve multiple steps and copious amounts of extraction solvents. In an effort to streamline the fatty acid extraction process, this study compared the standard Folch lipid extraction method to a one-step method involving a column that selectively elutes the lipid phase. The methods were tested on raw beef, salmon, and chicken. Compared to the standard Folch method, the one-step extraction process generally yielded statistically insignificant differences in chicken and salmon fatty acid concentrations, percent composition and weight percent. Initial testing showed that beef stearic, oleic and total fatty acid concentrations were significantly lower by 9-11% with the one-step method as compared to the Folch method, but retesting on a different batch of samples showed a significant 4-8% increase in several omega-3 and omega-6 fatty acid concentrations with the one-step method relative to the Folch. Overall, the findings reflect the utility of a one-step extraction method for routine and rapid monitoring of fatty acids in chicken and salmon. Inconsistencies in beef concentrations, although minor (within 11%), may be due to matrix effects. A one-step fatty acid extraction method has broad applications for rapidly and routinely monitoring fatty acids in the food supply and formulating controlled dietary interventions. © 2017 Institute of Food Technologists®.

  5. 77 FR 64768 - Regulations Regarding the Application of Section 172(h) Including Consolidated Groups; Correction

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-23

    ... treatment of multiple step plans for the acquisition of stock and CERTs involving members of a consolidated... language ``Service, 1111 Constitution Avenue NW.,'' is corrected to read ``Service, 1111 Constitution... from the bottom of the page, the language ``return group; (4) application of these'' is corrected to...

  6. Enhancing Public School Education: A Collaborative Partnership for School Resiliency

    ERIC Educational Resources Information Center

    Cunningham, Henry R.; Lewis, Starr

    2010-01-01

    Urban schools are plagued with multiple issues that contribute to their low graduation rate. University of Louisville took a step forward by partnering with the school district to transform five schools into high performing schools. Building on the strengths of these schools, a collaborative partnership was developed that involved the entire…

  7. An Approach towards Ultrasound Kidney Cysts Detection using Vector Graphic Image Analysis

    NASA Astrophysics Data System (ADS)

    Mahmud, Wan Mahani Hafizah Wan; Supriyanto, Eko

    2017-08-01

    This study develops new approach towards detection of kidney ultrasound image for both with single cyst as well as multiple cysts. 50 single cyst images and 25 multiple cysts images were used to test the developed algorithm. Steps involved in developing this algorithm were vector graphic image formation and analysis, thresholding, binarization, filtering as well as roundness test. Performance evaluation to 50 single cyst images gave accuracy of 92%, while for multiple cysts images, the accuracy was about 86.89% when tested to 25 multiple cysts images. This developed algorithm may be used in developing a computerized system such as computer aided diagnosis system to help medical experts in diagnosis of kidney cysts.

  8. Walker devices and microswitch technology to enhance assisted indoor ambulation by persons with multiple disabilities: three single-case studies.

    PubMed

    Lancioni, Giulio E; Singh, Nirbhay N; O'Reilly, Mark F; Sigafoos, Jeff; Oliva, Doretta; Campodonico, Francesca; Buono, Serafino

    2013-07-01

    These three single-case studies assessed the use of walker devices and microswitch technology for promoting ambulation behavior among persons with multiple disabilities. The walker devices were equipped with support and weight lifting features. The microswitch technology ensured that brief stimulation followed the participants' ambulation responses. The participants were two children (i.e., Study I and Study II) and one man (i.e., Study III) with poor ambulation performance. The ambulation efforts of the child in Study I involved regular steps, while those of the child in Study II involved pushing responses (i.e., he pushed himself forward with both feet while sitting on the walker's saddle). The man involved in Study III combined his poor ambulation performance with problem behavior, such as shouting or slapping his face. The results were positive for all three participants. The first two participants had a large increase in the number of steps/pushes performed during the ambulation events provided and in the percentages of those events that they completed independently. The third participant improved his ambulation performance as well as his general behavior (i.e., had a decline in problem behavior and an increase in indices of happiness). The wide-ranging implications of the results are discussed. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Evaluation of a shared-work program for reducing assistance provided to supported workers with severe multiple disabilities.

    PubMed

    Parsons, Marsha B; Reid, Dennis H; Green, Carolyn W; Browning, Leah B; Hensley, Mary B

    2002-01-01

    Concern has been expressed recently regarding the need to enhance the performance of individuals with highly significant disabilities in community-based, supported jobs. We evaluated a shared-work program for reducing job coach assistance provided to three workers with severe multiple disabilities in a publishing company. Following systematic observations of the assistance provided as each worker worked on entire job tasks, steps comprising the tasks were then re-assigned across workers. The re-assignment involved assigning each worker only those task steps for which the respective worker received the least amount of assistance (e.g., re-assigning steps that a worker could not complete due to physical disabilities), and ensuring the entire tasks were still completed by combining steps performed by all three workers. The shared-work program was accompanied by reductions in job coach assistance provided to each worker. Work productivity of the supported workers initially decreased but then increased to a level equivalent to the higher ranges of baseline productivity. These results suggested that the shared-work program appears to represent a viable means of enhancing supported work performance of people with severe multiple disabilities in some types of community jobs. Future research needs discussed focus on evaluating shared-work approaches with other jobs, and developing additional community work models specifically for people with highly significant disabilities.

  10. Process Writing and the Internet: Blogs and Ning Networks in the Classroom

    ERIC Educational Resources Information Center

    Boas, Isabela Villas

    2011-01-01

    In contrast to the product approach to writing, which is based on studying and replicating textual models, the process approach involves multiple and repeated steps that compel the writer to closely consider the topic, language, purpose for writing, and social reality of an audience. In addition to discussing the benefits of the process approach…

  11. Development and Application of a Two-Tier Multiple-Choice Diagnostic Test for High School Students' Understanding of Cell Division and Reproduction

    ERIC Educational Resources Information Center

    Sesli, Ertugrul; Kara, Yilmaz

    2012-01-01

    This study involved the development and application of a two-tier diagnostic test for measuring students' understanding of cell division and reproduction. The instrument development procedure had three general steps: defining the content boundaries of the test, collecting information on students' misconceptions, and instrument development.…

  12. A composite step conjugate gradients squared algorithm for solving nonsymmetric linear systems

    NASA Astrophysics Data System (ADS)

    Chan, Tony; Szeto, Tedd

    1994-03-01

    We propose a new and more stable variant of the CGS method [27] for solving nonsymmetric linear systems. The method is based on squaring the Composite Step BCG method, introduced recently by Bank and Chan [1,2], which itself is a stabilized variant of BCG in that it skips over steps for which the BCG iterate is not defined and causes one kind of breakdown in BCG. By doing this, we obtain a method (Composite Step CGS or CSCGS) which not only handles the breakdowns described above, but does so with the advantages of CGS, namely, no multiplications by the transpose matrix and a faster convergence rate than BCG. Our strategy for deciding whether to skip a step does not involve any machine dependent parameters and is designed to skip near breakdowns as well as produce smoother iterates. Numerical experiments show that the new method does produce improved performance over CGS on practical problems.

  13. Tumors Presenting as Multiple Cranial Nerve Palsies

    PubMed Central

    Kumar, Kishore; Ahmed, Rafeeq; Bajantri, Bharat; Singh, Amandeep; Abbas, Hafsa; Dejesus, Eddy; Khan, Rana Raheel; Niazi, Masooma; Chilimuri, Sridhar

    2017-01-01

    Cranial nerve palsy could be one of the presenting features of underlying benign or malignant tumors of the head and neck. The tumor can involve the cranial nerves by local compression, direct infiltration or by paraneoplastic process. Cranial nerve involvement depends on the anatomical course of the cranial nerve and the site of the tumor. Patients may present with single or multiple cranial nerve palsies. Multiple cranial nerve involvement could be sequential or discrete, unilateral or bilateral, painless or painful. The presentation could be acute, subacute or recurrent. Anatomic localization is the first step in the evaluation of these patients. The lesion could be in the brain stem, meninges, base of skull, extracranial or systemic disease itself. We present 3 cases of underlying neoplasms presenting as cranial nerve palsies: a case of glomus tumor presenting as cochlear, glossopharyngeal, vagus and hypoglossal nerve palsies, clivus tumor presenting as abducens nerve palsy, and diffuse large B-cell lymphoma presenting as oculomotor, trochlear, trigeminal and abducens nerve palsies due to paraneoplastic involvement. History and physical examination, imaging, autoantibodies and biopsy if feasible are useful for the diagnosis. Management outcomes depend on the treatment of the underlying tumor. PMID:28553221

  14. A Data Parallel Multizone Navier-Stokes Code

    NASA Technical Reports Server (NTRS)

    Jespersen, Dennis C.; Levit, Creon; Kwak, Dochan (Technical Monitor)

    1995-01-01

    We have developed a data parallel multizone compressible Navier-Stokes code on the Connection Machine CM-5. The code is set up for implicit time-stepping on single or multiple structured grids. For multiple grids and geometrically complex problems, we follow the "chimera" approach, where flow data on one zone is interpolated onto another in the region of overlap. We will describe our design philosophy and give some timing results for the current code. The design choices can be summarized as: 1. finite differences on structured grids; 2. implicit time-stepping with either distributed solves or data motion and local solves; 3. sequential stepping through multiple zones with interzone data transfer via a distributed data structure. We have implemented these ideas on the CM-5 using CMF (Connection Machine Fortran), a data parallel language which combines elements of Fortran 90 and certain extensions, and which bears a strong similarity to High Performance Fortran (HPF). One interesting feature is the issue of turbulence modeling, where the architecture of a parallel machine makes the use of an algebraic turbulence model awkward, whereas models based on transport equations are more natural. We will present some performance figures for the code on the CM-5, and consider the issues involved in transitioning the code to HPF for portability to other parallel platforms.

  15. A Practical Comparison of Motion Planning Techniques for Robotic Legs in Environments with Obstacles

    NASA Technical Reports Server (NTRS)

    Smith, Tristan B.; Chavez-Clemente, Daniel

    2009-01-01

    ATHLETE is a large six-legged tele-operated robot. Each foot is a wheel; travel can be achieved by walking, rolling, or some combination of the two. Operators control ATHLETE by selecting parameterized commands from a command dictionary. While rolling can be done efficiently, any motion involving steps is cumbersome - each step can require multiple commands and take many minutes to complete. In this paper, we consider four different algorithms that generate a sequence of commands to take a step. We consider a baseline heuristic, a randomized motion planning algorithm, and two variants of A* search. Results for a variety of terrains are presented, and we discuss the quantitative and qualitative tradeoffs between the approaches.

  16. Transgenic manipulation of a single polyamine in poplar cells affects the accumulation of all amino acids

    Treesearch

    Sridev Mohapatra; Rakesh Minocha; Stephanie Long; Subhash C. Minocha

    2010-01-01

    The polyamine metabolic pathway is intricately connected to metabolism of several amino acids. While ornithine and arginine are direct precursors of putrescine, they themselves are synthesized from glutamate in multiple steps involving several enzymes. Additionally, glutamate is an amino group donor for several other amino acids and acts as a substrate for biosynthesis...

  17. Interaction of tumor and host cells with adhesion and extracellular matrix molecules in the development of multiple myeloma.

    PubMed

    Teoh, G; Anderson, K C

    1997-02-01

    Adhesion molecules play an important role in the growth regulation and migration of multiple myeloma (MM) cells. They mediate homing of MM cells to the bone marrow and MM cell to bone marrow stromal cell adhesion, with resultant interleukin-6 related autocrine and paracine growth and antiapoptotic affects. Their pattern of expression on tumor cells correlates with the development of plasma cell leukemia or extramedullary disease. Clinically, expression of adhesion molecules on tumor cells or in the serum has already shown prognostic utility. Finally, since adhesion molecules are involved at multiple steps in the pathogenesis of MM, therapeutic studies may target these molecules.

  18. Neurofibromatoses: part 1 - diagnosis and differential diagnosis.

    PubMed

    Rodrigues, Luiz Oswaldo Carneiro; Batista, Pollyanna Barros; Goloni-Bertollo, Eny Maria; de Souza-Costa, Danielle; Eliam, Lucas; Eliam, Miguel; Cunha, Karin Soares Gonçalves; Darrigo-Junior, Luiz Guilherme; Ferraz-Filho, José Roberto Lopes; Geller, Mauro; Gianordoli-Nascimento, Ingrid F; Madeira, Luciana Gonçalves; Malloy-Diniz, Leandro Fernandes; Mendes, Hérika Martins; de Miranda, Débora Marques; Pavarino, Erika Cristina; Baptista-Pereira, Luciana; Rezende, Nilton A; Rodrigues, Luíza de Oliveira; da Silva, Carla Menezes; de Souza, Juliana Ferreira; de Souza, Márcio Leandro Ribeiro; Stangherlin, Aline; Valadares, Eugênia Ribeiro; Vidigal, Paula Vieira Teixeira

    2014-03-01

    Neurofibromatoses (NF) are a group of genetic multiple tumor growing predisposition diseases: neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2) and schwannomatosis (SCH), which have in common the neural origin of tumors and cutaneous signs. They affect nearly 80 thousand of Brazilians. In recent years, the increased scientific knowledge on NF has allowed better clinical management and reduced complication morbidity, resulting in higher quality of life for NF patients. In most cases, neurology, psychiatry, dermatology, clinical geneticists, oncology and internal medicine specialists are able to make the differential diagnosis between NF and other diseases and to identify major NF complications. Nevertheless, due to its great variability in phenotype expression, progressive course, multiple organs involvement and unpredictable natural evolution, NF often requires the support of neurofibromatoses specialists for proper treatment and genetic counseling. This Part 1 offers step-by-step guidelines for NF differential diagnosis. Part 2 will present the NF clinical management.

  19. Zn2+-dependent Activation of the Trk Signaling Pathway Induces Phosphorylation of the Brain-enriched Tyrosine Phosphatase STEP

    PubMed Central

    Poddar, Ranjana; Rajagopal, Sathyanarayanan; Shuttleworth, C. William; Paul, Surojit

    2016-01-01

    Excessive release of Zn2+ in the brain is implicated in the progression of acute brain injuries. Although several signaling cascades have been reported to be involved in Zn2+-induced neurotoxicity, a potential contribution of tyrosine phosphatases in this process has not been well explored. Here we show that exposure to high concentrations of Zn2+ led to a progressive increase in phosphorylation of the striatal-enriched phosphatase (STEP), a component of the excitotoxic-signaling pathway that plays a role in neuroprotection. Zn2+-mediated phosphorylation of STEP61 at multiple sites (hyperphosphorylation) was induced by the up-regulation of brain-derived neurotropic factor (BDNF), tropomyosin receptor kinase (Trk) signaling, and activation of cAMP-dependent PKA (protein kinase A). Mutational studies further show that differential phosphorylation of STEP61 at the PKA sites, Ser-160 and Ser-221 regulates the affinity of STEP61 toward its substrates. Consistent with these findings we also show that BDNF/Trk/PKA mediated signaling is required for Zn2+-induced phosphorylation of extracellular regulated kinase 2 (ERK2), a substrate of STEP that is involved in Zn2+-dependent neurotoxicity. The strong correlation between the temporal profile of STEP61 hyperphosphorylation and ERK2 phosphorylation indicates that loss of function of STEP61 through phosphorylation is necessary for maintaining sustained ERK2 phosphorylation. This interpretation is further supported by the findings that deletion of the STEP gene led to a rapid and sustained increase in ERK2 phosphorylation within minutes of exposure to Zn2+. The study provides further insight into the mechanisms of regulation of STEP61 and also offers a molecular basis for the Zn2+-induced sustained activation of ERK2. PMID:26574547

  20. The Multigrid-Mask Numerical Method for Solution of Incompressible Navier-Stokes Equations

    NASA Technical Reports Server (NTRS)

    Ku, Hwar-Ching; Popel, Aleksander S.

    1996-01-01

    A multigrid-mask method for solution of incompressible Navier-Stokes equations in primitive variable form has been developed. The main objective is to apply this method in conjunction with the pseudospectral element method solving flow past multiple objects. There are two key steps involved in calculating flow past multiple objects. The first step utilizes only Cartesian grid points. This homogeneous or mask method step permits flow into the interior rectangular elements contained in objects, but with the restriction that the velocity for those Cartesian elements within and on the surface of an object should be small or zero. This step easily produces an approximate flow field on Cartesian grid points covering the entire flow field. The second or heterogeneous step corrects the approximate flow field to account for the actual shape of the objects by solving the flow field based on the local coordinates surrounding each object and adapted to it. The noise occurring in data communication between the global (low frequency) coordinates and the local (high frequency) coordinates is eliminated by the multigrid method when the Schwarz Alternating Procedure (SAP) is implemented. Two dimensional flow past circular and elliptic cylinders will be presented to demonstrate the versatility of the proposed method. An interesting phenomenon is found that when the second elliptic cylinder is placed in the wake of the first elliptic cylinder a traction force results in a negative drag coefficient.

  1. Multiple Criteria Decision Analysis for Health Care Decision Making--An Introduction: Report 1 of the ISPOR MCDA Emerging Good Practices Task Force.

    PubMed

    Thokala, Praveen; Devlin, Nancy; Marsh, Kevin; Baltussen, Rob; Boysen, Meindert; Kalo, Zoltan; Longrenn, Thomas; Mussen, Filip; Peacock, Stuart; Watkins, John; Ijzerman, Maarten

    2016-01-01

    Health care decisions are complex and involve confronting trade-offs between multiple, often conflicting, objectives. Using structured, explicit approaches to decisions involving multiple criteria can improve the quality of decision making and a set of techniques, known under the collective heading multiple criteria decision analysis (MCDA), are useful for this purpose. MCDA methods are widely used in other sectors, and recently there has been an increase in health care applications. In 2014, ISPOR established an MCDA Emerging Good Practices Task Force. It was charged with establishing a common definition for MCDA in health care decision making and developing good practice guidelines for conducting MCDA to aid health care decision making. This initial ISPOR MCDA task force report provides an introduction to MCDA - it defines MCDA; provides examples of its use in different kinds of decision making in health care (including benefit risk analysis, health technology assessment, resource allocation, portfolio decision analysis, shared patient clinician decision making and prioritizing patients' access to services); provides an overview of the principal methods of MCDA; and describes the key steps involved. Upon reviewing this report, readers should have a solid overview of MCDA methods and their potential for supporting health care decision making. Copyright © 2016. Published by Elsevier Inc.

  2. Pre-orthographic character string processing and parietal cortex: a role for visual attention in reading?

    PubMed

    Lobier, Muriel; Peyrin, Carole; Le Bas, Jean-François; Valdois, Sylviane

    2012-07-01

    The visual front-end of reading is most often associated with orthographic processing. The left ventral occipito-temporal cortex seems to be preferentially tuned for letter string and word processing. In contrast, little is known of the mechanisms responsible for pre-orthographic processing: the processing of character strings regardless of character type. While the superior parietal lobule has been shown to be involved in multiple letter processing, further data is necessary to extend these results to non-letter characters. The purpose of this study is to identify the neural correlates of pre-orthographic character string processing independently of character type. Fourteen skilled adult readers carried out multiple and single element visual categorization tasks with alphanumeric (AN) and non-alphanumeric (nAN) characters under fMRI. The role of parietal cortex in multiple element processing was further probed with a priori defined anatomical regions of interest (ROIs). Participants activated posterior parietal cortex more strongly for multiple than single element processing. ROI analyses showed that bilateral SPL/BA7 was more strongly activated for multiple than single element processing, regardless of character type. In contrast, no multiple element specific activity was found in inferior parietal lobules. These results suggests that parietal mechanisms are involved in pre-orthographic character string processing. We argue that in general, attentional mechanisms are involved in visual word recognition, as an early step of word visual analysis. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. Lesson study on 2nd grader of elementary school to improve the student’s numeracy skill

    NASA Astrophysics Data System (ADS)

    Prabowo, A.; Asih; Jumardi

    2018-03-01

    The purpose of this research is to find the most appropriate learning media of multiplication and division for the 2nd graders of elementary school. The study used the steps in the lesson study, Plan-Do-See. Data were taken using observation instruments, video documentation, and learning evaluation tools. Initially, teachers used gravel as media of multiplication and division. Students can solve numeracy problems when they learn by those media. In test, 80% of students were failure when the teacher evaluates them. By involving experts and partner teachers at school, classroom teachers can solve problems by discover multiplication and division media with the drawing media created by the students themselves. At the end of the lesson, 100% of students have mastered multiplication and division with the media.

  4. Genomic and Coexpression Analyses Predict Multiple Genes Involved in Triterpene Saponin Biosynthesis in Medicago truncatula[C][W

    PubMed Central

    Naoumkina, Marina A.; Modolo, Luzia V.; Huhman, David V.; Urbanczyk-Wochniak, Ewa; Tang, Yuhong; Sumner, Lloyd W.; Dixon, Richard A.

    2010-01-01

    Saponins, an important group of bioactive plant natural products, are glycosides of triterpenoid or steroidal aglycones (sapogenins). Saponins possess many biological activities, including conferring potential health benefits for humans. However, most of the steps specific for the biosynthesis of triterpene saponins remain uncharacterized at the molecular level. Here, we use comprehensive gene expression clustering analysis to identify candidate genes involved in the elaboration, hydroxylation, and glycosylation of the triterpene skeleton in the model legume Medicago truncatula. Four candidate uridine diphosphate glycosyltransferases were expressed in Escherichia coli, one of which (UGT73F3) showed specificity for multiple sapogenins and was confirmed to glucosylate hederagenin at the C28 position. Genetic loss-of-function studies in M. truncatula confirmed the in vivo function of UGT73F3 in saponin biosynthesis. This report provides a basis for future studies to define genetically the roles of multiple cytochromes P450 and glycosyltransferases in triterpene saponin biosynthesis in Medicago. PMID:20348429

  5. Evaluation of a Technology for Teaching Complex Social Skills to Young Adults with Visual and Cognitive Impairments.

    ERIC Educational Resources Information Center

    Gumpel, Thomas P.; Nativ-Ari-Am, Hagit

    2001-01-01

    Two multiple baseline designs were used to evaluate a two-stage model for training four young adults with visual and cognitive impairments to grocery shop. A task-analytical flow chart of the behavioral skills involved in grocery shopping was used to increase completed skill steps and the number of correct items purchased. (Contains references.)…

  6. Multisensor data fusion across time and space

    NASA Astrophysics Data System (ADS)

    Villeneuve, Pierre V.; Beaven, Scott G.; Reed, Robert A.

    2014-06-01

    Field measurement campaigns typically deploy numerous sensors having different sampling characteristics for spatial, temporal, and spectral domains. Data analysis and exploitation is made more difficult and time consuming as the sample data grids between sensors do not align. This report summarizes our recent effort to demonstrate feasibility of a processing chain capable of "fusing" image data from multiple independent and asynchronous sensors into a form amenable to analysis and exploitation using commercially-available tools. Two important technical issues were addressed in this work: 1) Image spatial registration onto a common pixel grid, 2) Image temporal interpolation onto a common time base. The first step leverages existing image matching and registration algorithms. The second step relies upon a new and innovative use of optical flow algorithms to perform accurate temporal upsampling of slower frame rate imagery. Optical flow field vectors were first derived from high-frame rate, high-resolution imagery, and then finally used as a basis for temporal upsampling of the slower frame rate sensor's imagery. Optical flow field values are computed using a multi-scale image pyramid, thus allowing for more extreme object motion. This involves preprocessing imagery to varying resolution scales and initializing new vector flow estimates using that from the previous coarser-resolution image. Overall performance of this processing chain is demonstrated using sample data involving complex too motion observed by multiple sensors mounted to the same base. Multiple sensors were included, including a high-speed visible camera, up to a coarser resolution LWIR camera.

  7. To analyse a trace or not? Evaluating the decision-making process in the criminal investigation.

    PubMed

    Bitzer, Sonja; Ribaux, Olivier; Albertini, Nicola; Delémont, Olivier

    2016-05-01

    In order to broaden our knowledge and understanding of the decision steps in the criminal investigation process, we started by evaluating the decision to analyse a trace and the factors involved in this decision step. This decision step is embedded in the complete criminal investigation process, involving multiple decision and triaging steps. Considering robbery cases occurring in a geographic region during a 2-year-period, we have studied the factors influencing the decision to submit biological traces, directly sampled on the scene of the robbery or on collected objects, for analysis. The factors were categorised into five knowledge dimensions: strategic, immediate, physical, criminal and utility and decision tree analysis was carried out. Factors in each category played a role in the decision to analyse a biological trace. Interestingly, factors involving information available prior to the analysis are of importance, such as the fact that a positive result (a profile suitable for comparison) is already available in the case, or that a suspect has been identified through traditional police work before analysis. One factor that was taken into account, but was not significant, is the matrix of the trace. Hence, the decision to analyse a trace is not influenced by this variable. The decision to analyse a trace first is very complex and many of the tested variables were taken into account. The decisions are often made on a case-by-case basis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. The US Network of Pediatric Multiple Sclerosis Centers: Development, Progress, and Next Steps.

    PubMed

    Casper, T Charles; Rose, John W; Roalstad, Shelly; Waubant, Emmanuelle; Aaen, Gregory; Belman, Anita; Chitnis, Tanuja; Gorman, Mark; Krupp, Lauren; Lotze, Timothy E; Ness, Jayne; Patterson, Marc; Rodriguez, Moses; Weinstock-Guttman, Bianca; Browning, Brittan; Graves, Jennifer; Tillema, Jan-Mendelt; Benson, Leslie; Harris, Yolanda

    2015-09-01

    Multiple sclerosis and other demyelinating diseases in the pediatric population have received an increasing level of attention by clinicians and researchers. The low incidence of these diseases in children creates a need for the involvement of multiple clinical centers in research efforts. The Network of Pediatric Multiple Sclerosis Centers was created initially in 2006 to improve the diagnosis and care of children with demyelinating diseases. In 2010, the Network shifted its focus to multicenter research while continuing to advance the care of patients. The Network has obtained support from the National Multiple Sclerosis Society, the Guthy-Jackson Charitable Foundation, and the National Institutes of Health. The Network will continue to serve as a platform for conducting impactful research in pediatric demyelinating diseases of the central nervous system. This article provides a description of the history and development, organization, mission, research priorities, current studies, and future plans of the Network. © The Author(s) 2014.

  9. The US Network of Pediatric Multiple Sclerosis Centers: Development, Progress, and Next Steps

    PubMed Central

    Casper, T. Charles; Rose, John W.; Roalstad, Shelly; Waubant, Emmanuelle; Aaen, Gregory; Belman, Anita; Chitnis, Tanuja; Gorman, Mark; Krupp, Lauren; Lotze, Timothy E.; Ness, Jayne; Patterson, Marc; Rodriguez, Moses; Weinstock-Guttman, Bianca; Browning, Brittan; Graves, Jennifer; Tillema, Jan-Mendelt; Benson, Leslie; Harris, Yolanda

    2014-01-01

    Multiple sclerosis and other demyelinating diseases in the pediatric population have received an increasing level of attention by clinicians and researchers. The low incidence of these diseases in children creates a need for the involvement of multiple clinical centers in research efforts. The Network of Pediatric Multiple Sclerosis Centers was created initially in 2006 to improve the diagnosis and care of children with demyelinating diseases. In 2010, the Network shifted its focus to multicenter research while continuing to advance the care of patients. The Network has obtained support from the National Multiple Sclerosis Society, the Guthy-Jackson Charitable Foundation, and the National Institutes of Health. The Network will continue to serve as a platform for conducting impactful research in pediatric demyelinating diseases of the central nervous system. This article provides a description of the history and development, organization, mission, research priorities, current studies, and future plans of the Network. PMID:25270659

  10. RNA splicing process analysis for identifying antisense oligonucleotide inhibitors with padlock probe-based isothermal amplification.

    PubMed

    Ren, Xiaojun; Deng, Ruijie; Wang, Lida; Zhang, Kaixiang; Li, Jinghong

    2017-08-01

    RNA splicing, which mainly involves two transesterification steps, is a fundamental process of gene expression and its abnormal regulation contributes to serious genetic diseases. Antisense oligonucleotides (ASOs) are genetic control tools that can be used to specifically control genes through alteration of the RNA splicing pathway. Despite intensive research, how ASOs or various other factors influence the multiple processes of RNA splicing still remains obscure. This is largely due to an inability to analyze the splicing efficiency of each step in the RNA splicing process with high sensitivity. We addressed this limitation by introducing a padlock probe-based isothermal amplification assay to achieve quantification of the specific products in different splicing steps. With this amplified assay, the roles that ASOs play in RNA splicing inhibition in the first and second steps could be distinguished. We identified that 5'-ASO could block RNA splicing by inhibiting the first step, while 3'-ASO could block RNA splicing by inhibiting the second step. This method provides a versatile tool for assisting efficient ASO design and discovering new splicing modulators and therapeutic drugs.

  11. Catalog of Air Force Weather Technical Documents, 1941-2006

    DTIC Science & Technology

    2006-05-19

    radiosondes in current use in USA. Elementary discussion of statistical terms and concepts used for expressing accuracy or error is discussed. AWS TR 105...Techniques, Appendix B: Vorticity—An Elementary Discussion of the Concept, August 1956, 27pp. Formerly AWSM 105– 50/1A. Provides the necessary back...steps involved in ordinary multiple linear regression. Conditional probability is calculated using transnormalized variables in the multivariate normal

  12. Homology-integrated CRISPR-Cas (HI-CRISPR) system for one-step multigene disruption in Saccharomyces cerevisiae.

    PubMed

    Bao, Zehua; Xiao, Han; Liang, Jing; Zhang, Lu; Xiong, Xiong; Sun, Ning; Si, Tong; Zhao, Huimin

    2015-05-15

    One-step multiple gene disruption in the model organism Saccharomyces cerevisiae is a highly useful tool for both basic and applied research, but it remains a challenge. Here, we report a rapid, efficient, and potentially scalable strategy based on the type II Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR associated proteins (Cas) system to generate multiple gene disruptions simultaneously in S. cerevisiae. A 100 bp dsDNA mutagenizing homologous recombination donor is inserted between two direct repeats for each target gene in a CRISPR array consisting of multiple donor and guide sequence pairs. An ultrahigh copy number plasmid carrying iCas9, a variant of wild-type Cas9, trans-encoded RNA (tracrRNA), and a homology-integrated crRNA cassette is designed to greatly increase the gene disruption efficiency. As proof of concept, three genes, CAN1, ADE2, and LYP1, were simultaneously disrupted in 4 days with an efficiency ranging from 27 to 87%. Another three genes involved in an artificial hydrocortisone biosynthetic pathway, ATF2, GCY1, and YPR1, were simultaneously disrupted in 6 days with 100% efficiency. This homology-integrated CRISPR (HI-CRISPR) strategy represents a powerful tool for creating yeast strains with multiple gene knockouts.

  13. Coordinately Co-opted Multiple Transposable Elements Constitute an Enhancer for wnt5a Expression in the Mammalian Secondary Palate

    PubMed Central

    Kimura-Yoshida, Chiharu; Yan, Kuo; Bormuth, Olga; Ding, Qiong; Nakanishi, Akiko; Sasaki, Takeshi; Hirakawa, Mika; Sumiyama, Kenta; Furuta, Yasuhide; Tarabykin, Victor; Matsuo, Isao; Okada, Norihiro

    2016-01-01

    Acquisition of cis-regulatory elements is a major driving force of evolution, and there are several examples of developmental enhancers derived from transposable elements (TEs). However, it remains unclear whether one enhancer element could have been produced via cooperation among multiple, yet distinct, TEs during evolution. Here we show that an evolutionarily conserved genomic region named AS3_9 comprises three TEs (AmnSINE1, X6b_DNA and MER117), inserted side-by-side, and functions as a distal enhancer for wnt5a expression during morphogenesis of the mammalian secondary palate. Functional analysis of each TE revealed step-by-step retroposition/transposition and co-option together with acquisition of a binding site for Msx1 for its full enhancer function during mammalian evolution. The present study provides a new perspective suggesting that a huge variety of TEs, in combination, could have accelerated the diversity of cis-regulatory elements involved in morphological evolution. PMID:27741242

  14. Porous polycarbene-bearing membrane actuator for ultrasensitive weak-acid detection and real-time chemical reaction monitoring.

    PubMed

    Sun, Jian-Ke; Zhang, Weiyi; Guterman, Ryan; Lin, Hui-Juan; Yuan, Jiayin

    2018-04-30

    Soft actuators with integration of ultrasensitivity and capability of simultaneous interaction with multiple stimuli through an entire event ask for a high level of structure complexity, adaptability, and/or multi-responsiveness, which is a great challenge. Here, we develop a porous polycarbene-bearing membrane actuator built up from ionic complexation between a poly(ionic liquid) and trimesic acid (TA). The actuator features two concurrent structure gradients, i.e., an electrostatic complexation (EC) degree and a density distribution of a carbene-NH 3 adduct (CNA) along the membrane cross-section. The membrane actuator performs the highest sensitivity among the state-of-the-art soft proton actuators toward acetic acid at 10 -6  mol L -1 (M) level in aqueous media. Through competing actuation of the two gradients, it is capable of monitoring an entire process of proton-involved chemical reactions that comprise multiple stimuli and operational steps. The present achievement constitutes a significant step toward real-life application of soft actuators in chemical sensing and reaction technology.

  15. Electromagnetic micropores: fabrication and operation.

    PubMed

    Basore, Joseph R; Lavrik, Nickolay V; Baker, Lane A

    2010-12-21

    We describe the fabrication and characterization of electromagnetic micropores. These devices consist of a micropore encompassed by a microelectromagnetic trap. Fabrication of the device involves multiple photolithographic steps, combined with deep reactive ion etching and subsequent insulation steps. When immersed in an electrolyte solution, application of a constant potential across the micropore results in an ionic current. Energizing the electromagnetic trap surrounding the micropore produces regions of high magnetic field gradients in the vicinity of the micropore that can direct motion of a ferrofluid onto or off of the micropore. This results in dynamic gating of the ion current through the micropore structure. In this report, we detail fabrication and characterize the electrical and ionic properties of the prepared electromagnetic micropores.

  16. Evaluation of atomic pressure in the multiple time-step integration algorithm.

    PubMed

    Andoh, Yoshimichi; Yoshii, Noriyuki; Yamada, Atsushi; Okazaki, Susumu

    2017-04-15

    In molecular dynamics (MD) calculations, reduction in calculation time per MD loop is essential. A multiple time-step (MTS) integration algorithm, the RESPA (Tuckerman and Berne, J. Chem. Phys. 1992, 97, 1990-2001), enables reductions in calculation time by decreasing the frequency of time-consuming long-range interaction calculations. However, the RESPA MTS algorithm involves uncertainties in evaluating the atomic interaction-based pressure (i.e., atomic pressure) of systems with and without holonomic constraints. It is not clear which intermediate forces and constraint forces in the MTS integration procedure should be used to calculate the atomic pressure. In this article, we propose a series of equations to evaluate the atomic pressure in the RESPA MTS integration procedure on the basis of its equivalence to the Velocity-Verlet integration procedure with a single time step (STS). The equations guarantee time-reversibility even for the system with holonomic constrants. Furthermore, we generalize the equations to both (i) arbitrary number of inner time steps and (ii) arbitrary number of force components (RESPA levels). The atomic pressure calculated by our equations with the MTS integration shows excellent agreement with the reference value with the STS, whereas pressures calculated using the conventional ad hoc equations deviated from it. Our equations can be extended straightforwardly to the MTS integration algorithm for the isothermal NVT and isothermal-isobaric NPT ensembles. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  17. Comparative Roles of Overexpressed and Mutated H- and K-ras in Mammary Carcinogenesis.

    DTIC Science & Technology

    1996-08-01

    transgene of these tumors. 14. SUBJECT TERMS 15. NUMBER OF PAGES Breast Cancer , mammary carcinogenesis, oncogenes, ras genes, 44 replication defective...27 Appendix 5 29 Appendix 6 31 Appendix 7 33 Appendix 8 35 Appendix 9 37 Appendix 10 39 Introduction Breast cancer development involves multiple poorly...understood steps (25). Currently, several genes that may participate in breast cancer development are under investigation. The ras family of genes

  18. Adapting sensory data for multiple robots performing spill cleanup

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

    Storjohann, K.; Saltzen, E.

    1990-09-01

    This paper describes a possible method of converting a single performing robot algorithm into a multiple performing robot algorithm without the need to modify previously written codes. The algorithm to be converted involves spill detection and clean up by the HERMIES-III mobile robot. In order to achieve the goal of multiple performing robots with this algorithm, two steps are taken. First, the task is formally divided into two sub-tasks, spill detection and spill clean-up, the former of which is allocated to the added performing robot, HERMIES-IIB. Second, a inverse perspective mapping, is applied to the data acquired by the newmore » performing robot (HERMIES-IIB), allowing the data to be processed by the previously written algorithm without re-writing the code. 6 refs., 4 figs.« less

  19. Multiple-3D-object secure information system based on phase shifting method and single interference.

    PubMed

    Li, Wei-Na; Shi, Chen-Xiao; Piao, Mei-Lan; Kim, Nam

    2016-05-20

    We propose a multiple-3D-object secure information system for encrypting multiple three-dimensional (3D) objects based on the three-step phase shifting method. During the decryption procedure, five phase functions (PFs) are decreased to three PFs, in comparison with our previous method, which implies that one cross beam splitter is utilized to implement the single decryption interference. Moreover, the advantages of the proposed scheme also include: each 3D object can be decrypted discretionarily without decrypting a series of other objects earlier; the quality of the decrypted slice image of each object is high according to the correlation coefficient values, none of which is lower than 0.95; no iterative algorithm is involved. The feasibility of the proposed scheme is demonstrated by computer simulation results.

  20. HERMIES-3: A step toward autonomous mobility, manipulation, and perception

    NASA Technical Reports Server (NTRS)

    Weisbin, C. R.; Burks, B. L.; Einstein, J. R.; Feezell, R. R.; Manges, W. W.; Thompson, D. H.

    1989-01-01

    HERMIES-III is an autonomous robot comprised of a seven degree-of-freedom (DOF) manipulator designed for human scale tasks, a laser range finder, a sonar array, an omni-directional wheel-driven chassis, multiple cameras, and a dual computer system containing a 16-node hypercube expandable to 128 nodes. The current experimental program involves performance of human-scale tasks (e.g., valve manipulation, use of tools), integration of a dexterous manipulator and platform motion in geometrically complex environments, and effective use of multiple cooperating robots (HERMIES-IIB and HERMIES-III). The environment in which the robots operate has been designed to include multiple valves, pipes, meters, obstacles on the floor, valves occluded from view, and multiple paths of differing navigation complexity. The ongoing research program supports the development of autonomous capability for HERMIES-IIB and III to perform complex navigation and manipulation under time constraints, while dealing with imprecise sensory information.

  1. Quantification of triglyceride content in oleaginous materials using thermo-gravimetry

    DOE PAGES

    Maddi, Balakrishna; Vadlamani, Agasteswar; Viamajala, Sridhar; ...

    2017-10-16

    Laboratory analytical methods for quantification of triglyceride content in oleaginous biomass samples, especially microalgae, require toxic chemicals and/or organic solvents and involve multiple steps. We describe a simple triglyceride quantification method that uses thermo-gravimetry. This method is based on the observation that triglycerides undergo near-complete volatilization/degradation over a narrow temperature interval with a derivative weight loss peak at 420 °C when heated in an inert atmosphere. Degradation of the other constituents of oleaginous biomass (protein and carbohydrates) is largely complete after prolonged exposure of samples at 320 °C. Based on these observations, the triglyceride content of oleaginous biomass was estimatedmore » by using the following two-step process. In Step 1, samples were heated to 320 °C and kept isothermal at this temperature for 15 min. In Step 2, samples were heated from 320 °C to 420 °C and then kept isothermal at 420 °C for 15 min. The results show that mass loss in step 2 correlated well with triglyceride content estimates obtained from conventional techniques for diverse microalgae and oilseed samples.« less

  2. Alcohol and drug treatment involvement, 12-step attendance and abstinence: 9-year cross-lagged analysis of adults in an integrated health plan.

    PubMed

    Witbrodt, Jane; Ye, Yu; Bond, Jason; Chi, Felicia; Weisner, Constance; Mertens, Jennifer

    2014-04-01

    This study explored causal relationships between post-treatment 12-step attendance and abstinence at multiple data waves and examined indirect paths leading from treatment initiation to abstinence 9-years later. Adults (N = 1945) seeking help for alcohol or drug use disorders from integrated healthcare organization outpatient treatment programs were followed at 1-, 5-, 7- and 9-years. Path modeling with cross-lagged partial regression coefficients was used to test causal relationships. Cross-lagged paths indicated greater 12-step attendance during years 1 and 5 and were casually related to past-30-day abstinence at years 5 and 7 respectfully, suggesting 12-step attendance leads to abstinence (but not vice versa) well into the post-treatment period. Some gender differences were found in these relationships. Three significant time-lagged, indirect paths emerged linking treatment duration to year-9 abstinence. Conclusions are discussed in the context of other studies using longitudinal designs. For outpatient clients, results reinforce the value of lengthier treatment duration and 12-step attendance in year 1. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Quantification of triglyceride content in oleaginous materials using thermo-gravimetry

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

    Maddi, Balakrishna; Vadlamani, Agasteswar; Viamajala, Sridhar

    Laboratory analytical methods for quantification of triglyceride content in oleaginous biomass samples, especially microalgae, require toxic chemicals and/or organic solvents and involve multiple steps. We describe a simple triglyceride quantification method that uses thermo-gravimetry. This method is based on the observation that triglycerides undergo near-complete volatilization/degradation over a narrow temperature interval with a derivative weight loss peak at 420 °C when heated in an inert atmosphere. Degradation of the other constituents of oleaginous biomass (protein and carbohydrates) is largely complete after prolonged exposure of samples at 320 °C. Based on these observations, the triglyceride content of oleaginous biomass was estimatedmore » by using the following two-step process. In Step 1, samples were heated to 320 °C and kept isothermal at this temperature for 15 min. In Step 2, samples were heated from 320 °C to 420 °C and then kept isothermal at 420 °C for 15 min. The results show that mass loss in step 2 correlated well with triglyceride content estimates obtained from conventional techniques for diverse microalgae and oilseed samples.« less

  4. An Anti-Inflammatory Role of VEGFR2/Src Kinase Inhibitor in Herpes Simplex Virus 1-Induced Immunopathology▿

    PubMed Central

    Sharma, Shalini; Mulik, Sachin; Kumar, Naveen; Suryawanshi, Amol; Rouse, Barry T.

    2011-01-01

    Corneal neovascularization represents a key step in the blinding inflammatory stromal keratitis (SK) lesion caused by ocular infection with herpes simplex virus (HSV). In this report, we describe a novel approach for limiting the angiogenesis caused by HSV infection of the mouse eye. We show that topical or systemic administration of the Src kinase inhibitor (TG100572) that inhibits downstream molecules involved in the vascular endothelial growth factor (VEGF) signaling pathway resulted in markedly diminished levels of HSV-induced angiogenesis and significantly reduced the severity of SK lesions. Multiple mechanisms were involved in the inhibitory effects. These included blockade of IL-8/CXCL1 involved in inflammatory cells recruitment that are a source of VEGF, diminished cellular infiltration in the cornea, and reduced proliferation and migration of CD4+ T cells into the corneas. As multiple angiogenic factors (VEGF and basic fibroblast growth factor [bFGF]) play a role in promoting angiogenesis during SK and since Src kinases are involved in signaling by many of them, the use of Src kinase inhibition represents a promising way of limiting the severity of SK lesions the most common cause of infectious blindness in the Western world. PMID:21471229

  5. Enriching the biological space of natural products and charting drug metabolites, through real time biotransformation monitoring: The NMR tube bioreactor.

    PubMed

    Chatzikonstantinou, Alexandra V; Chatziathanasiadou, Maria V; Ravera, Enrico; Fragai, Marco; Parigi, Giacomo; Gerothanassis, Ioannis P; Luchinat, Claudio; Stamatis, Haralambos; Tzakos, Andreas G

    2018-01-01

    Natural products offer a wide range of biological activities, but they are not easily integrated in the drug discovery pipeline, because of their inherent scaffold intricacy and the associated complexity in their synthetic chemistry. Enzymes may be used to perform regioselective and stereoselective incorporation of functional groups in the natural product core, avoiding harsh reaction conditions, several protection/deprotection and purification steps. Herein, we developed a three step protocol carried out inside an NMR-tube. 1st-step: STD-NMR was used to predict the: i) capacity of natural products as enzyme substrates and ii) possible regioselectivity of the biotransformations. 2nd-step: The real-time formation of multiple-biotransformation products in the NMR-tube bioreactor was monitored in-situ. 3rd-step: STD-NMR was applied in the mixture of the biotransformed products to screen ligands for protein targets. Herein, we developed a simple and time-effective process, the "NMR-tube bioreactor", that is able to: (i) predict which component of a mixture of natural products can be enzymatically transformed, (ii) monitor in situ the transformation efficacy and regioselectivity in crude extracts and multiple substrate biotransformations without fractionation and (iii) simultaneously screen for interactions of the biotransformation products with pharmaceutical protein targets. We have developed a green, time-, and cost-effective process that provide a simple route from natural products to lead compounds for drug discovery. This process can speed up the most crucial steps in the early drug discovery process, and reduce the chemical manipulations usually involved in the pipeline, improving the environmental compatibility. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Short-Chain 3-Hydroxyacyl-Coenzyme A Dehydrogenase Associates with a Protein Super-Complex Integrating Multiple Metabolic Pathways

    PubMed Central

    Narayan, Srinivas B.; Master, Stephen R.; Sireci, Anthony N.; Bierl, Charlene; Stanley, Paige E.; Li, Changhong; Stanley, Charles A.; Bennett, Michael J.

    2012-01-01

    Proteins involved in mitochondrial metabolic pathways engage in functionally relevant multi-enzyme complexes. We previously described an interaction between short-chain 3-hydroxyacyl-coenzyme A dehydrogenase (SCHAD) and glutamate dehydrogenase (GDH) explaining the clinical phenotype of hyperinsulinism in SCHAD-deficient patients and adding SCHAD to the list of mitochondrial proteins capable of forming functional, multi-pathway complexes. In this work, we provide evidence of SCHAD's involvement in additional interactions forming tissue-specific metabolic super complexes involving both membrane-associated and matrix-dwelling enzymes and spanning multiple metabolic pathways. As an example, in murine liver, we find SCHAD interaction with aspartate transaminase (AST) and GDH from amino acid metabolic pathways, carbamoyl phosphate synthase I (CPS-1) from ureagenesis, other fatty acid oxidation and ketogenesis enzymes and fructose-bisphosphate aldolase, an extra-mitochondrial enzyme of the glycolytic pathway. Most of the interactions appear to be independent of SCHAD's role in the penultimate step of fatty acid oxidation suggesting an organizational, structural or non-enzymatic role for the SCHAD protein. PMID:22496890

  7. A rapid, one step molecular identification of Trichoderma citrinoviride and Trichoderma reesei.

    PubMed

    Saroj, Dina B; Dengeti, Shrinivas N; Aher, Supriya; Gupta, Anil K

    2015-06-01

    Trichoderma species are widely used as production hosts for industrial enzymes. Identification of Trichoderma species requires a complex molecular biology based identification involving amplification and sequencing of multiple genes. Industrial laboratories are required to run identification tests repeatedly in cell banking procedures and also to prove absence of production host in the product. Such demands can be fulfilled by a brief method which enables confirmation of strain identity. This communication describes one step identification method for two common Trichoderma species; T. citrinoviride and T. reesei, based on identification of polymorphic region in the nucleotide sequence of translation elongation factor 1 alpha. A unique forward primer and common reverse primer resulted in 153 and 139 bp amplicon for T. citrinoviride and T. reesei, respectively. Simplification was further introduced by using mycelium as template for PCR amplification. Method described in this communication allows rapid, one step identification of two Trichoderma species.

  8. Rapid prototyping of carbon-based chemiresistive gas sensors on paper

    PubMed Central

    Mirica, Katherine A.; Azzarelli, Joseph M.; Weis, Jonathan G.; Schnorr, Jan M.; Swager, Timothy M.

    2013-01-01

    Chemically functionalized carbon nanotubes (CNTs) are promising materials for sensing of gases and volatile organic compounds. However, the poor solubility of carbon nanotubes hinders their chemical functionalization and the subsequent integration of these materials into devices. This manuscript describes a solvent-free procedure for rapid prototyping of selective chemiresistors from CNTs and graphite on the surface of paper. This procedure enables fabrication of functional gas sensors from commercially available starting materials in less than 15 min. The first step of this procedure involves the generation of solid composites of CNTs or graphite with small molecule selectors—designed to interact with specific classes of gaseous analytes—by solvent-free mechanical mixing in a ball mill and subsequent compression. The second step involves deposition of chemiresistive sensors by mechanical abrasion of these solid composites onto the surface of paper. Parallel fabrication of multiple chemiresistors from diverse composites rapidly generates cross-reactive arrays capable of sensing and differentiating gases and volatile organic compounds at part-per-million and part-per-thousand concentrations. PMID:23942132

  9. Fast quantification of bovine milk proteins employing external cavity-quantum cascade laser spectroscopy.

    PubMed

    Schwaighofer, Andreas; Kuligowski, Julia; Quintás, Guillermo; Mayer, Helmut K; Lendl, Bernhard

    2018-06-30

    Analysis of proteins in bovine milk is usually tackled by time-consuming analytical approaches involving wet-chemical, multi-step sample clean-up procedures. The use of external cavity-quantum cascade laser (EC-QCL) based IR spectroscopy was evaluated as an alternative screening tool for direct and simultaneous quantification of individual proteins (i.e. casein and β-lactoglobulin) and total protein content in commercial bovine milk samples. Mid-IR spectra of protein standard mixtures were used for building partial least squares (PLS) regression models. A sample set comprising different milk types (pasteurized; differently processed extended shelf life, ESL; ultra-high temperature, UHT) was analysed and results were compared to reference methods. Concentration values of the QCL-IR spectroscopy approach obtained within several minutes are in good agreement with reference methods involving multiple sample preparation steps. The potential application as a fast screening method for estimating the heat load applied to liquid milk is demonstrated. Copyright © 2018 Elsevier Ltd. All rights reserved.

  10. A Gaussian Approximation Approach for Value of Information Analysis.

    PubMed

    Jalal, Hawre; Alarid-Escudero, Fernando

    2018-02-01

    Most decisions are associated with uncertainty. Value of information (VOI) analysis quantifies the opportunity loss associated with choosing a suboptimal intervention based on current imperfect information. VOI can inform the value of collecting additional information, resource allocation, research prioritization, and future research designs. However, in practice, VOI remains underused due to many conceptual and computational challenges associated with its application. Expected value of sample information (EVSI) is rooted in Bayesian statistical decision theory and measures the value of information from a finite sample. The past few years have witnessed a dramatic growth in computationally efficient methods to calculate EVSI, including metamodeling. However, little research has been done to simplify the experimental data collection step inherent to all EVSI computations, especially for correlated model parameters. This article proposes a general Gaussian approximation (GA) of the traditional Bayesian updating approach based on the original work by Raiffa and Schlaifer to compute EVSI. The proposed approach uses a single probabilistic sensitivity analysis (PSA) data set and involves 2 steps: 1) a linear metamodel step to compute the EVSI on the preposterior distributions and 2) a GA step to compute the preposterior distribution of the parameters of interest. The proposed approach is efficient and can be applied for a wide range of data collection designs involving multiple non-Gaussian parameters and unbalanced study designs. Our approach is particularly useful when the parameters of an economic evaluation are correlated or interact.

  11. Fields of Tension in a Boundary-Crossing World: Towards a Democratic Organization of the Self.

    PubMed

    Hermans, Hubert J M; Konopka, Agnieszka; Oosterwegel, Annerieke; Zomer, Peter

    2017-12-01

    In their study of the relationship between self and society, scientists have proposed taking society as a metaphor for understanding the dynamics of the self, such as the analogy between the self and the functioning of a totalitarian state or the analogy between the self and the functioning of a bureaucratic organization. In addition to these models, the present article proposes a democratic society as a metaphor for understanding the workings of a dialogical self in a globalizing, boundary-crossing world. The article follows four steps. In the first step the self is depicted as extended to the social and societal environment and made up of fields of tension in which a multiplicity of self-positions are involved in processes of positioning and counter-positioning and in relationships of social power. In the second step, the fertility of the democratic metaphor is demonstrated by referring to theory and research from three identity perspectives: multicultural, multiracial, and transgender. In the fields of tension emerging between the multiplicity of self-positions, new, hybrid, and mixed identities have a chance to emerge as adaptive responses to the limitations of existing societal structures. In the third step, we place the democratic self in a broader societal context by linking three levels of inclusiveness, proposed by Self-Categorization Theory (personal, social, and human) to recent conceptions of a cosmopolitan democracy. In the fourth and final step, a model is presented which allows the formulation of a series of specific research questions for future studies of a democratically organized self.

  12. Evaluating quality of patient care communication in integrated care settings: a mixed method approach.

    PubMed

    Gulmans, J; Vollenbroek-Hutten, M M R; Van Gemert-Pijnen, J E W C; Van Harten, W H

    2007-10-01

    Owing to the involvement of multiple professionals from various institutions, integrated care settings are prone to suboptimal patient care communication. To assure continuity, communication gaps should be identified for targeted improvement initiatives. However, available assessment methods are often one-sided evaluations not appropriate for integrated care settings. We developed an evaluation approach that takes into account the multiple communication links and evaluation perspectives inherent to these settings. In this study, we describe this approach, using the integrated care setting of Cerebral Palsy as illustration. The approach follows a three-step mixed design in which the results of each step are used to mark out the subsequent step's focus. The first step patient questionnaire aims to identify quality gaps experienced by patients, comparing their expectancies and experiences with respect to patient-professional and inter-professional communication. Resulting gaps form the input of in-depth interviews with a subset of patients to evaluate underlying factors of ineffective communication. Resulting factors form the input of the final step's focus group meetings with professionals to corroborate and complete the findings. By combining methods, the presented approach aims to minimize limitations inherent to the application of single methods. The comprehensiveness of the approach enables its applicability in various integrated care settings. Its sequential design allows for in-depth evaluation of relevant quality gaps. Further research is needed to evaluate the approach's feasibility in practice. In our subsequent study, we present the results of the approach in the integrated care setting of children with Cerebral Palsy in three Dutch care regions.

  13. One-step formation of w/o/w multiple emulsions stabilized by single amphiphilic block copolymers.

    PubMed

    Hong, Liangzhi; Sun, Guanqing; Cai, Jinge; Ngai, To

    2012-02-07

    Multiple emulsions are complex polydispersed systems in which both oil-in-water (O/W) and water-in-oil (W/O) emulsion exists simultaneously. They are often prepared accroding to a two-step process and commonly stabilized using a combination of hydrophilic and hydrophobic surfactants. Recently, some reports have shown that multiple emulsions can also be produced through one-step method with simultaneous occurrence of catastrophic and transitional phase inversions. However, these reported multiple emulsions need surfactant blends and are usually described as transitory or temporary systems. Herein, we report a one-step phase inversion process to produce water-in-oil-in-water (W/O/W) multiple emulsions stabilized solely by a synthetic diblock copolymer. Unlike the use of small molecule surfactant combinations, block copolymer stabilized multiple emulsions are remarkably stable and show the ability to separately encapsulate both polar and nonpolar cargos. The importance of the conformation of the copolymer surfactant at the interfaces with regards to the stability of the multiple emulsions using the one-step method is discussed.

  14. RNAi screen in Drosophila larvae identifies histone deacetylase 3 as a positive regulator of the hsp70 heat shock gene expression during heat shock.

    PubMed

    Achary, Bhavana G; Campbell, Katie M; Co, Ivy S; Gilmour, David S

    2014-05-01

    The transcription regulation of the Drosophila hsp70 gene is a complex process that involves the regulation of multiple steps, including the establishment of paused Pol II and release of Pol II into elongation upon heat shock activation. While the major players involved in the regulation of gene expression have been studied in detail, additional factors involved in this process continue to be discovered. To identify factors involved in hsp70 expression, we developed a screen that capitalizes on a visual assessment of heat shock activation using a hsp70-beta galactosidase reporter and publicly available RNAi fly lines to deplete candidate proteins. We validated the screen by showing that the depletion of HSF, CycT, Cdk9, Nurf 301, or ELL prevented the full induction of hsp70 by heat shock. Our screen also identified the histone deacetylase HDAC3 and its associated protein SMRTER as positive regulators of hsp70 activation. Additionally, we show that HDAC3 and SMRTER contribute to hsp70 gene expression at a step subsequent to HSF-mediated activation and release of the paused Pol II that resides at the promoter prior to heat shock induction. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Influence of the Supramolecular Micro-Assembly of Multiple Emulsions on their Biopharmaceutical Features and In vivo Therapeutic Response.

    PubMed

    Cilurzo, Felisa; Cristiano, Maria Chiara; Di Marzio, Luisa; Cosco, Donato; Carafa, Maria; Ventura, Cinzia Anna; Fresta, Massimo; Paolino, Donatella

    2015-01-01

    The ability of some surfactants to self-assemble in a water/oil bi-phase environment thus forming supramolecular structure leading to the formation of w/o/w multiple emulsions was investigated. The w/o/w multiple emulsions obtained by self-assembling (one-step preparation method) were compared with those prepared following the traditional two-step procedure. Methyl-nicotinate was used as a hydrophilic model drug. The formation of the multiple emulsion structure was evidenced by optical microscopy, which showed a mean size of the inner oil droplets of 6 μm and 10 μm for one-step and two-step multiple emulsions, respectively. The in vitrobiopharmaceutical features of the various w/o/w multiple emulsion formulations were evaluated by means of viscosimetry studies, drug release and in vitro percutaneous permeation experiments through human stratum corneum and viable epidermis membranes. The self-assembled multiple emulsions allowed a more gradual percutaneous permeation (a zero-order permeation rate) than the two-step ones. The in vivotopical carrier properties of the two different multiple emulsions were evaluated on healthy human volunteers by using the spectrophotometry of reflectance, an in vivonon invasive method. These multiple emulsion systems were also compared with conventional emulsion formulations. Our findings demonstrated that the multiple emulsions obtained by self-assembling were able to provide a more sustained drug delivery into the skin and hence a longer therapeutic action than two-step multiple emulsions and conventional emulsion formulations. Finally, our findings showed that the supramolecular micro-assembly of multiple emulsions was able to influence not only the biopharmaceutical characteristics but also the potential in vivotherapeutic response.

  16. Preparation of next-generation sequencing libraries using Nextera™ technology: simultaneous DNA fragmentation and adaptor tagging by in vitro transposition.

    PubMed

    Caruccio, Nicholas

    2011-01-01

    DNA library preparation is a common entry point and bottleneck for next-generation sequencing. Current methods generally consist of distinct steps that often involve significant sample loss and hands-on time: DNA fragmentation, end-polishing, and adaptor-ligation. In vitro transposition with Nextera™ Transposomes simultaneously fragments and covalently tags the target DNA, thereby combining these three distinct steps into a single reaction. Platform-specific sequencing adaptors can be added, and the sample can be enriched and bar-coded using limited-cycle PCR to prepare di-tagged DNA fragment libraries. Nextera technology offers a streamlined, efficient, and high-throughput method for generating bar-coded libraries compatible with multiple next-generation sequencing platforms.

  17. Multiple Imputation of Completely Missing Repeated Measures Data within Person from a Complex Sample: Application to Accelerometer Data in the National Health and Nutrition Examination Survey

    PubMed Central

    Liu, Benmei; Yu, Mandi; Graubard, Barry I; Troiano, Richard P; Schenker, Nathaniel

    2016-01-01

    The Physical Activity Monitor (PAM) component was introduced into the 2003-2004 National Health and Nutrition Examination Survey (NHANES) to collect objective information on physical activity including both movement intensity counts and ambulatory steps. Due to an error in the accelerometer device initialization process, the steps data were missing for all participants in several primary sampling units (PSUs), typically a single county or group of contiguous counties, who had intensity count data from their accelerometers. To avoid potential bias and loss in efficiency in estimation and inference involving the steps data, we considered methods to accurately impute the missing values for steps collected in the 2003-2004 NHANES. The objective was to come up with an efficient imputation method which minimized model-based assumptions. We adopted a multiple imputation approach based on Additive Regression, Bootstrapping and Predictive mean matching (ARBP) methods. This method fits alternative conditional expectation (ace) models, which use an automated procedure to estimate optimal transformations for both the predictor and response variables. This paper describes the approaches used in this imputation and evaluates the methods by comparing the distributions of the original and the imputed data. A simulation study using the observed data is also conducted as part of the model diagnostics. Finally some real data analyses are performed to compare the before and after imputation results. PMID:27488606

  18. One-step production of multiple emulsions: microfluidic, polymer-stabilized and particle-stabilized approaches.

    PubMed

    Clegg, Paul S; Tavacoli, Joe W; Wilde, Pete J

    2016-01-28

    Multiple emulsions have great potential for application in food science as a means to reduce fat content or for controlled encapsulation and release of actives. However, neither production nor stability is straightforward. Typically, multiple emulsions are prepared via two emulsification steps and a variety of approaches have been deployed to give long-term stability. It is well known that multiple emulsions can be prepared in a single step by harnessing emulsion inversion, although the resulting emulsions are usually short lived. Recently, several contrasting methods have been demonstrated which give rise to stable multiple emulsions via one-step production processes. Here we review the current state of microfluidic, polymer-stabilized and particle-stabilized approaches; these rely on phase separation, the role of electrolyte and the trapping of solvent with particles respectively.

  19. Force-Manipulation Single-Molecule Spectroscopy Studies of Enzymatic Dynamics

    NASA Astrophysics Data System (ADS)

    Lu, H. Peter; He, Yufan; Lu, Maolin; Cao, Jin; Guo, Qing

    2014-03-01

    Subtle conformational changes play a crucial role in protein functions, especially in enzymatic reactions involving complex substrate-enzyme interactions and chemical reactions. We applied AFM-enhanced and magnetic tweezers-correlated single-molecule spectroscopy to study the mechanisms and dynamics of enzymatic reactions involved with kinase and lysozyme proteins. Enzymatic reaction turnovers and the associated structure changes of individual protein molecules were observed simultaneously in real-time by single-molecule FRET detections. Our single-molecule spectroscopy measurements of enzymatic conformational dynamics have revealed time bunching effect and intermittent coherence in conformational state change dynamics involving in enzymatic reaction cycles. The coherent conformational state dynamics suggests that the enzymatic catalysis involves a multi-step conformational motion along the coordinates of substrate-enzyme complex formation and product releasing. Our results support a multiple-conformational state model, being consistent with a complementary conformation selection and induced-fit enzymatic loop-gated conformational change mechanism in substrate-enzyme active complex formation.

  20. Decision-making for foot-and-mouth disease control: Objectives matter

    USGS Publications Warehouse

    Probert, William J. M.; Shea, Katriona; Fonnesbeck, Christopher J.; Runge, Michael C.; Carpenter, Tim E.; Durr, Salome; Garner, M. Graeme; Harvey, Neil; Stevenson, Mark A.; Webb, Colleen T.; Werkman, Marleen; Tildesley, Michael J.; Ferrari, Matthew J.

    2016-01-01

    Formal decision-analytic methods can be used to frame disease control problems, the first step of which is to define a clear and specific objective. We demonstrate the imperative of framing clearly-defined management objectives in finding optimal control actions for control of disease outbreaks. We illustrate an analysis that can be applied rapidly at the start of an outbreak when there are multiple stakeholders involved with potentially multiple objectives, and when there are also multiple disease models upon which to compare control actions. The output of our analysis frames subsequent discourse between policy-makers, modellers and other stakeholders, by highlighting areas of discord among different management objectives and also among different models used in the analysis. We illustrate this approach in the context of a hypothetical foot-and-mouth disease (FMD) outbreak in Cumbria, UK using outputs from five rigorously-studied simulation models of FMD spread. We present both relative rankings and relative performance of controls within each model and across a range of objectives. Results illustrate how control actions change across both the base metric used to measure management success and across the statistic used to rank control actions according to said metric. This work represents a first step towards reconciling the extensive modelling work on disease control problems with frameworks for structured decision making.

  1. Sandwich ELISA Microarrays: Generating Reliable and Reproducible Assays for High-Throughput Screens

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

    Gonzalez, Rachel M.; Varnum, Susan M.; Zangar, Richard C.

    The sandwich ELISA microarray is a powerful screening tool in biomarker discovery and validation due to its ability to simultaneously probe for multiple proteins in a miniaturized assay. The technical challenges of generating and processing the arrays are numerous. However, careful attention to possible pitfalls in the development of your antibody microarray assay can overcome these challenges. In this chapter, we describe in detail the steps that are involved in generating a reliable and reproducible sandwich ELISA microarray assay.

  2. The Emerging Role of Zinc in the Pathogenesis of Multiple Sclerosis.

    PubMed

    Choi, Bo Young; Jung, Jong Won; Suh, Sang Won

    2017-09-28

    Our lab has previously demonstrated that multiple sclerosis-induced spinal cord white matter damage and motor deficits are mediated by the pathological disruption of zinc homeostasis. Abnormal vesicular zinc release and intracellular zinc accumulation may mediate several steps in the pathophysiological processes of multiple sclerosis (MS), such as matrix metallopeptidase 9 (MMP-9) activation, blood-brain barrier (BBB) disruption, and subsequent immune cell infiltration from peripheral systems. Oral administration of a zinc chelator decreased BBB disruption, immune cell infiltration, and spinal white matter myelin destruction. Therefore, we hypothesized that zinc released into the extracellular space during MS progression is involved in destruction of the myelin sheath in spinal cord white mater and in generation of motor deficits. To confirm our previous study, we employed zinc transporter 3 ( ZnT3 ) knockout mice to test whether vesicular zinc depletion shows protective effects on multiple sclerosis-induced white matter damage and motor deficits. ZnT3 gene deletion profoundly reduced the daily clinical score of experimental autoimmune encephalomyelitis (EAE) by suppression of inflammation and demyelination in the spinal cord. ZnT3 gene deletion also remarkably inhibited formation of multiple sclerosis-associated aberrant synaptic zinc patches, MMP-9 activation, and BBB disruption. These two studies strongly support our hypothesis that zinc release from presynaptic terminals may be involved in multiple sclerosis pathogenesis. Further studies will no doubt continue to add mechanistic detail to this process and with luck, clarify how these observations may lead to development of novel therapeutic approaches for the treatment of multiple sclerosis.

  3. Promoting ambulation responses among children with multiple disabilities through walkers and microswitches with contingent stimuli.

    PubMed

    Lancioni, Giulio E; Singh, Nirbhay N; O'Reilly, Mark F; Sigafoos, Jeff; Oliva, Doretta; Smaldone, Angela; La Martire, Maria L; Stasolla, Fabrizio; Castagnaro, Francesca; Groeneweg, Jop

    2010-01-01

    Children with severe or profound intellectual and motor disabilities often present problems of balance and ambulation and spend much of their time sitting or lying, with negative consequences for their development and social status. Recent research has shown the possibility of using a walker (support) device and microswitches with preferred stimuli to promote ambulation with these children. This study served as a replication of the aforementioned research and involved five new children with multiple disabilities. For four children, the study involved an ABAB design. For the fifth child, only an AB sequence was used. All children succeeded in increasing their frequencies of step responses during the B (intervention) phase(s) of the study, although the overall frequencies of those responses varied largely across them. These findings support the positive evidence already available about the effectiveness of this intervention approach in motivating and promoting children's ambulation. Practical implications of the findings are discussed. 2010 Elsevier Ltd. All rights reserved.

  4. Trends in computer applications in science assessment

    NASA Astrophysics Data System (ADS)

    Kumar, David D.; Helgeson, Stanley L.

    1995-03-01

    Seven computer applications to science assessment are reviewed. Conventional test administration includes record keeping, grading, and managing test banks. Multiple-choice testing involves forced selection of an answer from a menu, whereas constructed-response testing involves options for students to present their answers within a set standard deviation. Adaptive testing attempts to individualize the test to minimize the number of items and time needed to assess a student's knowledge. Figurai response testing assesses science proficiency in pictorial or graphic mode and requires the student to construct a mental image rather than selecting a response from a multiple choice menu. Simulations have been found useful for performance assessment on a large-scale basis in part because they make it possible to independently specify different aspects of a real experiment. An emerging approach to performance assessment is solution pathway analysis, which permits the analysis of the steps a student takes in solving a problem. Virtually all computer-based testing systems improve the quality and efficiency of record keeping and data analysis.

  5. 'Scaling-up is a craft not a science': Catalysing scale-up of health innovations in Ethiopia, India and Nigeria.

