Frequency response function (FRF) based updating of a laser spot welded structure

NASA Astrophysics Data System (ADS)

Zin, M. S. Mohd; Rani, M. N. Abdul; Yunus, M. A.; Sani, M. S. M.; Wan Iskandar Mirza, W. I. I.; Mat Isa, A. A.

2018-04-01

The objective of this paper is to present frequency response function (FRF) based updating as a method for matching the finite element (FE) model of a laser spot welded structure with a physical test structure. The FE model of the welded structure was developed using CQUAD4 and CWELD element connectors, and NASTRAN was used to calculate the natural frequencies, mode shapes and FRF. Minimization of the discrepancies between the finite element and experimental FRFs was carried out using the exceptional numerical capability of NASTRAN Sol 200. The experimental work was performed under free-free boundary conditions using LMS SCADAS. Avast improvement in the finite element FRF was achieved using the frequency response function (FRF) based updating with two different objective functions proposed.

Requirement for CD4 T Cell Help in Generating Functional CD8 T Cell Memory

NASA Astrophysics Data System (ADS)

Shedlock, Devon J.; Shen, Hao

2003-04-01

Although primary CD8 responses to acute infections are independent of CD4 help, it is unknown whether a similar situation applies to secondary responses. We show that depletion of CD4 cells during the recall response has minimal effect, whereas depletion during the priming phase leads to reduced responses by memory CD8 cells to reinfection. Memory CD8 cells generated in CD4+/+ mice responded normally when transferred into CD4-/- hosts, whereas memory CD8 cells generated in CD4-/- mice mounted defective recall responses in CD4+/+ adoptive hosts. These results demonstrate a previously undescribed role for CD4 help in the development of functional CD8 memory.

Optimisation of nano-silica modified self-compacting high-Volume fly ash mortar

NASA Astrophysics Data System (ADS)

Achara, Bitrus Emmanuel; Mohammed, Bashar S.; Fadhil Nuruddin, Muhd

2017-05-01

Evaluation of the effects of nano-silica amount and superplasticizer (SP) dosage on the compressive strength, porosity and slump flow on high-volume fly ash self-consolidating mortar was investigated. Multiobjective optimisation technique using Design-Expert software was applied to obtain solution based on desirability function that simultaneously optimises the variables and the responses. A desirability function of 0.811 gives the optimised solution. The experimental and predicted results showed minimal errors in all the measured responses.

Reliability, construct validity, and responsiveness of the neck disability index, patient-specific functional scale, and numeric pain rating scale in patients with cervical radiculopathy.

PubMed

Young, Ian A; Cleland, Joshua A; Michener, Lori A; Brown, Chris

2010-10-01

To examine the psychometric properties of the Neck Disability Index, Patient-Specific Functional Scale, and the Numeric Pain Rating Scale in a cohort of patients with cervical radiculopathy. A single-group repeated-measures design. Patients (n = 165) presenting to physical therapy with cervical radiculopathy completed the Neck Disability Index, Patient-Specific Functional Scale, and Numeric Pain Rating Scale at the baseline examination and at a follow-up. At the time of follow-up, all patients also completed the Global Rating of Change, which was used to dichotomize patients as improved or stable. Baseline and follow-up scores were used to determine the test-retest reliability, construct validity, and minimal levels of detectable and clinically important change for the Neck Disability Index, Patient-Specific Functional Scale, and Numeric Pain Rating Scale. Both the Neck Disability Index and Numeric Pain Rating Scale exhibited fair test-retest reliability, whereas the Patient-Specific Functional Scale exhibited poor reliability in patients with cervical radiculopathy. All three outcome measures showed adequate responsiveness in this patient population. The minimal detectable change was 13.4 for the Neck Disability Index, 3.3 for the Patient-Specific Functional Scale, and 4.1 for the Numeric Pain Rating Scale. The threshold for the minimal clinically important difference was 8.5 for the Neck Disability Index and 2.2 for both the Patient-Specific Functional Scale and Numeric Pain Rating Scale. In light of the varied distribution of symptoms in patients with cervical radiculopathy, future studies should investigate the psychometric properties of other neck-related disability measures in this patient population.

Hybrid NN/SVM Computational System for Optimizing Designs

NASA Technical Reports Server (NTRS)

Rai, Man Mohan

2009-01-01

A computational method and system based on a hybrid of an artificial neural network (NN) and a support vector machine (SVM) (see figure) has been conceived as a means of maximizing or minimizing an objective function, optionally subject to one or more constraints. Such maximization or minimization could be performed, for example, to optimize solve a data-regression or data-classification problem or to optimize a design associated with a response function. A response function can be considered as a subset of a response surface, which is a surface in a vector space of design and performance parameters. A typical example of a design problem that the method and system can be used to solve is that of an airfoil, for which a response function could be the spatial distribution of pressure over the airfoil. In this example, the response surface would describe the pressure distribution as a function of the operating conditions and the geometric parameters of the airfoil. The use of NNs to analyze physical objects in order to optimize their responses under specified physical conditions is well known. NN analysis is suitable for multidimensional interpolation of data that lack structure and enables the representation and optimization of a succession of numerical solutions of increasing complexity or increasing fidelity to the real world. NN analysis is especially useful in helping to satisfy multiple design objectives. Feedforward NNs can be used to make estimates based on nonlinear mathematical models. One difficulty associated with use of a feedforward NN arises from the need for nonlinear optimization to determine connection weights among input, intermediate, and output variables. It can be very expensive to train an NN in cases in which it is necessary to model large amounts of information. Less widely known (in comparison with NNs) are support vector machines (SVMs), which were originally applied in statistical learning theory. In terms that are necessarily oversimplified to fit the scope of this article, an SVM can be characterized as an algorithm that (1) effects a nonlinear mapping of input vectors into a higher-dimensional feature space and (2) involves a dual formulation of governing equations and constraints. One advantageous feature of the SVM approach is that an objective function (which one seeks to minimize to obtain coefficients that define an SVM mathematical model) is convex, so that unlike in the cases of many NN models, any local minimum of an SVM model is also a global minimum.

Prediction of Unsteady Aerodynamic Coefficients at High Angles of Attack

NASA Technical Reports Server (NTRS)

Pamadi, Bandu N.; Murphy, Patrick C.; Klein, Vladislav; Brandon, Jay M.

2001-01-01

The nonlinear indicial response method is used to model the unsteady aerodynamic coefficients in the low speed longitudinal oscillatory wind tunnel test data of the 0.1 scale model of the F-16XL aircraft. Exponential functions are used to approximate the deficiency function in the indicial response. Using one set of oscillatory wind tunnel data and parameter identification method, the unknown parameters in the exponential functions are estimated. The genetic algorithm is used as a least square minimizing algorithm. The assumed model structures and parameter estimates are validated by comparing the predictions with other sets of available oscillatory wind tunnel test data.

Evaluative measurement properties of the patient-specific functional scale for primary shoulder complaints in physical therapy practice.

PubMed

Koehorst, Marije L S; van Trijffel, Emiel; Lindeboom, Robert

2014-08-01

Clinical measurement, longitudinal. To assess the test-retest reliability, construct validity, and responsiveness of the Patient-Specific Functional Scale (PSFS) in patients with a primary shoulder complaint. Health measurement outcomes have become increasingly important for evaluating treatment. Patient-specific questionnaires are useful tools for determining treatment goals and evaluating treatment in individual patients. These questionnaires have not yet been validated in patients with nonspecific shoulder pain. Patients completed the PSFS, the numeric pain rating scale, and the Shoulder Pain and Disability Index at baseline, and after 1 week and 4 to 6 weeks. Test-retest reliability was determined using intraclass correlation coefficients. To assess convergent validity, change scores of the PSFS were correlated with the numeric pain rating scale and Shoulder Pain and Disability Index change scores. Responsiveness was assessed by calculating the area under the curve, the minimal clinically important change, and minimal detectable change, using the global rating of change as an external criterion. Fifty patients (37 men; mean age, 47.7 years) participated in the study. Reliability was high (intraclass correlation coefficient = 0.87; 95% confidence interval [CI]: 0.72, 0.94). The correlations between the change scores of the PSFS and those of the Shoulder Pain and Disability Index and numeric pain rating scale were 0.45 (95% CI: 0.17, 0.80) and 0.55 (95% CI: 0.29, 0.73), respectively. The area under the curve for the PSFS was 0.67 (95% CI: 0.51, 0.83). The minimal detectable change and minimal clinically important change were 0.97 and 1.29 points, respectively. These results suggest that the PSFS is a reliable, valid, and responsive instrument that can be used as an evaluative instrument in patients with a primary shoulder complaint.

7 CFR 4279.30 - Lenders' functions and responsibilities.

Code of Federal Regulations, 2014 CFR

2014-01-01

... the loan processing phase. The lender must analyze all credit factors associated with each proposed loan and apply its professional judgment to determine that the credit factors, considered in... environmental impacts of their proposals at the earliest planning stages; and to develop proposals that minimize...

7 CFR 4279.30 - Lenders' functions and responsibilities.

Code of Federal Regulations, 2011 CFR

2011-01-01

... the loan processing phase. The lender must analyze all credit factors associated with each proposed loan and apply its professional judgment to determine that the credit factors, considered in... environmental impacts of their proposals at the earliest planning stages; and to develop proposals that minimize...

Validity, responsiveness, minimal detectable change, and minimal clinically important change of the Pediatric Motor Activity Log in children with cerebral palsy.

PubMed

Lin, Keh-chung; Chen, Hui-fang; Chen, Chia-ling; Wang, Tien-ni; Wu, Ching-yi; Hsieh, Yu-wei; Wu, Li-ling

2012-01-01

This study examined criterion-related validity and clinimetric properties of the Pediatric Motor Activity Log (PMAL) in children with cerebral palsy. Study participants were 41 children (age range: 28-113 months) and their parents. Criterion-related validity was evaluated by the associations between the PMAL and criterion measures at baseline and posttreatment, including the self-care, mobility, and cognition subscale, the total performance of the Functional Independence Measure in children (WeeFIM), and the grasping and visual-motor integration of the Peabody Developmental Motor Scales. Pearson correlation coefficients were calculated. Responsiveness was examined using the paired t test and the standardized response mean, the minimal detectable change was captured at the 90% confidence level, and the minimal clinically important change was estimated using anchor-based and distribution-based approaches. The PMAL-QOM showed fair concurrent validity at pretreatment and posttreatment and predictive validity, whereas the PMAL-AOU had fair concurrent validity at posttreatment only. The PMAL-AOU and PMAL-QOM were both markedly responsive to change after treatment. Improvement of at least 0.67 points on the PMAL-AOU and 0.66 points on the PMAL-QOM can be considered as a true change, not measurement error. A mean change has to exceed the range of 0.39-0.94 on the PMAL-AOU and the range of 0.38-0.74 on the PMAL-QOM to be regarded as clinically important change. Copyright © 2011 Elsevier Ltd. All rights reserved.

Regulatory T Cells: Differentiation and Function.

PubMed

Plitas, George; Rudensky, Alexander Y

2016-09-02

The immune system of vertebrate animals has evolved to mount an effective defense against a diverse set of pathogens while minimizing transient or lasting impairment in tissue function that could result from the inflammation caused by immune responses to infectious agents. In addition, misguided immune responses to "self" and dietary antigens, as well as to commensal microorganisms, can lead to a variety of inflammatory disorders, including autoimmunity, metabolic syndrome, allergies, and cancer. Regulatory T cells expressing the X chromosome-linked transcription factor Foxp3 suppress inflammatory responses in diverse biological settings and serve as a vital mechanism of negative regulation of immune-mediated inflammation. Cancer Immunol Res; 4(9); 721-5. ©2016 AACR. ©2016 American Association for Cancer Research.

Comparison of reliability and responsiveness of patient-reported clinical outcome measures in knee osteoarthritis rehabilitation.

PubMed

Williams, Valerie J; Piva, Sara R; Irrgang, James J; Crossley, Chad; Fitzgerald, G Kelley

2012-08-01

Secondary analysis, pretreatment-posttreatment observational study. To compare the reliability and responsiveness of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the Knee Outcome Survey activities of daily living subscale (KOS-ADL), and the Lower Extremity Functional Scale (LEFS) in individuals with knee osteoarthritis (OA). The WOMAC is the current standard in patient-reported measures of function in patients with knee OA. The KOS-ADL and LEFS were designed for potential use in patients with knee OA. If the KOS-ADL and LEFS are to be considered viable alternatives to the WOMAC for measuring patient-reported function in individuals with knee OA, they should have measurement properties comparable to the WOMAC. It would also be important to determine whether either of these instruments may be superior to the WOMAC in terms of reliability or responsiveness in this population. Data from 168 subjects with knee OA, who participated in a rehabilitation program, were used in the analyses. Reliability and responsiveness of each outcome measure were estimated at follow-ups of 2, 6, and 12 months. Reliability was estimated by calculating the intraclass correlation coefficient (ICC2,1) for subjects who were unchanged in status from baseline at each follow-up time, based on a global rating of change score. To examine responsiveness, the standard error of the measurement, minimal detectable change, minimal clinically important difference, and the Guyatt responsiveness index were calculated for each outcome measure at each follow-up time. All 3 outcome measures demonstrated reasonable reliability and responsiveness to change. Reliability and responsiveness tended to decrease somewhat with increasing follow-up time. There were no substantial differences between outcome measures for reliability or any of the 3 measures of responsiveness at any follow-up time. The results do not indicate that one outcome measure is more reliable or responsive than another when applied to subjects with knee OA. We believe that all 3 instruments are appropriate outcome measures to examine change in functional status of patients with knee OA.

Modern control techniques in active flutter suppression using a control moment gyro

NASA Technical Reports Server (NTRS)

Buchek, P. M.

1974-01-01

Development of organized synthesis techniques, using concepts of modern control theory was studied for the design of active flutter suppression systems for two and three-dimensional lifting surfaces, utilizing a control moment gyro (CMG) to generate the required control torques. Incompressible flow theory is assumed, with the unsteady aerodynamic forces and moments for arbitrary airfoil motion obtained by using the convolution integral based on Wagner's indicial lift function. Linear optimal control theory is applied to find particular optimal sets of gain values which minimize a quadratic performance function. The closed loop system's response to impulsive gust disturbances and the resulting control power requirements are investigated, and the system eigenvalues necessary to minimize the maximum value of control power are determined.

Digital robust active control law synthesis for large order flexible structure using parameter optimization

NASA Technical Reports Server (NTRS)

Mukhopadhyay, V.

1988-01-01

A generic procedure for the parameter optimization of a digital control law for a large-order flexible flight vehicle or large space structure modeled as a sampled data system is presented. A linear quadratic Guassian type cost function was minimized, while satisfying a set of constraints on the steady-state rms values of selected design responses, using a constrained optimization technique to meet multiple design requirements. Analytical expressions for the gradients of the cost function and the design constraints on mean square responses with respect to the control law design variables are presented.

Transfer-function-parameter estimation from frequency response data: A FORTRAN program

NASA Technical Reports Server (NTRS)

Seidel, R. C.

1975-01-01

A FORTRAN computer program designed to fit a linear transfer function model to given frequency response magnitude and phase data is presented. A conjugate gradient search is used that minimizes the integral of the absolute value of the error squared between the model and the data. The search is constrained to insure model stability. A scaling of the model parameters by their own magnitude aids search convergence. Efficient computer algorithms result in a small and fast program suitable for a minicomputer. A sample problem with different model structures and parameter estimates is reported.

Uncertainty analysis of signal deconvolution using a measured instrument response function

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

Hartouni, E. P.; Beeman, B.; Caggiano, J. A.

2016-10-05

A common analysis procedure minimizes the ln-likelihood that a set of experimental observables matches a parameterized model of the observation. The model includes a description of the underlying physical process as well as the instrument response function (IRF). Here, we investigate the National Ignition Facility (NIF) neutron time-of-flight (nTOF) spectrometers, the IRF is constructed from measurements and models. IRF measurements have a finite precision that can make significant contributions to the uncertainty estimate of the physical model’s parameters. Finally, we apply a Bayesian analysis to properly account for IRF uncertainties in calculating the ln-likelihood function used to find the optimummore » physical parameters.« less

A method for decoding the neurophysiological spike-response transform.

PubMed

Stern, Estee; García-Crescioni, Keyla; Miller, Mark W; Peskin, Charles S; Brezina, Vladimir

2009-11-15

Many physiological responses elicited by neuronal spikes-intracellular calcium transients, synaptic potentials, muscle contractions-are built up of discrete, elementary responses to each spike. However, the spikes occur in trains of arbitrary temporal complexity, and each elementary response not only sums with previous ones, but can itself be modified by the previous history of the activity. A basic goal in system identification is to characterize the spike-response transform in terms of a small number of functions-the elementary response kernel and additional kernels or functions that describe the dependence on previous history-that will predict the response to any arbitrary spike train. Here we do this by developing further and generalizing the "synaptic decoding" approach of Sen et al. (1996). Given the spike times in a train and the observed overall response, we use least-squares minimization to construct the best estimated response and at the same time best estimates of the elementary response kernel and the other functions that characterize the spike-response transform. We avoid the need for any specific initial assumptions about these functions by using techniques of mathematical analysis and linear algebra that allow us to solve simultaneously for all of the numerical function values treated as independent parameters. The functions are such that they may be interpreted mechanistically. We examine the performance of the method as applied to synthetic data. We then use the method to decode real synaptic and muscle contraction transforms.

Smart Polymeric Hydrogels for Cartilage Tissue Engineering: A Review on the Chemistry and Biological Functions.

PubMed

Eslahi, Niloofar; Abdorahim, Marjan; Simchi, Abdolreza

2016-11-14

Stimuli responsive hydrogels (SRHs) are attractive bioscaffolds for tissue engineering. The structural similarity of SRHs to the extracellular matrix (ECM) of many tissues offers great advantages for a minimally invasive tissue repair. Among various potential applications of SRHs, cartilage regeneration has attracted significant attention. The repair of cartilage damage is challenging in orthopedics owing to its low repair capacity. Recent advances include development of injectable hydrogels to minimize invasive surgery with nanostructured features and rapid stimuli-responsive characteristics. Nanostructured SRHs with more structural similarity to natural ECM up-regulate cell-material interactions for faster tissue repair and more controlled stimuli-response to environmental changes. This review highlights most recent advances in the development of nanostructured or smart hydrogels for cartilage tissue engineering. Different types of stimuli-responsive hydrogels are introduced and their fabrication processes through physicochemical procedures are reported. The applications and characteristics of natural and synthetic polymers used in SRHs are also reviewed with an outline on clinical considerations and challenges.

Plant Responses to Rarified Atmospheres

NASA Technical Reports Server (NTRS)

Corey, Kenneth A.; Fowler, Philip A.; Wheeler, Raymond M.

2000-01-01

Reduced atmospheric pressures will likely be used to minimize mass and engineering requirements for plant growth habitats used in extraterrestrial applications. This report provides a brief survey of key literature related to responses of plants to atmospheric variables and a broad rationale for designing minimal atmospheres for future plant growth structures on the Martian surface. The literature and recent work suggest that atmospheric pressure limits for normal plant function are likely to be 10 kPa or perhaps slightly lower. At Kennedy Space Center, a chamber with high vacuum capability was used to design and begin construction of a system for testing plant responses to reduced pressure atmospheres. A test rack with lighting provided by 3, high-pressure sodium vapor lamps was built to conduct measurements of short-term plant responses. Initial experiments with lettuce showed that a pressure of 10 kPa resulted in a 6.1-fold increase in the rate of water loss compared to water loss at ambient pressure (101 kPa).