    PubMed

    Spicer, Neil; Bhattacharya, Dipankar; Dimka, Ritgak; Fanta, Feleke; Mangham-Jefferies, Lindsay; Schellenberg, Joanna; Tamire-Woldemariam, Addis; Walt, Gill; Wickremasinghe, Deepthi

    2014-11-01

    Donors and other development partners commonly introduce innovative practices and technologies to improve health in low and middle income countries. Yet many innovations that are effective in improving health and survival are slow to be translated into policy and implemented at scale. Understanding the factors influencing scale-up is important. We conducted a qualitative study involving 150 semi-structured interviews with government, development partners, civil society organisations and externally funded implementers, professional associations and academic institutions in 2012/13 to explore scale-up of innovative interventions targeting mothers and newborns in Ethiopia, the Indian state of Uttar Pradesh and the six states of northeast Nigeria, which are settings with high burdens of maternal and neonatal mortality. Interviews were analysed using a common analytic framework developed for cross-country comparison and themes were coded using Nvivo. We found that programme implementers across the three settings require multiple steps to catalyse scale-up. Advocating for government to adopt and finance health innovations requires: designing scalable innovations; embedding scale-up in programme design and allocating time and resources; building implementer capacity to catalyse scale-up; adopting effective approaches to advocacy; presenting strong evidence to support government decision making; involving government in programme design; invoking policy champions and networks; strengthening harmonisation among external programmes; aligning innovations with health systems and priorities. Other steps include: supporting government to develop policies and programmes and strengthening health systems and staff; promoting community uptake by involving media, community leaders, mobilisation teams and role models. We conclude that scale-up has no magic bullet solution - implementers must embrace multiple activities, and require substantial support from donors and governments in doing so. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. The Effects of Multiple-Step and Single-Step Directions on Fourth and Fifth Grade Students' Grammar Assessment Performance

    ERIC Educational Resources Information Center

    Mazerik, Matthew B.

    2006-01-01

    The mean scores of English Language Learners (ELL) and English Only (EO) students in 4th and 5th grade (N = 110), across the teacher-administered Grammar Skills Test, were examined for differences in participants' scores on assessments containing single-step directions and assessments containing multiple-step directions. The results indicated no…

  7. A clinical test of stepping and change of direction to identify multiple falling older adults.

    PubMed

    Dite, Wayne; Temple, Viviene A

    2002-11-01

    To establish the reliability and validity of a new clinical test of dynamic standing balance, the Four Square Step Test (FSST), to evaluate its sensitivity, specificity, and predictive value in identifying subjects who fall, and to compare it with 3 established balance and mobility tests. A 3-group comparison performed by using 3 validated tests and 1 new test. A rehabilitation center and university medical school in Australia. Eighty-one community-dwelling adults over the age of 65 years. Subjects were age- and gender-matched to form 3 groups: multiple fallers, nonmultiple fallers, and healthy comparisons. Not applicable. Time to complete the FSST and Timed Up and Go test and the number of steps to complete the Step Test and Functional Reach Test distance. High reliability was found for interrater (n=30, intraclass correlation coefficient [ICC]=.99) and retest reliability (n=20, ICC=.98). Evidence for validity was found through correlation with other existing balance tests. Validity was supported, with the FSST showing significantly better performance scores (P<.01) for each of the healthier and less impaired groups. The FSST also revealed a sensitivity of 85%, a specificity of 88% to 100%, and a positive predictive value of 86%. As a clinical test, the FSST is reliable, valid, easy to score, quick to administer, requires little space, and needs no special equipment. It is unique in that it involves stepping over low objects (2.5cm) and movement in 4 directions. The FSST had higher combined sensitivity and specificity for identifying differences between groups in the selected sample population of older adults than the 3 tests with which it was compared. Copyright 2002 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation

  8. Engagement in Multiple Steps of the Advance Care Planning Process: A Descriptive Study Among Diverse Older Adults

    PubMed Central

    Sudore, Rebecca L.; Schickedanz, Adam D.; Landefeld, C. Seth; Williams, Brie A.; Lindquist, Karla; Pantilat, Steven Z.; Schillinger, Dean

    2017-01-01

    Objectives Advance care planning (ACP) research and policy has focused on documentation, ignoring other ACP steps. We propose an ACP model based on the behavior change framework. We assess engagement in multiple steps of ACP six months after exposure to an advance directive. Design Descriptive study Setting County General Medicine clinic in San Francisco Participants 147 English/Spanish-speakers, aged ≥50 years (mean 61) given a standard (12th-grade reading level) and easy-to-read (5th grade) advance directive. Measurements Six months after exposure to advance directives, we measured self-reported ACP contemplation; discussions with family/friends and clinicians; and documentation. We examined associations between ACP steps and explored subject characteristics associated with ACP. Results Most participants (73%) were non-white and 31% had < high school education. Sixty one percent contemplated ACP, 56% discussed ACP with family/friends, 22% discussed with clinicians, and 13% documented ACP wishes. Compared to subjects who had not discussed ACP with family/friends, those who had were more likely to discuss ACP with their clinicians (36% vs. 2%, P<.001) and document ACP wishes (18% vs. 4%, P=.009). Latinos and subjects with < high school education more often discussed ACP with family/friends (P<.06) and clinicians (P<.03) than other ethnic groups and subjects with more education. Conclusion ACP involves distinct steps including contemplation, discussions, and documentation. The ACP paradigm should be broadened to include contemplation and discussions. Promoting discussions among family/friends may be one of the most important targets for ACP interventions, and literacy/language appropriate advance directives may help reverse patterns of socio-demographic disparities in ACP. PMID:18410324

  9. RNA splicing process analysis for identifying antisense oligonucleotide inhibitors with padlock probe-based isothermal amplification† †Electronic supplementary information (ESI) available: Additional experimental materials, methods, DNA sequences and supplementary figures and tables. See DOI: 10.1039/c7sc01336a Click here for additional data file.

    PubMed Central

    Ren, Xiaojun; Deng, Ruijie; Wang, Lida; Zhang, Kaixiang

    2017-01-01

    RNA splicing, which mainly involves two transesterification steps, is a fundamental process of gene expression and its abnormal regulation contributes to serious genetic diseases. Antisense oligonucleotides (ASOs) are genetic control tools that can be used to specifically control genes through alteration of the RNA splicing pathway. Despite intensive research, how ASOs or various other factors influence the multiple processes of RNA splicing still remains obscure. This is largely due to an inability to analyze the splicing efficiency of each step in the RNA splicing process with high sensitivity. We addressed this limitation by introducing a padlock probe-based isothermal amplification assay to achieve quantification of the specific products in different splicing steps. With this amplified assay, the roles that ASOs play in RNA splicing inhibition in the first and second steps could be distinguished. We identified that 5′-ASO could block RNA splicing by inhibiting the first step, while 3′-ASO could block RNA splicing by inhibiting the second step. This method provides a versatile tool for assisting efficient ASO design and discovering new splicing modulators and therapeutic drugs. PMID:28989608

  10. Mass Spectrometry: A Technique of Many Faces

    PubMed Central

    Olshina, Maya A.; Sharon, Michal

    2016-01-01

    Protein complexes form the critical foundation for a wide range of biological process, however understanding the intricate details of their activities is often challenging. In this review we describe how mass spectrometry plays a key role in the analysis of protein assemblies and the cellular pathways which they are involved in. Specifically, we discuss how the versatility of mass spectrometric approaches provides unprecedented information on multiple levels. We demonstrate this on the ubiquitin-proteasome proteolytic pathway, a process that is responsible for protein turnover. We follow the various steps of this degradation route and illustrate the different mass spectrometry workflows that were applied for elucidating molecular information. Overall, this review aims to stimulate the integrated use of multiple mass spectrometry approaches for analyzing complex biological systems. PMID:28100928

  11. Whole-genome multiple displacement amplification from single cells.

    PubMed

    Spits, Claudia; Le Caignec, Cédric; De Rycke, Martine; Van Haute, Lindsey; Van Steirteghem, André; Liebaers, Inge; Sermon, Karen

    2006-01-01

    Multiple displacement amplification (MDA) is a recently described method of whole-genome amplification (WGA) that has proven efficient in the amplification of small amounts of DNA, including DNA from single cells. Compared with PCR-based WGA methods, MDA generates DNA with a higher molecular weight and shows better genome coverage. This protocol was developed for preimplantation genetic diagnosis, and details a method for performing single-cell MDA using the phi29 DNA polymerase. It can also be useful for the amplification of other minute quantities of DNA, such as from forensic material or microdissected tissue. The protocol includes the collection and lysis of single cells, and all materials and steps involved in the MDA reaction. The whole procedure takes 3 h and generates 1-2 microg of DNA from a single cell, which is suitable for multiple downstream applications, such as sequencing, short tandem repeat analysis or array comparative genomic hybridization.

  12. Concanavalin-A conjugated fine-multiple emulsion loaded with 6-mercaptopurine.

    PubMed

    Khopade, A J; Jain, N K

    2000-01-01

    Fine-multiple (water-in-oil-in-water) emulsions were prepared by two-step emulsification using sonication. They were coated with concanavalin-A (Con-A) by three methods. The one involving covalent coupling of Con-A to the multiple emulsion incorporated anchor was better compared with lipid derivatized Con-A anchoring or the glutaraldehyde-based cross-linking method, as shown by the faster rate of dextran-induced aggregation. The selected multiple emulsions were characterized by physical properties such as droplet size, encapsulation efficiency, and zeta potential. Stability parameters such as droplet size, creaming, leakage, and aggregation as a function of relative turbidity were monitored over a 1-month period, which revealed good stability of the formulations. The release profile of 6-mercaptopurine followed zero-order kinetics. Pharmacokinetic studies showed an increase in half-life and bioavailability from multiple emulsion formulations administered intravenously. There was prolonged retention of drug in various tissues of rats when treated with Con-A-coated multiple emulsion as compared with uncoated one. Our study demonstrates the suitability of fine-multiple emulsion for intravenous administration and the potential for prolonged retention of drugs and targeting in biological systems.

  13. Stretching single atom contacts at multiple subatomic step-length.

    PubMed

    Wei, Yi-Min; Liang, Jing-Hong; Chen, Zhao-Bin; Zhou, Xiao-Shun; Mao, Bing-Wei; Oviedo, Oscar A; Leiva, Ezequiel P M

    2013-08-14

    This work describes jump-to-contact STM-break junction experiments leading to novel statistical distribution of last-step length associated with conductance of a single atom contact. Last-step length histograms are observed with up to five for Fe and three for Cu peaks at integral multiples close to 0.075 nm, a subatomic distance. A model is proposed in terms of gliding from a fcc hollow-site to a hcp hollow-site of adjacent atomic planes at 1/3 regular layer spacing along with tip stretching to account for the multiple subatomic step-length behavior.

  14. Making three-dimensional echocardiography more tangible: a workflow for three-dimensional printing with echocardiographic data.

    PubMed

    Mashari, Azad; Montealegre-Gallegos, Mario; Knio, Ziyad; Yeh, Lu; Jeganathan, Jelliffe; Matyal, Robina; Khabbaz, Kamal R; Mahmood, Feroze

    2016-12-01

    Three-dimensional (3D) printing is a rapidly evolving technology with several potential applications in the diagnosis and management of cardiac disease. Recently, 3D printing (i.e. rapid prototyping) derived from 3D transesophageal echocardiography (TEE) has become possible. Due to the multiple steps involved and the specific equipment required for each step, it might be difficult to start implementing echocardiography-derived 3D printing in a clinical setting. In this review, we provide an overview of this process, including its logistics and organization of tools and materials, 3D TEE image acquisition strategies, data export, format conversion, segmentation, and printing. Generation of patient-specific models of cardiac anatomy from echocardiographic data is a feasible, practical application of 3D printing technology. © 2016 The authors.

  15. An investigation of multidisciplinary complex health care interventions - steps towards an integrative treatment model in the rehabilitation of People with Multiple Sclerosis

    PubMed Central

    2012-01-01

    Background The Danish Multiple Sclerosis Society initiated a large-scale bridge building and integrative treatment project to take place from 2004–2010 at a specialized Multiple Sclerosis (MS) hospital. In this project, a team of five conventional health care practitioners and five alternative practitioners was set up to work together in developing and offering individualized treatments to 200 people with MS. The purpose of this paper is to present results from the six year treatment collaboration process regarding the development of an integrative treatment model. Discussion The collaborative work towards an integrative treatment model for people with MS, involved six steps: 1) Working with an initial model 2) Unfolding the different treatment philosophies 3) Discussing the elements of the Intervention-Mechanism-Context-Outcome-scheme (the IMCO-scheme) 4) Phrasing the common assumptions for an integrative MS program theory 5) Developing the integrative MS program theory 6) Building the integrative MS treatment model. The model includes important elements of the different treatment philosophies represented in the team and thereby describes a common understanding of the complexity of the courses of treatment. Summary An integrative team of practitioners has developed an integrative model for combined treatments of People with Multiple Sclerosis. The model unites different treatment philosophies and focuses on process-oriented factors and the strengthening of the patients’ resources and competences on a physical, an emotional and a cognitive level. PMID:22524586

  16. Self-Assembly through Noncovalent Preorganization of Reactants: Explaining the Formation of a Polyfluoroxometalate.

    PubMed

    Schreiber, Roy E; Avram, Liat; Neumann, Ronny

    2018-01-09

    High-order elementary reactions in homogeneous solutions involving more than two molecules are statistically improbable and very slow to proceed. They are not generally considered in classical transition-state or collision theories. Yet, rather selective, high-yield product formation is common in self-assembly processes that require many reaction steps. On the basis of recent observations of crystallization as well as reactions in dense phases, it is shown that self-assembly can occur by preorganization of reactants in a noncovalent supramolecular assembly, whereby directing forces can lead to an apparent one-step transformation of multiple reactants. A simple and general kinetic model for multiple reactant transformation in a dense phase that can account for many-bodied transformations was developed. Furthermore, the self-assembly of polyfluoroxometalate anion [H 2 F 6 NaW 18 O 56 ] 7- from simple tungstate Na 2 WO 2 F 4 was demonstrated by using 2D 19 F- 19 F NOESY, 2D 19 F- 19 F COSY NMR spectroscopy, a new 2D 19 F{ 183 W} NMR technique, as well as ESI-MS and diffusion NMR spectroscopy, and the crucial involvement of a supramolecular assembly was found. The deterministic kinetic reaction model explains the reaction in a dense phase and supports the suggested self-assembly mechanism. Reactions in dense phases may be of general importance in understanding other self-assembly reactions. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Treating alcoholism as a chronic disease: approaches to long-term continuing care.

    PubMed

    McKay, James R; Hiller-Sturmhofel, Susanne

    2011-01-01

    For many patients, alcohol and other drug (AOD) use disorders are chronic, recurring conditions involving multiple cycles of treatment, abstinence, and relapse. To disrupt this cycle, treatment can include continuing care to reduce the risk of relapse. The most commonly used treatment approach is initial intensive inpatient or outpatient care based on 12-step principles, followed by continuing care involving self-help groups, 12-step group counseling, or individual therapy. Although these programs can be effective, many patients drop out of initial treatment or do not complete continuing care. Thus, researchers and clinicians have begun to develop alternative approaches to enhance treatment retention in both initial and continuing care. One focus of these efforts has been the design of extended treatment models. These approaches increasingly blur the distinction between initial and continuing care and aim to prolong treatment participation by providing a continuum of care. Other researchers have focused on developing alternative treatment strategies (e.g., telephone-based interventions) that go beyond traditional settings and adaptive treatment algorithms that may improve outcomes for clients who do not respond well to traditional approaches.

  18. Task performance in virtual environments used for cognitive rehabilitation after traumatic brain injury.

    PubMed

    Christiansen, C; Abreu, B; Ottenbacher, K; Huffman, K; Masel, B; Culpepper, R

    1998-08-01

    This report describes a reliability study using a prototype computer-simulated virtual environment to assess basic daily living skills in a sample of persons with traumatic brain injury (TBI). The benefits of using virtual reality in training for situations where safety is a factor have been established in defense and industry, but have not been demonstrated in rehabilitation. Thirty subjects with TBI receiving comprehensive rehabilitation services at a residential facility. An immersive virtual kitchen was developed in which a meal preparation task involving multiple steps could be performed. The prototype was tested using subjects who completed the task twice within 7 days. The stability of performance was estimated using intraclass correlation coefficients (ICCs). The ICC value for total performance based on all steps involved in the meal preparation task was .73. When three items with low variance were removed the ICC improved to .81. Little evidence of vestibular optical side-effects was noted in the subjects tested. Adequate initial reliability exists to continue development of the environment as an assessment and training prototype for persons with brain injury.

  19. Characterization of Developer Application Methods Used in Fluorescent Penetrant Inspection

    NASA Astrophysics Data System (ADS)

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

    2006-03-01

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

  20. Biomimicry Promotes the Efficiency of a 10-Step Sequential Enzymatic Reaction on Nanoparticles, Converting Glucose to Lactate.

    PubMed

    Mukai, Chinatsu; Gao, Lizeng; Nelson, Jacquelyn L; Lata, James P; Cohen, Roy; Wu, Lauren; Hinchman, Meleana M; Bergkvist, Magnus; Sherwood, Robert W; Zhang, Sheng; Travis, Alexander J

    2017-01-02

    For nanobiotechnology to achieve its potential, complex organic-inorganic systems must grow to utilize the sequential functions of multiple biological components. Critical challenges exist: immobilizing enzymes can block substrate-binding sites or prohibit conformational changes, substrate composition can interfere with activity, and multistep reactions risk diffusion of intermediates. As a result, the most complex tethered reaction reported involves only 3 enzymes. Inspired by the oriented immobilization of glycolytic enzymes on the fibrous sheath of mammalian sperm, here we show a complex reaction of 10 enzymes tethered to nanoparticles. Although individual enzyme efficiency was higher in solution, the efficacy of the 10-step pathway measured by conversion of glucose to lactate was significantly higher when tethered. To our knowledge, this is the most complex organic-inorganic system described, and it shows that tethered, multi-step biological pathways can be reconstituted in hybrid systems to carry out functions such as energy production or delivery of molecular cargo. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Biomimicry promotes the efficiency of a 10-step sequential enzymatic reaction on nanoparticles, converting glucose to lactate

    PubMed Central

    Mukai, Chinatsu; Gao, Lizeng; Nelson, Jacquelyn L.; Lata, James P.; Cohen, Roy; Wu, Lauren; Hinchman, Meleana M.; Bergkvist, Magnus; Sherwood, Robert W.; Zhang, Sheng; Travis, Alexander J.

    2016-01-01

    For nanobiotechnology to achieve its potential, complex organic-inorganic systems must grow to utilize the sequential functions of multiple biological components. Critical challenges exist: immobilizing enzymes can block substrate-binding sites or prohibit conformational changes, substrate composition can interfere with activity, and multistep reactions risk diffusion of intermediates. As a result, the most complex tethered reaction reported involves only 3 enzymes. Inspired by the oriented immobilization of glycolytic enzymes on the fibrous sheath of mammalian sperm, here we show a complex reaction of 10 enzymes tethered to nanoparticles. Although individual enzyme efficiency was higher in solution, the efficacy of the 10-step pathway measured by conversion of glucose to lactate was significantly higher when tethered. To our knowledge, this is the most complex organic-inorganic system described, and it shows that tethered, multi-step biological pathways can be reconstituted in hybrid systems to carry out functions such as energy production or delivery of molecular cargo. PMID:27901298

  2. Portable, one-step, and rapid GMR biosensor platform with smartphone interface.

    PubMed

    Choi, Joohong; Gani, Adi Wijaya; Bechstein, Daniel J B; Lee, Jung-Rok; Utz, Paul J; Wang, Shan X

    2016-11-15

    Quantitative immunoassay tests in clinical laboratories require trained technicians, take hours to complete with multiple steps, and the instruments used are generally immobile-patient samples have to be sent in to the labs for analysis. This prevents quantitative immunoassay tests to be performed outside laboratory settings. A portable, quantitative immunoassay device will be valuable in rural and resource-limited areas, where access to healthcare is scarce or far away. We have invented Eigen Diagnosis Platform (EDP), a portable quantitative immunoassay platform based on Giant Magnetoresistance (GMR) biosensor technology. The platform does not require a trained technician to operate, and only requires one-step user involvement. It displays quantitative results in less than 15min after sample insertion, and each test costs less than US$4. The GMR biosensor employed in EDP is capable of detecting multiple biomarkers in one test, enabling a wide array of immune diagnostics to be performed simultaneously. In this paper, we describe the design of EDP, and demonstrate its capability. Multiplexed assay of human immunoglobulin G and M (IgG and IgM) antibodies with EDP achieves sensitivities down to 0.07 and 0.33 nanomolar, respectively. The platform will allow lab testing to be performed in remote areas, and open up applications of immunoassay testing in other non-clinical settings, such as home, school, and office. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Semi-autonomous remote sensing time series generation tool

    NASA Astrophysics Data System (ADS)

    Babu, Dinesh Kumar; Kaufmann, Christof; Schmidt, Marco; Dhams, Thorsten; Conrad, Christopher

    2017-10-01

    High spatial and temporal resolution data is vital for crop monitoring and phenology change detection. Due to the lack of satellite architecture and frequent cloud cover issues, availability of daily high spatial data is still far from reality. Remote sensing time series generation of high spatial and temporal data by data fusion seems to be a practical alternative. However, it is not an easy process, since it involves multiple steps and also requires multiple tools. In this paper, a framework of Geo Information System (GIS) based tool is presented for semi-autonomous time series generation. This tool will eliminate the difficulties by automating all the steps and enable the users to generate synthetic time series data with ease. Firstly, all the steps required for the time series generation process are identified and grouped into blocks based on their functionalities. Later two main frameworks are created, one to perform all the pre-processing steps on various satellite data and the other one to perform data fusion to generate time series. The two frameworks can be used individually to perform specific tasks or they could be combined to perform both the processes in one go. This tool can handle most of the known geo data formats currently available which makes it a generic tool for time series generation of various remote sensing satellite data. This tool is developed as a common platform with good interface which provides lot of functionalities to enable further development of more remote sensing applications. A detailed description on the capabilities and the advantages of the frameworks are given in this paper.

  4. Epigenetic Silencing of Plasmodium falciparum Genes Linked to Erythrocyte Invasion

    PubMed Central

    Cortés, Alfred; Carret, Celine; Kaneko, Osamu; Yim Lim, Brian Y. S.; Ivens, Alasdair; Holder, Anthony A

    2007-01-01

    The process of erythrocyte invasion by merozoites of Plasmodium falciparum involves multiple steps, including the formation of a moving junction between parasite and host cell, and it is characterised by the redundancy of many of the receptor–ligand interactions involved. Several parasite proteins that interact with erythrocyte receptors or participate in other steps of invasion are encoded by small subtelomerically located gene families of four to seven members. We report here that members of the eba, rhoph1/clag, acbp, and pfRh multigene families exist in either an active or a silenced state. In the case of two members of the rhoph1/clag family, clag3.1 and clag3.2, expression was mutually exclusive. Silencing was clonally transmitted and occurred in the absence of detectable DNA alterations, suggesting that it is epigenetic. This was demonstrated for eba-140. Our data demonstrate that variant or mutually exclusive expression and epigenetic silencing in Plasmodium are not unique to genes such as var, which encode proteins that are exported to the surface of the erythrocyte, but also occur for genes involved in host cell invasion. Clonal variant expression of invasion-related ligands increases the flexibility of the parasite to adapt to its human host. PMID:17676953

  5. Copper-catalyzed azide–alkyne cycloaddition (CuAAC) and beyond: new reactivity of copper(i) acetylides†

    PubMed Central

    Hein, Jason E.

    2011-01-01

    Copper-catalyzed azide–alkyne cycloaddition (CuAAC) is a widely utilized, reliable, and straightforward way for making covalent connections between building blocks containing various functional groups. It has been used in organic synthesis, medicinal chemistry, surface and polymer chemistry, and bioconjugation applications. Despite the apparent simplicity of the reaction, its mechanism involves multiple reversible steps involving coordination complexes of copper(i) acetylides of varying nuclearity. Understanding and controlling these equilibria is of paramount importance for channeling the reaction into the productive catalytic cycle. This tutorial review examines the history of the development of the CuAAC reaction, its key mechanistic aspects, and highlights the features that make it useful to practitioners in different fields of chemical science. PMID:20309487

  6. Species-specific challenges in dog cloning.

    PubMed

    Kim, G A; Oh, H J; Park, J E; Kim, M J; Park, E J; Jo, Y K; Jang, G; Kim, M K; Kim, H J; Lee, B C

    2012-12-01

    Somatic cell nuclear transfer (SCNT) is now an established procedure used in cloning of several species. SCNT in dogs involves multiple steps including the removal of the nuclear material, injection of a donor cell, fusion, activation of the reconstructed oocytes and finally transfer to a synchronized female recipient. There are therefore many factors that contribute to cloning efficiency. By performing a retrospective analysis of 2005-2012 published papers regarding dog cloning, we define the optimum procedure and summarize the specific feature for dog cloning. © 2012 Blackwell Verlag GmbH.

  7. Virtual screening for potential inhibitors of bacterial MurC and MurD ligases.

    PubMed

    Tomašić, Tihomir; Kovač, Andreja; Klebe, Gerhard; Blanot, Didier; Gobec, Stanislav; Kikelj, Danijel; Mašič, Lucija Peterlin

    2012-03-01

    Mur ligases are bacterial enzymes involved in the cytoplasmic steps of peptidoglycan biosynthesis and are viable targets for antibacterial drug discovery. We have performed virtual screening for potential ATP-competitive inhibitors targeting MurC and MurD ligases, using a protocol of consecutive hierarchical filters. Selected compounds were evaluated for inhibition of MurC and MurD ligases, and weak inhibitors possessing dual inhibitory activity have been identified. These compounds represent new scaffolds for further optimisation towards multiple Mur ligase inhibitors with improved inhibitory potency.

  8. Laser-assisted isotope separation of tritium

    DOEpatents

    Herman, Irving P.; Marling, Jack B.

    1983-01-01

    Methods for laser-assisted isotope separation of tritium, using infrared multiple photon dissociation of tritium-bearing products in the gas phase. One such process involves the steps of (1) catalytic exchange of a deuterium-bearing molecule XYD with tritiated water DTO from sources such as a heavy water fission reactor, to produce the tritium-bearing working molecules XYT and (2) photoselective dissociation of XYT to form a tritium-rich product. By an analogous procedure, tritium is separated from tritium-bearing materials that contain predominately hydrogen such as a light water coolant from fission or fusion reactors.

  9. Real-Time Optimal Flood Control Decision Making and Risk Propagation Under Multiple Uncertainties

    NASA Astrophysics Data System (ADS)

    Zhu, Feilin; Zhong, Ping-An; Sun, Yimeng; Yeh, William W.-G.

    2017-12-01

    Multiple uncertainties exist in the optimal flood control decision-making process, presenting risks involving flood control decisions. This paper defines the main steps in optimal flood control decision making that constitute the Forecast-Optimization-Decision Making (FODM) chain. We propose a framework for supporting optimal flood control decision making under multiple uncertainties and evaluate risk propagation along the FODM chain from a holistic perspective. To deal with uncertainties, we employ stochastic models at each link of the FODM chain. We generate synthetic ensemble flood forecasts via the martingale model of forecast evolution. We then establish a multiobjective stochastic programming with recourse model for optimal flood control operation. The Pareto front under uncertainty is derived via the constraint method coupled with a two-step process. We propose a novel SMAA-TOPSIS model for stochastic multicriteria decision making. Then we propose the risk assessment model, the risk of decision-making errors and rank uncertainty degree to quantify the risk propagation process along the FODM chain. We conduct numerical experiments to investigate the effects of flood forecast uncertainty on optimal flood control decision making and risk propagation. We apply the proposed methodology to a flood control system in the Daduhe River basin in China. The results indicate that the proposed method can provide valuable risk information in each link of the FODM chain and enable risk-informed decisions with higher reliability.

  10. Mixed linear-non-linear inversion of crustal deformation data: Bayesian inference of model, weighting and regularization parameters

    NASA Astrophysics Data System (ADS)

    Fukuda, Jun'ichi; Johnson, Kaj M.

    2010-06-01

    We present a unified theoretical framework and solution method for probabilistic, Bayesian inversions of crustal deformation data. The inversions involve multiple data sets with unknown relative weights, model parameters that are related linearly or non-linearly through theoretic models to observations, prior information on model parameters and regularization priors to stabilize underdetermined problems. To efficiently handle non-linear inversions in which some of the model parameters are linearly related to the observations, this method combines both analytical least-squares solutions and a Monte Carlo sampling technique. In this method, model parameters that are linearly and non-linearly related to observations, relative weights of multiple data sets and relative weights of prior information and regularization priors are determined in a unified Bayesian framework. In this paper, we define the mixed linear-non-linear inverse problem, outline the theoretical basis for the method, provide a step-by-step algorithm for the inversion, validate the inversion method using synthetic data and apply the method to two real data sets. We apply the method to inversions of multiple geodetic data sets with unknown relative data weights for interseismic fault slip and locking depth. We also apply the method to the problem of estimating the spatial distribution of coseismic slip on faults with unknown fault geometry, relative data weights and smoothing regularization weight.

  11. Multispectra CWT-based algorithm (MCWT) in mass spectra for peak extraction.

    PubMed

    Hsueh, Huey-Miin; Kuo, Hsun-Chih; Tsai, Chen-An

    2008-01-01

    An important objective in mass spectrometry (MS) is to identify a set of biomarkers that can be used to potentially distinguish patients between distinct treatments (or conditions) from tens or hundreds of spectra. A common two-step approach involving peak extraction and quantification is employed to identify the features of scientific interest. The selected features are then used for further investigation to understand underlying biological mechanism of individual protein or for development of genomic biomarkers to early diagnosis. However, the use of inadequate or ineffective peak detection and peak alignment algorithms in peak extraction step may lead to a high rate of false positives. Also, it is crucial to reduce the false positive rate in detecting biomarkers from ten or hundreds of spectra. Here a new procedure is introduced for feature extraction in mass spectrometry data that extends the continuous wavelet transform-based (CWT-based) algorithm to multiple spectra. The proposed multispectra CWT-based algorithm (MCWT) not only can perform peak detection for multiple spectra but also carry out peak alignment at the same time. The author' MCWT algorithm constructs a reference, which integrates information of multiple raw spectra, for feature extraction. The algorithm is applied to a SELDI-TOF mass spectra data set provided by CAMDA 2006 with known polypeptide m/z positions. This new approach is easy to implement and it outperforms the existing peak extraction method from the Bioconductor PROcess package.

  12. Automated Big Data Analysis in Bottom-up and Targeted Proteomics

    PubMed Central

    van der Plas-Duivesteijn, Suzanne; Domański, Dominik; Smith, Derek; Borchers, Christoph; Palmblad, Magnus; Mohamme, Yassene

    2014-01-01

    Similar to other data intensive sciences, analyzing mass spectrometry-based proteomics data involves multiple steps and diverse software using different algorithms and data formats and sizes. Besides that the distributed and evolving nature of the data in online repositories, another challenge is that a scientists have to deal with many steps of analysis pipelines. A documented data processing is also becoming an essential part for the overall reproducibility of the results. Thanks to different e-Science initiatives, scientific workflow engines have become a means for automated, sharable and reproducible data processing. While these are designed as general tools, they can be employed to solve different challenges that we are facing in handling our Big Data. Here we present three use cases: improving the performance of different spectral search engines by decomposing input data and recomposing the resulting files, building spectral libraries from more than 20 million spectra, and integrating information from multiple resources to select most appropriate peptides for targeted proteomics analyses. The three use cases demonstrate different challenges in exploiting proteomics data analysis. In the first we integrate local and cloud processing resources in order to obtain better performance resulting in more than 30-fold speed improvement. By considering search engines as legacy software our solution is applicable to multiple search algorithms. The second use case is an example of automated processing of many data files of different sizes and locations, starting with raw data and ending with the final, ready-to-use library. This demonstrates the robustness and fault tolerance when dealing with huge amount data stored in multiple files. The third use case demonstrates retrieval and integration of information and data from multiple online repositories. In addition to the diversity of data formats and Web interfaces, this use case also illustrates how to deal with incomplete data.

  13. Efficient Generation of Somatic Cell Nuclear Transfer-Competent Porcine Cells with Mutated Alleles at Multiple Target Loci by Using CRISPR/Cas9 Combined with Targeted Toxin-Based Selection System.

    PubMed

    Sato, Masahiro; Miyoshi, Kazuchika; Nakamura, Shingo; Ohtsuka, Masato; Sakurai, Takayuki; Watanabe, Satoshi; Kawaguchi, Hiroaki; Tanimoto, Akihide

    2017-12-04

    The recent advancement in genome editing such a CRISPR/Cas9 system has enabled isolation of cells with knocked multiple alleles through a one-step transfection. Somatic cell nuclear transfer (SCNT) has been frequently employed as one of the efficient tools for the production of genetically modified (GM) animals. To use GM cells as SCNT donor, efficient isolation of transfectants with mutations at multiple target loci is often required. The methods for the isolation of such GM cells largely rely on the use of drug selection-based approach using selectable genes; however, it is often difficult to isolate cells with mutations at multiple target loci. In this study, we used a novel approach for the efficient isolation of porcine cells with at least two target loci mutations by one-step introduction of CRISPR/Cas9-related components. A single guide (sg) RNA targeted to GGTA1 gene, involved in the synthesis of cell-surface α-Gal epitope (known as xenogenic antigen), is always a prerequisite. When the transfected cells were reacted with toxin-labeled BS-I-B₄ isolectin for 2 h at 37 C to eliminate α-Gal epitope-expressing cells, the surviving clones lacked α-Gal epitope expression and were highly expected to exhibit induced mutations at another target loci. Analysis of these α-Gal epitope-negative surviving cells demonstrated a 100% occurrence of genome editing at target loci. SCNT using these cells as donors resulted in the production of cloned blastocysts with the genotype similar to that of the donor cells used. Thus, this novel system will be useful for SCNT-mediated acquisition of GM cloned piglets, in which multiple target loci may be mutated.

  14. Multiple roles for the actin cytoskeleton during regulated exocytosis

    PubMed Central

    Porat-Shliom, Natalie; Milberg, Oleg; Masedunskas, Andrius; Weigert, Roberto

    2014-01-01

    Regulated exocytosis is the main mechanism utilized by specialized secretory cells to deliver molecules to the cell surface by virtue of membranous containers (i.e. secretory vesicles). The process involves a series of highly coordinated and sequential steps, which include the biogenesis of the vesicles, their delivery to the cell periphery, their fusion with the plasma membrane and the release of their content into the extracellular space. Each of these steps is regulated by the actin cytoskeleton. In this review, we summarize the current knowledge regarding the involvement of actin and its associated molecules during each of the exocytic steps in vertebrates, and suggest that the overall role of the actin cytoskeleton during regulated exocytosis is linked to the architecture and the physiology of the secretory cells under examination. Specifically, in neurons, neuroendocrine, endocrine, and hematopoietic cells, which contain small secretory vesicles that undergo rapid exocytosis (on the order of milliseconds), the actin cytoskeleton plays a role in pre-fusion events, where it acts primarily as a functional barrier and facilitates docking. In exocrine and other secretory cells, which contain large secretory vesicles that undergo slow exocytosis (seconds to minutes), the actin cytoskeleton plays a role in post-fusion events, where it regulates the dynamics of the fusion pore, facilitates the integration of the vesicles into the plasma membrane, provides structural support, and promotes the expulsion of large cargo molecules. PMID:22986507

  15. Advanced Neuropsychological Diagnostics Infrastructure (ANDI): A Normative Database Created from Control Datasets

    PubMed Central

    de Vent, Nathalie R.; Agelink van Rentergem, Joost A.; Schmand, Ben A.; Murre, Jaap M. J.; Huizenga, Hilde M.

    2016-01-01

    In the Advanced Neuropsychological Diagnostics Infrastructure (ANDI), datasets of several research groups are combined into a single database, containing scores on neuropsychological tests from healthy participants. For most popular neuropsychological tests the quantity, and range of these data surpasses that of traditional normative data, thereby enabling more accurate neuropsychological assessment. Because of the unique structure of the database, it facilitates normative comparison methods that were not feasible before, in particular those in which entire profiles of scores are evaluated. In this article, we describe the steps that were necessary to combine the separate datasets into a single database. These steps involve matching variables from multiple datasets, removing outlying values, determining the influence of demographic variables, and finding appropriate transformations to normality. Also, a brief description of the current contents of the ANDI database is given. PMID:27812340

  16. Advanced Neuropsychological Diagnostics Infrastructure (ANDI): A Normative Database Created from Control Datasets.

    PubMed

    de Vent, Nathalie R; Agelink van Rentergem, Joost A; Schmand, Ben A; Murre, Jaap M J; Huizenga, Hilde M

    2016-01-01

    In the Advanced Neuropsychological Diagnostics Infrastructure (ANDI), datasets of several research groups are combined into a single database, containing scores on neuropsychological tests from healthy participants. For most popular neuropsychological tests the quantity, and range of these data surpasses that of traditional normative data, thereby enabling more accurate neuropsychological assessment. Because of the unique structure of the database, it facilitates normative comparison methods that were not feasible before, in particular those in which entire profiles of scores are evaluated. In this article, we describe the steps that were necessary to combine the separate datasets into a single database. These steps involve matching variables from multiple datasets, removing outlying values, determining the influence of demographic variables, and finding appropriate transformations to normality. Also, a brief description of the current contents of the ANDI database is given.

  17. Measurements of Gluconeogenesis and Glycogenolysis: A Methodological Review

    PubMed Central

    Chung, Stephanie T.; Chacko, Shaji K.; Sunehag, Agneta L.

    2015-01-01

    Gluconeogenesis is a complex metabolic process that involves multiple enzymatic steps regulated by myriad factors, including substrate concentrations, the redox state, activation and inhibition of specific enzyme steps, and hormonal modulation. At present, the most widely accepted technique to determine gluconeogenesis is by measuring the incorporation of deuterium from the body water pool into newly formed glucose. However, several techniques using radioactive and stable-labeled isotopes have been used to quantitate the contribution and regulation of gluconeogenesis in humans. Each method has its advantages, methodological assumptions, and set of propagated errors. In this review, we examine the strengths and weaknesses of the most commonly used stable isotopes methods to measure gluconeogenesis in vivo. We discuss the advantages and limitations of each method and summarize the applicability of these measurements in understanding normal and pathophysiological conditions. PMID:26604176

  18. Genome-Wide Screening of Genes Showing Altered Expression in Liver Metastases of Human Colorectal Cancers by cDNA Microarray1

    PubMed Central

    Yanagawa, Rempei; Furukawa, Yoichi; Tsunoda, Tatsuhiko; Kitahara, Osamu; Kameyama, Masao; Murata, Kohei; Ishikawa, Osamu; Nakamura, Yusuke

    2001-01-01

    Abstract In spite of intensive and increasingly successful attempts to determine the multiple steps involved in colorectal carcinogenesis, the mechanisms responsible for metastasis of colorectal tumors to the liver remain to be clarified. To identify genes that are candidates for involvement in the metastatic process, we analyzed genome-wide expression profiles of 10 primary colorectal cancers and their corresponding metastatic lesions by means of a cDNA microarray consisting of 9121 human genes. This analysis identified 40 genes whose expression was commonly upregulated in metastatic lesions, and 7 that were commonly downregulated. The upregulated genes encoded proteins involved in cell adhesion, or remodeling of the actin cytoskeleton. Investigation of the functions of more of the altered genes should improve our understanding of metastasis and may identify diagnostic markers and/or novel molecular targets for prevention or therapy of metastatic lesions. PMID:11687950

  19. Contact formation and gettering of precipitated impurities by multiple firing during semiconductor device fabrication

    DOEpatents

    Sopori, Bhushan

    2014-05-27

    Methods for contact formation and gettering of precipitated impurities by multiple firing during semiconductor device fabrication are provided. In one embodiment, a method for fabricating an electrical semiconductor device comprises: a first step that includes gettering of impurities from a semiconductor wafer and forming a backsurface field; and a second step that includes forming a front contact for the semiconductor wafer, wherein the second step is performed after completion of the first step.

  20. HIA, the next step: Defining models and roles

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

    Putters, Kim

    If HIA is to be an effective instrument for optimising health interests in the policy making process it has to recognise the different contests in which policy is made and the relevance of both technical rationality and political rationality. Policy making may adopt a rational perspective in which there is a systematic and orderly progression from problem formulation to solution or a network perspective in which there are multiple interdependencies, extensive negotiation and compromise, and the steps from problem to formulation are not followed sequentially or in any particular order. Policy problems may be simple with clear causal pathways andmore » responsibilities or complex with unclear causal pathways and disputed responsibilities. Network analysis is required to show which stakeholders are involved, their support for health issues and the degree of consensus. From this analysis three models of HIA emerge. The first is the phases model which is fitted to simple problems and a rational perspective of policymaking. This model involves following structured steps. The second model is the rounds (Echternach) model that is fitted to complex problems and a network perspective of policymaking. This model is dynamic and concentrates on network solutions taking these steps in no particular order. The final model is the 'garbage can' model fitted to contexts which combine simple and complex problems. In this model HIA functions as a problem solver and signpost keeping all possible solutions and stakeholders in play and allowing solutions to emerge over time. HIA models should be the beginning rather than the conclusion of discussion the worlds of HIA and policymaking.« less

  1. Systematic gene deletions evidences that laccases are involved in several stages of wood degradation in the filamentous fungus Podospora anserina.

    PubMed

    Xie, Ning; Chapeland-Leclerc, Florence; Silar, Philippe; Ruprich-Robert, Gwenaël

    2014-01-01

    Transformation of plant biomass into biofuels may supply environmentally friendly alternative biological sources of energy. Laccases are supposed to be involved in the lysis of lignin, a prerequisite step for efficient breakdown of cellulose into fermentable sugars. The role in development and plant biomass degradation of the nine canonical laccases belonging to three different subfamilies and one related multicopper oxidase of the Ascomycota fungus Podospora anserina was investigated by targeted gene deletion. The 10 genes were inactivated singly, and multiple mutants were constructed by genetic crosses. lac6(Δ), lac8(Δ) and mco(Δ) mutants were significantly reduced in their ability to grow on lignin-containing materials, but also on cellulose and plastic. Furthermore, lac8(Δ), lac7(Δ), mco(Δ) and lac6(Δ) mutants were defective towards resistance to phenolic substrates and H2 O2 , which may also impact lignocellulose breakdown. Double and multiple mutants were generally more affected than single mutants, evidencing redundancy of function among laccases. Our study provides the first genetic evidences that laccases are major actors of wood utilization in a fungus and that they have multiple roles during this process apart from participation in lignin lysis. © 2013 Society for Applied Microbiology and John Wiley & Sons Ltd.

  2. Improved Aerogel Vacuum Thermal Insulation

    NASA Technical Reports Server (NTRS)

    Ruemmele, Warren P.; Bue, Grant C.

    2009-01-01

    An improved design concept for aerogel vacuum thermal-insulation panels calls for multiple layers of aerogel sandwiched between layers of aluminized Mylar (or equivalent) poly(ethylene terephthalate), as depicted in the figure. This concept is applicable to both the rigid (brick) form and the flexible (blanket) form of aerogel vacuum thermal-insulation panels. Heretofore, the fabrication of a typical aerogel vacuum insulating panel has involved encapsulation of a single layer of aerogel in poly(ethylene terephthalate) and pumping of gases out of the aerogel-filled volume. A multilayer panel according to the improved design concept is fabricated in basically the same way: Multiple alternating layers of aerogel and aluminized poly(ethylene terephthalate) are assembled, then encapsulated in an outer layer of poly(ethylene terephthalate), and then the volume containing the multilayer structure is evacuated as in the single-layer case. The multilayer concept makes it possible to reduce effective thermal conductivity of a panel below that of a comparable single-layer panel, without adding weight or incurring other performance penalties. Implementation of the multilayer concept is simple and relatively inexpensive, involving only a few additional fabrication steps to assemble the multiple layers prior to evacuation. For a panel of the blanket type, the multilayer concept, affords the additional advantage of reduced stiffness.

  3. The Steroidogenic Acute Regulatory Protein (StAR) Is Regulated by the H19/let-7 Axis.

    PubMed

    Men, Yi; Fan, Yanhong; Shen, Yuanyuan; Lu, Lingeng; Kallen, Amanda N

    2017-02-01

    The steroidogenic acute regulatory protein (StAR) governs the rate-limiting step in steroidogenesis, and its expression varies depending on the needs of the specific tissue. Tight control of steroid production is essential for multiple processes involved in reproduction, including follicular development, ovulation, and endometrial synchronization. Recently, there has been a growing interest in the role of noncoding RNAs in the regulation of reproduction. Here we demonstrate that StAR is a novel target of the microRNA let-7, which itself is regulated by the long noncoding RNA (lncRNA) H19. Using human and murine cell lines, we show that overexpression of H19 stimulates StAR expression by antagonizing let-7, which inhibits StAR at the post-transcriptional level. Our results uncover a novel mechanism underlying the regulation of StAR expression and represent the first example of lncRNA-mediated control of the rate-limiting step of steroidogenesis. This work thus adds to the body of literature describing the multiple roles in oncogenesis, cellular growth, glucose metabolism, and now regulation of steroidogenesis, of this complex lncRNA. Copyright © 2017 by the Endocrine Society.

  4. Molecular dynamics based enhanced sampling of collective variables with very large time steps.

    PubMed

    Chen, Pei-Yang; Tuckerman, Mark E

    2018-01-14

    Enhanced sampling techniques that target a set of collective variables and that use molecular dynamics as the driving engine have seen widespread application in the computational molecular sciences as a means to explore the free-energy landscapes of complex systems. The use of molecular dynamics as the fundamental driver of the sampling requires the introduction of a time step whose magnitude is limited by the fastest motions in a system. While standard multiple time-stepping methods allow larger time steps to be employed for the slower and computationally more expensive forces, the maximum achievable increase in time step is limited by resonance phenomena, which inextricably couple fast and slow motions. Recently, we introduced deterministic and stochastic resonance-free multiple time step algorithms for molecular dynamics that solve this resonance problem and allow ten- to twenty-fold gains in the large time step compared to standard multiple time step algorithms [P. Minary et al., Phys. Rev. Lett. 93, 150201 (2004); B. Leimkuhler et al., Mol. Phys. 111, 3579-3594 (2013)]. These methods are based on the imposition of isokinetic constraints that couple the physical system to Nosé-Hoover chains or Nosé-Hoover Langevin schemes. In this paper, we show how to adapt these methods for collective variable-based enhanced sampling techniques, specifically adiabatic free-energy dynamics/temperature-accelerated molecular dynamics, unified free-energy dynamics, and by extension, metadynamics, thus allowing simulations employing these methods to employ similarly very large time steps. The combination of resonance-free multiple time step integrators with free-energy-based enhanced sampling significantly improves the efficiency of conformational exploration.

  5. Molecular dynamics based enhanced sampling of collective variables with very large time steps

    NASA Astrophysics Data System (ADS)

    Chen, Pei-Yang; Tuckerman, Mark E.

    2018-01-01

    Enhanced sampling techniques that target a set of collective variables and that use molecular dynamics as the driving engine have seen widespread application in the computational molecular sciences as a means to explore the free-energy landscapes of complex systems. The use of molecular dynamics as the fundamental driver of the sampling requires the introduction of a time step whose magnitude is limited by the fastest motions in a system. While standard multiple time-stepping methods allow larger time steps to be employed for the slower and computationally more expensive forces, the maximum achievable increase in time step is limited by resonance phenomena, which inextricably couple fast and slow motions. Recently, we introduced deterministic and stochastic resonance-free multiple time step algorithms for molecular dynamics that solve this resonance problem and allow ten- to twenty-fold gains in the large time step compared to standard multiple time step algorithms [P. Minary et al., Phys. Rev. Lett. 93, 150201 (2004); B. Leimkuhler et al., Mol. Phys. 111, 3579-3594 (2013)]. These methods are based on the imposition of isokinetic constraints that couple the physical system to Nosé-Hoover chains or Nosé-Hoover Langevin schemes. In this paper, we show how to adapt these methods for collective variable-based enhanced sampling techniques, specifically adiabatic free-energy dynamics/temperature-accelerated molecular dynamics, unified free-energy dynamics, and by extension, metadynamics, thus allowing simulations employing these methods to employ similarly very large time steps. The combination of resonance-free multiple time step integrators with free-energy-based enhanced sampling significantly improves the efficiency of conformational exploration.

  6. Generation of Recombinant Polioviruses Harboring RNA Affinity Tags in the 5′ and 3′ Noncoding Regions of Genomic RNAs

    PubMed Central

    Flather, Dylan; Cathcart, Andrea L.; Cruz, Casey; Baggs, Eric; Ngo, Tuan; Gershon, Paul D.; Semler, Bert L.

    2016-01-01

    Despite being intensely studied for more than 50 years, a complete understanding of the enterovirus replication cycle remains elusive. Specifically, only a handful of cellular proteins have been shown to be involved in the RNA replication cycle of these viruses. In an effort to isolate and identify additional cellular proteins that function in enteroviral RNA replication, we have generated multiple recombinant polioviruses containing RNA affinity tags within the 3′ or 5′ noncoding region of the genome. These recombinant viruses retained RNA affinity sequences within the genome while remaining viable and infectious over multiple passages in cell culture. Further characterization of these viruses demonstrated that viral protein production and growth kinetics were unchanged or only slightly altered relative to wild type poliovirus. However, attempts to isolate these genetically-tagged viral genomes from infected cells have been hindered by high levels of co-purification of nonspecific proteins and the limited matrix-binding efficiency of RNA affinity sequences. Regardless, these recombinant viruses represent a step toward more thorough characterization of enterovirus ribonucleoprotein complexes involved in RNA replication. PMID:26861382

  7. Can Reduced-Step Polishers Be as Effective as Multiple-Step Polishers in Enhancing Surface Smoothness?

    PubMed

    Kemaloglu, Hande; Karacolak, Gamze; Turkun, L Sebnem

    2017-02-01

    The aim of this study was to evaluate the effects of various finishing and polishing systems on the final surface roughness of a resin composite. Hypotheses tested were: (1) reduced-step polishing systems are as effective as multiple-step systems on reducing the surface roughness of a resin composite and (2) the number of application steps in an F/P system has no effect on reducing surface roughness. Ninety discs of a nano-hybrid resin composite were fabricated and divided into nine groups (n = 10). Except the control, all of the specimens were roughened prior to be polished by: Enamel Plus Shiny, Venus Supra, One-gloss, Sof-Lex Wheels, Super-Snap, Enhance/PoGo, Clearfil Twist Dia, and rubber cups. The surface roughness was measured and the surfaces were examined under scanning electron microscope. Results were analyzed with analysis of variance and Holm-Sidak's multiple comparisons test (p < 0.05). Significant differences were found among the surface roughness of all groups (p < 0.05). The smoothest surfaces were obtained under Mylar strips and the results were not different than Super-Snap, Enhance/PoGo, and Sof-Lex Spiral Wheels. The group that showed the roughest surface was the rubber cup group and these results were similar to those of the One-gloss, Enamel Plus Shiny, and Venus Supra groups. (1) The number of application steps has no effect on the performance of F/P systems. (2) Reduced-step polishers used after a finisher can be preferable to multiple-step systems when used on nanohybrid resin composites. (3) The effect of F/P systems on surface roughness seems to be material-dependent rather than instrument- or system-dependent. Reduced-step systems used after a prepolisher can be an acceptable alternative to multiple-step systems on enhancing the surface smoothness of a nanohybrid composite; however, their effectiveness depends on the materials' properties. (J Esthet Restor Dent 29:31-40, 2017). © 2016 Wiley Periodicals, Inc.

  8. Step by Step: Biology Undergraduates' Problem-Solving Procedures during Multiple-Choice Assessment

    ERIC Educational Resources Information Center

    Prevost, Luanna B.; Lemons, Paula P.

    2016-01-01

    This study uses the theoretical framework of domain-specific problem solving to explore the procedures students use to solve multiple-choice problems about biology concepts. We designed several multiple-choice problems and administered them on four exams. We trained students to produce written descriptions of how they solved the problem, and this…

  9. Recoded and nonrecoded trinary signed-digit adders and multipliers with redundant-bit representations

    NASA Astrophysics Data System (ADS)

    Cherri, Abdallah K.; Alam, Mohammed S.

    1998-07-01

    Highly-efficient two-step recoded and one-step nonrecoded trinary signed-digit (TSD) carry-free adders subtracters are presented on the basis of redundant-bit representation for the operands digits. It has been shown that only 24 (30) minterms are needed to implement the two-step recoded (the one-step nonrecoded) TSD addition for any operand length. Optical implementation of the proposed arithmetic can be carried out by use of correlation- or matrix-multiplication-based schemes, saving 50% of the system memory. Furthermore, we present four different multiplication designs based on our proposed recoded and nonrecoded TSD adders. Our multiplication designs require a small number of reduced minterms to generate the multiplication partial products. Finally, a recently proposed pipelined iterative-tree algorithm can be used in the TSD adders multipliers; consequently, efficient use of all available adders can be made.

  10. Recoded and nonrecoded trinary signed-digit adders and multipliers with redundant-bit representations.

    PubMed

    Cherri, A K; Alam, M S

    1998-07-10

    Highly-efficient two-step recoded and one-step nonrecoded trinary signed-digit (TSD) carry-free adders-subtracters are presented on the basis of redundant-bit representation for the operands' digits. It has been shown that only 24 (30) minterms are needed to implement the two-step recoded (the one-step nonrecoded) TSD addition for any operand length. Optical implementation of the proposed arithmetic can be carried out by use of correlation- or matrix-multiplication-based schemes, saving 50% of the system memory. Furthermore, we present four different multiplication designs based on our proposed recoded and nonrecoded TSD adders. Our multiplication designs require a small number of reduced minterms to generate the multiplication partial products. Finally, a recently proposed pipelined iterative-tree algorithm can be used in the TSD adders-multipliers; consequently, efficient use of all available adders can be made.

  11. Optimized breeding strategies for multiple trait integration: II. Process efficiency in event pyramiding and trait fixation.

    PubMed

    Peng, Ting; Sun, Xiaochun; Mumm, Rita H

    2014-01-01

    Multiple trait integration (MTI) is a multi-step process of converting an elite variety/hybrid for value-added traits (e.g. transgenic events) through backcross breeding. From a breeding standpoint, MTI involves four steps: single event introgression, event pyramiding, trait fixation, and version testing. This study explores the feasibility of marker-aided backcross conversion of a target maize hybrid for 15 transgenic events in the light of the overall goal of MTI of recovering equivalent performance in the finished hybrid conversion along with reliable expression of the value-added traits. Using the results to optimize single event introgression (Peng et al. Optimized breeding strategies for multiple trait integration: I. Minimizing linkage drag in single event introgression. Mol Breed, 2013) which produced single event conversions of recurrent parents (RPs) with ≤8 cM of residual non-recurrent parent (NRP) germplasm with ~1 cM of NRP germplasm in the 20 cM regions flanking the event, this study focused on optimizing process efficiency in the second and third steps in MTI: event pyramiding and trait fixation. Using computer simulation and probability theory, we aimed to (1) fit an optimal breeding strategy for pyramiding of eight events into the female RP and seven in the male RP, and (2) identify optimal breeding strategies for trait fixation to create a 'finished' conversion of each RP homozygous for all events. In addition, next-generation seed needs were taken into account for a practical approach to process efficiency. Building on work by Ishii and Yonezawa (Optimization of the marker-based procedures for pyramiding genes from multiple donor lines: I. Schedule of crossing between the donor lines. Crop Sci 47:537-546, 2007a), a symmetric crossing schedule for event pyramiding was devised for stacking eight (seven) events in a given RP. Options for trait fixation breeding strategies considered selfing and doubled haploid approaches to achieve homozygosity as well as seed chipping and tissue sampling approaches to facilitate genotyping. With selfing approaches, two generations of selfing rather than one for trait fixation (i.e. 'F2 enrichment' as per Bonnett et al. in Strategies for efficient implementation of molecular markers in wheat breeding. Mol Breed 15:75-85, 2005) were utilized to eliminate bottlenecking due to extremely low frequencies of desired genotypes in the population. The efficiency indicators such as total number of plants grown across generations, total number of marker data points, total number of generations, number of seeds sampled by seed chipping, number of plants requiring tissue sampling, and number of pollinations (i.e. selfing and crossing) were considered in comparisons of breeding strategies. A breeding strategy involving seed chipping and a two-generation selfing approach (SC + SELF) was determined to be the most efficient breeding strategy in terms of time to market and resource requirements. Doubled haploidy may have limited utility in trait fixation for MTI under the defined breeding scenario. This outcome paves the way for optimizing the last step in the MTI process, version testing, which involves hybridization of female and male RP conversions to create versions of the converted hybrid for performance evaluation and possible commercial release.

  12. The kinetics of influenza-virus adsorption on iron oxide in the process of viral purification and concentration

    PubMed Central

    Larin, N. M.; Gallimore, P. H.

    1971-01-01

    This paper reports a study carried out to clarify the mechanisms involved in adsorption of influenza A and B viruses on iron oxide. Accordingly, the amounts of virus that are adsorbed from virus suspensions of varying concentrations per unit surface area of magnetic or non-magnetic oxide at fixed temperature and time have been determined. The principles involved are clearly the same as those involved in multiple equilibria during the interaction of particles with a large number of combining sites with different intrinsic affinity. Consequently, the amount of virus that is adsorbed per unit mass of iron oxide depends on the size of the adsorbent area, not on its magnetic property. Owing to a significant difference between the affinities of influenza A and B particles for the binding sites on iron oxide, unit surface area of the adsorbent is invariably capable of adsorbing significantly greater amounts of influenza A than B particles. The practical implications of these findings are that a better understanding of the mechanisms involved in virus adsorption on iron oxide will permit a more efficient separation of virus particles from impurities. The simplicity and the rapidity of the technique and the cheapness of the equipment required suggest that the iron oxide method is of great value for both small- or large-scale viral purification, whether it is used as a single step procedure or as a primary step followed by zonal separation. PMID:5291749

  13. In Vitro and In Vivo Single Myosin Step-Sizes in Striated Muscle a

    PubMed Central

    Burghardt, Thomas P.; Sun, Xiaojing; Wang, Yihua; Ajtai, Katalin

    2016-01-01

    Myosin in muscle transduces ATP free energy into the mechanical work of moving actin. It has a motor domain transducer containing ATP and actin binding sites, and, mechanical elements coupling motor impulse to the myosin filament backbone providing transduction/mechanical-coupling. The mechanical coupler is a lever-arm stabilized by bound essential and regulatory light chains. The lever-arm rotates cyclically to impel bound filamentous actin. Linear actin displacement due to lever-arm rotation is the myosin step-size. A high-throughput quantum dot labeled actin in vitro motility assay (Qdot assay) measures motor step-size in the context of an ensemble of actomyosin interactions. The ensemble context imposes a constant velocity constraint for myosins interacting with one actin filament. In a cardiac myosin producing multiple step-sizes, a “second characterization” is step-frequency that adjusts longer step-size to lower frequency maintaining a linear actin velocity identical to that from a shorter step-size and higher frequency actomyosin cycle. The step-frequency characteristic involves and integrates myosin enzyme kinetics, mechanical strain, and other ensemble affected characteristics. The high-throughput Qdot assay suits a new paradigm calling for wide surveillance of the vast number of disease or aging relevant myosin isoforms that contrasts with the alternative model calling for exhaustive research on a tiny subset myosin forms. The zebrafish embryo assay (Z assay) performs single myosin step-size and step-frequency assaying in vivo combining single myosin mechanical and whole muscle physiological characterizations in one model organism. The Qdot and Z assays cover “bottom-up” and “top-down” assaying of myosin characteristics. PMID:26728749

  14. Microstructural stability of fine-grained fully lamellar XD TiAl alloys by step aging

    NASA Astrophysics Data System (ADS)

    Zhu, Hanliang; Maruyama, K.; Seo, D. Y.; Au, P.

    2005-05-01

    XD TiAl alloys (Ti-45 and 47Al-2Nb-2Mn+0.8 vol pct TiB2) (at. pct) were oil quenched to produce fine-grained fully lamellar (FGFL) structures, and aging treatments at different temperatures for different durations were carried out to stabilize the FGFL structures. Microstructural examinations show that the aging treatments cause phase transformation of α 2 to γ, resulting in stabilization of the lamellar structure, as indicated by a significant decrease in α 2 volume fraction. However, several degradation processes are also introduced. After aging, within lamellar colonies, the α 2 lamellae become finer due to dissolution, whereas most of the γ lamellae coarsen. The dissolution of α 2 involves longitudinal dissolution and lateral dissolution. In addition, at lamellar colony boundaries, lamellar termination migration, nucleation and growth of γ grains, and discontinuous coarsening occur. With the exception of longitudinal dissolution, all the other transformation modes are considered as degradation processes as they result in a reduction in α 2/ γ interfaces. Different phase transformation modes are present to varying degrees in the aged FGFL structures, depending on aging conditions and Al content. A multiple step aging reduces the drive force for phase transformation at high temperature by promoting phase transformation via longitudinal dissolution at low temperatures. As a result, this aging procedure effectively stabilizes the lamellar structure and suppresses other degradation processes. Therefore, the multiple step aging is suggested to be an optimal aging condition for stabilizing FGFL XD TiAl alloys.

  15. Identification of microRNA-mRNA modules using microarray data.

    PubMed

    Jayaswal, Vivek; Lutherborrow, Mark; Ma, David D F; Yang, Yee H

    2011-03-06

    MicroRNAs (miRNAs) are post-transcriptional regulators of mRNA expression and are involved in numerous cellular processes. Consequently, miRNAs are an important component of gene regulatory networks and an improved understanding of miRNAs will further our knowledge of these networks. There is a many-to-many relationship between miRNAs and mRNAs because a single miRNA targets multiple mRNAs and a single mRNA is targeted by multiple miRNAs. However, most of the current methods for the identification of regulatory miRNAs and their target mRNAs ignore this biological observation and focus on miRNA-mRNA pairs. We propose a two-step method for the identification of many-to-many relationships between miRNAs and mRNAs. In the first step, we obtain miRNA and mRNA clusters using a combination of miRNA-target mRNA prediction algorithms and microarray expression data. In the second step, we determine the associations between miRNA clusters and mRNA clusters based on changes in miRNA and mRNA expression profiles. We consider the miRNA-mRNA clusters with statistically significant associations to be potentially regulatory and, therefore, of biological interest. Our method reduces the interactions between several hundred miRNAs and several thousand mRNAs to a few miRNA-mRNA groups, thereby facilitating a more meaningful biological analysis and a more targeted experimental validation.

  16. Use of the false discovery rate for evaluating clinical safety data.

    PubMed

    Mehrotra, Devan V; Heyse, Joseph F

    2004-06-01

    Clinical adverse experience (AE) data are routinely evaluated using between group P values for every AE encountered within each of several body systems. If the P values are reported and interpreted without multiplicity considerations, there is a potential for an excess of false positive findings. Procedures based on confidence interval estimates of treatment effects have the same potential for false positive findings as P value methods. Excess false positive findings can needlessly complicate the safety profile of a safe drug or vaccine. Accordingly, we propose a novel method for addressing multiplicity in the evaluation of adverse experience data arising in clinical trial settings. The method involves a two-step application of adjusted P values based on the Benjamini and Hochberg false discovery rate (FDR). Data from three moderate to large vaccine trials are used to illustrate our proposed 'Double FDR' approach, and to reinforce the potential impact of failing to account for multiplicity. This work was in collaboration with the late Professor John W. Tukey who coined the term 'Double FDR'.

  17. Technical note: Simultaneous fully dynamic characterization of multiple input–output relationships in climate models

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

    Kravitz, Ben; MacMartin, Douglas G.; Rasch, Philip J.

    We introduce system identification techniques to climate science wherein multiple dynamic input–output relationships can be simultaneously characterized in a single simulation. This method, involving multiple small perturbations (in space and time) of an input field while monitoring output fields to quantify responses, allows for identification of different timescales of climate response to forcing without substantially pushing the climate far away from a steady state. We use this technique to determine the steady-state responses of low cloud fraction and latent heat flux to heating perturbations over 22 regions spanning Earth's oceans. We show that the response characteristics are similar to thosemore » of step-change simulations, but in this new method the responses for 22 regions can be characterized simultaneously. Moreover, we can estimate the timescale over which the steady-state response emerges. The proposed methodology could be useful for a wide variety of purposes in climate science, including characterization of teleconnections and uncertainty quantification to identify the effects of climate model tuning parameters.« less

  18. Technical note: Simultaneous fully dynamic characterization of multiple input–output relationships in climate models

    DOE PAGES

    Kravitz, Ben; MacMartin, Douglas G.; Rasch, Philip J.; ...

    2017-02-17

    We introduce system identification techniques to climate science wherein multiple dynamic input–output relationships can be simultaneously characterized in a single simulation. This method, involving multiple small perturbations (in space and time) of an input field while monitoring output fields to quantify responses, allows for identification of different timescales of climate response to forcing without substantially pushing the climate far away from a steady state. We use this technique to determine the steady-state responses of low cloud fraction and latent heat flux to heating perturbations over 22 regions spanning Earth's oceans. We show that the response characteristics are similar to thosemore » of step-change simulations, but in this new method the responses for 22 regions can be characterized simultaneously. Moreover, we can estimate the timescale over which the steady-state response emerges. The proposed methodology could be useful for a wide variety of purposes in climate science, including characterization of teleconnections and uncertainty quantification to identify the effects of climate model tuning parameters.« less

  19. ADVANCED SULFUR CONTROL CONCEPTS

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

    Apostolos A. Nikolopoulos; Santosh K. Gangwal; William J. McMichael

    Conventional sulfur removal in integrated gasification combined cycle (IGCC) power plants involves numerous steps: COS (carbonyl sulfide) hydrolysis, amine scrubbing/regeneration, Claus process, and tail-gas treatment. Advanced sulfur removal in IGCC systems involves typically the use of zinc oxide-based sorbents. The sulfides sorbent is regenerated using dilute air to produce a dilute SO{sub 2} (sulfur dioxide) tail gas. Under previous contracts the highly effective first generation Direct Sulfur Recovery Process (DSRP) for catalytic reduction of this SO{sub 2} tail gas to elemental sulfur was developed. This process is currently undergoing field-testing. In this project, advanced concepts were evaluated to reduce themore » number of unit operations in sulfur removal and recovery. Substantial effort was directed towards developing sorbents that could be directly regenerated to elemental sulfur in an Advanced Hot Gas Process (AHGP). Development of this process has been described in detail in Appendices A-F. RTI began the development of the Single-step Sulfur Recovery Process (SSRP) to eliminate the use of sorbents and multiple reactors in sulfur removal and recovery. This process showed promising preliminary results and thus further process development of AHGP was abandoned in favor of SSRP. The SSRP is a direct Claus process that consists of injecting SO{sub 2} directly into the quenched coal gas from a coal gasifier, and reacting the H{sub 2}S-SO{sub 2} mixture over a selective catalyst to both remove and recover sulfur in a single step. The process is conducted at gasifier pressure and 125 to 160 C. The proposed commercial embodiment of the SSRP involves a liquid phase of molten sulfur with dispersed catalyst in a slurry bubble-column reactor (SBCR).« less

  20. Formalized Conflicts Detection Based on the Analysis of Multiple Emails: An Approach Combining Statistics and Ontologies

    NASA Astrophysics Data System (ADS)

    Zakaria, Chahnez; Curé, Olivier; Salzano, Gabriella; Smaïli, Kamel

    In Computer Supported Cooperative Work (CSCW), it is crucial for project leaders to detect conflicting situations as early as possible. Generally, this task is performed manually by studying a set of documents exchanged between team members. In this paper, we propose a full-fledged automatic solution that identifies documents, subjects and actors involved in relational conflicts. Our approach detects conflicts in emails, probably the most popular type of documents in CSCW, but the methods used can handle other text-based documents. These methods rely on the combination of statistical and ontological operations. The proposed solution is decomposed in several steps: (i) we enrich a simple negative emotion ontology with terms occuring in the corpus of emails, (ii) we categorize each conflicting email according to the concepts of this ontology and (iii) we identify emails, subjects and team members involved in conflicting emails using possibilistic description logic and a set of proposed measures. Each of these steps are evaluated and validated on concrete examples. Moreover, this approach's framework is generic and can be easily adapted to domains other than conflicts, e.g. security issues, and extended with operations making use of our proposed set of measures.

  1. SUMMIT (Serially Unified Multicenter Multiple Sclerosis Investigation): creating a repository of deeply phenotyped contemporary multiple sclerosis cohorts.