Extended polarization in 3rd order SCC-DFTB from chemical potential equilization

PubMed Central

Kaminski, Steve; Giese, Timothy J.; Gaus, Michael; York, Darrin M.; Elstner, Marcus

2012-01-01

In this work we augment the approximate density functional method SCC-DFTB (DFTB3) with the chemical potential equilization (CPE) approach in order to improve the performance for molecular electronic polarizabilities. The CPE method, originally implemented for NDDO type methods by Giese and York, has been shown to emend minimal basis methods wrt response properties significantly, and has been applied to SCC-DFTB recently. CPE allows to overcome this inherent limitation of minimal basis methods by supplying an additional response density. The systematic underestimation is thereby corrected quantitatively without the need to extend the atomic orbital basis, i.e. without increasing the overall computational cost significantly. Especially the dependency of polarizability as a function of molecular charge state was significantly improved from the CPE extension of DFTB3. The empirical parameters introduced by the CPE approach were optimized for 172 organic molecules in order to match the results from density functional methods (DFT) methods using large basis sets. However, the first order derivatives of molecular polarizabilities, as e.g. required to compute Raman activities, are not improved by the current CPE implementation, i.e. Raman spectra are not improved. PMID:22894819

Tire Force Estimation using a Proportional Integral Observer

NASA Astrophysics Data System (ADS)

Farhat, Ahmad; Koenig, Damien; Hernandez-Alcantara, Diana; Morales-Menendez, Ruben

2017-01-01

This paper addresses a method for detecting critical stability situations in the lateral vehicle dynamics by estimating the non-linear part of the tire forces. These forces indicate the road holding performance of the vehicle. The estimation method is based on a robust fault detection and estimation approach which minimize the disturbance and uncertainties to residual sensitivity. It consists in the design of a Proportional Integral Observer (PIO), while minimizing the well known H ∞ norm for the worst case uncertainties and disturbance attenuation, and combining a transient response specification. This multi-objective problem is formulated as a Linear Matrix Inequalities (LMI) feasibility problem where a cost function subject to LMI constraints is minimized. This approach is employed to generate a set of switched robust observers for uncertain switched systems, where the convergence of the observer is ensured using a Multiple Lyapunov Function (MLF). Whilst the forces to be estimated can not be physically measured, a simulation scenario with CarSimTM is presented to illustrate the developed method.

What genes make a tree a tree?

Treesearch

Andrew T. Groover

2005-01-01

Woody growth is evolutionarily ancient, yet has been gained and lost multiple times in plant evolution and is readily enhanced or minimized in eudicot speciation. New molecular genetic and genomic studies in Populus and Arabidopsis that are defining the genes responsible for cambium function and woody growth suggest that the genes...

Synthesis of feedback systems with large plant ignorance for prescribed time domain tolerances

NASA Technical Reports Server (NTRS)

Horowitz, I. M.; Sidi, M.

1971-01-01

There is given a minimum-phase plant transfer function, with prescribed bounds on its parameter values. The plant is imbedded in a two-degree-of freedom feedback system, which is to be designed such that the system time response to a deterministic input lies within specified boundaries. Subject to the above, the design should be such as to minimize the effect of sensor noise at the input to the plant. This report presents a design procedure for this purpose, based on frequency response concepts. The time-domain tolerances are translated into equivalent frequency response tolerances. The latter lead to bounds on the loop transmission function in the form of continuous curves on the Nichols chart. The properties of the loop transmission function which satisfy these bounds with minimum effect of sensor noise, are derived.

A kinetic investigation of interacting, stimulated T cells identifies conditions for rapid functional enhancement, minimal phenotype differentiation, and improved adoptive cell transfer tumor eradication.

PubMed

Zhou, Jing; Bethune, Michael T; Malkova, Natalia; Sutherland, Alexander M; Comin-Anduix, Begonya; Su, Yapeng; Baltimore, David; Ribas, Antoni; Heath, James R

2018-01-01

For adoptive cell transfer (ACT) immunotherapy of tumor-reactive T cells, an effective therapeutic outcome depends upon cell dose, cell expansion in vivo through a minimally differentiated phenotype, long term persistence, and strong cytolytic effector function. An incomplete understanding of the biological coupling between T cell expansion, differentiation, and response to stimulation hinders the co-optimization of these factors. We report on a biophysical investigation of how the short-term kinetics of T cell functional activation, through molecular stimulation and cell-cell interactions, competes with phenotype differentiation. T cells receive molecular stimulation for a few minutes to a few hours in bulk culture. Following this priming period, the cells are then analyzed at the transcriptional level, or isolated as single cells, with continuing molecular stimulation, within microchambers for analysis via 11-plex secreted protein assays. We resolve a rapid feedback mechanism, promoted by T cell-T cell contact interactions, which strongly amplifies T cell functional performance while yielding only minimal phenotype differentiation. When tested in mouse models of ACT, optimally primed T cells lead to complete tumor eradication. A similar kinetic process is identified in CD8+ and CD4+ T cells collected from a patient with metastatic melanoma.

A kinetic investigation of interacting, stimulated T cells identifies conditions for rapid functional enhancement, minimal phenotype differentiation, and improved adoptive cell transfer tumor eradication

PubMed Central

Zhou, Jing; Bethune, Michael T.; Malkova, Natalia; Sutherland, Alexander M.; Comin-Anduix, Begonya; Su, Yapeng; Baltimore, David; Ribas, Antoni

2018-01-01

For adoptive cell transfer (ACT) immunotherapy of tumor-reactive T cells, an effective therapeutic outcome depends upon cell dose, cell expansion in vivo through a minimally differentiated phenotype, long term persistence, and strong cytolytic effector function. An incomplete understanding of the biological coupling between T cell expansion, differentiation, and response to stimulation hinders the co-optimization of these factors. We report on a biophysical investigation of how the short-term kinetics of T cell functional activation, through molecular stimulation and cell-cell interactions, competes with phenotype differentiation. T cells receive molecular stimulation for a few minutes to a few hours in bulk culture. Following this priming period, the cells are then analyzed at the transcriptional level, or isolated as single cells, with continuing molecular stimulation, within microchambers for analysis via 11-plex secreted protein assays. We resolve a rapid feedback mechanism, promoted by T cell—T cell contact interactions, which strongly amplifies T cell functional performance while yielding only minimal phenotype differentiation. When tested in mouse models of ACT, optimally primed T cells lead to complete tumor eradication. A similar kinetic process is identified in CD8+ and CD4+ T cells collected from a patient with metastatic melanoma. PMID:29360859

Microbial functional diversity covaries with permafrost thaw-induced environmental heterogeneity in tundra soil.

PubMed

Yuan, Mengting M; Zhang, Jin; Xue, Kai; Wu, Liyou; Deng, Ye; Deng, Jie; Hale, Lauren; Zhou, Xishu; He, Zhili; Yang, Yunfeng; Van Nostrand, Joy D; Schuur, Edward A G; Konstantinidis, Konstantinos T; Penton, Christopher R; Cole, James R; Tiedje, James M; Luo, Yiqi; Zhou, Jizhong

2018-01-01

Permafrost soil in high latitude tundra is one of the largest terrestrial carbon (C) stocks and is highly sensitive to climate warming. Understanding microbial responses to warming-induced environmental changes is critical to evaluating their influences on soil biogeochemical cycles. In this study, a functional gene array (i.e., geochip 4.2) was used to analyze the functional capacities of soil microbial communities collected from a naturally degrading permafrost region in Central Alaska. Varied thaw history was reported to be the main driver of soil and plant differences across a gradient of minimally, moderately, and extensively thawed sites. Compared with the minimally thawed site, the number of detected functional gene probes across the 15-65 cm depth profile at the moderately and extensively thawed sites decreased by 25% and 5%, while the community functional gene β-diversity increased by 34% and 45%, respectively, revealing decreased functional gene richness but increased community heterogeneity along the thaw progression. Particularly, the moderately thawed site contained microbial communities with the highest abundances of many genes involved in prokaryotic C degradation, ammonification, and nitrification processes, but lower abundances of fungal C decomposition and anaerobic-related genes. Significant correlations were observed between functional gene abundance and vascular plant primary productivity, suggesting that plant growth and species composition could be co-evolving traits together with microbial community composition. Altogether, this study reveals the complex responses of microbial functional potentials to thaw-related soil and plant changes and provides information on potential microbially mediated biogeochemical cycles in tundra ecosystems. © 2017 John Wiley & Sons Ltd.

A method for decoding the neurophysiological spike-response transform

PubMed Central

Stern, Estee; García-Crescioni, Keyla; Miller, Mark W.; Peskin, Charles S.; Brezina, Vladimir

2009-01-01

Many physiological responses elicited by neuronal spikes—intracellular calcium transients, synaptic potentials, muscle contractions—are built up of discrete, elementary responses to each spike. However, the spikes occur in trains of arbitrary temporal complexity, and each elementary response not only sums with previous ones, but can itself be modified by the previous history of the activity. A basic goal in system identification is to characterize the spike-response transform in terms of a small number of functions—the elementary response kernel and additional kernels or functions that describe the dependence on previous history—that will predict the response to any arbitrary spike train. Here we do this by developing further and generalizing the “synaptic decoding” approach of Sen et al. (J Neurosci 16:6307-6318, 1996). Given the spike times in a train and the observed overall response, we use least-squares minimization to construct the best estimated response and at the same time best estimates of the elementary response kernel and the other functions that characterize the spike-response transform. We avoid the need for any specific initial assumptions about these functions by using techniques of mathematical analysis and linear algebra that allow us to solve simultaneously for all of the numerical function values treated as independent parameters. The functions are such that they may be interpreted mechanistically. We examine the performance of the method as applied to synthetic data. We then use the method to decode real synaptic and muscle contraction transforms. PMID:19695289

Derived Manding in Children with Autism: Synthesizing Skinner's Verbal Behavior with Relational Frame Theory

PubMed Central

2005-01-01

Mand functions for two stimuli (A1 and A2) were trained for 3 children with autism and were then incorporated into two related conditional discriminations (A1-B1/A2 -B2 and B1-C1/B2-C2). Tests were conducted to probe for a derived transfer of mand response functions from A1 and A2 to C1 and C2, respectively. When 1 participant failed to demonstrate derived transfer of mand response functions, transfer training using exemplars was conducted. When participants had demonstrated derived transfer of mand functions, the X1 and X2 tokens that were employed as reinforcers for mand responses were incorporated into two conditional discriminations (X1-Y1/X2-Y2 and Y1-Z1/Y2-Z2). Tests were conducted for derived transfer of reinforcing functions. Finally, tests were conducted to determine if the participants would demonstrate derived manding for the derived reinforcers (present C1 and C2 to mand for Z1 and Z2, respectively). Derived transfer of functions was observed when the sequence of training and testing was reversed (i.e., training and testing reinforcing functions before mand response functions) and when only minimal instructions were provided. PMID:16463526

Evaluation of modulation transfer function of optical lens system by support vector regression methodologies - A comparative study

NASA Astrophysics Data System (ADS)

Petković, Dalibor; Shamshirband, Shahaboddin; Saboohi, Hadi; Ang, Tan Fong; Anuar, Nor Badrul; Rahman, Zulkanain Abdul; Pavlović, Nenad T.

2014-07-01

The quantitative assessment of image quality is an important consideration in any type of imaging system. The modulation transfer function (MTF) is a graphical description of the sharpness and contrast of an imaging system or of its individual components. The MTF is also known and spatial frequency response. The MTF curve has different meanings according to the corresponding frequency. The MTF of an optical system specifies the contrast transmitted by the system as a function of image size, and is determined by the inherent optical properties of the system. In this study, the polynomial and radial basis function (RBF) are applied as the kernel function of Support Vector Regression (SVR) to estimate and predict estimate MTF value of the actual optical system according to experimental tests. Instead of minimizing the observed training error, SVR_poly and SVR_rbf attempt to minimize the generalization error bound so as to achieve generalized performance. The experimental results show that an improvement in predictive accuracy and capability of generalization can be achieved by the SVR_rbf approach in compare to SVR_poly soft computing methodology.

77 FR 28703 - Endangered and Threatened Wildlife and Plants; Threatened Status for Eriogonum codium (Umtanum...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-15

... necessarily designed to be a response, rather than a regulatory activity. All collecting is prohibited on the... be designed to minimize surface disturbance in the vicinity of sensitive resources, and fire control... benefit Umtanum desert buckwheat, these programs do not appear to have been designed to function as...

The Ethical Function of Research and Teaching

ERIC Educational Resources Information Center

Tabensky, Pedro Alexis

2014-01-01

It is the epistemic as well as the ethical responsibility of academics to aim to approach their research and teaching with a proper understanding of the ultimate ethical purpose or telos of their defining activities and products, which is the practical aim of promoting human flourishing. Minimally, academics should aim at understanding, and a key…

Time-Separating Heating and Sensor Functions of Thermistors in Precision Thermal Control Applications

NASA Technical Reports Server (NTRS)

Cho, Hyung J.; Sukhatme, Kalyani G.; Mahoney, John C.; Penanen, Konstantin Penanen; Vargas, Rudolph, Jr.

2010-01-01

A method allows combining the functions of a heater and a thermometer in a single device, a thermistor, with minimal temperature read errors. Because thermistors typically have a much smaller thermal mass than the objects they monitor, the thermal time to equilibrate the thermometer to the temperature of the object is typically much shorter than the thermal time of the object to change its temperature in response to an external perturbation.

Parameter Estimation of Actuators for Benchmark Active Control Technology (BACT) Wind Tunnel Model with Analysis of Wear and Aerodynamic Loading Effects

NASA Technical Reports Server (NTRS)

Waszak, Martin R.; Fung, Jimmy

1998-01-01

This report describes the development of transfer function models for the trailing-edge and upper and lower spoiler actuators of the Benchmark Active Control Technology (BACT) wind tunnel model for application to control system analysis and design. A simple nonlinear least-squares parameter estimation approach is applied to determine transfer function parameters from frequency response data. Unconstrained quasi-Newton minimization of weighted frequency response error was employed to estimate the transfer function parameters. An analysis of the behavior of the actuators over time to assess the effects of wear and aerodynamic load by using the transfer function models is also presented. The frequency responses indicate consistent actuator behavior throughout the wind tunnel test and only slight degradation in effectiveness due to aerodynamic hinge loading. The resulting actuator models have been used in design, analysis, and simulation of controllers for the BACT to successfully suppress flutter over a wide range of conditions.

Analysis of counting data: Development of the SATLAS Python package

NASA Astrophysics Data System (ADS)

Gins, W.; de Groote, R. P.; Bissell, M. L.; Granados Buitrago, C.; Ferrer, R.; Lynch, K. M.; Neyens, G.; Sels, S.

2018-01-01

For the analysis of low-statistics counting experiments, a traditional nonlinear least squares minimization routine may not always provide correct parameter and uncertainty estimates due to the assumptions inherent in the algorithm(s). In response to this, a user-friendly Python package (SATLAS) was written to provide an easy interface between the data and a variety of minimization algorithms which are suited for analyzinglow, as well as high, statistics data. The advantage of this package is that it allows the user to define their own model function and then compare different minimization routines to determine the optimal parameter values and their respective (correlated) errors. Experimental validation of the different approaches in the package is done through analysis of hyperfine structure data of 203Fr gathered by the CRIS experiment at ISOLDE, CERN.

Using impedance cardiography to assess left ventricular systolic function via postural change in patients with heart failure.

PubMed

DeMarzo, Arthur P; Calvin, James E; Kelly, Russell F; Stamos, Thomas D

2005-01-01

For the diagnosis and management of heart failure, it would be useful to have a simple point-of-care test for assessing ventricular function that could be performed by a nurse. An impedance cardiography (ICG) parameter called systolic amplitude (SA) can serve as an indicator of left ventricular systolic function (LVSF). This study tested the hypothesis that patients with normal LVSF should have a significant increase in SA in response to an increase in end-diastolic volume caused by postural change from sitting upright to supine, while patients with depressed LVSF associated with heart failure should have a minimal increase or a decrease in SA from upright to supine. ICG data were obtained in 12 patients without heart disease and with normal LVSF and 18 patients with clinically diagnosed heart failure. Consistent with the hypothesis, patients with normal LVSF had a significant increase in SA from upright to supine, whereas heart failure patients had a minimal increase or a decrease in SA from upright to supine. This ICG procedure may be useful for monitoring the trend of patient response to titration of beta blockers and other medications. ICG potentially could be used to detect worsening LVSF and provide a means of measurement for adjusting treatment.

Is forced oscillation technique the next respiratory function test of choice in childhood asthma.

PubMed

Alblooshi, Afaf; Alkalbani, Alia; Albadi, Ghaya; Narchi, Hassib; Hall, Graham

2017-12-26

Respiratory diseases, especially asthma, are common in children. While spirometry contributes to asthma diagnosis and management in older children, it has a limited role in younger children whom are often unable to perform forced expiratory manoeuvre. The development of novel diagnostic methods which require minimal effort, such as forced oscillation technique (FOT) is, therefore, a welcome and promising addition. FOT involves applying external, small amplitude oscillations to the respiratory system during tidal breathing. Therefore, it requires minimal effort and cooperation. The FOT has the potential to facilitate asthma diagnosis and management in pre-school children by faciliting the objective measurement of baseline lung function and airway reactivity in children unable to successfully perform spirometry. Traditionally the use of FOT was limited to specialised centres. However, the availability of commercial equipment resulted in its use both in research and in clinical practice. In this article, we review the available literature on the use of FOT in childhood asthma. The technical aspects of FOT are described followed by a discussion of its practical aspects in the clinical field including the measurement of baseline lung function and associated reference ranges, bronchodilator responsiveness and bronchial hyper-responsiveness. We also highlight the difficulties and limitations that might be encountered and future research directions.

An investigation of soil-structure interaction effects observed at the MIT Green Building

USGS Publications Warehouse

Taciroglu, Ertugrul; Çelebi, Mehmet; Ghahari, S. Farid; Abazarsa, Fariba

2016-01-01

The soil-foundation impedance function of the MIT Green Building is identified from its response signals recorded during an earthquake. Estimation of foundation impedance functions from seismic response signals is a challenging task, because: (1) the foundation input motions (FIMs) are not directly measurable, (2) the as-built properties of the super-structure are only approximately known, and (3) the soil-foundation impedance functions are inherently frequency-dependent. In the present study, aforementioned difficulties are circumvented by using, in succession, a blind modal identification (BMID) method, a simplified Timoshenko beam model (TBM), and a parametric updating of transfer functions (TFs). First, the flexible-base modal properties of the building are identified from response signals using the BMID method. Then, a flexible-base TBM is updated using the identified modal data. Finally, the frequency-dependent soil-foundation impedance function is estimated by minimizing the discrepancy between TFs (of pairs instrumented floors) that are (1) obtained experimentally from earthquake data and (2) analytically from the updated TBM. Using the fully identified flexible-base TBM, the FIMs as well as building responses at locations without instruments can be predicted, as demonstrated in the present study.