    PubMed

    Bove, Riley; Chitnis, Tanuja; Cree, Bruce Ac; Tintoré, Mar; Naegelin, Yvonne; Uitdehaag, Bernard Mj; Kappos, Ludwig; Khoury, Samia J; Montalban, Xavier; Hauser, Stephen L; Weiner, Howard L

    2017-08-01

    There is a pressing need for robust longitudinal cohort studies in the modern treatment era of multiple sclerosis. Build a multiple sclerosis (MS) cohort repository to capture the variability of disability accumulation, as well as provide the depth of characterization (clinical, radiologic, genetic, biospecimens) required to adequately model and ultimately predict a patient's course. Serially Unified Multicenter Multiple Sclerosis Investigation (SUMMIT) is an international multi-center, prospectively enrolled cohort with over a decade of comprehensive follow-up on more than 1000 patients from two large North American academic MS Centers (Brigham and Women's Hospital (Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women's Hospital (CLIMB; BWH)) and University of California, San Francisco (Expression/genomics, Proteomics, Imaging, and Clinical (EPIC))). It is bringing online more than 2500 patients from additional international MS Centers (Basel (Universitätsspital Basel (UHB)), VU University Medical Center MS Center Amsterdam (MSCA), Multiple Sclerosis Center of Catalonia-Vall d'Hebron Hospital (Barcelona clinically isolated syndrome (CIS) cohort), and American University of Beirut Medical Center (AUBMC-Multiple Sclerosis Interdisciplinary Research (AMIR)). We provide evidence for harmonization of two of the initial cohorts in terms of the characterization of demographics, disease, and treatment-related variables; demonstrate several proof-of-principle analyses examining genetic and radiologic predictors of disease progression; and discuss the steps involved in expanding SUMMIT into a repository accessible to the broader scientific community.

  2. Method of making nanopatterns and nanostructures and nanopatterned functional oxide materials

    DOEpatents

    Dravid, Vinayak P; Donthu, Suresh K; Pan, Zixiao

    2014-02-11

    Method for nanopatterning of inorganic materials, such as ceramic (e.g. metal oxide) materials, and organic materials, such as polymer materials, on a variety of substrates to form nanopatterns and/or nanostructures with control of dimensions and location, all without the need for etching the materials and without the need for re-alignment between multiple patterning steps in forming nanostructures, such as heterostructures comprising multiple materials. The method involves patterning a resist-coated substrate using electron beam lithography, removing a portion of the resist to provide a patterned resist-coated substrate, and spin coating the patterned resist-coated substrate with a liquid precursor, such as a sol precursor, of the inorganic or organic material. The remaining resist is removed and the spin coated substrate is heated at an elevated temperature to crystallize the deposited precursor material.

  3. Inflammatory pathways in cervical cancer - the UCT contribution.

    PubMed

    Sales, Kurt Jason; Katz, Arieh Anthony

    2012-03-23

    Cervical cancer is the leading gynaecological malignancy in Southern Africa. The main causal factor for development of the disease is infection of the cervix with human papillomavirus. It is a multi-step disease with several contributing co-factors including multiple sexual partners, a compromised immune system and cervical inflammation caused by infections with Chlamydia trachomatis or Neisseria gonorrhoeae. Inflammation involves extensive tissue remodelling events which are orchestrated by complex networks of cytokines, chemokines and bio-active lipids working across multiple cellular compartments to maintain tissue homeostasis. Many pathological disorders or diseases, including cervical cancer, are characterised by the exacerbated activation and maintenance of inflammatory pathways. In this review we highlight our findings pertaining to activation of inflammatory pathways in cervical cancers, addressing their potential role in pathological changes of the cervix and the significance of these findings for intervention strategies.

  4. A supramolecular approach to fabricate highly emissive smart materials

    PubMed Central

    Liu, Kai; Yao, Yuxing; Kang, Yuetong; Liu, Yu; Han, Yuchun; Wang, Yilin; Li, Zhibo; Zhang, Xi

    2013-01-01

    The aromatic chromophores, for example, perylene diimides (PDIs) are well known for their desirable absorption and emission properties. However, their stacking nature hinders the exploitation of these properties and further applications. To fabricate emissive aggregates or solid-state materials, it has been common practice to decrease the degree of stacking of PDIs by incorporating substituents into the parent aromatic ring. However, such practice often involves difficultorganic synthesis with multiple steps. A supramolecular approach is established here to fabricate highly fluorescent and responsive soft materials, which has greatly decreases the number of required synthetic steps and also allows for a system with switchable photophysical properties. The highly fluorescent smart material exhibits great adaptivity and can be used as a supramolecular sensor for the rapid detection of spermine with high sensitivity and selectivity, which is crucial for the early diagnosis of malignant tumors. PMID:23917964

  5. Questioned document workflow for handwriting with automated tools

    NASA Astrophysics Data System (ADS)

    Das, Krishnanand; Srihari, Sargur N.; Srinivasan, Harish

    2012-01-01

    During the last few years many document recognition methods have been developed to determine whether a handwriting specimen can be attributed to a known writer. However, in practice, the work-flow of the document examiner continues to be manual-intensive. Before a systematic or computational, approach can be developed, an articulation of the steps involved in handwriting comparison is needed. We describe the work flow of handwritten questioned document examination, as described in a standards manual, and the steps where existing automation tools can be used. A well-known ransom note case is considered as an example, where one encounters testing for multiple writers of the same document, determining whether the writing is disguised, known writing is formal while questioned writing is informal, etc. The findings for the particular ransom note case using the tools are given. Also observations are made for developing a more fully automated approach to handwriting examination.

  6. Evidence integration in model-based tree search

    PubMed Central

    Solway, Alec; Botvinick, Matthew M.

    2015-01-01

    Research on the dynamics of reward-based, goal-directed decision making has largely focused on simple choice, where participants decide among a set of unitary, mutually exclusive options. Recent work suggests that the deliberation process underlying simple choice can be understood in terms of evidence integration: Noisy evidence in favor of each option accrues over time, until the evidence in favor of one option is significantly greater than the rest. However, real-life decisions often involve not one, but several steps of action, requiring a consideration of cumulative rewards and a sensitivity to recursive decision structure. We present results from two experiments that leveraged techniques previously applied to simple choice to shed light on the deliberation process underlying multistep choice. We interpret the results from these experiments in terms of a new computational model, which extends the evidence accumulation perspective to multiple steps of action. PMID:26324932

  7. Free-Energy Landscape of the Dissolution of Gibbsite at High pH.

    PubMed

    Shen, Zhizhang; Kerisit, Sebastien N; Stack, Andrew G; Rosso, Kevin M

    2018-04-05

    The individual elementary reactions involved in the dissolution of a solid into solution remain mostly speculative due to a lack of direct experimental probes. In this regard, we have applied atomistic simulations to map the free-energy landscape of the dissolution of gibbsite from a step edge as a model of metal hydroxide dissolution. The overall reaction combines kink formation and kink propagation. Two individual reactions were found to be rate-limiting for kink formation, that is, the displacement of Al from a step site to a ledge adatom site and its detachment from ledge/terrace adatom sites into the solution. As a result, a pool of mobile and labile adsorbed species, or adatoms, exists before the release of Al into solution. Because of the quasi-hexagonal symmetry of gibbsite, kink site propagation can occur in multiple directions. Overall, our results will enable the development of microscopic mechanistic models of metal oxide dissolution.

  8. Analytical Prediction of Damage Growth in Notched Composite Panels Loaded in Axial Compression

    NASA Technical Reports Server (NTRS)

    Ambur, Damodar R.; McGowan, David M.; Davila, Carlos G.

    1999-01-01

    A progressive failure analysis method based on shell elements is developed for the computation of damage initiation and growth in stiffened thick-skin stitched graphite-epoxy panels loaded in axial compression. The analysis method involves a step-by-step simulation of material degradation based on ply-level failure mechanisms. High computational efficiency is derived from the use of superposed layers of shell elements to model each ply orientation in the laminate. Multiple integration points through the thickness are used to obtain the correct bending effects through the thickness without the need for ply-by-ply evaluations of the state of the material. The analysis results are compared with experimental results for three stiffened panels with notches oriented at 0, 15 and 30 degrees to the panel width dimension. A parametric study is performed to investigate the damage growth retardation characteristics of the Kevlar stitch lines in the pan

  9. Transforming the Army Central Registry Family Violence File into a Relational Database for the Purpose of Facilitating Epidemiological Research

    DTIC Science & Technology

    2005-07-01

    child abuse events. ACR data were originally collected for administrative purposes and, without significant adaptation, are not immediately suitable for epidemiological analyses. Our ultimate research goal is to link ACR data for individuals involved in single or multiple events as victims, perpetrators, or both to health behavior, health outcome and demographic data. This will allow us to identity precipitating factors,follow individuals after an event, and understand how different events are related. This report details the steps taken to transform the ACR data into a

  10. Refeeding syndrome.

    PubMed

    Fernández López, M T; López Otero, M J; Alvarez Vázquez, P; Arias Delgado, J; Varela Correa, J J

    2009-01-01

    Refeeding syndrome is a complex syndrome that occurs as a result of reintroducing nutrition (oral, enteral or parenteral) to patients who are starved or malnourished. Patients can develop fluid-balance abnormalities, electrolyte disorders (hypophosphataemia, hypokalaemia and hypomagnesaemia), abnormal glucose metabolism and certain vitamin deficiencies. Refeeding syndrome encompasses abnormalities affecting multiple organ systems, including neurological, pulmonary, cardiac, neuromuscular and haematological functions. Pathogenic mechanisms involved in the refeeding syndrome and clinical manifestations have been reviewed. We provide suggestions for the prevention and treatment of refeeding syndrome. The most important steps are to identify patients at risk, reintroduce nutrition cautiously and correct electrolyte and vitamin deficiencies properly.

  11. Type-II generalized family-wise error rate formulas with application to sample size determination.

    PubMed

    Delorme, Phillipe; de Micheaux, Pierre Lafaye; Liquet, Benoit; Riou, Jérémie

    2016-07-20

    Multiple endpoints are increasingly used in clinical trials. The significance of some of these clinical trials is established if at least r null hypotheses are rejected among m that are simultaneously tested. The usual approach in multiple hypothesis testing is to control the family-wise error rate, which is defined as the probability that at least one type-I error is made. More recently, the q-generalized family-wise error rate has been introduced to control the probability of making at least q false rejections. For procedures controlling this global type-I error rate, we define a type-II r-generalized family-wise error rate, which is directly related to the r-power defined as the probability of rejecting at least r false null hypotheses. We obtain very general power formulas that can be used to compute the sample size for single-step and step-wise procedures. These are implemented in our R package rPowerSampleSize available on the CRAN, making them directly available to end users. Complexities of the formulas are presented to gain insight into computation time issues. Comparison with Monte Carlo strategy is also presented. We compute sample sizes for two clinical trials involving multiple endpoints: one designed to investigate the effectiveness of a drug against acute heart failure and the other for the immunogenicity of a vaccine strategy against pneumococcus. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  12. A Study on Segmented Multiple-Step Forming of Doubly Curved Thick Plate by Reconfigurable Multi-Punch Dies

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

    Ko, Young Ho; Han, Myoung Soo; Han, Jong Man

    2007-05-17

    Doubly curved thick plate forming in shipbuilding industries is currently performed by a thermal forming process, called as Line Heating by using gas flame torches. Due to the empirical manual work of it, the industries are eager for an alternative way to manufacture curved thick plates for ships. It was envisaged in this study to manufacture doubly curved thick plates by the multi-punch die forming. Experiments and finite element analyses were conducted to evaluate the feasibility of the reconfigurable discrete die forming to the thick plates. Single and segmented multiple step forming procedures were considered from both forming efficiency andmore » accuracy. Configuration of the multi-punch dies suitable for the segmented multiple step forming was also explored. As a result, Segmented multiple step forming with matched dies had a limited formability when the objective shapes become complicate, while a unmatched die configuration provided better possibility to manufacture large curved plates for ships.« less

  13. Lower limb muscle moments and power during recovery from forward loss of balance in male and female single and multiple steppers.

    PubMed

    Carty, Christopher P; Cronin, Neil J; Lichtwark, Glen A; Mills, Peter M; Barrett, Rod S

    2012-12-01

    Studying recovery responses to loss of balance may help to explain why older adults are susceptible to falls. The purpose of the present study was to assess whether male and female older adults, that use a single or multiple step recovery strategy, differ in the proportion of lower limb strength used and power produced during the stepping phase of balance recovery. Eighty-four community-dwelling older adults (47 men, 37 women) participated in the study. Isometric strength of the ankle, knee and hip joint flexors and extensors was assessed using a dynamometer. Loss of balance was induced by releasing participants from a static forward lean (4 trials at each of 3 forward lean angles). Participants were instructed to recover with a single step and were subsequently classified as using a single or multiple step recovery strategy for each trial. (1) Females were weaker than males and the proportion of females that were able to recover with a single step were lower than for males at each lean magnitude. (2) Multiple compared to single steppers used a significantly higher proportion of their hip extension strength and produced less knee and ankle joint peak power during stepping, at the intermediate lean angle. Strength deficits in female compared to male participants may explain why a lower proportion of female participants were able to recover with a single step. The inability to generate sufficient power in the stepping limb appears to be a limiting factor in single step recovery from forward loss of balance. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

  14. Affordable Window Insulation with R-10/inch Rating

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

    Jenifer Marchesi Redouane Begag; Je Kyun Lee; Danny Ou

    2004-10-15

    During the performance of contract DE-FC26-00-NT40998, entitled ''Affordable Window Insulation with R-10/inch Value'', research was conducted at Aspen Aerogels, Inc. to develop new transparent aerogel materials suitable for window insulation applications. The project requirements were to develop a formulation or multiple formulations that have high transparency (85-90%) in the visible region, are hydrophobic (will not opacify with exposure to water vapor or liquid), and have at least 2% resiliency (interpreted as recoverable 2% strain and better than 5% strain to failure in compression). Results from an unrelated project showed that silica aerogels covalently bonded to organic polymers exhibit excellent mechanicalmore » properties. At the outset of this project, we believed that such a route is the best to improve mechanical properties. We have applied Design of Experiment (DOE) techniques to optimize formulations including both silica aerogels and organically modified silica aerogels (''Ormosils''). We used these DOE results to optimize formulations around the local/global optimization points. This report documents that we succeeded in developing a number of formulations that meet all of the stated criteria. We successfully developed formulations utilizing a two-step approach where the first step involves acid catalyzed hydrolysis and the second step involves base catalyzed condensation to make the gels. The gels were dried using supercritical CO{sub 2} and we were able to make 1 foot x 1 foot x 0.5 inch panels that met the criteria established.« less

  15. One-step formation of multiple Pickering emulsions stabilized by self-assembled poly(dodecyl acrylate-co-acrylic acid) nanoparticles.

    PubMed

    Zhu, Ye; Sun, Jianhua; Yi, Chenglin; Wei, Wei; Liu, Xiaoya

    2016-09-13

    In this study, a one-step generation of stable multiple Pickering emulsions using pH-responsive polymeric nanoparticles as the only emulsifier was reported. The polymeric nanoparticles were self-assembled from an amphiphilic random copolymer poly(dodecyl acrylate-co-acrylic acid) (PDAA), and the effect of the copolymer content on the size and morphology of PDAA nanoparticles was determined by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The emulsification study of PDAA nanoparticles revealed that multiple Pickering emulsions could be generated through a one-step phase inversion process by using PDAA nanoparticles as the stabilizer. Moreover, the emulsification performance of PDAA nanoparticles at different pH values demonstrated that multiple emulsions with long-time stability could only be stabilized by PDAA nanoparticles at pH 5.5, indicating that the surface wettability of PDAA nanoparticles plays a crucial role in determining the type and stability of the prepared Pickering emulsions. Additionally, the polarity of oil does not affect the emulsification performance of PDAA nanoparticles, and a wide range of oils could be used as the oil phase to prepare multiple emulsions. These results demonstrated that multiple Pickering emulsions could be generated via the one-step emulsification process using self-assembled polymeric nanoparticles as the stabilizer, and the prepared multiple emulsions have promising potential to be applied in the cosmetic, medical, and food industries.

  16. Impact of favorite stimuli automatically delivered on step responses of persons with multiple disabilities during their use of walker devices.

    PubMed

    Lancioni, Giulio E; Singh, Nirbhay N; O'Reilly, Mark F; Campodonico, Francesca; Piazzolla, Giorgia; Scalini, Lorenza; Oliva, Doretta

    2005-01-01

    Favorite stimuli were automatically delivered contingent on the performance of steps by two persons (a boy and a woman) with multiple disabilities during their use of support walker devices. The study lasted about 4 months and was carried out according to a multiple baseline design across participants. Recording concerned the participants' frequencies of steps and their indices of happiness during baseline and intervention sessions. Data showed that both participants had a significant increase in each of these two measures during the intervention phase. Implications of the findings and new research issues are discussed.

  17. Protocols for In Vitro Mass Multiplication and Analysis of Medicinally Important Phenolics of a Salep Orchid, Satyrium nepalense D.Don ("Salam Mishri").

    PubMed

    Babbar, Shashi B; Singh, Deepak K

    2016-01-01

    Satyrium nepalense is a rare and threatened medicinal orchid, populations of which in its native habitats are dwindling because of indiscriminate collections and habitat destruction, thus necessitating the development of methods for its in situ and ex situ conservation. Because of non-endospermous nature of the seeds and the immature embryos at seed dispersal stage, orchids cannot be seed-propagated as other plants. Micropropagation, using plant tissue culture techniques, offers an effective method for the multiplication of orchids. In this chapter, a five-step efficient reproducible protocol for large-scale in vitro multiplication of Satyrium nepalense is described. The first step involves asymbiotic germination of seeds isolated from immature green pods and cultured on Mitra's medium (M) gelled with 0.8 % agar and supplemented with 2 % sucrose and 1 % peptone (hereafter referred to as basal medium, BM). On this medium, seeds start germinating after a week of culture. Protocorms developed from the seeds are sub-cultured on BM fortified with 4 μM kinetin (Kn) after 8 weeks, for shoot differentiation and multiplication. The shoots developed on Kn-supplemented medium are transferred to BM alone for their elongation for the same period. The elongated shoots are transferred to the rooting medium, comprising BM supplemented with 0.5 or 1.0 μM indole-3-butyric acid, for further 8 weeks. The regenerated plantlets are transferred to a potting mix of sand and vermiculite (1:1) for acclimatization. The tubers and leaves excised from both in vitro-developed plants and those from their native habitats are analyzed and compared for the contents and concentration of medicinally important phenolics using high-performance liquid chromatography (HPLC), details of which are provided in this chapter.

  18. Fast matrix multiplication and its algebraic neighbourhood

    NASA Astrophysics Data System (ADS)

    Pan, V. Ya.

    2017-11-01

    Matrix multiplication is among the most fundamental operations of modern computations. By 1969 it was still commonly believed that the classical algorithm was optimal, although the experts already knew that this was not so. Worldwide interest in matrix multiplication instantly exploded in 1969, when Strassen decreased the exponent 3 of cubic time to 2.807. Then everyone expected to see matrix multiplication performed in quadratic or nearly quadratic time very soon. Further progress, however, turned out to be capricious. It was at stalemate for almost a decade, then a combination of surprising techniques (completely independent of Strassen's original ones and much more advanced) enabled a new decrease of the exponent in 1978-1981 and then again in 1986, to 2.376. By 2017 the exponent has still not passed through the barrier of 2.373, but most disturbing was the curse of recursion — even the decrease of exponents below 2.7733 required numerous recursive steps, and each of them squared the problem size. As a result, all algorithms supporting such exponents supersede the classical algorithm only for inputs of immense sizes, far beyond any potential interest for the user. We survey the long study of fast matrix multiplication, focusing on neglected algorithms for feasible matrix multiplication. We comment on their design, the techniques involved, implementation issues, the impact of their study on the modern theory and practice of Algebraic Computations, and perspectives for fast matrix multiplication. Bibliography: 163 titles.

  19. Formulation of an explicit-multiple-time-step time integration method for use in a global primitive equation grid model

    NASA Technical Reports Server (NTRS)

    Chao, W. C.

    1982-01-01

    With appropriate modifications, a recently proposed explicit-multiple-time-step scheme (EMTSS) is incorporated into the UCLA model. In this scheme, the linearized terms in the governing equations that generate the gravity waves are split into different vertical modes. Each mode is integrated with an optimal time step, and at periodic intervals these modes are recombined. The other terms are integrated with a time step dictated by the CFL condition for low-frequency waves. This large time step requires a special modification of the advective terms in the polar region to maintain stability. Test runs for 72 h show that EMTSS is a stable, efficient and accurate scheme.

  20. Recent Enhancements To The FUN3D Flow Solver For Moving-Mesh Applications

    NASA Technical Reports Server (NTRS)

    Biedron, Robert T,; Thomas, James L.

    2009-01-01

    An unsteady Reynolds-averaged Navier-Stokes solver for unstructured grids has been extended to handle general mesh movement involving rigid, deforming, and overset meshes. Mesh deformation is achieved through analogy to elastic media by solving the linear elasticity equations. A general method for specifying the motion of moving bodies within the mesh has been implemented that allows for inherited motion through parent-child relationships, enabling simulations involving multiple moving bodies. Several example calculations are shown to illustrate the range of potential applications. For problems in which an isolated body is rotating with a fixed rate, a noninertial reference-frame formulation is available. An example calculation for a tilt-wing rotor is used to demonstrate that the time-dependent moving grid and noninertial formulations produce the same results in the limit of zero time-step size.

  1. Analytical derivation: An epistemic game for solving mathematically based physics problems

    NASA Astrophysics Data System (ADS)

    Bajracharya, Rabindra R.; Thompson, John R.

    2016-06-01

    Problem solving, which often involves multiple steps, is an integral part of physics learning and teaching. Using the perspective of the epistemic game, we documented a specific game that is commonly pursued by students while solving mathematically based physics problems: the analytical derivation game. This game involves deriving an equation through symbolic manipulations and routine mathematical operations, usually without any physical interpretation of the processes. This game often creates cognitive obstacles in students, preventing them from using alternative resources or better approaches during problem solving. We conducted hour-long, semi-structured, individual interviews with fourteen introductory physics students. Students were asked to solve four "pseudophysics" problems containing algebraic and graphical representations. The problems required the application of the fundamental theorem of calculus (FTC), which is one of the most frequently used mathematical concepts in physics problem solving. We show that the analytical derivation game is necessary, but not sufficient, to solve mathematically based physics problems, specifically those involving graphical representations.

  2. Mechanisms and time-resolved dynamics for trihydrogen cation (H 3 +) formation from organic molecules in strong laser fields

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

    Ekanayake, Nagitha; Nairat, Muath; Kaderiya, Balram

    Strong-field laser-matter interactions often lead to exotic chemical reactions. Trihydrogen cation formation from organic molecules is one such case that requires multiple bonds to break and form. Here, we present evidence for the existence of two different reaction pathways for H 3 + formation from organic molecules irradiated by a strong-field laser. Assignment of the two pathways was accomplished through analysis of femtosecond time-resolved strong-field ionization and photoion-photoion coincidence measurements carried out on methanol isotopomers, ethylene glycol, and acetone. Ab initio molecular dynamics simulations suggest the formation occurs via two steps: the initial formation of a neutral hydrogen molecule, followedmore » by the abstraction of a proton from the remaining CHOH 2+ fragment by the roaming H 2 molecule. This reaction has similarities to the H 2+H 2 + mechanism leading to formation of H 3 + in the universe. These exotic chemical reaction mechanisms, involving roaming H 2 molecules, are found to occur in the ~100 fs timescale. Roaming molecule reactions may help to explain unlikely chemical processes, involving dissociation and formation of multiple chemical bonds, occurring under strong laser fields.« less

  3. Mechanisms and time-resolved dynamics for trihydrogen cation (H 3 +) formation from organic molecules in strong laser fields

    DOE PAGES

    Ekanayake, Nagitha; Nairat, Muath; Kaderiya, Balram; ...

    2017-07-05

    Strong-field laser-matter interactions often lead to exotic chemical reactions. Trihydrogen cation formation from organic molecules is one such case that requires multiple bonds to break and form. Here, we present evidence for the existence of two different reaction pathways for H 3 + formation from organic molecules irradiated by a strong-field laser. Assignment of the two pathways was accomplished through analysis of femtosecond time-resolved strong-field ionization and photoion-photoion coincidence measurements carried out on methanol isotopomers, ethylene glycol, and acetone. Ab initio molecular dynamics simulations suggest the formation occurs via two steps: the initial formation of a neutral hydrogen molecule, followedmore » by the abstraction of a proton from the remaining CHOH 2+ fragment by the roaming H 2 molecule. This reaction has similarities to the H 2+H 2 + mechanism leading to formation of H 3 + in the universe. These exotic chemical reaction mechanisms, involving roaming H 2 molecules, are found to occur in the ~100 fs timescale. Roaming molecule reactions may help to explain unlikely chemical processes, involving dissociation and formation of multiple chemical bonds, occurring under strong laser fields.« less

  4. Long range personalized cancer treatment strategies incorporating evolutionary dynamics.

    PubMed

    Yeang, Chen-Hsiang; Beckman, Robert A

    2016-10-22

    Current cancer precision medicine strategies match therapies to static consensus molecular properties of an individual's cancer, thus determining the next therapeutic maneuver. These strategies typically maintain a constant treatment while the cancer is not worsening. However, cancers feature complicated sub-clonal structure and dynamic evolution. We have recently shown, in a comprehensive simulation of two non-cross resistant therapies across a broad parameter space representing realistic tumors, that substantial improvement in cure rates and median survival can be obtained utilizing dynamic precision medicine strategies. These dynamic strategies explicitly consider intratumoral heterogeneity and evolutionary dynamics, including predicted future drug resistance states, and reevaluate optimal therapy every 45 days. However, the optimization is performed in single 45 day steps ("single-step optimization"). Herein we evaluate analogous strategies that think multiple therapeutic maneuvers ahead, considering potential outcomes at 5 steps ahead ("multi-step optimization") or 40 steps ahead ("adaptive long term optimization (ALTO)") when recommending the optimal therapy in each 45 day block, in simulations involving both 2 and 3 non-cross resistant therapies. We also evaluate an ALTO approach for situations where simultaneous combination therapy is not feasible ("Adaptive long term optimization: serial monotherapy only (ALTO-SMO)"). Simulations utilize populations of 764,000 and 1,700,000 virtual patients for 2 and 3 drug cases, respectively. Each virtual patient represents a unique clinical presentation including sizes of major and minor tumor subclones, growth rates, evolution rates, and drug sensitivities. While multi-step optimization and ALTO provide no significant average survival benefit, cure rates are significantly increased by ALTO. Furthermore, in the subset of individual virtual patients demonstrating clinically significant difference in outcome between approaches, by far the majority show an advantage of multi-step or ALTO over single-step optimization. ALTO-SMO delivers cure rates superior or equal to those of single- or multi-step optimization, in 2 and 3 drug cases respectively. In selected virtual patients incurable by dynamic precision medicine using single-step optimization, analogous strategies that "think ahead" can deliver long-term survival and cure without any disadvantage for non-responders. When therapies require dose reduction in combination (due to toxicity), optimal strategies feature complex patterns involving rapidly interleaved pulses of combinations and high dose monotherapy. This article was reviewed by Wendy Cornell, Marek Kimmel, and Andrzej Swierniak. Wendy Cornell and Andrzej Swierniak are external reviewers (not members of the Biology Direct editorial board). Andrzej Swierniak was nominated by Marek Kimmel.

  5. Determining geometric error model parameters of a terrestrial laser scanner through Two-face, Length-consistency, and Network methods

    PubMed Central

    Wang, Ling; Muralikrishnan, Bala; Rachakonda, Prem; Sawyer, Daniel

    2017-01-01

    Terrestrial laser scanners (TLS) are increasingly used in large-scale manufacturing and assembly where required measurement uncertainties are on the order of few tenths of a millimeter or smaller. In order to meet these stringent requirements, systematic errors within a TLS are compensated in-situ through self-calibration. In the Network method of self-calibration, numerous targets distributed in the work-volume are measured from multiple locations with the TLS to determine parameters of the TLS error model. In this paper, we propose two new self-calibration methods, the Two-face method and the Length-consistency method. The Length-consistency method is proposed as a more efficient way of realizing the Network method where the length between any pair of targets from multiple TLS positions are compared to determine TLS model parameters. The Two-face method is a two-step process. In the first step, many model parameters are determined directly from the difference between front-face and back-face measurements of targets distributed in the work volume. In the second step, all remaining model parameters are determined through the Length-consistency method. We compare the Two-face method, the Length-consistency method, and the Network method in terms of the uncertainties in the model parameters, and demonstrate the validity of our techniques using a calibrated scale bar and front-face back-face target measurements. The clear advantage of these self-calibration methods is that a reference instrument or calibrated artifacts are not required, thus significantly lowering the cost involved in the calibration process. PMID:28890607

  6. Method of upgrading oils containing hydroxyaromatic hydrocarbon compounds to highly aromatic gasoline

    DOEpatents

    Baker, Eddie G.; Elliott, Douglas C.

    1993-01-01

    The present invention is a multi-stepped method of converting an oil which is produced by various biomass and coal conversion processes and contains primarily single and multiple ring hydroxyaromatic hydrocarbon compounds to highly aromatic gasoline. The single and multiple ring hydroxyaromatic hydrocarbon compounds in a raw oil material are first deoxygenated to produce a deoxygenated oil material containing single and multiple ring aromatic compounds. Then, water is removed from the deoxygenated oil material. The next step is distillation to remove the single ring aromatic compouns as gasoline. In the third step, the multiple ring aromatics remaining in the deoxygenated oil material are cracked in the presence of hydrogen to produce a cracked oil material containing single ring aromatic compounds. Finally, the cracked oil material is then distilled to remove the single ring aromatics as gasoline.

  7. Method of upgrading oils containing hydroxyaromatic hydrocarbon compounds to highly aromatic gasoline

    DOEpatents

    Baker, E.G.; Elliott, D.C.

    1993-01-19

    The present invention is a multi-stepped method of converting an oil which is produced by various biomass and coal conversion processes and contains primarily single and multiple ring hydroxyaromatic hydrocarbon compounds to highly aromatic gasoline. The single and multiple ring hydroxyaromatic hydrocarbon compounds in a raw oil material are first deoxygenated to produce a deoxygenated oil material containing single and multiple ring aromatic compounds. Then, water is removed from the deoxygenated oil material. The next step is distillation to remove the single ring aromatic compounds as gasoline. In the third step, the multiple ring aromatics remaining in the deoxygenated oil material are cracked in the presence of hydrogen to produce a cracked oil material containing single ring aromatic compounds. Finally, the cracked oil material is then distilled to remove the single ring aromatics as gasoline.

  8. Dynamic changes in cortical tensions in multiple cell types during germband retraction

    NASA Astrophysics Data System (ADS)

    Hutson, M. Shane; Lacy, Monica E.; McCleery, W. Tyler

    The process of germband retraction in Drosophila embryogenesis involves the coordinated mechanics of both germband and amnioserosa cells. These two tissues simultaneously and coordinately uncurl from their interlocking U-like shapes. As tissue-level retraction proceeds, individual cells change shape in stereotypical ways. Using time-lapse confocal images, analysis of dynamic cellular triple-junction angles, and whole-embryo finite-element models, we have quantified dynamic changes in cortical tensions - including their anisotropy - in both germband and amnioserosa cells. We find a strong transition midway through the two-hour course of retraction at which point tensions and anisotropies undergo a near step change. These changes take place among amnioserosa cells, in multiple segments of the germband, and at the interface between these two tissues. Research was supported by NIH Grant Numbers 1R01GM099107 and 1R21AR068933.

  9. A Multicriteria Decision Making Approach for Estimating the Number of Clusters in a Data Set

    PubMed Central

    Peng, Yi; Zhang, Yong; Kou, Gang; Shi, Yong

    2012-01-01

    Determining the number of clusters in a data set is an essential yet difficult step in cluster analysis. Since this task involves more than one criterion, it can be modeled as a multiple criteria decision making (MCDM) problem. This paper proposes a multiple criteria decision making (MCDM)-based approach to estimate the number of clusters for a given data set. In this approach, MCDM methods consider different numbers of clusters as alternatives and the outputs of any clustering algorithm on validity measures as criteria. The proposed method is examined by an experimental study using three MCDM methods, the well-known clustering algorithm–k-means, ten relative measures, and fifteen public-domain UCI machine learning data sets. The results show that MCDM methods work fairly well in estimating the number of clusters in the data and outperform the ten relative measures considered in the study. PMID:22870181

  10. Capacity for visual features in mental rotation

    PubMed Central

    Xu, Yangqing; Franconeri, Steven L.

    2015-01-01

    Although mental rotation is a core component of scientific reasoning, we still know little about its underlying mechanism. For instance - how much visual information can we rotate at once? Participants rotated a simple multi-part shape, requiring them to maintain attachments between features and moving parts. The capacity of this aspect of mental rotation was strikingly low – only one feature could remain attached to one part. Behavioral and eyetracking data showed that this single feature remained ‘glued’ via a singular focus of attention, typically on the object’s top. We argue that the architecture of the human visual system is not suited for keeping multiple features attached to multiple parts during mental rotation. Such measurement of the capacity limits may prove to be a critical step in dissecting the suite of visuospatial tools involved in mental rotation, leading to insights for improvement of pedagogy in science education contexts. PMID:26174781

  11. Obesity resistance and multiple mechanisms of triglyceride synthesis in mice lacking Dgat.

    PubMed

    Smith, S J; Cases, S; Jensen, D R; Chen, H C; Sande, E; Tow, B; Sanan, D A; Raber, J; Eckel, R H; Farese, R V

    2000-05-01

    Triglycerides (or triacylglycerols) represent the major form of stored energy in eukaryotes. Triglyceride synthesis has been assumed to occur primarily through acyl CoA:diacylglycerol transferase (Dgat), a microsomal enzyme that catalyses the final and only committed step in the glycerol phosphate pathway. Therefore, Dgat has been considered necessary for adipose tissue formation and essential for survival. Here we show that Dgat-deficient (Dgat-/-) mice are viable and can still synthesize triglycerides. Moreover, these mice are lean and resistant to diet-induced obesity. The obesity resistance involves increased energy expenditure and increased activity. Dgat deficiency also alters triglyceride metabolism in other tissues, including the mammary gland, where lactation is defective in Dgat-/- females. Our findings indicate that multiple mechanisms exist for triglyceride synthesis and suggest that the selective inhibition of Dgat-mediated triglyceride synthesis may be useful for treating obesity.

  12. Capacity for Visual Features in Mental Rotation.

    PubMed

    Xu, Yangqing; Franconeri, Steven L

    2015-08-01

    Although mental rotation is a core component of scientific reasoning, little is known about its underlying mechanisms. For instance, how much visual information can someone rotate at once? We asked participants to rotate a simple multipart shape, requiring them to maintain attachments between features and moving parts. The capacity of this aspect of mental rotation was strikingly low: Only one feature could remain attached to one part. Behavioral and eye-tracking data showed that this single feature remained "glued" via a singular focus of attention, typically on the object's top. We argue that the architecture of the human visual system is not suited for keeping multiple features attached to multiple parts during mental rotation. Such measurement of capacity limits may prove to be a critical step in dissecting the suite of visuospatial tools involved in mental rotation, leading to insights for improvement of pedagogy in science-education contexts. © The Author(s) 2015.

  13. Methods for understanding super-efficient data envelopment analysis results with an application to hospital inpatient surgery.

    PubMed

    O'Neill, Liam; Dexter, Franklin

    2005-11-01

    We compare two techniques for increasing the transparency and face validity of Data Envelopment Analysis (DEA) results for managers at a single decision-making unit: multifactor efficiency (MFE) and non-radial super-efficiency (NRSE). Both methods incorporate the slack values from the super-efficient DEA model to provide a more robust performance measure than radial super-efficiency scores. MFE and NRSE are equivalent for unique optimal solutions and a single output. MFE incorporates the slack values from multiple output variables, whereas NRSE does not. MFE can be more transparent to managers since it involves no additional optimization steps beyond the DEA, whereas NRSE requires several. We compare results for operating room managers at an Iowa hospital evaluating its growth potential for multiple surgical specialties. In addition, we address the problem of upward bias of the slack values of the super-efficient DEA model.

  14. A comparison of African American and Caucasian stimulant users in 12-step facilitation treatment

    PubMed Central

    Peavy, K. Michelle; Garrett, Sharon; Doyle, Suzanne; Donovan, Dennis

    2017-01-01

    Engagement in 12-step meetings and activities has been shown to be a powerful aid to recovery from substance use disorders. However, only limited attention has been given to ethnic and racial differences in attitudes toward 12-step and involvement. This study utilized data from a large multisite trial testing the effectiveness of a 12-step facilitation therapy with stimulant-dependent treatment seekers. We compared baseline differences and treatment outcomes between African American and Caucasian participants. A select few baseline differences were found (i.e., African Americans reported higher levels of spirituality than Caucasians; African American participants indicated more perceived benefits of 12-step involvement; Caucasians were more likely to endorse future involvement in 12-step). There were no outcome differences (e.g., substance use outcomes, 12-step meeting attendance). The tested intervention produced similar outcomes for both groups, indicating that it may be useful across racial categories. PMID:27294812

  15. A comparison of African American and Caucasian stimulant users in 12-step facilitation treatment.

    PubMed

    Peavy, K Michelle; Garrett, Sharon; Doyle, Suzanne; Donovan, Dennis

    2017-01-01

    Engagement in 12-step meetings and activities has been shown to be a powerful aid to recovery from substance use disorders. However, only limited attention has been given to ethnic and racial differences in attitudes toward 12-step and involvement. This study utilized data from a large multisite trial testing the effectiveness of a 12-step facilitation therapy with stimulant-dependent treatment seekers. We compared baseline differences and treatment outcomes between African American and Caucasian participants. A select few baseline differences were found (i.e., African Americans reported higher levels of spirituality than Caucasians; African American participants indicated more perceived benefits of 12-step involvement; Caucasians were more likely to endorse future involvement in 12-step). There were no outcome differences (e.g., substance use outcomes, 12-step meeting attendance). The tested intervention produced similar outcomes for both groups, indicating that it may be useful across racial categories.

  16. Synthesis of phenanthridinones from N-methoxybenzamides and arenes by multiple palladium-catalyzed C-H activation steps at room temperature.

    PubMed

    Karthikeyan, Jaganathan; Cheng, Chien-Hong

    2011-10-10

    Many steps make light work: substituted phenanthridinones can be obtained with high regioselectivity and in very good yields by palladium-catalyzed cyclization reactions of N-methoxybenzamides with arenes. The reaction proceeds through multiple oxidative C-H activation and C-C/C-N formation steps in one pot at room temperature, and thus provides a simple method for generating bioactive phenanthridinones. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Using Multiple-Stimulus without Replacement Preference Assessments to Increase Student Engagement and Performance

    ERIC Educational Resources Information Center

    Weaver, Adam D.; McKevitt, Brian C.; Farris, Allie M.

    2017-01-01

    Multiple-stimulus without replacement preference assessment is a research-based method for identifying appropriate rewards for students with emotional and behavioral disorders. This article presents a brief history of how this technology evolved and describes a step-by-step approach for conducting the procedure. A discussion of necessary materials…

  18. Validity of the Instrumented Push and Release Test to Quantify Postural Responses in Persons With Multiple Sclerosis.

    PubMed

    El-Gohary, Mahmoud; Peterson, Daniel; Gera, Geetanjali; Horak, Fay B; Huisinga, Jessie M

    2017-07-01

    To test the validity of wearable inertial sensors to provide objective measures of postural stepping responses to the push and release clinical test in people with multiple sclerosis. Cross-sectional study. University medical center balance disorder laboratory. Total sample N=73; persons with multiple sclerosis (PwMS) n=52; healthy controls n=21. Stepping latency, time and number of steps required to reach stability, and initial step length were calculated using 3 inertial measurement units placed on participants' lumbar spine and feet. Correlations between inertial sensor measures and measures obtained from the laboratory-based systems were moderate to strong and statistically significant for all variables: time to release (r=.992), latency (r=.655), time to stability (r=.847), time of first heel strike (r=.665), number of steps (r=.825), and first step length (r=.592). Compared with healthy controls, PwMS demonstrated a longer time to stability and required a larger number of steps to reach stability. The instrumented push and release test is a valid measure of postural responses in PwMS and could be used as a clinical outcome measures for patient care decisions or for clinical trials aimed at improving postural control in PwMS. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  19. Systematic procedure for designing processes with multiple environmental objectives.

    PubMed

    Kim, Ki-Joo; Smith, Raymond L

    2005-04-01

    Evaluation of multiple objectives is very important in designing environmentally benign processes. It requires a systematic procedure for solving multiobjective decision-making problems due to the complex nature of the problems, the need for complex assessments, and the complicated analysis of multidimensional results. In this paper, a novel systematic procedure is presented for designing processes with multiple environmental objectives. This procedure has four steps: initialization, screening, evaluation, and visualization. The first two steps are used for systematic problem formulation based on mass and energy estimation and order of magnitude analysis. In the third step, an efficient parallel multiobjective steady-state genetic algorithm is applied to design environmentally benign and economically viable processes and to provide more accurate and uniform Pareto optimal solutions. In the last step a new visualization technique for illustrating multiple objectives and their design parameters on the same diagram is developed. Through these integrated steps the decision-maker can easily determine design alternatives with respect to his or her preferences. Most importantly, this technique is independent of the number of objectives and design parameters. As a case study, acetic acid recovery from aqueous waste mixtures is investigated by minimizing eight potential environmental impacts and maximizing total profit. After applying the systematic procedure, the most preferred design alternatives and their design parameters are easily identified.

  20. Why pleiotropic interventions are needed for Alzheimer's disease.

    PubMed

    Frautschy, Sally A; Cole, Greg M

    2010-06-01

    Alzheimer's disease (AD) involves a complex pathological cascade thought to be initially triggered by the accumulation of beta-amyloid (Abeta) peptide aggregates or aberrant amyloid precursor protein (APP) processing. Much is known of the factors initiating the disease process decades prior to the onset of cognitive deficits, but an unclear understanding of events immediately preceding and precipitating cognitive decline is a major factor limiting the rapid development of adequate prevention and treatment strategies. Multiple pathways are known to contribute to cognitive deficits by disruption of neuronal signal transduction pathways involved in memory. These pathways are altered by aberrant signaling, inflammation, oxidative damage, tau pathology, neuron loss, and synapse loss. We need to develop stage-specific interventions that not only block causal events in pathogenesis (aberrant tau phosphorylation, Abeta production and accumulation, and oxidative damage), but also address damage from these pathways that will not be reversed by targeting prodromal pathways. This approach would not only focus on blocking early events in pathogenesis, but also adequately correct for loss of synapses, substrates for neuroprotective pathways (e.g., docosahexaenoic acid), defects in energy metabolism, and adverse consequences of inappropriate compensatory responses (aberrant sprouting). Monotherapy targeting early single steps in this complicated cascade may explain disappointments in trials with agents inhibiting production, clearance, or aggregation of the initiating Abeta peptide or its aggregates. Both plaque and tangle pathogenesis have already reached AD levels in the more vulnerable brain regions during the "prodromal" period prior to conversion to "mild cognitive impairment (MCI)." Furthermore, many of the pathological events are no longer proceeding in series, but are going on in parallel. By the MCI stage, we stand a greater chance of success by considering pleiotropic drugs or cocktails that can independently limit the parallel steps of the AD cascade at all stages, but that do not completely inhibit the constitutive normal functions of these pathways. Based on this hypothesis, efforts in our laboratories have focused on the pleiotropic activities of omega-3 fatty acids and the anti-inflammatory, antioxidant, and anti-amyloid activity of curcumin in multiple models that cover many steps of the AD pathogenic cascade (Cole and Frautschy, Alzheimers Dement 2:284-286, 2006).

  1. A Selection Method That Succeeds!

    ERIC Educational Resources Information Center

    Weitman, Catheryn J.

    Provided a structural selection method is carried out, it is possible to find quality early childhood personnel. The hiring process involves five definite steps, each of which establishes a base for the next. A needs assessment formulating basic minimal qualifications is the first step. The second step involves review of current job descriptions…

  2. Blocks in the asymmetric simple exclusion process

    NASA Astrophysics Data System (ADS)

    Tracy, Craig A.; Widom, Harold

    2017-12-01

    In earlier work, the authors obtained formulas for the probability in the asymmetric simple exclusion process that the mth particle from the left is at site x at time t. They were expressed in general as sums of multiple integrals and, for the case of step initial condition, as an integral involving a Fredholm determinant. In the present work, these results are generalized to the case where the mth particle is the left-most one in a contiguous block of L particles. The earlier work depended in a crucial way on two combinatorial identities, and the present work begins with a generalization of these identities to general L.

  3. Ligand Binding: Molecular Mechanics Calculation of the Streptavidin-Biotin Rupture Force

    NASA Astrophysics Data System (ADS)

    Grubmuller, Helmut; Heymann, Berthold; Tavan, Paul

    1996-02-01

    The force required to rupture the streptavidin-biotin complex was calculated here by computer simulations. The computed force agrees well with that obtained by recent single molecule atomic force microscope experiments. These simulations suggest a detailed multiple-pathway rupture mechanism involving five major unbinding steps. Binding forces and specificity are attributed to a hydrogen bond network between the biotin ligand and residues within the binding pocket of streptavidin. During rupture, additional water bridges substantially enhance the stability of the complex and even dominate the binding inter-actions. In contrast, steric restraints do not appear to contribute to the binding forces, although conformational motions were observed.

  4. Quantitative Glycomics Strategies*

    PubMed Central

    Mechref, Yehia; Hu, Yunli; Desantos-Garcia, Janie L.; Hussein, Ahmed; Tang, Haixu

    2013-01-01

    The correlations between protein glycosylation and many biological processes and diseases are increasing the demand for quantitative glycomics strategies enabling sensitive monitoring of changes in the abundance and structure of glycans. This is currently attained through multiple strategies employing several analytical techniques such as capillary electrophoresis, liquid chromatography, and mass spectrometry. The detection and quantification of glycans often involve labeling with ionic and/or hydrophobic reagents. This step is needed in order to enhance detection in spectroscopic and mass spectrometric measurements. Recently, labeling with stable isotopic reagents has also been presented as a very viable strategy enabling relative quantitation. The different strategies available for reliable and sensitive quantitative glycomics are herein described and discussed. PMID:23325767

  5. Monitoring the condition of natural resources in US national parks.

    PubMed

    Fancy, S G; Gross, J E; Carter, S L

    2009-04-01

    The National Park Service has developed a long-term ecological monitoring program for 32 ecoregional networks containing more than 270 parks with significant natural resources. The monitoring program assists park managers in developing a broad-based understanding of the status and trends of park resources as a basis for making decisions and working with other agencies and the public for the long-term protection of park ecosystems. We found that the basic steps involved in planning and designing a long-term ecological monitoring program were the same for a range of ecological systems including coral reefs, deserts, arctic tundra, prairie grasslands, caves, and tropical rainforests. These steps involve (1) clearly defining goals and objectives, (2) compiling and summarizing existing information, (3) developing conceptual models, (4) prioritizing and selecting indicators, (5) developing an overall sampling design, (6) developing monitoring protocols, and (7) establishing data management, analysis, and reporting procedures. The broad-based, scientifically sound information obtained through this systems-based monitoring program will have multiple applications for management decision-making, research, education, and promoting public understanding of park resources. When combined with an effective education program, monitoring results can contribute not only to park issues, but also to larger quality-of-life issues that affect surrounding communities and can contribute significantly to the environmental health of the nation.

  6. Three children with autism spectrum disorder learn to perform a three-step communication sequence using an iPad®-based speech-generating device.

    PubMed

    Waddington, Hannah; Sigafoos, Jeff; Lancioni, Giulio E; O'Reilly, Mark F; van der Meer, Larah; Carnett, Amarie; Stevens, Michelle; Roche, Laura; Hodis, Flaviu; Green, Vanessa A; Sutherland, Dean; Lang, Russell; Marschik, Peter B

    2014-12-01

    Many children with autism spectrum disorder (ASD) have limited or absent speech and might therefore benefit from learning to use a speech-generating device (SGD). The purpose of this study was to evaluate a procedure aimed at teaching three children with ASD to use an iPad(®)-based SGD to make a general request for access to toys, then make a specific request for one of two toys, and then communicate a thank-you response after receiving the requested toy. A multiple-baseline across participants design was used to determine whether systematic instruction involving least-to-most-prompting, time delay, error correction, and reinforcement was effective in teaching the three children to engage in this requesting and social communication sequence. Generalization and follow-up probes were conducted for two of the three participants. With intervention, all three children showed improvement in performing the communication sequence. This improvement was maintained with an unfamiliar communication partner and during the follow-up sessions. With systematic instruction, children with ASD and severe communication impairment can learn to use an iPad-based SGD to complete multi-step communication sequences that involve requesting and social communication functions. Copyright © 2014 ISDN. Published by Elsevier Ltd. All rights reserved.

  7. Characterizing the Joint Effect of Diverse Test-Statistic Correlation Structures and Effect Size on False Discovery Rates in a Multiple-Comparison Study of Many Outcome Measures

    NASA Technical Reports Server (NTRS)

    Feiveson, Alan H.; Ploutz-Snyder, Robert; Fiedler, James

    2011-01-01

    In their 2009 Annals of Statistics paper, Gavrilov, Benjamini, and Sarkar report the results of a simulation assessing the robustness of their adaptive step-down procedure (GBS) for controlling the false discovery rate (FDR) when normally distributed test statistics are serially correlated. In this study we extend the investigation to the case of multiple comparisons involving correlated non-central t-statistics, in particular when several treatments or time periods are being compared to a control in a repeated-measures design with many dependent outcome measures. In addition, we consider several dependence structures other than serial correlation and illustrate how the FDR depends on the interaction between effect size and the type of correlation structure as indexed by Foerstner s distance metric from an identity. The relationship between the correlation matrix R of the original dependent variables and R, the correlation matrix of associated t-statistics is also studied. In general R depends not only on R, but also on sample size and the signed effect sizes for the multiple comparisons.

  8. Implementing Immediate Postpartum Long-Acting Reversible Contraception Programs.

    PubMed

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

    2017-01-01

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

  9. Using the Knowledge, Process, Practice (KPP) model for driving the design and development of online postgraduate medical education.

    PubMed

    Shaw, Tim; Barnet, Stewart; Mcgregor, Deborah; Avery, Jennifer

    2015-01-01

    Online learning is a primary delivery method for continuing health education programs. It is critical that programs have curricula objectives linked to educational models that support learning. Using a proven educational modelling process ensures that curricula objectives are met and a solid basis for learning and assessment is achieved. To develop an educational design model that produces an educationally sound program development plan for use by anyone involved in online course development. We have described the development of a generic educational model designed for continuing health education programs. The Knowledge, Process, Practice (KPP) model is founded on recognised educational theory and online education practice. This paper presents a step-by-step guide on using this model for program development that encases reliable learning and evaluation. The model supports a three-step approach, KPP, based on learning outcomes and supporting appropriate assessment activities. It provides a program structure for online or blended learning that is explicit, educationally defensible, and supports multiple assessment points for health professionals. The KPP model is based on best practice educational design using a structure that can be adapted for a variety of online or flexibly delivered postgraduate medical education programs.

  10. Kinetic mechanism of human DNA ligase I reveals magnesium-dependent changes in the rate-limiting step that compromise ligation efficiency.

    PubMed

    Taylor, Mark R; Conrad, John A; Wahl, Daniel; O'Brien, Patrick J

    2011-07-01

    DNA ligase I (LIG1) catalyzes the ligation of single-strand breaks to complete DNA replication and repair. The energy of ATP is used to form a new phosphodiester bond in DNA via a reaction mechanism that involves three distinct chemical steps: enzyme adenylylation, adenylyl transfer to DNA, and nick sealing. We used steady state and pre-steady state kinetics to characterize the minimal mechanism for DNA ligation catalyzed by human LIG1. The ATP dependence of the reaction indicates that LIG1 requires multiple Mg(2+) ions for catalysis and that an essential Mg(2+) ion binds more tightly to ATP than to the enzyme. Further dissection of the magnesium ion dependence of individual reaction steps revealed that the affinity for Mg(2+) changes along the reaction coordinate. At saturating concentrations of ATP and Mg(2+) ions, the three chemical steps occur at similar rates, and the efficiency of ligation is high. However, under conditions of limiting Mg(2+), the nick-sealing step becomes rate-limiting, and the adenylylated DNA intermediate is prematurely released into solution. Subsequent adenylylation of enzyme prevents rebinding to the adenylylated DNA intermediate comprising an Achilles' heel of LIG1. These ligase-generated 5'-adenylylated nicks constitute persistent breaks that are a threat to genomic stability if they are not repaired. The kinetic and thermodynamic framework that we have determined for LIG1 provides a starting point for understanding the mechanism and specificity of mammalian DNA ligases.

  11. Voluntary stepping behavior under single- and dual-task conditions in chronic stroke survivors: A comparison between the involved and uninvolved legs.

    PubMed

    Melzer, Itshak; Goldring, Melissa; Melzer, Yehudit; Green, Elad; Tzedek, Irit

    2010-12-01

    If balance is lost, quick step execution can prevent falls. Research has shown that speed of voluntary stepping was able to predict future falls in old adults. The aim of the study was to investigate voluntary stepping behavior, as well as to compare timing and leg push-off force-time relation parameters of involved and uninvolved legs in stroke survivors during single- and dual-task conditions. We also aimed to compare timing and leg push-off force-time relation parameters between stroke survivors and healthy individuals in both task conditions. Ten stroke survivors performed a voluntary step execution test with their involved and uninvolved legs under two conditions: while focusing only on the stepping task and while a separate attention-demanding task was performed simultaneously. Temporal parameters related to the step time were measured including the duration of the step initiation phase, the preparatory phase, the swing phase, and the total step time. In addition, force-time parameters representing the push-off power during stepping were calculated from ground reaction data and compared with 10 healthy controls. The involved legs of stroke survivors had a significantly slower stepping time than uninvolved legs due to increased swing phase duration during both single- and dual-task conditions. For dual compared to single task, the stepping time increased significantly due to a significant increase in the duration of step initiation. In general, the force time parameters were significantly different in both legs of stroke survivors as compared to healthy controls, with no significant effect of dual compared with single-task conditions in both groups. The inability of stroke survivors to swing the involved leg quickly may be the most significant factor contributing to the large number of falls to the paretic side. The results suggest that stroke survivors were unable to rapidly produce muscle force in fast actions. This may be the mechanism of delayed execution of a fast step when balance is lost, thus increasing the likelihood of falls in stroke survivors. Copyright © 2010 Elsevier Ltd. All rights reserved.

  12. Regionally Adaptable Ground Motion Prediction Equation (GMPE) from Empirical Models of Fourier and Duration of Ground Motion

    NASA Astrophysics Data System (ADS)

    Bora, Sanjay; Scherbaum, Frank; Kuehn, Nicolas; Stafford, Peter; Edwards, Benjamin

    2016-04-01

    The current practice of deriving empirical ground motion prediction equations (GMPEs) involves using ground motions recorded at multiple sites. However, in applications like site-specific (e.g., critical facility) hazard ground motions obtained from the GMPEs are need to be adjusted/corrected to a particular site/site-condition under investigation. This study presents a complete framework for developing a response spectral GMPE, within which the issue of adjustment of ground motions is addressed in a manner consistent with the linear system framework. The present approach is a two-step process in which the first step consists of deriving two separate empirical models, one for Fourier amplitude spectra (FAS) and the other for a random vibration theory (RVT) optimized duration (Drvto) of ground motion. In the second step the two models are combined within the RVT framework to obtain full response spectral amplitudes. Additionally, the framework also involves a stochastic model based extrapolation of individual Fourier spectra to extend the useable frequency limit of the empirically derived FAS model. The stochastic model parameters were determined by inverting the Fourier spectral data using an approach similar to the one as described in Edwards and Faeh (2013). Comparison of median predicted response spectra from present approach with those from other regional GMPEs indicates that the present approach can also be used as a stand-alone model. The dataset used for the presented analysis is a subset of the recently compiled database RESORCE-2012 across Europe, the Middle East and the Mediterranean region.

  13. Planning for Sustainability of an Evidence-Based Mental Health Promotion Program in Canadian Elementary Schools.

    PubMed

    Leadbeater, Bonnie J; Gladstone, Emilie J; Sukhawathanakul, Paweena

    2015-09-01

    Substantial research illuminates many factors effecting the implementation of evidence-based mental health promotion programs in schools; however, research on how schools plan for sustaining their investments in these programs is limited. In this qualitative study, we elicited descriptions of opportunities and challenges for sustainability. We interviewed 24 individuals from schools involved in a longitudinal, qualitative research project that followed uptake and implementation of the evidence-based WITS Programs across 2 years (Leadbeater et al. 2012). WITS stands for Walk away, Ignore, Talk it out and Seek help and the online WITS Programs focus on preventing peer victimization ( www.witsprograms.ca ). Our findings suggest that sustainability planning in schools is not merely a next step following high quality implementation, but rather involves multiple ongoing processes that need to be anticipated and supported by school leadership and program champions and developers in order to realize investments in evidence-based programs.

  14. Dynamics of Leading-strand Lesion Skipping by the Replisome

    PubMed Central

    Yeeles, Joseph T.P.; Marians, Kenneth J.

    2013-01-01

    SUMMARY The E. coli replisome stalls transiently when it encounters a lesion in the leading-strand template, skipping over the damage by reinitiating replication at a new primer synthesized downstream by the primase. We report here that template unwinding and lagging-strand synthesis continue downstream of the lesion at a reduced rate after replisome stalling, that one replisome is capable of skipping multiple lesions, and that the rate limiting steps of replication restart involve the synthesis and activation of the new primer downstream. We also find little support for the concept that polymerase uncoupling, where extensive lagging-strand synthesis proceeds downstream in the absence of leading-strand synthesis, involves physical separation of the leading-strand polymerase from the replisome. Instead, our data indicate that extensive uncoupled replication likely results from a failure of the leading-strand polymerase still associated with the DNA helicase and the lagging-strand polymerase that are proceeding downstream to reinitiate synthesis. PMID:24268579

  15. Influence of phase inversion on the formation and stability of one-step multiple emulsions.

    PubMed

    Morais, Jacqueline M; Rocha-Filho, Pedro A; Burgess, Diane J

    2009-07-21

    A novel method of preparation of water-in-oil-in-micelle-containing water (W/O/W(m)) multiple emulsions using the one-step emulsification method is reported. These multiple emulsions were normal (not temporary) and stable over a 60 day test period. Previously, reported multiple emulsion by the one-step method were abnormal systems that formed at the inversion point of simple emulsion (where there is an incompatibility in the Ostwald and Bancroft theories, and typically these are O/W/O systems). Pseudoternary phase diagrams and bidimensional process-composition (phase inversion) maps were constructed to assist in process and composition optimization. The surfactants used were PEG40 hydrogenated castor oil and sorbitan oleate, and mineral and vegetables oils were investigated. Physicochemical characterization studies showed experimentally, for the first time, the significance of the ultralow surface tension point on multiple emulsion formation by one-step via phase inversion processes. Although the significance of ultralow surface tension has been speculated previously, to the best of our knowledge, this is the first experimental confirmation. The multiple emulsion system reported here was dependent not only upon the emulsification temperature, but also upon the component ratios, therefore both the emulsion phase inversion and the phase inversion temperature were considered to fully explain their formation. Accordingly, it is hypothesized that the formation of these normal multiple emulsions is not a result of a temporary incompatibility (at the inversion point) during simple emulsion preparation, as previously reported. Rather, these normal W/O/W(m) emulsions are a result of the simultaneous occurrence of catastrophic and transitional phase inversion processes. The formation of the primary emulsions (W/O) is in accordance with the Ostwald theory ,and the formation of the multiple emulsions (W/O/W(m)) is in agreement with the Bancroft theory.

  16. Multiple Neuropeptide-Coding Genes Involved in Planarian Pharynx Extension.

    PubMed

    Shimoyama, Seira; Inoue, Takeshi; Kashima, Makoto; Agata, Kiyokazu

    2016-06-01

    Planarian feeding behavior involves three steps: moving toward food, extending the pharynx from their planarian's ventral side after arriving at the food, and ingesting the food through the pharynx. Although pharynx extension is a remarkable behavior, it remains unknown what neuronal cell types are involved in its regulation. To identify neurons involved in regulating pharynx extension, we quantitatively analyzed pharynx extension and sought to identify these neurons by RNA interference (RNAi) and in situ hybridization. This assay, when performed using planarians with amputation of various body parts, clearly showed that the head portion is indispensable for inducing pharynx extension. We thus tested the effects of knockdown of brain neurons such as serotonergic, GABAergic, and dopaminergic neurons by RNAi, but did not observe any effects on pharynx extension behavior. However, animals with RNAi of the Prohormone Convertase 2 (PC2, a neuropeptide processing enzyme) gene did not perform the pharynx extension behavior, suggesting the possible involvement of neuropeptide(s in the regulation of pharynx extension. We screened 24 neuropeptide-coding genes, analyzed their functions by RNAi using the pharynx extension assay system, and identified at least five neuropeptide genes involved in pharynx extension. These was expressed in different cells or neurons, and some of them were expressed in the brain, suggesting complex regulation of planarian feeding behavior by the nervous system.

  17. PVT: An Efficient Computational Procedure to Speed up Next-generation Sequence Analysis

    PubMed Central

    2014-01-01

    Background High-throughput Next-Generation Sequencing (NGS) techniques are advancing genomics and molecular biology research. This technology generates substantially large data which puts up a major challenge to the scientists for an efficient, cost and time effective solution to analyse such data. Further, for the different types of NGS data, there are certain common challenging steps involved in analysing those data. Spliced alignment is one such fundamental step in NGS data analysis which is extremely computational intensive as well as time consuming. There exists serious problem even with the most widely used spliced alignment tools. TopHat is one such widely used spliced alignment tools which although supports multithreading, does not efficiently utilize computational resources in terms of CPU utilization and memory. Here we have introduced PVT (Pipelined Version of TopHat) where we take up a modular approach by breaking TopHat’s serial execution into a pipeline of multiple stages, thereby increasing the degree of parallelization and computational resource utilization. Thus we address the discrepancies in TopHat so as to analyze large NGS data efficiently. Results We analysed the SRA dataset (SRX026839 and SRX026838) consisting of single end reads and SRA data SRR1027730 consisting of paired-end reads. We used TopHat v2.0.8 to analyse these datasets and noted the CPU usage, memory footprint and execution time during spliced alignment. With this basic information, we designed PVT, a pipelined version of TopHat that removes the redundant computational steps during ‘spliced alignment’ and breaks the job into a pipeline of multiple stages (each comprising of different step(s)) to improve its resource utilization, thus reducing the execution time. Conclusions PVT provides an improvement over TopHat for spliced alignment of NGS data analysis. PVT thus resulted in the reduction of the execution time to ~23% for the single end read dataset. Further, PVT designed for paired end reads showed an improved performance of ~41% over TopHat (for the chosen data) with respect to execution time. Moreover we propose PVT-Cloud which implements PVT pipeline in cloud computing system. PMID:24894600

  18. PVT: an efficient computational procedure to speed up next-generation sequence analysis.

    PubMed

    Maji, Ranjan Kumar; Sarkar, Arijita; Khatua, Sunirmal; Dasgupta, Subhasis; Ghosh, Zhumur

    2014-06-04

    High-throughput Next-Generation Sequencing (NGS) techniques are advancing genomics and molecular biology research. This technology generates substantially large data which puts up a major challenge to the scientists for an efficient, cost and time effective solution to analyse such data. Further, for the different types of NGS data, there are certain common challenging steps involved in analysing those data. Spliced alignment is one such fundamental step in NGS data analysis which is extremely computational intensive as well as time consuming. There exists serious problem even with the most widely used spliced alignment tools. TopHat is one such widely used spliced alignment tools which although supports multithreading, does not efficiently utilize computational resources in terms of CPU utilization and memory. Here we have introduced PVT (Pipelined Version of TopHat) where we take up a modular approach by breaking TopHat's serial execution into a pipeline of multiple stages, thereby increasing the degree of parallelization and computational resource utilization. Thus we address the discrepancies in TopHat so as to analyze large NGS data efficiently. We analysed the SRA dataset (SRX026839 and SRX026838) consisting of single end reads and SRA data SRR1027730 consisting of paired-end reads. We used TopHat v2.0.8 to analyse these datasets and noted the CPU usage, memory footprint and execution time during spliced alignment. With this basic information, we designed PVT, a pipelined version of TopHat that removes the redundant computational steps during 'spliced alignment' and breaks the job into a pipeline of multiple stages (each comprising of different step(s)) to improve its resource utilization, thus reducing the execution time. PVT provides an improvement over TopHat for spliced alignment of NGS data analysis. PVT thus resulted in the reduction of the execution time to ~23% for the single end read dataset. Further, PVT designed for paired end reads showed an improved performance of ~41% over TopHat (for the chosen data) with respect to execution time. Moreover we propose PVT-Cloud which implements PVT pipeline in cloud computing system.

  19. Three-dimensional Aerographite-GaN hybrid networks: Single step fabrication of porous and mechanically flexible materials for multifunctional applications

    PubMed Central

    Schuchardt, Arnim; Braniste, Tudor; Mishra, Yogendra K.; Deng, Mao; Mecklenburg, Matthias; Stevens-Kalceff, Marion A.; Raevschi, Simion; Schulte, Karl; Kienle, Lorenz; Adelung, Rainer; Tiginyanu, Ion

    2015-01-01

    Three dimensional (3D) elastic hybrid networks built from interconnected nano- and microstructure building units, in the form of semiconducting-carbonaceous materials, are potential candidates for advanced technological applications. However, fabrication of these 3D hybrid networks by simple and versatile methods is a challenging task due to the involvement of complex and multiple synthesis processes. In this paper, we demonstrate the growth of Aerographite-GaN 3D hybrid networks using ultralight and extremely porous carbon based Aerographite material as templates by a single step hydride vapor phase epitaxy process. The GaN nano- and microstructures grow on the surface of Aerographite tubes and follow the network architecture of the Aerographite template without agglomeration. The synthesized 3D networks are integrated with the properties from both, i.e., nanoscale GaN structures and Aerographite in the form of flexible and semiconducting composites which could be exploited as next generation materials for electronic, photonic, and sensors applications. PMID:25744694

  20. Free-Energy Landscape of the Dissolution of Gibbsite at High pH

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

    Shen, Zhizhang; Kerisit, Sebastien N.; Stack, Andrew G.

    The individual elementary reactions involved in the dissolution of a solid into solution remain mostly speculative due to a lack of suitable, direct experimental probes. In this regard, we have applied atomistic simulations to map the free energy landscape of the dissolution of gibbsite from a step edge, as a model of metal hydroxide dissolution. The overall reaction combines kink site formation and kink site propagation. Two individual reactions were found to be rate-limiting for kink site formation, that is, the displacement of Al from a step site to a ledge adatom site and its detachment from ledge/terrace adatom sitesmore » into the solution. As a result, a pool of mobile and labile Al adsorbed species, or adatoms, exists before the release of Al into solution. Because of the quasi-hexagonal symmetry of gibbsite, kink site propagation can occur in multiple directions. Overall, the simulation results will enable the development of microscopic mechanistic models of metal oxide dissolution.« less

  1. Measurements of Gluconeogenesis and Glycogenolysis: A Methodological Review.

    PubMed

    Chung, Stephanie T; Chacko, Shaji K; Sunehag, Agneta L; Haymond, Morey W

    2015-12-01

    Gluconeogenesis is a complex metabolic process that involves multiple enzymatic steps regulated by myriad factors, including substrate concentrations, the redox state, activation and inhibition of specific enzyme steps, and hormonal modulation. At present, the most widely accepted technique to determine gluconeogenesis is by measuring the incorporation of deuterium from the body water pool into newly formed glucose. However, several techniques using radioactive and stable-labeled isotopes have been used to quantitate the contribution and regulation of gluconeogenesis in humans. Each method has its advantages, methodological assumptions, and set of propagated errors. In this review, we examine the strengths and weaknesses of the most commonly used stable isotopes methods to measure gluconeogenesis in vivo. We discuss the advantages and limitations of each method and summarize the applicability of these measurements in understanding normal and pathophysiological conditions. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  2. An Examination of Four Traditional School Physical Activity Models on Children's Step Counts and MVPA.

    PubMed

    Brusseau, Timothy A; Kulinna, Pamela H

    2015-03-01

    Schools have been identified as primary societal institutions for promoting children's physical activity (PA); however, limited evidence exists demonstrating which traditional school-based PA models maximize children's PA. The purpose of this study was to compare step counts and moderate-to-vigorous physical activity (MVPA) across 4 traditional school PA modules. Step count and MVPA data were collected on 5 consecutive school days from 298 children (Mage = 10.0 ± 0.6 years; 55% female) in Grade 5. PA was measured using the NL-1000 piezoelectric pedometer. The 4 models included (a) recess only, (b) multiple recesses, (c) recess and physical education (PE), and (d) multiple recesses and PE. Children accumulated the greatest PA on days that they had PE and multiple recess opportunities (5,242 ± 1,690 steps; 15.3 ± 8.8 min of MVPA). Children accumulated the least amount of PA on days with only 1 recess opportunity (3,312 ± 445 steps; 7.1 ± 2.3 min of MVPA). Across all models, children accumulated an additional 1,140 steps and 4.1 min of MVPA on PE days. It appears that PE is the most important school PA opportunity for maximizing children's PA. However, on days without PE, a 2nd recess can increase school PA by 20% (Δ = 850 steps; 3.8 min of MVPA).

  3. Estimating V0[subscript 2]max Using a Personalized Step Test

    ERIC Educational Resources Information Center

    Webb, Carrie; Vehrs, Pat R.; George, James D.; Hager, Ronald

    2014-01-01

    The purpose of this study was to develop a step test with a personalized step rate and step height to predict cardiorespiratory fitness in 80 college-aged males and females using the self-reported perceived functional ability scale and data collected during the step test. Multiple linear regression analysis yielded a model (R = 0.90, SEE = 3.43…

  4. An Improved Single-Step Cloning Strategy Simplifies the Agrobacterium tumefaciens-Mediated Transformation (ATMT)-Based Gene-Disruption Method for Verticillium dahliae.

    PubMed

    Wang, Sheng; Xing, Haiying; Hua, Chenlei; Guo, Hui-Shan; Zhang, Jie

    2016-06-01

    The soilborne fungal pathogen Verticillium dahliae infects a broad range of plant species to cause severe diseases. The availability of Verticillium genome sequences has provided opportunities for large-scale investigations of individual gene function in Verticillium strains using Agrobacterium tumefaciens-mediated transformation (ATMT)-based gene-disruption strategies. Traditional ATMT vectors require multiple cloning steps and elaborate characterization procedures to achieve successful gene replacement; thus, these vectors are not suitable for high-throughput ATMT-based gene deletion. Several advancements have been made that either involve simplification of the steps required for gene-deletion vector construction or increase the efficiency of the technique for rapid recombinant characterization. However, an ATMT binary vector that is both simple and efficient is still lacking. Here, we generated a USER-ATMT dual-selection (DS) binary vector, which combines both the advantages of the USER single-step cloning technique and the efficiency of the herpes simplex virus thymidine kinase negative-selection marker. Highly efficient deletion of three different genes in V. dahliae using the USER-ATMT-DS vector enabled verification that this newly-generated vector not only facilitates the cloning process but also simplifies the subsequent identification of fungal homologous recombinants. The results suggest that the USER-ATMT-DS vector is applicable for efficient gene deletion and suitable for large-scale gene deletion in V. dahliae.

  5. Keeping a Step Ahead: formative phase of a workplace intervention trial to prevent obesity.

    PubMed

    Zapka, Jane; Lemon, Stephenie C; Estabrook, Barbara B; Jolicoeur, Denise G

    2007-11-01

    Ecological interventions hold promise for promoting overweight and obesity prevention in worksites. Given the paucity of evaluative research in the hospital worksite setting, considerable formative work is required for successful implementation and evaluation. This paper describes the formative phases of Step Ahead, a site-randomized controlled trial of a multilevel intervention that promotes physical activity and healthy eating in six hospitals in central Massachusetts. The purpose of the formative research phase was to increase the feasibility, effectiveness, and likelihood of sustainability of the intervention. The Step Ahead ecological intervention approach targets change at the organization, interpersonal work environment, and individual levels. The intervention was developed using fundamental steps of intervention mapping and important tenets of participatory research. Formative research methods were used to engage leadership support and assistance and to develop an intervention plan that is both theoretically and practically grounded. This report uses observational data, program minutes and reports, and process tracking data. Leadership involvement (key informant interviews and advisory boards), employee focus groups and advisory boards, and quantitative environmental assessments cultivated participation and support. Determining multiple foci of change and designing measurable objectives and generic assessment tools to document progress are complex challenges encountered in planning phases. Multilevel trials in diverse organizations require flexibility and balance of theory application and practice-based perspectives to affect impact and outcome objectives. Formative research is an essential component.

  6. Clinical Importance of Steps Taken per Day among Persons with Multiple Sclerosis

    PubMed Central

    Motl, Robert W.; Pilutti, Lara A.; Learmonth, Yvonne C.; Goldman, Myla D.; Brown, Ted

    2013-01-01

    Background The number of steps taken per day (steps/day) provides a reliable and valid outcome of free-living walking behavior in persons with multiple sclerosis (MS). Objective This study examined the clinical meaningfulness of steps/day using the minimal clinically important difference (MCID) value across stages representing the developing impact of MS. Methods This study was a secondary analysis of de-identified data from 15 investigations totaling 786 persons with MS and 157 healthy controls. All participants provided demographic information and wore an accelerometer or pedometer during the waking hours of a 7-day period. Those with MS further provided real-life, health, and clinical information and completed the Multiple Sclerosis Walking Scale-12 (MSWS-12) and Patient Determined Disease Steps (PDDS) scale. MCID estimates were based on regression analyses and analysis of variance for between group differences. Results The mean MCID from self-report scales that capture subtle changes in ambulation (1-point change in PDSS scores and 10-point change in MSWS-12 scores) was 779 steps/day (14% of mean score for MS sample); the mean MCID for clinical/health outcomes (MS type, duration, weight status) was 1,455 steps/day (26% of mean score for MS sample); real-life anchors (unemployment, divorce, assistive device use) resulted in a mean MCID of 2,580 steps/day (45% of mean score for MS sample); and the MCID for the cumulative impact of MS (MS vs. control) was 2,747 steps/day (48% of mean score for MS sample). Conclusion The change in motion sensor output of ∼800 steps/day appears to represent a lower-bound estimate of clinically meaningful change in free-living walking behavior in interventions of MS. PMID:24023843

  7. Multiple Time-Step Dual-Hamiltonian Hybrid Molecular Dynamics — Monte Carlo Canonical Propagation Algorithm

    PubMed Central

    Weare, Jonathan; Dinner, Aaron R.; Roux, Benoît

    2016-01-01

    A multiple time-step integrator based on a dual Hamiltonian and a hybrid method combining molecular dynamics (MD) and Monte Carlo (MC) is proposed to sample systems in the canonical ensemble. The Dual Hamiltonian Multiple Time-Step (DHMTS) algorithm is based on two similar Hamiltonians: a computationally expensive one that serves as a reference and a computationally inexpensive one to which the workload is shifted. The central assumption is that the difference between the two Hamiltonians is slowly varying. Earlier work has shown that such dual Hamiltonian multiple time-step schemes effectively precondition nonlinear differential equations for dynamics by reformulating them into a recursive root finding problem that can be solved by propagating a correction term through an internal loop, analogous to RESPA. Of special interest in the present context, a hybrid MD-MC version of the DHMTS algorithm is introduced to enforce detailed balance via a Metropolis acceptance criterion and ensure consistency with the Boltzmann distribution. The Metropolis criterion suppresses the discretization errors normally associated with the propagation according to the computationally inexpensive Hamiltonian, treating the discretization error as an external work. Illustrative tests are carried out to demonstrate the effectiveness of the method. PMID:26918826

  8. Verification and Validation of Digitally Upgraded Control Rooms

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

    Boring, Ronald; Lau, Nathan

    2015-09-01

    As nuclear power plants undertake main control room modernization, a challenge is the lack of a clearly defined human factors process to follow. Verification and validation (V&V) as applied in the nuclear power community has tended to involve efforts such as integrated system validation, which comes at the tail end of the design stage. To fill in guidance gaps and create a step-by-step process for control room modernization, we have developed the Guideline for Operational Nuclear Usability and Knowledge Elicitation (GONUKE). This approach builds on best practices in the software industry, which prescribe an iterative user-centered approach featuring multiple cyclesmore » of design and evaluation. Nuclear regulatory guidance for control room design emphasizes summative evaluation—which occurs after the design is complete. In the GONUKE approach, evaluation is also performed at the formative stage of design—early in the design cycle using mockups and prototypes for evaluation. The evaluation may involve expert review (e.g., software heuristic evaluation at the formative stage and design verification against human factors standards like NUREG-0700 at the summative stage). The evaluation may also involve user testing (e.g., usability testing at the formative stage and integrated system validation at the summative stage). An additional, often overlooked component of evaluation is knowledge elicitation, which captures operator insights into the system. In this report we outline these evaluation types across design phases that support the overall modernization process. The objective is to provide industry-suitable guidance for steps to be taken in support of the design and evaluation of a new human-machine interface (HMI) in the control room. We suggest the value of early-stage V&V and highlight how this early-stage V&V can help improve the design process for control room modernization. We argue that there is a need to overcome two shortcomings of V&V in current practice—the propensity for late-stage V&V and the use of increasingly complex psychological assessment measures for V&V.« less

  9. Processing of zero-derived words in English: an fMRI investigation.

    PubMed

    Pliatsikas, Christos; Wheeldon, Linda; Lahiri, Aditi; Hansen, Peter C

    2014-01-01

    Derivational morphological processes allow us to create new words (e.g. punish (V) to noun (N) punishment) from base forms. The number of steps from the basic units to derived words often varies (e.g., nationalitybridge-V) i.e., zero-derivation (Aronoff, 1980). We compared the processing of one-step (soaking

  10. Collaborative Behavioral Management for Drug-Involved Parolees: Rationale and Design of the Step'n Out Study

    ERIC Educational Resources Information Center

    Friedmann, Peter D.; Katz, Elizabeth C.; Rhodes, Anne G.; Taxman, Faye S.; O'Connell, Daniel J.; Frisman, Linda K.; Burdon, William M.; Fletcher, Bennett W.; Litt, Mark D.; Clarke, Jennifer; Martin, Steven S.

    2008-01-01

    This article describes the rationale, study design, and implementation for the Step'n Out study of the Criminal Justice Drug Abuse Treatment Studies. Step'n Out tests the relative effectiveness of collaborative behavioral management of drug-involved parolees. Collaborative behavioral management integrates the roles of parole officers and treatment…

  11. Kinetic Mechanism of the Dechlorinating Flavin-dependent Monooxygenase HadA*

    PubMed Central

    Pimviriyakul, Panu; Thotsaporn, Kittisak; Sucharitakul, Jeerus; Chaiyen, Pimchai

    2017-01-01

    The accumulation of chlorophenols (CPs) in the environment, due to their wide use as agrochemicals, has become a serious environmental problem. These organic halides can be degraded by aerobic microorganisms, where the initial steps of various biodegradation pathways include an oxidative dechlorinating process in which chloride is replaced by a hydroxyl substituent. Harnessing these dechlorinating processes could provide an opportunity for environmental remediation, but detailed catalytic mechanisms for these enzymes are not yet known. To close this gap, we now report transient kinetics and product analysis of the dechlorinating flavin-dependent monooxygenase, HadA, from the aerobic organism Ralstonia pickettii DTP0602, identifying several mechanistic properties that differ from other enzymes in the same class. We first overexpressed and purified HadA to homogeneity. Analyses of the products from single and multiple turnover reactions demonstrated that HadA prefers 4-CP and 2-CP over CPs with multiple substituents. Stopped-flow and rapid-quench flow experiments of HadA with 4-CP show the involvement of specific intermediates (C4a-hydroperoxy-FAD and C4a-hydroxy-FAD) in the reaction, define rate constants and the order of substrate binding, and demonstrate that the hydroxylation step occurs prior to chloride elimination. The data also identify the non-productive and productive paths of the HadA reactions and demonstrate that product formation is the rate-limiting step. This is the first elucidation of the kinetic mechanism of a two-component flavin-dependent monooxygenase that can catalyze oxidative dechlorination of various CPs, and as such it will serve as the basis for future investigation of enzyme variants that will be useful for applications in detoxifying chemicals hazardous to human health. PMID:28159841

  12. A judicious multiple hypothesis tracker with interacting feature extraction

    NASA Astrophysics Data System (ADS)

    McAnanama, James G.; Kirubarajan, T.

    2009-05-01

    The multiple hypotheses tracker (mht) is recognized as an optimal tracking method due to the enumeration of all possible measurement-to-track associations, which does not involve any approximation in its original formulation. However, its practical implementation is limited by the NP-hard nature of this enumeration. As a result, a number of maintenance techniques such as pruning and merging have been proposed to bound the computational complexity. It is possible to improve the performance of a tracker, mht or not, using feature information (e.g., signal strength, size, type) in addition to kinematic data. However, in most tracking systems, the extraction of features from the raw sensor data is typically independent of the subsequent association and filtering stages. In this paper, a new approach, called the Judicious Multi Hypotheses Tracker (jmht), whereby there is an interaction between feature extraction and the mht, is presented. The measure of the quality of feature extraction is input into measurement-to-track association while the prediction step feeds back the parameters to be used in the next round of feature extraction. The motivation for this forward and backward interaction between feature extraction and tracking is to improve the performance in both steps. This approach allows for a more rational partitioning of the feature space and removes unlikely features from the assignment problem. Simulation results demonstrate the benefits of the proposed approach.

  13. Interactome analysis of the lymphocytic choriomeningitis virus nucleoprotein in infected cells reveals ATPase Na+/K+ transporting subunit Alpha 1 and prohibitin as host-cell factors involved in the life cycle of mammarenaviruses

    PubMed Central

    Iwasaki, Masaharu; Caì, Yíngyún; de la Torre, Juan C.

    2018-01-01

    Several mammalian arenaviruses (mammarenaviruses) cause hemorrhagic fevers in humans and pose serious public health concerns in their endemic regions. Additionally, mounting evidence indicates that the worldwide-distributed, prototypic mammarenavirus, lymphocytic choriomeningitis virus (LCMV), is a neglected human pathogen of clinical significance. Concerns about human-pathogenic mammarenaviruses are exacerbated by of the lack of licensed vaccines, and current anti-mammarenavirus therapy is limited to off-label use of ribavirin that is only partially effective. Detailed understanding of virus/host-cell interactions may facilitate the development of novel anti-mammarenavirus strategies by targeting components of the host-cell machinery that are required for efficient virus multiplication. Here we document the generation of a recombinant LCMV encoding a nucleoprotein (NP) containing an affinity tag (rLCMV/Strep-NP) and its use to capture the NP-interactome in infected cells. Our proteomic approach combined with genetics and pharmacological validation assays identified ATPase Na+/K+ transporting subunit alpha 1 (ATP1A1) and prohibitin (PHB) as pro-viral factors. Cell-based assays revealed that ATP1A1 and PHB are involved in different steps of the virus life cycle. Accordingly, we observed a synergistic inhibitory effect on LCMV multiplication with a combination of ATP1A1 and PHB inhibitors. We show that ATP1A1 inhibitors suppress multiplication of Lassa virus and Candid#1, a live-attenuated vaccine strain of Junín virus, suggesting that the requirement of ATP1A1 in virus multiplication is conserved among genetically distantly related mammarenaviruses. Our findings suggest that clinically approved inhibitors of ATP1A1, like digoxin, could be repurposed to treat infections by mammarenaviruses pathogenic for humans. PMID:29462184

  14. Long genes and genes with multiple splice variants are enriched in pathways linked to cancer and other multigenic diseases.

    PubMed

    Sahakyan, Aleksandr B; Balasubramanian, Shankar

    2016-03-12

    The role of random mutations and genetic errors in defining the etiology of cancer and other multigenic diseases has recently received much attention. With the view that complex genes should be particularly vulnerable to such events, here we explore the link between the simple properties of the human genes, such as transcript length, number of splice variants, exon/intron composition, and their involvement in the pathways linked to cancer and other multigenic diseases. We reveal a substantial enrichment of cancer pathways with long genes and genes that have multiple splice variants. Although the latter two factors are interdependent, we show that the overall gene length and splicing complexity increase in cancer pathways in a partially decoupled manner. Our systematic survey for the pathways enriched with top lengthy genes and with genes that have multiple splice variants reveal, along with cancer pathways, the pathways involved in various neuronal processes, cardiomyopathies and type II diabetes. We outline a correlation between the gene length and the number of somatic mutations. Our work is a step forward in the assessment of the role of simple gene characteristics in cancer and a wider range of multigenic diseases. We demonstrate a significant accumulation of long genes and genes with multiple splice variants in pathways of multigenic diseases that have already been associated with de novo mutations. Unlike the cancer pathways, we note that the pathways of neuronal processes, cardiomyopathies and type II diabetes contain genes long enough for topoisomerase-dependent gene expression to also be a potential contributing factor in the emergence of pathologies, should topoisomerases become impaired.

  15. Collaborative Behavioral Management for Drug-Involved Parolees: Rationale and Design of the Step'n Out Study

    PubMed Central

    FRIEDMANN, PETER D.; KATZ, ELIZABETH C.; RHODES, ANNE G.; TAXMAN, FAYE S.; O'CONNELL, DANIEL J.; FRISMAN, LINDA K.; BURDON, WILLIAM M.; FLETCHER, BENNETT W.; LITT, MARK D.; CLARKE, JENNIFER; MARTIN, STEVEN S.

    2009-01-01

    This article describes the rationale, study design, and implementation for the Step'n Out study of the Criminal Justice Drug Abuse Treatment Studies. Step'n Out tests the relative effectiveness of collaborative behavioral management of drug-involved parolees. Collaborative behavioral management integrates the roles of parole officers and treatment counselors to provide role induction counseling, contract for pro-social behavior, and deliver contingent reinforcement of behaviors consistent with treatment objectives. The Step'n Out study will randomize 450 drug-involved parolees to collaborative behavioral management or usual parole. Follow-up at 3-and 9-months will assess primary outcomes of rearrest, crime and drug use. If collaborative behavioral management is effective, its wider adoption could improve the outcomes of community reentry of drug-involved ex-offenders. PMID:19809591

  16. Empirically Examining the Risk of Intimate Partner Violence: The Revised Domestic Violence Screening Instrument (DVSI-R)

    PubMed Central

    Grant, Stephen R

    2006-01-01

    SYNOPSIS Objective This study extends recent research on assessing the risk of intimate partner violence by determining the concurrent and predictive validity of a revised version of the Domestic Violence Screening Instrument (DVSI-R) and whether evidence of such validity is sustained independent of perpetrator demographic characteristics and forms of intimate violence. The analyses highlight violent incidents involving multiple victims as an indicator of “severe” violence. Previous research did not address these issues. Methods Data were analyzed on 14,970 assessments conducted in the State of Connecticut from September 1, 2004 through May 2, 2005. Hierarchical regression and receiver operating characteristic analyses were used to address the objectives of this research. Results The empirical findings support the concurrent and predictive validity of the DVSI-R and show that it is robust in its applicability. The findings further show that incidents involving multiple victims are highly associated with DVSI-R risk scores and recidivistic violence. Conclusion Validating and demonstrating the robustness of a risk assessment instrument is only a first step in preventing violence involving intimate partners or others in family or family-like relationships. The challenge is to train professionals responsible for addressing the problem of such violence to link valid risk assessments to well-crafted strategies of supervision and treatment so that the victimized or other potential victims are protected and perpetrators are held accountable for their actions. PMID:16827441

  17. Determinants of 12-step group affiliation and moderators of the affiliation-abstinence relationship.

    PubMed

    Timko, Christine; Billow, Rachel; DeBenedetti, Anna

    2006-06-28

    This study examined characteristics of substance use disorder (SUD) outpatients at intake to treatment (N=345) that were associated with more 12-step group attendance and involvement, Steps worked, and acceptance of 12-step philosophy at a 6-month follow-up (N=281, 81.4%). Patient characteristics covered the domains of sociodemographics, SUD severity, personal functioning, and previous help received. Distinguishing baseline characteristics of patients who attended more 12-step group meetings during follow-up were being less-educated, more engaged in religious practices, and more extroverted and interpersonally competent, and having had more previous 12-step group exposure. These patient characteristics were generally similar to those associated with more 12-step meeting involvement and philosophy acceptance. More 12-step meeting attendance and involvement were related to abstinence at 6 months. Associations of attendance with abstinence were stronger among patients who were younger, white, less-educated, unstably employed, less religious, and less interpersonally skilled. These patients may have had fewer available social resources and so benefitted more from the fellowship and support for abstinence that 12-step group members often provide. We suggest methods by which treatment providers may encourage 12-step group affiliation among patients likely to benefit from it on substance use outcomes.

  18. Business Modeling to Implement an eHealth Portal for Infection Control: A Reflection on Co-Creation With Stakeholders.

    PubMed

    van Limburg, Maarten; Wentzel, Jobke; Sanderman, Robbert; van Gemert-Pijnen, Lisette

    2015-08-13

    It is acknowledged that the success and uptake of eHealth improve with the involvement of users and stakeholders to make technology reflect their needs. Involving stakeholders in implementation research is thus a crucial element in developing eHealth technology. Business modeling is an approach to guide implementation research for eHealth. Stakeholders are involved in business modeling by identifying relevant stakeholders, conducting value co-creation dialogs, and co-creating a business model. Because implementation activities are often underestimated as a crucial step while developing eHealth, comprehensive and applicable approaches geared toward business modeling in eHealth are scarce. This paper demonstrates the potential of several stakeholder-oriented analysis methods and their practical application was demonstrated using Infectionmanager as an example case. In this paper, we aim to demonstrate how business modeling, with the focus on stakeholder involvement, is used to co-create an eHealth implementation. We divided business modeling in 4 main research steps. As part of stakeholder identification, we performed literature scans, expert recommendations, and snowball sampling (Step 1). For stakeholder analyzes, we performed "basic stakeholder analysis," stakeholder salience, and ranking/analytic hierarchy process (Step 2). For value co-creation dialogs, we performed a process analysis and stakeholder interviews based on the business model canvas (Step 3). Finally, for business model generation, we combined all findings into the business model canvas (Step 4). Based on the applied methods, we synthesized a step-by-step guide for business modeling with stakeholder-oriented analysis methods that we consider suitable for implementing eHealth. The step-by-step guide for business modeling with stakeholder involvement enables eHealth researchers to apply a systematic and multidisciplinary, co-creative approach for implementing eHealth. Business modeling becomes an active part in the entire development process of eHealth and starts an early focus on implementation, in which stakeholders help to co-create the basis necessary for a satisfying success and uptake of the eHealth technology.

  19. Rational reduction of periodic propagators for off-period observations.

    PubMed

    Blanton, Wyndham B; Logan, John W; Pines, Alexander

    2004-02-01

    Many common solid-state nuclear magnetic resonance problems take advantage of the periodicity of the underlying Hamiltonian to simplify the computation of an observation. Most of the time-domain methods used, however, require the time step between observations to be some integer or reciprocal-integer multiple of the period, thereby restricting the observation bandwidth. Calculations of off-period observations are usually reduced to brute force direct methods resulting in many demanding matrix multiplications. For large spin systems, the matrix multiplication becomes the limiting step. A simple method that can dramatically reduce the number of matrix multiplications required to calculate the time evolution when the observation time step is some rational fraction of the period of the Hamiltonian is presented. The algorithm implements two different optimization routines. One uses pattern matching and additional memory storage, while the other recursively generates the propagators via time shifting. The net result is a significant speed improvement for some types of time-domain calculations.

  20. Genome-Wide Detection and Analysis of Multifunctional Genes

    PubMed Central

    Pritykin, Yuri; Ghersi, Dario; Singh, Mona

    2015-01-01

    Many genes can play a role in multiple biological processes or molecular functions. Identifying multifunctional genes at the genome-wide level and studying their properties can shed light upon the complexity of molecular events that underpin cellular functioning, thereby leading to a better understanding of the functional landscape of the cell. However, to date, genome-wide analysis of multifunctional genes (and the proteins they encode) has been limited. Here we introduce a computational approach that uses known functional annotations to extract genes playing a role in at least two distinct biological processes. We leverage functional genomics data sets for three organisms—H. sapiens, D. melanogaster, and S. cerevisiae—and show that, as compared to other annotated genes, genes involved in multiple biological processes possess distinct physicochemical properties, are more broadly expressed, tend to be more central in protein interaction networks, tend to be more evolutionarily conserved, and are more likely to be essential. We also find that multifunctional genes are significantly more likely to be involved in human disorders. These same features also hold when multifunctionality is defined with respect to molecular functions instead of biological processes. Our analysis uncovers key features about multifunctional genes, and is a step towards a better genome-wide understanding of gene multifunctionality. PMID:26436655

  1. FLARE (Facility for Laboratory Reconnection Experiments): A Major Next-Step for Laboratory Studies of Magnetic Reconnection

    NASA Astrophysics Data System (ADS)

    Ji, H.; Bhattacharjee, A.; Prager, S.; Daughton, W. S.; Bale, S. D.; Carter, T. A.; Crocker, N.; Drake, J. F.; Egedal, J.; Sarff, J.; Wallace, J.; Belova, E.; Ellis, R.; Fox, W. R., II; Heitzenroeder, P.; Kalish, M.; Jara-Almonte, J.; Myers, C. E.; Que, W.; Ren, Y.; Titus, P.; Yamada, M.; Yoo, J.

    2014-12-01

    A new intermediate-scale plasma experiment, called the Facility for Laboratory Reconnection Experiments or FLARE, is under construction at Princeton as a joint project by five universities and two national labs to study magnetic reconnection in regimes directly relevant to space, solar and astrophysical plasmas. The currently existing small-scale experiments have been focusing on the single X-line reconnection process in plasmas either with small effective sizes or at low Lundquist numbers, both of which are typically very large in natural plasmas. These new regimes involve multiple X-lines as guided by a reconnection "phase diagram", in which different coupling mechanisms from the global system scale to the local dissipation scale are classified into different reconnection phases [H. Ji & W. Daughton, Phys. Plasmas 18, 111207 (2011)]. The design of the FLARE device is based on the existing Magnetic Reconnection Experiment (MRX) at Princeton (http://mrx.pppl.gov) and is to provide experimental access to the new phases involving multiple X-lines at large effective sizes and high Lundquist numbers, directly relevant to space and solar plasmas. The motivating major physics questions, the construction status, and the planned collaborative research especially with space and solar research communities will be discussed.

  2. FLARE (Facility for Laboratory Reconnection Experiments): A Major Next-Step for Laboratory Studies of Magnetic Reconnection

    NASA Astrophysics Data System (ADS)

    Ji, Hantao; Bhattacharjee, A.; Prager, S.; Daughton, W.; Bale, Stuart D.; Carter, T.; Crocker, N.; Drake, J.; Egedal, J.; Sarff, J.; Fox, W.; Jara-Almonte, J.; Myers, C.; Ren, Y.; Yamada, M.; Yoo, J.

    2015-04-01

    A new intermediate-scale plasma experiment, called the Facility for Laboratory Reconnection Experiments or FLARE (flare.pppl.gov), is under construction at Princeton as a joint project by five universities and two national labs to study magnetic reconnection in regimes directly relevant to heliophysical and astrophysical plasmas. The currently existing small-scale experiments have been focusing on the single X-line reconnection process in plasmas either with small effective sizes or at low Lundquist numbers, both of which are typically very large in natural plasmas. These new regimes involve multiple X-lines as guided by a reconnection "phase diagram", in which different coupling mechanisms from the global system scale to the local dissipation scale are classified into different reconnection phases [H. Ji & W. Daughton, Phys. Plasmas 18, 111207 (2011)]. The design of the FLARE device is based on the existing Magnetic Reconnection Experiment (MRX) (mrx.pppl.gov) and is to provide experimental access to the new phases involving multiple X-lines at large effective sizes and high Lundquist numbers, directly relevant to magnetospheric, solar wind, and solar coronal plasmas. After a brief summary of recent laboratory results on the topic of magnetic reconnection, the motivating major physics questions, the construction status, and the planned collaborative research especially with heliophysics communities will be discussed.

  3. Cryotherapy simulator for localized prostate cancer.

    PubMed

    Hahn, James K; Manyak, Michael J; Jin, Ge; Kim, Dongho; Rewcastle, John; Kim, Sunil; Walsh, Raymond J

    2002-01-01

    Cryotherapy is a treatment modality that uses a technique to selectively freeze tissue and thereby cause controlled tissue destruction. The procedure involves placement of multiple small diameter probes through the perineum into the prostate tissue at selected spatial intervals. Transrectal ultrasound is used to properly position the cylindrical probes before activation of the liquid Argon cooling element, which lowers the tissue temperature below -40 degrees Centigrade. Tissue effect is monitored by transrectal ultrasound changes as well as thermocouples placed in the tissue. The computer-based cryotherapy simulation system mimics the major surgical steps involved in the procedure. The simulated real-time ultrasound display is generated from 3-D ultrasound datasets where the interaction of the ultrasound with the instruments as well as the frozen tissue is simulated by image processing. The thermal and mechanical simulations of the tissue are done using a modified finite-difference/finite-element method optimized for real-time performance. The simulator developed is a part of a comprehensive training program, including a computer-based learning system and hands-on training program with a proctor, designed to familiarize the physician with the technique and equipment involved.

  4. Multiple stage miniature stepping motor

    DOEpatents

    Niven, William A.; Shikany, S. David; Shira, Michael L.

    1981-01-01

    A stepping motor comprising a plurality of stages which may be selectively activated to effect stepping movement of the motor, and which are mounted along a common rotor shaft to achieve considerable reduction in motor size and minimum diameter, whereby sequential activation of the stages results in successive rotor steps with direction being determined by the particular activating sequence followed.

  5. Resonant Raman scattering in single crystal of congruent LiTaO 3 : Effect of excitation energy

    NASA Astrophysics Data System (ADS)

    Bhaumik, Indranil; Kumar, Shailendra; Ganesamoorthy, S.; Bhatt, R.; Karnal, A. K.; Raja Sekhar, B. N.

    2011-12-01

    Large dispersion in the peak position of the OH - stretching mode (˜687.9 and ˜2167.7 cm -1/eV for fundamental and 3rd harmonic, respectively) is observed by Resonance Raman studies in congruent lithium tantalate single crystal under varying excitation energies. This is explained by considering the involvement of multiple LO phonons in the interaction with OH - stretching vibration and the resonantly excited electrons. The intensity of the peaks is also found to vary with the excitation energy. FWHM increases with the increase in excitation energy because of individual contributions of the increasing number of resonance steps to the broadening.

  6. The Virtual Mission - A step-wise approach to large space missions

    NASA Technical Reports Server (NTRS)

    Hansen, Elaine; Jones, Morgan; Hooke, Adrian; Pomphrey, Richard

    1992-01-01

    Attention is given to the Virtual Mission (VM) concept, wherein multiple scientific instruments will be on different platforms, in different orbits, operated from different control centers, at different institutions, and reporting to different user groups. The VM concept enables NASA's science and application users to accomplish their broad science goals with a fleet made up of smaller, more focused spacecraft and to alleviate the difficulties involved with single, large, complex spacecraft. The concept makes possible the stepwise 'go-as-you-pay' extensible approach recommended by Augustine (1990). It enables scientists to mix and match the use of many smaller satellites in novel ways to respond to new scientific ideas and needs.

  7. Transdisciplinary translational behavioral (TDTB) research: opportunities, barriers, and innovations.

    PubMed

    Czajkowski, Susan M; Lynch, Minda R; Hall, Kara L; Stipelman, Brooke A; Haverkos, Lynne; Perl, Harold; Scott, Marcia S; Shirley, Mariela C

    2016-03-01

    The translation of basic behavioral science discoveries into practical strategies represents a promising approach to developing more effective preventive interventions to improve health. Since translational research inevitably involves making use of diverse perspectives from multiple disciplines, it is best conducted as a transdisciplinary enterprise. In this paper, we discuss current strategies used by NIH to support transdisciplinary translational behavioral (TDTB) research, summarize successful efforts, and highlight challenges encountered in conducting such work (ranging from conceptual to organizational to methodological). Using examples from NIH-funded projects we illustrate the potential benefits of, and barriers to, pursuing this type of research and discuss next steps and potential future directions for NIH-supported TDTB research.

  8. Gas diffusion as a new fluidic unit operation for centrifugal microfluidic platforms.

    PubMed

    Ymbern, Oriol; Sández, Natàlia; Calvo-López, Antonio; Puyol, Mar; Alonso-Chamarro, Julian

    2014-03-07

    A centrifugal microfluidic platform prototype with an integrated membrane for gas diffusion is presented for the first time. The centrifugal platform allows multiple and parallel analysis on a single disk and integrates at least ten independent microfluidic subunits, which allow both calibration and sample determination. It is constructed with a polymeric substrate material and it is designed to perform colorimetric determinations by the use of a simple miniaturized optical detection system. The determination of three different analytes, sulfur dioxide, nitrite and carbon dioxide, is carried out as a proof of concept of a versatile microfluidic system for the determination of analytes which involve a gas diffusion separation step during the analytical procedure.

  9. Tracking problem solving by multivariate pattern analysis and Hidden Markov Model algorithms.

    PubMed

    Anderson, John R

    2012-03-01

    Multivariate pattern analysis can be combined with Hidden Markov Model algorithms to track the second-by-second thinking as people solve complex problems. Two applications of this methodology are illustrated with a data set taken from children as they interacted with an intelligent tutoring system for algebra. The first "mind reading" application involves using fMRI activity to track what students are doing as they solve a sequence of algebra problems. The methodology achieves considerable accuracy at determining both what problem-solving step the students are taking and whether they are performing that step correctly. The second "model discovery" application involves using statistical model evaluation to determine how many substates are involved in performing a step of algebraic problem solving. This research indicates that different steps involve different numbers of substates and these substates are associated with different fluency in algebra problem solving. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. A two-step hierarchical hypothesis set testing framework, with applications to gene expression data on ordered categories

    PubMed Central

    2014-01-01

    Background In complex large-scale experiments, in addition to simultaneously considering a large number of features, multiple hypotheses are often being tested for each feature. This leads to a problem of multi-dimensional multiple testing. For example, in gene expression studies over ordered categories (such as time-course or dose-response experiments), interest is often in testing differential expression across several categories for each gene. In this paper, we consider a framework for testing multiple sets of hypothesis, which can be applied to a wide range of problems. Results We adopt the concept of the overall false discovery rate (OFDR) for controlling false discoveries on the hypothesis set level. Based on an existing procedure for identifying differentially expressed gene sets, we discuss a general two-step hierarchical hypothesis set testing procedure, which controls the overall false discovery rate under independence across hypothesis sets. In addition, we discuss the concept of the mixed-directional false discovery rate (mdFDR), and extend the general procedure to enable directional decisions for two-sided alternatives. We applied the framework to the case of microarray time-course/dose-response experiments, and proposed three procedures for testing differential expression and making multiple directional decisions for each gene. Simulation studies confirm the control of the OFDR and mdFDR by the proposed procedures under independence and positive correlations across genes. Simulation results also show that two of our new procedures achieve higher power than previous methods. Finally, the proposed methodology is applied to a microarray dose-response study, to identify 17 β-estradiol sensitive genes in breast cancer cells that are induced at low concentrations. Conclusions The framework we discuss provides a platform for multiple testing procedures covering situations involving two (or potentially more) sources of multiplicity. The framework is easy to use and adaptable to various practical settings that frequently occur in large-scale experiments. Procedures generated from the framework are shown to maintain control of the OFDR and mdFDR, quantities that are especially relevant in the case of multiple hypothesis set testing. The procedures work well in both simulations and real datasets, and are shown to have better power than existing methods. PMID:24731138

  11. Walk Ratio (Step Length/Cadence) as a Summary Index of Neuromotor Control of Gait: Application to Multiple Sclerosis

    ERIC Educational Resources Information Center

    Rota, Viviana; Perucca, Laura; Simone, Anna; Tesio, Luigi

    2011-01-01

    In healthy adults, the step length/cadence ratio [walk ratio (WR) in mm/(steps/min) and normalized for height] is known to be constant around 6.5 mm/(step/min). It is a speed-independent index of the overall neuromotor gait control, in as much as it reflects energy expenditure, balance, between-step variability, and attentional demand. The speed…

  12. Altering the selection capabilities of common cloning vectors via restriction enzyme mediated gene disruption

    PubMed Central

    2013-01-01

    Background The cloning of gene sequences forms the basis for many molecular biological studies. One important step in the cloning process is the isolation of bacterial transformants carrying vector DNA. This involves a vector-encoded selectable marker gene, which in most cases, confers resistance to an antibiotic. However, there are a number of circumstances in which a different selectable marker is required or may be preferable. Such situations can include restrictions to host strain choice, two phase cloning experiments and mutagenesis experiments, issues that result in additional unnecessary cloning steps, in which the DNA needs to be subcloned into a vector with a suitable selectable marker. Results We have used restriction enzyme mediated gene disruption to modify the selectable marker gene of a given vector by cloning a different selectable marker gene into the original marker present in that vector. Cloning a new selectable marker into a pre-existing marker was found to change the selection phenotype conferred by that vector, which we were able to demonstrate using multiple commonly used vectors and multiple resistance markers. This methodology was also successfully applied not only to cloning vectors, but also to expression vectors while keeping the expression characteristics of the vector unaltered. Conclusions Changing the selectable marker of a given vector has a number of advantages and applications. This rapid and efficient method could be used for co-expression of recombinant proteins, optimisation of two phase cloning procedures, as well as multiple genetic manipulations within the same host strain without the need to remove a pre-existing selectable marker in a previously genetically modified strain. PMID:23497512

  13. 12-step affiliation and attendance following treatment for comorbid substance dependence and depression: a latent growth curve mediation model.

    PubMed

    Worley, Matthew J; Tate, Susan R; McQuaid, John R; Granholm, Eric L; Brown, Sandra A

    2013-01-01

    Among substance-dependent individuals, comorbid major depressive disorder (MDD) is associated with greater severity and poorer treatment outcomes, but little research has examined mediators of posttreatment substance use outcomes within this population. Using latent growth curve models, the authors tested relationships between individual rates of change in 12-step involvement and substance use, utilizing posttreatment follow-up data from a trial of group Twelve-Step Facilitation (TSF) and integrated cognitive-behavioral therapy (ICBT) for veterans with substance dependence and MDD. Although TSF patients were higher on 12-step affiliation and meeting attendance at end-of-treatment as compared with ICBT, they also experienced significantly greater reductions in these variables during the year following treatment, ending at similar levels as ICBT. Veterans in TSF also had significantly greater increases in drinking frequency during follow-up, and this group difference was mediated by their greater reductions in 12-step affiliation and meeting attendance. Patients with comorbid depression appear to have difficulty sustaining high levels of 12-step involvement after the conclusion of formal 12-step interventions, which predicts poorer drinking outcomes over time. Modifications to TSF and other formal 12-step protocols or continued therapeutic contact may be necessary to sustain 12-step involvement and reduced drinking for patients with substance dependence and MDD.

  14. Involving Practicing Scientists in K-12 Science Teacher Professional Development

    NASA Astrophysics Data System (ADS)

    Bertram, K. B.

    2011-12-01

    The Science Teacher Education Program (STEP) offered a unique framework for creating professional development courses focused on Arctic research from 2006-2009. Under the STEP framework, science, technology, engineering, and math (STEM) training was delivered by teams of practicing Arctic researchers in partnership with master teachers with 20+ years experience teaching STEM content in K-12 classrooms. Courses based on the framework were offered to educators across Alaska. STEP offered in-person summer-intensive institutes and follow-on audio-conferenced field-test courses during the academic year, supplemented by online scientist mentorship for teachers. During STEP courses, teams of scientists offered in-depth STEM content instruction at the graduate level for teachers of all grade levels. STEP graduate-level training culminated in the translation of information and data learned from Arctic scientists into standard-aligned lessons designed for immediate use in K-12 classrooms. This presentation will focus on research that explored the question: To what degree was scientist involvement beneficial to teacher training and to what degree was STEP scientist involvement beneficial to scientist instructors? Data sources reveal consistently high levels of ongoing (4 year) scientist and teacher participation; high STEM content learning outcomes for teachers; high STEM content learning outcomes for students; high ratings of STEP courses by scientists and teachers; and a discussion of the reasons scientists indicate they benefited from STEP involvement. Analyses of open-ended comments by teachers and scientists support and clarify these findings. A grounded theory approach was used to analyze teacher and scientist qualitative feedback. Comments were coded and patterns analyzed in three databases. The vast majority of teacher open-ended comments indicate that STEP involvement improved K-12 STEM classroom instruction, and the vast majority of scientist open-ended comments focus on the benefits scientists received from networking with K-12 teachers. The classroom lessons resulting from STEP have been so popular among teachers, the Alaska Department of Education and Early Development recently contracted with the PI to create a website that will make the STEP database open to teachers across Alaska. When the Alaska Department of Education and Early Development launched the new website in August 2011, the name of the STEP program was changed to the Alaska K-12 Science Curricular Initiative (AKSCI). The STEP courses serving as the foundation to the new AKSCI site are located under the "History" tab of the new website.

  15. W/O/W multiple emulsions with diclofenac sodium.

    PubMed

    Lindenstruth, Kai; Müller, Bernd W

    2004-11-01

    The disperse oil droplets of W/O/W multiple emulsions contain small water droplets, in which drugs could be incorporated, but the structure of these emulsions is also the reason for possible instability. Due to the middle oil phase which acts as a 'semipermeable' membrane the passage of water across the oil phase can take place. However, the emulsions have been produced in a two-step-production process so not only the leakage of encapsulated drug molecules out of the inner water phase during storage but also a production-induced reduction of the encapsulation rate should be considered. The aim of this study was to ascertain how far the production-induced reduction of the encapsulation rate relates to the size of inner water droplets and to evaluate the relevance of multiple emulsions as drug carrier for diclofenac sodium. Therefore multiple emulsions were produced according to a central composite design. During the second production step it was observed that the parameters pressure and temperature have an influence on the size of the oil droplets in the W/O/W multiple emulsions. Further experiments with different W/O emulsions resulted in W/O/W multiple emulsions with different encapsulation rates of diclofenac sodium, due to the different sizes of the inner water droplets, which were obtained in the first production step.

  16. Multilevel resistive information storage and retrieval

    DOEpatents

    Lohn, Andrew; Mickel, Patrick R.

    2016-08-09

    The present invention relates to resistive random-access memory (RRAM or ReRAM) systems, as well as methods of employing multiple state variables to form degenerate states in such memory systems. The methods herein allow for precise write and read steps to form multiple state variables, and these steps can be performed electrically. Such an approach allows for multilevel, high density memory systems with enhanced information storage capacity and simplified information retrieval.

  17. Do You Know What I Feel? A First Step towards a Physiological Measure of the Subjective Well-Being of Persons with Profound Intellectual and Multiple Disabilities

    ERIC Educational Resources Information Center

    Vos, Pieter; De Cock, Paul; Petry, Katja; Van Den Noortgate, Wim; Maes, Bea

    2010-01-01

    Background: Because of limited communicative skills, it is not self-evident to measure subjective well-being in people with profound intellectual and multiple disabilities. As a first step towards a non-interpretive measure of subjective well-being, we explored how the respiratory, cardiovascular and electro dermal response systems were associated…

  18. Barriers to participation in global surgery academic collaborations, and possible solutions: a qualitative study.

    PubMed

    Fallah, Parisa Nicole; Bernstein, Mark

    2018-04-06

    OBJECTIVE There is a global lack of access to surgical care, and this issue disproportionately affects those in low- and middle-income countries. Global surgery academic collaborations (GSACs) between surgeons in high-income countries and those in low- and middle-income countries are one possible sustainable way to address the global surgical need. The objective of this study was to examine the barriers to participation in GSACs and to suggest ways to increase involvement. METHODS A convenience sample of 86 surgeons, anesthesiologists, other physicians, residents, fellows, and nurses from the US, Canada, and Norway was used. Participants were all health care providers from multiple specialties and multiple academic centers with varied involvement in GSACs. More than half of the participants were neurosurgeons. Participants were interviewed in person or over Skype in Toronto over the course of 2 months by using a predetermined set of open-ended questions. Thematic content analysis was used to evaluate the participants' responses. RESULTS Based on the data, 3 main themes arose that pointed to individual, community, and system barriers for involvement in GSACs. Individual barriers included loss of income, family commitments, young career, responsibility to local patients, skepticism of global surgery efforts, ethical concerns, and safety concerns. Community barriers included insufficient mentorship and lack of support from colleagues. System barriers included lack of time, minimal academic recognition, insufficient awareness, insufficient administrative support and organization, and low political and funding support. CONCLUSIONS Steps can be taken to address some of these barriers and to increase the involvement of surgeons from high-income countries in GSACs. This could lead to a necessary scale-up of global surgery efforts that may help increase worldwide access to surgical care.

  19. Assembling programmable FRET-based photonic networks using designer DNA scaffolds

    PubMed Central

    Buckhout-White, Susan; Spillmann, Christopher M; Algar, W. Russ; Khachatrian, Ani; Melinger, Joseph S.; Goldman, Ellen R.; Ancona, Mario G.; Medintz, Igor L.

    2014-01-01

    DNA demonstrates a remarkable capacity for creating designer nanostructures and devices. A growing number of these structures utilize Förster resonance energy transfer (FRET) as part of the device's functionality, readout or characterization, and, as device sophistication increases so do the concomitant FRET requirements. Here we create multi-dye FRET cascades and assess how well DNA can marshal organic dyes into nanoantennae that focus excitonic energy. We evaluate 36 increasingly complex designs including linear, bifurcated, Holliday junction, 8-arm star and dendrimers involving up to five different dyes engaging in four-consecutive FRET steps, while systematically varying fluorophore spacing by Förster distance (R0). Decreasing R0 while augmenting cross-sectional collection area with multiple donors significantly increases terminal exciton delivery efficiency within dendrimers compared with the first linear constructs. Förster modelling confirms that best results are obtained when there are multiple interacting FRET pathways rather than independent channels by which excitons travel from initial donor(s) to final acceptor. PMID:25504073

  20. Modified protrusion arch for anterior crossbite correction - a case report.

    PubMed

    Roy, Abhishek Singha; Singh, Gulshan Kr; Tandon, Pradeep; Chaudhary, Ramsukh

    2013-01-01

    Borderline and mild skeletal Class III relationships in adult patients are usually treated by orthodontic camouflage. Reasonably rood results have been achieved with nonsurgical teatment of anterior crossbite. Class III malocclusion may be associated with mandibular prognathism, maxillary retrognathism, or both. Class III maxillary retrognathism generally involves anterior crossbite, which must be opened if upper labial brackets are to be bonded. If multiple teeth are in crossbite, after opening the bite usual step is to ligate forward or advancement arch made of 0.018" or 0.020" stainless steel or NiTi wire main arch that must be kept separated 2 mm from the slot ofupper incisor braces. Two stops or omegas are made 1 mm mesial to the tubes of the molar bands that will impede main arch from slipping,and in this manner the arch will push the anterior teeth forward Here we have fabricated a modified multiple loop protrusion arch to correct an anterior crossbite with severe crowding that was not amenable to correct by advancement arches.

  1. Structural Inheritance of the Actin Cytoskeletal Organization Determines the Body Axis in Regenerating Hydra.

    PubMed

    Livshits, Anton; Shani-Zerbib, Lital; Maroudas-Sacks, Yonit; Braun, Erez; Keren, Kinneret

    2017-02-07

    Understanding how mechanics complement bio-signaling in defining patterns during morphogenesis is an outstanding challenge. Here, we utilize the multicellular polyp Hydra to investigate the role of the actomyosin cytoskeleton in morphogenesis. We find that the supra-cellular actin fiber organization is inherited from the parent Hydra and determines the body axis in regenerating tissue segments. This form of structural inheritance is non-trivial because of the tissue folding and dynamic actin reorganization involved. We further show that the emergence of multiple body axes can be traced to discrepancies in actin fiber alignment at early stages of the regeneration process. Mechanical constraints induced by anchoring regenerating Hydra on stiff wires suppressed the emergence of multiple body axes, highlighting the importance of mechanical feedbacks in defining and stabilizing the body axis. Together, these results constitute an important step toward the development of an integrated view of morphogenesis that incorporates mechanics. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  2. U.S. Forest Service Leads Climate Change Adaptation in the Western United States

    NASA Astrophysics Data System (ADS)

    Halofsky, J.; Peterson, D. L.

    2014-12-01

    Effective climate change engagement on public lands is characterized by (1) an enduring science-management partnership, (2) involvement of key stakeholders, (3) consideration of broad landscapes with multiple landowners, (4) science-based, peer-reviewed assessments of sensitivity of natural resources to climate change, (5) adaptation strategies and tactics developed by resource managers, (6) leadership and a workforce motivated to implement climate-smart practices in resource planning and project management. Using this approach, the U.S. Forest Service, in partnership with other organizations, has developed climate change vulnerability assessments and adaptation plans for diverse ecosystems and multiple resources in national forests and other lands in the western United States, although implementation (step 6) has been slow in some cases. Hundreds of meetings, strategies, plans, and panels have focused on climate change adaptation over the past decade, but only direct engagement between scientists and resource managers (less research, less planning, more action) has resulted in substantive outcomes and increased organizational capacity for climate-smart management.

  3. Causal mediation analysis with a binary outcome and multiple continuous or ordinal mediators: Simulations and application to an alcohol intervention.

    PubMed

    Nguyen, Trang Quynh; Webb-Vargas, Yenny; Koning, Ina M; Stuart, Elizabeth A

    We investigate a method to estimate the combined effect of multiple continuous/ordinal mediators on a binary outcome: 1) fit a structural equation model with probit link for the outcome and identity/probit link for continuous/ordinal mediators, 2) predict potential outcome probabilities, and 3) compute natural direct and indirect effects. Step 2 involves rescaling the latent continuous variable underlying the outcome to address residual mediator variance/covariance. We evaluate the estimation of risk-difference- and risk-ratio-based effects (RDs, RRs) using the ML, WLSMV and Bayes estimators in Mplus. Across most variations in path-coefficient and mediator-residual-correlation signs and strengths, and confounding situations investigated, the method performs well with all estimators, but favors ML/WLSMV for RDs with continuous mediators, and Bayes for RRs with ordinal mediators. Bayes outperforms WLSMV/ML regardless of mediator type when estimating RRs with small potential outcome probabilities and in two other special cases. An adolescent alcohol prevention study is used for illustration.

  4. Two-step emulsification process for water-in-oil-in-water multiple emulsions stabilized by lamellar liquid crystals.

    PubMed

    Ito, Toshifumi; Tsuji, Yukitaka; Aramaki, Kenji; Tonooka, Noriaki

    2012-01-01

    Multiple emulsions, also called complex emulsions or multiphase emulsions, include water-in-oil-in-water (W/O/W)-type and oil-in-water-in-oil (O/W/O)-type emulsions. W/O/W-type multiple emulsions, obtained by utilizing lamellar liquid crystal with a layer structure showing optical anisotropy at the periphery of emulsion droplets, are superior in stability to O/W/O-type emulsions. In this study, we investigated a two-step emulsification process for a W/O/W-type multiple emulsion utilizing liquid crystal emulsification. We found that a W/O/W-type multiple emulsion containing lamellar liquid crystal can be prepared by mixing a W/O-type emulsion (prepared by primary emulsification) with a lamellar liquid crystal obtained from poly(oxyethylene) stearyl ether, cetyl alcohol, and water, and by dispersing and emulsifying the mixture in an outer aqueous phase. When poly(oxyethylene) stearyl ether and cetyl alcohol are each used in a given amount and the amount of water added is varied from 0 to 15 g (total amount of emulsion, 100 g), a W/O/W-type multiple emulsion is efficiently prepared. When the W/O/W-type multiple emulsion was held in a thermostatic bath at 25°C, the droplet size distribution showed no change 0, 30, or 60 days after preparation. Moreover, the W/O/W-type multiple emulsion strongly encapsulated Uranine in the inner aqueous phase as compared with emulsions prepared by one-step emulsification.

  5. Development of a Magnetic Microbead Affinity Selection Screen (MagMASS) Using Mass Spectrometry for Ligands to the Retinoid X Receptor-α

    NASA Astrophysics Data System (ADS)

    Rush, Michael D.; Walker, Elisabeth M.; Prehna, Gerd; Burton, Tristesse; van Breemen, Richard B.

    2017-03-01

    To overcome limiting factors in mass spectrometry-based screening methods such as automation while still facilitating the screening of complex mixtures such as botanical extracts, magnetic microbead affinity selection screening (MagMASS) was developed. The screening process involves immobilization of a target protein on a magnetic microbead using a variety of possible chemistries, incubation with mixtures of molecules containing possible ligands, a washing step that removes non-bound compounds while a magnetic field retains the beads in the microtiter well, and an organic solvent release step followed by LC-MS analysis. Using retinoid X receptor-α (RXRα) as an example, which is a nuclear receptor and target for anti-inflammation therapy as well as cancer treatment and prevention, a MagMASS assay was developed and compared with an existing screening assay, pulsed ultrafiltration (PUF)-MS. Optimization of MagMASS involved evaluation of multiple protein constructs and several magnetic bead immobilization chemistries. The full-length RXRα construct immobilized with amylose beads provided optimum results. Additional enhancements of MagMASS were the application of 96-well plates to enable automation, use of UHPLC instead of HPLC for faster MS analyses, and application of metabolomics software for faster, automated data analysis. Performance of MagMASS was demonstrated using mixtures of synthetic compounds and known ligands spiked into botanical extracts.

  6. Emotional Speech Perception Unfolding in Time: The Role of the Basal Ganglia

    PubMed Central

    Paulmann, Silke; Ott, Derek V. M.; Kotz, Sonja A.

    2011-01-01

    The basal ganglia (BG) have repeatedly been linked to emotional speech processing in studies involving patients with neurodegenerative and structural changes of the BG. However, the majority of previous studies did not consider that (i) emotional speech processing entails multiple processing steps, and the possibility that (ii) the BG may engage in one rather than the other of these processing steps. In the present study we investigate three different stages of emotional speech processing (emotional salience detection, meaning-related processing, and identification) in the same patient group to verify whether lesions to the BG affect these stages in a qualitatively different manner. Specifically, we explore early implicit emotional speech processing (probe verification) in an ERP experiment followed by an explicit behavioral emotional recognition task. In both experiments, participants listened to emotional sentences expressing one of four emotions (anger, fear, disgust, happiness) or neutral sentences. In line with previous evidence patients and healthy controls show differentiation of emotional and neutral sentences in the P200 component (emotional salience detection) and a following negative-going brain wave (meaning-related processing). However, the behavioral recognition (identification stage) of emotional sentences was impaired in BG patients, but not in healthy controls. The current data provide further support that the BG are involved in late, explicit rather than early emotional speech processing stages. PMID:21437277

  7. Fostering Autonomy through Syllabus Design: A Step-by-Step Guide for Success

    ERIC Educational Resources Information Center

    Ramírez Espinosa, Alexánder

    2016-01-01

    Promoting learner autonomy is relevant in the field of applied linguistics due to the multiple benefits it brings to the process of learning a new language. However, despite the vast array of research on how to foster autonomy in the language classroom, it is difficult to find step-by-step processes to design syllabi and curricula focused on the…

  8. Multisensor Arrays for Greater Reliability and Accuracy

    NASA Technical Reports Server (NTRS)

    Immer, Christopher; Eckhoff, Anthony; Lane, John; Perotti, Jose; Randazzo, John; Blalock, Norman; Ree, Jeff

    2004-01-01

    Arrays of multiple, nominally identical sensors with sensor-output-processing electronic hardware and software are being developed in order to obtain accuracy, reliability, and lifetime greater than those of single sensors. The conceptual basis of this development lies in the statistical behavior of multiple sensors and a multisensor-array (MSA) algorithm that exploits that behavior. In addition, advances in microelectromechanical systems (MEMS) and integrated circuits are exploited. A typical sensor unit according to this concept includes multiple MEMS sensors and sensor-readout circuitry fabricated together on a single chip and packaged compactly with a microprocessor that performs several functions, including execution of the MSA algorithm. In the MSA algorithm, the readings from all the sensors in an array at a given instant of time are compared and the reliability of each sensor is quantified. This comparison of readings and quantification of reliabilities involves the calculation of the ratio between every sensor reading and every other sensor reading, plus calculation of the sum of all such ratios. Then one output reading for the given instant of time is computed as a weighted average of the readings of all the sensors. In this computation, the weight for each sensor is the aforementioned value used to quantify its reliability. In an optional variant of the MSA algorithm that can be implemented easily, a running sum of the reliability value for each sensor at previous time steps as well as at the present time step is used as the weight of the sensor in calculating the weighted average at the present time step. In this variant, the weight of a sensor that continually fails gradually decreases, so that eventually, its influence over the output reading becomes minimal: In effect, the sensor system "learns" which sensors to trust and which not to trust. The MSA algorithm incorporates a criterion for deciding whether there remain enough sensor readings that approximate each other sufficiently closely to constitute a majority for the purpose of quantifying reliability. This criterion is, simply, that if there do not exist at least three sensors having weights greater than a prescribed minimum acceptable value, then the array as a whole is deemed to have failed.

  9. A Collaborative Approach for Scoping Ecosystem Services with Stakeholders: The Case of Arrábida Natural Park.

    PubMed

    Lopes, Rita; Videira, Nuno

    2016-08-01

    This paper presents an innovative approach for conducting collaborative scoping processes aiming to elicit multiple values of ecosystem services. The proposed methodology rests on three steps combining different participatory tools that promote a comprehensive examination of the perceptions hold by relevant stakeholder groups. The first step consists of an institutional and stakeholder analysis developed in the study area. The second includes a participatory workshop, where a sequence of scoping exercises is conducted with the active collaboration of the invited stakeholders. The final step aims to validate scoping results and develop dependency networks between organizations and the identified ecosystem services. The approach was tested in the Arrábida Natural Park, a marine and coastal protected area in Portugal. Invited participants were able to identify an extensive list of ecosystem services in the natural area, establish linkages between those services and human wellbeing, identify drivers of change and perform a preliminary screening of the associated ecological, social, and economic values. The case study evaluation provided positive feedback on the usefulness of the approach, which advances the existing set of methods for participatory identification of ecosystem services and sets the scene for involvement of stakeholder groups in assessment and management processes.

  10. Two-step crystal growth mechanism during crystallization of an undercooled Ni50Al50 alloy

    NASA Astrophysics Data System (ADS)

    An, Simin; Li, Jiahao; Li, Yang; Li, Shunning; Wang, Qi; Liu, Baixin

    2016-08-01

    Crystallization processes are always accompanied by the emergence of multiple intermediate states, of which the structures and transition dynamics are far from clarity, since it is difficult to experimentally observe the microscopic pathway. To insight the structural evolution and the crystallization dynamics, we perform large-scale molecular dynamics simulations to investigate the time-dependent crystallization behavior of the NiAl intermetallic upon rapid solidification. The simulation results reveal that the crystallization process occurs via a two-step growth mechanism, involving the formation of initial non-equilibrium long range order (NLRO) regions and of the subsequent equilibrium long range order (ELRO) regions. The formation of the NLRO regions makes the grains rather inhomogeneous, while the rearrangement of the NLRO regions into the ELRO regions makes the grains more ordered and compact. This two-step growth mechanism is actually controlled by the evolution of the coordination polyhedra, which are characterized predominantly by the transformation from five-fold symmetry to four-fold and six-fold symmetry. From liquids to NLRO and further to ELRO, the five-fold symmetry of these polyhedra gradually fades, and finally vanishes when B2 structure is distributed throughout the grain bulk. The energy decrease along the pathway further implies the reliability of the proposed crystallization processes.

  11. A Collaborative Approach for Scoping Ecosystem Services with Stakeholders: The Case of Arrábida Natural Park

    NASA Astrophysics Data System (ADS)

    Lopes, Rita; Videira, Nuno

    2016-08-01

    This paper presents an innovative approach for conducting collaborative scoping processes aiming to elicit multiple values of ecosystem services. The proposed methodology rests on three steps combining different participatory tools that promote a comprehensive examination of the perceptions hold by relevant stakeholder groups. The first step consists of an institutional and stakeholder analysis developed in the study area. The second includes a participatory workshop, where a sequence of scoping exercises is conducted with the active collaboration of the invited stakeholders. The final step aims to validate scoping results and develop dependency networks between organizations and the identified ecosystem services. The approach was tested in the Arrábida Natural Park, a marine and coastal protected area in Portugal. Invited participants were able to identify an extensive list of ecosystem services in the natural area, establish linkages between those services and human wellbeing, identify drivers of change and perform a preliminary screening of the associated ecological, social, and economic values. The case study evaluation provided positive feedback on the usefulness of the approach, which advances the existing set of methods for participatory identification of ecosystem services and sets the scene for involvement of stakeholder groups in assessment and management processes.

  12. Metabolomics: A potential way to know the role of vitamin D on multiple sclerosis.

    PubMed

    Luque-Córdoba, Diego; Luque de Castro, María D

    2017-03-20

    The literature about the influence of vitamin D on multiple sclerosis (MS) is very controversial, possibly as a result of the way through which the research on the subject has been conducted. The studies developed so far have been focused exclusively on gene expression: the effect of a given vitamin D metabolite on target receptors. The influence of the vitamin D status (either natural or after supplementation) on MS has been studied by measurement of the 25 monohydroxylated metabolite (also known as circulating form), despite the 1,25 dihydroxylated metabolite is considered the active form. In the light of the multiple metabolic pathways in which both forms of vitamin D (D 2 and D 3 ) are involved, monitoring of the metabolites is crucial to know the activity of the target enzymes as a function of both the state of the MS patient and the clinical treatment applied. The study of metabolomics aspects is here proposed to clarify the present controversy. In "omics" terms, our proposal is to take profit from up-stream information-thus is, from metabolomics to genomics-with a potential subsequent step to systems biology, if required. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Hypothesis: neoplasms in myotonic dystrophy

    PubMed Central

    Hilbert, James E.; Martens, William; Thornton, Charles A.; Moxley, Richard T.; Greene, Mark H.

    2011-01-01

    Tumorigenesis is a multi-step process due to an accumulation of genetic mutations in multiple genes in diverse pathways which ultimately lead to loss of control over cell growth. It is well known that inheritance of rare germline mutations in genes involved in tumorigenesis pathways confer high lifetime risk of neoplasia in affected individuals. Furthermore, a substantial number of multiple malformation syndromes include cancer susceptibility in their phenotype. Studies of the mechanisms underlying these inherited syndromes have added to the understanding of both normal development and the pathophysiology of carcinogenesis. Myotonic dystrophy (DM) represents a group of autosomal dominant, multisystemic diseases that share the clinical features of myotonia, muscle weakness, and early-onset cataracts. Myotonic dystrophy type 1 (DM1) and myotonic dystrophy type 2 (DM2) result from unstable nucleotide repeat expansions in their respective genes. There have been multiple reports of tumors in individuals with DM, most commonly benign calcifying cutaneous tumors known as pilomatricomas. We provide a summary of the tumors reported in DM and a hypothesis for a possible mechanism of tumorigenesis. We hope to stimulate further study into the potential role of DM genes in tumorigenesis, and help define DM pathogenesis, and facilitate developing novel treatment modalities. PMID:19642006

  14. Multiple speckle illumination for optical-resolution photoacoustic imaging

    NASA Astrophysics Data System (ADS)

    Poisson, Florian; Stasio, Nicolino; Moser, Christophe; Psaltis, Demetri; Bossy, Emmanuel

    2017-03-01

    Optical-resolution photoacoustic microscopy offers exquisite and specific contrast to optical absorption. Conventional approaches generally involves raster scanning a focused spot over the sample. Here, we demonstrate that a full-field illumination approach with multiple speckle illumination can also provide diffraction-limited optical-resolution photoacoustic images. Two different proof-of-concepts are demonstrated with micro-structured test samples. The first approach follows the principle of correlation/ghost imaging,1, 2 and is based on cross-correlating photoacoustic signals under multiple speckle illumination with known speckle patterns measured during a calibration step. The second approach is a speckle scanning microscopy technique, which adapts the technique proposed in fluorescence microscopy by Bertolotti and al.:3 in our work, spatially unresolved photoacoustic measurements are performed for various translations of unknown speckle patterns. A phase-retrieval algorithm is used to reconstruct the object from the knowledge of the modulus of its Fourier Transform yielded by the measurements. Because speckle patterns naturally appear in many various situations, including propagation through biological tissue or multi-mode fibers (for which focusing light is either very demanding if not impossible), speckle-illumination-based photoacoustic microscopy provides a powerful framework for the development of novel reconstruction approaches, well-suited to compressed sensing approaches.2

  15. Efficient hybrid metrology for focus, CD, and overlay

    NASA Astrophysics Data System (ADS)

    Tel, W. T.; Segers, B.; Anunciado, R.; Zhang, Y.; Wong, P.; Hasan, T.; Prentice, C.

    2017-03-01

    In the advent of multiple patterning techniques in semiconductor industry, metrology has progressively become a burden. With multiple patterning techniques such as Litho-Etch-Litho-Etch and Sidewall Assisted Double Patterning, the number of processing step have increased significantly and therefore, so as the amount of metrology steps needed for both control and yield monitoring. The amount of metrology needed is increasing in each and every node as more layers needed multiple patterning steps, and more patterning steps per layer. In addition to this, there is that need for guided defect inspection, which in itself requires substantially denser focus, overlay, and CD metrology as before. Metrology efficiency will therefore be cruicial to the next semiconductor nodes. ASML's emulated wafer concept offers a highly efficient method for hybrid metrology for focus, CD, and overlay. In this concept metrology is combined with scanner's sensor data in order to predict the on-product performance. The principle underlying the method is to isolate and estimate individual root-causes which are then combined to compute the on-product performance. The goal is to use all the information available to avoid ever increasing amounts of metrology.

  16. Electronic measurement apparatus movable in a cased borehole and compensating for casing resistance differences

    DOEpatents

    Vail, W.B. III.

    1991-12-24

    Methods of operation are described for an apparatus having at least two pairs of voltage measurement electrodes vertically disposed in a cased well to measure the resistivity of adjacent geological formations from inside the cased well. During stationary measurements with the apparatus at a fixed vertical depth within the cased well, the invention herein discloses methods of operation which include a measurement step and subsequent first and second compensation steps respectively resulting in improved accuracy of measurement. The invention also discloses multiple frequency methods of operation resulting in improved accuracy of measurement while the apparatus is simultaneously moved vertically in the cased well. The multiple frequency methods of operation disclose a first A.C. current having a first frequency that is conducted from the casing into formation and a second A.C. current having a second frequency that is conducted along the casing. The multiple frequency methods of operation simultaneously provide the measurement step and two compensation steps necessary to acquire accurate results while the apparatus is moved vertically in the cased well. 6 figures.

  17. Electronic measurement apparatus movable in a cased borehole and compensating for casing resistance differences

    DOEpatents

    Vail, III, William B.

    1991-01-01

    Methods of operation of an apparatus having at least two pairs of voltage measurement electrodes vertically disposed in a cased well to measure the resistivity of adjacent geological formations from inside the cased well. During stationary measurements with the apparatus at a fixed vertical depth within the cased well, the invention herein discloses methods of operation which include a measurement step and subsequent first and second compensation steps respectively resulting in improved accuracy of measurement. The invention also discloses multiple frequency methods of operation resulting in improved accuracy of measurement while the apparatus is simultaneously moved vertically in the cased well. The multiple frequency methods of operation disclose a first A.C. current having a first frequency that is conducted from the casing into formation and a second A.C. current having a second frequency that is conducted along the casing. The multiple frequency methods of operation simultaneously provide the measurement step and two compensation steps necessary to acquire accurate results while the apparatus is moved vertically in the cased well.

  18. Rapid fabrication of microneedles using magnetorheological drawing lithography.

    PubMed

    Chen, Zhipeng; Ren, Lei; Li, Jiyu; Yao, Lebin; Chen, Yan; Liu, Bin; Jiang, Lelun

    2018-01-01

    Microneedles are micron-sized needles that are widely applied in biomedical fields owing to their painless, minimally invasive, and convenient operation. However, most microneedle fabrication approaches are costly, time consuming, involve multiple steps, and require expensive equipment. In this study, we present a novel magnetorheological drawing lithography (MRDL) method to efficiently fabricate microneedle, bio-inspired microneedle, and molding-free microneedle array. With the assistance of an external magnetic field, the 3D structure of a microneedle can be directly drawn from a droplet of curable magnetorheological fluid. The formation process of a microneedle consists of two key stages, elasto-capillary self-thinning and magneto-capillary self-shrinking, which greatly affect the microneedle height and tip radius. Penetration and fracture tests demonstrated that the microneedle had sufficient strength and toughness for skin penetration. Microneedle arrays and a bio-inspired microneedle were also fabricated, which further demonstrated the versatility and flexibility of the MRDL method. Microneedles have been widely applied in biomedical fields owing to their painless, minimally invasive, and convenient operation. However, most microneedle fabrication approaches are costly, time consuming, involve multiple steps, and require expensive equipment. Furthermore, most researchers have focused on the biomedical applications of microneedles but have given little attention to the optimization of the fabrication process. This research presents a novel magnetorheological drawing lithography (MRDL) method to fabricate microneedle, bio-inspired microneedle, and molding-free microneedle array. In this proposed technique, a droplet of curable magnetorheological fluid (CMRF) is drawn directly from almost any substrate to produce a 3D microneedle under an external magnetic field. This method not only inherits the advantages of thermal drawing approach without the need for a mask and light irradiation but also eliminates the requirement for drawing temperature adjustment. The MRDL method is extremely simple and can even produce the complex and multiscale structure of bio-inspired microneedle. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  19. AgMIP: Next Generation Models and Assessments

    NASA Astrophysics Data System (ADS)

    Rosenzweig, C.