Unconstrained Recovery Characterization of Shape-Memory Polymer Networks for Cardiovascular Applications

PubMed Central

Yakacki, Christopher M.; Shandas, Robin; Lanning, Craig; Rech, Bryan; Eckstein, Alex; Gall, Ken

2009-01-01

Shape-memory materials have been proposed in biomedical device design due to their ability to facilitate minimally invasive surgery and recover to a predetermined shape in-vivo. Use of the shape-memory effect in polymers is proposed for cardiovascular stent interventions to reduce the catheter size for delivery and offer highly controlled and tailored deployment at body temperature. Shape-memory polymer networks were synthesized via photopolymerization of tert-butyl acrylate and poly (ethylene glycol) dimethacrylate to provide precise control over the thermomechanical response of the system. The free recovery response of the polymer stents at body temperature was studied as a function of glass transition temperature (Tg), crosslink density, geometrical perforation, and deformation temperature, all of which can be independently controlled. Room temperature storage of the stents was shown to be highly dependent on Tg and crosslink density. The pressurized response of the stents is also demonstrated to depend on crosslink density. This polymer system exhibits a wide range of shape-memory and thermomechanical responses to adapt and meet specific needs of minimally invasive cardiovascular devices. PMID:17296222

Cognitive and evoked response measures of information processing in schizophrenics with and without a family history of schizophrenia.

PubMed

Asarnow, R F; Cromwell, R L; Rennick, P M

1978-10-01

Twenty-four male schizophrenics, 12 (SFH) with schizophrenia in the immediate family and 12 (SNFH) with no evidence of schizophrenia in the family background, and 24 male control subjects, 12 highly educated (HEC), and 12 minimally educated (MEC), were assessed for premorbid social adjustment and were administered the Digit Symbol Substitution Test, a size estimation task, and the EEG average evoked response (AER) at different levels of stimulus intensity. As predicted from the stimulus redundancy formulation, the SFH patients were poorer in premorbid adjustment, were less often paranoid, functioned at a lower level of cognitive efficiency (poor digit symbol and greater absolute error on size estimation), were more chronic, and, in some respects, had size estimation indices of minimal scanning. Contrary to prediction, the SFH group had the strongest and most sustained augmenting response on AER, while the SNFH group shifted from an augmenting to a reducing pattern of response. The relationship between an absence of AER reducing and the presence of cognitive impairment in the SFH group was a major focus of discussion.

Challenges and solutions for realistic room simulation

NASA Astrophysics Data System (ADS)

Begault, Durand R.

2002-05-01

Virtual room acoustic simulation (auralization) techniques have traditionally focused on answering questions related to speech intelligibility or musical quality, typically in large volumetric spaces. More recently, auralization techniques have been found to be important for the externalization of headphone-reproduced virtual acoustic images. Although externalization can be accomplished using a minimal simulation, data indicate that realistic auralizations need to be responsive to head motion cues for accurate localization. Computational demands increase when providing for the simulation of coupled spaces, small rooms lacking meaningful reverberant decays, or reflective surfaces in outdoor environments. Auditory threshold data for both early reflections and late reverberant energy levels indicate that much of the information captured in acoustical measurements is inaudible, minimizing the intensive computational requirements of real-time auralization systems. Results are presented for early reflection thresholds as a function of azimuth angle, arrival time, and sound-source type, and reverberation thresholds as a function of reverberation time and level within 250-Hz-2-kHz octave bands. Good agreement is found between data obtained in virtual room simulations and those obtained in real rooms, allowing a strategy for minimizing computational requirements of real-time auralization systems.

Development of Point of Care Testing Device for Neurovascular Coupling From Simultaneous Recording of EEG and NIRS During Anodal Transcranial Direct Current Stimulation

PubMed Central

Jindal, Utkarsh; Sood, Mehak; Dutta, Anirban; Chowdhury, Shubhajit Roy

2015-01-01

This paper presents a point of care testing device for neurovascular coupling (NVC) from simultaneous recording of electroencephalogram (EEG) and near infrared spectroscopy (NIRS) during anodal transcranial direct current stimulation (tDCS). Here, anodal tDCS modulated cortical neural activity leading to hemodynamic response can be used to identify the impaired cerebral microvessels functionality. The impairments in the cerebral microvessels functionality may lead to impairments in the cerebrovascular reactivity (CVR), where severely reduced CVR predicts the chances of transient ischemic attack and ipsilateral stroke. The neural and hemodynamic responses to anodal tDCS were studied through joint imaging with EEG and NIRS, where NIRS provided optical measurement of changes in tissue oxy-(\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}$HbO2)$ \\end{document} and deoxy-(\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}$Hb$ \\end{document}) hemoglobin concentration and EEG captured alterations in the underlying neuronal current generators. Then, a cross-correlation method for the assessment of NVC underlying the site of anodal tDCS is presented. The feasibility studies on healthy subjects and stroke survivors showed detectable changes in the EEG and the NIRS responses to a 0.526 A/\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}$\\mathrm{m}^{2}$ \\end{document} of anodal tDCS. The NIRS system was bench tested on 15 healthy subjects that showed a statistically significant (p < 0.01) difference in the signal-to-noise ratio (SNR) between the ON- and OFF-states of anodal tDCS where the mean SNR of the NIRS device was found to be 42.33 ± 1.33 dB in the ON-state and 40.67 ± 1.23 dB in the OFF-state. Moreover, the clinical study conducted on 14 stroke survivors revealed that the lesioned hemisphere with impaired circulation showed significantly (p < 0.01) less change in \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}$HbO2$ \\end{document} than the nonlesioned side in response to anodal tDCS. The EEG study on healthy subjects showed a statistically significant (p < 0.05) decrease around individual alpha frequency in the alpha band (8−13 Hz) following anodal tDCS. Moreover, the joint EEG-NIRS imaging on 4 stroke survivors showed an immediate increase in the theta band (4−8 Hz) EEG activity after the start of anodal tDCS at the nonlesioned hemisphere. Furthermore, cross-correlation function revealed a significant (95% confidence interval) negative cross correlation only at the nonlesioned hemisphere during anodal tDCS, where the log-transformed mean-power of EEG within 0.5−11.25 Hz lagged \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}$HbO2$ \\end{document} response in one of the stroke survivors with white matter lesions. Therefore, it was concluded that the anodal tDCS can perturb the local neural and the vascular activity (via NVC) which can be used for assessing regional NVC functionality where confirmatory clinical studies are required. PMID:27170897

Niches in the urban forest: Organizations and their role in acquiring metropolitan open space.

Treesearch

Jane A. Ruliffson; Paul H. Gobster; Robert G. Haight; Francis R. Homans

2002-01-01

As a response strategy to minimize the impacts of urban sprawl, public and private organizations are striving to acquire open lands that will contribute to a resilient and multifunctional urban forest. In the Chicago metropolitan region, we interviewed representatives of 15 organizations to understand the land acquisition process--the structures and functions of...

The auditory brain-stem response to complex sounds: a potential biomarker for guiding treatment of psychosis.

PubMed

Tarasenko, Melissa A; Swerdlow, Neal R; Makeig, Scott; Braff, David L; Light, Gregory A

2014-01-01

Cognitive deficits limit psychosocial functioning in schizophrenia. For many patients, cognitive remediation approaches have yielded encouraging results. Nevertheless, therapeutic response is variable, and outcome studies consistently identify individuals who respond minimally to these interventions. Biomarkers that can assist in identifying patients likely to benefit from particular forms of cognitive remediation are needed. Here, we describe an event-related potential (ERP) biomarker - the auditory brain-stem response (ABR) to complex sounds (cABR) - that appears to be particularly well-suited for predicting response to at least one form of cognitive remediation that targets auditory information processing. Uniquely, the cABR quantifies the fidelity of sound encoded at the level of the brainstem and midbrain. This ERP biomarker has revealed auditory processing abnormalities in various neurodevelopmental disorders, correlates with functioning across several cognitive domains, and appears to be responsive to targeted auditory training. We present preliminary cABR data from 18 schizophrenia patients and propose further investigation of this biomarker for predicting and tracking response to cognitive interventions.

Characterizations of BC501A and BC537 liquid scintillator detectors.

PubMed

Qin, Jianguo; Lai, Caifeng; Ye, Bangjiao; Liu, Rong; Zhang, Xinwei; Jiang, Li

2015-10-01

Two 2″×2″ liquid scintillator detectors BC537 and BC501A have been characterized for their responses and efficiencies to γ-ray detection. Light output resolution and response functions were derived by least-squares minimization of a simulated response function, fitted to experimental data. The γ-ray response matrix and detection efficiency were simulated with Monte Carlo (MC) methods and validated. For photon energies below 2.4 MeVee, the resolution, as well as the efficiency, of BC501A is better than BC537 scintillator. The situation is reversed when the energy is higher than 2.4 MeVee. BC537 has higher γ-ray detection efficiency than BC501A if the impinging photon energy is more than 2 MeV due to different ratios of C to H/D atoms. Copyright © 2015 Elsevier Ltd. All rights reserved.

NEWSUMT: A FORTRAN program for inequality constrained function minimization, users guide

NASA Technical Reports Server (NTRS)

Miura, H.; Schmit, L. A., Jr.

1979-01-01

A computer program written in FORTRAN subroutine form for the solution of linear and nonlinear constrained and unconstrained function minimization problems is presented. The algorithm is the sequence of unconstrained minimizations using the Newton's method for unconstrained function minimizations. The use of NEWSUMT and the definition of all parameters are described.

Sparing functional anatomical structures during intensity-modulated radiotherapy: an old problem, a new solution.

PubMed

Tan, Wenyong; Han, Guang; Wei, Shaozhong; Hu, Desheng

2014-08-01

During intensity-modulated radiotherapy, an organ is usually assumed to be functionally homogeneous and, generally, its anatomical and spatial heterogeneity with respect to radiation response are not taken into consideration. However, advances in imaging and radiation techniques as well as an improved understanding of the radiobiological response of organs have raised the possibility of sparing the critical functional structures within various organs at risk during intensity-modulated radiotherapy. Here, we discuss these structures, which include the critical brain structure, or neural nuclei, and the nerve fiber tracts in the CNS, head and neck structures related to radiation-induced salivary and swallowing dysfunction, and functional structures in the heart and lung. We suggest that these structures can be used as potential surrogate organs at risk in order to minimize their radiation dose and/or irradiated volume without compromising the dose coverage of the target volume during radiation treatment.

Changing the S and MA [Safety and Mission Assurance] Paradigm

NASA Technical Reports Server (NTRS)

Malone, Roy W., Jr.

2010-01-01

Objectives: 1) Optimize S&MA organization to best facilitate Shuttle transition in 2010, successfully support Ares developmental responsibilities, and minimize the impacts of the gap between last Shuttle flight and start of Ares V Project. 2) Improve leveraging of critical skills and experience between Shuttle and Ares. 3) Split technical and supervisory functions to facilitate technical penetration. 4) Create Chief Safety and Mission Assurance Officer (CSO) stand-alone position for successfully implementation of S&MA Technical Authority. 5) Minimize disruption to customers. 6) Provide early involvement of S&MA leadership team and frequent/open communications with S&MA team members and steak-holders.

Application of higher harmonic blade feathering for helicopter vibration reduction

NASA Technical Reports Server (NTRS)

Powers, R. W.

1978-01-01

Higher harmonic blade feathering for helicopter vibration reduction is considered. Recent wind tunnel tests confirmed the effectiveness of higher harmonic control in reducing articulated rotor vibratory hub loads. Several predictive analyses developed in support of the NASA program were shown to be capable of calculating single harmonic control inputs required to minimize a single 4P hub response. In addition, a multiple-input, multiple-output harmonic control predictive analysis was developed. All techniques developed thus far obtain a solution by extracting empirical transfer functions from sampled data. Algorithm data sampling and processing requirements are minimal to encourage adaptive control system application of such techniques in a flight environment.

Minimally invasive surgery for esophageal achalasia.

PubMed

Chen, Huan-Wen; Du, Ming

2016-07-01

Esophageal achalasia is due to the esophagus of neuromuscular dysfunction caused by esophageal functional disease. Its main feature is the lack of esophageal peristalsis, the lower esophageal sphincter pressure and to reduce the swallow's relaxation response. Lower esophageal muscular dissection is one of the main ways to treat esophageal achalasia. At present, the period of muscular layer under the thoracoscope esophagus dissection is one of the treatment of esophageal achalasia. Combined with our experience in minimally invasive esophageal surgery, to improved incision and operation procedure, and adopts the model of the complete period of muscular layer under the thoracoscope esophagus dissection in the treatment of esophageal achalasia.

Minimally invasive surgery for esophageal achalasia

PubMed Central

Chen, Huan-Wen

2016-01-01

Esophageal achalasia is due to the esophagus of neuromuscular dysfunction caused by esophageal functional disease. Its main feature is the lack of esophageal peristalsis, the lower esophageal sphincter pressure and to reduce the swallow’s relaxation response. Lower esophageal muscular dissection is one of the main ways to treat esophageal achalasia. At present, the period of muscular layer under the thoracoscope esophagus dissection is one of the treatment of esophageal achalasia. Combined with our experience in minimally invasive esophageal surgery, to improved incision and operation procedure, and adopts the model of the complete period of muscular layer under the thoracoscope esophagus dissection in the treatment of esophageal achalasia. PMID:27499977

Intraoperative Functional Ultrasound Imaging of Human Brain Activity.

PubMed

Imbault, Marion; Chauvet, Dorian; Gennisson, Jean-Luc; Capelle, Laurent; Tanter, Mickael

2017-08-04

The functional mapping of brain activity is essential to perform optimal glioma surgery and to minimize the risk of postoperative deficits. We introduce a new, portable neuroimaging modality of the human brain based on functional ultrasound (fUS) for deep functional cortical mapping. Using plane-wave transmissions at an ultrafast frame rate (1 kHz), fUS is performed during surgery to measure transient changes in cerebral blood volume with a high spatiotemporal resolution (250 µm, 1 ms). fUS identifies, maps and differentiates regions of brain activation during task-evoked cortical responses within the depth of a sulcus in both awake and anaesthetized patients.

Time domain simulation of the response of geometrically nonlinear panels subjected to random loading

NASA Technical Reports Server (NTRS)

Moyer, E. Thomas, Jr.

1988-01-01

The response of composite panels subjected to random pressure loads large enough to cause geometrically nonlinear responses is studied. A time domain simulation is employed to solve the equations of motion. An adaptive time stepping algorithm is employed to minimize intermittent transients. A modified algorithm for the prediction of response spectral density is presented which predicts smooth spectral peaks for discrete time histories. Results are presented for a number of input pressure levels and damping coefficients. Response distributions are calculated and compared with the analytical solution of the Fokker-Planck equations. RMS response is reported as a function of input pressure level and damping coefficient. Spectral densities are calculated for a number of examples.

Restoring function in major depressive disorder: A systematic review.

PubMed

Sheehan, David V; Nakagome, Kazuyuki; Asami, Yuko; Pappadopulos, Elizabeth A; Boucher, Matthieu

2017-06-01

Functional impairment contributes to significant disability and economic burden in major depressive disorder (MDD). Treatment response is measured by improvement in depressive symptoms, but functional improvement often lags behind symptomatic improvement. Residual deficits are associated with relapse of depressive symptoms. A literature search was conducted using the following terms: "major depressive disorder," "functional impairment," "functional outcomes," "recovery of function," "treatment outcome," "outcome assessment," "social functioning," "presenteeism," "absenteeism," "psychiatric status rating scales," and "quality of life." Search limits included publication date (January 1, 1995 to August 31, 2016), English language, and human clinical trials. Controlled, acute-phase, nonrecurrent MDD treatment studies in adults were included if a functional outcome was measured at baseline and endpoint. The qualitative analysis included 35 controlled studies. The Sheehan Disability Scale was the most commonly used functional assessment. Antidepressant treatments significantly improved functional outcomes. Early treatment response predicted functional improvement, while baseline disease severity did not. Clinical studies utilized various methodologies and assessments for functional impairment, and were not standardized or adequately powered. The lack of synchronicity between symptomatic and functional improvement highlights an unmet need for MDD. Treatment guided by routine monitoring of symptoms and functionality may minimize residual functional impairments. Copyright © 2017. Published by Elsevier B.V.

Temperature fluctuations during deep temperature cryopreservation reduce PBMC recovery, viability and T-cell function.

PubMed

Germann, Anja; Oh, Young-Joo; Schmidt, Tomm; Schön, Uwe; Zimmermann, Heiko; von Briesen, Hagen

2013-10-01

The ability to analyze cryopreserved peripheral blood mononuclear cell (PBMC) from biobanks for antigen-specific immunity is necessary to evaluate response to immune-based therapies. To ensure comparable assay results, collaborative research in multicenter trials needs reliable and reproducible cryopreservation that maintains cell viability and functionality. A standardized cryopreservation procedure is comprised of not only sample collection, preparation and freezing but also low temperature storage in liquid nitrogen without any temperature fluctuations, to avoid cell damage. Therefore, we have developed a storage approach to minimize suboptimal storage conditions in order to maximize cell viability, recovery and T-cell functionality. We compared the influence of repeated temperature fluctuations on cell health from sample storage, sample sorting and removal in comparison to sample storage without temperature rises. We found that cyclical temperature shifts during low temperature storage reduce cell viability, recovery and immune response against specific-antigens. We showed that samples handled under a protective hood system, to avoid or minimize such repeated temperature rises, have comparable cell viability and cell recovery rates to samples stored without any temperature fluctuations. Also T-cell functionality could be considerably increased with the use of the protective hood system compared to sample handling without such a protection system. This data suggests that the impact of temperature fluctuation on cell integrity should be carefully considered in future clinical vaccine trials and consideration should be given to optimal sample storage conditions. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

The effect of micro-ECoG substrate footprint on the meningeal tissue response

NASA Astrophysics Data System (ADS)

Schendel, Amelia A.; Nonte, Michael W.; Vokoun, Corinne; Richner, Thomas J.; Brodnick, Sarah K.; Atry, Farid; Frye, Seth; Bostrom, Paige; Pashaie, Ramin; Thongpang, Sanitta; Eliceiri, Kevin W.; Williams, Justin C.

2014-08-01

Objective. There is great interest in designing implantable neural electrode arrays that maximize function while minimizing tissue effects and damage. Although it has been shown that substrate geometry plays a key role in the tissue response to intracortically implanted, penetrating neural interfaces, there has been minimal investigation into the effect of substrate footprint on the tissue response to surface electrode arrays. This study investigates the effect of micro-electrocorticography (micro-ECoG) device geometry on the longitudinal tissue response. Approach. The meningeal tissue response to two micro-ECoG devices with differing geometries was evaluated. The first device had each electrode site and trace individually insulated, with open regions in between, while the second device had a solid substrate, in which all 16 electrode sites were embedded in a continuous insulating sheet. These devices were implanted bilaterally in rats, beneath cranial windows, through which the meningeal tissue response was monitored for one month after implantation. Electrode site impedance spectra were also monitored during the implantation period. Main results. It was observed that collagenous scar tissue formed around both types of devices. However, the distribution of the tissue growth was different between the two array designs. The mesh devices experienced thick tissue growth between the device and the cranial window, and minimal tissue growth between the device and the brain, while the solid device showed the opposite effect, with thick tissue forming between the brain and the electrode sites. Significance. These data suggest that an open architecture device would be more ideal for neural recording applications, in which a low impedance path from the brain to the electrode sites is critical for maximum recording quality.