    2014-12-01

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

  20. Numerically accurate computational techniques for optimal estimator analyses of multi-parameter models

    NASA Astrophysics Data System (ADS)

    Berger, Lukas; Kleinheinz, Konstantin; Attili, Antonio; Bisetti, Fabrizio; Pitsch, Heinz; Mueller, Michael E.

    2018-05-01

    Modelling unclosed terms in partial differential equations typically involves two steps: First, a set of known quantities needs to be specified as input parameters for a model, and second, a specific functional form needs to be defined to model the unclosed terms by the input parameters. Both steps involve a certain modelling error, with the former known as the irreducible error and the latter referred to as the functional error. Typically, only the total modelling error, which is the sum of functional and irreducible error, is assessed, but the concept of the optimal estimator enables the separate analysis of the total and the irreducible errors, yielding a systematic modelling error decomposition. In this work, attention is paid to the techniques themselves required for the practical computation of irreducible errors. Typically, histograms are used for optimal estimator analyses, but this technique is found to add a non-negligible spurious contribution to the irreducible error if models with multiple input parameters are assessed. Thus, the error decomposition of an optimal estimator analysis becomes inaccurate, and misleading conclusions concerning modelling errors may be drawn. In this work, numerically accurate techniques for optimal estimator analyses are identified and a suitable evaluation of irreducible errors is presented. Four different computational techniques are considered: a histogram technique, artificial neural networks, multivariate adaptive regression splines, and an additive model based on a kernel method. For multiple input parameter models, only artificial neural networks and multivariate adaptive regression splines are found to yield satisfactorily accurate results. Beyond a certain number of input parameters, the assessment of models in an optimal estimator analysis even becomes practically infeasible if histograms are used. The optimal estimator analysis in this paper is applied to modelling the filtered soot intermittency in large eddy simulations using a dataset of a direct numerical simulation of a non-premixed sooting turbulent flame.

  1. A basket two-part model to analyze medical expenditure on interdependent multiple sectors.

    PubMed

    Sugawara, Shinya; Wu, Tianyi; Yamanishi, Kenji

    2018-05-01

    This study proposes a novel statistical methodology to analyze expenditure on multiple medical sectors using consumer data. Conventionally, medical expenditure has been analyzed by two-part models, which separately consider purchase decision and amount of expenditure. We extend the traditional two-part models by adding the step of basket analysis for dimension reduction. This new step enables us to analyze complicated interdependence between multiple sectors without an identification problem. As an empirical application for the proposed method, we analyze data of 13 medical sectors from the Medical Expenditure Panel Survey. In comparison with the results of previous studies that analyzed the multiple sector independently, our method provides more detailed implications of the impacts of individual socioeconomic status on the composition of joint purchases from multiple medical sectors; our method has a better prediction performance.

  2. Speckle evolution with multiple steps of least-squares phase removal

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

    Chen Mingzhou; Dainty, Chris; Roux, Filippus S.

    2011-08-15

    We study numerically the evolution of speckle fields due to the annihilation of optical vortices after the least-squares phase has been removed. A process with multiple steps of least-squares phase removal is carried out to minimize both vortex density and scintillation index. Statistical results show that almost all the optical vortices can be removed from a speckle field, which finally decays into a quasiplane wave after such an iterative process.

  3. KEEPING A STEP AHEAD - FORMATIVE PHASE OF A WORKPLACE INTERVENTION TRIAL TO PREVENT OBESITY

    PubMed Central

    Zapka, Jane; Lemon, Stephenie C.; Estabrook, Barbara B.; Jolicoeur, Denise G.

    2008-01-01

    Background Ecological interventions hold promise for promoting overweight and obesity prevention in worksites. Given the paucity of evaluative research in the hospital worksite setting, considerable formative work is required for successful implementation and evaluation. Purpose This paper describes the formative phases of Step Ahead, a site-randomized controlled trial of a multi-level intervention that promotes physical activity and healthy eating in 6 hospitals in central Massachusetts. The purpose of the formative research phase was to increase the feasibility, effectiveness and likelihood of sustainability of the intervention. Design and Procedures The Step Ahead ecological intervention approach targets change at the organization, the interpersonal work environment and the individual levels. The intervention was developed using fundamental steps of intervention mapping and important tenets of participatory research. Formative research methods were used to engage leadership support and assistance and to develop an intervention plan that is both theoretically and practically grounded. This report uses observational data, program minutes and reports, and process tracking data. Developmental Strategies and Observations Leadership involvement (key informant interviews and advisory boards), employee focus groups and advisory boards, and quantitative environmental assessments cultivated participation and support. Determining multiple foci of change and designing measurable objectives and generic assessment tools to document progress are complex challenges encountered in planning phases. Lessons Learned Multi-level trials in diverse organizations require flexibility and balance of theory application and practice-based perspectives to affect impact and outcome objectives. Formative research is an essential component. PMID:18073339

  4. Business Modeling to Implement an eHealth Portal for Infection Control: A Reflection on Co-Creation With Stakeholders

    PubMed Central

    Wentzel, Jobke; Sanderman, Robbert; van Gemert-Pijnen, Lisette

    2015-01-01

    Background It is acknowledged that the success and uptake of eHealth improve with the involvement of users and stakeholders to make technology reflect their needs. Involving stakeholders in implementation research is thus a crucial element in developing eHealth technology. Business modeling is an approach to guide implementation research for eHealth. Stakeholders are involved in business modeling by identifying relevant stakeholders, conducting value co-creation dialogs, and co-creating a business model. Because implementation activities are often underestimated as a crucial step while developing eHealth, comprehensive and applicable approaches geared toward business modeling in eHealth are scarce. Objective This paper demonstrates the potential of several stakeholder-oriented analysis methods and their practical application was demonstrated using Infectionmanager as an example case. In this paper, we aim to demonstrate how business modeling, with the focus on stakeholder involvement, is used to co-create an eHealth implementation. Methods We divided business modeling in 4 main research steps. As part of stakeholder identification, we performed literature scans, expert recommendations, and snowball sampling (Step 1). For stakeholder analyzes, we performed “basic stakeholder analysis,” stakeholder salience, and ranking/analytic hierarchy process (Step 2). For value co-creation dialogs, we performed a process analysis and stakeholder interviews based on the business model canvas (Step 3). Finally, for business model generation, we combined all findings into the business model canvas (Step 4). Results Based on the applied methods, we synthesized a step-by-step guide for business modeling with stakeholder-oriented analysis methods that we consider suitable for implementing eHealth. Conclusions The step-by-step guide for business modeling with stakeholder involvement enables eHealth researchers to apply a systematic and multidisciplinary, co-creative approach for implementing eHealth. Business modeling becomes an active part in the entire development process of eHealth and starts an early focus on implementation, in which stakeholders help to co-create the basis necessary for a satisfying success and uptake of the eHealth technology. PMID:26272510

  5. Evaluation of the molecular level visualisation approach for teaching and learning chemistry in Thailand

    NASA Astrophysics Data System (ADS)

    Phenglengdi, Butsari

    This research evaluates the use of a molecular level visualisation approach in Thai secondary schools. The goal is to obtain insights about the usefulness of this approach, and to examine possible improvements in how the approach might be applied in the future. The methodology used for this research used both qualitative and quantitative approaches. Data were collected in the form of pre- and post-intervention multiple choice questions, open-ended-questions, drawing exercises, one-to-one interviews and video recordings of class activity. The research was conducted in two phases, involving a total of 261 students from the 11th Grade in Thailand. The use of VisChem animations in three studies was evaluated in Phase I. Study 1 was a pilot study exploring the benefits of incorporating VisChem animations to portray the molecular level. Study 2 compared test results between students exposed to these animations of molecular level events, and those not. Finally, in Study 3, test results were gathered from different types of schools (a rural school, a city school, and a university school). The results showed that students (and teachers) had misconceptions at the molecular level, and VisChem animations could help students understand chemistry concepts at the molecular level across all three types of schools. While the animation treatment group had a better score on the topic of states of water, the non-animation treatment group had a better score on the topic of dissolving sodium chloride in water than the animation group. The molecular level visualisation approach as a learning design was evaluated in Phase II. This approach involved a combination of VisChem animations, pictures, and diagrams together with the seven-step VisChem learning design. The study involved three classes of students, each with a different treatment, described as Class A - Traditional approach; Class B - VisChem animations with traditional approach; and Class C - Molecular level visualisation approach. Pre-test and post-test scores were compared across the three classes. The results from the multiple choice and calculation tests showed that the Class C - molecular level visualisation approach group demonstrated a deeper understanding of chemistry concepts than students in Classes A and B. However, the results showed that all the students were unable to perform satisfactorily on the calculation tests because the students had insufficient prior knowledge about stoichiometry to connect with the new knowledge. In the drawing tests the students exposed to the molecular level visualisation approach had a better mental model than the other classes, albeit with some remaining misconceptions. The findings highlight the intersecting nature of the teacher, student, and modelling in chemistry teaching. Use of a multi-step molecular level visualisation approach that encourages observation, reflection of prior understanding, and multiple opportunities at viewing (and using various visualisation elements), are key elements leading to a deeper understanding of chemistry. Presentation of the multi-step molecular level visualisation approach must be coupled with careful consideration of student prior knowledge, and with adequate guidance from a teacher who understands the topics at a deep level.

  6. Executive Functions Underlying Multiplicative Reasoning: Problem Type Matters

    ERIC Educational Resources Information Center

    Agostino, Alba; Johnson, Janice; Pascual-Leone, Juan

    2010-01-01

    We investigated the extent to which inhibition, updating, shifting, and mental-attentional capacity ("M"-capacity) contribute to children's ability to solve multiplication word problems. A total of 155 children in Grades 3-6 (8- to 13-year-olds) completed a set of multiplication word problems at two levels of difficulty: one-step and multiple-step…

  7. Mutations in PCYT1A cause spondylometaphyseal dysplasia with cone-rod dystrophy.

    PubMed

    Yamamoto, Guilherme L; Baratela, Wagner A R; Almeida, Tatiana F; Lazar, Monize; Afonso, Clara L; Oyamada, Maria K; Suzuki, Lisa; Oliveira, Luiz A N; Ramos, Ester S; Kim, Chong A; Passos-Bueno, Maria Rita; Bertola, Débora R

    2014-01-02

    Spondylometaphyseal dysplasia with cone-rod dystrophy is a rare autosomal-recessive disorder characterized by severe short stature, progressive lower-limb bowing, flattened vertebral bodies, metaphyseal involvement, and visual impairment caused by cone-rod dystrophy. Whole-exome sequencing of four individuals affected by this disorder from two Brazilian families identified two previously unreported homozygous mutations in PCYT1A. This gene encodes the alpha isoform of the phosphate cytidylyltransferase 1 choline enzyme, which is responsible for converting phosphocholine into cytidine diphosphate-choline, a key intermediate step in the phosphatidylcholine biosynthesis pathway. A different enzymatic defect in this pathway has been previously associated with a muscular dystrophy with mitochondrial structural abnormalities that does not have cartilage and/or bone or retinal involvement. Thus, the deregulation of the phosphatidylcholine pathway may play a role in multiple genetic diseases in humans, and further studies are necessary to uncover its precise pathogenic mechanisms and the entirety of its phenotypic spectrum. Copyright © 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  8. Influence of primary fragment excitation energy and spin distributions on fission observables

    NASA Astrophysics Data System (ADS)

    Litaize, Olivier; Thulliez, Loïc; Serot, Olivier; Chebboubi, Abdelaziz; Tamagno, Pierre

    2018-03-01

    Fission observables in the case of 252Cf(sf) are investigated by exploring several models involved in the excitation energy sharing and spin-parity assignment between primary fission fragments. In a first step the parameters used in the FIFRELIN Monte Carlo code "reference route" are presented: two parameters for the mass dependent temperature ratio law and two constant spin cut-off parameters for light and heavy fragment groups respectively. These parameters determine the initial fragment entry zone in excitation energy and spin-parity (E*, Jπ). They are chosen to reproduce the light and heavy average prompt neutron multiplicities. When these target observables are achieved all other fission observables can be predicted. We show here the influence of input parameters on the saw-tooth curve and we discuss the influence of a mass and energy-dependent spin cut-off model on gamma-rays related fission observables. The part of the model involving level densities, neutron transmission coefficients or photon strength functions remains unchanged.

  9. SREBP-regulated lipid metabolism: convergent physiology - divergent pathophysiology.

    PubMed

    Shimano, Hitoshi; Sato, Ryuichiro

    2017-12-01

    Cellular lipid metabolism and homeostasis are controlled by sterol regulatory-element binding proteins (SREBPs). In addition to performing canonical functions in the transcriptional regulation of genes involved in the biosynthesis and uptake of lipids, genome-wide system analyses have revealed that these versatile transcription factors act as important nodes of convergence and divergence within biological signalling networks. Thus, they are involved in myriad physiological and pathophysiological processes, highlighting the importance of lipid metabolism in biology. Changes in cell metabolism and growth are reciprocally linked through SREBPs. Anabolic and growth signalling pathways branch off and connect to multiple steps of SREBP activation and form complex regulatory networks. In addition, SREBPs are implicated in numerous pathogenic processes such as endoplasmic reticulum stress, inflammation, autophagy and apoptosis, and in this way, they contribute to obesity, dyslipidaemia, diabetes mellitus, nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, chronic kidney disease, neurodegenerative diseases and cancers. This Review aims to provide a comprehensive understanding of the role of SREBPs in physiology and pathophysiology at the cell, organ and organism levels.

  10. Vascular Cell Induction Culture System Using Arabidopsis Leaves (VISUAL) Reveals the Sequential Differentiation of Sieve Element-Like Cells.

    PubMed

    Kondo, Yuki; Nurani, Alif Meem; Saito, Chieko; Ichihashi, Yasunori; Saito, Masato; Yamazaki, Kyoko; Mitsuda, Nobutaka; Ohme-Takagi, Masaru; Fukuda, Hiroo

    2016-06-01

    Cell differentiation is a complex process involving multiple steps, from initial cell fate specification to final differentiation. Procambial/cambial cells, which act as vascular stem cells, differentiate into both xylem and phloem cells during vascular development. Recent studies have identified regulatory cascades for xylem differentiation. However, the molecular mechanism underlying phloem differentiation is largely unexplored due to technical challenges. Here, we established an ectopic induction system for phloem differentiation named Vascular Cell Induction Culture System Using Arabidopsis Leaves (VISUAL). Our results verified similarities between VISUAL-induced Arabidopsis thaliana phloem cells and in vivo sieve elements. We performed network analysis using transcriptome data with VISUAL to dissect the processes underlying phloem differentiation, eventually identifying a factor involved in the regulation of the master transcription factor gene APL Thus, our culture system opens up new avenues not only for genetic studies of phloem differentiation, but also for future investigations of multidirectional differentiation from vascular stem cells. © 2016 American Society of Plant Biologists. All rights reserved.

  11. Reliability of spatial-temporal gait parameters during dual-task interference in people with multiple sclerosis. A cross-sectional study.

    PubMed

    Monticone, Marco; Ambrosini, Emilia; Fiorentini, Roberta; Rocca, Barbara; Liquori, Valentina; Pedrocchi, Alessandra; Ferrante, Simona

    2014-09-01

    To evaluate the reliability and minimum detectable change (MDC) of spatial-temporal gait parameters in subjects with multiple sclerosis (MS) during dual tasking. This cross-sectional study involved 25 healthy subjects (mean age 49.9 ± 15.8 years) and 25 people with MS (mean age 49.2 ± 11.5 years). Gait under motor-cognitive and motor-motor dual tasking conditions was evaluated in two sessions separated by a one-day interval using the GAITRite Walkway System. Test-retest reliability was assessed using intraclass correlation coefficients (ICCs), standard errors of measurement (SEM), and coefficients of variation (CV). MDC scores were computed for the velocity, cadence, step and stride length, step and stride time, double support time, the % of gait cycle for single support and stance phase, and base of support. All of the gait parameters reported good to excellent ICCs under both conditions, with healthy subject values of >0.69 and MS subject values of >0.84. SEM values were always below 18% for both groups of subjects. The gait patterns of the people with MS were slightly more variable than those of the normal controls (CVs: 5.88-41.53% vs 2.84-30.48%). The assessment of quantitative gait parameters in healthy subjects and people with MS is highly reliable under both of the investigated dual tasking conditions. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Using regression equations built from summary data in the psychological assessment of the individual case: extension to multiple regression.

    PubMed

    Crawford, John R; Garthwaite, Paul H; Denham, Annie K; Chelune, Gordon J

    2012-12-01

    Regression equations have many useful roles in psychological assessment. Moreover, there is a large reservoir of published data that could be used to build regression equations; these equations could then be employed to test a wide variety of hypotheses concerning the functioning of individual cases. This resource is currently underused because (a) not all psychologists are aware that regression equations can be built not only from raw data but also using only basic summary data for a sample, and (b) the computations involved are tedious and prone to error. In an attempt to overcome these barriers, Crawford and Garthwaite (2007) provided methods to build and apply simple linear regression models using summary statistics as data. In the present study, we extend this work to set out the steps required to build multiple regression models from sample summary statistics and the further steps required to compute the associated statistics for drawing inferences concerning an individual case. We also develop, describe, and make available a computer program that implements these methods. Although there are caveats associated with the use of the methods, these need to be balanced against pragmatic considerations and against the alternative of either entirely ignoring a pertinent data set or using it informally to provide a clinical "guesstimate." Upgraded versions of earlier programs for regression in the single case are also provided; these add the point and interval estimates of effect size developed in the present article.

  13. The Virtual Physiological Human - a European initiative for in silico human modelling -.

    PubMed

    Viceconti, Marco; Clapworthy, Gordon; Van Sint Jan, Serge

    2008-12-01

    The Virtual Physiological Human (VPH) is an initiative, strongly supported by the European Commission (EC), that seeks to develop an integrated model of human physiology at multiple scales from the whole body through the organ, tissue, cell and molecular levels to the genomic level. VPH had its beginnings in 2005 with informal discussions amongst like-minded scientists which led to the STEP project, a Coordination Action funded by the EC that began in early 2006. The STEP project greatly accelerated the progress of the VPH and proved to be a catalyst for wide-ranging discussions within Europe and for outreach activities designed to develop a broad international approach to the huge scientific and technological challenges involved in this area. This paper provides an overview of the VPH and the developments it has engendered in the rapidly expanding worldwide activities associated with the physiome. It then uses one particular project, the Living Human Project, to illustrate the type of advances that are taking place to further the aims of the VPH and similar initiatives worldwide.

  14. HGF/scatter factor selectively promotes cell invasion by increasing integrin avidity.

    PubMed

    Trusolino, L; Cavassa, S; Angelini, P; Andó, M; Bertotti, A; Comoglio, P M; Boccaccio, C

    2000-08-01

    Hepatocyte growth factor/scatter factor (HGF/SF) controls a genetic program known as 'invasive growth', which involves as critical steps cell adhesion, migration, and trespassing of basement membranes. We show here that in MDA-MB-231 carcinoma cells, these steps are elicited by HGF/SF but not by epidermal growth factor (EGF). Neither factor substantially alters the production or activity of extracellular matrix proteases. HGF/SF, but not EGF, selectively promotes cell adhesion on laminins 1 and 5, fibronectin, and vitronectin through a PI3-K-dependent mechanism. Increased adhesion is followed by enhanced invasiveness through isolated matrix proteins as well as through reconstituted basement membranes. Inhibition assays using function-blocking antibodies show that this phenomenon is mediated by multiple integrins including beta1, beta3, beta4, and beta5. HGF/SF triggers clustering of all these integrins at actin-rich adhesive sites and lamellipodia but does not quantitatively modify their membrane expression. These data suggest that HGF/SF promotes cell adhesion and invasiveness by increasing the avidity of integrins for their specific ligands.

  15. Maturation of sperm volume regulation in the rat epididymis

    PubMed Central

    Damm, Oliver S.; Cooper, Trevor G.

    2010-01-01

    Sperm maturation in the epididymis may involve differences between mature and immature spermatozoa in their volume regulatory osmolyte response. Spermatozoa obtained from the rat caput and cauda epididymidis were examined for their ability to regulate volume after transfer from in situ epididymal osmolality (measured to be 343 ± 13 and 365 ± 19 mmol kg−1, respectively) to that of the female tract in single- and multiple-step protocols. Cells withstood the single-step treatment better than the multistep protocol. Sperm volume estimates by flow cytometric measurements of forward scatter of cells with intact head membranes was more sensitive than those by assessing cell coiling microscopically. At osmolalites below 210 mmol kg−1 both caput and cauda cells ruptured, limiting the use of flow cytometry. Above this critical value, the use of quinine showed that both caput and cauda cells could regulate volume, but cauda cells were the more effective. Of several organic osmolytes studied, myo-inositol, glutamate and KCl caused only temporary and slight swelling of spermatozoa cells in hypotonic medium. Spermatozoa of both maturities seemed to use potassium as the preferred osmolyte for regulating volume. PMID:20531277

  16. A preliminary model of work during initial examination and treatment planning appointments.

    PubMed

    Irwin, J Y; Torres-Urquidy, M H; Schleyer, T; Monaco, V

    2009-01-10

    Objective This study's objective was to formally describe the work process for charting and treatment planning in general dental practice to inform the design of a new clinical computing environment.Methods Using a process called contextual inquiry, researchers observed 23 comprehensive examination and treatment planning sessions during 14 visits to 12 general US dental offices. For each visit, field notes were analysed and reformulated as formalised models. Subsequently, each model type was consolidated across all offices and visits. Interruptions to the workflow, called breakdowns, were identified.Results Clinical work during dental examination and treatment planning appointments is a highly collaborative activity involving dentists, hygienists and assistants. Personnel with multiple overlapping roles complete complex multi-step tasks supported by a large and varied collection of equipment, artifacts and technology. Most of the breakdowns were related to technology which interrupted the workflow, caused rework and increased the number of steps in work processes.Conclusion Current dental software could be significantly improved with regard to its support for communication and collaboration, workflow, information design and presentation, information content, and data entry.

  17. Response surface optimization of medium components for naringinase production from Staphylococcus xylosus MAK2.

    PubMed

    Puri, Munish; Kaur, Aneet; Singh, Ram Sarup; Singh, Anubhav

    2010-09-01

    Response surface methodology was used to optimize the fermentation medium for enhancing naringinase production by Staphylococcus xylosus. The first step of this process involved the individual adjustment and optimization of various medium components at shake flask level. Sources of carbon (sucrose) and nitrogen (sodium nitrate), as well as an inducer (naringin) and pH levels were all found to be the important factors significantly affecting naringinase production. In the second step, a 22 full factorial central composite design was applied to determine the optimal levels of each of the significant variables. A second-order polynomial was derived by multiple regression analysis on the experimental data. Using this methodology, the optimum values for the critical components were obtained as follows: sucrose, 10.0%; sodium nitrate, 10.0%; pH 5.6; biomass concentration, 1.58%; and naringin, 0.50% (w/v), respectively. Under optimal conditions, the experimental naringinase production was 8.45 U/mL. The determination coefficients (R(2)) were 0.9908 and 0.9950 for naringinase activity and biomass production, respectively, indicating an adequate degree of reliability in the model.

  18. Ergonomic analyses within the French transport and logistics sector: first steps towards a new "act elsewhere" prevention approach.

    PubMed

    Wioland, Liên

    2013-10-01

    Statistics from the French Employee National Health Insurance Fund indicate high accident levels in the transport sector. This study represents initial thinking on a new approach to transport sector prevention based on the assumption that a work situation could be improved by acting on another interconnected work situation. Ergonomic analysis of two connected work situations, involving the road haulage drivers and cross-docking platform employees, was performed to test this assumption. Our results show that drivers are exposed to a number of identified risks, but their multiple tasks raise the question of activity intensification. The conditions, under which the drivers will perform their work and take to the road, are partly determined by the quality and organisation of the platform with which they interact. We make a number of recommendations (e.g. changing handling equipment, re-appraising certain jobs) to improve platform organisation and employee working conditions with the aim of also improving driver conditions. These initial steps in this prevention approach appear promising, but more detailed investigation is required. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Keeping Track Every Step of the Way

    NASA Technical Reports Server (NTRS)

    2001-01-01

    Knowledge Sharing Systems, Inc., a producer of intellectual assets management software systems for the federal government, universities, non-profit laboratories, and private companies, constructed and presently manages the NASA Technology Tracking System, also known as TechTracS. Under contract to Langley Research Center, TechTracS identifies and captures all NASA technologies, manages the patent prosecution process, and then tracks their progress en route to commercialization. The system supports all steps involved in various technology transfer activities, and is considered the premier intellectual asset management system used in the federal government today. NASA TechTracS consists of multiple relational databases and web servers, located at each of the 10 field centers, as well as NASA Headquarters. The system is capable of supporting the following functions: planning commercial technologies; commercialization activities; reporting new technologies and inventions; and processing and tracking intellectual property rights, licensing, partnerships, awards, and success stories. NASA TechTracS is critical to the Agency's ongoing mission to commercialize its revolutionary technologies in a variety of sectors within private industry, both aerospace and non- aerospace.

  20. Evaluating the efficiency of a zakat institution over a period of time using data envelopment analysis

    NASA Astrophysics Data System (ADS)

    Krishnan, Anath Rau; Hamzah, Ahmad Aizuddin

    2017-08-01

    It is crucial for a zakat institution to evaluate and understand how efficiently they have operated in the past, thus ideal strategies could be developed for future improvement. However, evaluating the efficiency of a zakat institution is actually a challenging process as it involves the presence of multiple inputs or/and outputs. This paper proposes a step-by-step procedure comprising two data envelopment analysis models, namely dual Charnes-Cooper-Rhodes and slack-based model to quantitatively measure the overall efficiency of a zakat institution over a period of time. The applicability of the proposed procedure was demonstrated by evaluating the efficiency of Pusat Zakat Sabah, Malaysia from the year of 2007 up to 2015 by treating each year as a decision making unit. Two inputs (i.e. number of staff and number of branches) and two outputs (i.e. total collection and total distribution) were used to measure the overall efficiency achieved each year. The causes of inefficiency and strategy for future improvement were discussed based on the results.

  1. Two-step relaxation mode analysis with multiple evolution times applied to all-atom molecular dynamics protein simulation.

    PubMed

    Karasawa, N; Mitsutake, A; Takano, H

    2017-12-01

    Proteins implement their functionalities when folded into specific three-dimensional structures, and their functions are related to the protein structures and dynamics. Previously, we applied a relaxation mode analysis (RMA) method to protein systems; this method approximately estimates the slow relaxation modes and times via simulation and enables investigation of the dynamic properties underlying the protein structural fluctuations. Recently, two-step RMA with multiple evolution times has been proposed and applied to a slightly complex homopolymer system, i.e., a single [n]polycatenane. This method can be applied to more complex heteropolymer systems, i.e., protein systems, to estimate the relaxation modes and times more accurately. In two-step RMA, we first perform RMA and obtain rough estimates of the relaxation modes and times. Then, we apply RMA with multiple evolution times to a small number of the slowest relaxation modes obtained in the previous calculation. Herein, we apply this method to the results of principal component analysis (PCA). First, PCA is applied to a 2-μs molecular dynamics simulation of hen egg-white lysozyme in aqueous solution. Then, the two-step RMA method with multiple evolution times is applied to the obtained principal components. The slow relaxation modes and corresponding relaxation times for the principal components are much improved by the second RMA.

  2. Two-step relaxation mode analysis with multiple evolution times applied to all-atom molecular dynamics protein simulation

    NASA Astrophysics Data System (ADS)

    Karasawa, N.; Mitsutake, A.; Takano, H.

    2017-12-01

    Proteins implement their functionalities when folded into specific three-dimensional structures, and their functions are related to the protein structures and dynamics. Previously, we applied a relaxation mode analysis (RMA) method to protein systems; this method approximately estimates the slow relaxation modes and times via simulation and enables investigation of the dynamic properties underlying the protein structural fluctuations. Recently, two-step RMA with multiple evolution times has been proposed and applied to a slightly complex homopolymer system, i.e., a single [n ] polycatenane. This method can be applied to more complex heteropolymer systems, i.e., protein systems, to estimate the relaxation modes and times more accurately. In two-step RMA, we first perform RMA and obtain rough estimates of the relaxation modes and times. Then, we apply RMA with multiple evolution times to a small number of the slowest relaxation modes obtained in the previous calculation. Herein, we apply this method to the results of principal component analysis (PCA). First, PCA is applied to a 2-μ s molecular dynamics simulation of hen egg-white lysozyme in aqueous solution. Then, the two-step RMA method with multiple evolution times is applied to the obtained principal components. The slow relaxation modes and corresponding relaxation times for the principal components are much improved by the second RMA.

  3. VLT/I Instrumentation: Lessons Learned FORUM

    NASA Astrophysics Data System (ADS)

    Monnet, G.; Bacon, R.

    2003-09-01

    This paper is the result of a joint effort by ESO and its Scientific and Technical Committee (STC) to extract the main lessons from last April's 'VLT/VLTI Instrumentation: Lessons learned' Forum and start applying them, in particular in the framework of the development of second generation VLT -and soon VLTI- instruments. This is but one step in a continuing effort to optimize these complex and challenging developments which involve a significant fraction of Europe's astronomical instrument builders in the near-UV to mid-IR range. With a major effort in the European radio community to build multiple receiver systems for ALMA now being pursued at an accelerated pace, it was also vital to revisit very quickly our whole procurement strategy in this area.

  4. Extraction and identification of flavonoids from parsley extracts by HPLC analysis

    NASA Astrophysics Data System (ADS)

    Stan, M.; Soran, M. L.; Varodi, C.; Lung, I.

    2012-02-01

    Flavonoids are phenolic compounds isolated from a wide variety of plants, and are valuable for their multiple properties, including antioxidant and antimicrobial activities. In the present work, parsley (Petroselinum crispum L.) extracts were obtained by three different extraction techniques: maceration, ultrasonic-assisted and microwave-assisted solvent extractions. The extractions were performed with ethanol-water mixtures in various ratios. From these extracts, flavonoids like the flavones apigenin and luteolin, and the flavonols quercetin and kaempferol were identified using an HPLC Shimadzu apparatus equipped with PDA and MS detectors. The separation method involved a gradient step. The mobile phase consisted of two solvents: acetonitrile and distilled water with 0.1% formic acid. The separation was performed on a RP-C18 column.

  5. Chemopreventive role of green tea in head and neck cancers.

    PubMed

    Kim, Yoo Suk; Kim, Chul-Ho

    2014-03-01

    In the era of personalized medicine, selecting the ideal treatment modality for head and neck cancer is becoming more complex. Also, despite the use of the newest agents, overall survival has not been improved notably over the past few decades. Currently, in accordance with the development of diagnostic tools, prevention and early detection of cancer are being emphasized more in obtaining better treatment outcomes. Among the various cancer preventative methods, the use of green tea is one of the most common approaches, and tea is known to be involved in multiple steps of carcinogenesis. Thus, in this short review, the protective roles of green tea components against the initiation, progression, and metastasis of head and neck malignancies will be discussed.

  6. Subsonic Glideback Rocket Demonstrator Flight Testing

    NASA Technical Reports Server (NTRS)

    DeTurris, Dianne J.; Foster, Trevor J.; Barthel, Paul E.; Macy, Daniel J.; Droney, Christopher K.; Talay, Theodore A. (Technical Monitor)

    2001-01-01

    For the past two years, Cal Poly's rocket program has been aggressively exploring the concept of remotely controlled, fixed wing, flyable rocket boosters. This program, embodied by a group of student engineers known as Cal Poly Space Systems, has successfully demonstrated the idea of a rocket design that incorporates a vertical launch pattern followed by a horizontal return flight and landing. Though the design is meant for supersonic flight, CPSS demonstrators are deployed at a subsonic speed. Many steps have been taken by the club that allowed the evolution of the StarBooster prototype to reach its current size: a ten-foot tall, one-foot diameter, composite material rocket. Progress is currently being made that involves multiple boosters along with a second stage, third rocket.

  7. Simultaneous Separation of Actinium and Radium Isotopes from a Proton Irradiated Thorium Matrix

    DOE PAGES

    Mastren, Tara; Radchenko, Valery; Owens, Allison; ...

    2017-08-15

    A new method has been developed for the isolation of 223,224,225Ra, in high yield and purity, from a proton irradiated 232Th matrix. We report an all-aqueous process using multiple solid-supported adsorption steps including a citrate chelation method developed to remove >99.9% of the barium contaminants by activity from the final radium product. Moreover, we developed a procedure involving the use of three columns in succession, and the separation of 223,224,225Ra from the thorium matrix was obtained with an overall recovery yield of 91 ± 3%, average radiochemical purity of 99.9%, and production yields that correspond to physical yields based onmore » previously measured excitation functions.« less

  8. Combined mining: discovering informative knowledge in complex data.

    PubMed

    Cao, Longbing; Zhang, Huaifeng; Zhao, Yanchang; Luo, Dan; Zhang, Chengqi

    2011-06-01

    Enterprise data mining applications often involve complex data such as multiple large heterogeneous data sources, user preferences, and business impact. In such situations, a single method or one-step mining is often limited in discovering informative knowledge. It would also be very time and space consuming, if not impossible, to join relevant large data sources for mining patterns consisting of multiple aspects of information. It is crucial to develop effective approaches for mining patterns combining necessary information from multiple relevant business lines, catering for real business settings and decision-making actions rather than just providing a single line of patterns. The recent years have seen increasing efforts on mining more informative patterns, e.g., integrating frequent pattern mining with classifications to generate frequent pattern-based classifiers. Rather than presenting a specific algorithm, this paper builds on our existing works and proposes combined mining as a general approach to mining for informative patterns combining components from either multiple data sets or multiple features or by multiple methods on demand. We summarize general frameworks, paradigms, and basic processes for multifeature combined mining, multisource combined mining, and multimethod combined mining. Novel types of combined patterns, such as incremental cluster patterns, can result from such frameworks, which cannot be directly produced by the existing methods. A set of real-world case studies has been conducted to test the frameworks, with some of them briefed in this paper. They identify combined patterns for informing government debt prevention and improving government service objectives, which show the flexibility and instantiation capability of combined mining in discovering informative knowledge in complex data.

  9. MIMO nonlinear ultrasonic tomography by propagation and backpropagation method.

    PubMed

    Dong, Chengdong; Jin, Yuanwei

    2013-03-01

    This paper develops a fast ultrasonic tomographic imaging method in a multiple-input multiple-output (MIMO) configuration using the propagation and backpropagation (PBP) method. By this method, ultrasonic excitation signals from multiple sources are transmitted simultaneously to probe the objects immersed in the medium. The scattering signals are recorded by multiple receivers. Utilizing the nonlinear ultrasonic wave propagation equation and the received time domain scattered signals, the objects are to be reconstructed iteratively in three steps. First, the propagation step calculates the predicted acoustic potential data at the receivers using an initial guess. Second, the difference signal between the predicted value and the measured data is calculated. Third, the backpropagation step computes updated acoustical potential data by backpropagating the difference signal to the same medium computationally. Unlike the conventional PBP method for tomographic imaging where each source takes turns to excite the acoustical field until all the sources are used, the developed MIMO-PBP method achieves faster image reconstruction by utilizing multiple source simultaneous excitation. Furthermore, we develop an orthogonal waveform signaling method using a waveform delay scheme to reduce the impact of speckle patterns in the reconstructed images. By numerical experiments we demonstrate that the proposed MIMO-PBP tomographic imaging method results in faster convergence and achieves superior imaging quality.

  10. Structural changes at the metal ion binding site during the phosphoglucomutase reaction.

    PubMed

    Ray, W J; Post, C B; Liu, Y; Rhyu, G I

    1993-01-12

    An electron density map of the reactive, Cd2+ form of crystalline phosphoglucomutase from X-ray diffraction studies shows that the enzymic phosphate donates a nonbridging oxygen to the ligand sphere of the bound metal ion, which appears to be tetracoordinate. 31P and 113Cd NMR spectroscopy are used to assess changes in the properties of bound Cd2+ produced by substrate/product and by substrate/product analog inhibitors. The approximately 50 ppm downfield shift of the 113Cd resonance on formation of the complex of dephosphoenzyme and glucose 1,6-bisphosphate is associated with the initial sugar-phosphate binding step and likely involves a change in the geometry of the coordinating ligands. This interpretation is supported by spectral studies involving various complexes of the active Co2+ and Ni(2+)-enzyme. In addition, there is a loss of the 31P-113Cd J coupling that characterizes the monophosphate complexes of the Cd2+ enzyme either during or immediately after the PO3- transfer step that produces the bisphosphate complex, indicating a further change at the metal binding site. The implications of these observations with respect to the PO3- transfer process in the phosphoglucomutase reaction are considered. The apparent plasticity of the ligand sphere of the active site metal ion in this system may allow a single metal ion to act as a chaperone for a nonbridging oxygen during PO3- transfer or to allow a change in metal ion coordination during catalysis. A general NMR line shape/chemical-exchange analysis for evaluating binding in protein-ligand systems when exchange is intermediate to fast on the NMR time scale is described. Its application to the present system involves multiple exchange sites that depend on a single binding rate, thereby adding further constraints to the analysis.

  11. "It Might Actually Work This Time": Benefits and Barriers to Adapted 12-Step Facilitation Therapy and Mutual-Help Group Attendance From the Perspective of Dually Diagnosed Individuals.

    PubMed

    Hagler, Kylee J; Rice, Samara L; Muñoz, Rosa E; Salvador, Julie G; Forcehimes, Alyssa A; Bogenschutz, Michael P

    2015-01-01

    Most U.S. healthcare professionals encourage mutual-help group involvement as an adjunct to treatment or aftercare for individuals with substance use disorders, yet there are multiple challenges in engaging in these community groups. Dually diagnosed individuals (DDIs) may face additional challenges in affiliating with mutual-help groups. Twelve-step facilitation for DDIs (TSF-DD), a manualized treatment to facilitate mutual-help group involvement, was developed to help patients engage in Double Trouble in Recovery (DTR), a mutual-help group tailored to DDIs. Given the promising role that TSF-DD and DTR may have for increasing abstinence while managing psychiatric symptoms, the aim of the current study was to systematically examine reasons for TSF-DD and DTR attendance from the perspective of DDIs using focus group data. Participants were a subset (n = 15) of individuals diagnosed with an alcohol use disorder as well as a major depressive, bipolar, or psychotic disorder who participated in a parent study testing the efficacy of TSF-DD for increasing mutual-help group involvement and reducing alcohol use. Analyses of focus group data revealed that participants construed DTR and TSF-DD as helpful tools in the understanding and management of their disorders. Relative to other mutual-help groups in which participants reported feeling ostracized because of their dual diagnoses, participants reported that it was beneficial to learn about dual disorders in a safe and accepting environment. Participants also expressed aspects that they disliked. Results from this study yield helpful empirical recommendations to healthcare professionals seeking to increase DDIs' participation in DTR or other mutual-help groups.

  12. Mother Involvement as an Influence on Father Involvement with Early Adolescents

    PubMed Central

    Pleck, Joseph H.; Hofferth, Sandra L.

    2009-01-01

    This study hypothesized that father involvement is influenced by mothers' level of involvement as well as by marital conflict, mothers' work hours, and fathers' status as biological or step father. The analysis also tested hypotheses about mother involvement as a potential mediator of the effects of marital conflict and maternal work hours on father involvement, and hypotheses about factors influencing mother involvement. Children aged 10-14 from the NLSY79 who resided with their biological or step father and with their mother reported on each parent's involvement with them. As hypothesized, father involvement was predicted by mother involvement, and the reciprocal influence was not significant. Father involvement was associated with low marital conflict and being a biological father. Mothers' involvement partially mediated the effects of marital conflict on father involvement. If the mediating role of maternal involvement is not taken into account, the effect of marital conflict on father involvement is overestimated. PMID:21776195

  13. Multiplication Fact Fluency Using Doubles

    ERIC Educational Resources Information Center

    Flowers, Judith M.; Rubenstein, Rheta N.

    2010-01-01

    Not knowing multiplication facts creates a gap in a student's mathematics development and undermines confidence and disposition toward further mathematical learning. Learning multiplication facts is a first step in proportional reasoning, "the capstone of elementary arithmetic and the gateway to higher mathematics" (NRC 2001, p. 242). Proportional…

  14. Applying the Verona coding definitions of emotional sequences (VR-CoDES) in the dental context involving patients with complex communication needs: An exploratory study.

    PubMed

    Zhou, Yuefang; Black, Rolf; Freeman, Ruth; Herron, Daniel; Humphris, Gerry; Menzies, Rachel; Quinn, Sandra; Scott, Lesley; Waller, Annalu

    2014-11-01

    The VR-CoDES has been previously applied in the dental context. However, we know little about how dental patients with intellectual disabilities (ID) and complex communication needs express their emotional distress during dental visits. This is the first study explored the applicability of the VR-CoDES to a dental context involving patients with ID. Fourteen dental consultations were video recorded and coded using the VR-CoDES, assisted with the additional guidelines for the VR-CoDES in a dental context. Both inter- and intra-coder reliabilities were checked on the seven consultations where cues were observed. Sixteen cues (eight non-verbal) were identified within seven of the 14 consultations. Twenty responses were observed (12 reducing space) with four multiple responses. Cohen's Kappa were 0.76 (inter-coder) and 0.88 (intra-coder). With the additional guidelines, cues and responses were reliably identified. Cue expression was exhibited by non-verbal expression of emotion with people with ID in the literature. Further guidance is needed to improve the coding accuracy on multiple providers' responses and to investigate potential impacts of conflicting responses on patients. The findings provided a useful initial step towards an ongoing exploration of how healthcare providers identify and manage emotional distress of patients with ID. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  15. Grandparenting and adolescent adjustment in two-parent biological, lone-parent, and step-families.

    PubMed

    Attar-Schwartz, Shalhevet; Tan, Jo-Pei; Buchanan, Ann; Flouri, Eirini; Griggs, Julia

    2009-02-01

    There is limited research on the links between grandparenting and adolescents' well-being, especially from the perspective of the adolescents. The study examined whether grandparent involvement varied in two-parent biological, lone-parent, and step-families and whether this had a different contribution to the emotional and behavioral adjustment of adolescents across different family structures. The study is based on a sample of 1,515 secondary school students (ages 11-16 years) from England and Wales who completed a structured questionnaire. Findings of hierarchical regression analyses showed that among the whole sample, greater grandparent involvement was associated with fewer emotional problems (p < .01) and with more prosocial behavior (p < .001). In addition, while there were no differences in the level of grandparent involvement across the different family structures, grandparent involvement was more strongly associated with reduced adjustment difficulties among adolescents from lone-parent and step-families than those from two-parent biological families. A possible implication is that the positive role of grandparent involvement in lone-parent and step- families should be more emphasized in family psychology. (PsycINFO Database Record (c) 2009 APA, all rights reserved).

  16. The Relationship Between Non-Symbolic Multiplication and Division in Childhood

    PubMed Central

    McCrink, Koleen; Shafto, Patrick; Barth, Hilary

    2016-01-01

    Children without formal education in addition and subtraction are able to perform multi-step operations over an approximate number of objects. Further, their performance improves when solving approximate (but not exact) addition and subtraction problems that allow for inversion as a shortcut (e.g., a + b − b = a). The current study examines children’s ability to perform multi-step operations, and the potential for an inversion benefit, for the operations of approximate, non-symbolic multiplication and division. Children were trained to compute a multiplication and division scaling factor (*2 or /2, *4 or /4), and then tested on problems that combined two of these factors in a way that either allowed for an inversion shortcut (e.g., 8 * 4 / 4) or did not (e.g., 8 * 4 / 2). Children’s performance was significantly better than chance for all scaling factors during training, and they successfully computed the outcomes of the multi-step testing problems. They did not exhibit a performance benefit for problems with the a * b / b structure, suggesting they did not draw upon inversion reasoning as a logical shortcut to help them solve the multi-step test problems. PMID:26880261

  17. A multiple-objective optimal exploration strategy

    USGS Publications Warehouse

    Christakos, G.; Olea, R.A.

    1988-01-01

    Exploration for natural resources is accomplished through partial sampling of extensive domains. Such imperfect knowledge is subject to sampling error. Complex systems of equations resulting from modelling based on the theory of correlated random fields are reduced to simple analytical expressions providing global indices of estimation variance. The indices are utilized by multiple objective decision criteria to find the best sampling strategies. The approach is not limited by geometric nature of the sampling, covers a wide range in spatial continuity and leads to a step-by-step procedure. ?? 1988.

  18. Key Steps in the Special Review Process

    EPA Pesticide Factsheets

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

  19. Scanning sequences after Gibbs sampling to find multiple occurrences of functional elements

    PubMed Central

    Tharakaraman, Kannan; Mariño-Ramírez, Leonardo; Sheetlin, Sergey L; Landsman, David; Spouge, John L

    2006-01-01

    Background Many DNA regulatory elements occur as multiple instances within a target promoter. Gibbs sampling programs for finding DNA regulatory elements de novo can be prohibitively slow in locating all instances of such an element in a sequence set. Results We describe an improvement to the A-GLAM computer program, which predicts regulatory elements within DNA sequences with Gibbs sampling. The improvement adds an optional "scanning step" after Gibbs sampling. Gibbs sampling produces a position specific scoring matrix (PSSM). The new scanning step resembles an iterative PSI-BLAST search based on the PSSM. First, it assigns an "individual score" to each subsequence of appropriate length within the input sequences using the initial PSSM. Second, it computes an E-value from each individual score, to assess the agreement between the corresponding subsequence and the PSSM. Third, it permits subsequences with E-values falling below a threshold to contribute to the underlying PSSM, which is then updated using the Bayesian calculus. A-GLAM iterates its scanning step to convergence, at which point no new subsequences contribute to the PSSM. After convergence, A-GLAM reports predicted regulatory elements within each sequence in order of increasing E-values, so users have a statistical evaluation of the predicted elements in a convenient presentation. Thus, although the Gibbs sampling step in A-GLAM finds at most one regulatory element per input sequence, the scanning step can now rapidly locate further instances of the element in each sequence. Conclusion Datasets from experiments determining the binding sites of transcription factors were used to evaluate the improvement to A-GLAM. Typically, the datasets included several sequences containing multiple instances of a regulatory motif. The improvements to A-GLAM permitted it to predict the multiple instances. PMID:16961919

  20. MicroRNA and receptor mediated signaling pathways as potential therapeutic targets in heart failure.

    PubMed

    Tuttolomondo, Antonino; Simonetta, Irene; Pinto, Antonio

    2016-11-01

    Cardiac remodelling is a complex pathogenetic pathway involving genome expression, molecular, cellular, and interstitial changes that cause changes in size, shape and function of the heart after cardiac injury. Areas covered: We will review recent advances in understanding the role of several receptor-mediated signaling pathways and micro-RNAs, in addition to their potential as candidate target pathways in the pathogenesis of heart failure. The myocyte is the main target cell involved in the remodelling process via ischemia, cell necrosis and apoptosis (by means of various receptor pathways), and other mechanisms mediated by micro-RNAs. We will analyze the role of some receptor mediated signaling pathways such as natriuretic peptides, mediators of glycogen synthase kinase 3 and ERK1/2 pathways, beta-adrenergic receptor subtypes and relaxin receptor signaling mechanisms, TNF/TNF receptor family and TWEAK/Fn14 axis, and some micro-RNAs as candidate target pathways in pathogenesis of heart failure. These mediators of receptor-mediated pathways and micro-RNA are the most addressed targets of emerging therapies in modern heart failure treatment strategies. Expert opinion: Future treatment strategies should address mediators involved in multiple steps within heart failure pathogenetic pathways.

  1. Validated analytical methodology for the simultaneous determination of a wide range of pesticides in human blood using GC-MS/MS and LC-ESI/MS/MS and its application in two poisoning cases.

    PubMed

    Luzardo, Octavio P; Almeida-González, Maira; Ruiz-Suárez, Norberto; Zumbado, Manuel; Henríquez-Hernández, Luis A; Meilán, María José; Camacho, María; Boada, Luis D

    2015-09-01

    Pesticides are frequently responsible for human poisoning and often the information on the involved substance is lacking. The great variety of pesticides that could be responsible for intoxication makes necessary the development of powerful and versatile analytical methodologies, which allows the identification of the unknown toxic substance. Here we developed a methodology for simultaneous identification and quantification in human blood of 109 highly toxic pesticides. The application of this analytical scheme would help in minimizing the cost of this type of chemical identification, maximizing the chances of identifying the pesticide involved. In the methodology that we present here, we use a liquid-liquid extraction, followed by one single purification step, and quantitation of analytes by a combination of liquid and gas chromatography, both coupled to triple quadrupole mass spectrometry, which is operated in the mode of multiple reaction monitoring. The methodology has been fully validated, and its applicability has been demonstrated in two recent cases involving one self-poisoning fatality and one non-fatal homicidal attempt. Copyright © 2015 The Chartered Society of Forensic Sciences. Published by Elsevier Ireland Ltd. All rights reserved.

  2. New particle formation and growth from methanesulfonic acid, trimethylamine and water.

    PubMed

    Chen, Haihan; Ezell, Michael J; Arquero, Kristine D; Varner, Mychel E; Dawson, Matthew L; Gerber, R Benny; Finlayson-Pitts, Barbara J

    2015-05-28

    New particle formation from gas-to-particle conversion represents a dominant source of atmospheric particles and affects radiative forcing, climate and human health. The species involved in new particle formation and the underlying mechanisms remain uncertain. Although sulfuric acid is commonly recognized as driving new particle formation, increasing evidence suggests the involvement of other species. Here we study particle formation and growth from methanesulfonic acid, trimethylamine and water at reaction times from 2.3 to 32 s where particles are 2-10 nm in diameter using a newly designed and tested flow system. The flow system has multiple inlets to facilitate changing the mixing sequence of gaseous precursors. The relative humidity and precursor concentrations, as well as the mixing sequence, are varied to explore their effects on particle formation and growth in order to provide insight into the important mechanistic steps. We show that water is involved in the formation of initial clusters, greatly enhancing their formation as well as growth into detectable size ranges. A kinetics box model is developed that quantitatively reproduces the experimental data under various conditions. Although the proposed scheme is not definitive, it suggests that incorporating such mechanisms into atmospheric models may be feasible in the near future.

  3. What’s bad in cancer is good in the embryo: Importance of EMT in neural crest development

    PubMed Central

    Kerosuo, Laura; Bronner-Fraser, Marianne

    2012-01-01

    Although the epithelial to mesenchymal transition (EMT) is famous for its role in cancer metastasis, it also is a normal developmental event in which epithelial cells are converted into migratory mesenchymal cells. A prime example of EMT during development occurs when neural crest (NC) cells emigrate from the neural tube thus providing an excellent model to study the principles of EMT in a nonmalignant environment. NC cells start life as neuroepithelial cells intermixed with precursors of the central nervous system. After EMT, they delaminate and begin migrating, often to distant sites in the embryo. While proliferating and maintaining multipotency and cell survival the transitioning neural crest cells lose apicobasal polarity and the basement membrane is broken down. This review discusses how these events are coordinated and regulated, by series of events involving signaling factors, gene regulatory interactions, as well as epigenetic and post-transcriptional modifications. Even though the series of events involved in NC EMT are well known, the sequence in which these steps take place remains a subject of debate, raising the intriguing possibility that, rather than being a single event, neural crest EMT may involve multiple parallel mechanisms. PMID:22430756

  4. A Two-Step Approach for Producing an Ultrafine-Grain Structure in Cu-30Zn Brass (Postprint)

    DTIC Science & Technology

    2015-08-13

    crystallization anneal at 400 °C (0.55Tm, where Tm is the melting point ) for times ranging from 1 min to 10 hours, followed by water quenching; an additional...200 words) A two-step approach involving cryogenic rolling and subsequent recrystallization annealing was developed to produce an ultrafine-grain...b s t r a c t A two-step approach involving cryogenic rolling and subsequent recrystallization annealing was devel- oped to produce an ultrafine

  5. Oxidative stress induced oligomerization inhibits the activity of the non-receptor tyrosine phosphatase STEP61

    PubMed Central

    Deb, Ishani; Poddar, Ranjana; Paul, Surojit

    2011-01-01

    The neuron-specific tyrosine phosphatase STEP (STriatal Enriched Phosphatase) is emerging as an important mediator of glutamatergic transmission in the brain. STEP is also thought to be involved in the etiology of neurodegenerative disorders that are linked to oxidative stress such as Alzheimer's disease and cerebral ischemia. However the mechanism by which oxidative stress can modulate STEP activity is still unclear. In the present study we have investigated whether dimerization may play a role in regulating the activity of STEP. Our findings show that STEP61, the membrane associated isoform, can undergo homodimerization under basal conditions in neurons. Dimerization of STEP61 involves intermolecular disulfide bond formation between two cysteine residues (Cys 65 and Cys 76 respectively) present in the hydrophobic region at the N-terminus specific to STEP61. Oxidative stress-induced by hydrogen peroxide leads to a significant increase in the formation of dimers and higher order oligomers of STEP61. Using two substrates, para-nitrophenylphosphate and ERK MAPK we further demonstrate that oligomerization leads to a significant reduction in its enzymatic activity. PMID:21198639

  6. Contribution of lower limb eccentric work and different step responses to balance recovery among older adults.

    PubMed

    Nagano, Hanatsu; Levinger, Pazit; Downie, Calum; Hayes, Alan; Begg, Rezaul

    2015-09-01

    Falls during walking reflect susceptibility to balance loss and the individual's capacity to recover stability. Balance can be recovered using either one step or multiple steps but both responses are impaired with ageing. To investigate older adults' (n=15, 72.5±4.8 yrs) recovery step control a tether-release procedure was devised to induce unanticipated forward balance loss. Three-dimensional position-time data combined with foot-ground reaction forces were used to measure balance recovery. Dependent variables were; margin of stability (MoS) and available response time (ART) for spatial and temporal balance measures in the transverse and sagittal planes; lower limb joint angles and joint negative/positive work; and spatio-temporal gait parameters. Relative to multi-step responses, single-step recovery was more effective in maintaining balance, indicated by greater MoS and longer ART. MoS in the sagittal plane measure and ART in the transverse plane distinguished single step responses from multiple steps. When MoS and ART were negative (<0), balance was not secured and additional steps would be required to establish the new base of support for balance recovery. Single-step responses demonstrated greater step length and velocity and when the recovery foot landed, greater centre of mass downward velocity. Single-step strategies also showed greater ankle dorsiflexion, increased knee maximum flexion and more negative work at the ankle and knee. Collectively these findings suggest that single-step responses are more effective in forward balance recovery by directing falling momentum downward to be absorbed as lower limb eccentric work. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. A small step in VLC systems - a big step in Li-Fi implementation

    NASA Astrophysics Data System (ADS)

    Rîurean, S. M.; Nagy, A. A.; Leba, M.; Ionica, A. C.

    2018-01-01

    Light is part of our sustainable environmental life so, using it would be the handiest and cheapest way for wireless communication. Since ever, light has been used to send messages in different ways and now, due to the high technological improvements, bits through light, at high speed on multiple paths, allow humans to communicate. Using the lighting system both for illumination and communication represents lately one of the worldwide main research issues with several implementations with real benefits. This paper presents a viable VLC system, that proves its sustainability for sending by light information not only few millimetres but meters away. This system has multiple potential applications in different areas where other communication systems are bottlenecked, too expensive, unavailable or even forbidden. Since a Li-Fi fully developed system requires bidirectional, multiple access communication, there are still some challenges towards a functional Li-Fi wireless network. Although important steps have been made, Li-Fi is still under experimental stage.

  8. Improvement of surgical margin with a coupled saline-radio-frequency device for multiple colorectal liver metastases.

    PubMed

    Ogata, Satoshi; Kianmanesh, Reza; Varma, Deepak; Belghiti, Jacques

    2005-01-01

    Complete resection of colorectal liver metastases (LM) has been the only curative treatment. However, when LM are multiple and bilobar, only a few patients are candidates for curative surgery. We report on a 53-year-old woman with synchronous multiple and bilobar LM from sigmoidal cancer who became resectable after a multimodal strategy including preoperative systemic chemotherapy and two-step surgery. The spectacular decrease in tumor size after systemic chemotherapy led us to perform two-step surgery, including right portal-vein ligation and left liver metastasectomies, with a coupled saline-radiofrequency device, in order to improve the surgical margin. An extended right hepatectomy was performed later to remove the remaining right liver lesions. The patient was discharged after 28 days without major complication and was recurrence-free 14 months later. We conclude that improving the surgical margin with a coupled saline-radiofrequency device is feasible and effective, avoiding small remnant liver even after multiple tumorectomies. The multimodal strategy, including preoperative chemotherapy, two-step surgery, and tumorectomies, using a coupled saline-radiofrequency device, could increase the number of patients with diffuse bilobar liver metastases who can benefit from liver resection.

  9. Parents Are Lifesavers. A Handbook for Parent Involvement in Schools.

    ERIC Educational Resources Information Center

    Batey, Carol S.

    Practical and well-defined solutions are presented to build effective and long-lasting partnerships among parents, educators, and community members for the improvement of schools. A step-by-step model is presented, with an outline to guide anyone attempting to involve parents in their children's schools. Chapter 1, "My Journey to Parent…

  10. Guidelines for conducting TMDL consultations on selenium

    Treesearch

    Dennis A. Lemly

    2000-01-01

    This report was prepared to provide Environmental Contaminants Specialists in the U.S. Fish and Wildlife Service (Service) with a step-by-step procedure for consultations involving Total Maximum Daily Loads (TMDL's) for selenium. The need for this information stems from recent actions taken by the U.S. Environmental Protection Agency (EPA) that will involve the...

  11. Teachers as Child Advocates: A Continuum of Involvement.

    ERIC Educational Resources Information Center

    Lindamood, Judy B.

    1995-01-01

    Describes the steps to increasing levels of teacher involvement in child advocacy. Steps range from "dreamer" with a vision of a better condition, to "volunteer" who gives time and energy without compensation, to "fighter" who uses conflict and dissension to achieve goals. Suggests that this simple continuum encourages teachers to become involved…

  12. Step by Step to Smoke-Free Schools.

    ERIC Educational Resources Information Center

    VanSciver, James H.; Roberts, H. Earl

    1989-01-01

    This ERIC digest discusses ways of effectively banning smoking in schools so that controversies do not continue after implementation of the policy. By advocating a process approach, the document cites steps taken by the Lake Forest School Board to prohibit smoking in and around school grounds. Step one involved committee planning involving…

  13. The effects of continuing care on emerging adult outcomes following residential addiction treatment.

    PubMed

    Bergman, Brandon G; Hoeppner, Bettina B; Nelson, Lindsay M; Slaymaker, Valerie; Kelly, John F

    2015-08-01

    Professional continuing care services enhance recovery rates among adults and adolescents, though less is known about emerging adults (18-25 years old). Despite benefit shown from emerging adults' participation in 12-step mutual-help organizations (MHOs), it is unclear whether participation offers benefit independent of professional continuing care services. Greater knowledge in this area would inform clinical referral and linkage efforts. Emerging adults (N=284; 74% male; 95% Caucasian) were assessed during the year after residential treatment on outpatient sessions per week, percent days in residential treatment and residing in a sober living environment, substance use disorder (SUD) medication use, active 12-step MHO involvement (e.g., having a sponsor, completing step work, contact with members outside meetings), and continuous abstinence (dichotomized yes/no). One generalized estimating equation (GEE) model tested the unique effect of each professional service on abstinence, and, in a separate GEE model, the unique effect of 12-step MHO involvement on abstinence over and above professional services, independent of individual covariates. Apart from SUD medication, all professional continuing care services were significantly associated with abstinence over and above individual factors. In the more comprehensive model, relative to zero 12-step MHO activities, odds of abstinence were 1.3 times greater if patients were involved in one activity, and 3.2 times greater if involved in five activities (lowest mean number of activities in the sample across all follow-ups). Both active involvement in 12-step MHOs and recovery-supportive, professional services that link patients with these community-based resources may enhance outcomes for emerging adults after residential treatment. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  14. Multi-view video segmentation and tracking for video surveillance

    NASA Astrophysics Data System (ADS)

    Mohammadi, Gelareh; Dufaux, Frederic; Minh, Thien Ha; Ebrahimi, Touradj

    2009-05-01

    Tracking moving objects is a critical step for smart video surveillance systems. Despite the complexity increase, multiple camera systems exhibit the undoubted advantages of covering wide areas and handling the occurrence of occlusions by exploiting the different viewpoints. The technical problems in multiple camera systems are several: installation, calibration, objects matching, switching, data fusion, and occlusion handling. In this paper, we address the issue of tracking moving objects in an environment covered by multiple un-calibrated cameras with overlapping fields of view, typical of most surveillance setups. Our main objective is to create a framework that can be used to integrate objecttracking information from multiple video sources. Basically, the proposed technique consists of the following steps. We first perform a single-view tracking algorithm on each camera view, and then apply a consistent object labeling algorithm on all views. In the next step, we verify objects in each view separately for inconsistencies. Correspondent objects are extracted through a Homography transform from one view to the other and vice versa. Having found the correspondent objects of different views, we partition each object into homogeneous regions. In the last step, we apply the Homography transform to find the region map of first view in the second view and vice versa. For each region (in the main frame and mapped frame) a set of descriptors are extracted to find the best match between two views based on region descriptors similarity. This method is able to deal with multiple objects. Track management issues such as occlusion, appearance and disappearance of objects are resolved using information from all views. This method is capable of tracking rigid and deformable objects and this versatility lets it to be suitable for different application scenarios.

  15. A perturbation-based balance training program for older adults: study protocol for a randomised controlled trial

    PubMed Central

    Mansfield, Avril; Peters, Amy L; Liu, Barbara A; Maki, Brian E

    2007-01-01

    Background Previous research investigating exercise as a means of falls prevention in older adults has shown mixed results. Lack of specificity of the intervention may be an important factor contributing to negative results. Change-in-support (CIS) balance reactions, which involve very rapid stepping or grasping movements of the limbs, play a critical role in preventing falls; hence, a training program that improves ability to execute effective CIS reactions could potentially have a profound effect in reducing risk of falling. This paper describes: 1) the development of a perturbation-based balance training program that targets specific previously-reported age-related impairments in CIS reactions, and 2) a study protocol to evaluate the efficacy of this new training program. Methods/Design The training program involves use of unpredictable, multi-directional moving-platform perturbations to evoke stepping and grasping reactions. Perturbation magnitude is gradually increased over the course of the 6-week program, and concurrent cognitive and movement tasks are included during later sessions. The program was developed in accordance with well-established principles of motor learning, such as individualisation, specificity, overload, adaptation-progression and variability. Specific goals are to reduce the frequency of multiple-step responses, reduce the frequency of collisions between the stepping foot and stance leg, and increase the speed of grasping reactions. A randomised control trial will be performed to evaluate the efficacy of the training program. A total of 30 community-dwelling older adults (age 64–80) with a recent history of instability or falling will be assigned to either the perturbation-based training or a control group (flexibility/relaxation training), using a stratified randomisation that controls for gender, age and baseline stepping/grasping performance. CIS reactions will be tested immediately before and after the six weeks of training, using platform perturbations as well as a distinctly different method of perturbation (waist pulls) in order to evaluate the generalisability of the training effects. Discussion This study will determine whether perturbation-based balance training can help to reverse specific age-related impairments in balance-recovery reactions. These results will help to guide the development of more effective falls prevention programs, which may ultimately lead to reduced health-care costs and enhanced mobility, independence and quality of life. PMID:17540020

  16. Future aircraft networks and schedules

    NASA Astrophysics Data System (ADS)

    Shu, Yan

    2011-07-01

    Because of the importance of air transportation scheduling, the emergence of small aircraft and the vision of future fuel-efficient aircraft, this thesis has focused on the study of aircraft scheduling and network design involving multiple types of aircraft and flight services. It develops models and solution algorithms for the schedule design problem and analyzes the computational results. First, based on the current development of small aircraft and on-demand flight services, this thesis expands a business model for integrating on-demand flight services with the traditional scheduled flight services. This thesis proposes a three-step approach to the design of aircraft schedules and networks from scratch under the model. In the first step, both a frequency assignment model for scheduled flights that incorporates a passenger path choice model and a frequency assignment model for on-demand flights that incorporates a passenger mode choice model are created. In the second step, a rough fleet assignment model that determines a set of flight legs, each of which is assigned an aircraft type and a rough departure time is constructed. In the third step, a timetable model that determines an exact departure time for each flight leg is developed. Based on the models proposed in the three steps, this thesis creates schedule design instances that involve almost all the major airports and markets in the United States. The instances of the frequency assignment model created in this thesis are large-scale non-convex mixed-integer programming problems, and this dissertation develops an overall network structure and proposes iterative algorithms for solving these instances. The instances of both the rough fleet assignment model and the timetable model created in this thesis are large-scale mixed-integer programming problems, and this dissertation develops subproblem schemes for solving these instances. Based on these solution algorithms, this dissertation also presents computational results of these large-scale instances. To validate the models and solution algorithms developed, this thesis also compares the daily flight schedules that it designs with the schedules of the existing airlines. Furthermore, it creates instances that represent different economic and fuel-prices conditions and derives schedules under these different conditions. In addition, it discusses the implication of using new aircraft in the future flight schedules. Finally, future research in three areas---model, computational method, and simulation for validation---is proposed.

  17. A perturbation-based balance training program for older adults: study protocol for a randomised controlled trial.

    PubMed

    Mansfield, Avril; Peters, Amy L; Liu, Barbara A; Maki, Brian E

    2007-05-31

    Previous research investigating exercise as a means of falls prevention in older adults has shown mixed results. Lack of specificity of the intervention may be an important factor contributing to negative results. Change-in-support (CIS) balance reactions, which involve very rapid stepping or grasping movements of the limbs, play a critical role in preventing falls; hence, a training program that improves ability to execute effective CIS reactions could potentially have a profound effect in reducing risk of falling. This paper describes: 1) the development of a perturbation-based balance training program that targets specific previously-reported age-related impairments in CIS reactions, and 2) a study protocol to evaluate the efficacy of this new training program. The training program involves use of unpredictable, multi-directional moving-platform perturbations to evoke stepping and grasping reactions. Perturbation magnitude is gradually increased over the course of the 6-week program, and concurrent cognitive and movement tasks are included during later sessions. The program was developed in accordance with well-established principles of motor learning, such as individualisation, specificity, overload, adaptation-progression and variability. Specific goals are to reduce the frequency of multiple-step responses, reduce the frequency of collisions between the stepping foot and stance leg, and increase the speed of grasping reactions. A randomised control trial will be performed to evaluate the efficacy of the training program. A total of 30 community-dwelling older adults (age 64-80) with a recent history of instability or falling will be assigned to either the perturbation-based training or a control group (flexibility/relaxation training), using a stratified randomisation that controls for gender, age and baseline stepping/grasping performance. CIS reactions will be tested immediately before and after the six weeks of training, using platform perturbations as well as a distinctly different method of perturbation (waist pulls) in order to evaluate the generalisability of the training effects. This study will determine whether perturbation-based balance training can help to reverse specific age-related impairments in balance-recovery reactions. These results will help to guide the development of more effective falls prevention programs, which may ultimately lead to reduced health-care costs and enhanced mobility, independence and quality of life.

  18. Comparing Anisotropic Output-Based Grid Adaptation Methods by Decomposition

    NASA Technical Reports Server (NTRS)

    Park, Michael A.; Loseille, Adrien; Krakos, Joshua A.; Michal, Todd

    2015-01-01

    Anisotropic grid adaptation is examined by decomposing the steps of flow solution, ad- joint solution, error estimation, metric construction, and simplex grid adaptation. Multiple implementations of each of these steps are evaluated by comparison to each other and expected analytic results when available. For example, grids are adapted to analytic metric fields and grid measures are computed to illustrate the properties of multiple independent implementations of grid adaptation mechanics. Different implementations of each step in the adaptation process can be evaluated in a system where the other components of the adaptive cycle are fixed. Detailed examination of these properties allows comparison of different methods to identify the current state of the art and where further development should be targeted.

  19. An integrated one-step system to extract, analyze and annotate all relevant information from image-based cell screening of chemical libraries.

    PubMed

    Rabal, Obdulia; Link, Wolfgang; Serelde, Beatriz G; Bischoff, James R; Oyarzabal, Julen

    2010-04-01

    Here we report the development and validation of a complete solution to manage and analyze the data produced by image-based phenotypic screening campaigns of small-molecule libraries. In one step initial crude images are analyzed for multiple cytological features, statistical analysis is performed and molecules that produce the desired phenotypic profile are identified. A naïve Bayes classifier, integrating chemical and phenotypic spaces, is built and utilized during the process to assess those images initially classified as "fuzzy"-an automated iterative feedback tuning. Simultaneously, all this information is directly annotated in a relational database containing the chemical data. This novel fully automated method was validated by conducting a re-analysis of results from a high-content screening campaign involving 33 992 molecules used to identify inhibitors of the PI3K/Akt signaling pathway. Ninety-two percent of confirmed hits identified by the conventional multistep analysis method were identified using this integrated one-step system as well as 40 new hits, 14.9% of the total, originally false negatives. Ninety-six percent of true negatives were properly recognized too. A web-based access to the database, with customizable data retrieval and visualization tools, facilitates the posterior analysis of annotated cytological features which allows identification of additional phenotypic profiles; thus, further analysis of original crude images is not required.