Identification of natural frequencies and modal damping ratios of aerospace structures from response data

NASA Technical Reports Server (NTRS)

Michalopoulos, C. D.

1976-01-01

An analysis of one and multidegree of freedom systems with classical damping is presented. Definition and minimization of error functions for each system are discussed. Systems with classical and nonclassical normal modes are studied, and results for first order perturbation are given. An alternative method of matching power spectral densities is provided, and numerical results are reviewed.

Selective antagonism of AMPA receptors unmasks kainate receptor-mediated responses in hippocampal neurons.

PubMed

Paternain, A V; Morales, M; Lerma, J

1995-01-01

Although both protein and mRNAs for kainate receptor subunits are abundant in several brain regions, the responsiveness of AMPA receptors to kainate has made it difficult to demonstrate the presence of functional kainate-type receptors in native cells. Recently, however, we have shown that many hippocampal neurons in culture express glutamate receptors of the kainate type. The large nondesensitizing response that kainate induces at AMPA receptors precludes detection and analysis of smaller, rapidly desensitizing currents induced by kainate at kainate receptors. Consequently, the functional significance of these strongly desensitizing glutamate receptors remains enigmatic. We report here that the family of new noncompetitive antagonists of AMPA receptors (GYKI 52466 and 53655) minimally affects kainate-induced responses at kainate receptors while completely blocking AMPA receptor-mediated currents, making it possible to separate the responses mediated by each receptor. These compounds will allow determination of the role played by kainate receptors in synaptic transmission and plasticity in the mammalian brain, as well as evaluation of their involvement in neurotoxicity.

Individualized Cognitive Modeling for Close-Loop Task Mitigation

NASA Technical Reports Server (NTRS)

Zhang, Guangfan; Xu, Roger; Wang, Wei; Li, Jiang; Schnell, Tom; Keller, Mike

2010-01-01

An accurate real-time operator functional state assessment makes it possible to perform task management, minimize risks, and improve mission performance. In this paper, we discuss the development of an individualized operator functional state assessment model that identifies states likely leading to operational errors. To address large individual variations, we use two different approaches to build a model for each individual using its data as well as data from subjects with similar responses. If a subject's response is similar to that of the individual of interest in a specific functional state, all the training data from this subject will be used to build the individual model. The individualization methods have been successfully verified and validated with a driving test data set provided by University of Iowa. With the individualized models, the mean squared error can be significantly decreased (by around 20%).

In Situ Poling and Imidization of Amorphous Piezoelectric Polyimides

NASA Technical Reports Server (NTRS)

Park, Cheol; Ounaies, Zoubeida; Wise, Kristopher E.; Harrison, Joycelyn S.; Bushnell, Dennis M. (Technical Monitor)

2002-01-01

An amorphous piezoelectric polyimide containing polar functional groups has been developed using a combination of experimental and molecular modeling for potential use in high temperature applications. This amorphous polyimide, (Beta-CN)APB/ODPA, has exhibited good thermal stability and piezoelectric response at temperatures up to 150C. Density functional calculations predicted that a partially cured amic acid (open imide ring) possesses a dipole moment four times larger than the fully imidized closed ring. In situ poling and imidization of the partially cured (Beta-CN)APB/ODPA, was studied in an attempt to maximize the degree of dipolar orientation and the resultant piezoelectric response. A positive corona poling was used to minimize localized arcing during poling and to allow use of higher poling fields without dielectric breakdown. The dielectric relaxation strength, remanent polarization, and piezoelectric response were evaluated as a function of the poling profile. The partially cured, corona poled polymers exhibited higher dielectric relaxation strength (delta varepsilon), remanent polarization (Pr) and piezoelectric strain coefficient (d33) than the fully cured, conventionally poled ones.

Evaluation of space shuttle main engine fluid dynamic frequency response characteristics

NASA Technical Reports Server (NTRS)

Gardner, T. G.

1980-01-01

In order to determine the POGO stability characteristics of the space shuttle main engine liquid oxygen (LOX) system, the fluid dynamic frequency response functions between elements in the SSME LOX system was evaluated, both analytically and experimentally. For the experimental data evaluation, a software package was written for the Hewlett-Packard 5451C Fourier analyzer. The POGO analysis software is documented and consists of five separate segments. Each segment is stored on the 5451C disc as an individual program and performs its own unique function. Two separate data reduction methods, a signal calibration, coherence or pulser signal based frequency response function blanking, and automatic plotting features are included in the program. The 5451C allows variable parameter transfer from program to program. This feature is used to advantage and requires only minimal user interface during the data reduction process. Experimental results are included and compared with the analytical predictions in order to adjust the general model and arrive at a realistic simulation of the POGO characteristics.

Construction of a pulse-coupled dipole network capable of fear-like and relief-like responses

NASA Astrophysics Data System (ADS)

Lungsi Sharma, B.

2016-07-01

The challenge for neuroscience as an interdisciplinary programme is the integration of ideas among the disciplines to achieve a common goal. This paper deals with the problem of deriving a pulse-coupled neural network that is capable of demonstrating behavioural responses (fear-like and relief-like). Current pulse-coupled neural networks are designed mostly for engineering applications, particularly image processing. The discovered neural network was constructed using the method of minimal anatomies approach. The behavioural response of a level-coded activity-based model was used as a reference. Although the spiking-based model and the activity-based model are of different scales, the use of model-reference principle means that the characteristics that is referenced is its functional properties. It is demonstrated that this strategy of dissection and systematic construction is effective in the functional design of pulse-coupled neural network system with nonlinear signalling. The differential equations for the elastic weights in the reference model are replicated in the pulse-coupled network geometrically. The network reflects a possible solution to the problem of punishment and avoidance. The network developed in this work is a new network topology for pulse-coupled neural networks. Therefore, the model-reference principle is a powerful tool in connecting neuroscience disciplines. The continuity of concepts and phenomena is further maintained by systematic construction using methods like the method of minimal anatomies.

Benchmarking B-Cell Epitope Prediction with Quantitative Dose-Response Data on Antipeptide Antibodies: Towards Novel Pharmaceutical Product Development

PubMed Central

Caoili, Salvador Eugenio C.

2014-01-01

B-cell epitope prediction can enable novel pharmaceutical product development. However, a mechanistically framed consensus has yet to emerge on benchmarking such prediction, thus presenting an opportunity to establish standards of practice that circumvent epistemic inconsistencies of casting the epitope prediction task as a binary-classification problem. As an alternative to conventional dichotomous qualitative benchmark data, quantitative dose-response data on antibody-mediated biological effects are more meaningful from an information-theoretic perspective in the sense that such effects may be expressed as probabilities (e.g., of functional inhibition by antibody) for which the Shannon information entropy (SIE) can be evaluated as a measure of informativeness. Accordingly, half-maximal biological effects (e.g., at median inhibitory concentrations of antibody) correspond to maximally informative data while undetectable and maximal biological effects correspond to minimally informative data. This applies to benchmarking B-cell epitope prediction for the design of peptide-based immunogens that elicit antipeptide antibodies with functionally relevant cross-reactivity. Presently, the Immune Epitope Database (IEDB) contains relatively few quantitative dose-response data on such cross-reactivity. Only a small fraction of these IEDB data is maximally informative, and many more of them are minimally informative (i.e., with zero SIE). Nevertheless, the numerous qualitative data in IEDB suggest how to overcome the paucity of informative benchmark data. PMID:24949474

Functional Connectivity Substrates for tDCS Response in Minimally Conscious State Patients

PubMed Central

Cavaliere, Carlo; Aiello, Marco; Di Perri, Carol; Amico, Enrico; Martial, Charlotte; Thibaut, Aurore; Laureys, Steven; Soddu, Andrea

2016-01-01

Transcranial direct current stimulation (tDCS) is a non-invasive technique recently employed in disorders of consciousness, and determining a transitory recovery of signs of consciousness in almost half of minimally conscious state (MCS) patients. Although the rising evidences about its possible role in the treatment of many neurological and psychiatric conditions exist, no evidences exist about brain functional connectivity substrates underlying tDCS response. We retrospectively evaluated resting state functional Magnetic Resonance Imaging (fMRI) of 16 sub-acute and chronic MCS patients (6 tDCS responders) who successively received a single left dorsolateral prefrontal cortex (DLPFC) tDCS in a double-blind randomized cross-over trial. A seed-based approach for regions of left extrinsic control network (ECN) and default-mode network (DMN) was performed. tDCS responders showed an increased left intra-network connectivity for regions co-activated with left DLPFC, and significantly with left inferior frontal gyrus. Non-responders (NR) MCS patients showed an increased connectivity between left DLPFC and midline cortical structures, including anterior cingulate cortex and precuneus. Our findings suggest that a prior high connectivity with regions belonging to ECN can facilitate transitory recovery of consciousness in a subgroup of MCS patients that underwent tDCS treatment. Therefore, resting state-fMRI could be very valuable in detecting the neuronal conditions necessary for tDCS to improve behavior in MCS. PMID:27857682

Optically based quantification of absolute cerebral metabolic rate of oxygen (CMRO2) with high spatial resolution in rodents

NASA Astrophysics Data System (ADS)

Yaseen, Mohammad A.; Srinivasan, Vivek J.; Sakadžić, Sava; Vinogradov, Sergei A.; Boas, David A.

2010-02-01

Measuring oxygen delivery in brain tissue is important for identifying the pathophysiological changes associated with brain injury and various diseases such as cancer, stroke, and Alzheimer's disease. We have developed a multi-modal imaging system for minimally invasive measurement of cerebral oxygenation and blood flow in small animals with high spatial resolution. The system allows for simultaneous measurement of blood flow using Fourier-domain optical coherence tomography, and oxygen partial pressure (pO2) using either confocal or multiphoton phosphorescence lifetime imaging with exogenous porphyrin-based dyes sensitive to dissolved oxygen. Here we present the changes in pO2 and blood flow in superficial cortical vessels of Sprague Dawley rats in response to conditions such as hypoxia, hyperoxia, and functional stimulation. pO2 measurements display considerable heterogeneity over distances that cannot be resolved with more widely used oxygen-monitoring techniques such as BOLD-fMRI. Large increases in blood flow are observed in response to functional stimulation and hypoxia. Our system allows for quantification of cerebral metabolic rate of oxygen (CMRO2) with high spatial resolution, providing a better understanding of metabolic dynamics during functional stimulation and under various neuropathologies. Ultimately, better insight into the underlying mechanisms of neuropathologies will facilitate the development of improved therapeutic strategies to minimize damage to brain tissue.

Functional Connectivity Substrates for tDCS Response in Minimally Conscious State Patients.

PubMed

Cavaliere, Carlo; Aiello, Marco; Di Perri, Carol; Amico, Enrico; Martial, Charlotte; Thibaut, Aurore; Laureys, Steven; Soddu, Andrea

2016-01-01

Transcranial direct current stimulation (tDCS) is a non-invasive technique recently employed in disorders of consciousness, and determining a transitory recovery of signs of consciousness in almost half of minimally conscious state (MCS) patients. Although the rising evidences about its possible role in the treatment of many neurological and psychiatric conditions exist, no evidences exist about brain functional connectivity substrates underlying tDCS response. We retrospectively evaluated resting state functional Magnetic Resonance Imaging (fMRI) of 16 sub-acute and chronic MCS patients (6 tDCS responders) who successively received a single left dorsolateral prefrontal cortex (DLPFC) tDCS in a double-blind randomized cross-over trial. A seed-based approach for regions of left extrinsic control network (ECN) and default-mode network (DMN) was performed. tDCS responders showed an increased left intra-network connectivity for regions co-activated with left DLPFC, and significantly with left inferior frontal gyrus. Non-responders (NR) MCS patients showed an increased connectivity between left DLPFC and midline cortical structures, including anterior cingulate cortex and precuneus. Our findings suggest that a prior high connectivity with regions belonging to ECN can facilitate transitory recovery of consciousness in a subgroup of MCS patients that underwent tDCS treatment. Therefore, resting state-fMRI could be very valuable in detecting the neuronal conditions necessary for tDCS to improve behavior in MCS.

Psychometric properties of self-reported questionnaires for the evaluation of symptoms and functional limitations in individuals with rotator cuff disorders: a systematic review.

PubMed

St-Pierre, Corinne; Desmeules, François; Dionne, Clermont E; Frémont, Pierre; MacDermid, Joy C; Roy, Jean-Sébastien

2016-01-01

To conduct a systematic review of the psychometric properties (reliability, validity and responsiveness) of self-report questionnaires used to assess symptoms and functional limitations of individuals with rotator cuff (RC) disorders. A systematic search in three databases (Cinahl, Medline and Embase) was conducted. Data extraction and critical methodological appraisal were performed independently by three raters using structured tools, and agreement was achieved by consensus. A descriptive synthesis was performed. One-hundred and twenty articles reporting on 11 questionnaires were included. All questionnaires were highly reliable and responsive to change, and showed construct validity; seven questionnaires also shown known-group validity. The minimal detectable change ranged from 6.4% to 20.8% of total score; only two questionnaires (American Shoulder and Elbow Surgeon questionnaire [ASES] and Upper Limb Functional Index [ULFI]) had a measurement error below 10% of global score. Minimal clinically important differences were established for eight questionnaires, and ranged from 8% to 20% of total score. Overall, included questionnaires showed acceptable psychometric properties for individuals with RC disorders. The ASES and ULFI have the smallest absolute error of measurement, while the Western Ontario RC Index is one of the most responsive questionnaires for individuals suffering from RC disorders. All included questionnaires are reliable, valid and responsive for the evaluation of individuals with RC disorders. As all included questionnaires showed good psychometric properties for the targeted population, the choice should be made according to the purpose of the evaluation and to the construct being evaluated by the questionnaire. The WORC, a RC-specific questionnaire, appeared to be more responsive. It should therefore be used to evaluate change in time. If the evaluation is time-limited, shorter questionnaires or short versions should be considered (such as Quick DASH or SST).

Early detection of consciousness in patients with acute severe traumatic brain injury.

PubMed

Edlow, Brian L; Chatelle, Camille; Spencer, Camille A; Chu, Catherine J; Bodien, Yelena G; O'Connor, Kathryn L; Hirschberg, Ronald E; Hochberg, Leigh R; Giacino, Joseph T; Rosenthal, Eric S; Wu, Ona

2017-09-01

See Schiff (doi:10.1093/awx209) for a scientific commentary on this article. Patients with acute severe traumatic brain injury may recover consciousness before self-expression. Without behavioural evidence of consciousness at the bedside, clinicians may render an inaccurate prognosis, increasing the likelihood of withholding life-sustaining therapies or denying rehabilitative services. Task-based functional magnetic resonance imaging and electroencephalography techniques have revealed covert consciousness in the chronic setting, but these techniques have not been tested in the intensive care unit. We prospectively enrolled 16 patients admitted to the intensive care unit for acute severe traumatic brain injury to test two hypotheses: (i) in patients who lack behavioural evidence of language expression and comprehension, functional magnetic resonance imaging and electroencephalography detect command-following during a motor imagery task (i.e. cognitive motor dissociation) and association cortex responses during language and music stimuli (i.e. higher-order cortex motor dissociation); and (ii) early responses to these paradigms are associated with better 6-month outcomes on the Glasgow Outcome Scale-Extended. Patients underwent functional magnetic resonance imaging on post-injury Day 9.2 ± 5.0 and electroencephalography on Day 9.8 ± 4.6. At the time of imaging, behavioural evaluation with the Coma Recovery Scale-Revised indicated coma (n = 2), vegetative state (n = 3), minimally conscious state without language (n = 3), minimally conscious state with language (n = 4) or post-traumatic confusional state (n = 4). Cognitive motor dissociation was identified in four patients, including three whose behavioural diagnosis suggested a vegetative state. Higher-order cortex motor dissociation was identified in two additional patients. Complete absence of responses to language, music and motor imagery was only observed in coma patients. In patients with behavioural evidence of language function, responses to language and music were more frequently observed than responses to motor imagery (62.5-80% versus 33.3-42.9%). Similarly, in 16 matched healthy subjects, responses to language and music were more frequently observed than responses to motor imagery (87.5-100% versus 68.8-75.0%). Except for one patient who died in the intensive care unit, all patients with cognitive motor dissociation and higher-order cortex motor dissociation recovered beyond a confusional state by 6 months. However, 6-month outcomes were not associated with early functional magnetic resonance imaging and electroencephalography responses for the entire cohort. These observations suggest that functional magnetic resonance imaging and electroencephalography can detect command-following and higher-order cortical function in patients with acute severe traumatic brain injury. Early detection of covert consciousness and cortical responses in the intensive care unit could alter time-sensitive decisions about withholding life-sustaining therapies. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Rudimentary Reading Repertoires via Stimulus Equivalence and Recombination of Minimal Verbal Units

PubMed Central

Matos, Maria Amelia; Avanzi, Alessandra Lopes; McIlvane, William J

2006-01-01

We report a study with sixteen low-SES Brazilian children that sought to establish a repertoire of relations involving dictated words, printed words, and corresponding pictures. Children were taught: (1) in response to dictated words, to select corresponding pictures; (2) in response to syllables presented in both visual and auditory formats, to select words which contained a corresponding syllable in either the first or the last position; (3) in response to dictated-word samples, to “construct” corresponding printed words via arranging their constituent syllabic components; and (4) in response to printed word samples, to construct identical printed words by arranging their syllabic constituents. After training on the first two types of tasks, children were given tests for potentially emergent relations involving printed words and pictures. Almost all exhibited relations consistent with stimulus equivalence. They also displayed emergent naming performances––not only with training words but also with new words that were recombinations of their constituent syllables. The present work was inspired by Sidman's stimulus equivalence paradigm and by Skinner's functional analysis of verbal relations, particularly as applied to conceptions of minimal behavioral units and creativity (i.e., behavioral flexibility) in the analytical units applied to verbal relations. PMID:22477340

Density and delay of punishment of free-operant avoidance1

PubMed Central

Baron, Alan; Kaufman, Arnold; Fazzini, Dan

1969-01-01

In two experiments, the free-operant shock-avoidance behavior of rats was punished by electric shock. Two aspects of the schedule of response-produced shock were varied: the frequency of punishment over time (punishment density) and the temporal interval between the punished response and the punishment (punishment delay). The general finding was that response-produced shock suppressed avoidance responding under most of the density-delay combinations studied, and suppression increased as a function of increases in density and decreases in delay. Rate increases of small magnitude also were observed, usually as an initial reaction to the lesser densities and longer delays. Response suppression, while decreasing the number of punishment shocks received, also increased the number of avoidance shocks, so that the total number of shocks received usually was greater than the minimal number possible. The results were discussed from the standpoint of similarities between the effects of punishing positively and negatively reinforced behavior. The finding that subjects did not minimize the total number of shocks suggested that when avoidance behavior is punished, responding is controlled more by the local consequences of responding than by overall shock frequencies during the course of the session. PMID:16811408

What energy functions can be minimized via graph cuts?