  20. Assessing the Effectiveness of First Step to Success: Are Short-Term Results the First Step to Long-Term Behavioral Improvements?

    ERIC Educational Resources Information Center

    Sumi, W. Carl; Woodbridge, Michelle W.; Javitz, Harold S.; Thornton, S. Patrick; Wagner, Mary; Rouspil, Kristen; Yu, Jennifer W.; Seeley, John R.; Walker, Hill M.; Golly, Annemieke; Small, Jason W.; Feil, Edward G.; Severson, Herbert H.

    2013-01-01

    This article reports on the effectiveness of First Step to Success, a secondary-level intervention appropriate for students in early elementary school who experience moderate to severe behavior problems and are at risk for academic failure. The authors demonstrate the intervention's short-term effects on multiple behavioral and academic outcomes…

  1. Novel multi-system functional gains via task specific training in spinal cord injured male rats.

    PubMed

    Ward, Patricia J; Herrity, April N; Smith, Rebecca R; Willhite, Andrea; Harrison, Benjamin J; Petruska, Jeffrey C; Harkema, Susan J; Hubscher, Charles H

    2014-05-01

    Locomotor training (LT) after spinal cord injury (SCI) is a rehabilitative therapy used to enhance locomotor recovery. There is evidence, primarily anecdotal, also associating LT with improvements in bladder function and reduction in some types of SCI-related pain. In the present study, we determined if a step training paradigm could improve outcome measures of locomotion, bladder function, and pain/allodynia. After a T10 contusive SCI trained animals (adult male Wistar rats), trained animals began quadrupedal step training beginning 2 weeks post-SCI for 1 h/day. End of study experiments (3 months of training) revealed significant changes in limb kinematics, gait, and hindlimb flexor-extensor bursting patterns relative to non-trained controls. Importantly, micturition function, evaluated with terminal transvesical cystometry, was significantly improved in the step trained group (increased voiding efficiency, intercontraction interval, and contraction amplitude). Because both SCI and LT affect neurotrophin signaling, and neurotrophins are involved with post-SCI plasticity in micturition pathways, we measured bladder neurotrophin mRNA. Training regulated the expression of nerve growth factor (NGF) but not BDNF or NT3. Bladder NGF mRNA levels were inversely related to bladder function in the trained group. Monitoring of overground locomotion and neuropathic pain throughout the study revealed significant improvements, beginning after 3 weeks of training, which in both cases remained consistent for the study duration. These novel findings, improving non-locomotor in addition to locomotor functions, demonstrate that step training post-SCI could contribute to multiple quality of life gains, targeting patient-centered high priority deficits.

  2. The customer-centered innovation map.

    PubMed

    Bettencourt, Lance A; Ulwick, Anthony W

    2008-05-01

    We all know that people "hire" products and services to get a job done. Surgeons hire scalpels to dissect soft tissue. Janitors hire soap dispensers and paper towels to remove grime from their hands. To find ways to innovate, it's critical to deconstruct the job the customer is trying to get done from beginning to end, to gain a complete view of all the points at which a customer might desire more help from a product or service. A methodology called job mapping helps companies analyze the biggest drawbacks of the products and services customers currently use and discover opportunities for innovation. It involves breaking down the task the customer wants to accomplish into the eight universal steps of a job: (1) defining the objectives, (2) locating the necessary inputs, (3) preparing the physical environment, (4) confirming that everything is ready, (5) executing the task, (6) monitoring its progress, (7) making modifications as necessary, and (8) concluding the job. Job mapping differs substantively from process mapping in that the goal is to identify what customers are trying to get done at every step, not what they are doing currently. For example, when an anesthesiologist checks a monitor during a surgical procedure, the action taken is just a means to the end. Detecting a change in patient vital signs is the job the doctor is trying to get done. Within each of the discrete steps lie multiple opportunities for making the job simpler, easier, or faster. By mapping out every step of the job and locating those opportunities, companies can discover new ways to differentiate their offerings.

  3. Rearrangement of competing U2 RNA helices within the spliceosome promotes multiple steps in splicing

    PubMed Central

    Perriman, Rhonda J.; Ares, Manuel

    2007-01-01

    Nuclear pre-messenger RNA (pre-mRNA) splicing requires multiple spliceosomal small nuclear RNA (snRNA) and pre-mRNA rearrangements. Here we reveal a new snRNA conformational switch in which successive roles for two competing U2 helices, stem IIa and stem IIc, promote distinct splicing steps. When stem IIa is stabilized by loss of stem IIc, rapid ATP-independent and Cus2p-insensitive prespliceosome formation occurs. In contrast, hyperstabilized stem IIc improves the first splicing step on aberrant branchpoint pre-mRNAs and rescues temperature-sensitive U6–U57C, a U6 mutation that also suppresses first-step splicing defects of branchpoint mutations. A second, later role for stem IIa is revealed by its suppression of a cold-sensitive allele of the second-step splicing factor PRP16. Our data expose a spliceosomal progression cycle of U2 stem IIa formation, disruption by stem IIc, and then reformation of stem IIa before the second catalytic step. We propose that the competing stem IIa and stem IIc helices are key spliceosomal RNA elements that optimize juxtaposition of the proper reactive sites during splicing. PMID:17403781

  4. Immunoglobulin A multiple myeloma with cutaneous involvement in a dog.

    PubMed

    Mayer, Monique N; Kerr, Moira E; Grier, Candace K; Macdonald, Valerie S

    2008-07-01

    An 8-year-old rottweiler, diagnosed with multiple myeloma and multiple sites of cutaneous involvement, was treated with chemotherapy and radiation therapy. The diagnostic criteria for canine multiple myeloma, limitations of diagnostic testing for light chain proteinuria in dogs, and the role of radiation therapy in multiple myeloma patients is discussed.

  5. Immunoglobulin A multiple myeloma with cutaneous involvement in a dog

    PubMed Central

    Mayer, Monique N.; Kerr, Moira E.; Grier, Candace K.; MacDonald, Valerie S.

    2008-01-01

    An 8-year-old rottweiler, diagnosed with multiple myeloma and multiple sites of cutaneous involvement, was treated with chemotherapy and radiation therapy. The diagnostic criteria for canine multiple myeloma, limitations of diagnostic testing for light chain proteinuria in dogs, and the role of radiation therapy in multiple myeloma patients is discussed. PMID:18827847

  6. Controlled Release Strategies for Bone, Cartilage, and Osteochondral Engineering—Part II: Challenges on the Evolution from Single to Multiple Bioactive Factor Delivery

    PubMed Central

    Santo, Vítor E.; Mano, João F.; Reis, Rui L.

    2013-01-01

    The development of controlled release systems for the regeneration of bone, cartilage, and osteochondral interface is one of the hot topics in the field of tissue engineering and regenerative medicine. However, the majority of the developed systems consider only the release of a single growth factor, which is a limiting step for the success of the therapy. More recent studies have been focused on the design and tailoring of appropriate combinations of bioactive factors to match the desired goals regarding tissue regeneration. In fact, considering the complexity of extracellular matrix and the diversity of growth factors and cytokines involved in each biological response, it is expected that an appropriate combination of bioactive factors could lead to more successful outcomes in tissue regeneration. In this review, the evolution on the development of dual and multiple bioactive factor release systems for bone, cartilage, and osteochondral interface is overviewed, specifically the relevance of parameters such as dosage and spatiotemporal distribution of bioactive factors. A comprehensive collection of studies focused on the delivery of bioactive factors is also presented while highlighting the increasing impact of platelet-rich plasma as an autologous source of multiple growth factors. PMID:23249320

  7. The carboxyl-terminus directs TAF(I)48 to the nucleus and nucleolus and associates with multiple nuclear import receptors.

    PubMed

    Dynes, Joseph L; Xu, Shuping; Bothner, Sarah; Lahti, Jill M; Hori, Roderick T

    2004-03-01

    The protein complex Selectivity Factor 1, composed of TBP, TAF(I)48, TAF(I)63 and TAF(I)110, is required for rRNA transcription by RNA polymerase I in the nucleolus. The steps involved in targeting Selectivity Factor 1 will be dependent on the transport pathways that are used and the localization signals that direct this trafficking. In order to investigate these issues, we characterized human TAF(I)48, a subunit of Selectivity Factor 1. By domain analysis of TAF(I)48, the carboxyl-terminal 51 residues were found to be required for the localization of TAF(I)48, as well as sufficient to direct Green Fluorescent Protein to the nucleus and nucleolus. The carboxyl-terminus of TAF(I)48 also has the ability to associate with multiple members of the beta-karyopherin family of nuclear import receptors, including importin beta (karyopherin beta1), transportin (karyopherin beta2) and RanBP5 (karyopherin beta3), in a Ran-dependent manner. This property of interacting with multiple beta-karyopherins has been previously reported for the nuclear localization signals of some ribosomal proteins that are likewise directed to the nucleolus. This study identifies the first nuclear import sequence identified within the TBP-Associated Factor subunits of Selectivity Factor 1.

  8. Father Involvement and Young, Rural African American Men's Engagement in Substance Misuse and Multiple Sexual Partnerships.

    PubMed

    Barton, Allen W; Kogan, Steven M; Cho, Junhan; Brown, Geoffrey L

    2015-12-01

    This study was designed to examine the associations of biological father and social father involvement during childhood with African American young men's development and engagement in risk behaviors. With a sample of 505 young men living in the rural South of the United States, a dual mediation model was tested in which retrospective reports of involvement from biological fathers and social fathers were linked to young men's substance misuse and multiple sexual partnerships through men's relational schemas and future expectations. Results from structural equation modeling indicated that levels of involvement from biological fathers and social fathers predicted young men's relational schemas; only biological fathers' involvement predicted future expectations. In turn, future expectations predicted levels of substance misuse, and negative relational schemas predicted multiple sexual partnerships. Biological fathers' involvement evinced significant indirect associations with young men's substance misuse and multiple sexual partnerships through both schemas and expectations; social fathers' involvement exhibited an indirect association with multiple sexual partnerships through relational schemas. Findings highlight the unique influences of biological fathers and social fathers on multiple domains of African American young men's psychosocial development that subsequently render young men more or less likely to engage in risk behaviors.

  9. Involvement of the Reparative DNA Polymerase Pol X of African Swine Fever Virus in the Maintenance of Viral Genome Stability In Vivo

    PubMed Central

    Redrejo-Rodríguez, Modesto; Rodríguez, Javier M.; Suárez, Cristina; Salas, José

    2013-01-01

    The function of the African swine fever virus (ASFV) reparative DNA polymerase, Pol X, was investigated in the context of virus infection. Pol X is a late structural protein that localizes at cytoplasmic viral factories during DNA replication. Using an ASFV deletion mutant lacking the Pol X gene, we have shown that Pol X is not required for virus growth in Vero cells or swine macrophages under one-step growth conditions. However, at a low multiplicity of infection, when multiple rounds of replication occur, the growth of the mutant virus is impaired in swine macrophages but not in Vero cells, suggesting that Pol X is needed to repair the accumulated DNA damage. The replication of the mutant virus in Vero cells presents sensitivity to oxidative damage, and mutational analysis of viral DNA shows that deletion of Pol X results in an increase in the mutation frequency in macrophages. Therefore, our data reveal a biological role for ASFV Pol X in the context of the infected cell in the preservation of viral genetic information. PMID:23824796

  10. Genetic Differences Between Humans and Great Apes -- Implications for the Evolution of Humans

    NASA Astrophysics Data System (ADS)

    Varki, Ajit

    2004-06-01

    At the level of individual protein sequences, humans are 97-100% identical to the great apes, our closest evolutionary relatives. The evolution of humans (and of human intelligence) from a common ancestor with the chimpanzee and bonobo involved many steps, influenced by interactions amongst factors of genetic, developmental, ecological, microbial, climatic, behavioral, cultural and social origin. The genetic factors can be approached by direct comparisons of human and great ape genomes, genes and gene products, and by elucidating biochemical and biological consequences of any differences found. We have discovered multiple genetic and biochemical differences between humans and great apes, particularly with respect to a family of cell surface molecules called sialic acids, as well as in the metabolism of thyroid hormones. The hormone differences have potential consequences for human brain development. The differences in sialic acid biology have multiple implications for the human condition, ranging from susceptibility or resistance to microbial pathogens, effects on endogenous receptors in the immune system, and potential effects on placental signaling, expression of oncofetal antigens in cancers, consequences of dietary intake of animal foods, and development of the mammalian brain.

  11. Knowledge-based expert systems and a proof-of-concept case study for multiple sequence alignment construction and analysis.

    PubMed

    Aniba, Mohamed Radhouene; Siguenza, Sophie; Friedrich, Anne; Plewniak, Frédéric; Poch, Olivier; Marchler-Bauer, Aron; Thompson, Julie Dawn

    2009-01-01

    The traditional approach to bioinformatics analyses relies on independent task-specific services and applications, using different input and output formats, often idiosyncratic, and frequently not designed to inter-operate. In general, such analyses were performed by experts who manually verified the results obtained at each step in the process. Today, the amount of bioinformatics information continuously being produced means that handling the various applications used to study this information presents a major data management and analysis challenge to researchers. It is now impossible to manually analyse all this information and new approaches are needed that are capable of processing the large-scale heterogeneous data in order to extract the pertinent information. We review the recent use of integrated expert systems aimed at providing more efficient knowledge extraction for bioinformatics research. A general methodology for building knowledge-based expert systems is described, focusing on the unstructured information management architecture, UIMA, which provides facilities for both data and process management. A case study involving a multiple alignment expert system prototype called AlexSys is also presented.

  12. Knowledge-based expert systems and a proof-of-concept case study for multiple sequence alignment construction and analysis

    PubMed Central

    Aniba, Mohamed Radhouene; Siguenza, Sophie; Friedrich, Anne; Plewniak, Frédéric; Poch, Olivier; Marchler-Bauer, Aron

    2009-01-01

    The traditional approach to bioinformatics analyses relies on independent task-specific services and applications, using different input and output formats, often idiosyncratic, and frequently not designed to inter-operate. In general, such analyses were performed by experts who manually verified the results obtained at each step in the process. Today, the amount of bioinformatics information continuously being produced means that handling the various applications used to study this information presents a major data management and analysis challenge to researchers. It is now impossible to manually analyse all this information and new approaches are needed that are capable of processing the large-scale heterogeneous data in order to extract the pertinent information. We review the recent use of integrated expert systems aimed at providing more efficient knowledge extraction for bioinformatics research. A general methodology for building knowledge-based expert systems is described, focusing on the unstructured information management architecture, UIMA, which provides facilities for both data and process management. A case study involving a multiple alignment expert system prototype called AlexSys is also presented. PMID:18971242

  13. Causal mediation analysis with a binary outcome and multiple continuous or ordinal mediators: Simulations and application to an alcohol intervention

    PubMed Central

    Nguyen, Trang Quynh; Webb-Vargas, Yenny; Koning, Ina M.; Stuart, Elizabeth A.

    2016-01-01

    We investigate a method to estimate the combined effect of multiple continuous/ordinal mediators on a binary outcome: 1) fit a structural equation model with probit link for the outcome and identity/probit link for continuous/ordinal mediators, 2) predict potential outcome probabilities, and 3) compute natural direct and indirect effects. Step 2 involves rescaling the latent continuous variable underlying the outcome to address residual mediator variance/covariance. We evaluate the estimation of risk-difference- and risk-ratio-based effects (RDs, RRs) using the ML, WLSMV and Bayes estimators in Mplus. Across most variations in path-coefficient and mediator-residual-correlation signs and strengths, and confounding situations investigated, the method performs well with all estimators, but favors ML/WLSMV for RDs with continuous mediators, and Bayes for RRs with ordinal mediators. Bayes outperforms WLSMV/ML regardless of mediator type when estimating RRs with small potential outcome probabilities and in two other special cases. An adolescent alcohol prevention study is used for illustration. PMID:27158217

  14. Step-rate cut-points for physical activity intensity in patients with multiple sclerosis: The effect of disability status.

    PubMed

    Agiovlasitis, Stamatis; Sandroff, Brian M; Motl, Robert W

    2016-02-15

    Evaluating the relationship between step-rate and rate of oxygen uptake (VO2) may allow for practical physical activity assessment in patients with multiple sclerosis (MS) of differing disability levels. To examine whether the VO2 to step-rate relationship during over-ground walking differs across varying disability levels among patients with MS and to develop step-rate thresholds for moderate- and vigorous-intensity physical activity. Adults with MS (N=58; age: 51 ± 9 years; 48 women) completed one over-ground walking trial at comfortable speed, one at 0.22 m · s(-1) slower, and one at 0.22 m · s(-1) faster. Each trial lasted 6 min. VO2 was measured with portable spirometry and steps with hand-tally. Disability status was classified as mild, moderate, or severe based on Expanded Disability Status Scale scores. Multi-level regression indicated that step-rate, disability status, and height significantly predicted VO2 (p<0.05). Based on this model, we developed step-rate thresholds for activity intensity that vary by disability status and height. A separate regression without height allowed for development of step-rate thresholds that vary only by disability status. The VO2 during over-ground walking differs among ambulatory patients with MS based on disability level and height, yielding different step-rate thresholds for physical activity intensity. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Hunting down the chimera of multiple disciplinarity in conservation science.

    PubMed

    Pooley, Simon P; Mendelsohn, J Andrew; Milner-Gulland, E J

    2014-02-01

    The consensus is that both ecological and social factors are essential dimensions of conservation research and practice. However, much of the literature on multiple disciplinary collaboration focuses on the difficulties of undertaking it. This review of the challenges of conducting multiple disciplinary collaboration offers a framework for thinking about the diversity and complexity of this endeavor. We focused on conceptual challenges, of which 5 main categories emerged: methodological challenges, value judgments, theories of knowledge, disciplinary prejudices, and interdisciplinary communication. The major problems identified in these areas have proved remarkably persistent in the literature surveyed (c.1960-2012). Reasons for these failures to learn from past experience include the pressure to produce positive outcomes and gloss over disagreements, the ephemeral nature of many such projects and resulting lack of institutional memory, and the apparent complexity and incoherence of the endeavor. We suggest that multiple disciplinary collaboration requires conceptual integration among carefully selected multiple disciplinary team members united in investigating a shared problem or question. We outline a 9-point sequence of steps for setting up a successful multiple disciplinary project. This encompasses points on recruitment, involving stakeholders, developing research questions, negotiating power dynamics and hidden values and conceptual differences, explaining and choosing appropriate methods, developing a shared language, facilitating on-going communications, and discussing data integration and project outcomes. Although numerous solutions to the challenges of multiple disciplinary research have been proposed, lessons learned are often lost when projects end or experienced individuals move on. We urge multiple disciplinary teams to capture the challenges recognized, and solutions proposed, by their researchers while projects are in process. A database of well-documented case studies would showcase theories and methods from a variety of disciplines and their interactions, enable better comparative study and evaluation, and provide a useful resource for developing future projects and training multiple disciplinary researchers. © 2013 The Authors. Conservation Biology published by Wiley Periodicals, Inc. on behalf of Society for Conservation Biology.

  16. Hunting Down the Chimera of Multiple Disciplinarity in Conservation Science

    PubMed Central

    POOLEY, SIMON P; MENDELSOHN, J ANDREW; MILNER-GULLAND, E J

    2014-01-01

    The consensus is that both ecological and social factors are essential dimensions of conservation research and practice. However, much of the literature on multiple disciplinary collaboration focuses on the difficulties of undertaking it. This review of the challenges of conducting multiple disciplinary collaboration offers a framework for thinking about the diversity and complexity of this endeavor. We focused on conceptual challenges, of which 5 main categories emerged: methodological challenges, value judgments, theories of knowledge, disciplinary prejudices, and interdisciplinary communication. The major problems identified in these areas have proved remarkably persistent in the literature surveyed (c.1960–2012). Reasons for these failures to learn from past experience include the pressure to produce positive outcomes and gloss over disagreements, the ephemeral nature of many such projects and resulting lack of institutional memory, and the apparent complexity and incoherence of the endeavor. We suggest that multiple disciplinary collaboration requires conceptual integration among carefully selected multiple disciplinary team members united in investigating a shared problem or question. We outline a 9-point sequence of steps for setting up a successful multiple disciplinary project. This encompasses points on recruitment, involving stakeholders, developing research questions, negotiating power dynamics and hidden values and conceptual differences, explaining and choosing appropriate methods, developing a shared language, facilitating on-going communications, and discussing data integration and project outcomes. Although numerous solutions to the challenges of multiple disciplinary research have been proposed, lessons learned are often lost when projects end or experienced individuals move on. We urge multiple disciplinary teams to capture the challenges recognized, and solutions proposed, by their researchers while projects are in process. A database of well-documented case studies would showcase theories and methods from a variety of disciplines and their interactions, enable better comparative study and evaluation, and provide a useful resource for developing future projects and training multiple disciplinary researchers. PMID:24299167

  17. Child Sexual Abuse Prevention: How to Take the First Steps.

    ERIC Educational Resources Information Center

    Anderson, Cordelia

    This booklet provides advice and guidelines for persons interested in developing and implementing child sexual abuse prevention programs. Eight steps to child sexual abuse prevention are outlined. Step 1 involves recognition that child sexual abuse can be prevented, and provides facts to use when discussing sexual abuse. Step 2 highlights ways of…

  18. A Dynamic Pathway for Stone-Wales Bond Rotation on Carbon Nanotubes through Diamond-Like Bonds

    NASA Technical Reports Server (NTRS)

    Wei, Chen-Yu; Srivastava, Deepak; Cho, Kyeong-Jae; Menon, Madhu

    2003-01-01

    A new lower energy barrier with a two-step pathway of Stone-Wales (SW) ,ond rotation on carbon nanotubes (CNTs) is found through molecular dynamics (MD) simulations of CNTs under tension. The first step involves going over to a stable sp3-like metastable configuration with half rotated and partially tilted C-C bond. The second step involves going over to the fully rotated C-C bond with the formation of a SW defect in the nanotube. The energy barrier for this two-step dynamic pathway is significantly lower than the previously known static barrier for in-plane rotation of the C-C bond on a tensile strained (> 4%) CNT.

  19. Boric acid reversibly inhibits the second step of pre-mRNA splicing.

    PubMed

    Shomron, Noam; Ast, Gil

    2003-09-25

    Several approaches have been used to identify the factors involved in mRNA splicing. None of them, however, comprises a straightforward reversible method for inhibiting the second step of splicing using an external reagent other than a chelator. This investigation demonstrates that the addition of boric acid to an in vitro pre-mRNA splicing reaction causes a dose-dependent reversible inhibition effect on the second step of splicing. The mechanism of action does not involve chelation of several metal ions; hindrance of 3' splice-site; or binding to hSlu7. This study presents a novel method for specific reversible inhibition of the second step of pre-mRNA splicing.

  20. One Step Quantum Key Distribution Based on EPR Entanglement.

    PubMed

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

    2016-06-30

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

  1. The multiple resource inventory decision-making process

    Treesearch

    Victor A. Rudis

    1993-01-01

    A model of the multiple resource inventory decision-making process is presented that identifies steps in conducting inventories, describes the infrastructure, and points out knowledge gaps that are common to many interdisciplinary studies.Successful efforts to date suggest the need to bridge the gaps by sharing elements, maintain dialogue among stakeholders in multiple...

  2. Neuroborreliosis with extrapyramidal symptoms: a case report.

    PubMed

    Biesiada, Grazyna; Czapiel, Jacek; Sobczyk-Krupiarz, Iwona; Garlicki, Aleksander; Mach, Tomasz

    2008-05-01

    The disease of Lyme is a tick-borne infection. It involves skin, the nervous system, joints and the heart. Spirochaeta Borrelia burgdorferi is the etiologic agent of the disease. In the majority of cases, clinical symptoms, like migrating erythema, occur from 3 to 30 days, sometimes to 3 months after a bite from a tick. The early disseminated infection involves multiple migrating erythema, neuroborreliosis, arthritis, myocarditis and other organ-related symptoms. The late stage of chronic infection involves chronic atrophic leg dermatitis, neurological and rheumatological symptoms, and other organ-related symptoms which persist for above 12 months. The diagnosis of the disease of Lyme is based upon specific clinical symptoms confirmed by serologic tests. The two-step diagnostic protocol including the ELISA method, confirmed by the Western-blot test, is optimal. The present article describes a case of a 59-year-old man, a computer specialist, who often spends his free time walking in woods for recreation, and who was bitten by a tick 3 years before hospitalization. The bite resulted in migrating erythema that subsided without antimicrobial treatment. In spite of this, the man had not changed his hobby exposing himself to bites from ticks. One year later, multiple migrating erythema and extrapyramidalis symptoms appeared without any other organ malfunctions. In the current year, the patient was admitted to the Infectious Diseases Hospital, and received antibiotics (ceftriaxon) with following neurological improvement. Several months later, extrapyramidal symptoms increased. On the day of admission to the hospital, the neurologic examination showed abnormalities of upper and lower limbs movements (propulsive walking and the right lower leg traction), the right hand tremor, pouts of the face, and sleepiness.

  3. Aircraft Loss-of-Control Accident Prevention: Switching Control of the GTM Aircraft with Elevator Jam Failures

    NASA Technical Reports Server (NTRS)

    Chang, Bor-Chin; Kwatny, Harry G.; Belcastro, Christine; Belcastro, Celeste

    2008-01-01

    Switching control, servomechanism, and H2 control theory are used to provide a practical and easy-to-implement solution for the actuator jam problem. A jammed actuator not only causes a reduction of control authority, but also creates a persistent disturbance with uncertain amplitude. The longitudinal dynamics model of the NASA GTM UAV is employed to demonstrate that a single fixed reconfigured controller design based on the proposed approach is capable of accommodating an elevator jam failure with arbitrary jam position as long as the thrust control has enough control authority. This paper is a first step towards solving a more comprehensive in-flight loss-of-control accident prevention problem that involves multiple actuator failures, structure damages, unanticipated faults, and nonlinear upset regime recovery, etc.

  4. Bioactivities, isolation and purification methods of polysaccharides from natural products: A review.

    PubMed

    Shi, Lei

    2016-11-01

    Polysaccharides play multiple roles and have extensive bioactivities in life process and an immense potential in healthcare, food and cosmetic industries, due to their therapeutic effects and relatively low toxicity. This review describes their major functions involved in antitumor, anti-virus, and anti-inflammatory bioactivities. Due to their enormous structural heterogeneity, the approaches for isolation and purification of polysaccharides are distinct from that of the other macromolecules such as proteins, etc. Yet, to achieve the homogeneity is the initial step for studies of polysaccharide structure, pharmacology, and its structure-activity relationships. According to the experiences accumulated by our lab and the published literatures, this review also introduces the methods widely used in isolation and purification of polysaccharides. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Non-Hodgkin's lymphoma in McKusick syndrome. A case report.

    PubMed

    Torkzad, M R; Hjalmar, V; Blomqvist, L

    2002-07-01

    The McKusick syndrome in a female who developed highly malignant lymphoma at the age of 23, with multiple parenchymal lesions involving both kidneys, the lungs and the pancreas and also splenomegaly but without lymphadenopathy, is described together with diagnostic imaging findings. McKusick syndrome is associated with impaired cell-mediated immunity and might, like several other similar syndromes, harbor an increased risk of certain types of lymphoma. To our knowledge, there are no previous reports of non-Hodgkin's lymphoma in a patient with McKusick syndrome. The increased incidence of lymphoma in certain cases of congenital immunodeficiency raises the issue of a possible relationship between McKusick syndrome and lymphoma and could perhaps serve as one of the primary steps for a further characterization of this syndrome.

  6. Development of Underwater Laser Scaling Adapter

    NASA Astrophysics Data System (ADS)

    Bluss, Kaspars

    2012-12-01

    In this paper the developed laser scaling adapter is presented. The scaling adapter is equipped with a twin laser unit where the two parallel laser beams are projected onto any target giving an exact indication of scale. The body of the laser scaling adapter is made of Teflon, the density of which is approximately two times the water density. The development involved multiple challenges - numerical hydrodynamic calculations for choosing an appropriate shape which would reduce the effects of turbulence, an accurate sealing of the power supply and the laser diodes, and others. The precision is estimated by the partial derivation method. Both experimental and theoretical data conclude the overall precision error to be in the 1% margin. This paper presents the development steps of such an underwater laser scaling adapter for a remotely operated vehicle (ROV).

  7. Fair Play Game: A Group Contingency Strategy to Increase Students' Active Behaviours in Physical Education

    ERIC Educational Resources Information Center

    Vidoni, Carla; Lee, Chang-Hung; Azevedo, L. B.

    2014-01-01

    A dependent group contingency strategy called Fair Play Game was applied to promote increase in number of steps during physical education classes for sixth-grade students. Results from a multiple baseline design across three classes showed that the mean number of steps for baseline vs. intervention were: Class 1: 43 vs. 64 steps/minute; Class 2:…

  8. Reliability and Concurrent Validity of the Narrow Path Walking Test in Persons With Multiple Sclerosis.

    PubMed

    Rosenblum, Uri; Melzer, Itshak

    2017-01-01

    About 90% of people with multiple sclerosis (PwMS) have gait instability and 50% fall. Reliable and clinically feasible methods of gait instability assessment are needed. The study investigated the reliability and validity of the Narrow Path Walking Test (NPWT) under single-task (ST) and dual-task (DT) conditions for PwMS. Thirty PwMS performed the NPWT on 2 different occasions, a week apart. Number of Steps, Trial Time, Trial Velocity, Step Length, Number of Step Errors, Number of Cognitive Task Errors, and Number of Balance Losses were measured. Intraclass correlation coefficients (ICC2,1) were calculated from the average values of NPWT parameters. Absolute reliability was quantified from standard error of measurement (SEM) and smallest real difference (SRD). Concurrent validity of NPWT with Functional Reach Test, Four Square Step Test (FSST), 12-item Multiple Sclerosis Walking Scale (MSWS-12), and 2 Minute Walking Test (2MWT) was determined using partial correlations. Intraclass correlation coefficients (ICCs) for most NPWT parameters during ST and DT ranged from 0.46-0.94 and 0.55-0.95, respectively. The highest relative reliability was found for Number of Step Errors (ICC = 0.94 and 0.93, for ST and DT, respectively) and Trial Velocity (ICC = 0.83 and 0.86, for ST and DT, respectively). Absolute reliability was high for Number of Step Errors in ST (SEM % = 19.53%) and DT (SEM % = 18.14%) and low for Trial Velocity in ST (SEM % = 6.88%) and DT (SEM % = 7.29%). Significant correlations for Number of Step Errors and Trial Velocity were found with FSST, MSWS-12, and 2MWT. In persons with PwMS performing the NPWT, Number of Step Errors and Trial Velocity were highly reliable parameters. Based on correlations with other measures of gait instability, Number of Step Errors was the most valid parameter of dynamic balance under the conditions of our test.Video Abstract available for more insights from the authors (see Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A159).

  9. Involvement of α-, γ- and δ-Tocopherol Isomers from
Pumpkin (Cucurbita pepo L.) Seed Oil or Oil Mixtures in
the Biphasic DPPH˙ Disappearance Kinetics

    PubMed Central

    Broznić, Dalibor; Milin, Čedomila

    2016-01-01

    Summary The antioxidant activity of three types of pumpkin seed oil or oil mixtures (cold- -pressed, produced from roasted seed paste and salad) produced in the northern part of Croatia and the kinetics of their behaviour as free radical scavengers were investigated using DPPH˙. In addition, the involvement of oil tocopherol isomers (α-, γ- and δ-) in different steps of DPPH˙ disappearance and their impact on the rate of reaction were analysed. The kinetics of DPPH˙ disappearance is a two-step process. In the first step, rapid disappearance of DPPH˙ occurs during the first 11 min of the reaction, depending on the oil type, followed by a slower decline in the second step. To describe DPPH˙ disappearance kinetics, six mathematical models (mono- and biphasic) were tested. Our findings showed that γ- and δ-tocopherols affected DPPH˙ disappearance during the first step, and α-tocopherol in the second step of the reaction. Moreover, α-tocopherol demonstrated 30 times higher antioxidant activity than γ- and δ-tocopherols. The results indicated the biphasic double-exponential behaviour of DPPH˙ disappearance in oil samples, due to the complexity of reactions that involve different tocopherol isomers and proceed through different chemical pathways. PMID:27904410

  10. Involvement of α-, γ- and δ-Tocopherol Isomers from
Pumpkin (Cucurbita pepo L.) Seed Oil or Oil Mixtures in
the Biphasic DPPH˙ Disappearance Kinetics.

    PubMed

    Broznić, Dalibor; Jurešić, Gordana Čanadi; Milin, Čedomila

    2016-06-01

    The antioxidant activity of three types of pumpkin seed oil or oil mixtures (cold- -pressed, produced from roasted seed paste and salad) produced in the northern part of Croatia and the kinetics of their behaviour as free radical scavengers were investigated using DPPH˙. In addition, the involvement of oil tocopherol isomers (α-, γ- and δ-) in different steps of DPPH˙ disappearance and their impact on the rate of reaction were analysed. The kinetics of DPPH˙ disappearance is a two-step process. In the first step, rapid disappearance of DPPH˙ occurs during the first 11 min of the reaction, depending on the oil type, followed by a slower decline in the second step. To describe DPPH˙ disappearance kinetics, six mathematical models (mono- and biphasic) were tested. Our findings showed that γ- and δ-tocopherols affected DPPH˙ disappearance during the first step, and α-tocopherol in the second step of the reaction. Moreover, α-tocopherol demonstrated 30 times higher antioxidant activity than γ- and δ-tocopherols. The results indicated the biphasic double-exponential behaviour of DPPH˙ disappearance in oil samples, due to the complexity of reactions that involve different tocopherol isomers and proceed through different chemical pathways.

  11. Metabolic pathways as possible therapeutic targets for progressive multiple sclerosis.

    PubMed

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

    2017-08-01

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

  12. Adaptive Time Stepping for Transient Network Flow Simulation in Rocket Propulsion Systems

    NASA Technical Reports Server (NTRS)

    Majumdar, Alok K.; Ravindran, S. S.

    2017-01-01

    Fluid and thermal transients found in rocket propulsion systems such as propellant feedline system is a complex process involving fast phases followed by slow phases. Therefore their time accurate computation requires use of short time step initially followed by the use of much larger time step. Yet there are instances that involve fast-slow-fast phases. In this paper, we present a feedback control based adaptive time stepping algorithm, and discuss its use in network flow simulation of fluid and thermal transients. The time step is automatically controlled during the simulation by monitoring changes in certain key variables and by feedback. In order to demonstrate the viability of time adaptivity for engineering problems, we applied it to simulate water hammer and cryogenic chill down in pipelines. Our comparison and validation demonstrate the accuracy and efficiency of this adaptive strategy.

  13. Obstacle stepping involves spinal anticipatory activity associated with quadrupedal limb coordination.

    PubMed

    Michel, J; van Hedel, H J A; Dietz, V

    2008-04-01

    Obstacle avoidance steps are associated with a facilitation of spinal reflexes in leg muscles. Here we have examined the involvement of both leg and arm muscles. Subjects walking with reduced vision on a treadmill were acoustically informed about an approaching obstacle and received feedback about task performance. Reflex responses evoked by tibial nerve stimulation were observed in all arm and leg muscles examined in this study. They were enhanced before the execution of obstacle avoidance compared with normal steps and showed an exponential adaptation in contralateral arm flexor muscles corresponding to the improvement of task performance. This enhancement was absent when the body was partially supported during the task. During the execution of obstacle steps, electromyographic activity in the arm muscles mimicked the preceding reflex behaviour with respect to enhancement and adaptation. Our results demonstrate an anticipatory quadrupedal limb coordination with an involvement of proximal arm muscles in the acquisition and performance of this precision locomotor task. This is presumably achieved by an up-regulated activity of coupled cervico-thoracal interneuronal circuits.

  14. Risk of falls in older people during fast-walking--the TASCOG study.

    PubMed

    Callisaya, M L; Blizzard, L; McGinley, J L; Srikanth, V K

    2012-07-01

    To investigate the relationship between fast-walking and falls in older people. Individuals aged 60-86 years were randomly selected from the electoral roll (n=176). Gait speed, step length, cadence and a walk ratio were recorded during preferred- and fast-walking using an instrumented walkway. Falls were recorded prospectively over 12 months. Log multinomial regression was used to estimate the relative risk of single and multiple falls associated with gait variables during fast-walking and change between preferred- and fast-walking. Covariates included age, sex, mood, physical activity, sensorimotor and cognitive measures. The risk of multiple falls was increased for those with a smaller walk ratio (shorter steps, faster cadence) during fast-walking (RR 0.92, CI 0.87, 0.97) and greater reduction in the walk ratio (smaller increase in step length, larger increase in cadence) when changing to fast-walking (RR 0.73, CI 0.63, 0.85). These gait patterns were associated with poorer physiological and cognitive function (p<0.05). A higher risk of multiple falls was also seen for those in the fastest quarter of gait speed (p=0.01) at fast-walking. A trend for better reaction time, balance, memory and physical activity for higher categories of gait speed was stronger for fallers than non-fallers (p<0.05). Tests of fast-walking may be useful in identifying older individuals at risk of multiple falls. There may be two distinct groups at risk--the frail person with short shuffling steps, and the healthy person exposed to greater risk. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Multiple non-syndromic odontogenic keratocysts in three siblings

    PubMed Central

    Nirwan, Amit; Wanjari, Sangeeta Panjab; Saikhedkar, Rashmi; Karun, Vinayak

    2013-01-01

    Occurrence of multiple cysts (MC) involving the jaw is rare. When multiple, it is usually associated with a syndrome. Occurrence of MC without syndromic association is extremely rare. Multiple odontogenic cysts mostly could be odontogenic keratocysts or dentigerous cysts. Odontogenic keratocyst shows involvement of mandible over maxilla, with peak incidence in second and third decade and it is exceedingly rare before 10 years of age. However multiple odontogenic keratocysts found in children are often reflective of nevoid basal cell carcinoma syndrome. Here is a case report which documents multiple jaw cysts involving both the jaws, in three siblings of ages 10, 13 and 17 years with negative parental history. All three reported cases were free of any systemic involvement. As odontogenic keratocyst spreads through bone marrow, destruction is more before any clinical manifestation. Therefore, early detection and intervention are essential in preventing extensive destruction. PMID:23505078

  16. PREDICTIVE MEASURES OF A RESIDENT'S PERFORMANCE ON WRITTEN ORTHOPAEDIC BOARD SCORES

    PubMed Central

    Dyrstad, Bradley W; Pope, David; Milbrandt, Joseph C; Beck, Ryan T; Weinhoeft, Anita L.; Idusuyi, Osaretin B

    2011-01-01

    Objective Residency programs are continually attempting to predict the performance of both current and potential residents. Previous studies have supported the use of USMLE Steps 1 and 2 as predictors of Orthopaedic In-Training Examination (OITE) and eventual American Board of Orthopaedic Surgery success, while others show no significant correlation. A strong performance on OITE examinations does correlate with strong residency performance, and some believe OITE scores are good predictors of future written board success. The current study was designed to examine potential differences in resident assessment measures and their predictive value for written boards. Design/Methods A retrospective review of resident performance data was performed for the past 10 years. Personalized information was removed by the residency coordinator. USMLE Step 1, USMLE Step 2, Orthopaedic In-Training Examination (from first to fifth years of training), and written orthopaedic specialty board scores were collected. Subsequently, the residents were separated into two groups, those scoring above the 35th percentile on written boards and those scoring below. Data were analyzed using correlation and regression analyses to compare and contrast the scores across all tests. Results A significant difference was seen between the groups in regard to USMLE scores for both Step 1 and 2. Also, a significant difference was found between OITE scores for both the second and fifth years. Positive correlations were found for USMLE Step 1, Step 2, OITE 2 and OITE 5 when compared to performance on written boards. One resident initially failed written boards, but passed on the second attempt This resident consistently scored in the 20th and 30th percentiles on the in-training examinations. Conclusions USMLE Step 1 and 2 scores along with OITE scores are helpful in gauging an orthopaedic resident’s performance on written boards. Lower USMLE scores along with consistently low OITE scores likely identify residents at risk of failing their written boards. Close monitoring of the annual OITE scores is recommended and may be useful to identify struggling residents. Future work involving multiple institutions is warranted and would ensure applicability of our findings to other orthopedic residency programs. PMID:22096449

  17. Predicting severe injury using vehicle telemetry data.

    PubMed

    Ayoung-Chee, Patricia; Mack, Christopher D; Kaufman, Robert; Bulger, Eileen

    2013-01-01

    In 2010, the National Highway Traffic Safety Administration standardized collision data collected by event data recorders, which may help determine appropriate emergency medical service (EMS) response. Previous models (e.g., General Motors ) predict severe injury (Injury Severity Score [ISS] > 15) using occupant demographics and collision data. Occupant information is not automatically available, and 12% of calls from advanced automatic collision notification providers are unanswered. To better inform EMS triage, our goal was to create a predictive model only using vehicle collision data. Using the National Automotive Sampling System Crashworthiness Data System data set, we included front-seat occupants in late-model vehicles (2000 and later) in nonrollover and rollover crashes in years 2000 to 2010. Telematic (change in velocity, direction of force, seat belt use, vehicle type and curb weight, as well as multiple impact) and nontelematic variables (maximum intrusion, narrow impact, and passenger ejection) were included. Missing data were multiply imputed. The University of Washington model was tested to predict severe injury before application of guidelines (Step 0) and for occupants who did not meet Steps 1 and 2 criteria (Step 3) of the Centers for Disease Control and Prevention Field Triage Guidelines. A probability threshold of 20% was chosen in accordance with Centers for Disease Control and Prevention recommendations. There were 28,633 crashes, involving 33,956 vehicles and 52,033 occupants, of whom 9.9% had severe injury. At Step 0, the University of Washington model sensitivity was 40.0% and positive predictive value (PPV) was 20.7%. At Step 3, the sensitivity was 32.3 % and PPV was 10.1%. Model analysis excluding nontelematic variables decreased sensitivity and PPV. The sensitivity of the re-created General Motors model was 38.5% at Step 0 and 28.1% at Step 3. We designed a model using only vehicle collision data that was predictive of severe injury at collision notification and in the field and was comparable with an existing model. These models demonstrate the potential use of advanced automatic collision notification in planning EMS response. Prognostic study, level II.

  18. A theoretically based determination of bowen-ratio fetch requirements

    USGS Publications Warehouse

    Stannard, D.I.

    1997-01-01

    Determination of fetch requirements for accurate Bowen-ratio measurements of latent- and sensible-heat fluxes is more involved than for eddy-correlation measurements because Bowen-ratio sensors are located at two heights, rather than just one. A simple solution to the diffusion equation is used to derive an expression for Bowen-ratio fetch requirements, downwind of a step change in surface fluxes. These requirements are then compared to eddy-correlation fetch requirements based on the same diffusion equation solution. When the eddy-correlation and upper Bowen-ratio sensor heights are equal, and the available energy upwind and downwind of the step change is constant, the Bowen-ratio method requires less fetch than does eddy correlation. Differences in fetch requirements between the two methods are greatest over relatively smooth surfaces. Bowen-ratio fetch can be reduced significantly by lowering the lower sensor, as well as the upper sensor. The Bowen-ratio fetch model was tested using data from a field experiment where multiple Bowen-ratio systems were deployed simultaneously at various fetches and heights above a field of bermudagrass. Initial comparisons were poor, but improved greatly when the model was modified (and operated numerically) to account for the large roughness of the upwind cotton field.

  19. 3D-printed tracheoesophageal puncture and prosthesis placement simulator.

    PubMed

    Barber, Samuel R; Kozin, Elliott D; Naunheim, Matthew R; Sethi, Rosh; Remenschneider, Aaron K; Deschler, Daniel G

    A tracheoesophageal prosthesis (TEP) allows for speech after total laryngectomy. However, TEP placement is technically challenging, requiring a coordinated series of steps. Surgical simulators improve technical skills and reduce operative time. We hypothesize that a reusable 3-dimensional (3D)-printed TEP simulator will facilitate comprehension and rehearsal prior to actual procedures. The simulator was designed using Fusion360 (Autodesk, San Rafael, CA). Components were 3D-printed in-house using an Ultimaker 2+ (Ultimaker, Netherlands). Squid simulated the common tracheoesophageal wall. A Blom-Singer TEP (InHealth Technologies, Carpinteria, CA) replicated placement. Subjects watched an instructional video and completed pre- and post-simulation surveys. The simulator comprised 3D-printed parts: the esophageal lumen and superficial stoma. Squid was placed between components. Ten trainees participated. Significant differences existed between junior and senior residents with surveys regarding anatomy knowledge(p<0.05), technical details(p<0.01), and equipment setup(p<0.01). Subjects agreed that simulation felt accurate, and rehearsal raised confidence in future procedures. A 3D-printed TEP simulator is feasible for surgical training. Simulation involving multiple steps may accelerate technical skills and improve education. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Evolution of complexity in the volvocine algae: transitions in individuality through Darwin's eye.

    PubMed

    Herron, Matthew D; Michod, Richard E

    2008-02-01

    The transition from unicellular to differentiated multicellular organisms constitutes an increase in the level complexity, because previously existing individuals are combined to form a new, higher-level individual. The volvocine algae represent a unique opportunity to study this transition because they diverged relatively recently from unicellular relatives and because extant species display a range of intermediate grades between unicellular and multicellular, with functional specialization of cells. Following the approach Darwin used to understand "organs of extreme perfection" such as the vertebrate eye, this jump in complexity can be reduced to a series of small steps that cumulatively describe a gradual transition between the two levels. We use phylogenetic reconstructions of ancestral character states to trace the evolution of steps involved in this transition in volvocine algae. The history of these characters includes several well-supported instances of multiple origins and reversals. The inferred changes can be understood as components of cooperation-conflict-conflict mediation cycles as predicted by multilevel selection theory. One such cycle may have taken place early in volvocine evolution, leading to the highly integrated colonies seen in extant volvocine algae. A second cycle, in which the defection of somatic cells must be prevented, may still be in progress.

  1. Cloud parallel processing of tandem mass spectrometry based proteomics data.

    PubMed

    Mohammed, Yassene; Mostovenko, Ekaterina; Henneman, Alex A; Marissen, Rob J; Deelder, André M; Palmblad, Magnus

    2012-10-05

    Data analysis in mass spectrometry based proteomics struggles to keep pace with the advances in instrumentation and the increasing rate of data acquisition. Analyzing this data involves multiple steps requiring diverse software, using different algorithms and data formats. Speed and performance of the mass spectral search engines are continuously improving, although not necessarily as needed to face the challenges of acquired big data. Improving and parallelizing the search algorithms is one possibility; data decomposition presents another, simpler strategy for introducing parallelism. We describe a general method for parallelizing identification of tandem mass spectra using data decomposition that keeps the search engine intact and wraps the parallelization around it. We introduce two algorithms for decomposing mzXML files and recomposing resulting pepXML files. This makes the approach applicable to different search engines, including those relying on sequence databases and those searching spectral libraries. We use cloud computing to deliver the computational power and scientific workflow engines to interface and automate the different processing steps. We show how to leverage these technologies to achieve faster data analysis in proteomics and present three scientific workflows for parallel database as well as spectral library search using our data decomposition programs, X!Tandem and SpectraST.

  2. Image reconstruction: an overview for clinicians.

    PubMed

    Hansen, Michael S; Kellman, Peter

    2015-03-01

    Image reconstruction plays a critical role in the clinical use of magnetic resonance imaging (MRI). The MRI raw data is not acquired in image space and the role of the image reconstruction process is to transform the acquired raw data into images that can be interpreted clinically. This process involves multiple signal processing steps that each have an impact on the image quality. This review explains the basic terminology used for describing and quantifying image quality in terms of signal-to-noise ratio and point spread function. In this context, several commonly used image reconstruction components are discussed. The image reconstruction components covered include noise prewhitening for phased array data acquisition, interpolation needed to reconstruct square pixels, raw data filtering for reducing Gibbs ringing artifacts, Fourier transforms connecting the raw data with image space, and phased array coil combination. The treatment of phased array coils includes a general explanation of parallel imaging as a coil combination technique. The review is aimed at readers with no signal processing experience and should enable them to understand what role basic image reconstruction steps play in the formation of clinical images and how the resulting image quality is described. © 2014 Wiley Periodicals, Inc.

  3. Furfural reduction mechanism of a zinc-dependent alcohol dehydrogenase from Cupriavidus necator JMP134

    PubMed Central

    Kang, ChulHee; Hayes, Robert; Sanchez, Emiliano J.; Webb, Brian N.; Li, Qunrui; Hooper, Travis; Nissen, Mark S.; Xun, Luying

    2012-01-01

    Summary FurX is a tetrameric Zn-dependent alcohol dehydrogenase (ADH) from Cupriavidus necator JMP134. The enzyme rapidly reduces furfural with NADH as the reducing power. For the first time among characterized ADHs, the high-resolution structures of all reaction steps were obtained in a time-resolved manner, thereby illustrating the complete catalytic events of NADH-dependent reduction of furfural and the dynamic Zn2+ coordination among Glu66, water, substrate and product. In the fully closed conformation of the NADH complex, the catalytic turnover proved faster than observed for the partially closed conformation due to an effective proton transfer network. The domain motion triggered by NAD(H) association/dissociation appeared to facilitate dynamic interchanges in Zn2+ coordination with substrate and product molecules, ultimately increasing the enzymatic turnover rate. NAD+ dissociation appeared to be a slow process, involving multiple steps in concert with a domain opening and reconfiguration of Glu66. This agrees with the report that the cofactor is not dissociated from FurX during ethanol-dependent reduction of furfural, in which ethanol reduces NAD+ to NADH that is subsequently used for furfural reduction. PMID:22081946

  4. Sludge Washing and Demonstration of the DWPF Nitric/Formic Flowsheet in the SRNL Shielded Cells for Sludge Batch 9 Qualification

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

    Pareizs, J.; Newell, D.; Martino, C.

    Savannah River National Laboratory (SRNL) was requested by Savannah River Remediation (SRR) to qualify the next batch of sludge – Sludge Batch 9 (SB9). Current practice is to prepare sludge batches in Tank 51 by transferring sludge to Tank 51 from other tanks. The sludge is washed and transferred to Tank 40, the current Defense Waste Process Facility (DWPF) feed tank. Prior to sludge transfer from Tank 51 to Tank 40, the Tank 51 sludge must be qualified. SRNL qualifies the sludge in multiple steps. First, a Tank 51 sample is received, then characterized, washed, and again characterized. SRNL thenmore » demonstrates the DWPF Chemical Process Cell (CPC) flowsheet with the sludge. The final step of qualification involves chemical durability measurements of glass fabricated in the DWPF CPC demonstrations. In past sludge batches, SRNL had completed the DWPF demonstration with Tank 51 sludge. For SB9, SRNL has been requested to process a blend of Tank 51 and Tank 40 at a targeted ratio of 44% Tank 51 and 56% Tank 40 on an insoluble solids basis.« less

  5. Patient Privacy, Consent, and Identity Management in Health Information Exchange

    PubMed Central

    Hosek, Susan D.; Straus, Susan G.

    2013-01-01

    Abstract The Military Health System (MHS) and the Veterans Health Administration (VHA) have been among the nation's leaders in health information technology (IT), including the development of health IT systems and electronic health records that summarize patients' care from multiple providers. Health IT interoperability within MHS and across MHS partners, including VHA, is one of ten goals in the current MHS Strategic Plan. As a step toward achieving improved interoperability, the MHS is seeking to develop a research roadmap to better coordinate health IT research efforts, address IT capability gaps, and reduce programmatic risk for its enterprise projects. This article contributes to that effort by identifying gaps in research, policy, and practice involving patient privacy, consent, and identity management that need to be addressed to bring about improved quality and efficiency of care through health information exchange. Major challenges include (1) designing a meaningful patient consent procedure, (2) recording patients' consent preferences and designing procedures to implement restrictions on disclosures of protected health information, and (3) advancing knowledge regarding the best technical approaches to performing patient identity matches and how best to monitor results over time. Using a sociotechnical framework, this article suggests steps for overcoming these challenges and topics for future research. PMID:28083296

  6. Early and transient stages of Cu oxidation: Atomistic insights from theoretical simulations and in situ experiments

    NASA Astrophysics Data System (ADS)

    Zhu, Qing; Zou, Lianfeng; Zhou, Guangwen; Saidi, Wissam A.; Yang, Judith C.

    2016-10-01

    Understanding of metal oxidation is critical to corrosion control, catalysis synthesis, and advanced materials engineering. Although, metal oxidation process is rather complicated, different processes, many of them coupled, are involved from the onset of reaction. Since first introduced, there has been great success in applying heteroepitaxial theory to the oxide growth on a metal surface as demonstrated in the Cu oxidation experiments. In this paper, we review the recent progress in experimental findings on Cu oxidation as well as the advances in the theoretical simulations of the Cu oxidation process. We focus on the effects of defects such as step edges, present on realistic metal surfaces, on the oxide growth dynamics. We show that the surface steps can change the mass transport of both Cu and O atoms during oxide growth, and ultimately lead to the formation of different oxide morphology. We also review the oxidation of Cu alloys and explore the effect of a secondary element to the oxide growth on a Cu surface. From the review of the work on Cu oxidation, we demonstrate the correlation of theoretical simulations at multiple scales with various experimental techniques.

  7. The Association between Endometriomas and Ovarian Cancer: Preventive Effect of Inhibiting Ovulation and Menstruation during Reproductive Life

    PubMed Central

    Grandi, Giovanni; Toss, Angela; Cortesi, Laura; Botticelli, Laura; Volpe, Annibale; Cagnacci, Angelo

    2015-01-01

    Although endometriosis frequently involves multiple sites in the pelvis, malignancies associated with this disease are mostly confined to the ovaries, evolving from an endometrioma. Endometriomas present a 2-3-fold increased risk of transformation in clear-cell, endometrioid, and possibly low-grade serous ovarian cancers, but not in mucinous ovarian cancers. These last cancers are, in some aspects, different from the other epithelial ovarian cancers, as they do not appear to be decreased by the inhibition of ovulation and menstruation. The step by step process of transformation from typical endometrioma, through atypical endometrioma, finally to ovarian cancer seems mainly related to oxidative stress, inflammation, hyperestrogenism, and specific molecular alterations. Particularly, activation of oncogenic KRAS and PI3K pathways and inactivation of tumor suppressor genes PTEN and ARID1A are suggested as major pathogenic mechanisms for endometriosis associated clear-cell and endometrioid ovarian cancer. Both the risk for endometriomas and their associated ovarian cancers seems to be highly and similarly decreased by the inhibition of ovulation and retrograde menstruation, suggesting a common pathogenetic mechanism and common possible preventive strategies during reproductive life. PMID:26413541

  8. The Association between Endometriomas and Ovarian Cancer: Preventive Effect of Inhibiting Ovulation and Menstruation during Reproductive Life.

    PubMed

    Grandi, Giovanni; Toss, Angela; Cortesi, Laura; Botticelli, Laura; Volpe, Annibale; Cagnacci, Angelo

    2015-01-01

    Although endometriosis frequently involves multiple sites in the pelvis, malignancies associated with this disease are mostly confined to the ovaries, evolving from an endometrioma. Endometriomas present a 2-3-fold increased risk of transformation in clear-cell, endometrioid, and possibly low-grade serous ovarian cancers, but not in mucinous ovarian cancers. These last cancers are, in some aspects, different from the other epithelial ovarian cancers, as they do not appear to be decreased by the inhibition of ovulation and menstruation. The step by step process of transformation from typical endometrioma, through atypical endometrioma, finally to ovarian cancer seems mainly related to oxidative stress, inflammation, hyperestrogenism, and specific molecular alterations. Particularly, activation of oncogenic KRAS and PI3K pathways and inactivation of tumor suppressor genes PTEN and ARID1A are suggested as major pathogenic mechanisms for endometriosis associated clear-cell and endometrioid ovarian cancer. Both the risk for endometriomas and their associated ovarian cancers seems to be highly and similarly decreased by the inhibition of ovulation and retrograde menstruation, suggesting a common pathogenetic mechanism and common possible preventive strategies during reproductive life.

  9. Full kinetics investigation of the formation reaction of phosphonate esters in the gas-phase: a theoretical study.

    PubMed

    Kazemian, Mohammad Amin; Habibi-Khorassani, Sayyed Mostafa; Maghsoodlu, Malek Taher; Ebrahimi, Ali

    2014-04-01

    In the present work, the proposed multiple-mechanisms have been investigated theoretically for the reaction between triphenyl phosphite and dimethyl acetylenedicarboxylate in the presence of N-H acid such as aniline for generation of phosphonate esters using ab initio molecular orbital theory in gas phase. The profile of the potential energy surface was constructed at the HF/6-311G(d,p) level of theory. The kinetics of the gas phase reaction was studied by evaluating the reaction path of various mechanisms. Between 12 speculative proposed mechanisms {step₁, step₂ (with four possibilities), step₃ (with three possibilities), and step₄} only the third speculative mechanism was recognized as a desirable mechanism. Theoretical kinetics data involving k and E(a), activation (ΔG(‡), ΔS(‡) and ΔH(‡)), and thermodynamic parameters (ΔG°, ΔS° and ΔH°) were calculated for each step of the various mechanisms. Step₁ of the desirable mechanism was identified as the rate determining step. Comparison of the theoretical desirable mechanism with the rate law that has been previously obtained by UV spectrophotometry experiments indicated that the results are in good agreement.

  10. Dynamics and molecular determinants of cytoplasmic lipid droplet clustering and dispersion.

    PubMed

    Orlicky, David J; Monks, Jenifer; Stefanski, Adrianne L; McManaman, James L

    2013-01-01

    Perilipin-1 (Plin1), a prominent cytoplasmic lipid droplet (CLD) binding phosphoprotein and key physiological regulator of triglyceride storage and lipolysis in adipocytes, is thought to regulate the fragmentation and dispersion of CLD that occurs in response to β-adrenergic activation of adenylate cyclase. Here we investigate the dynamics and molecular determinants of these processes using cell lines stably expressing recombinant forms of Plin1 and/or other members of the perilipin family. Plin1 and a C-terminal CLD-binding fragment of Plin1 (Plin1CT) induced formation of single dense CLD clusters near the microtubule organizing center, whereas neither an N-terminal CLD-binding fragment of Plin1, nor Plin2 or Plin3 induced clustering. Clustered CLD coated by Plin1, or Plin1CT, dispersed in response to isoproterenol, or other agents that activate adenylate cyclase, in a process inhibited by the protein kinase A inhibitor, H89, and blocked by microtubule disruption. Isoproterenol-stimulated phosphorylation of CLD-associated Plin1 on serine 492 preceded their dispersion, and live cell imaging showed that cluster dispersion involved initial fragmentation of tight clusters into multiple smaller clusters, which then fragmented into well-dispersed individual CLD. siRNA knockdown of the cortical actin binding protein, moesin, induced disaggregation of tight clusters into multiple smaller clusters, and inhibited the reaggregation of dispersed CLD into tight clusters. Together these data suggest that the clustering and dispersion processes involve a complex orchestration of phosphorylation-dependent, microtubule-dependent and independent, and microfilament dependent steps.

  11. The Development of Ciprofloxacin Resistance in Pseudomonas aeruginosa Involves Multiple Response Stages and Multiple Proteins ▿ † ‡

    PubMed Central

    Su, Hsun-Cheng; Ramkissoon, Kevin; Doolittle, Janet; Clark, Martha; Khatun, Jainab; Secrest, Ashley; Wolfgang, Matthew C.; Giddings, Morgan C.

    2010-01-01

    Microbes have developed resistance to nearly every antibiotic, yet the steps leading to drug resistance remain unclear. Here we report a multistage process by which Pseudomonas aeruginosa acquires drug resistance following exposure to ciprofloxacin at levels ranging from 0.5× to 8× the initial MIC. In stage I, susceptible cells are killed en masse by the exposure. In stage II, a small, slow to nongrowing population survives antibiotic exposure that does not exhibit significantly increased resistance according to the MIC measure. In stage III, exhibited at 0.5× to 4× the MIC, a growing population emerges to reconstitute the population, and these cells display heritable increases in drug resistance of up to 50 times the original level. We studied the stage III cells by proteomic methods to uncover differences in the regulatory pathways that are involved in this phenotype, revealing upregulation of phosphorylation on two proteins, succinate-semialdehyde dehydrogenase (SSADH) and methylmalonate-semialdehyde dehydrogenase (MMSADH), and also revealing upregulation of a highly conserved protein of unknown function. Transposon disruption in the encoding genes for each of these targets substantially dampened the ability of cells to develop the stage III phenotype. Considering these results in combination with computational models of resistance and genomic sequencing results, we postulate that stage III heritable resistance develops from a combination of both genomic mutations and modulation of one or more preexisting cellular pathways. PMID:20696867

  12. Isotopic and trace element characteristics of an unusual refractory inclusion from Essebi

    NASA Technical Reports Server (NTRS)

    Deloule, E.; Kennedy, A. K.; Hutcheon, I. D.; Elgoresy, A.

    1993-01-01

    The isotopic and chemical properties of Ca-Al-rich inclusions (CAI) provide important clues to the early solar nebula environment. While the abundances of refractory major and trace elements are similar to those expected for high temperature condensates, the variety of textural, chemical, and isotopic signatures indicate most CAI experienced complex, multi-stage histories involving repeated episodes of condensation, evaporation, and metamorphism. Evidence of multiple processes is especially apparent in an unusual refractory inclusion from Essebi (URIE) described by El Goresy et al. The melilite (mel)-rich core of URIE contains polygonal framboids of spinel (sp) and hibonite (hb) or sp and fassaite (fas) and is surrounded by a rim sequence consisting of five layers. In contrast to rims on Allende, the mineralogy of the URIE rim layers becomes increasingly refractory from the core outwards, ending in a layer of spinel-Al2O3 solid solution + Sc-rich fassaite. The chemical and mineralogical features of URIE are inconsistent with crystallization from a homogeneous melt, and El Goresy et al. proposed a multi-step history involving condensation of sp + hb and aggregation into framboids, capture of framboids by a refractory silicate melt droplet, condensation of rim layers, and alteration of mel to calcite and feldspathoid. The PANURGE ion probe was used to investigate the isotopic and trace element characteristics of URIE to develop a more complete picture of the multiple processes leading to formation and metamorphism.

  13. Statistical identification of stimulus-activated network nodes in multi-neuron voltage-sensitive dye optical recordings.

    PubMed

    Fathiazar, Elham; Anemuller, Jorn; Kretzberg, Jutta

    2016-08-01

    Voltage-Sensitive Dye (VSD) imaging is an optical imaging method that allows measuring the graded voltage changes of multiple neurons simultaneously. In neuroscience, this method is used to reveal networks of neurons involved in certain tasks. However, the recorded relative dye fluorescence changes are usually low and signals are superimposed by noise and artifacts. Therefore, establishing a reliable method to identify which cells are activated by specific stimulus conditions is the first step to identify functional networks. In this paper, we present a statistical method to identify stimulus-activated network nodes as cells, whose activities during sensory network stimulation differ significantly from the un-stimulated control condition. This method is demonstrated based on voltage-sensitive dye recordings from up to 100 neurons in a ganglion of the medicinal leech responding to tactile skin stimulation. Without relying on any prior physiological knowledge, the network nodes identified by our statistical analysis were found to match well with published cell types involved in tactile stimulus processing and to be consistent across stimulus conditions and preparations.

  14. Global transcriptomic profiling of aspen trees under elevated [CO2] to identify potential molecular mechanisms responsible for enhanced radial growth.

    PubMed

    Wei, Hairong; Gou, Jiqing; Yordanov, Yordan; Zhang, Huaxin; Thakur, Ramesh; Jones, Wendy; Burton, Andrew

    2013-03-01

    Aspen (Populus tremuloides) trees growing under elevated [CO(2)] at a free-air CO(2) enrichment (FACE) site produced significantly more biomass than control trees. We investigated the molecular mechanisms underlying the observed increase in biomass by producing transcriptomic profiles of the vascular cambium zone (VCZ) and leaves, and then performed a comparative study to identify significantly changed genes and pathways after 12 years exposure to elevated [CO(2)]. In leaves, elevated [CO(2)] enhanced expression of genes related to Calvin cycle activity and linked pathways. In the VCZ, the pathways involved in cell growth, cell division, hormone metabolism, and secondary cell wall formation were altered while auxin conjugation, ABA synthesis, and cytokinin glucosylation and degradation were inhibited. Similarly, the genes involved in hemicellulose and pectin biosynthesis were enhanced, but some genes that catalyze important steps in lignin biosynthesis pathway were inhibited. Evidence from systemic analysis supported the functioning of multiple molecular mechanisms that underpin the enhanced radial growth in response to elevated [CO(2)].

  15. Anticipation and Choice Heuristics in the Dynamic Consumption of Pain Relief

    PubMed Central

    Story, Giles W.; Vlaev, Ivo; Dayan, Peter; Seymour, Ben; Darzi, Ara; Dolan, Raymond J.

    2015-01-01

    Humans frequently need to allocate resources across multiple time-steps. Economic theory proposes that subjects do so according to a stable set of intertemporal preferences, but the computational demands of such decisions encourage the use of formally less competent heuristics. Few empirical studies have examined dynamic resource allocation decisions systematically. Here we conducted an experiment involving the dynamic consumption over approximately 15 minutes of a limited budget of relief from moderately painful stimuli. We had previously elicited the participants’ time preferences for the same painful stimuli in one-off choices, allowing us to assess self-consistency. Participants exhibited three characteristic behaviors: saving relief until the end, spreading relief across time, and early spending, of which the last was markedly less prominent. The likelihood that behavior was heuristic rather than normative is suggested by the weak correspondence between one-off and dynamic choices. We show that the consumption choices are consistent with a combination of simple heuristics involving early-spending, spreading or saving of relief until the end, with subjects predominantly exhibiting the last two. PMID:25793302

  16. Anticipation and choice heuristics in the dynamic consumption of pain relief.

    PubMed

    Story, Giles W; Vlaev, Ivo; Dayan, Peter; Seymour, Ben; Darzi, Ara; Dolan, Raymond J

    2015-03-01

    Humans frequently need to allocate resources across multiple time-steps. Economic theory proposes that subjects do so according to a stable set of intertemporal preferences, but the computational demands of such decisions encourage the use of formally less competent heuristics. Few empirical studies have examined dynamic resource allocation decisions systematically. Here we conducted an experiment involving the dynamic consumption over approximately 15 minutes of a limited budget of relief from moderately painful stimuli. We had previously elicited the participants' time preferences for the same painful stimuli in one-off choices, allowing us to assess self-consistency. Participants exhibited three characteristic behaviors: saving relief until the end, spreading relief across time, and early spending, of which the last was markedly less prominent. The likelihood that behavior was heuristic rather than normative is suggested by the weak correspondence between one-off and dynamic choices. We show that the consumption choices are consistent with a combination of simple heuristics involving early-spending, spreading or saving of relief until the end, with subjects predominantly exhibiting the last two.

  17. Protein synthesis in sperm: dialog between mitochondria and cytoplasm.

    PubMed

    Gur, Yael; Breitbart, Haim

    2008-01-30

    Ejaculated sperm are capable of using mRNAs transcripts for protein translation during the final maturation steps before fertilization. In a capacitation-dependent process, nuclear-encoded mRNAs are translated by mitochondrial-type ribosomes while the cytoplasmic translation machinery is not involved. Our findings suggest that new proteins are synthesized to replace degraded proteins while swimming and waiting in the female reproductive tract before fertilization, or produced due to the specific needs of the capacitating spermatozoa. In addition, a growing number of articles have reported evidence for the correlation of nuclear-encoded mRNA and protein synthesis in somatic mitochondria. It is known that all of the proteins necessary for the replication, transcription and translation of the genes encoded in mtDNA are now encoded in the nuclear genome. This genetic investment is far out of proportion to the number of proteins involved, as there have been multiple movements and duplications of genes. However, the evolutionary retention (or secondary uptake) of the mitochondrial machinery for translation of nuclear-encoded mRNAs may shed light on this paradox.

  18. Morphing Aircraft Structures: Research in AFRL/RB

    DTIC Science & Technology

    2008-09-01

    various iterative steps in the process, etc. The solver also internally controls the step size for integration, as this is independent of the step...Coupling of Substructures for Dynamic Analyses,” AIAA Journal , Vol. 6, No. 7, 1968, pp. 1313-1319. 2“Using the State-Dependent Modal Force (MFORCE),” AFL...an actuation system consisting of multiple internal actuators, centrally computer controlled to implement any commanded morphing configuration; and

  19. A comparison of the effects of visual deprivation and regular body weight support treadmill training on improving over-ground walking of stroke patients: a multiple baseline single subject design.

    PubMed

    Kim, Jeong-Soo; Kang, Sun-Young; Jeon, Hye-Seon

    2015-01-01

    The body-weight-support treadmill (BWST) is commonly used for gait rehabilitation, but other forms of BWST are in development, such as visual-deprivation BWST (VDBWST). In this study, we compare the effect of VDBWST training and conventional BWST training on spatiotemporal gait parameters for three individuals who had hemiparetic strokes. We used a single-subject experimental design, alternating multiple baselines across the individuals. We recruited three individuals with hemiparesis from stroke; two on the left side and one on the right. For the main outcome measures we assessed spatiotemporal gait parameters using GAITRite, including: gait velocity; cadence; step time of the affected side (STA); step time of the non-affected side (STN); step length of the affected side (SLA); step length of the non-affected side (SLN); step-time asymmetry (ST-asymmetry); and step-length asymmetry (SL-asymmetry). Gait velocity, cadence, SLA, and SLN increased from baseline after both interventions, but STA, ST-asymmetry, and SL-asymmetry decreased from the baseline after the interventions. The VDBWST was significantly more effective than the BWST for increasing gait velocity and cadence and for decreasing ST-asymmetry. VDBWST is more effective than BWST for improving gait performance during the rehabilitation for ground walking.

  20. A longitudinal study of the comparative efficacy of Women for Sobriety, LifeRing, SMART Recovery, and 12-step groups for those with AUD.

    PubMed

    Zemore, Sarah E; Lui, Camillia; Mericle, Amy; Hemberg, Jordana; Kaskutas, Lee Ann

    2018-05-01

    Despite the effectiveness of 12-step groups, most people reporting a prior alcohol use disorder (AUD) do not sustain involvement in such groups at beneficial levels. This highlights the need for research on other mutual help groups that address alcohol problems and may attract those who avoid 12-step groups. The current study addresses this need, offering outcome data from the first longitudinal, comparative study of 12-step groups and their alternatives: The Peer ALlternatives for Addiction (PAL) Study. Adults with a lifetime AUD were surveyed at baseline (N=647), 6months (81% response rate) and 12months (83% response rate). Members of the largest known secular mutual help alternatives, namely Women for Sobriety (WFS), LifeRing, and SMART, were recruited in collaboration with group directors; current 12-step attendees were recruited from an online meeting hub. Online surveys assessed demographic and clinical variables; mutual help involvement; and alcohol and drug use and severity. Analyses involved multivariate logistic GEEs separately modelling alcohol abstinence, alcohol problems, and total abstinence across 6 and 12months. Key predictors were baseline primary group affiliation (PGA); primary group involvement (PGI) at both baseline and 6months; and the interaction between baseline PGA and 6-month PGI. The critical effects of interest were the interactions, expressing whether associations between changes in PGI from baseline to 6months and substance use outcomes differed by primary group. None of the interactions between baseline PGA and 6-month PGI were significant, suggesting no differences in the efficacy of WFS, LifeRing, or SMART, vs. 12-step groups. Nevertheless, some PGA main effects emerged. Compared to 12-step members, those identifying SMART as their primary group at baseline fared worse across outcomes, and those affiliating with LifeRing showed lower odds of total abstinence. Still, these effects became nonsignificant when controlling for baseline alcohol recovery goal, suggesting that any group differences may be explained by selection of those with weaker abstinence motivation into LifeRing and (especially) SMART. This study makes a valuable contribution in view of the extremely limited evidence on mutual help alternatives. Results tentatively suggest that WFS, LifeRing, and SMART are as effective as 12-step groups for those with AUDs, and that this population has the best odds of success when committing to lifetime total abstinence. An optimal care plan may thus involve facilitating involvement in a broad array of mutual help groups and supporting abstinence motivation. Copyright © 2018 Elsevier Inc. All rights reserved.

  1. A Generalized Approach for the Interpretation of Geophysical Well Logs in Ground-Water Studies - Theory and Application

    USGS Publications Warehouse

    Paillet, Frederick L.; Crowder, R.E.

    1996-01-01

    Quantitative analysis of geophysical logs in ground-water studies often involves at least as broad a range of applications and variation in lithology as is typically encountered in petroleum exploration, making such logs difficult to calibrate and complicating inversion problem formulation. At the same time, data inversion and analysis depend on inversion model formulation and refinement, so that log interpretation cannot be deferred to a geophysical log specialist unless active involvement with interpretation can be maintained by such an expert over the lifetime of the project. We propose a generalized log-interpretation procedure designed to guide hydrogeologists in the interpretation of geophysical logs, and in the integration of log data into ground-water models that may be systematically refined and improved in an iterative way. The procedure is designed to maximize the effective use of three primary contributions from geophysical logs: (1) The continuous depth scale of the measurements along the well bore; (2) The in situ measurement of lithologic properties and the correlation with hydraulic properties of the formations over a finite sample volume; and (3) Multiple independent measurements that can potentially be inverted for multiple physical or hydraulic properties of interest. The approach is formulated in the context of geophysical inversion theory, and is designed to be interfaced with surface geophysical soundings and conventional hydraulic testing. The step-by-step procedures given in our generalized interpretation and inversion technique are based on both qualitative analysis designed to assist formulation of the interpretation model, and quantitative analysis used to assign numerical values to model parameters. The approach bases a decision as to whether quantitative inversion is statistically warranted by formulating an over-determined inversion. If no such inversion is consistent with the inversion model, quantitative inversion is judged not possible with the given data set. Additional statistical criteria such as the statistical significance of regressions are used to guide the subsequent calibration of geophysical data in terms of hydraulic variables in those situations where quantitative data inversion is considered appropriate.

  2. Implementation of Competency-Based Pharmacy Education (CBPE)

    PubMed Central

    Koster, Andries; Schalekamp, Tom; Meijerman, Irma

    2017-01-01

    Implementation of competency-based pharmacy education (CBPE) is a time-consuming, complicated process, which requires agreement on the tasks of a pharmacist, commitment, institutional stability, and a goal-directed developmental perspective of all stakeholders involved. In this article the main steps in the development of a fully-developed competency-based pharmacy curriculum (bachelor, master) are described and tips are given for a successful implementation. After the choice for entering into CBPE is made and a competency framework is adopted (step 1), intended learning outcomes are defined (step 2), followed by analyzing the required developmental trajectory (step 3) and the selection of appropriate assessment methods (step 4). Designing the teaching-learning environment involves the selection of learning activities, student experiences, and instructional methods (step 5). Finally, an iterative process of evaluation and adjustment of individual courses, and the curriculum as a whole, is entered (step 6). Successful implementation of CBPE requires a system of effective quality management and continuous professional development as a teacher. In this article suggestions for the organization of CBPE and references to more detailed literature are given, hoping to facilitate the implementation of CBPE. PMID:28970422

  3. Remote Access to the PXRR Macromolecular Crystallography Facilities at the NSLS

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

    Soares, A.S.; Schneider, D. K.; Skinner, J. M.

    2008-09-01

    The most recent surge of innovations that have simplified and streamlined the process of determining macromolecular structures by crystallography owes much to the efforts of the structural genomics community. However, this was only the last step in a long evolution that saw the metamorphosis of crystallography from an heroic effort that involved years of dedication and skill into a straightforward measurement that is occasionally almost trivial. Many of the steps in this remarkable odyssey involved reducing the physical labor that is demanded of experimenters in the field. Other steps reduced the technical expertise required for conducting those experiments.

  4. Remote Access to the PXRR Macromolecular Crystallography Facilities at the NSLS

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

    A Soares; D Schneider; J Skinner

    2011-12-31

    The most recent surge of innovations that have simplified and streamlined the process of determining macromolecular structures by crystallography owes much to the efforts of the structural genomics community. However, this was only the last step in a long evolution that saw the metamorphosis of crystallography from an heroic effort that involved years of dedication and skill into a straightforward measurement that is occasionally almost trivial. Many of the steps in this remarkable odyssey involved reducing the physical labor that is demanded of experimenters in the field. Other steps reduced the technical expertise required for conducting those experiments.

  5. One Step Quantum Key Distribution Based on EPR Entanglement

    PubMed Central

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

    2016-01-01

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

  6. Audiovisual Fundamentals; Basic Equipment Operation and Simple Materials Production.

    ERIC Educational Resources Information Center

    Bullard, John R.; Mether, Calvin E.

    A guide illustrated with simple sketches explains the functions and step-by-step uses of audiovisual (AV) equipment. Principles of projection, audio, AV equipment, lettering, limited-quantity and quantity duplication, and materials preservation are outlined. Apparatus discussed include overhead, opaque, slide-filmstrip, and multiple-loading slide…

  7. Design-for-manufacture of gradient-index optical systems using time-varying boundary condition diffusion

    NASA Astrophysics Data System (ADS)

    Harkrider, Curtis Jason

    2000-08-01

    The incorporation of gradient-index (GRIN) material into optical systems offers novel and practical solutions to lens design problems. However, widespread use of gradient-index optics has been limited by poor correlation between gradient-index designs and the refractive index profiles produced by ion exchange between glass and molten salt. Previously, a design-for- manufacture model was introduced that connected the design and fabrication processes through use of diffusion modeling linked with lens design software. This project extends the design-for-manufacture model into a time- varying boundary condition (TVBC) diffusion model. TVBC incorporates the time-dependent phenomenon of melt poisoning and introduces a new index profile control method, multiple-step diffusion. The ions displaced from the glass during the ion exchange fabrication process can reduce the total change in refractive index (Δn). Chemical equilibrium is used to model this melt poisoning process. Equilibrium experiments are performed in a titania silicate glass and chemically analyzed. The equilibrium model is fit to ion concentration data that is used to calculate ion exchange boundary conditions. The boundary conditions are changed purposely to control the refractive index profile in multiple-step TVBC diffusion. The glass sample is alternated between ion exchange with a molten salt bath and annealing. The time of each diffusion step can be used to exert control on the index profile. The TVBC computer model is experimentally verified and incorporated into the design- for-manufacture subroutine that runs in lens design software. The TVBC design-for-manufacture model is useful for fabrication-based tolerance analysis of gradient-index lenses and for the design of manufactureable GRIN lenses. Several optical elements are designed and fabricated using multiple-step diffusion, verifying the accuracy of the model. The strength of multiple-step diffusion process lies in its versatility. An axicon, imaging lens, and curved radial lens, all with different index profile requirements, are designed out of a single glass composition.

  8. Limited-memory fast gradient descent method for graph regularized nonnegative matrix factorization.

    PubMed

    Guan, Naiyang; Wei, Lei; Luo, Zhigang; Tao, Dacheng

    2013-01-01

    Graph regularized nonnegative matrix factorization (GNMF) decomposes a nonnegative data matrix X[Symbol:see text]R(m x n) to the product of two lower-rank nonnegative factor matrices, i.e.,W[Symbol:see text]R(m x r) and H[Symbol:see text]R(r x n) (r < min {m,n}) and aims to preserve the local geometric structure of the dataset by minimizing squared Euclidean distance or Kullback-Leibler (KL) divergence between X and WH. The multiplicative update rule (MUR) is usually applied to optimize GNMF, but it suffers from the drawback of slow-convergence because it intrinsically advances one step along the rescaled negative gradient direction with a non-optimal step size. Recently, a multiple step-sizes fast gradient descent (MFGD) method has been proposed for optimizing NMF which accelerates MUR by searching the optimal step-size along the rescaled negative gradient direction with Newton's method. However, the computational cost of MFGD is high because 1) the high-dimensional Hessian matrix is dense and costs too much memory; and 2) the Hessian inverse operator and its multiplication with gradient cost too much time. To overcome these deficiencies of MFGD, we propose an efficient limited-memory FGD (L-FGD) method for optimizing GNMF. In particular, we apply the limited-memory BFGS (L-BFGS) method to directly approximate the multiplication of the inverse Hessian and the gradient for searching the optimal step size in MFGD. The preliminary results on real-world datasets show that L-FGD is more efficient than both MFGD and MUR. To evaluate the effectiveness of L-FGD, we validate its clustering performance for optimizing KL-divergence based GNMF on two popular face image datasets including ORL and PIE and two text corpora including Reuters and TDT2. The experimental results confirm the effectiveness of L-FGD by comparing it with the representative GNMF solvers.

  9. Treating electron transport in MCNP{sup trademark}

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

    Hughes, H.G.

    1996-12-31

    The transport of electrons and other charged particles is fundamentally different from that of neutrons and photons. A neutron, in aluminum slowing down from 0.5 MeV to 0.0625 MeV will have about 30 collisions; a photon will have fewer than ten. An electron with the same energy loss will undergo 10{sup 5} individual interactions. This great increase in computational complexity makes a single- collision Monte Carlo approach to electron transport unfeasible for many situations of practical interest. Considerable theoretical work has been done to develop a variety of analytic and semi-analytic multiple-scattering theories for the transport of charged particles. Themore » theories used in the algorithms in MCNP are the Goudsmit-Saunderson theory for angular deflections, the Landau an theory of energy-loss fluctuations, and the Blunck-Leisegang enhancements of the Landau theory. In order to follow an electron through a significant energy loss, it is necessary to break the electron`s path into many steps. These steps are chosen to be long enough to encompass many collisions (so that multiple-scattering theories are valid) but short enough that the mean energy loss in any one step is small (for the approximations in the multiple-scattering theories). The energy loss and angular deflection of the electron during each step can then be sampled from probability distributions based on the appropriate multiple- scattering theories. This subsumption of the effects of many individual collisions into single steps that are sampled probabilistically constitutes the ``condensed history`` Monte Carlo method. This method is exemplified in the ETRAN series of electron/photon transport codes. The ETRAN codes are also the basis for the Integrated TIGER Series, a system of general-purpose, application-oriented electron/photon transport codes. The electron physics in MCNP is similar to that of the Integrated TIGER Series.« less

  10. Experimental studies of systematic multiple-energy operation at HIMAC synchrotron

    NASA Astrophysics Data System (ADS)

    Mizushima, K.; Katagiri, K.; Iwata, Y.; Furukawa, T.; Fujimoto, T.; Sato, S.; Hara, Y.; Shirai, T.; Noda, K.

    2014-07-01

    Multiple-energy synchrotron operation providing carbon-ion beams with various energies has been used for scanned particle therapy at NIRS. An energy range from 430 to 56 MeV/u and about 200 steps within this range are required to vary the Bragg peak position for effective treatment. The treatment also demands the slow extraction of beam with highly reliable properties, such as spill, position and size, for all energies. We propose an approach to generating multiple-energy operation meeting these requirements within a short time. In this approach, the device settings at most energy steps are determined without manual adjustments by using systematic parameter tuning depending on the beam energy. Experimental verification was carried out at the HIMAC synchrotron, and its results proved that this approach can greatly reduce the adjustment period.

  11. Facilitating Involvement in Alcoholics Anonymous During Outpatient Treatment: A Randomized Clinical Trial

    PubMed Central

    Walitzer, Kimberly S.; Dermen, Kurt H.; Barrick, Christopher

    2009-01-01

    AIM This study evaluated two strategies to facilitate involvement in Alcoholics Anonymous (AA) – a 12-step-based directive approach and a motivational enhancement approach – during skills-focused individual treatment. DESIGN Randomized controlled trial with assessments at baseline, end of treatment, and 3, 6, 9, and 12 months after treatment. PARTICIPANTS, SETTING, and INTERVENTION 169 alcoholic outpatients (57 women) randomly assigned to one of three conditions: a directive approach to facilitating AA, a motivational enhancement approach to facilitating AA, or treatment as usual with no special emphasis on AA. MEASUREMENTS Self-report of AA meeting attendance and involvement, alcohol consumption (percent days abstinent, percent days heavy drinking), and negative alcohol consequences. FINDINGS Participants exposed to the 12-step directive condition for facilitating AA involvement reported more AA meeting attendance, more evidence of active involvement in AA, and a higher percent days abstinent relative to participants in the treatment-as-usual comparison group. Evidence suggested also that the effect of the directive strategy on abstinent days was partially mediated through AA involvement. The motivational enhancement approach to facilitating AA had no effect on outcome measures. CONCLUSIONS These results suggest that treatment providers can use a 12-step-based directive approach to effectively facilitate involvement in AA and thereby improve client outcome. PMID:19207347

  12. The Move to Field Based Teacher Education: A Practical Guide for Field Hands. Teacher Education Forum; Volume 4, Number 14.

    ERIC Educational Resources Information Center

    Rockwood, Stacy F.

    This paper outlines the procedures used at the University of Cincinnati for establishing a field based elementary teacher education program in the form of a field guide. The first step involves a meeting with university faculty to discuss the implications of such a program. Step two involves meeting with the elementary school principal and selling…

  13. A facile single-step synthesis of ternary multicore magneto-plasmonic nanoparticles.

    PubMed

    Benelmekki, Maria; Bohra, Murtaza; Kim, Jeong-Hwan; Diaz, Rosa E; Vernieres, Jerome; Grammatikopoulos, Panagiotis; Sowwan, Mukhles

    2014-04-07

    We report a facile single-step synthesis of ternary hybrid nanoparticles (NPs) composed of multiple dumbbell-like iron-silver (FeAg) cores encapsulated by a silicon (Si) shell using a versatile co-sputter gas-condensation technique. In comparison to previously reported binary magneto-plasmonic NPs, the advantage conferred by a Si shell is to bind the multiple magneto-plasmonic (FeAg) cores together and prevent them from aggregation at the same time. Further, we demonstrate that the size of the NPs and number of cores in each NP can be modulated over a wide range by tuning the experimental parameters.

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

    PubMed

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

    2015-01-01

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

  15. Circadian processes in the RNA life cycle.

    PubMed

    Torres, Manon; Becquet, Denis; Franc, Jean-Louis; François-Bellan, Anne-Marie

    2018-05-01

    The circadian clock drives daily rhythms of multiple physiological processes, allowing organisms to anticipate and adjust to periodic changes in environmental conditions. These physiological rhythms are associated with robust oscillations in the expression of at least 30% of expressed genes. While the ability for the endogenous timekeeping system to generate a 24-hr cycle is a cell-autonomous mechanism based on negative autoregulatory feedback loops of transcription and translation involving core-clock genes and their protein products, it is now increasingly evident that additional mechanisms also govern the circadian oscillations of clock-controlled genes. Such mechanisms can take place post-transcriptionally during the course of the RNA life cycle. It has been shown that many steps during RNA processing are regulated in a circadian manner, thus contributing to circadian gene expression. These steps include mRNA capping, alternative splicing, changes in splicing efficiency, and changes in RNA stability controlled by the tail length of polyadenylation or the use of alternative polyadenylation sites. RNA transport can also follow a circadian pattern, with a circadian nuclear retention driven by rhythmic expression within the nucleus of particular bodies (the paraspeckles) and circadian export to the cytoplasm driven by rhythmic proteins acting like cargo. Finally, RNA degradation may also follow a circadian pattern through the rhythmic involvement of miRNAs. In this review, we summarize the current knowledge of the post-transcriptional circadian mechanisms known to play a prominent role in shaping circadian gene expression in mammals. This article is categorized under: RNA Processing > Splicing Regulation/Alternative Splicing RNA Processing > RNA Editing and Modification RNA Export and Localization > Nuclear Export/Import. © 2018 Wiley Periodicals, Inc.

  16. Novel One-Tube-One-Step Real-Time Methodology for Rapid Transcriptomic Biomarker Detection: Signal Amplification by Ternary Initiation Complexes.

    PubMed

    Fujita, Hiroto; Kataoka, Yuka; Tobita, Seiji; Kuwahara, Masayasu; Sugimoto, Naoki

    2016-07-19

    We have developed a novel RNA detection method, termed signal amplification by ternary initiation complexes (SATIC), in which an analyte sample is simply mixed with the relevant reagents and allowed to stand for a short time under isothermal conditions (37 °C). The advantage of the technique is that there is no requirement for (i) heat annealing, (ii) thermal cycling during the reaction, (iii) a reverse transcription step, or (iv) enzymatic or mechanical fragmentation of the target RNA. SATIC involves the formation of a ternary initiation complex between the target RNA, a circular DNA template, and a DNA primer, followed by rolling circle amplification (RCA) to generate multiple copies of G-quadruplex (G4) on a long DNA strand like beads on a string. The G4s can be specifically fluorescence-stained with N(3)-hydroxyethyl thioflavin T (ThT-HE), which emits weakly with single- and double-stranded RNA/DNA but strongly with parallel G4s. An improved dual SATIC system, which involves the formation of two different ternary initiation complexes in the RCA process, exhibited a wide quantitative detection range of 1-5000 pM. Furthermore, this enabled visual observation-based RNA detection, which is more rapid and convenient than conventional isothermal methods, such as reverse transcription-loop-mediated isothermal amplification, signal mediated amplification of RNA technology, and RNA-primed rolling circle amplification. Thus, SATIC methodology may serve as an on-site and real-time measurement technique for transcriptomic biomarkers for various diseases.

  17. Neurosurgical endoscopic training via a realistic 3-dimensional model with pathology.

    PubMed

    Waran, Vicknes; Narayanan, Vairavan; Karuppiah, Ravindran; Thambynayagam, Hari Chandran; Muthusamy, Kalai Arasu; Rahman, Zainal Ariff Abdul; Kirollos, Ramez Wadie

    2015-02-01

    Training in intraventricular endoscopy is particularly challenging because the volume of cases is relatively small and the techniques involved are unlike those usually used in conventional neurosurgery. Present training models are inadequate for various reasons. Using 3-dimensional (3D) printing techniques, models with pathology can be created using actual patient's imaging data. This technical article introduces a new training model based on a patient with hydrocephalus secondary to a pineal tumour, enabling the models to be used to simulate third ventriculostomies and pineal biopsies. Multiple models of the head of a patient with hydrocephalus were created using 3D rapid prototyping technique. These models were modified to allow for a fluid-filled ventricular system under appropriate tension. The models were qualitatively assessed in the various steps involved in an endoscopic third ventriculostomy and intraventricular biopsy procedure, initially by 3 independent neurosurgeons and subsequently by 12 participants of an intraventricular endoscopy workshop. All 3 surgeons agreed on the ease and usefulness of these models in the teaching of endoscopic third ventriculostomy, performing endoscopic biopsies, and the integration of navigation to ventriculoscopy. Their overall score for the ventricular model realism was above average. The 12 participants of the intraventricular endoscopy workshop averaged between a score of 4.0 to 4.6 of 5 for every individual step of the procedure. Neurosurgical endoscopic training currently is a long process of stepwise training. These 3D printed models provide a realistic simulation environment for a neuroendoscopy procedure that allows safe and effective teaching of navigation and endoscopy in a standardized and repetitive fashion.

  18. An easy-to-use calculating machine to simulate steady state and non-steady-state preparative separations by multiple dual mode counter-current chromatography with semi-continuous loading of feed mixtures.

    PubMed

    Kostanyan, Artak E; Shishilov, Oleg N

    2018-06-01

    Multiple dual mode counter-current chromatography (MDM CCC) separation processes with semi-continuous large sample loading consist of a succession of two counter-current steps: with "x" phase (first step) and "y" phase (second step) flow periods. A feed mixture dissolved in the "x" phase is continuously loaded into a CCC machine at the beginning of the first step of each cycle over a constant time with the volumetric rate equal to the flow rate of the pure "x" phase. An easy-to-use calculating machine is developed to simulate the chromatograms and the amounts of solutes eluted with the phases at each cycle for steady-state (the duration of the flow periods of the phases is kept constant for all the cycles) and non-steady-state (with variable duration of alternating phase elution steps) separations. Using the calculating machine, the separation of mixtures containing up to five components can be simulated and designed. Examples of the application of the calculating machine for the simulation of MDM CCC processes are discussed. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. A Two-Step Approach to Uncertainty Quantification of Core Simulators

    DOE PAGES

    Yankov, Artem; Collins, Benjamin; Klein, Markus; ...

    2012-01-01

    For the multiple sources of error introduced into the standard computational regime for simulating reactor cores, rigorous uncertainty analysis methods are available primarily to quantify the effects of cross section uncertainties. Two methods for propagating cross section uncertainties through core simulators are the XSUSA statistical approach and the “two-step” method. The XSUSA approach, which is based on the SUSA code package, is fundamentally a stochastic sampling method. Alternatively, the two-step method utilizes generalized perturbation theory in the first step and stochastic sampling in the second step. The consistency of these two methods in quantifying uncertainties in the multiplication factor andmore » in the core power distribution was examined in the framework of phase I-3 of the OECD Uncertainty Analysis in Modeling benchmark. With the Three Mile Island Unit 1 core as a base model for analysis, the XSUSA and two-step methods were applied with certain limitations, and the results were compared to those produced by other stochastic sampling-based codes. Based on the uncertainty analysis results, conclusions were drawn as to the method that is currently more viable for computing uncertainties in burnup and transient calculations.« less

  20. Science plus management equals successful remediation: A case study

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

    Buehlman, M.D.; Rogers, D.T.; Payne, F.C.

    A case study involving a Brownfields site in southeastern Michigan clearly illustrates the elements of successful remediation. The site`s soil was contaminated with polychlorinated biphenyls (PCBs) and its groundwater with a variety of chlorinated solvents. The original estimate for remediation has exceeded $30 million. Several phases of investigation were conducted to evaluate the nature and sources of contaminants, the site`s hydrogeology, potential risks to human health and the environment, and feasible remedial technologies. Multiple cleanup criteria were established for different affected areas based on the results of the investigations, changes that were taking place with the state cleanup regulations andmore » standards and subsequent negotiations with state and federal regulators. Innovative remedial technologies were selected. The result was a remediation that met or exceeded all soil and groundwater cleanup objectives, was performed on schedule, and was highly cost-effective. The final cost was limited to $3 million--one-tenth of the original estimate. The success of this project involved meticulous scientific study and comprehensive understanding of applicable regulatory requirements and available remediation technologies. It also required effective project management to coordinate the multidisciplinary efforts involved and to maintain the constant vertical and horizontal communications necessary to ensure sound decisions at every step in the process.« less

  1. Introduction to bioinformatics.

    PubMed

    Can, Tolga

    2014-01-01

    Bioinformatics is an interdisciplinary field mainly involving molecular biology and genetics, computer science, mathematics, and statistics. Data intensive, large-scale biological problems are addressed from a computational point of view. The most common problems are modeling biological processes at the molecular level and making inferences from collected data. A bioinformatics solution usually involves the following steps: Collect statistics from biological data. Build a computational model. Solve a computational modeling problem. Test and evaluate a computational algorithm. This chapter gives a brief introduction to bioinformatics by first providing an introduction to biological terminology and then discussing some classical bioinformatics problems organized by the types of data sources. Sequence analysis is the analysis of DNA and protein sequences for clues regarding function and includes subproblems such as identification of homologs, multiple sequence alignment, searching sequence patterns, and evolutionary analyses. Protein structures are three-dimensional data and the associated problems are structure prediction (secondary and tertiary), analysis of protein structures for clues regarding function, and structural alignment. Gene expression data is usually represented as matrices and analysis of microarray data mostly involves statistics analysis, classification, and clustering approaches. Biological networks such as gene regulatory networks, metabolic pathways, and protein-protein interaction networks are usually modeled as graphs and graph theoretic approaches are used to solve associated problems such as construction and analysis of large-scale networks.

  2. Implementation of a standardized handoff protocol for post-operative admissions to the surgical intensive care unit.

    PubMed

    Mukhopadhyay, Dhriti; Wiggins-Dohlvik, Katie C; MrDutt, Mary M; Hamaker, Jeffrey S; Machen, Graham L; Davis, Matthew L; Regner, Justin L; Smith, Randall W; Ciceri, David P; Shake, Jay G

    2018-01-01

    The transfer of critically ill patients from the operating room (OR) to the surgical intensive care unit (SICU) involves handoffs between multiple providers. Incomplete handoffs lead to poor communication, a major contributor to sentinel events. Our aim was to determine whether handoff standardization led to improvements in caregiver involvement and communication. A prospective intervention study was designed to observe thirty one patient handoffs from OR to SICU for 49 critical parameters including caregiver presence, peri-operative details, and time required to complete key steps. Following a six month implementation period, thirty one handoffs were observed to determine improvement. A significant improvement in presence of physician providers including intensivists and surgeons was observed (p = 0.0004 and p < 0.0001, respectively). Critical details were communicated more consistently, including procedure performed (p = 0.0048), complications (p < 0.0001), difficult airways (p < 0.0001), ventilator settings (p < 0.0001) and pressor requirements (p = 0.0134). Conversely, handoff duration did not increase significantly (p = 0.22). Implementation of a standardized protocol for handoffs between OR and SICU significantly improved caregiver involvement and reduced information omission without affecting provider time commitment. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. LOX-mediated collagen crosslinking is responsible for fibrosis-enhanced metastasis

    PubMed Central

    Cox, Thomas R.; Bird, Demelza; Baker, Ann-Marie; Barker, Holly E.; Ho, Melisa W-Y.; Lang, Georgina; Erler, Janine T.

    2013-01-01

    Tumor metastasis is a highly complex, dynamic and inefficient process involving multiple steps, yet accounts for over 90% of cancer patient deaths. Although it has long been known that fibrotic signals enhance tumor progression and metastasis, the underlying molecular mechanisms are still unclear. Identifying events involved in creating environments that promote metastatic colonization and growth is critical for the development of effective cancer therapies. Here, we demonstrate a critical role for lysyl oxidase (LOX) in establishing a milieu within fibrosing tissues that is favorable to growth of metastastic tumor cells. We show that LOX-dependent collagen crosslinking is involved in creating a growth-permissive fibrotic microenvironment capable of supporting metastatic growth by enhancing tumor cell persistence and survival. We show that therapeutic targeting of LOX abrogates not only the extent to which fibrosis manifests, but also prevents fibrosis-enhanced metastatic colonization. Finally, we show that the LOX-mediated collagen cross-linking directly increases tumor cell proliferation, enhancing metastatic colonization and growth manifesting in vivo as increased metastasis. This is the first time that crosslinking of collagen I has been shown to enhance metastatic growth. These findings provide an important link between extracellular matrix homeostasis, fibrosis and cancer with important clinical implications for both the treatment of fibrotic disease and cancer. PMID:23345161

  4. Single-Molecule Spectroscopy and Imaging Studies of Protein Dynamics

    NASA Astrophysics Data System (ADS)

    Lu, H. Peter

    2012-04-01

    Enzymatic reactions and protein-protein interactions are traditionally studied at the ensemble level, despite significant static and dynamic inhomogeneities. Subtle conformational changes play a crucial role in protein functions, and these protein conformations are highly dynamic rather than being static. We applied AFM-enhanced single-molecule spectroscopy to study the mechanisms and dynamics of enzymatic reactions involved with kinase and lysozyme proteins. Enzymatic reaction turnovers and the associated structure changes of individual protein molecules were observed simultaneously in real-time by single-molecule FRET detections. Our single-molecule spectroscopy measurements of T4 lysozyme and HPPK enzymatic conformational dynamics have revealed time bunching effect and intermittent coherence in conformational state change dynamics involving in enzymatic reaction cycles. The coherent conformational state dynamics suggests that the enzymatic catalysis involves a multi-step conformational motion along the coordinates of substrate-enzyme complex formation and product releasing, presenting as an extreme dynamic behavior intrinsically related to the time bunching effect that we have reported previously. Our results of HPPK interaction with substrate support a multiple-conformational state model, being consistent with a complementary conformation selection and induced-fit enzymatic loop-gated conformational change mechanism in substrate-enzyme active complex formation. Our new approach is applicable to a wide range of single-molecule FRET measurements for protein conformational changes under enzymatic reactions.

  5. Localization of a translocation breakpoint involved in Smith-Lemli-Opitz syndrome

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

    Alley, T.L.; Gray, B.A.; Lee, S.

    1994-09-01

    Smith-Lemli-Opitz syndrome (SLOS) is a multiple congenital anomaly/mental retardation syndrome, with features including toe syndactyly, genital anomalies, unusual facies, and occasional organ malformations. The gene(s) for this autosomal recessive disorder has not been mapped. Recent biochemical studies suggest that the defect may involve the penultimate step in cholesterol synthesis, as patients have low serum cholesterol and increased 7-dehydrocholesterol (7-DHC) levels. However, the enzyme putatively involved (7-DHC reductase) has not been isolated. We identified an SLOS patient with a de novo balanced chromosome translocation [t(7;20)(q32.1;q13.2)], and we propose that the translocation interrupts one of the patient`s SLOS alleles. We are pursuingmore » positional cloning to identify the SLOS gene. Using fluorescence in situ hybridization (FISH), we recently identified a chromosome 7 yeast artificial chromosome (YAC) that spans the breakpoint and places it onto physical and genetic maps. We are in the process of narrowing this region via overlapping YACs and YAC subclones, from which we will isolate candidate cDNAs. Any candidate gene disrupted by the translocation and mutated on the other allele will be proven to be the SLOS gene. Functional analysis of an SLOS cDNA may also determine its relationship to cholesterol metabolism and the observed biochemical abnormalities.« less

  6. Design of the Steps to Health Study of Physical Activity in Survivors of Endometrial Cancer: Testing a Social Cognitive Theory Model.

    PubMed

    Basen-Engquist, Karen; Carmack, Cindy L; Perkins, Heidi; Hughes, Daniel; Serice, Susan; Scruggs, Stacie; Pinto, Bernardine; Waters, Andrew

    2011-01-01

    Physical activity has been shown to benefit cancer survivors' physical functioning, emotional well-being, and symptoms. Physical activity may be of particular benefit to survivors of endometrial cancer because they are more likely to be obese and sedentary than the general population, as these are risk factors for the disease, and thus experience a number of related co-morbid health problems. However, there is little research systematically studying mechanisms of physical activity adherence in cancer survivor populations. This paper describes the design of the Steps to Health study, which applies a Social Cognitive Theory-based model of endometrial cancer survivors' adoption and maintenance of exercise in the context of an intervention to increase walking or other moderate intensity cardiovascular activity. In Steps to Health we will test the influence of self-efficacy and outcome expectations on adherence to exercise recommendations, as well as studying the determinants of self-efficacy. Endometrial cancer survivors who are at least 6 months post-treatment are provided with an intervention involving print materials and telephone counseling, and complete assessments of fitness, activity, self-efficacy and outcome expectations, and determinants of self-efficacy every two months for a six month period. In addition to testing an innovative model, the Steps to Health study employs multiple assessment methods, including ecological momentary assessment, implicit tests of cognitive variables, and ambulatory monitoring of physical activity. The study results can be used to develop more effective interventions for increasing physical activity in sedentary cancer survivors by taking into account the full complement of sources of self-efficacy information and outcome expectations.

  7. Eating and drinking interventions for people at risk of lacking decision-making capacity: who decides and how?

    PubMed

    Clarke, Gemma; Galbraith, Sarah; Woodward, Jeremy; Holland, Anthony; Barclay, Stephen

    2015-06-11

    Some people with progressive neurological diseases find they need additional support with eating and drinking at mealtimes, and may require artificial nutrition and hydration. Decisions concerning artificial nutrition and hydration at the end of life are ethically complex, particularly if the individual lacks decision-making capacity. Decisions may concern issues of life and death: weighing the potential for increasing morbidity and prolonging suffering, with potentially shortening life. When individuals lack decision-making capacity, the standard processes of obtaining informed consent for medical interventions are disrupted. Increasingly multi-professional groups are being utilised to make difficult ethical decisions within healthcare. This paper reports upon a service evaluation which examined decision-making within a UK hospital Feeding Issues Multi-Professional Team. A three month observation of a hospital-based multi-professional team concerning feeding issues, and a one year examination of their records. The key research questions are: a) How are decisions made concerning artificial nutrition for individuals at risk of lacking decision-making capacity? b) What are the key decision-making factors that are balanced? c) Who is involved in the decision-making process? Decision-making was not a singular decision, but rather involved many different steps. Discussions involving relatives and other clinicians, often took place outside of meetings. Topics of discussion varied but the outcome relied upon balancing the information along four interdependent axes: (1) Risks, burdens and benefits; (2) Treatment goals; (3) Normative ethical values; (4) Interested parties. Decision-making was a dynamic ongoing process with many people involved. The multiple points of decision-making, and the number of people involved with the decision-making process, mean the question of 'who decides' cannot be fully answered. There is a potential for anonymity of multiple decision-makers to arise. Decisions in real world clinical practice may not fit precisely into a model of decision-making. The findings from this service evaluation illustrate that within multi-professional team decision-making; decisions may contain elements of both substituted and supported decision-making, and may be better represented as existing upon a continuum.

  8. Gaze Fluctuations Are Not Additively Decomposable: Reply to Bogartz and Staub

    ERIC Educational Resources Information Center

    Kelty-Stephen, Damian G.; Mirman, Daniel

    2013-01-01

    Our previous work interpreted single-lognormal fits to inter-gaze distance (i.e., "gaze steps") histograms as evidence of multiplicativity and hence interactions across scales in visual cognition. Bogartz and Staub (2012) proposed that gaze steps are additively decomposable into fixations and saccades, matching the histograms better and…

  9. The use of poly-cation oxides to lower the temperature of two-step thermochemical water splitting

    DOE PAGES

    Zhai, Shang; Rojas, Jimmy; Ahlborg, Nadia; ...

    2018-01-01

    We report the discovery of a new class of oxides – poly-cation oxides (PCOs) – that consist of multiple cations and can thermochemically split water in a two-step cycle to produce hydrogen (H 2 ) and oxygen (O 2 ).

  10. Applied Missing Data Analysis. Methodology in the Social Sciences Series

    ERIC Educational Resources Information Center

    Enders, Craig K.

    2010-01-01

    Walking readers step by step through complex concepts, this book translates missing data techniques into something that applied researchers and graduate students can understand and utilize in their own research. Enders explains the rationale and procedural details for maximum likelihood estimation, Bayesian estimation, multiple imputation, and…

  11. Comparison of the phenolic composition of fruit juices by single step gradient HPLC analysis of multiple components versus multiple chromatographic runs optimised for individual families.

    PubMed

    Bremner, P D; Blacklock, C J; Paganga, G; Mullen, W; Rice-Evans, C A; Crozier, A

    2000-06-01

    After minimal sample preparation, two different HPLC methodologies, one based on a single gradient reversed-phase HPLC step, the other on multiple HPLC runs each optimised for specific components, were used to investigate the composition of flavonoids and phenolic acids in apple and tomato juices. The principal components in apple juice were identified as chlorogenic acid, phloridzin, caffeic acid and p-coumaric acid. Tomato juice was found to contain chlorogenic acid, caffeic acid, p-coumaric acid, naringenin and rutin. The quantitative estimates of the levels of these compounds, obtained with the two HPLC procedures, were very similar, demonstrating that either method can be used to analyse accurately the phenolic components of apple and tomato juices. Chlorogenic acid in tomato juice was the only component not fully resolved in the single run study and the multiple run analysis prior to enzyme treatment. The single run system of analysis is recommended for the initial investigation of plant phenolics and the multiple run approach for analyses where chromatographic resolution requires improvement.

  12. Predictors of 12-Step Attendance and Participation for Individuals With Stimulant Use Disorders.

    PubMed

    Hatch-Maillette, Mary; Wells, Elizabeth A; Doyle, Suzanne R; Brigham, Gregory S; Daley, Dennis; DiCenzo, Jessica; Donovan, Dennis; Garrett, Sharon; Horigian, Viviana E; Jenkins, Lindsay; Killeen, Therese; Owens, Mandy; Perl, Harold I

    2016-09-01

    Few studies have examined the effectiveness of 12-step peer recovery support programs with drug use disorders, especially stimulant use, and it is difficult to know how outcomes related to 12-step attendance and participation generalize to individuals with non-alcohol substance use disorders (SUDs). A clinical trial of 12-step facilitation (N=471) focusing on individuals with cocaine or methamphetamine use disorders allowed examination of four questions: Q1) To what extent do treatment-seeking stimulant users use 12-step programs and, which ones? Q2) Do factors previously found to predict 12-step participation among those with alcohol use disorders also predict participation among stimulant users? Q3) What specific baseline "12-step readiness" factors predict subsequent 12-step participation and attendance? And Q4) Does stimulant drug of choice differentially predict 12-step participation and attendance? The four outcomes variables, attendance, speaking, duties at 12-step meetings, and other peer recovery support activities, were not related to baseline demographic or substance problem history or severity. Drug of choice was associated with differential days of Alcoholics Anonymous (AA) and Narcotics Anonymous (NA) attendance among those who reported attending, and cocaine users reported more days of attending AA or NA at 1-, 3- and 6-month follow-ups than did methamphetamine users. Pre-randomization measures of perceived benefit of 12-step groups predicted 12-step attendance at 3- and 6-month follow-ups. Pre-randomization 12-step attendance significantly predicted number of other self-help activities at end-of-treatment, 3- and 6-month follow-ups. Pre-randomization perceived benefit and problem severity both predicted number of self-help activities at end-of-treatment and 3-month follow-up. Pre-randomization perceived barriers to 12-step groups were negatively associated with self-help activities at end-of-treatment and 3-month follow-up. Whether or not one participated in any duties was predicted at all time points by pre-randomization involvement in self-help activities. The primary finding of this study is one of continuity: prior attendance and active involvement with 12-step programs were the main signs pointing to future involvement. Limitations and recommendations are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Predictors of 12-Step Attendance and Participation for Individuals with Stimulant Use Disorders

    PubMed Central

    Hatch-Maillette, Mary; Wells, Elizabeth A.; Doyle, Suzanne R.; Brigham, Gregory S.; Daley, Dennis; DiCenzo, Jessica; Donovan, Dennis; Garrett, Sharon; Horigian, Viviana E.; Jenkins, Lindsay; Killeen, Therese; Owens, Mandy; Perl, Harold I.

    2017-01-01

    Objective Few studies have examined the effectiveness of 12-step peer recovery support programs with drug use disorders, especially stimulant use, and it is difficult to know how outcomes related to 12-step attendance and participation generalize to individuals with non-alcohol substance use disorders (SUDs). Method A clinical trial of 12-step facilitation (N=471) focusing on individuals with cocaine or methamphetamine use disorders allowed examination of four questions: Q1) To what extent do treatment-seeking stimulant users use 12-step programs and, which ones? Q2) Do factors previously found to predict 12-step participation among those with alcohol use disorders also predict participation among stimulant users? Q3) What specific baseline “12-step readiness” factors predict subsequent 12-step participation and attendance? And Q4) Does stimulant drug of choice differentially predict 12-step participation and attendance? Results The four outcomes variables, Attendance, Speaking, Duties at 12-step meetings, and other peer recovery support Activities, were not related to baseline demographic or substance problem history or severity. Drug of choice was associated with differential days of Alcoholics Anonymous (AA) and Narcotics Anonymous (NA) attendance among those who reported attending, and cocaine users reported more days of attending AA or NA at 1-, 3- and 6-month follow-ups than did methamphetamine users. Pre-randomization measures of Perceived Benefit of 12-step groups predicted 12-step Attendance at 3- and 6-month follow-ups. Pre-randomization 12-step Attendance significantly predicted number of other Self-Help Activities at end-of-treatment, 3- and 6-month follow-ups. Pre-randomization Perceived Benefit and problem severity both predicted number of Self-Help Activities at end-of-treatment and 3-month follow-up. Pre-randomization Perceived Barriers to 12-step groups were negatively associated with Self-Help Activities at end-of-treatment and 3-month follow-up. Whether or not one participated in any Duties was predicted at all time points by pre-randomization involvement in Self-Help Activities. Conclusions The primary finding of this study is one of continuity: prior attendance and active involvement with 12-step programs were the main signs pointing to future involvement. Limitations and Recommendations are discussed. PMID:27431050

  14. Probability genotype imputation method and integrated weighted lasso for QTL identification.

    PubMed

    Demetrashvili, Nino; Van den Heuvel, Edwin R; Wit, Ernst C

    2013-12-30

    Many QTL studies have two common features: (1) often there is missing marker information, (2) among many markers involved in the biological process only a few are causal. In statistics, the second issue falls under the headings "sparsity" and "causal inference". The goal of this work is to develop a two-step statistical methodology for QTL mapping for markers with binary genotypes. The first step introduces a novel imputation method for missing genotypes. Outcomes of the proposed imputation method are probabilities which serve as weights to the second step, namely in weighted lasso. The sparse phenotype inference is employed to select a set of predictive markers for the trait of interest. Simulation studies validate the proposed methodology under a wide range of realistic settings. Furthermore, the methodology outperforms alternative imputation and variable selection methods in such studies. The methodology was applied to an Arabidopsis experiment, containing 69 markers for 165 recombinant inbred lines of a F8 generation. The results confirm previously identified regions, however several new markers are also found. On the basis of the inferred ROC behavior these markers show good potential for being real, especially for the germination trait Gmax. Our imputation method shows higher accuracy in terms of sensitivity and specificity compared to alternative imputation method. Also, the proposed weighted lasso outperforms commonly practiced multiple regression as well as the traditional lasso and adaptive lasso with three weighting schemes. This means that under realistic missing data settings this methodology can be used for QTL identification.

  15. SQERTSS: Dynamic rank based throttling of transition probabilities in kinetic Monte Carlo simulations

    DOE PAGES

    Danielson, Thomas; Sutton, Jonathan E.; Hin, Céline; ...

    2017-06-09

    Lattice based Kinetic Monte Carlo (KMC) simulations offer a powerful simulation technique for investigating large reaction networks while retaining spatial configuration information, unlike ordinary differential equations. However, large chemical reaction networks can contain reaction processes with rates spanning multiple orders of magnitude. This can lead to the problem of “KMC stiffness” (similar to stiffness in differential equations), where the computational expense has the potential to be overwhelmed by very short time-steps during KMC simulations, with the simulation spending an inordinate amount of KMC steps / cpu-time simulating fast frivolous processes (FFPs) without progressing the system (reaction network). In order tomore » achieve simulation times that are experimentally relevant or desired for predictions, a dynamic throttling algorithm involving separation of the processes into speed-ranks based on event frequencies has been designed and implemented with the intent of decreasing the probability of FFP events, and increasing the probability of slow process events -- allowing rate limiting events to become more likely to be observed in KMC simulations. This Staggered Quasi-Equilibrium Rank-based Throttling for Steady-state (SQERTSS) algorithm designed for use in achieving and simulating steady-state conditions in KMC simulations. Lastly, as shown in this work, the SQERTSS algorithm also works for transient conditions: the correct configuration space and final state will still be achieved if the required assumptions are not violated, with the caveat that the sizes of the time-steps may be distorted during the transient period.« less

  16. SQERTSS: Dynamic rank based throttling of transition probabilities in kinetic Monte Carlo simulations

    NASA Astrophysics Data System (ADS)

    Danielson, Thomas; Sutton, Jonathan E.; Hin, Céline; Savara, Aditya

    2017-10-01

    Lattice based Kinetic Monte Carlo (KMC) simulations offer a powerful simulation technique for investigating large reaction networks while retaining spatial configuration information, unlike ordinary differential equations. However, large chemical reaction networks can contain reaction processes with rates spanning multiple orders of magnitude. This can lead to the problem of "KMC stiffness" (similar to stiffness in differential equations), where the computational expense has the potential to be overwhelmed by very short time-steps during KMC simulations, with the simulation spending an inordinate amount of KMC steps/CPU time simulating fast frivolous processes (FFPs) without progressing the system (reaction network). In order to achieve simulation times that are experimentally relevant or desired for predictions, a dynamic throttling algorithm involving separation of the processes into speed-ranks based on event frequencies has been designed and implemented with the intent of decreasing the probability of FFP events, and increasing the probability of slow process events-allowing rate limiting events to become more likely to be observed in KMC simulations. This Staggered Quasi-Equilibrium Rank-based Throttling for Steady-state (SQERTSS) algorithm is designed for use in achieving and simulating steady-state conditions in KMC simulations. As shown in this work, the SQERTSS algorithm also works for transient conditions: the correct configuration space and final state will still be achieved if the required assumptions are not violated, with the caveat that the sizes of the time-steps may be distorted during the transient period.

  17. Development of DKB ETL module in case of data conversion

    NASA Astrophysics Data System (ADS)

    Kaida, A. Y.; Golosova, M. V.; Grigorieva, M. A.; Gubin, M. Y.

    2018-05-01

    Modern scientific experiments involve the producing of huge volumes of data that requires new approaches in data processing and storage. These data themselves, as well as their processing and storage, are accompanied by a valuable amount of additional information, called metadata, distributed over multiple informational systems and repositories, and having a complicated, heterogeneous structure. Gathering these metadata for experiments in the field of high energy nuclear physics (HENP) is a complex issue, requiring the quest for solutions outside the box. One of the tasks is to integrate metadata from different repositories into some kind of a central storage. During the integration process, metadata taken from original source repositories go through several processing steps: metadata aggregation, transformation according to the current data model and loading it to the general storage in a standardized form. The R&D project of ATLAS experiment on LHC, Data Knowledge Base, is aimed to provide fast and easy access to significant information about LHC experiments for the scientific community. The data integration subsystem, being developed for the DKB project, can be represented as a number of particular pipelines, arranging data flow from data sources to the main DKB storage. The data transformation process, represented by a single pipeline, can be considered as a number of successive data transformation steps, where each step is implemented as an individual program module. This article outlines the specifics of program modules, used in the dataflow, and describes one of the modules developed and integrated into the data integration subsystem of DKB.

  18. Demonstrating Enzyme Activation: Calcium/Calmodulin Activation of Phosphodiesterase

    ERIC Educational Resources Information Center

    Porta, Angela R.

    2004-01-01

    Demonstrating the steps of a signal transduction cascade usually involves radioactive materials and thus precludes its use in undergraduate teaching labs. Developing labs that allow the visual demonstration of these steps without the use of radioactivity is important for allowing students hands-on methods of illustrating each step of a signal…

  19. Steps in the open space planning process

    Treesearch

    Stephanie B. Kelly; Melissa M. Ryan

    1995-01-01

    This paper presents the steps involved in developing an open space plan. The steps are generic in that the methods may be applied various size communities. The intent is to provide a framework to develop an open space plan that meets Massachusetts requirements for funding of open space acquisition.

  20. [Information management in multicenter studies: the Brazilian longitudinal study for adult health].

    PubMed

    Duncan, Bruce Bartholow; Vigo, Álvaro; Hernandez, Émerson; Luft, Vivian Cristine; Ahlert, Hubert; Bergmann, Kaiser; Mota, Eduardo

    2013-06-01

    Information management in large multicenter studies requires a specialized approach. The Estudo Longitudinal da Saúde do Adulto (ELSA-Brasil - Brazilian Longitudinal Study for Adult Health) has created a Datacenter to enter and manage its data system. The aim of this paper is to describe the steps involved, including the information entry, transmission and management methods. A web system was developed in order to allow, in a safe and confidential way, online data entry, checking and editing, as well as the incorporation of data collected on paper. Additionally, a Picture Archiving and Communication System was implemented and customized for echocardiography and retinography. It stores the images received from the Investigation Centers and makes them available at the Reading Centers. Finally, data extraction and cleaning processes were developed to create databases in formats that enable analyses in multiple statistical packages.

  1. Sensory illusions: Common mistakes in physics regarding sound, light and radio waves

    NASA Astrophysics Data System (ADS)

    Briles, T. M.; Tabor-Morris, A. E.

    2013-03-01

    Optical illusions are well known as effects that we see that are not representative of reality. Sensory illusions are similar but can involve other senses than sight, such as hearing or touch. One mistake commonly noted among instructors is that students often mis-identify radio signals as sound waves and not as part of the electromagnetic spectrum. A survey of physics students from multiple high schools highlights the frequency of this common misconception, as well as other nuances on this misunderstanding. Many students appear to conclude that, since they experience radio broadcasts as sound, then sound waves are the actual transmission of radio signals and not, as is actually true, a representation of those waves as produced by the translator box, the radio. Steps to help students identify and correct sensory illusion misconceptions are discussed. School of Education

  2. The Domino Way to Heterocycles

    PubMed Central

    Padwa, Albert; Bur, Scott K.

    2007-01-01

    Sequential transformations enable the facile synthesis of complex target molecules from simple building blocks in a single preparative step. Their value is amplified if they also create multiple stereogenic centers. In the ongoing search for new domino processes, emphasis is usually placed on sequential reactions which occur cleanly and without forming by-products. As a prerequisite for an ideally proceeding one-pot sequential transformation, the reactivity pattern of all participating components has to be such that each building block gets involved in a reaction only when it is supposed to do so. The development of sequences that combine transformations of fundamentally different mechanisms broadens the scope of such procedures in synthetic chemistry. This mini review contains a representative sampling from the last 15 years on the kinds of reactions that have been sequenced into cascades to produce heterocyclic molecules. PMID:17940591

  3. A new approach to the design of information systems for foodservice management in health care facilities.

    PubMed

    Matthews, M E; Norback, J P

    1984-06-01

    An organizational framework for integrating foodservice data into an information system for management decision making is presented. The framework involves the application to foodservice of principles developed by the disciplines of managerial economics and accounting, mathematics, computer science, and information systems. The first step is to conceptualize a foodservice system from an input-output perspective, in which inputs are units of resources available to managers and outputs are servings of menu items. Next, methods of full cost accounting, from the management accounting literature, are suggested as a mechanism for developing and assigning costs of using resources within a foodservice operation. Then matrix multiplication is used to illustrate types of information that matrix data structures could make available for management planning and control when combined with a conversational mode of computer programming.

  4. Patterning of mammalian somites by surface ectoderm and notochord: evidence for sclerotome induction by a hedgehog homolog.

    PubMed

    Fan, C M; Tessier-Lavigne, M

    1994-12-30

    An early step in the development of vertebrae, ribs, muscle, and dermis is the differentiation of the somitic mesoderm into dermomyotome dorsally and sclerotome ventrally. To analyze this process, we have developed an in vitro assay for somitic mesoderm differentiation. We show that sclerotomal markers can be induced by a diffusible factor secreted by notochord and floor plate and that heterologous cells expressing Sonic hedgehog (shh/vhh-1) mimic this effect. In contrast, expression of dermomyotomal markers can be caused by a contact-dependent signal from surface ectoderm and a diffusible signal from dorsal neural tube. Our results extend previous studies by suggesting that dorsoventral patterning of somites involves the coordinate action of multiple dorsalizing and ventralizing signals and that a diffusible form of Shh/Vhh-1 mediates sclerotome induction.

  5. Hemagglutinin-Mediated Membrane Fusion: A Biophysical Perspective.

    PubMed

    Boonstra, Sander; Blijleven, Jelle S; Roos, Wouter H; Onck, Patrick R; van der Giessen, Erik; van Oijen, Antoine M

    2018-05-20

    Influenza hemagglutinin (HA) is a viral membrane protein responsible for the initial steps of the entry of influenza virus into the host cell. It mediates binding of the virus particle to the host-cell membrane and catalyzes fusion of the viral membrane with that of the host. HA is therefore a major target in the development of antiviral strategies. The fusion of two membranes involves high activation barriers and proceeds through several intermediate states. Here, we provide a biophysical description of the membrane fusion process, relating its kinetic and thermodynamic properties to the large conformational changes taking place in HA and placing these in the context of multiple HA proteins working together to mediate fusion. Furthermore, we highlight the role of novel single-particle experiments and computational approaches in understanding the fusion process and their complementarity with other biophysical approaches.

  6. Generic mission planning concepts for space astronomy missions

    NASA Technical Reports Server (NTRS)

    Guffin, O. T.; Onken, J. F.

    1993-01-01

    The past two decades have seen the rapid development of space astronomy, both manned and unmanned, and the concurrent proliferation of the operational concepts and software that have been produced to support each individual project. Having been involved in four of these missions since the '70's and three yet to fly in the present decade, the authors believe it is time to step back and evaluate this body of experience from a macro-systems point of view to determine the potential for generic mission planning concepts that could be applied to future missions. This paper presents an organized evaluation of astronomy mission planning functions, functional flows, iteration cycles, replanning activities, and the requirements that drive individual concepts to specific solutions. The conclusions drawn from this exercise are then used to propose a generic concept that could support multiple missions.

  7. Multifocal pigmented villonodular synovitis in a child. A case report.

    PubMed

    Kay, R M; Eckardt, J J; Mirra, J M

    1996-01-01

    Pigmented villonodular synovitis is a well-described disease that almost universally involves a single site. This is a report of an unusual case of multiple site involvement of pigmented villonodular synovitis in a child. In addition to multiple site involvement, the case is unusual for several reasons: asymmetric involvement, involvement of both upper and lower extremities, involvement of the pes anserine tendons, and the patient is an otherwise healthy child.

  8. Domain Definition and Search Techniques in Meta-Analyses of L2 Research (or Why 18 Meta-Analyses of Feedback Have Different Results)

    ERIC Educational Resources Information Center

    Plonsky, Luke; Brown, Dan

    2015-01-01

    Applied linguists have turned increasingly in recent years to meta-analysis as the preferred means of synthesizing quantitative research. The first step in the meta-analytic process involves defining a domain of interest. Despite its apparent simplicity, this step involves a great deal of subjectivity on the part of the meta-analyst. This article…

  9. Partitioning the Fitness Components of RNA Populations Evolving In Vitro

    PubMed Central

    Díaz Arenas, Carolina; Lehman, Niles

    2013-01-01

    All individuals in an evolving population compete for resources, and their performance is measured by a fitness metric. The performance of the individuals is relative to their abilities and to the biotic surroundings – the conditions under which they are competing – and involves many components. Molecules evolving in a test tube can also face complex environments and dynamics, and their fitness measurements should reflect the complexity of various contributing factors as well. Here, the fitnesses of a set of ligase ribozymes evolved by the continuous in vitro evolution system were measured. During these evolution cycles there are three different catalytic steps, ligation, reverse transcription, and forward transcription, each with a potential differential influence on the total fitness of each ligase. For six distinct ligase ribozyme genotypes that resulted from continuous evolution experiments, the rates of reaction were measured for each catalytic step by tracking the kinetics of enzymes reacting with their substrates. The reaction products were analyzed for the amount of product formed per time. Each catalytic step of the evolution cycle was found to have a differential incidence in the total fitness of the ligases, and therefore the total fitness of any ligase cannot be inferred from only one catalytic step of the evolution cycle. Generally, the ribozyme-directed ligation step tends to impart the largest effect on overall fitness. Yet it was found that the ligase genotypes have different absolute fitness values, and that they exploit different stages of the overall cycle to gain a net advantage. This is a new example of molecular niche partitioning that may allow for coexistence of more than one species in a population. The dissection of molecular events into multiple components of fitness provides new insights into molecular evolutionary studies in the laboratory, and has the potential to explain heretofore counterintuitive findings. PMID:24391957

  10. Study Behaviors and USMLE Step 1 Performance: Implications of a Student Self-Directed Parallel Curriculum.

    PubMed

    Burk-Rafel, Jesse; Santen, Sally A; Purkiss, Joel

    2017-11-01

    To determine medical students' study behaviors when preparing for the United States Medical Licensing Examination (USMLE) Step 1, and how these behaviors are associated with Step 1 scores when controlling for likely covariates. The authors distributed a study-behaviors survey in 2014 and 2015 at their institution to two cohorts of medical students who had recently taken Step 1. Demographic and academic data were linked to responses. Descriptive statistics, bivariate correlations, and multiple linear regression analyses were performed. Of 332 medical students, 274 (82.5%) participated. Most students (n = 211; 77.0%) began studying for Step 1 during their preclinical curriculum, increasing their intensity during a protected study period during which they averaged 11.0 hours studying per day (standard deviation [SD] 2.1) over a period of 35.3 days (SD 6.2). Students used numerous third-party resources, including reading an exam-specific 700-page review book on average 2.1 times (SD 0.8) and completing an average of 3,597 practice multiple-choice questions (SD 1,611). Initiating study prior to the designated study period, increased review book usage, and attempting more practice questions were all associated with higher Step 1 scores, even when controlling for Medical College Admission Test scores, preclinical exam performance, and self-identified score goal (adjusted R = 0.56, P < .001). Medical students at one public institution engaged in a self-directed, "parallel" Step 1 curriculum using third-party study resources. Several study behaviors were associated with improved USMLE Step 1 performance, informing both institutional- and student-directed preparation for this high-stakes exam.

  11. Assembly and multiple gene expression of thermophilic enzymes in Escherichia coli for in vitro metabolic engineering.

    PubMed

    Ninh, Pham Huynh; Honda, Kohsuke; Sakai, Takaaki; Okano, Kenji; Ohtake, Hisao

    2015-01-01

    In vitro reconstitution of an artificial metabolic pathway is an emerging approach for the biocatalytic production of industrial chemicals. However, several enzymes have to be separately prepared (and purified) for the construction of an in vitro metabolic pathway, thereby limiting the practical applicability of this approach. In this study, genes encoding the nine thermophilic enzymes involved in a non-ATP-forming chimeric glycolytic pathway were assembled in an artificial operon and co-expressed in a single recombinant Escherichia coli strain. Gene expression levels of the thermophilic enzymes were controlled by their sequential order in the artificial operon. The specific activities of the recombinant enzymes in the cell-free extract of the multiple-gene-expression E. coli were 5.0-1,370 times higher than those in an enzyme cocktail prepared from a mixture of single-gene-expression strains, in each of which a single one of the nine thermophilic enzymes was overproduced. Heat treatment of a crude extract of the multiple-gene-expression cells led to the denaturation of indigenous proteins and one-step preparation of an in vitro synthetic pathway comprising only a limited number of thermotolerant enzymes. Coupling this in vitro pathway with other thermophilic enzymes including the H2 O-forming NADH oxidase or the malate/lactate dehydrogenase facilitated one-pot conversion of glucose to pyruvate or lactate, respectively. © 2014 Wiley Periodicals, Inc.

  12. Multiple dual mode counter-current chromatography with variable duration of alternating phase elution steps.

    PubMed

    Kostanyan, Artak E; Erastov, Andrey A; Shishilov, Oleg N

    2014-06-20

    The multiple dual mode (MDM) counter-current chromatography separation processes consist of a succession of two isocratic counter-current steps and are characterized by the shuttle (forward and back) transport of the sample in chromatographic columns. In this paper, the improved MDM method based on variable duration of alternating phase elution steps has been developed and validated. The MDM separation processes with variable duration of phase elution steps are analyzed. Basing on the cell model, analytical solutions are developed for impulse and non-impulse sample loading at the beginning of the column. Using the analytical solutions, a calculation program is presented to facilitate the simulation of MDM with variable duration of phase elution steps, which can be used to select optimal process conditions for the separation of a given feed mixture. Two options of the MDM separation are analyzed: 1 - with one-step solute elution: the separation is conducted so, that the sample is transferred forward and back with upper and lower phases inside the column until the desired separation of the components is reached, and then each individual component elutes entirely within one step; 2 - with multi-step solute elution, when the fractions of individual components are collected in over several steps. It is demonstrated that proper selection of the duration of individual cycles (phase flow times) can greatly increase the separation efficiency of CCC columns. Experiments were carried out using model mixtures of compounds from the GUESSmix with solvent systems hexane/ethyl acetate/methanol/water. The experimental results are compared to the predictions of the theory. A good agreement between theory and experiment has been demonstrated. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. A new method for registration of heterogeneous sensors in a dimensional measurement system

    NASA Astrophysics Data System (ADS)

    Zhao, Yan; Wang, Zhong; Fu, Luhua; Qu, Xinghua; Zhang, Heng; Liu, Changjie

    2017-10-01

    Registration of multiple sensors is a basic step in multi-sensor dimensional or coordinate measuring systems before any measurement. In most cases, a common standard is used to be measured by all sensors, and this may work well for general registration of multiple homogeneous sensors. However, when inhomogeneous sensors detect a common standard, it is usually very difficult to obtain the same information, because of the different working principles of the sensors. In this paper, a new method called multiple steps registration is proposed to register two sensors: a video camera sensor (VCS) and a tactile probe sensor (TPS). In this method, the two sensors measure two separated standards: a chrome circle on a reticle and a reference sphere with a constant distance between them, fixed on a steel plate. The VCS captures only the circle and the TPS touches only the sphere. Both simulations and real experiments demonstrate that the proposed method is robust and accurate in the registration of multiple inhomogeneous sensors in a dimensional measurement system.

  14. Performance evaluation of the multiple root node approach to the Rete pattern matcher for production systems

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

    Sohn, A.; Gaudiot, J.-L.

    1991-12-31

    Much effort has been expanded on special architectures and algorithms dedicated to efficient processing of the pattern matching step of production systems. In this paper, the authors investigate the possible improvement on the Rete pattern matcher for production systems. Inefficiencies in the Rete match algorithm have been identified, based on which they introduce a pattern matcher with multiple root nodes. A complete implementation of the multiple root node-based production system interpreter is presented to investigate its relative algorithmic behavior over the Rete-based Ops5 production system interpreter. Benchmark production system programs are executed (not simulated) on a sequential machine Sun 4/490more » by using both interpreters and various experimental results are presented. Their investigation indicates that the multiple root node-based production system interpreter would give a maximum of up to 6-fold improvement over the Lisp implementation of the Rete-based Ops5 for the match step.« less

  15. A 24-Week Multi-Modality Exercise Program Improves Executive Control in Older Adults with a Self-Reported Cognitive Complaint: Evidence from the Antisaccade Task.

    PubMed

    Heath, Matthew; Shellington, Erin; Titheridge, Sam; Gill, Dawn P; Petrella, Robert J

    2017-01-01

    Exercise programs involving aerobic and resistance training (i.e., multiple-modality) have shown promise in improving cognition and executive control in older adults at risk, or experiencing, cognitive decline. It is, however, unclear whether cognitive training within a multiple-modality program elicits an additive benefit to executive/cognitive processes. This is an important question to resolve in order to identify optimal training programs that delay, or ameliorate, executive deficits in persons at risk for further cognitive decline. In the present study, individuals with a self-reported cognitive complaint (SCC) participated in a 24-week multiple-modality (i.e., the M2 group) exercise intervention program. In addition, a separate group of individuals with a SCC completed the same aerobic and resistance training as the M2 group but also completed a cognitive-based stepping task (i.e., multiple-modality, mind-motor intervention: M4 group). Notably, pre- and post-intervention executive control was examined via the antisaccade task (i.e., eye movement mirror-symmetrical to a target). Antisaccades are an ideal tool for the study of individuals with subtle executive deficits because of its hands- and language-free nature and because the task's neural mechanisms are linked to neuropathology in cognitive decline (i.e., prefrontal cortex). Results showed that M2 and M4 group antisaccade reaction times reliably decreased from pre- to post-intervention and the magnitude of the decrease was consistent across groups. Thus, multi-modality exercise training improved executive performance in persons with a SCC independent of mind-motor training. Accordingly, we propose that multiple-modality training provides a sufficient intervention to improve executive control in persons with a SCC.

  16. Community-based participatory research: development of an emergency department-based youth violence intervention using concept mapping.

    PubMed

    Snider, Carolyn E; Kirst, Maritt; Abubakar, Shakira; Ahmad, Farah; Nathens, Avery B

    2010-08-01

    Emergency departments (EDs) see a high number of youths injured by violence. In Ontario, the most common cause of injury for youths visiting EDs is assault. Secondary prevention strategies using the teachable moment (i.e., events that can lead individuals to make positive changes in their lives) are ideal for use by clinicians. An opportunity exists to take advantage of the teachable moment in the ED in an effort to prevent future occurrences of injury in at-risk youths. However, little is known about perceptions of youths, parents, and community organizations about such interventions in EDs. The aims of this study were to engage youths, parents, and frontline community workers in conceptualizing a hospital-based violence prevention intervention and to identify outcomes relevant to the community. Concept mapping is an innovative, mixed-method research approach. It combines structured qualitative processes such as brainstorming and group sorting, with various statistical analyses such as multidimensional scaling and hierarchical clustering, to develop a conceptual framework, and allows for an objective presentation of qualitative data. Concept mapping involves multiple structured steps: 1) brainstorming, 2) sorting, 3) rating, and 4) interpretation. For this study, the first three steps occurred online, and the fourth step occurred during a community meeting. Over 90 participants were involved, including youths, parents, and community youth workers. A two-dimensional point map was created and clusters formed to create a visual display of participant ideas on an ED-based youth violence prevention intervention. Issues related to youth violence prevention that were rated of highest importance and most realistic for hospital involvement included mentorship, the development of youth support groups in the hospital, training doctors and nurses to ask questions about the violent event, and treating youth with respect. Small-group discussions on the various clusters developed job descriptions, a list of essential services, and suggestions on ways to create a more youth-friendly environment in the hospital. A large-group discussion revealed outcomes that participants felt should be measured to determine the success of an intervention program. This study has been the springboard for the development of an ED-based youth violence intervention that is supported by the community and affected youth. Using information generated by youth that is grounded in their experience through participatory research methods is feasible for the development of successful and meaningful youth violence prevention interventions.