PubMed

Kolmogorov, Vladimir; Zabih, Ramin

2004-02-01

In the last few years, several new algorithms based on graph cuts have been developed to solve energy minimization problems in computer vision. Each of these techniques constructs a graph such that the minimum cut on the graph also minimizes the energy. Yet, because these graph constructions are complex and highly specific to a particular energy function, graph cuts have seen limited application to date. In this paper, we give a characterization of the energy functions that can be minimized by graph cuts. Our results are restricted to functions of binary variables. However, our work generalizes many previous constructions and is easily applicable to vision problems that involve large numbers of labels, such as stereo, motion, image restoration, and scene reconstruction. We give a precise characterization of what energy functions can be minimized using graph cuts, among the energy functions that can be written as a sum of terms containing three or fewer binary variables. We also provide a general-purpose construction to minimize such an energy function. Finally, we give a necessary condition for any energy function of binary variables to be minimized by graph cuts. Researchers who are considering the use of graph cuts to optimize a particular energy function can use our results to determine if this is possible and then follow our construction to create the appropriate graph. A software implementation is freely available.

Responsiveness of SF-36 and Lower Extremity Functional Scale for assessing outcomes in traumatic injuries of lower extremities.

PubMed

Pan, Shin-Liang; Liang, Huey-Wen; Hou, Wen-Hsuan; Yeh, Tian-Shin

2014-11-01

To assess the responsiveness of one generic questionnaire, Medical Outcomes Study Short Form-36 (SF-36), and one region-specific outcome measure, Lower Extremity Functional Scale (LEFS), in patients with traumatic injuries of lower extremities. A prospective and observational study of patients after traumatic injuries of lower extremities. Assessments were performed at baseline and 3 months later. In-patients and out-patients in two university hospitals in Taiwan. A convenience sample of 109 subjects were evaluated and 94 (86%) were followed. Not applicable. Assessments of responsiveness with distribution-based approach (effect size, standardized response mean [SRM], minimal detectable change) and anchor-based approach (receiver's operating curve analysis, ROC analysis). LEFS and physical component score (PCS) of SF-36 were all responsive to global improvement, with fair-to-good accuracy in discriminating between participants with and without improvement. The area under curve gained by ROC analysis for LEFS and SF-36 PCS was similar (0.65 vs. 0.70, p=0.26). Our findings revealed comparable responsiveness of LEFS and PCS of SF-36 in a sample of subjects with traumatic injuries of lower limbs. Either type of functional measure would be suitable for use in clinical trials where improvement in function was an endpoint of interest. Copyright © 2014 Elsevier Ltd. All rights reserved.

Prostatic arterial embolization: post-procedural follow-up.

PubMed

Fernandes, Lucia; Rio Tinto, Hugo; Pereira, Jose; Duarte, Marisa; Bilhim, Tiago; Martins Pisco, João

2012-12-01

Prostatic arterial embolization (PAE) gained special attention in the past years as a potential minimally invasive technique for benign prostatic hyperplasia. Treatment decisions are based on morbidity and quality-of-life issues and the patient has a central role in decision-making. Medical therapy is a first-line treatment option and surgery is usually performed to improve symptoms and decrease the progression of disease in patients who develop complications or who have inadequately controlled symptoms on medical treatment. The use of validated questionnaires to assess disease severity and sexual function, uroflowmetry studies, prostate-specific antigen and prostate volume measurements are essential when evaluating patients before PAE and to evaluate response to treatment. PAE may be performed safely with minimal morbidity and without associated mortality. The minimally invasive nature of the technique inducing a significant improvement in symptom severity associated with prostate volume reduction and a slight improvement in the sexual function are major advantages. However, as with other surgical therapies for benign prostatic hyperplasia, up to 15% of patients fail to show improvement significantly after PAE, and there is a modest improvement of the peak urinary flow. Copyright © 2012 Elsevier Inc. All rights reserved.

Nonlinear transient analysis by energy minimization: A theoretical basis for the ACTION computer code. [predicting the response of a lightweight aircraft during a crash

NASA Technical Reports Server (NTRS)

Kamat, M. P.

1980-01-01

The formulation basis for establishing the static or dynamic equilibrium configurations of finite element models of structures which may behave in the nonlinear range are provided. With both geometric and time independent material nonlinearities included, the development is restricted to simple one and two dimensional finite elements which are regarded as being the basic elements for modeling full aircraft-like structures under crash conditions. Representations of a rigid link and an impenetrable contact plane are added to the deformation model so that any number of nodes of the finite element model may be connected by a rigid link or may contact the plane. Equilibrium configurations are derived as the stationary conditions of a potential function of the generalized nodal variables of the model. Minimization of the nonlinear potential function is achieved by using the best current variable metric update formula for use in unconstrained minimization. Powell's conjugate gradient algorithm, which offers very low storage requirements at some slight increase in the total number of calculations, is the other alternative algorithm to be used for extremely large scale problems.

Ultraviolet-B radiation increases serum 25-hydroxyvitamin D levels: the effect of UVB dose and skin color.

PubMed

Armas, Laura A G; Dowell, Susan; Akhter, Mohammed; Duthuluru, Sowjanya; Huerter, Christopher; Hollis, Bruce W; Lund, Richard; Heaney, Robert P

2007-10-01

Ultraviolet (UV)-B light increases vitamin D levels, but the dose response and the effect of skin pigmentation have not been well characterized. We sought to define the relationship between UVB exposure and 25-hydroxyvitamin D (25-OH-D) concentrations as a function of skin pigmentation. Seventy two participants with various skin tones had 90% of their skin exposed to UVB light (20-80 mJ/cm2) 3 times a week for 4 weeks. Serum 25-OH-D was measured weekly. Eighty percent of the variation in treatment response was explained by UVB dose and skin tone. Therapeutically important changes in 25-OH-D were achieved with minimal tanning. Four weeks was not long enough to reach a steady state at the higher dose rates. The response of 25-OH-D levels to UVB light is dependent on skin pigmentation and the amount of UVB given, and useful increases in vitamin D status can be achieved by defined UVB doses small enough to produce only minimal tanning.

Challenges to the successful implementation of 3-D sound

NASA Astrophysics Data System (ADS)

Begault, Durand R.

1991-11-01

The major challenges for the successful implementation of 3-D audio systems involve minimizing reversals, intracranially heard sound, and localization error for listeners. Designers of 3-D audio systems are faced with additional challenges in data reduction and low-frequency response characteristics. The relationship of the head-related transfer function (HRTF) to these challenges is shown, along with some preliminary psychoacoustic results gathered at NASA-Ames.

The Oral Minimal Model Method

PubMed Central

Cobelli, Claudio; Dalla Man, Chiara; Toffolo, Gianna; Basu, Rita; Vella, Adrian; Rizza, Robert

2014-01-01

The simultaneous assessment of insulin action, secretion, and hepatic extraction is key to understanding postprandial glucose metabolism in nondiabetic and diabetic humans. We review the oral minimal method (i.e., models that allow the estimation of insulin sensitivity, β-cell responsivity, and hepatic insulin extraction from a mixed-meal or an oral glucose tolerance test). Both of these oral tests are more physiologic and simpler to administer than those based on an intravenous test (e.g., a glucose clamp or an intravenous glucose tolerance test). The focus of this review is on indices provided by physiological-based models and their validation against the glucose clamp technique. We discuss first the oral minimal model method rationale, data, and protocols. Then we present the three minimal models and the indices they provide. The disposition index paradigm, a widely used β-cell function metric, is revisited in the context of individual versus population modeling. Adding a glucose tracer to the oral dose significantly enhances the assessment of insulin action by segregating insulin sensitivity into its glucose disposal and hepatic components. The oral minimal model method, by quantitatively portraying the complex relationships between the major players of glucose metabolism, is able to provide novel insights regarding the regulation of postprandial metabolism. PMID:24651807

The Auditory Brain-Stem Response to Complex Sounds: A Potential Biomarker for Guiding Treatment of Psychosis

PubMed Central

Tarasenko, Melissa A.; Swerdlow, Neal R.; Makeig, Scott; Braff, David L.; Light, Gregory A.

2014-01-01

Cognitive deficits limit psychosocial functioning in schizophrenia. For many patients, cognitive remediation approaches have yielded encouraging results. Nevertheless, therapeutic response is variable, and outcome studies consistently identify individuals who respond minimally to these interventions. Biomarkers that can assist in identifying patients likely to benefit from particular forms of cognitive remediation are needed. Here, we describe an event-related potential (ERP) biomarker – the auditory brain-stem response (ABR) to complex sounds (cABR) – that appears to be particularly well-suited for predicting response to at least one form of cognitive remediation that targets auditory information processing. Uniquely, the cABR quantifies the fidelity of sound encoded at the level of the brainstem and midbrain. This ERP biomarker has revealed auditory processing abnormalities in various neurodevelopmental disorders, correlates with functioning across several cognitive domains, and appears to be responsive to targeted auditory training. We present preliminary cABR data from 18 schizophrenia patients and propose further investigation of this biomarker for predicting and tracking response to cognitive interventions. PMID:25352811

Efficient data communication protocols for wireless networks

NASA Astrophysics Data System (ADS)

Zeydan, Engin

In this dissertation, efficient decentralized algorithms are investigated for cost minimization problems in wireless networks. For wireless sensor networks, we investigate both the reduction in the energy consumption and throughput maximization problems separately using multi-hop data aggregation for correlated data in wireless sensor networks. The proposed algorithms exploit data redundancy using a game theoretic framework. For energy minimization, routes are chosen to minimize the total energy expended by the network using best response dynamics to local data. The cost function used in routing takes into account distance, interference and in-network data aggregation. The proposed energy-efficient correlation-aware routing algorithm significantly reduces the energy consumption in the network and converges in a finite number of steps iteratively. For throughput maximization, we consider both the interference distribution across the network and correlation between forwarded data when establishing routes. Nodes along each route are chosen to minimize the interference impact in their neighborhood and to maximize the in-network data aggregation. The resulting network topology maximizes the global network throughput and the algorithm is guaranteed to converge with a finite number of steps using best response dynamics. For multiple antenna wireless ad-hoc networks, we present distributed cooperative and regret-matching based learning schemes for joint transmit beanformer and power level selection problem for nodes operating in multi-user interference environment. Total network transmit power is minimized while ensuring a constant received signal-to-interference and noise ratio at each receiver. In cooperative and regret-matching based power minimization algorithms, transmit beanformers are selected from a predefined codebook to minimize the total power. By selecting transmit beamformers judiciously and performing power adaptation, the cooperative algorithm is shown to converge to pure strategy Nash equilibrium with high probability throughout the iterations in the interference impaired network. On the other hand, the regret-matching learning algorithm is noncooperative and requires minimum amount of overhead. The proposed cooperative and regret-matching based distributed algorithms are also compared with centralized solutions through simulation results.

Responsible gambling: general principles and minimal requirements.

PubMed

Blaszczynski, Alex; Collins, Peter; Fong, Davis; Ladouceur, Robert; Nower, Lia; Shaffer, Howard J; Tavares, Hermano; Venisse, Jean-Luc

2011-12-01

Many international jurisdictions have introduced responsible gambling programs. These programs intend to minimize negative consequences of excessive gambling, but vary considerably in their aims, focus, and content. Many responsible gambling programs lack a conceptual framework and, in the absence of empirical data, their components are based only on general considerations and impressions. This paper outlines the consensus viewpoint of an international group of researchers suggesting fundamental responsible gambling principles, roles of key stakeholders, and minimal requirements that stakeholders can use to frame and inform responsible gambling programs across jurisdictions. Such a framework does not purport to offer value statements regarding the legal status of gambling or its expansion. Rather, it proposes gambling-related initiatives aimed at government, industry, and individuals to promote responsible gambling and consumer protection. This paper argues that there is a set of basic principles and minimal requirements that should form the basis for every responsible gambling program.

Progression from Vegetative to Minimally Conscious State Is Associated with Changes in Brain Neural Response to Passive Tasks: A Longitudinal Single-Case Functional MRI Study.

PubMed

Tomaiuolo, Francesco; Cecchetti, Luca; Gibson, Raechelle M; Logi, Fiammetta; Owen, Adrian M; Malasoma, Franco; Cozza, Sabino; Pietrini, Pietro; Ricciardi, Emiliano

2016-07-01

Functional magnetic resonance imaging (fMRI) may be adopted as a complementary tool for bedside observation in the disorders of consciousness (DOC). However, the diagnostic value of this technique is still debated because of the lack of accuracy in determining levels of consciousness within a single patient. Recently, Giacino and colleagues (2014) hypothesized that a longitudinal fMRI evaluation may provide a more informative assessment in the detection of residual awareness. The aim of this study was to measure the correspondence between clinically defined level of awareness and neural responses within a single DOC patient. We used a follow-up fMRI design in combination with a passive speech-processing task. Patient's consciousness was measured through time by using the Coma Recovery Scale. The patient progressed from a vegetative state (VS) to a minimally conscious state (MCS). Patient's task-related neural responses mirrored the clinical change from a VS to an MCS. Specifically, while in an MCS, but not a VS, the patient showed a selective recruitment of the left angular gyrus when he listened to a native speech narrative, as compared to the reverse presentation of the same stimulus. Furthermore, the patient showed an increased response in the language-related brain network and a greater deactivation in the default mode network following his progression to an MCS. Our findings indicate that longitudinal assessment of brain responses to passive stimuli can contribute to the definition of the clinical status in individual patients with DOC and represents an adequate counterpart of the bedside assessment during the diagnostic decision-making process. (JINS, 2016, 22, 620-630).

Functional characterization of blue-light-induced responses and PHOTOTROPIN 1 gene in Welwitschia mirabilis.

PubMed

Ishishita, Kazuhiro; Suetsugu, Noriyuki; Hirose, Yuki; Higa, Takeshi; Doi, Michio; Wada, Masamitsu; Matsushita, Tomonao; Gotoh, Eiji

2016-03-01

The blue light (BL) receptor phototropin (phot) is specifically found in green plants; it regulates various BL-induced responses such as phototropism, chloroplast movement, stomatal opening, and leaf flattening. In Arabidopsis thaliana, two phototropins--phot1 and phot2--respond to blue light in overlapping but distinct ways. These BL-receptor-mediated responses enhance the photosynthetic activity of plants under weak light and minimize photodamage under strong light conditions. Welwitschia mirabilis Hook.f. found in the Namib Desert, and it has adapted to severe environmental stresses such as limiting water and strong sunlight. Although the plant has physiologically and ecologically unique features, it is unknown whether phototropin is functional in this plant. In this study, we assessed the functioning of phot-mediated BL responses in W. mirabilis. BL-dependent phototropism and stomatal opening was observed but light-dependent chloroplast movement was not detected. We performed a functional analysis of the PHOT1 gene of W. mirabilis, WmPHOT1, in Arabidopsis thaliana. We generated transgenic A. thaliana lines expressing WmPHOT1 in a phot1 phot2 double mutant background. Several Wmphot1 transgenic plants showed normal growth, although phot1 phot2 double mutant plants showed stunted growth. Furthermore, Wmphot1 transgenic plants showed normal phot1-mediated responses including phototropism, chloroplast accumulation, stomatal opening, and leaf flattening, but lacked the chloroplast avoidance response that is specifically mediated by phot2. Thus, our findings indicate that W. mirabilis possesses typical phot-mediated BL responses that were at least partially mediated by functional phototropin 1, an ortholog of Atphot1.

Ho:YAG laser arthroscopy of the knee

NASA Astrophysics Data System (ADS)

Sisto, Domenick J.; Blazina, Martin E.; Hirsh, Linda C.

1994-09-01

The HO:YAG laser is a near-contact laser with a capacity to ablate or cut tissues. The ablation function allows the surgeon to remove meniscal tissue, lyse and resect adhesions, melt loose bodies, and dissolve inflamed synovium. The cutting function of the laser is utilized to perform a lateral release or resect torn menisci. The laser can also be utilized to drill holes in Grade IV chondromalacic lesions to initiate a healing response. The laser has been embraced by orthopaedic surgeons because of its shape and versatility. The tip is only 2 mm wide and can be delivered into the tight posterior compartments of the knee with no damaging contact with the articular surfaces. The laser coagulates as it works and bleeding is minimized. The laser can function both as a cutting and ablating tool. The laser can also drill holes into subchondral bone to, hopefully, initiate a healing response.

Comparison of polynomial approximations and artificial neural nets for response surfaces in engineering optimization

NASA Technical Reports Server (NTRS)

Carpenter, William C.

1991-01-01

Engineering optimization problems involve minimizing some function subject to constraints. In areas such as aircraft optimization, the constraint equations may be from numerous disciplines such as transfer of information between these disciplines and the optimization algorithm. They are also suited to problems which may require numerous re-optimizations such as in multi-objective function optimization or to problems where the design space contains numerous local minima, thus requiring repeated optimizations from different initial designs. Their use has been limited, however, by the fact that development of response surfaces randomly selected or preselected points in the design space. Thus, they have been thought to be inefficient compared to algorithms to the optimum solution. A development has taken place in the last several years which may effect the desirability of using response surfaces. It may be possible that artificial neural nets are more efficient in developing response surfaces than polynomial approximations which have been used in the past. This development is the concern of the work.

Minimization of a Class of Matrix Trace Functions by Means of Refined Majorization.

ERIC Educational Resources Information Center

Kiers, Henk A. L.; ten Berge, Jos M. F.

1992-01-01

A procedure is described for minimizing a class of matrix trace functions, which is a refinement of an earlier procedure for minimizing the class of matrix trace functions using majorization. Several trial analyses demonstrate that the revised procedure is more efficient than the earlier majorization-based procedure. (SLD)

The hydroclimatic and ecophysiological basis of cloud forest distributions under current and projected climates

PubMed Central

Oliveira, Rafael S.; Eller, Cleiton B.; Bittencourt, Paulo R. L.; Mulligan, Mark

2014-01-01

Background Tropical montane cloud forests (TMCFs) are characterized by a unique set of biological and hydroclimatic features, including frequent and/or persistent fog, cool temperatures, and high biodiversity and endemism. These forests are one of the most vulnerable ecosystems to climate change given their small geographic range, high endemism and dependence on a rare microclimatic envelope. The frequency of atmospheric water deficits for some TMCFs is likely to increase in the future, but the consequences for the integrity and distribution of these ecosystems are uncertain. In order to investigate plant and ecosystem responses to climate change, we need to know how TMCF species function in response to current climate, which factors shape function and ecology most and how these will change into the future. Scope This review focuses on recent advances in ecophysiological research of TMCF plants to establish a link between TMCF hydrometeorological conditions and vegetation distribution, functioning and survival. The hydraulic characteristics of TMCF trees are discussed, together with the prevalence and ecological consequences of foliar uptake of fog water (FWU) in TMCFs, a key process that allows efficient acquisition of water during cloud immersion periods, minimizing water deficits and favouring survival of species prone to drought-induced hydraulic failure. Conclusions Fog occurrence is the single most important microclimatic feature affecting the distribution and function of TMCF plants. Plants in TMCFs are very vulnerable to drought (possessing a small hydraulic safety margin), and the presence of fog and FWU minimizes the occurrence of tree water deficits and thus favours the survival of TMCF trees where such deficits may occur. Characterizing the interplay between microclimatic dynamics and plant water relations is key to foster more realistic projections about climate change effects on TMCF functioning and distribution. PMID:24759267

Minimally verbal school-aged children with autism spectrum disorder: the neglected end of the spectrum.