  17. A study of X100 pipeline steel passivation in mildly alkaline bicarbonate solutions using electrochemical impedance spectroscopy under potentiodynamic conditions and Mott-Schottky

    NASA Astrophysics Data System (ADS)

    Gadala, Ibrahim M.; Alfantazi, Akram

    2015-12-01

    The key steps involved in X100 pipeline steel passivation in bicarbonate-based simulated soil solutions from the pre-passive to transpassive potential regions have been analyzed here using a step-wise anodizing-electrochemical impedance spectroscopy (EIS) routine. Pre-passive steps involve parallel dissolution-adsorption in early stages followed by clear diffusion-adsorption control shortly before iron hydroxide formation. Aggressive NS4 chlorides/sulfate promote steel dissolution whilst inhibiting diffusion in pre-passive steps. Diffusive and adsorptive effects remain during iron hydroxide formation, but withdraw shortly thereafter during its removal and the development of the stable iron carbonate passive layer. Passive layer protectiveness is evaluated using EIS fitting, current density analysis, and correlations with semiconductive parameters, consistently revealing improved robustness in colder, bicarbonate-rich, chloride/sulfate-free conditions. Ferrous oxide formation at higher potentials results in markedly lower impedances with disordered behavior, and the involvement of the iron(III) valence state is observed in Mott-Schottky tests exclusively for 75 °C conditions.

  18. 2-Step Maximum Likelihood Channel Estimation for Multicode DS-CDMA with Frequency-Domain Equalization

    NASA Astrophysics Data System (ADS)

    Kojima, Yohei; Takeda, Kazuaki; Adachi, Fumiyuki

    Frequency-domain equalization (FDE) based on the minimum mean square error (MMSE) criterion can provide better downlink bit error rate (BER) performance of direct sequence code division multiple access (DS-CDMA) than the conventional rake combining in a frequency-selective fading channel. FDE requires accurate channel estimation. In this paper, we propose a new 2-step maximum likelihood channel estimation (MLCE) for DS-CDMA with FDE in a very slow frequency-selective fading environment. The 1st step uses the conventional pilot-assisted MMSE-CE and the 2nd step carries out the MLCE using decision feedback from the 1st step. The BER performance improvement achieved by 2-step MLCE over pilot assisted MMSE-CE is confirmed by computer simulation.

  19. Comparison of 12-step Groups to Mutual Help Alternatives for AUD in a Large, National Study: Differences in Membership Characteristics and Group Participation, Cohesion, and Satisfaction

    PubMed Central

    Zemore, Sarah E.; Kaskutas, Lee Ann; Mericle, Amy; Hemberg, Jordana

    2016-01-01

    Background Many studies suggest that participation in 12-step groups contributes to better recovery outcomes, but people often object to such groups and most do not sustain regular involvement. Yet, research on alternatives to 12-step groups is very sparse. The present study aimed to extend the knowledge base on mutual help group alternatives for those with an alcohol use disorder (AUD), sampling from large, active, abstinence-focused groups including Women for Sobriety (WFS), LifeRing, and SMART Recovery (SMART). This paper presents a cross-sectional analysis of this longitudinal study, using baseline data to describe the profile and participation characteristics of attendees of these groups in comparison to 12-step members. Methods Data from participants 18 and over with a lifetime AUD (N=651) were collected using web-based surveys. Members of alternative 12-step groups were recruited in collaboration with group directors, who helped publicize the study by emailing meeting conveners and attendees and posting announcements on social media. A comparison group of current (past-30-day) 12-step attendees was recruited from an online meeting hub for recovering persons. Interested parties were directed to a webpage where they were screened, and eligible participants completed an online survey assessing demographic and clinical variables; in-person and online mutual help involvement; and group satisfaction and cohesion. Analyses involved comparing those identifying WFS, SMART, and LifeRing as their primary group to 12-step members on the above characteristics. Results Compared to 12-step members, members of the mutual help alternatives were less religious and generally higher on education and income. WFS and LifeRing members were also older, more likely to be married, and lower on lifetime drug and psychiatric severity; meanwhile, LifeRing and SMART members were less likely to endorse the most stringent abstinence goal. Finally, despite lower levels of in-person meeting attendance, members of all the 12-step alternatives showed equivalent activity involvement and higher levels of satisfaction and cohesion, compared to 12-step members. Conclusions Results suggest differences across 12-step groups and their alternatives that may be relevant when advising clients on a choice of mutual help group. Meanwhile, findings for high levels of participation, satisfaction, and cohesion among members of the mutual help alternatives suggest promise for these groups in addressing addiction problems. PMID:28017180

  20. Comparison of 12-step groups to mutual help alternatives for AUD in a large, national study: Differences in membership characteristics and group participation, cohesion, and satisfaction.

    PubMed

    Zemore, Sarah E; Kaskutas, Lee Ann; Mericle, Amy; Hemberg, Jordana

    2017-02-01

    Many studies suggest that participation in 12-step groups contributes to better recovery outcomes, but people often object to such groups and most do not sustain regular involvement. Yet, research on alternatives to 12-step groups is very sparse. The present study aimed to extend the knowledge base on mutual help group alternatives for those with an alcohol use disorder (AUD), sampling from large, active, abstinence-focused groups including Women for Sobriety (WFS), LifeRing, and SMART Recovery (SMART). This paper presents a cross-sectional analysis of this longitudinal study, using baseline data to describe the profile and participation characteristics of attendees of these groups in comparison to 12-step members. Data from participants 18 and over with a lifetime AUD (N=651) were collected using Web-based surveys. Members of alternative 12-step groups were recruited in collaboration with group directors, who helped publicize the study by emailing meeting conveners and attendees and posting announcements on social media. A comparison group of current (past-30-day) 12-step attendees was recruited from an online meeting hub for recovering persons. Interested parties were directed to a Webpage where they were screened, and eligible participants completed an online survey assessing demographic and clinical variables; in-person and online mutual help involvement; and group satisfaction and cohesion. Analyses involved comparing those identifying WFS, SMART, and LifeRing as their primary group to 12-step members on the above characteristics. Compared to 12-step members, members of the mutual help alternatives were less religious and generally higher on education and income. WFS and LifeRing members were also older, more likely to be married, and lower on lifetime drug and psychiatric severity; meanwhile, LifeRing and SMART members were less likely to endorse the most stringent abstinence goal. Finally, despite lower levels of in-person meeting attendance, members of all the 12-step alternatives showed equivalent activity involvement and higher levels of satisfaction and cohesion, compared to 12-step members. Results suggest differences across 12-step groups and their alternatives that may be relevant when advising clients on a choice of mutual help group. Meanwhile, findings for high levels of participation, satisfaction, and cohesion among members of the mutual help alternatives suggest promise for these groups in addressing addiction problems. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Sudden multiple fractures in a patient with sarcoidosis in multiple organs.

    PubMed

    Sada, Mitsuru; Saraya, Takeshi; Ishii, Haruyuki; Goto, Hajime

    2014-04-07

    A 30-year-old man who incidentally fractured his right olecranon and other multiple phalanges was admitted to our hospital. He had a 2-year history of uveitis and bilateral hilar lymphadenopathy (BHL), and pulmonary sarcoidosis was diagnosed from transbronchial lung biopsy. Right elbow arthrodesis was performed, and biopsied specimens showed non-caseating epithelioid cell granuloma, suggesting osseous sarcoidosis. He was discharged uneventfully without further treatment, but BHL had progressed with the appearance of lung parenchymal lesions 3 months later. At that time, involvement of other organs was also noted on Gallium-67 scintigraphy, showing accumulations in BHL, axillary and inguinal lymph nodes, enlarged liver and spleen and subcutaneous areas. After initiation of steroid therapy, multiple organ involvement improved, and no further bone involvement has been recognised to date. Osseous sarcoidosis complicated by bone fracture is an extremely rare presentation, but should be considered in patients with sarcoidosis, especially when multiple organs are involved.

  2. A step-by-step translation of evidence into a psychosocial intervention for everyday activities in dementia: a focus group study.

    PubMed

    Giebel, Clarissa M; Challis, David; Hooper, Nigel M; Ferris, Sally

    2018-03-01

    In order to increase the efficacy of psychosocial interventions in dementia, a step-by-step process translating evidence and public engagement should be adhered to. This paper describes such a process by involving a two-stage focus group with people with dementia (PwD), informal carers, and staff. Based on previous evidence, general aspects of effective interventions were drawn out. These were tested in the first stage of focus groups, one with informal carers and PwD and one with staff. Findings from this stage helped shape the intervention further specifying its content. In the second stage, participants were consulted about the detailed components. The extant evidence base and focus groups helped to identify six practical and situation-specific elements worthy of consideration in planning such an intervention, including underlying theory and personal motivations for participation. Carers, PwD, and staff highlighted the importance of rapport between practitioners and PwD prior to commencing the intervention. It was also considered important that the intervention would be personalised to each individual. This paper shows how valuable public involvement can be to intervention development, and outlines a process of public involvement for future intervention development. The next step would be to formally test the intervention.

  3. Federation in genomics pipelines: techniques and challenges.

    PubMed

    Chaterji, Somali; Koo, Jinkyu; Li, Ninghui; Meyer, Folker; Grama, Ananth; Bagchi, Saurabh

    2017-08-29

    Federation is a popular concept in building distributed cyberinfrastructures, whereby computational resources are provided by multiple organizations through a unified portal, decreasing the complexity of moving data back and forth among multiple organizations. Federation has been used in bioinformatics only to a limited extent, namely, federation of datastores, e.g. SBGrid Consortium for structural biology and Gene Expression Omnibus (GEO) for functional genomics. Here, we posit that it is important to federate both computational resources (CPU, GPU, FPGA, etc.) and datastores to support popular bioinformatics portals, with fast-increasing data volumes and increasing processing requirements. A prime example, and one that we discuss here, is in genomics and metagenomics. It is critical that the processing of the data be done without having to transport the data across large network distances. We exemplify our design and development through our experience with metagenomics-RAST (MG-RAST), the most popular metagenomics analysis pipeline. Currently, it is hosted completely at Argonne National Laboratory. However, through a recently started collaborative National Institutes of Health project, we are taking steps toward federating this infrastructure. Being a widely used resource, we have to move toward federation without disrupting 50 K annual users. In this article, we describe the computational tools that will be useful for federating a bioinformatics infrastructure and the open research challenges that we see in federating such infrastructures. It is hoped that our manuscript can serve to spur greater federation of bioinformatics infrastructures by showing the steps involved, and thus, allow them to scale to support larger user bases. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  4. The cold adapted and temperature sensitive influenza A/Ann Arbor/6/60 virus, the master donor virus for live attenuated influenza vaccines, has multiple defects in replication at the restrictive temperature

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

    Chan, Winnie; Zhou, Helen; Kemble, George

    2008-10-25

    We have previously determined that the temperature sensitive (ts) and attenuated (att) phenotypes of the cold adapted influenza A/Ann Arbor/6/60 strain (MDV-A), the master donor virus for the live attenuated influenza A vaccines (FluMist), are specified by the five amino acids in the PB1, PB2 and NP gene segments. To understand how these loci control the ts phenotype of MDV-A, replication of MDV-A at the non-permissive temperature (39 deg. C) was compared with recombinant wild-type A/Ann Arbor/6/60 (rWt). The mRNA and protein synthesis of MDV-A in the infected MDCK cells were not significantly reduced at 39 deg. C during amore » single-step replication, however, vRNA synthesis was reduced and the nuclear-cytoplasmic export of viral RNP (vRNP) was blocked. In addition, the virions released from MDV-A infected cells at 39 deg. C exhibited irregular morphology and had a greatly reduced amount of the M1 protein incorporated. The reduced M1 protein incorporation and vRNP export blockage correlated well with the virus ts phenotype because these defects could be partially alleviated by removing the three ts loci from the PB1 gene. The virions and vRNPs isolated from the MDV-A infected cells contained a higher level of heat shock protein 70 (Hsp70) than those of rWt, however, whether Hsp70 is involved in thermal inhibition of MDV-A replication remains to be determined. Our studies demonstrate that restrictive replication of MDV-A at the non-permissive temperature occurs in multiple steps of the virus replication cycle.« less

  5. Preventing mental illness: closing the evidence-practice gap through workforce and services planning.

    PubMed

    Furber, Gareth; Segal, Leonie; Leach, Matthew; Turnbull, Catherine; Procter, Nicholas; Diamond, Mark; Miller, Stephanie; McGorry, Patrick

    2015-07-24

    Mental illness is prevalent across the globe and affects multiple aspects of life. Despite advances in treatment, there is little evidence that prevalence rates of mental illness are falling. While the prevention of cardiovascular disease and cancers are common in the policy dialogue and in service delivery, the prevention of mental illness remains a neglected area. There is accumulating evidence that mental illness is at least partially preventable, with increasing recognition that its antecedents are often found in infancy, childhood, adolescence and youth, creating multiple opportunities into young adulthood for prevention. Developing valid and reproducible methods for translating the evidence base in mental illness prevention into actionable policy recommendations is a crucial step in taking the prevention agenda forward. Building on an aetiological model of adult mental illness that emphasizes the importance of intervening during infancy, childhood, adolescence and youth, we adapted a workforce and service planning framework, originally applied to diabetes care, to the analysis of the workforce and service structures required for best-practice prevention of mental illness. The resulting framework consists of 6 steps that include identifying priority risk factors, profiling the population in terms of these risk factors to identify at-risk groups, matching these at-risk groups to best-practice interventions, translation of these interventions to competencies, translation of competencies to workforce and service estimates, and finally, exploring the policy implications of these workforce and services estimates. The framework outlines the specific tasks involved in translating the evidence-base in prevention, to clearly actionable workforce, service delivery and funding recommendations. The framework describes the means to deliver mental illness prevention that the literature indicates is achievable, and is the basis of an ongoing project to model the workforce and service structures required for mental illness prevention.

  6. Application of models to conservation planning for terrestrial birds in North America

    USGS Publications Warehouse

    Fitzgerald, Jane A.; Thogmartin, Wayne E.; Dettmers, Randy; Jones, Tim; Rustay, Christopher; Ruth, Janet M.; Thompson, Frank R.; Will, Tom; Millspaugh, Joshua J.; Thompson, Frank R.

    2009-01-01

    Partners in Flight (PIF), a public–private coalition for the conservation of land birds, has developed one of four international bird conservation plans recognized under the auspices of the North American Bird Conservation Initiative (NABCI). Partners in Flight prioritized species most in need of conservation attention and set range-wide population goals for 448 species of terrestrial birds. Partnerships are now tasked with developing spatially explicit estimates of the distribution, and abundance of priority species across large ecoregions and identifying habitat acreages needed to support populations at prescribed levels. The PIF Five Elements process of conservation design identifies five steps needed to implement all bird conservation at the ecoregional scale. Habitat assessment and landscape characterization describe the current amounts of different habitat types and summarize patch characteristics, and landscape configurations that define the ability of a landscape to sustain healthy bird populations and are a valuable first step to describing the planning area before pursuing more complex species-specific models. Spatially linked database models, landscape-scale habitat suitability models, and statistical models are viable alternatives for predicting habitat suitability or bird abundance across large planning areas to help assess conservation opportunities, design landscapes to meet population objectives, and monitor change in habitat suitability or bird numbers over time.Bird conservation in the United States is a good example of the use of models in large-scale wildlife conservation planning because of its geographic extent, focus on multiple species, involvement of multiple partners, and use of simple to complex models. We provide some background on the recent development of bird conservation initiatives in the United States and the approaches used for regional conservation assessment and planning. We focus on approaches being used for landscape characterization and assessment, and bird population response modeling.

  7. Probing the Compound I-like reactivity of a bare high-valent oxo iron porphyrin complex: the oxidation of tertiary amines.

    PubMed

    Chiavarino, Barbara; Cipollini, Romano; Crestoni, Maria Elisa; Fornarini, Simonetta; Lanucara, Francesco; Lapi, Andrea

    2008-03-12

    The mechanisms of oxidative N-dealkylation of amines by heme enzymes including peroxidases and cytochromes P450 and by functional models for the active Compound I species have long been studied. A debated issue has concerned in particular the character of the primary step initiating the oxidation sequence, either a hydrogen atom transfer (HAT) or an electron transfer (ET) event, facing problems such as the possible contribution of multiple oxidants and complex environmental effects. In the present study, an oxo iron(IV) porphyrin radical cation intermediate 1, [(TPFPP)*+ Fe(IV)=O]+ (TPFPP = meso-tetrakis (pentafluorophenyl)porphinato dianion), functional model of Compound I, has been produced as a bare species. The gas-phase reaction with amines (A) studied by ESI-FT-ICR mass spectrometry has revealed for the first time the elementary steps and the ionic intermediates involved in the oxidative activation. Ionic products are formed involving ET (A*+, the amine radical cation), formal hydride transfer (HT) from the amine ([A(-H)]+, an iminium ion), and oxygen atom transfer (OAT) to the amine (A(O), likely a carbinolamine product), whereas an ionic product involving a net initial HAT event is never observed. The reaction appears to be initiated by an ET event for the majority of the tested amines which included tertiary aliphatic and aromatic amines as well as a cyclic and a secondary amine. For a series of N,N-dimethylanilines the reaction efficiency for the ET activated pathways was found to correlate with the ionization energy of the amine. A stepwise pathway accounts for the C-H bond activation resulting in the formal HT product, namely a primary ET process forming A*+, which is deprotonated at the alpha-C-H bond forming an N-methyl-N-arylaminomethyl radical, A(-H)*, readily oxidized to the iminium ion, [A(-H)]+. The kinetic isotope effect (KIE) for proton transfer (PT) increases as the acidity of the amine radical cation increases and the PT reaction to the base, the ferryl group of (TPFPP)Fe(IV)=O, approaches thermoneutrality. The ET reaction displayed by 1 with gaseous N,N-dimethylaniline finds a counterpart in the ET reactivity of FeO+, reportedly a potent oxidant in the gas phase, and with the barrierless ET process for a model (P)*+ Fe(IV)=O species (where P is the porphine dianion) as found by theoretical calculations. Finally, the remarkable OAT reactivity of 1 with C6F5N(CH3)2 may hint to a mechanism along a route of diverse spin multiplicity.

  8. Summer Training and Education Program (STEP): Report on the 1987 Experience.

    ERIC Educational Resources Information Center

    Sipe, Cynthia L.; And Others

    The Summer Training and Education Program (STEP) was developed in 1984 as a strategy for reducing the number of young people who leave school without the skills and motivation necessary for productive employment. The STEP intervention involves collaboration between the public schools and the federal Summer Youth Employment and Training Program…

  9. Abundance of ammonia oxidizing bacteria and archaea under long-term maize cropping systems.

    USDA-ARS?s Scientific Manuscript database

    Nitrification involves the oxidation of ammonium and is an important component of the overall N cycle. Nitrification occurs in two steps; first by oxidizing ammonium to nitrite, and then to nitrate. The first step is often the rate limiting step. Until recently ammonia-oxidizing bacteria were though...

  10. Lights, Camera, Action: Facilitating the Design and Production of Effective Instructional Videos

    ERIC Educational Resources Information Center

    Di Paolo, Terry; Wakefield, Jenny S.; Mills, Leila A.; Baker, Laura

    2017-01-01

    This paper outlines a rudimentary process intended to guide faculty in K-12 and higher education through the steps involved to produce video for their classes. The process comprises four steps: planning, development, delivery and reflection. Each step is infused with instructional design information intended to support the collaboration between…

  11. Ethnography, Step by Step (2nd Edition), by David M. Fetterman, Thousand Oaks, Ca: Sage, 1998..

    ERIC Educational Resources Information Center

    Green, Jennifer C.; Buell, James

    2000-01-01

    Reviews this edition, which like the first is primarily an organized presentation of fieldwork vignettes and instructive examples from research and evaluation contexts. The presentation is organized by the steps involved in ethnographic fieldwork. This edition is updated with references to electronic technology. (SLD)

  12. Quick and Easy Adaptations and Accommodations for Early Childhood Students

    ERIC Educational Resources Information Center

    Breitfelder, Leisa M.

    2008-01-01

    Research-based information is used to support the idea of the use of adaptations and accommodations for early childhood students who have varying disabilities. Multiple adaptations and accommodations are outlined. A step-by-step plan is provided on how to make specific adaptations and accommodations to fit the specific needs of early childhood…

  13. Stutter-Step Models of Performance in School

    ERIC Educational Resources Information Center

    Morgan, Stephen L.; Leenman, Theodore S.; Todd, Jennifer J.; Kentucky; Weeden, Kim A.

    2013-01-01

    To evaluate a stutter-step model of academic performance in high school, this article adopts a unique measure of the beliefs of 12,591 high school sophomores from the Education Longitudinal Study, 2002-2006. Verbatim responses to questions on occupational plans are coded to capture specific job titles, the listing of multiple jobs, and the listing…

  14. Discussion of "Simple design criterion for residual energy on embankment dam stepped spillways" by Stefan Felder and Hubert Chanson

    USDA-ARS?s Scientific Manuscript database

    Researchers from the University of Queensland of New South Wales provided guidance to designers regarding the hydraulic performance of embankment dam stepped spillways. Their research compares a number of high-quality physical model data sets from multiple laboratories, emphasizing the variability ...

  15. Evidence-Based Assessment of Attention-Deficit/Hyperactivity Disorder: Using Multiple Sources of Information

    ERIC Educational Resources Information Center

    Frazier, Thomas W.; Youngstrom, Eric A.

    2006-01-01

    In this article, the authors illustrate a step-by-step process of acquiring and integrating information according to the recommendations of evidence-based practices. A case example models the process, leading to specific recommendations regarding instruments and strategies for evidence-based assessment (EBA) of attention-deficit/hyperactivity…

  16. From Recombinant Expression to Crystals: A Step-by-Step Guide to GPCR Crystallography.

    PubMed

    Shukla, Arun K; Kumari, Punita; Ghosh, Eshan; Nidhi, Kumari

    2015-01-01

    G protein-coupled receptors (GPCRs) are the primary targets of drugs prescribed for many human pathophysiological conditions such as hypertension, allergies, schizophrenia, asthma, and various types of cancer. High-resolution structure determination of GPCRs has been a key focus area in GPCR biology to understand the basic mechanism of their activation and signaling and to materialize the long-standing dream of structure-based drug design on these versatile receptors. There has been tremendous effort at this front in the past two decades and it has culminated into crystal structures of 27 different receptors so far. The recent progress in crystallization and structure determination of GPCRs has been driven by innovation and cutting-edge developments at every step involved in the process of crystallization. Here, we present a step-by-step description of various steps involved in GPCR crystallization starting from recombinant expression to obtaining diffracting crystals. We also discuss the next frontiers in GPCR biology that are likely to be a primary focus for crystallography efforts in the next decade or so. © 2015 Elsevier Inc. All rights reserved.

  17. SRSF3 represses the expression of PDCD4 protein by coordinated regulation of alternative splicing, export and translation

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

    Park, Seung Kuk; Jeong, Sunjoo, E-mail: sjsj@dankook.ac.kr

    2016-02-05

    Gene expression is regulated at multiple steps, such as transcription, splicing, export, degradation and translation. Considering diverse roles of SR proteins, we determined whether the tumor-related splicing factor SRSF3 regulates the expression of the tumor-suppressor protein, PDCD4, at multiple steps. As we have reported previously, knockdown of SRSF3 increased the PDCD4 protein level in SW480 colon cancer cells. More interestingly, here we showed that the alternative splicing and the nuclear export of minor isoforms of pdcd4 mRNA were repressed by SRSF3, but the translation step was unaffected. In contrast, only the translation step of the major isoform of pdcd4 mRNAmore » was repressed by SRSF3. Therefore, overexpression of SRSF3 might be relevant to the repression of all isoforms of PDCD4 protein levels in most types of cancer cell. We propose that SRSF3 could act as a coordinator of the expression of PDCD4 protein via two mechanisms on two alternatively spliced mRNA isoforms.« less

  18. Orthogonal tandem catalysis

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

    Lohr, Tracy L.; Marks, Tobin J.

    2015-05-20

    Tandem catalysis is a growing field that is beginning to yield important scientific and technological advances toward new and more efficient catalytic processes. 'One-pot' tandem reactions, where multiple catalysts and reagents, combined in a single reaction vessel undergo a sequence of precisely staged catalytic steps, are highly attractive from the standpoint of reducing both waste and time. Orthogonal tandem catalysis is a subset of one-pot reactions in which more than one catalyst is used to promote two or more mechanistically distinct reaction steps. This Perspective summarizes and analyses some of the recent developments and successes in orthogonal tandem catalysis, withmore » particular focus on recent strategies to address catalyst incompatibility. We also highlight the concept of thermodynamic leveraging by coupling multiple catalyst cycles to effect challenging transformations not observed in single-step processes, and to encourage application of this technique to energetically unfavourable or demanding reactions.« less

  19. MIMO equalization with adaptive step size for few-mode fiber transmission systems.

    PubMed

    van Uden, Roy G H; Okonkwo, Chigo M; Sleiffer, Vincent A J M; de Waardt, Hugo; Koonen, Antonius M J

    2014-01-13

    Optical multiple-input multiple-output (MIMO) transmission systems generally employ minimum mean squared error time or frequency domain equalizers. Using an experimental 3-mode dual polarization coherent transmission setup, we show that the convergence time of the MMSE time domain equalizer (TDE) and frequency domain equalizer (FDE) can be reduced by approximately 50% and 30%, respectively. The criterion used to estimate the system convergence time is the time it takes for the MIMO equalizer to reach an average output error which is within a margin of 5% of the average output error after 50,000 symbols. The convergence reduction difference between the TDE and FDE is attributed to the limited maximum step size for stable convergence of the frequency domain equalizer. The adaptive step size requires a small overhead in the form of a lookup table. It is highlighted that the convergence time reduction is achieved without sacrificing optical signal-to-noise ratio performance.

  20. Limits of acceptable change and natural resources planning: when is LAC useful, when is it not?

    Treesearch

    David N. Cole; Stephen F. McCool

    1997-01-01

    There are ways to improve the LAC process and its implementational procedures. One significant procedural modification is the addition of a new step. This step — which becomes the first step in the process — involves more explicitly defining goals and desired conditions. For other steps in the process, clarifications of concept and terminology are advanced, as are...

  1. Characteristics of students participating in Collegiate Recovery Programs: A national survey

    PubMed Central

    Laudet, Alexandre B.; Harris, Kitty; Kimball, Thomas; Winters, Ken C.; Moberg, D. Paul

    2014-01-01

    Relapse rates are high among individuals with substance use disorders (SUD), and for young people pursuing a college education, the high rates of substance use on campus can jeopardize recovery. Collegiate Recovery Programs (CRPs) are an innovative campus-based model of recovery support that is gaining popularity but remains under-investigated. This study reports on the first nationwide survey of CRP-enrolled students (N = 486 from 29 different CRPs). Using an online survey, we collected information on background, SUD and recovery history, and current functioning. Most students (43% females, mean age = 26) had used multiple substances, had high levels of SUD severity, high rates of treatment and 12-step participation. Fully 40% smoke. Many reported criminal justice involvement and periods of homelessness. Notably, many reported being in recovery from, and currently engaging in multiple behavioral addictions-e.g., eating disorders, and sex and love addiction. Findings highlight the high rates of co-occurring addictions in this under-examined population and underline the need for treatment, recovery support programs and college health services to provide integrated support for mental health and behavioral addictions to SUD-affected young people. PMID:25481690

  2. Using Cognitive Agents to Train Negotiation Skills

    PubMed Central

    Stevens, Christopher A.; Daamen, Jeroen; Gaudrain, Emma; Renkema, Tom; Top, Jakob Dirk; Cnossen, Fokie; Taatgen, Niels A.

    2018-01-01

    Training negotiation is difficult because it is a complex, dynamic activity that involves multiple parties. It is often not clear how to create situations in which students can practice negotiation or how to measure students' progress. Some have begun to address these issues by creating artificial software agents with which students can train. These agents have the advantage that they can be “reset,” and played against multiple times. This allows students to learn from their mistakes and try different strategies. However, these agents are often based on normative theories of how negotiators should conduct themselves, not necessarily how people actually behave in negotiations. Here, we take a step toward addressing this gap by developing an agent grounded in a cognitive architecture, ACT-R. This agent contains a model of theory-of-mind, the ability of humans to reason about the mental states of others. It uses this model to try to infer the strategy of the opponent and respond accordingly. In a series of experiments, we show that this agent replicates some aspects of human performance, is plausible to human negotiators, and can lead to learning gains in a small-scale negotiation task. PMID:29535654

  3. Partial volume segmentation in 3D of lesions and tissues in magnetic resonance images

    NASA Astrophysics Data System (ADS)

    Johnston, Brian; Atkins, M. Stella; Booth, Kellogg S.

    1994-05-01

    An important first step in diagnosis and treatment planning using tomographic imaging is differentiating and quantifying diseased as well as healthy tissue. One of the difficulties encountered in solving this problem to date has been distinguishing the partial volume constituents of each voxel in the image volume. Most proposed solutions to this problem involve analysis of planar images, in sequence, in two dimensions only. We have extended a model-based method of image segmentation which applies the technique of iterated conditional modes in three dimensions. A minimum of user intervention is required to train the algorithm. Partial volume estimates for each voxel in the image are obtained yielding fractional compositions of multiple tissue types for individual voxels. A multispectral approach is applied, where spatially registered data sets are available. The algorithm is simple and has been parallelized using a dataflow programming environment to reduce the computational burden. The algorithm has been used to segment dual echo MRI data sets of multiple sclerosis patients using lesions, gray matter, white matter, and cerebrospinal fluid as the partial volume constituents. The results of the application of the algorithm to these datasets is presented and compared to the manual lesion segmentation of the same data.

  4. Management of heart failure in the new era: the role of scores.

    PubMed

    Mantegazza, Valentina; Badagliacca, Roberto; Nodari, Savina; Parati, Gianfranco; Lombardi, Carolina; Di Somma, Salvatore; Carluccio, Erberto; Dini, Frank Lloyd; Correale, Michele; Magrì, Damiano; Agostoni, Piergiuseppe

    2016-08-01

    Heart failure is a widespread syndrome involving several organs, still characterized by high mortality and morbidity, and whose clinical course is heterogeneous and hardly predictable.In this scenario, the assessment of heart failure prognosis represents a fundamental step in clinical practice. A single parameter is always unable to provide a very precise prognosis. Therefore, risk scores based on multiple parameters have been introduced, but their clinical utility is still modest. In this review, we evaluated several prognostic models for acute, right, chronic, and end-stage heart failure based on multiple parameters. In particular, for chronic heart failure we considered risk scores essentially based on clinical evaluation, comorbidities analysis, baroreflex sensitivity, heart rate variability, sleep disorders, laboratory tests, echocardiographic imaging, and cardiopulmonary exercise test parameters. What is at present established is that a single parameter is not sufficient for an accurate prediction of prognosis in heart failure because of the complex nature of the disease. However, none of the scoring systems available is widely used, being in some cases complex, not user-friendly, or based on expensive or not easily available parameters. We believe that multiparametric scores for risk assessment in heart failure are promising but their widespread use needs to be experienced.

  5. Using Cognitive Agents to Train Negotiation Skills.

    PubMed

    Stevens, Christopher A; Daamen, Jeroen; Gaudrain, Emma; Renkema, Tom; Top, Jakob Dirk; Cnossen, Fokie; Taatgen, Niels A

    2018-01-01

    Training negotiation is difficult because it is a complex, dynamic activity that involves multiple parties. It is often not clear how to create situations in which students can practice negotiation or how to measure students' progress. Some have begun to address these issues by creating artificial software agents with which students can train. These agents have the advantage that they can be "reset," and played against multiple times. This allows students to learn from their mistakes and try different strategies. However, these agents are often based on normative theories of how negotiators should conduct themselves, not necessarily how people actually behave in negotiations. Here, we take a step toward addressing this gap by developing an agent grounded in a cognitive architecture, ACT-R. This agent contains a model of theory-of-mind, the ability of humans to reason about the mental states of others. It uses this model to try to infer the strategy of the opponent and respond accordingly. In a series of experiments, we show that this agent replicates some aspects of human performance, is plausible to human negotiators, and can lead to learning gains in a small-scale negotiation task.

  6. Arabidopsis KANADI1 acts as a transcriptional repressor by interacting with a specific cis-element and regulates auxin biosynthesis, transport, and signaling in opposition to HD-ZIPIII factors.

    PubMed

    Huang, Tengbo; Harrar, Yaël; Lin, Changfa; Reinhart, Brenda; Newell, Nicole R; Talavera-Rauh, Franklin; Hokin, Samuel A; Barton, M Kathryn; Kerstetter, Randall A

    2014-01-01

    The formation of leaves and other lateral organs in plants depends on the proper specification of adaxial-abaxial (upper-lower) polarity. KANADI1 (KAN1), a member of the GARP family of transcription factors, is a key regulator of abaxial identity, leaf growth, and meristem formation in Arabidopsis thaliana. Here, we demonstrate that the Myb-like domain in KAN1 binds the 6-bp motif GNATA(A/T) and that this motif alone is sufficient to squelch transcription of a linked reporter in vivo. In addition, we report that KAN1 acts as a transcriptional repressor. Among its targets are genes involved in auxin biosynthesis, auxin transport, and auxin response. Furthermore, we find that the adaxializing HD-ZIPIII transcription factor REVOLUTA has opposing effects on multiple components of the auxin pathway. We hypothesize that HD-ZIPIII and KANADI transcription factors pattern auxin accumulation and responsiveness in the embryo. Specifically, we propose the opposing actions of KANADI and HD-ZIPIII factors on cotyledon formation (KANADI represses and HD-ZIPIII promotes cotyledon formation) occur through their opposing actions on genes acting at multiple steps in the auxin pathway.

  7. Enhancing the functional properties of thermophilic enzymes by chemical modification and immobilization.

    PubMed

    Cowan, Don A; Fernandez-Lafuente, Roberto

    2011-09-10

    The immobilization of proteins (mostly typically enzymes) onto solid supports is mature technology and has been used successfully to enhance biocatalytic processes in a wide range of industrial applications. However, continued developments in immobilization technology have led to more sophisticated and specialized applications of the process. A combination of targeted chemistries, for both the support and the protein, sometimes in combination with additional chemical and/or genetic engineering, has led to the development of methods for the modification of protein functional properties, for enhancing protein stability and for the recovery of specific proteins from complex mixtures. In particular, the development of effective methods for immobilizing large multi-subunit proteins with multiple covalent linkages (multi-point immobilization) has been effective in stabilizing proteins where subunit dissociation is the initial step in enzyme inactivation. In some instances, multiple benefits are achievable in a single process. Here we comprehensively review the literature pertaining to immobilization and chemical modification of different enzyme classes from thermophiles, with emphasis on the chemistries involved and their implications for modification of the enzyme functional properties. We also highlight the potential for synergies in the combined use of immobilization and other chemical modifications. Copyright © 2011 Elsevier Inc. All rights reserved.

  8. Multiple environment single system quantum mechanical/molecular mechanical (MESS-QM/MM) calculations. 1. Estimation of polarization energies.

    PubMed

    Sodt, Alexander J; Mei, Ye; König, Gerhard; Tao, Peng; Steele, Ryan P; Brooks, Bernard R; Shao, Yihan

    2015-03-05

    In combined quantum mechanical/molecular mechanical (QM/MM) free energy calculations, it is often advantageous to have a frozen geometry for the quantum mechanical (QM) region. For such multiple-environment single-system (MESS) cases, two schemes are proposed here for estimating the polarization energy: the first scheme, termed MESS-E, involves a Roothaan step extrapolation of the self-consistent field (SCF) energy; whereas the other scheme, termed MESS-H, employs a Newton-Raphson correction using an approximate inverse electronic Hessian of the QM region (which is constructed only once). Both schemes are extremely efficient, because the expensive Fock updates and SCF iterations in standard QM/MM calculations are completely avoided at each configuration. They produce reasonably accurate QM/MM polarization energies: MESS-E can predict the polarization energy within 0.25 kcal/mol in terms of the mean signed error for two of our test cases, solvated methanol and solvated β-alanine, using the M06-2X or ωB97X-D functionals; MESS-H can reproduce the polarization energy within 0.2 kcal/mol for these two cases and for the oxyluciferin-luciferase complex, if the approximate inverse electronic Hessians are constructed with sufficient accuracy.

  9. Relationships between trunk performance, gait and postural control in persons with multiple sclerosis.

    PubMed

    Freund, Jane E; Stetts, Deborah M; Vallabhajosula, Srikant

    2016-06-30

    Multiple sclerosis (MS) is a chronic progressive disease of the central nervous system. Compared to healthy individuals, persons with multiple sclerosis (PwMS) have increased postural sway in quiet stance, decreased gait speed and increased fall incidence. Trunk performance has been implicated in postural control, gait dysfunction, and fall prevention in older adults. However, the relationship of trunk performance to postural control and gait has not been adequately studied in PwMS. To compare trunk muscle structure and performance in PwMS to healthy age and gendered-matched controls (HC); to determine the effects of isometric trunk endurance testing on postural control in both populations; and to determine the relationship of trunk performance with postural control, gait and step activity in PwMS. Fifteen PwMS and HC completed ultrasound imaging of trunk muscles, 10 m walk test, isometric trunk endurance tests, and postural sway test. Participants wore a step activity monitor for 7 days. PwMS had worse isometric trunk endurance compared to HC. PwMS trunk flexion endurance negatively correlated to several postural control measures and positively correlated to gait speed and step activity. Clinicians should consider evaluation and interventions directed at impaired trunk endurance in PwMS.

  10. Multiple time step integrators in ab initio molecular dynamics.

    PubMed

    Luehr, Nathan; Markland, Thomas E; Martínez, Todd J

    2014-02-28

    Multiple time-scale algorithms exploit the natural separation of time-scales in chemical systems to greatly accelerate the efficiency of molecular dynamics simulations. Although the utility of these methods in systems where the interactions are described by empirical potentials is now well established, their application to ab initio molecular dynamics calculations has been limited by difficulties associated with splitting the ab initio potential into fast and slowly varying components. Here we present two schemes that enable efficient time-scale separation in ab initio calculations: one based on fragment decomposition and the other on range separation of the Coulomb operator in the electronic Hamiltonian. We demonstrate for both water clusters and a solvated hydroxide ion that multiple time-scale molecular dynamics allows for outer time steps of 2.5 fs, which are as large as those obtained when such schemes are applied to empirical potentials, while still allowing for bonds to be broken and reformed throughout the dynamics. This permits computational speedups of up to 4.4x, compared to standard Born-Oppenheimer ab initio molecular dynamics with a 0.5 fs time step, while maintaining the same energy conservation and accuracy.

  11. Proposed variations of the stepped-wedge design can be used to accommodate multiple interventions.

    PubMed

    Lyons, Vivian H; Li, Lingyu; Hughes, James P; Rowhani-Rahbar, Ali

    2017-06-01

    Stepped-wedge design (SWD) cluster-randomized trials have traditionally been used for evaluating a single intervention. We aimed to explore design variants suitable for evaluating multiple interventions in an SWD trial. We identified four specific variants of the traditional SWD that would allow two interventions to be conducted within a single cluster-randomized trial: concurrent, replacement, supplementation, and factorial SWDs. These variants were chosen to flexibly accommodate study characteristics that limit a one-size-fits-all approach for multiple interventions. In the concurrent SWD, each cluster receives only one intervention, unlike the other variants. The replacement SWD supports two interventions that will not or cannot be used at the same time. The supplementation SWD is appropriate when the second intervention requires the presence of the first intervention, and the factorial SWD supports the evaluation of intervention interactions. The precision for estimating intervention effects varies across the four variants. Selection of the appropriate design variant should be driven by the research question while considering the trade-off between the number of steps, number of clusters, restrictions for concurrent implementation of the interventions, lingering effects of each intervention, and precision of the intervention effect estimates. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Peer Interventions to Promote Health: Conceptual Considerations

    PubMed Central

    Simoni, Jane M.; Franks, Julie C.; Lehavot, Keren; Yard, Samantha S.

    2013-01-01

    Peers have intervened to promote health since ancient times, yet few attempts have been made to describe theoretically their role and their interventions. After a brief overview of the history and variety of peer-based health interventions, a 4-part definition of peer interveners is presented here with a consideration of the dimensions of their involvement in health promotion. Then, a 2-step process is proposed as a means of conceptualizing peer interventions to promote health. Step 1 involves establishing a theoretical framework for the intervention’s main focus (i.e., education, social support, social norms, self-efficacy, and patient advocacy), and Step 2 involves identifying a theory that justifies the use of peers and might explain their impact. As examples, the following might be referred to: theoretical perspectives from the mutual support group and self-help literature, social cognitive and social learning theories, the social support literature, social comparison theory, social network approaches, and empowerment models. PMID:21729015

  13. Water: A Recycling Success Story.

    ERIC Educational Resources Information Center

    Swinehart, Rebecca, Ed.

    1995-01-01

    This activity involves elementary students in simulating water purification techniques by finding ways to clear up soapy water. An introduction discusses water use and conservation. Materials needed and step-by-step procedure are provided. (LZ)

  14. For Better Soil, Let Earthworms Toil.

    ERIC Educational Resources Information Center

    Swinehart, Rebecca, Ed.

    1995-01-01

    This activity involves elementary students in investigating how earthworms affect soil fertility. An introduction discusses topsoil loss and the connections between soil and earthworm ecology. Materials needed and step-by-step procedure are provided. (LZ)

  15. Multiple Family Groups: An Engaging Intervention for Child Welfare-Involved Families

    ERIC Educational Resources Information Center

    Gopalan, Geetha; Bannon, William; Dean-Assael, Kara; Fuss, Ashley; Gardner, Lauren; LaBarbera, Brooke; McKay, Mary

    2011-01-01

    Differences between child welfare- and nonchild welfare-involved families regarding barriers to child mental health care, attendance, program satisfaction, and relationship with facilitators are examined for a multiple family group service delivery model aimed at reducing childhood disruptive behaviors. Although child welfare-involved caregivers…

  16. Atomic Resolution in Situ Imaging of a Double-Bilayer Multistep Growth Mode in Gallium Nitride Nanowires

    DOE PAGES

    Gamalski, A. D.; Tersoff, J.; Stach, E. A.

    2016-04-13

    We study the growth of GaN nanowires from liquid Au–Ga catalysts using environmental transmission electron microscopy. GaN wires grow in either (11¯20) or (11¯00) directions, by the addition of {11¯00} double bilayers via step flow with multiple steps. Step-train growth is not typically seen with liquid catalysts, and we suggest that it results from low step mobility related to the unusual double-height step structure. Finally, the results here illustrate the surprising dynamics of catalytic GaN wire growth at the nanoscale and highlight striking differences between the growth of GaN and other III–V semiconductor nanowires.

  17. New Parents’ Psychological Adjustment and Trajectories of Early Parental Involvement

    PubMed Central

    Jia, Rongfang; Kotila, Letitia E.; Schoppe-Sullivan, Sarah J.; Kamp Dush, Claire M.

    2016-01-01

    Trajectories of parental involvement time (engagement and child care) across 3, 6, and 9 months postpartum and associations with parents’ own and their partners’ psychological adjustment (dysphoria, anxiety, and empathic personal distress) were examined using a sample of dual-earner couples experiencing first-time parenthood (N = 182 couples). Using time diary measures that captured intensive parenting moments, hierarchical linear modeling analyses revealed that patterns of associations between psychological adjustment and parental involvement time depended on the parenting domain, aspect of psychological adjustment, and parent gender. Psychological adjustment difficulties tended to bias the 2-parent system toward a gendered pattern of “mother step in” and “father step out,” as father involvement tended to decrease, and mother involvement either remained unchanged or increased, in response to their own and their partners’ psychological adjustment difficulties. In contrast, few significant effects were found in models using parental involvement to predict psychological adjustment. PMID:27397935

  18. Identification of the potentiating mutations and synergistic epistasis that enabled the evolution of inter-species cooperation

    DOE PAGES

    Douglas, Sarah M.; Chubiz, Lon M.; Harcombe, William R.; ...

    2017-05-11

    Microbes often engage in cooperation through releasing biosynthetic compounds required by other species to grow. Given that production of costly biosynthetic metabolites is generally subjected to multiple layers of negative feedback, single mutations may frequently be insufficient to generate cooperative phenotypes. Synergistic epistatic interactions between multiple coordinated changes may thus often underlie the evolution of cooperation through overproduction of metabolites. To test the importance of synergistic mutations in cooperation we used an engineered bacterial consortium of an Escherichia coli methionine auxotroph and Salmonella enterica. S. enterica relies on carbon by-products from E. coli if lactose is the only carbon source.more » Directly selecting wild-type S. enterica in an environment that favored cooperation through secretion of methionine only once led to a methionine producer, and this producer both took a long time to emerge and was not very effective at cooperating. On the other hand, when an initial selection for resistance of S. enterica to a toxic methionine analog, ethionine, was used, subsequent selection for cooperation with E. coli was rapid, and the resulting double mutants were much more effective at cooperation. We found that potentiating mutations in metJ increase expression of metA, which encodes the first step of methionine biosynthesis. This increase in expression is required for the previously identified actualizing mutations in metA to generate cooperation. This work highlights that where biosynthesis of metabolites involves multiple layers of regulation, significant secretion of those metabolites may require multiple mutations, thereby constraining the evolution of cooperation.« less

  19. Using stereophotogrammetric technology for obtaining intraoral digital impressions of implants.

    PubMed

    Pradíes, Guillermo; Ferreiroa, Alberto; Özcan, Mutlu; Giménez, Beatriz; Martínez-Rus, Francisco

    2014-04-01

    The procedure for making impressions of multiple implants continues to be a challenge, despite the various techniques proposed to date. The authors' objective in this case report is to describe a novel digital impression method for multiple implants involving the use of stereophotogrammetric technology. The authors present three cases of patients who had multiple implants in which the impressions were obtained with this technology. Initially, a stereo camera with an infrared flash detects the position of special flag abutments screwed into the implants. This process is based on registering the x, y and z coordinates of each implant and the distances between them. This information is converted into a stereolithographic (STL) file. To add the soft-tissue information, the user must obtain another STL file by using an intraoral or extraoral scanner. In the first case presented, this information was acquired from the plaster model with an extraoral scanner; in the second case, from a Digital Imaging and Communication in Medicine (DICOM) file of the plaster model obtained with cone-beam computed tomography; and in the third case, through an intraoral digital impression with a confocal scanner. In the three cases, the frameworks manufactured from this technique showed a correct clinical passive fit. At follow-up appointments held six, 12 and 24 months after insertion of the prosthesis, no complications were reported. Stereophotogrammetric technology is a viable, accurate and easy technique for making multiple implant impressions. Clinicians can use stereophotogrammetric technology to acquire reliable digital master models as a first step in producing frameworks with a correct passive fit.

  20. Identification of the potentiating mutations and synergistic epistasis that enabled the evolution of inter-species cooperation

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

    Douglas, Sarah M.; Chubiz, Lon M.; Harcombe, William R.

    Microbes often engage in cooperation through releasing biosynthetic compounds required by other species to grow. Given that production of costly biosynthetic metabolites is generally subjected to multiple layers of negative feedback, single mutations may frequently be insufficient to generate cooperative phenotypes. Synergistic epistatic interactions between multiple coordinated changes may thus often underlie the evolution of cooperation through overproduction of metabolites. To test the importance of synergistic mutations in cooperation we used an engineered bacterial consortium of an Escherichia coli methionine auxotroph and Salmonella enterica. S. enterica relies on carbon by-products from E. coli if lactose is the only carbon source.more » Directly selecting wild-type S. enterica in an environment that favored cooperation through secretion of methionine only once led to a methionine producer, and this producer both took a long time to emerge and was not very effective at cooperating. On the other hand, when an initial selection for resistance of S. enterica to a toxic methionine analog, ethionine, was used, subsequent selection for cooperation with E. coli was rapid, and the resulting double mutants were much more effective at cooperation. We found that potentiating mutations in metJ increase expression of metA, which encodes the first step of methionine biosynthesis. This increase in expression is required for the previously identified actualizing mutations in metA to generate cooperation. This work highlights that where biosynthesis of metabolites involves multiple layers of regulation, significant secretion of those metabolites may require multiple mutations, thereby constraining the evolution of cooperation.« less

  1. Proof-of-Concept of the Phytoimmobilization Technology for TNX Outfall Delta: Final Report

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

    Kaplan, D.I.

    2001-06-04

    A series of proof-of-principle studies was initiated to evaluate the soil remediation technology, phytoimmobilization, for application at the TNX Outfall Delta (TNX OD) operable unit. Phytoimmobilization involves two steps. The first step is entitled phytoextraction, and it takes place mostly during the spring and summer. During this step the plants extract contaminants from the sediment into the roots and then translocate the contaminants to the aboveground plant parts. The second step is referred to as sequestration and it takes place largely during the autumn and winter when annual plants senesce or deciduous trees drop their leaves. This step involves themore » immobilization of the contaminant once it leaches form the fallen leaves into a ''geomat,'' a geotextile embedded with mineral sequestering agents. This final report describes the results to date, including those reported in the status report (Kaplan et al. 2000a), those completed since the report was issued, and the preliminary calculations of the phytoimmobilization effectiveness.« less

  2. Multiple intensity distributions from a single optical element

    NASA Astrophysics Data System (ADS)

    Berens, Michael; Bruneton, Adrien; Bäuerle, Axel; Traub, Martin; Wester, Rolf; Stollenwerk, Jochen; Loosen, Peter

    2013-09-01

    We report on an extension of the previously published two-step freeform optics tailoring algorithm using a Monge-Kantorovich mass transportation framework. The algorithm's ability to design multiple freeform surfaces allows for the inclusion of multiple distinct light paths and hence the implementation of multiple lighting functions in a single optical element. We demonstrate the procedure in the context of automotive lighting, in which a fog lamp and a daytime running lamp are integrated in a single optical element illuminated by two distinct groups of LEDs.

  3. Multiple cranial neuropathy: a common diagnostic problem.

    PubMed

    Garg, R K; Karak, B

    1999-10-01

    Syndrome of multiple cranial palsies is a common clinical problem routinely encountered in neurological practice. Anatomical patterns of cranial nerves involvement help in localizing the lesion. Various infections, malignant neoplasms and autoimmune vasculitis are common disorders leading to various syndromes of multiple cranial nerve palsies. A large number of diffuse neurological disorders (e.g. Gullian-Barre syndrome, myopathies) may also present with syndrome of multiple cranial nerve palsies. Despite extensive biochemical and radiological work-up the accurate diagnosis may not be established. Few such patients represent "idiopathic" variety of multiple cranial nerve involvement and show good response to corticosteroids. Widespread and sequential involvements of cranial nerves frequently suggest possibility of malignant infiltration of meninges, however, confirmation of diagnosis may not be possible before autopsy.

  4. Consistency of internal fluxes in a hydrological model running at multiple time steps

    NASA Astrophysics Data System (ADS)

    Ficchi, Andrea; Perrin, Charles; Andréassian, Vazken

    2016-04-01

    Improving hydrological models remains a difficult task and many ways can be explored, among which one can find the improvement of spatial representation, the search for more robust parametrization, the better formulation of some processes or the modification of model structures by trial-and-error procedure. Several past works indicate that model parameters and structure can be dependent on the modelling time step, and there is thus some rationale in investigating how a model behaves across various modelling time steps, to find solutions for improvements. Here we analyse the impact of data time step on the consistency of the internal fluxes of a rainfall-runoff model run at various time steps, by using a large data set of 240 catchments. To this end, fine time step hydro-climatic information at sub-hourly resolution is used as input of a parsimonious rainfall-runoff model (GR) that is run at eight different model time steps (from 6 minutes to one day). The initial structure of the tested model (i.e. the baseline) corresponds to the daily model GR4J (Perrin et al., 2003), adapted to be run at variable sub-daily time steps. The modelled fluxes considered are interception, actual evapotranspiration and intercatchment groundwater flows. Observations of these fluxes are not available, but the comparison of modelled fluxes at multiple time steps gives additional information for model identification. The joint analysis of flow simulation performance and consistency of internal fluxes at different time steps provides guidance to the identification of the model components that should be improved. Our analysis indicates that the baseline model structure is to be modified at sub-daily time steps to warrant the consistency and realism of the modelled fluxes. For the baseline model improvement, particular attention is devoted to the interception model component, whose output flux showed the strongest sensitivity to modelling time step. The dependency of the optimal model complexity on time step is also analysed. References: Perrin, C., Michel, C., Andréassian, V., 2003. Improvement of a parsimonious model for streamflow simulation. Journal of Hydrology, 279(1-4): 275-289. DOI:10.1016/S0022-1694(03)00225-7

  5. Theory and Performance of AIMS for Active Interrogation

    NASA Astrophysics Data System (ADS)

    Walters, William J.; Royston, Katherine E. K.; Haghighat, Alireza

    2014-06-01

    A hybrid Monte Carlo and deterministic methodology has been developed for application to active interrogation systems. The methodology consists of four steps: i) determination of neutron flux distribution due to neutron source transport and subcritical multiplication; ii) generation of gamma source distribution from (n, γ) interactions; iii) determination of gamma current at a detector window; iv) detection of gammas by the detector. This paper discusses the theory and results of the first three steps for the case of a cargo container with a sphere of HEU in third-density water. In the first step, a response-function formulation has been developed to calculate the subcritical multiplication and neutron flux distribution. Response coefficients are pre-calculated using the MCNP5 Monte Carlo code. The second step uses the calculated neutron flux distribution and Bugle-96 (n, γ) cross sections to find the resulting gamma source distribution. Finally, in the third step the gamma source distribution is coupled with a pre-calculated adjoint function to determine the gamma flux at a detector window. A code, AIMS (Active Interrogation for Monitoring Special-Nuclear-materials), has been written to output the gamma current for an source-detector assembly scanning across the cargo using the pre-calculated values and takes significantly less time than a reference MCNP5 calculation.

  6. Sequential infiltration synthesis for enhancing multiple-patterning lithography

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

    Darling, Seth B.; Elam, Jeffrey W.; Tseng, Yu-Chih

    Simplified methods of multiple-patterning photolithography using sequential infiltration synthesis to modify the photoresist such that it withstands plasma etching better than unmodified resist and replaces one or more hard masks and/or a freezing step in MPL processes including litho-etch-litho-etch photolithography or litho-freeze-litho-etch photolithography.

  7. A MULTIPLE GRID ALGORITHM FOR ONE-DIMENSIONAL TRANSIENT OPEN CHANNEL FLOWS. (R825200)

    EPA Science Inventory

    Numerical modeling of open channel flows with shocks using explicit finite difference schemes is constrained by the choice of time step, which is limited by the CFL stability criteria. To overcome this limitation, in this work we introduce the application of a multiple grid al...

  8. Multiple Family Groups for Child Behavior Difficulties: Retention Among Child Welfare-Involved Caregivers

    ERIC Educational Resources Information Center

    Gopalan, Geetha; Fuss, Ashley; Wisdom, Jennifer P.

    2015-01-01

    Purpose: The Multiple Family Group (MFG) service delivery model to reduce childhood disruptive behavior disorders has shown promise in engaging child welfare-involved families. This qualitative study examines caregivers' perceptions of factors that influence retention in MFGs among child welfare-involved families. Methods: Twenty-five…

  9. Multiple testing and power calculations in genetic association studies.

    PubMed

    So, Hon-Cheong; Sham, Pak C

    2011-01-01

    Modern genetic association studies typically involve multiple single-nucleotide polymorphisms (SNPs) and/or multiple genes. With the development of high-throughput genotyping technologies and the reduction in genotyping cost, investigators can now assay up to a million SNPs for direct or indirect association with disease phenotypes. In addition, some studies involve multiple disease or related phenotypes and use multiple methods of statistical analysis. The combination of multiple genetic loci, multiple phenotypes, and multiple methods of evaluating associations between genotype and phenotype means that modern genetic studies often involve the testing of an enormous number of hypotheses. When multiple hypothesis tests are performed in a study, there is a risk of inflation of the type I error rate (i.e., the chance of falsely claiming an association when there is none). Several methods for multiple-testing correction are in popular use, and they all have strengths and weaknesses. Because no single method is universally adopted or always appropriate, it is important to understand the principles, strengths, and weaknesses of the methods so that they can be applied appropriately in practice. In this article, we review the three principle methods for multiple-testing correction and provide guidance for calculating statistical power.

  10. Sour pressure swing adsorption process

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

    Bhadra, Shubhra Jyoti; Wright, Andrew David; Hufton, Jeffrey Raymond

    Methods and apparatuses for separating CO.sub.2 and sulfur-containing compounds from a synthesis gas obtained from gasification of a carbonaceous feedstock. The primary separating steps are performed using a sour pressure swing adsorption (SPSA) system, followed by an acid gas enrichment system and a sulfur removal unit. The SPSA system includes multiple pressure equalization steps and a rinse step using a rinse gas that is supplied from a source other than directly from one of the adsorber beds of the SPSA system.

  11. Preprocessing and Analysis of LC-MS-Based Proteomic Data

    PubMed Central

    Tsai, Tsung-Heng; Wang, Minkun; Ressom, Habtom W.

    2016-01-01

    Liquid chromatography coupled with mass spectrometry (LC-MS) has been widely used for profiling protein expression levels. This chapter is focused on LC-MS data preprocessing, which is a crucial step in the analysis of LC-MS based proteomics. We provide a high-level overview, highlight associated challenges, and present a step-by-step example for analysis of data from LC-MS based untargeted proteomic study. Furthermore, key procedures and relevant issues with the subsequent analysis by multiple reaction monitoring (MRM) are discussed. PMID:26519169

  12. Forest Soil Bacteria: Diversity, Involvement in Ecosystem Processes, and Response to Global Change

    PubMed Central

    Lladó, Salvador; López-Mondéjar, Rubén

    2017-01-01

    SUMMARY The ecology of forest soils is an important field of research due to the role of forests as carbon sinks. Consequently, a significant amount of information has been accumulated concerning their ecology, especially for temperate and boreal forests. Although most studies have focused on fungi, forest soil bacteria also play important roles in this environment. In forest soils, bacteria inhabit multiple habitats with specific properties, including bulk soil, rhizosphere, litter, and deadwood habitats, where their communities are shaped by nutrient availability and biotic interactions. Bacteria contribute to a range of essential soil processes involved in the cycling of carbon, nitrogen, and phosphorus. They take part in the decomposition of dead plant biomass and are highly important for the decomposition of dead fungal mycelia. In rhizospheres of forest trees, bacteria interact with plant roots and mycorrhizal fungi as commensalists or mycorrhiza helpers. Bacteria also mediate multiple critical steps in the nitrogen cycle, including N fixation. Bacterial communities in forest soils respond to the effects of global change, such as climate warming, increased levels of carbon dioxide, or anthropogenic nitrogen deposition. This response, however, often reflects the specificities of each studied forest ecosystem, and it is still impossible to fully incorporate bacteria into predictive models. The understanding of bacterial ecology in forest soils has advanced dramatically in recent years, but it is still incomplete. The exact extent of the contribution of bacteria to forest ecosystem processes will be recognized only in the future, when the activities of all soil community members are studied simultaneously. PMID:28404790

  13. Dynamics and Molecular Determinants of Cytoplasmic Lipid Droplet Clustering and Dispersion

    PubMed Central

    Stefanski, Adrianne L.; McManaman, James L.

    2013-01-01

    Perilipin-1 (Plin1), a prominent cytoplasmic lipid droplet (CLD) binding phosphoprotein and key physiological regulator of triglyceride storage and lipolysis in adipocytes, is thought to regulate the fragmentation and dispersion of CLD that occurs in response to β-adrenergic activation of adenylate cyclase. Here we investigate the dynamics and molecular determinants of these processes using cell lines stably expressing recombinant forms of Plin1 and/or other members of the perilipin family. Plin1 and a C-terminal CLD-binding fragment of Plin1 (Plin1CT) induced formation of single dense CLD clusters near the microtubule organizing center, whereas neither an N-terminal CLD-binding fragment of Plin1, nor Plin2 or Plin3 induced clustering. Clustered CLD coated by Plin1, or Plin1CT, dispersed in response to isoproterenol, or other agents that activate adenylate cyclase, in a process inhibited by the protein kinase A inhibitor, H89, and blocked by microtubule disruption. Isoproterenol-stimulated phosphorylation of CLD-associated Plin1 on serine 492 preceded their dispersion, and live cell imaging showed that cluster dispersion involved initial fragmentation of tight clusters into multiple smaller clusters, which then fragmented into well-dispersed individual CLD. siRNA knockdown of the cortical actin binding protein, moesin, induced disaggregation of tight clusters into multiple smaller clusters, and inhibited the reaggregation of dispersed CLD into tight clusters. Together these data suggest that the clustering and dispersion processes involve a complex orchestration of phosphorylation-dependent, microtubule-dependent and independent, and microfilament dependent steps. PMID:23825572

  14. Forest Soil Bacteria: Diversity, Involvement in Ecosystem Processes, and Response to Global Change.

    PubMed

    Lladó, Salvador; López-Mondéjar, Rubén; Baldrian, Petr

    2017-06-01

    The ecology of forest soils is an important field of research due to the role of forests as carbon sinks. Consequently, a significant amount of information has been accumulated concerning their ecology, especially for temperate and boreal forests. Although most studies have focused on fungi, forest soil bacteria also play important roles in this environment. In forest soils, bacteria inhabit multiple habitats with specific properties, including bulk soil, rhizosphere, litter, and deadwood habitats, where their communities are shaped by nutrient availability and biotic interactions. Bacteria contribute to a range of essential soil processes involved in the cycling of carbon, nitrogen, and phosphorus. They take part in the decomposition of dead plant biomass and are highly important for the decomposition of dead fungal mycelia. In rhizospheres of forest trees, bacteria interact with plant roots and mycorrhizal fungi as commensalists or mycorrhiza helpers. Bacteria also mediate multiple critical steps in the nitrogen cycle, including N fixation. Bacterial communities in forest soils respond to the effects of global change, such as climate warming, increased levels of carbon dioxide, or anthropogenic nitrogen deposition. This response, however, often reflects the specificities of each studied forest ecosystem, and it is still impossible to fully incorporate bacteria into predictive models. The understanding of bacterial ecology in forest soils has advanced dramatically in recent years, but it is still incomplete. The exact extent of the contribution of bacteria to forest ecosystem processes will be recognized only in the future, when the activities of all soil community members are studied simultaneously. Copyright © 2017 American Society for Microbiology.

  15. Drug hypersensitivity in human immunodeficiency virus-infected patient: challenging diagnosis and management

    PubMed Central

    Widhani, Alvina; Karjadi, Teguh Harjono

    2014-01-01

    Human immunodeficiency virus (HIV)-infected patients present complex immunological alterations. Multiple drugs that usually prescribed for prevention or treatment of opportunistic infections and antiretroviral pose these patients a higher risk of developing drug hypersensitivity. All antiretroviral agents and drugs to treat opportunistic infections have been reported to cause drug hypersensitivity reactions. Allergic reactions with antiretroviral are not restricted to older agents, although newer drugs usually more tolerated. Cutaneous adverse drug reactions are the most common manifestation of drug hypersensitivity in HIV, typically manifesting as maculopapular rash with or without systemic symptoms in the presence or absence of internal organ involvement. The onset of an allergic reaction is usually delayed. Severe drug hypersensitity reactions as erythema multiforme, Stevens Johnson syndrome and toxic epidermal necrolysis develop more often in HIV-infected patients compared to other populations. Mild to moderate rash without systemic symptom or organ involvement usually do not need drug discontinuation. Appropriate diagnosis and management of drug hypersensitivity reactions are essential, especially in patients with very low CD4+ T-cell count and multiple opportunistic infections. Clinicians should aware of different half-life of each drug when decided to stop the drug. Knowledge of the metabolism, recognition of the risk factors, and the ability to suggest the probability of particular drug as causative are also important points. A step wise rechallenge test or desensitization with the offending drug might be a preferable action and more commonly used in managing drug hypersensitivity in HIV-infected patients. Desensitization protocols have been successfully done for several antiretroviral and opportunistic infection drugs. PMID:24527412

  16. Nonlinear coupled mode approach for modeling counterpropagating solitons in the presence of disorder-induced multiple scattering in photonic crystal waveguides

    NASA Astrophysics Data System (ADS)

    Mann, Nishan; Hughes, Stephen

    2018-02-01

    We present the analytical and numerical details behind our recently published article [Phys. Rev. Lett. 118, 253901 (2017), 10.1103/PhysRevLett.118.253901], describing the impact of disorder-induced multiple scattering on counterpropagating solitons in photonic crystal waveguides. Unlike current nonlinear approaches using the coupled mode formalism, we account for the effects of intraunit cell multiple scattering. To solve the resulting system of coupled semilinear partial differential equations, we introduce a modified Crank-Nicolson-type norm-preserving implicit finite difference scheme inspired by the transfer matrix method. We provide estimates of the numerical dispersion characteristics of our scheme so that optimal step sizes can be chosen to either minimize numerical dispersion or to mimic the exact dispersion. We then show numerical results of a fundamental soliton propagating in the presence of multiple scattering to demonstrate that choosing a subunit cell spatial step size is critical in accurately capturing the effects of multiple scattering, and illustrate the stochastic nature of disorder by simulating soliton propagation in various instances of disordered photonic crystal waveguides. Our approach is easily extended to include a wide range of optical nonlinearities and is applicable to various photonic nanostructures where power propagation is bidirectional, either by choice, or as a result of multiple scattering.

  17. Methods of operation of apparatus measuring formation resistivity from within a cased well having one measurement and two compensation steps

    DOEpatents

    Vail, III, William B.

    1993-01-01

    Methods of operation of an apparatus having at least two pairs of voltage measurement electrodes vertically disposed in a cased well to measure the resistivity of adjacent geological formations from inside the cased well. During stationary measurements with the apparatus at a fixed vertical depth within the cased well, the invention herein discloses methods of operation which include a measurement step and subsequent first and second compensation steps respectively resulting in improved accuracy of measurement. First and second order errors of measurement are identified, and the measurement step and two compensation steps provide methods to substantially eliminate their influence on the results. A multiple frequency apparatus adapted to movement within the well is described which simultaneously provide the measurement and two compensation steps.

  18. Efficacy and Safety of a Novel Three-Step Medial Release Technique in Varus Total Knee Arthroplasty.

    PubMed

    Kim, Min Woo; Koh, In Jun; Kim, Ju Hwan; Jung, Jae Jong; In, Yong

    2015-09-01

    We investigated the efficacy and safety of our novel three-step medial release technique in varus total knee arthroplasty (TKA) over time. Two hundred sixty seven consecutive varus TKAs were performed by applying the algorithmic release technique which consisted of sequential release of the deep medial collateral ligament (step 1), the semimembranosus (step 2), and multiple needle puncturing of the superficial medial collateral ligament (step 3). One hundred seventeen, 114, and 36 knees were balanced after step 1, 2, and 3 releases, respectively. There were no significant differences in changes of medial and lateral laxities between groups in over a year. Our novel stepwise medial release technique was efficacious and safe in balancing varus knees during TKA. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. A Taxonomy of Instructional Strategies in Early Childhood Education; Toward a Developmental Theory of Instructional Design.

    ERIC Educational Resources Information Center

    Vance, Barbara

    This paper suggests two steps in instructional deisgn for early childhood that can be derived from a recent major paper on instructional strategy taxonomy. These steps, together with the instructional design variables involved in each step, are reviewed relative to current research in child development and early education. The variables reviewed…

  20. Development of a modularized two-step (M2S) chromosome integration technique for integration of multiple transcription units in Saccharomyces cerevisiae.

    PubMed

    Li, Siwei; Ding, Wentao; Zhang, Xueli; Jiang, Huifeng; Bi, Changhao

    2016-01-01

    Saccharomyces cerevisiae has already been used for heterologous production of fuel chemicals and valuable natural products. The establishment of complicated heterologous biosynthetic pathways in S. cerevisiae became the research focus of Synthetic Biology and Metabolic Engineering. Thus, simple and efficient genomic integration techniques of large number of transcription units are demanded urgently. An efficient DNA assembly and chromosomal integration method was created by combining homologous recombination (HR) in S. cerevisiae and Golden Gate DNA assembly method, designated as modularized two-step (M2S) technique. Two major assembly steps are performed consecutively to integrate multiple transcription units simultaneously. In Step 1, Modularized scaffold containing a head-to-head promoter module and a pair of terminators was assembled with two genes. Thus, two transcription units were assembled with Golden Gate method into one scaffold in one reaction. In Step 2, the two transcription units were mixed with modules of selective markers and integration sites and transformed into S. cerevisiae for assembly and integration. In both steps, universal primers were designed for identification of correct clones. Establishment of a functional β-carotene biosynthetic pathway in S. cerevisiae within 5 days demonstrated high efficiency of this method, and a 10-transcriptional-unit pathway integration illustrated the capacity of this method. Modular design of transcription units and integration elements simplified assembly and integration procedure, and eliminated frequent designing and synthesis of DNA fragments in previous methods. Also, by assembling most parts in Step 1 in vitro, the number of DNA cassettes for homologous integration in Step 2 was significantly reduced. Thus, high assembly efficiency, high integration capacity, and low error rate were achieved.

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