PubMed

Tager-Flusberg, Helen; Kasari, Connie

2013-12-01

It is currently estimated that about 30% of children with autism spectrum disorder remain minimally verbal, even after receiving years of interventions and a range of educational opportunities. Very little is known about the individuals at this end of the autism spectrum, in part because this is a highly variable population with no single set of defining characteristics or patterns of skills or deficits, and in part because it is extremely challenging to provide reliable or valid assessments of their developmental functioning. In this paper, we summarize current knowledge based on research including minimally verbal children. We review promising new novel methods for assessing the verbal and nonverbal abilities of minimally verbal school-aged children, including eye-tracking and brain-imaging methods that do not require overt responses. We then review what is known about interventions that may be effective in improving language and communication skills, including discussion of both nonaugmentative and augmentative methods. In the final section of the paper, we discuss the gaps in the literature and needs for future research. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.

The Eng1 β-Glucanase Enhances Histoplasma Virulence by Reducing β-Glucan Exposure

PubMed Central

Garfoot, Andrew L.; Shen, Qian; Wüthrich, Marcel; Klein, Bruce S.

2016-01-01

ABSTRACT The fungal pathogen Histoplasma capsulatum parasitizes host phagocytes. To avoid antimicrobial immune responses, Histoplasma yeasts must minimize their detection by host receptors while simultaneously interacting with the phagocyte. Pathogenic Histoplasma yeast cells, but not avirulent mycelial cells, secrete the Eng1 protein, which is a member of the glycosylhydrolase 81 (GH81) family. We show that Histoplasma Eng1 is a glucanase that hydrolyzes β-(1,3)-glycosyl linkages but is not required for Histoplasma growth in vitro or for cell separation. However, Histoplasma yeasts lacking Eng1 function have attenuated virulence in vivo, particularly during the cell-mediated immunity stage. Histoplasma yeasts deficient for Eng1 show increased exposure of cell wall β-glucans, which results in enhanced binding to the Dectin-1 β-glucan receptor. Consistent with this, Eng1-deficient yeasts trigger increased tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) cytokine production from macrophages and dendritic cells. While not responsible for large-scale cell wall structure and function, the secreted Eng1 reduces levels of exposed β-glucans at the yeast cell wall, thereby diminishing potential recognition by Dectin-1 and proinflammatory cytokine production by phagocytes. In α-glucan-producing Histoplasma strains, Eng1 acts in concert with α-glucan to minimize β-glucan exposure: α-glucan provides a masking function by covering the β-glucan-rich cell wall, while Eng1 removes any remaining exposed β-glucans. Thus, Histoplasma Eng1 has evolved a specialized pathogenesis function to remove exposed β-glucans, thereby enhancing the ability of yeasts to escape detection by host phagocytes. PMID:27094334

Propagation of Computational Uncertainty Using the Modern Design of Experiments

NASA Technical Reports Server (NTRS)

DeLoach, Richard

2007-01-01

This paper describes the use of formally designed experiments to aid in the error analysis of a computational experiment. A method is described by which the underlying code is approximated with relatively low-order polynomial graduating functions represented by truncated Taylor series approximations to the true underlying response function. A resource-minimal approach is outlined by which such graduating functions can be estimated from a minimum number of case runs of the underlying computational code. Certain practical considerations are discussed, including ways and means of coping with high-order response functions. The distributional properties of prediction residuals are presented and discussed. A practical method is presented for quantifying that component of the prediction uncertainty of a computational code that can be attributed to imperfect knowledge of independent variable levels. This method is illustrated with a recent assessment of uncertainty in computational estimates of Space Shuttle thermal and structural reentry loads attributable to ice and foam debris impact on ascent.

Comparative responsiveness and minimal clinically important differences for idiopathic ulnar impaction syndrome.

PubMed

Kim, Jae Kwang; Park, Eun Soo

2013-05-01

Patient-reported questionnaires have been widely used to predict symptom severity and functional disability in musculoskeletal disease. Importantly, questionnaires can detect clinical changes in patients; however, this impact has not been determined for ulnar impaction syndrome. We asked (1) which of Patient-Rated Wrist Evaluation (PRWE), DASH, and other physical measures was more responsive to clinical improvements, and (2) what was the minimal clinically important difference for the PRWE and DASH after ulnar shortening osteotomy for idiopathic ulnar impaction syndrome. All patients who underwent ulnar shortening osteotomy between March 2008 and February 2011 for idiopathic ulnar impaction syndrome were enrolled in this study. All patients completed the PRWE and DASH questionnaires, and all were evaluated for grip strength and wrist ROM, preoperatively and 12 months postoperatively. We compared the effect sizes observed by each of these instruments. Effect size is calculated by dividing the mean change in a score of each instrument during a specified interval by the standard deviation of the baseline score. In addition, patient-perceived overall improvement was used as the anchor to determine the minimal clinically important differences on the PRWE and DASH 12 months after surgery. The average score of each item except for wrist flexion and supination improved after surgery. The PRWE was more sensitive than the DASH or than physical measurements in detecting clinical changes. The effect sizes and standardized response means of the outcome measures were as follows: PRWE (1.51, 1.64), DASH (1.12, 1.24), grip strength (0.59, 0.68), wrist pronation (0.33, 0.41), and wrist extension (0.28, 0.36). Patient-perceived overall improvement and score changes of the PRWE and DASH correlated significantly. Minimal clinically important differences were 17 points (of a possible 100) for the PRWE and 13.5 for the DASH (also of 100), and minimal detectable changes were 7.7 points for the PRWE and 9.3 points for the DASH. Although the PRWE and DASH were highly sensitive to clinical changes, the PRWE was more sensitive in terms of detecting clinical changes after ulnar shortening osteotomy for idiopathic ulnar impaction syndrome. A minimal change of 17 PRWE points or 13.5 DASH points was necessary to achieve a benefit that patients perceived as clinically important. The minimal clinically important differences using these instruments were higher than the values produced by measurement errors.

Heat shock protein vaccines against glioblastoma: from bench to bedside.

PubMed

Ampie, Leonel; Choy, Winward; Lamano, Jonathan B; Fakurnejad, Shayan; Bloch, Orin; Parsa, Andrew T

2015-07-01

Current adjuvant treatment regimens available for the treatment of glioblastoma are widely ineffective and offer a dismal prognosis. Advancements in conventional treatment strategies have only yielded modest improvements in overall survival. Immunotherapy remains a promising adjuvant in the treatment of GBM through eliciting tumor specific immune responses capable of producing sustained antitumor response while minimizing systemic toxicity. Heat shock proteins (HSP) function as intracellular chaperones and have been implicated in the activation of both innate and adaptive immune systems. Vaccines formulated from HSP-peptide complexes, derived from autologous tumor, have been applied to the field of immunotherapy for glioblastoma. The results from the phase I and II clinical trials have been promising. Here we review the role of HSP in cellular function and immunity, and its application in the treatment of glioblastoma.

Changes in cerebral metabolism in patients with a minimally conscious state responding to zolpidem

PubMed Central

Chatelle, Camille; Thibaut, Aurore; Gosseries, Olivia; Bruno, Marie-Aurélie; Demertzi, Athena; Bernard, Claire; Hustinx, Roland; Tshibanda, Luaba; Bahri, Mohamed A.; Laureys, Steven

2014-01-01

Background: Zolpidem, a short-acting non-benzodiazepine GABA agonist hypnotic, has been shown to induce paradoxical responses in some patients with disorders of consciousness (DOC), leading to recovery of arousal and cognitive abilities. We here assessed zolpidem-induced changes in regional brain metabolism in three patients with known zolpidem response in chronic post-anoxic minimally conscious state (MCS). Methods: [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) and standardized clinical assessments using the Coma Recovery Scale-Revised were performed after administration of 10 mg zolpidem or placebo in a randomized double blind 2-day protocol. PET data preprocessing and comparison with a healthy age-matched control group were performed using statistical parametric mapping (SPM8). Results: Behaviorally, all patients recovered functional communication after administration of zolpidem (i.e., emergence from the MCS). FDG-PET showed increased metabolism in dorsolateral prefrontal and mesiofrontal cortices after zolpidem but not after placebo administration. Conclusion: Our data show a metabolic activation of prefrontal areas, corroborating the proposed mesocircuit hypothesis to explain the paradoxical effect of zolpidem observed in some patients with DOC. It also suggests the key role of the prefrontal cortices in the recovery of functional communication and object use in hypoxic patients with chronic MCS. PMID:25520636

Measurement Properties of the Smartphone-Based B-B Score in Current Shoulder Pathologies

PubMed Central

Pichonnaz, Claude; Duc, Cyntia; Gleeson, Nigel; Ancey, Céline; Jaccard, Hervé; Lécureux, Estelle; Farron, Alain; Jolles, Brigitte M.; Aminian, Kamiar

2015-01-01

This study is aimed at the determination of the measurement properties of the shoulder function B-B Score measured with a smartphone. This score measures the symmetry between sides of a power-related metric for two selected movements, with 100% representing perfect symmetry. Twenty healthy participants, 20 patients with rotator cuff conditions, 23 with fractures, 22 with capsulitis, and 23 with shoulder instabilities were measured twice across a six-month interval using the B-B Score and shoulder function questionnaires. The discriminative power, responsiveness, diagnostic power, concurrent validity, minimal detectable change (MDC), minimal clinically important improvement (MCII), and patient acceptable symptom state (PASS) were evaluated. Significant differences with the control group and significant baseline—six-month differences were found for the rotator cuff condition, fracture, and capsulitis patient groups. The B-B Score was responsive and demonstrated excellent diagnostic power, except for shoulder instability. The correlations with clinical scores were generally moderate to high, but lower for instability. The MDC was 18.1%, the MCII was 25.2%, and the PASS was 77.6. No floor effect was observed. The B-B Score demonstrated excellent measurement properties in populations with rotator cuff conditions, proximal humerus fractures, and capsulitis, and can thus be used as a routine test to evaluate those patients. PMID:26506355

Prediction of thermal conductivity of polyvinylpyrrolidone (PVP) electrospun nanocomposite fibers using artificial neural network and prey-predator algorithm.

PubMed

Khan, Waseem S; Hamadneh, Nawaf N; Khan, Waqar A

2017-01-01

In this study, multilayer perception neural network (MLPNN) was employed to predict thermal conductivity of PVP electrospun nanocomposite fibers with multiwalled carbon nanotubes (MWCNTs) and Nickel Zinc ferrites [(Ni0.6Zn0.4) Fe2O4]. This is the second attempt on the application of MLPNN with prey predator algorithm for the prediction of thermal conductivity of PVP electrospun nanocomposite fibers. The prey predator algorithm was used to train the neural networks to find the best models. The best models have the minimal of sum squared error between the experimental testing data and the corresponding models results. The minimal error was found to be 0.0028 for MWCNTs model and 0.00199 for Ni-Zn ferrites model. The predicted artificial neural networks (ANNs) responses were analyzed statistically using z-test, correlation coefficient, and the error functions for both inclusions. The predicted ANN responses for PVP electrospun nanocomposite fibers were compared with the experimental data and were found in good agreement.

Surgical Management of the Thick-Skinned Nose.

PubMed

Davis, Richard E; Hrisomalos, Emily N

2018-02-01

When executed properly, open structure rhinoplasty can dramatically improve the consistency, durability, and quality of the cosmetic surgical outcome. Moreover, in expert hands, dramatic transformations in skeletal architecture can be accomplished with minimal risk and unparalleled control, all while preserving nasal airway function. While skeletal enhancements have become increasingly more controlled and precise, the outer skin-soft tissue envelope (SSTE) often presents a formidable obstacle to a satisfactory cosmetic result. In noses with unusually thick skin, excessive skin volume and characteristically hostile healing responses frequently combine to obscure or sometimes even negate cosmetic skeletal modifications and taint the surgical outcome. For this challenging patient subgroup, care must be taken to optimize the SSTE using a graduated treatment strategy directed at minimizing skin thickness and controlling unfavorable healing responses. When appropriate efforts are implemented to manage thick nasal skin, cosmetic outcomes are often substantially improved, sometimes even negating the ill-effects of thick skin altogether. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Detecting number processing and mental calculation in patients with disorders of consciousness using a hybrid brain-computer interface system.

PubMed

Li, Yuanqing; Pan, Jiahui; He, Yanbin; Wang, Fei; Laureys, Steven; Xie, Qiuyou; Yu, Ronghao

2015-12-15

For patients with disorders of consciousness such as coma, a vegetative state or a minimally conscious state, one challenge is to detect and assess the residual cognitive functions in their brains. Number processing and mental calculation are important brain functions but are difficult to detect in patients with disorders of consciousness using motor response-based clinical assessment scales such as the Coma Recovery Scale-Revised due to the patients' motor impairments and inability to provide sufficient motor responses for number- and calculation-based communication. In this study, we presented a hybrid brain-computer interface that combines P300 and steady state visual evoked potentials to detect number processing and mental calculation in Han Chinese patients with disorders of consciousness. Eleven patients with disorders of consciousness who were in a vegetative state (n = 6) or in a minimally conscious state (n = 3) or who emerged from a minimally conscious state (n = 2) participated in the brain-computer interface-based experiment. During the experiment, the patients with disorders of consciousness were instructed to perform three tasks, i.e., number recognition, number comparison, and mental calculation, including addition and subtraction. In each experimental trial, an arithmetic problem was first presented. Next, two number buttons, only one of which was the correct answer to the problem, flickered at different frequencies to evoke steady state visual evoked potentials, while the frames of the two buttons flashed in a random order to evoke P300 potentials. The patients needed to focus on the target number button (the correct answer). Finally, the brain-computer interface system detected P300 and steady state visual evoked potentials to determine the button to which the patients attended, further presenting the results as feedback. Two of the six patients who were in a vegetative state, one of the three patients who were in a minimally conscious state, and the two patients that emerged from a minimally conscious state achieved accuracies significantly greater than the chance level. Furthermore, P300 potentials and steady state visual evoked potentials were observed in the electroencephalography signals from the five patients. Number processing and arithmetic abilities as well as command following were demonstrated in the five patients. Furthermore, our results suggested that through brain-computer interface systems, many cognitive experiments may be conducted in patients with disorders of consciousness, although they cannot provide sufficient behavioral responses.

ATM directs DNA damage responses and proteostasis via genetically separable pathways

PubMed Central

Lee, Ji-Hoon; Mand, Michael R.; Kao, Chung-Hsuan; Zhou, Yi; Ryu, Seung W.; Richards, Alicia L.; Coon, Joshua J.; Paull, Tanya T.

2018-01-01

The protein kinase ATM is a master regulator of the DNA damage response but also responds directly to oxidative stress. Loss of ATM causes Ataxia telangiectasia, a neurodegenerative disorder with pleiotropic symptoms that include cerebellar dysfunction, cancer, diabetes, and premature aging. Here, we genetically separated DNA damage activation of ATM from oxidative activation using separation-of-function mutations. We found that deficiency in ATM activation by Mre11-Rad50-Nbs1 and DNA double-strand breaks resulted in loss of cell viability, checkpoint activation, and DNA end resection in response to DNA damage. In contrast, loss of oxidative activation of ATM had minimal effects on DNA damage-related outcomes but blocked ATM-mediated initiation of checkpoint responses after oxidative stress and resulted in deficiencies in mitochondrial function and autophagy. In addition, expression of ATM lacking oxidative activation generates widespread protein aggregation. These results indicate a direct relationship between the mechanism of ATM activation and its effects on cellular metabolism and DNA damage responses in human cells and implicates ATM in the control of protein homeostasis. PMID:29317520

Chromatographic peak resolution using Microsoft Excel Solver. The merit of time shifting input arrays.

PubMed

Dasgupta, Purnendu K

2008-12-05

Resolution of overlapped chromatographic peaks is generally accomplished by modeling the peaks as Gaussian or modified Gaussian functions. It is possible, even preferable, to use actual single analyte input responses for this purpose and a nonlinear least squares minimization routine such as that provided by Microsoft Excel Solver can then provide the resolution. In practice, the quality of the results obtained varies greatly due to small shifts in retention time. I show here that such deconvolution can be considerably improved if one or more of the response arrays are iteratively shifted in time.

Functional Bregman Divergence and Bayesian Estimation of Distributions (Preprint)

DTIC Science & Technology

2008-01-01

shows that if the set of possible minimizers A includes EPF [F ], then g∗ = EPF [F ] minimizes the expectation of any Bregman divergence. Note the theorem...probability distribution PF defined over the set M. Let A be a set of functions that includes EPF [F ] if it exists. Suppose the function g∗ minimizes...the expected Bregman divergence between the random function F and any function g ∈ A such that g∗ = arg inf g∈A EPF [dφ(F, g)]. Then, if g∗ exists

On a cost functional for H2/H(infinity) minimization

NASA Technical Reports Server (NTRS)

Macmartin, Douglas G.; Hall, Steven R.; Mustafa, Denis

1990-01-01

A cost functional is proposed and investigated which is motivated by minimizing the energy in a structure using only collocated feedback. Defined for an H(infinity)-norm bounded system, this cost functional also overbounds the H2 cost. Some properties of this cost functional are given, and preliminary results on the procedure for minimizing it are presented. The frequency domain cost functional is shown to have a time domain representation in terms of a Stackelberg non-zero sum differential game.

Threshold responses of Amazonian stream fishes to timing and extent of deforestation.

PubMed

Brejão, Gabriel L; Hoeinghaus, David J; Pérez-Mayorga, María Angélica; Ferraz, Silvio F B; Casatti, Lilian

2017-12-06

Deforestation is a primary driver of biodiversity change through habitat loss and fragmentation. Stream biodiversity may not respond to deforestation in a simple linear relationship. Rather, threshold responses to extent and timing of deforestation may occur. Identification of critical deforestation thresholds is needed for effective conservation and management. We tested for threshold responses of fish species and functional groups to degree of watershed and riparian zone deforestation and time since impact in 75 streams in the western Brazilian Amazon. We used remote sensing to assess deforestation from 1984 to 2011. Fish assemblages were sampled with seines and dip nets in a standardized manner. Fish species (n = 84) were classified into 20 functional groups based on ecomorphological traits associated with habitat use, feeding, and locomotion. Threshold responses were quantified using threshold indicator taxa analysis. Negative threshold responses to deforestation were common and consistently occurred at very low levels of deforestation (<20%) and soon after impact (<10 years). Sensitive species were functionally unique and associated with complex habitats and structures of allochthonous origin found in forested watersheds. Positive threshold responses of species were less common and generally occurred at >70% deforestation and >10 years after impact. Findings were similar at the community level for both taxonomic and functional analyses. Because most negative threshold responses occurred at low levels of deforestation and soon after impact, even minimal change is expected to negatively affect biodiversity. Delayed positive threshold responses to extreme deforestation by a few species do not offset the loss of sensitive taxa and likely contribute to biotic homogenization. © 2017 Society for Conservation Biology.

On a Minimum Problem in Smectic Elastomers

NASA Astrophysics Data System (ADS)

Buonsanti, Michele; Giovine, Pasquale

2008-07-01

Smectic elastomers are layered materials exhibiting a solid-like elastic response along the layer normal and a rubbery one in the plane. Balance equations for smectic elastomers are derived from the general theory of continua with constrained microstructure. In this work we investigate a very simple minimum problem based on multi-well potentials where the microstructure is taken into account. The set of polymeric strains minimizing the elastic energy contains a one-parameter family of simple strain associated with a micro-variation of the degree of freedom. We develop the energy functional through two terms, the first one nematic and the second one considering the tilting phenomenon; after, by developing in the rubber elasticity framework, we minimize over the tilt rotation angle and extract the engineering stress.

Digital robust active control law synthesis for large order systems using constrained optimization

NASA Technical Reports Server (NTRS)

Mukhopadhyay, Vivek

1987-01-01

This paper presents a direct digital control law synthesis procedure for a large order, sampled data, linear feedback system using constrained optimization techniques to meet multiple design requirements. A linear quadratic Gaussian type cost function is minimized while satisfying a set of constraints on the design loads and responses. General expressions for gradients of the cost function and constraints, with respect to the digital control law design variables are derived analytically and computed by solving a set of discrete Liapunov equations. The designer can choose the structure of the control law and the design variables, hence a stable classical control law as well as an estimator-based full or reduced order control law can be used as an initial starting point. Selected design responses can be treated as constraints instead of lumping them into the cost function. This feature can be used to modify a control law, to meet individual root mean square response limitations as well as minimum single value restrictions. Low order, robust digital control laws were synthesized for gust load alleviation of a flexible remotely piloted drone aircraft.

Secondary Psychometric Examination of the Dimensional Obsessive-Compulsive Scale: Classical Testing, Item Response Theory, and Differential Item Functioning.

PubMed

Thibodeau, Michel A; Leonard, Rachel C; Abramowitz, Jonathan S; Riemann, Bradley C

2015-12-01

The Dimensional Obsessive-Compulsive Scale (DOCS) is a promising measure of obsessive-compulsive disorder (OCD) symptoms but has received minimal psychometric attention. We evaluated the utility and reliability of DOCS scores. The study included 832 students and 300 patients with OCD. Confirmatory factor analysis supported the originally proposed four-factor structure. DOCS total and subscale scores exhibited good to excellent internal consistency in both samples (α = .82 to α = .96). Patient DOCS total scores reduced substantially during treatment (t = 16.01, d = 1.02). DOCS total scores discriminated between students and patients (sensitivity = 0.76, 1 - specificity = 0.23). The measure did not exhibit gender-based differential item functioning as tested by Mantel-Haenszel chi-square tests. Expected response options for each item were plotted as a function of item response theory and demonstrated that DOCS scores incrementally discriminate OCD symptoms ranging from low to extremely high severity. Incremental differences in DOCS scores appear to represent unbiased and reliable differences in true OCD symptom severity. © The Author(s) 2014.

Development of an Empirical Model for Optimization of Machining Parameters to Minimize Power Consumption

NASA Astrophysics Data System (ADS)

Kant Garg, Girish; Garg, Suman; Sangwan, K. S.

2018-04-01

The manufacturing sector consumes huge energy demand and the machine tools used in this sector have very less energy efficiency. Selection of the optimum machining parameters for machine tools is significant for energy saving and for reduction of environmental emission. In this work an empirical model is developed to minimize the power consumption using response surface methodology. The experiments are performed on a lathe machine tool during the turning of AISI 6061 Aluminum with coated tungsten inserts. The relationship between the power consumption and machining parameters is adequately modeled. This model is used for formulation of minimum power consumption criterion as a function of optimal machining parameters using desirability function approach. The influence of machining parameters on the energy consumption has been found using the analysis of variance. The validation of the developed empirical model is proved using the confirmation experiments. The results indicate that the developed model is effective and has potential to be adopted by the industry for minimum power consumption of machine tools.

Hemorrhagic iliopsoas bursitis complicating well-functioning ceramic-on-ceramic total hip arthroplasty.

PubMed

Park, Kyung Soon; Diwanji, Sanket R; Kim, Hyung Keun; Song, Eun Kyoo; Yoon, Taek Rim

2009-08-01

Iliopsoas bursitis has been increasingly recognized as a complication of total hip arthroplasty and is usually associated with polyethylene wear. Here, the authors report a case of hemorrhagic iliopsoas bursitis complicating an otherwise well-functioning ceramic-on-ceramic arthroplasty performed by minimal invasive modified 2-incision technique. The bursitis in turn resulted in femoral nerve palsy and femoral vein compression. In this report, there was no evidence to support that the bursitis was due to an inflammatory response to ceramic wear particles or any other wear particles originating from the total hip arthroplasty.

Climate Intervention as an Optimization Problem

NASA Astrophysics Data System (ADS)

Caldeira, Ken; Ban-Weiss, George A.

2010-05-01

Typically, climate models simulations of intentional intervention in the climate system have taken the approach of imposing a change (eg, in solar flux, aerosol concentrations, aerosol emissions) and then predicting how that imposed change might affect Earth's climate or chemistry. Computations proceed from cause to effect. However, humans often proceed from "What do I want?" to "How do I get it?" One approach to thinking about intentional intervention in the climate system ("geoengineering") is to ask "What kind of climate do we want?" and then ask "What pattern of radiative forcing would come closest to achieving that desired climate state?" This involves defining climate goals and a cost function that measures how closely those goals are attained. (An important next step is to ask "How would we go about producing these desired patterns of radiative forcing?" However, this question is beyond the scope of our present study.) We performed a variety of climate simulations in NCAR's CAM3.1 atmospheric general circulation model with a slab ocean model and thermodynamic sea ice model. We then evaluated, for a specific set of climate forcing basis functions (ie, aerosol concentration distributions), the extent to which the climate response to a linear combination of those basis functions was similar to a linear combination of the climate response to each basis function taken individually. We then developed several cost functions (eg, relative to the 1xCO2 climate, minimize rms difference in zonal and annual mean land temperature, minimize rms difference in zonal and annual mean runoff, minimize rms difference in a combination of these temperature and runoff indices) and then predicted optimal combinations of our basis functions that would minimize these cost functions. Lastly, we produced forward simulations of the predicted optimal radiative forcing patterns and compared these with our expected results. Obviously, our climate model is much simpler than reality and predictions from individual models do not provide a sound basis for action; nevertheless, our model results indicate that the general approach outlined here can lead to patterns of radiative forcing that make the zonal annual mean climate of a high CO2 world markedly more similar to that of a low CO2 world simultaneously for both temperature and hydrological indices, where degree of similarity is measured using our explicit cost functions. We restricted ourselves to zonally uniform aerosol concentrations distributions that can be defined in terms of a positive-definite quadratic equation on the sine of latitude. Under this constraint, applying an aerosol distribution in a 2xCO2 climate that minimized a combination of rms difference in zonal and annual mean land temperature and runoff relative to the 1xCO2 climate, the rms difference in zonal and annual mean temperatures was reduced by ~90% and the rms difference in zonal and annual mean runoff was reduced by ~80%. This indicates that there may be potential for stratospheric aerosols to diminish simultaneously both temperature and hydrological cycle changes caused by excess CO2 in the atmosphere. Clearly, our model does not include many factors (eg, socio-political consequences, chemical consequences, ocean circulation changes, aerosol transport and microphysics) so we do not argue strongly for our specific climate model results, however, we do argue strongly in favor of our methodological approach. The proposed approach is general, in the sense that cost functions can be developed that represent different valuations. While the choice of appropriate cost functions is inherently a value judgment, evaluating those functions for a specific climate simulation is a quantitative exercise. Thus, the use of explicit cost functions in evaluating model results for climate intervention scenarios is a clear way of separating value judgments from purely scientific and technical issues.

Swiss national community survey on functioning after spinal cord injury: Protocol, characteristics of participants and determinants of non-response.

PubMed

Brinkhof, Martin W G; Fekete, Christine; Chamberlain, Jonviea D; Post, Marcel W M; Gemperli, Armin

2016-02-01

To detail the protocol, recruitment, study population, response, and data quality of the first population-based community survey of the Swiss Spinal Cord Injury (SwiSCI) Cohort Study. The survey consisted of 3 successive modules administered between September 2011 and March 2013. The first two modules queried demographics, lesion characteristics and key domains of functioning. The third module collected information on psychological personal factors and health behaviour; work integration; or health services and aging. Community-dwelling persons with chronic spinal cord injury in Switzerland. Descriptive analyses of the recruitment process, participant characteristics, and correspondence between self-reported and clinical data. Determinants for participation and the impact of non-response on survey results were assessed. Out of 3,144 eligible persons 1,549 participated in the first two modules (cumulative response rate 49.3%). Approximately three-quarters of participants were male, with a median age of 53 years, and 78% had traumatic spinal cord injury. Record-linkage with medical records demonstrated substantial agreement with self-reported demographic and lesion characteristics. A minimal non-response bias was found. The community survey was effective in recruiting an unbiased sample, thus providing valuable information to study functioning, health maintenance, and quality of life in the Swiss SCI community.

Making every word count for nonresponsive patients.

PubMed

Naci, Lorina; Owen, Adrian M

2013-10-01

Despite the apparent absence of external signs of consciousness, a significant small proportion of patients with disorders of consciousness can respond to commands by willfully modulating their brain activity, even respond to yes or no questions, by performing mental imagery tasks. However, little is known about the mental life of such responsive patients, for example, with regard to whether they can have coherent thoughts or selectively maintain attention to specific events in their environment. The ability to selectively pay attention would provide evidence of a patient's preserved cognition and a method for brain-based communication, thus far untested with functional magnetic resonance imaging in this patient group. To test whether selective auditory attention can be used to detect conscious awareness and communicate with behaviorally nonresponsive patients. Case study performed in 3 patients with severe brain injury, 2 diagnosed as being in a minimally conscious state and 1 as being in a vegetative state. The patients constituted a convenience sample. Functional magnetic resonance imaging data were acquired as the patients were asked to selectively attend to auditory stimuli, thereby conveying their ability to follow commands and communicate. All patients demonstrated command following according to instructions. Two patients (1 in a minimally conscious state and 1 in a vegetative state) were also able to guide their attention to repeatedly communicate correct answers to binary (yes or no) questions. To our knowledge, we show for the first time with functional magnetic resonance imaging that behaviorally nonresponsive patients can use selective auditory attention to convey their ability to follow commands and communicate. One patient in a minimally conscious state was able to use attention to establish functional communication in the scanner, despite his inability to produce any communication responses in repeated bedside examinations. More important, 1 patient, who had been in a vegetative state for 12 years before the scanning and subsequent to it, was able to use attention to correctly communicate answers to several binary questions. The technique may be useful in establishing basic communication with patients who appear unresponsive to bedside examinations and cannot respond with existing neuroimaging methods.

Mutations M287L and Q266I in the Glycine Receptor α1 Subunit Change Sensitivity to Volatile Anesthetics in Oocytes and Neurons, but Not the Minimal Alveolar Concentration in Knockin Mice

PubMed Central

Borghese, Cecilia M.; Xiong, Wei; Oh, S. Irene; Ho, Angel; Mihic, S. John; Zhang, Li; Lovinger, David M.; Homanics, Gregg E.; Eger, Edmond I; Harris, R. Adron

2012-01-01

Background Volatile anesthetics (VAs) alter the function of key central nervous system proteins but it is not clear which, if any, of these targets mediates the immobility produced by VAs in the face of noxious stimulation. A leading candidate is the glycine receptor, a ligand-gated ion channel important for spinal physiology. VAs variously enhance such function, and blockade of spinal GlyRs with strychnine affects the minimal alveolar concentration (an anesthetic EC50) in proportion to the degree of enhancement. Methods We produced single amino acid mutations into the glycine receptorα1 subunit that increased (M287L, third transmembrane region) or decreased (Q266I, second transmembrane region) sensitivity to isoflurane in recombinant receptors, and introduced such receptors into mice. The resulting knockin mice presented impaired glycinergic transmission, but heterozygous animals survived to adulthood, and we determined the effect of isoflurane on glycine-evoked responses of brain stem neurons from the knockin mice, and the minimal alveolar concentration for isoflurane and other VAs in the immature and mature knockin mice. Results Studies of glycine-evoked currents in brain stem neurons from knock-in mice confirmed the changes seen with recombinant receptors. No increases in the minimal alveolar concentration were found in knockin mice, but the minimal alveolar concentration for isoflurane and enflurane (but not halothane) decreased in 2-week-old Q266I mice. This change is opposite to the one expected for a mutation that decreases the sensitivity to volatile anesthetics. Conclusion Taken together, these results indicate that glycine receptors containing the α1 subunit are not likely to be crucial for the action of isoflurane and other VAs. PMID:22885675

HYBRID NEURAL NETWORK AND SUPPORT VECTOR MACHINE METHOD FOR OPTIMIZATION

NASA Technical Reports Server (NTRS)

Rai, Man Mohan (Inventor)

2005-01-01

System and method for optimization of a design associated with a response function, using a hybrid neural net and support vector machine (NN/SVM) analysis to minimize or maximize an objective function, optionally subject to one or more constraints. As a first example, the NN/SVM analysis is applied iteratively to design of an aerodynamic component, such as an airfoil shape, where the objective function measures deviation from a target pressure distribution on the perimeter of the aerodynamic component. As a second example, the NN/SVM analysis is applied to data classification of a sequence of data points in a multidimensional space. The NN/SVM analysis is also applied to data regression.

Hybrid Neural Network and Support Vector Machine Method for Optimization

NASA Technical Reports Server (NTRS)

Rai, Man Mohan (Inventor)

2007-01-01

System and method for optimization of a design associated with a response function, using a hybrid neural net and support vector machine (NN/SVM) analysis to minimize or maximize an objective function, optionally subject to one or more constraints. As a first example, the NN/SVM analysis is applied iteratively to design of an aerodynamic component, such as an airfoil shape, where the objective function measures deviation from a target pressure distribution on the perimeter of the aerodynamic component. As a second example, the NN/SVM analysis is applied to data classification of a sequence of data points in a multidimensional space. The NN/SVM analysis is also applied to data regression.

Systems and Methods for Peak-Seeking Control

NASA Technical Reports Server (NTRS)

Ryan, John J (Inventor); Speyer, Jason L (Inventor)

2013-01-01

A computerized system and method for peak-seeking-control that uses a unique Kalman filter design to optimize a control loop, in real time, to either maximize or minimize a performance function of a physical object ("plant"). The system and method achieves more accurate and efficient peak-seeking-control by using a time-varying Kalman filter to estimate both the performance function gradient (slope) and Hessian (curvature) based on direct position measurements of the plant, and does not rely upon modeling the plant response to persistent excitation. The system and method can be naturally applied in various applications in which plant performance functions have multiple independent parameters, and it does not depend upon frequency separation to distinguish between system dimensions.

Responsiveness of the numeric pain rating scale in patients with shoulder pain and the effect of surgical status.

PubMed

Michener, Lori A; Snyder, Alison R; Leggin, Brian G

2011-02-01

The Numeric Pain Rating Scale (NPRS) is commonly used to assess pain. Change in the NPRS across time can be interpreted with responsiveness indices. To determine the minimal clinically important difference (MCID) of the NPRS. Single-group repeated measures. Outpatient rehabilitation clinics. Patients with shoulder pain (N = 136). At the initial evaluation patients completed the Penn Shoulder Score (PSS), which includes pain, satisfaction, and function sections. Pain was measured using an 11-point NPRS for 3 conditions of pain: at rest, with normal daily activities, and with strenuous activities. The NPRS average was calculated by averaging the NPRS scores for 3 conditions of pain. The final PSS was completed after 3-4 wk of rehabilitation. To determine the MCID for the NPRS average, the minimal detectible change of 8.6 points for the PSS function scale (0-60 points) was used as an external criterion anchor to classify patients as meaningfully improved (≥8.6 point change) or not improved (<8.6-point change). The MCID for the NPRS average was also determined for subgroups of surgical and nonsurgical patients. Cohen's effect sizes were calculated as a measure of group responsiveness for the NPRS average. Using a receiver-operating-characteristic analysis, the MCID for the average NPRS for all patients was 2.17, and it was 2.17 for both the surgical and nonsurgical subgroup: area-under-the-curve range .74-.76 (95%CI: .55-.95). The effect size for all patients was 1.84, and it was 1.51 and 1.94 for the surgical and nonsurgical groups, respectively. The NPRS average of 3 pain questions demonstrated responsiveness with an MCID of 2.17 in patients with shoulder pain receiving rehabilitation for 3-4 wk. The effect sizes indicated a large effect. However, responsiveness values are not static. Further research is indicated to assess responsiveness of the NPRS average in different types of patients with shoulder pain.

Chemometric optimization of the robustness of the near infrared spectroscopic method in wheat quality control.

PubMed

Pojić, Milica; Rakić, Dušan; Lazić, Zivorad

2015-01-01

A chemometric approach was applied for the optimization of the robustness of the NIRS method for wheat quality control. Due to the high number of experimental (n=6) and response variables to be studied (n=7) the optimization experiment was divided into two stages: screening stage in order to evaluate which of the considered variables were significant, and optimization stage to optimize the identified factors in the previously selected experimental domain. The significant variables were identified by using fractional factorial experimental design, whilst Box-Wilson rotatable central composite design (CCRD) was run to obtain the optimal values for the significant variables. The measured responses included: moisture, protein and wet gluten content, Zeleny sedimentation value and deformation energy. In order to achieve the minimal variation in responses, the optimal factor settings were found by minimizing the propagation of error (POE). The simultaneous optimization of factors was conducted by desirability function. The highest desirability of 87.63% was accomplished by setting up experimental conditions as follows: 19.9°C for sample temperature, 19.3°C for ambient temperature and 240V for instrument voltage. Copyright © 2014 Elsevier B.V. All rights reserved.

Patient-reported outcome measures in arthroplasty registries

PubMed Central

Bohm, Eric; Franklin, Patricia; Lyman, Stephen; Denissen, Geke; Dawson, Jill; Dunn, Jennifer; Eresian Chenok, Kate; Dunbar, Michael; Overgaard, Søren; Garellick, Göran; Lübbeke, Anne

2016-01-01

Abstract — The International Society of Arthroplasty Registries (ISAR) Patient-Reported Outcome Measures (PROMs) Working Group have evaluated and recommended best practices in the selection, administration, and interpretation of PROMs for hip and knee arthroplasty registries. The 2 generic PROMs in common use are the Short Form health surveys (SF-36 or SF-12) and EuroQol 5-dimension (EQ-5D). The Working Group recommends that registries should choose specific PROMs that have been appropriately developed with good measurement properties for arthroplasty patients. The Working Group recommend the use of a 1-item pain question (“During the past 4 weeks, how would you describe the pain you usually have in your [right/left] [hip/knee]?”; response: none, very mild, mild, moderate, or severe) and a single-item satisfaction outcome (“How satisfied are you with your [right/left] [hip/knee] replacement?”; response: very unsatisfied, dissatisfied, neutral, satisfied, or very satisfied). Survey logistics include patient instructions, paper- and electronic-based data collection, reminders for follow-up, centralized as opposed to hospital-based follow-up, sample size, patient- or joint-specific evaluation, collection intervals, frequency of response, missing values, and factors in establishing a PROMs registry program. The Working Group recommends including age, sex, diagnosis at joint, general health status preoperatively, and joint pain and function score in case-mix adjustment models. Interpretation and statistical analysis should consider the absolute level of pain, function, and general health status as well as improvement, missing data, approaches to analysis and case-mix adjustment, minimal clinically important difference, and minimal detectable change. The Working Group recommends data collection immediately before and 1 year after surgery, a threshold of 60% for acceptable frequency of response, documentation of non-responders, and documentation of incomplete or missing data. PMID:27228230

Psychometric performance and responsiveness of the functional outcomes of sleep questionnaire and sleep apnea quality of life instrument in a randomized trial: the HomePAP study.

PubMed

Billings, Martha E; Rosen, Carol L; Auckley, Dennis; Benca, Ruth; Foldvary-Schaefer, Nancy; Iber, Conrad; Zee, Phyllis C; Redline, Susan; Kapur, Vishesh K

2014-12-01

Measures of health-related quality of life (HRQL) specific for sleep disorders have had limited psychometric evaluation in the context of randomized controlled trials (RCTs). We investigated the psychometric properties of the Functional Outcomes of Sleep Questionnaire (FOSQ) and Sleep Apnea Quality of Life Instrument (SAQLI). We evaluated the FOSQ and SAQLI construct and criterion validity, determined a minimally important difference, and assessed for associations of responsiveness to baseline subject characteristics and continuous positive airway pressure (CPAP) adherence in a RCT population. Secondary analysis of data collected in a multisite RCT of home versus laboratory-based diagnosis and treatment of obstructive sleep apnea (HomePAP trial). Individuals enrolled in the HomePAP trial (n = 335). N/A. The FOSQ and SAQLI subscores demonstrated high reliability and criterion validity, correlating with Medical Outcomes Study 36-Item Short Form Survey domains. Correlations were weaker with the Epworth Sleepiness Scale (ESS). Both the FOSQ and SAQLI scores improved after 3 mo with CPAP therapy. Averaging 4 h or more of CPAP use was associated with an increase in the FOSQ beyond the minimally important difference. Baseline depressive symptoms and sleepiness predicted FOSQ and SAQLI responsiveness; demographic, objective obstructive sleep apnea (OSA) severity and sleep habits were not predictive in linear regression. The FOSQ and SAQLI are responsive to CPAP intervention, with the FOSQ being more sensitive to differences in CPAP adherence than the SAQLI. These instruments provide unique information about health outcomes beyond that provided by changes in physiological measures of OSA severity (apnea-hypopnea index). Portable Monitoring for Diagnosis and Management of Sleep Apnea (HomePAP) URL: http://clinicaltrials.gov/show/NCT00642486. NIH clinical trials registry number: NCT00642486. © 2014 Associated Professional Sleep Societies, LLC.

Proteomic Basis of the Antibody Response to Monkeypox Virus Infection Examined in Cynomolgus Macaques and a Comparison to Human Smallpox Vaccination

DTIC Science & Technology

2010-12-30

collected after challenges were gamma- irradiated (6 Mrad) to destroy any infectious virus. Previous results indicated minimal damage to serum immuno...in Sf9 insect cells using Gateway baculovirus expression (Invitrogen). All ORF clones were fully sequenced. Recombinant proteins carried GST-tags and... insect cell expression, increased the likelihood that all products were correctly folded and functional. Successfully cloned, expressed and size

Majorization as a Tool for Optimizing a Class of Matrix Functions.

ERIC Educational Resources Information Center

Kiers, Henk A.

1990-01-01

General algorithms are presented that can be used for optimizing matrix trace functions subject to certain constraints on the parameters. The parameter set that minimizes the majorizing function also decreases the matrix trace function, providing a monotonically convergent algorithm for minimizing the matrix trace function iteratively. (SLD)

GATA Factor Regulation in Excess Nitrogen Occurs Independently of Gtr-Ego Complex-Dependent TorC1 Activation.

PubMed

Tate, Jennifer J; Georis, Isabelle; Rai, Rajendra; Vierendeels, Fabienne; Dubois, Evelyne; Cooper, Terrance G

2015-05-29

The TorC1 protein kinase complex is a central component in a eukaryotic cell's response to varying nitrogen availability, with kinase activity being stimulated in nitrogen excess by increased intracellular leucine. This leucine-dependent TorC1 activation requires functional Gtr1/2 and Ego1/3 complexes. Rapamycin inhibition of TorC1 elicits nuclear localization of Gln3, a GATA-family transcription activator responsible for the expression of genes encoding proteins required to transport and degrade poor nitrogen sources, e.g., proline. In nitrogen-replete conditions, Gln3 is cytoplasmic and Gln3-mediated transcription minimal, whereas in nitrogen limiting or starvation conditions, or after rapamycin treatment, Gln3 is nuclear and transcription greatly increased. Increasing evidence supports the idea that TorC1 activation may not be as central to nitrogen-responsive intracellular Gln3 localization as envisioned previously. To test this idea directly, we determined whether Gtr1/2- and Ego1/3-dependent TorC1 activation also was required for cytoplasmic Gln3 sequestration and repressed GATA factor-mediated transcription by abolishing the Gtr-Ego complex proteins. We show that Gln3 is sequestered in the cytoplasm of gtr1Δ, gtr2Δ, ego1Δ, and ego3Δ strains either long term in logarithmically glutamine-grown cells or short term after refeeding glutamine to nitrogen-limited or -starved cells; GATA factor-dependent transcription also was minimal. However, in all but a gtr1Δ, nuclear Gln3 localization in response to nitrogen limitation or starvation was adversely affected. Our data demonstrate: (i) Gtr-Ego-dependent TorC1 activation is not required for cytoplasmic Gln3 sequestration in nitrogen-rich conditions; (ii) a novel Gtr-Ego-TorC1 activation-independent mechanism sequesters Gln3 in the cytoplasm; (iii) Gtr and Ego complex proteins participate in nuclear Gln3-Myc(13) localization, heretofore unrecognized functions for these proteins; and (iv) the importance of searching for new mechanisms associated with TorC1 activation and/or the regulation of Gln3 localization/function in response to changes in the cells' nitrogen environment. Copyright © 2015 Tate et al.

GATA Factor Regulation in Excess Nitrogen Occurs Independently of Gtr-Ego Complex-Dependent TorC1 Activation

PubMed Central

Tate, Jennifer J.; Georis, Isabelle; Rai, Rajendra; Vierendeels, Fabienne; Dubois, Evelyne; Cooper, Terrance G.

2015-01-01

The TorC1 protein kinase complex is a central component in a eukaryotic cell’s response to varying nitrogen availability, with kinase activity being stimulated in nitrogen excess by increased intracellular leucine. This leucine-dependent TorC1 activation requires functional Gtr1/2 and Ego1/3 complexes. Rapamycin inhibition of TorC1 elicits nuclear localization of Gln3, a GATA-family transcription activator responsible for the expression of genes encoding proteins required to transport and degrade poor nitrogen sources, e.g., proline. In nitrogen-replete conditions, Gln3 is cytoplasmic and Gln3-mediated transcription minimal, whereas in nitrogen limiting or starvation conditions, or after rapamycin treatment, Gln3 is nuclear and transcription greatly increased. Increasing evidence supports the idea that TorC1 activation may not be as central to nitrogen-responsive intracellular Gln3 localization as envisioned previously. To test this idea directly, we determined whether Gtr1/2- and Ego1/3-dependent TorC1 activation also was required for cytoplasmic Gln3 sequestration and repressed GATA factor-mediated transcription by abolishing the Gtr-Ego complex proteins. We show that Gln3 is sequestered in the cytoplasm of gtr1Δ, gtr2Δ, ego1Δ, and ego3Δ strains either long term in logarithmically glutamine-grown cells or short term after refeeding glutamine to nitrogen-limited or -starved cells; GATA factor−dependent transcription also was minimal. However, in all but a gtr1Δ, nuclear Gln3 localization in response to nitrogen limitation or starvation was adversely affected. Our data demonstrate: (i) Gtr-Ego-dependent TorC1 activation is not required for cytoplasmic Gln3 sequestration in nitrogen-rich conditions; (ii) a novel Gtr-Ego-TorC1 activation-independent mechanism sequesters Gln3 in the cytoplasm; (iii) Gtr and Ego complex proteins participate in nuclear Gln3-Myc13 localization, heretofore unrecognized functions for these proteins; and (iv) the importance of searching for new mechanisms associated with TorC1 activation and/or the regulation of Gln3 localization/function in response to changes in the cells’ nitrogen environment. PMID:26024867

Characteristics and application of spherical-type activation detectors in neutron spectrum measurements at a boron neutron capture therapy (BNCT) facility

NASA Astrophysics Data System (ADS)

Lin, Heng-Xiao; Chen, Wei-Lin; Liu, Yuan-Hao; Sheu, Rong-Jiun

2016-03-01

A set of spherical-type activation detectors was developed aiming to provide better determination of the neutron spectrum at the Tsing Hua Open-pool Reactor (THOR) BNCT facility. An activation foil embedded in a specially designed spherical holder exhibits three advantages: (1) minimizing the effect of neutron angular dependence, (2) creating response functions with broadened coverage of neutron energies by introducing additional moderators or absorbers to the central activation foil, and (3) reducing irradiation time because of improved detection efficiencies to epithermal neutron beam. This paper presents the design concept and the calculated response functions of new detectors. Theoretical and experimental demonstrations of the performance of the detectors are provided through comparisons of the unfolded neutron spectra determined using this method and conventional multiple-foil activation techniques.

Constrained minimization of smooth functions using a genetic algorithm

NASA Technical Reports Server (NTRS)

Moerder, Daniel D.; Pamadi, Bandu N.

1994-01-01

The use of genetic algorithms for minimization of differentiable functions that are subject to differentiable constraints is considered. A technique is demonstrated for converting the solution of the necessary conditions for a constrained minimum into an unconstrained function minimization. This technique is extended as a global constrained optimization algorithm. The theory is applied to calculating minimum-fuel ascent control settings for an energy state model of an aerospace plane.

Can neutrino mass be deduced from beta particle spectrum?

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

Semkow, T.M.

1993-12-31

With 17-keV neutrino faith being uncertain, it is important to examine the effects of detector resolution and response on the detection limits of massive neutrino. The authors use Fermi theory and generate by Monte Carlo up to 5-10{sup 9} {beta}{sup {minus}} decay events from {sup 35}S. The {beta}{sup {minus}} spectra are then resolved by {chi}{sup 2} minimization. We show that given high statistics and accurate knowledge of the response function it should be possible to detect neutrino mass with a proportional detector, particularly with the gas-scintillation proportional detector, in addition to semiconductor, in addition to semiconductor detectors. This paper presentsmore » a design of double-chamber Xe gas-scintillation proportional detector in which the backscattering effects are suppressed. However, even the slight uncertainties in the response functions as well as {approximately} 10{sup {minus}3} relative energy nonlinearities in the {beta}{sup {minus}} spectrum may create an artificial effect of neutrino mass.« less

Efficient sensitivity analysis and optimization of a helicopter rotor

NASA Technical Reports Server (NTRS)

Lim, Joon W.; Chopra, Inderjit

1989-01-01

Aeroelastic optimization of a system essentially consists of the determination of the optimum values of design variables which minimize the objective function and satisfy certain aeroelastic and geometric constraints. The process of aeroelastic optimization analysis is illustrated. To carry out aeroelastic optimization effectively, one needs a reliable analysis procedure to determine steady response and stability of a rotor system in forward flight. The rotor dynamic analysis used in the present study developed inhouse at the University of Maryland is based on finite elements in space and time. The analysis consists of two major phases: vehicle trim and rotor steady response (coupled trim analysis), and aeroelastic stability of the blade. For a reduction of helicopter vibration, the optimization process requires the sensitivity derivatives of the objective function and aeroelastic stability constraints. For this, the derivatives of steady response, hub loads and blade stability roots are calculated using a direct analytical approach. An automated optimization procedure is developed by coupling the rotor dynamic analysis, design sensitivity analysis and constrained optimization code CONMIN.

Quality of Life after Open or Minimally Invasive Esophagectomy in Patients With Esophageal Cancer-A Systematic Review.

PubMed

Taioli, Emanuela; Schwartz, Rebecca M; Lieberman-Cribbin, Wil; Moskowitz, Gil; van Gerwen, Maaike; Flores, Raja

2017-01-01

Although esophageal cancer is rare in the United States, 5-year survival and quality of life (QoL) are poor following esophageal cancer surgery. Although esophageal cancer has been surgically treated with esophagectomy through thoracotomy, an open procedure, minimally invasive surgical procedures have been recently introduced to decrease the risk of complications and improve QoL after surgery. The current study is a systematic review of the published literature to assess differences in QoL after traditional (open) or minimally invasive esophagectomy. We hypothesized that QoL is consistently better in patients treated with minimally invasive surgery than in those treated with a more traditional and invasive approach. Although global health, social function, and emotional function improved more commonly after minimally invasive surgery compared with open surgery, physical function and role function, as well as symptoms including choking, dysphagia, eating problems, and trouble swallowing saliva, declined for both surgery types. Cognitive function was equivocal across both groups. The potential small benefits in global and mental health status among those who experience minimally invasive surgery should be considered with caution given the possibility of publication and selection bias. Copyright © 2017 Elsevier Inc. All rights reserved.

Suppression of bovine lymphocyte function by treatment with physiologic concentrations of cortisone

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

Ojo-Amaize, E.A.; Paape, M.J.; Guidry, A.J.

1986-03-01

The blastogenic response of peripheral blood lymphocytes (PBL) (8 cows) to capsular antigen extract of Staphylococcus aureus, PHA and LPS was measured in vitro using /sup 5/H-thymidine pulse labelling. isolated PBL were treated in vitro for 6-8 days with 10, 25 and 45 ng/ml cortisone. These concentrations simulate serum corticosteroid levels during environmental stress, acute clinical mastitis and ACTH therapy, respectively. To determine the minimal concentration of cortisone that would induce suppression, PBL were also incubated with increasing concentrations of cortisone starting at 10 pg/ml. All concentrations of cortisone caused a significant (P<0.01) depression of lymphocyte blastogenic response to S.more » aureus, PHA and LPS. Macrophage depletion experiments showed no macrophage suppressor effects. Both the blastogenic response of untreated peripheral blood lymphocytes to S. aureus, PHA and LPS and the degree to which that response was suppressed by cortisone differed significantly among cows. Results indicate that cortisone levels found during physiological stress and after therapeutic administration of ACTH can suppress lymphocyte function.« less

[Functional morphology of the submandibular salivary glands of white rats during aging involution].

PubMed

Rybakova, M G

1979-12-01

Functional morphology of different zones of submandibular glands of albino rats was studied quantitatively with due regard for the stages of neuroendocrine system involution. It is shown that function of salivary glands during ageing is not altered; cyclic fluctuations with estral cycle phases are maintained similarly to those in young animals. But the basal level of proteins and mucopolysaccharides is reduced, their mean levels being equal to the minimal level in young animals. On the other hand, activation of enzymes responsible for energy and transport processes takes place and their relationships change. The data obtained prove the relationship between salivary and endocrine glands and confirm the viewpoint that in early age involution disintegration occurs between different parameters of the functional activity of salivary glands rather than there take place changes in their function.

Mechanical effort predicts the selection of ankle over hip strategies in nonstepping postural responses

PubMed Central

Jonkers, Ilse; De Schutter, Joris; De Groote, Friedl

2016-01-01

Experimental studies have shown that a continuum of ankle and hip strategies is used to restore posture following an external perturbation. Postural responses can be modeled by feedback control with feedback gains that optimize a specific objective. On the one hand, feedback gains that minimize effort have been used to predict muscle activity during perturbed standing. On the other hand, hip and ankle strategies have been predicted by minimizing postural instability and deviation from upright posture. It remains unclear, however, whether and how effort minimization influences the selection of a specific postural response. We hypothesize that the relative importance of minimizing mechanical work vs. postural instability influences the strategy used to restore upright posture. This hypothesis was investigated based on experiments and predictive simulations of the postural response following a backward support surface translation. Peak hip flexion angle was significantly correlated with three experimentally determined measures of effort, i.e., mechanical work, mean muscle activity and metabolic energy. Furthermore, a continuum of ankle and hip strategies was predicted in simulation when changing the relative importance of minimizing mechanical work and postural instability, with increased weighting of mechanical work resulting in an ankle strategy. In conclusion, the combination of experimental measurements and predictive simulations of the postural response to a backward support surface translation showed that the trade-off between effort and postural instability minimization can explain the selection of a specific postural response in the continuum of potential ankle and hip strategies. PMID:27489362

Minimal Network Topologies for Signal Processing during Collective Cell Chemotaxis.

PubMed

Yue, Haicen; Camley, Brian A; Rappel, Wouter-Jan

2018-06-19

Cell-cell communication plays an important role in collective cell migration. However, it remains unclear how cells in a group cooperatively process external signals to determine the group's direction of motion. Although the topology of signaling pathways is vitally important in single-cell chemotaxis, the signaling topology for collective chemotaxis has not been systematically studied. Here, we combine mathematical analysis and simulations to find minimal network topologies for multicellular signal processing in collective chemotaxis. We focus on border cell cluster chemotaxis in the Drosophila egg chamber, in which responses to several experimental perturbations of the signaling network are known. Our minimal signaling network includes only four elements: a chemoattractant, the protein Rac (indicating cell activation), cell protrusion, and a hypothesized global factor responsible for cell-cell interaction. Experimental data on cell protrusion statistics allows us to systematically narrow the number of possible topologies from more than 40,000,000 to only six minimal topologies with six interactions between the four elements. This analysis does not require a specific functional form of the interactions, and only qualitative features are needed; it is thus robust to many modeling choices. Simulations of a stochastic biochemical model of border cell chemotaxis show that the qualitative selection procedure accurately determines which topologies are consistent with the experiment. We fit our model for all six proposed topologies; each produces results that are consistent with all experimentally available data. Finally, we suggest experiments to further discriminate possible pathway topologies. Copyright © 2018 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Reliability and Responsiveness of NutriQoL® Questionnaire.

PubMed

Cuerda, Maria Cristina; Apezetxea, Antonio; Carrillo, Lourdes; Casanueva, Felipe; Cuesta, Federico; Irles, Jose Antonio; Virgili, Maria Nuria; Layola, Miquel; Lizán, Luis

2016-10-01

NutriQoL ® (Nestlé Health Science, Vevay, Switzerland) is a questionnaire developed to assess the health-related quality-of-life (HRQoL) of patients with home enteral nutrition (HEN) irrespective of their underlying condition and route of administration. The aim of this work is assessing the questionnaire's reliability and responsiveness to change. Two cohorts of patients with HEN and their primary caregivers were enrolled to assess reliability and responsiveness, respectively. All participants had to be 18 years of age or older, without mental deterioration (≤3 or 4 errors in the Pfeiffer's test) and with sufficient functional status (>40 points on Karnovsky's performance status scale). When the patients' ability to respond to the questionnaire was impaired due to underlying disease, their caregivers answered on their behalf. NutriQoL was administered in two and three visits to reliability and responsiveness cohorts, respectively. Test-retest reliability and internal consistency were assessed by the intra-class correlation coefficient (ICC) and the Cronbach's α, respectively. Responsiveness was evaluated by standardized effect size and standardized response mean between basal visit and third visit. Finally, the minimal clinically important difference (MCID) was estimated. A total of 54 and 86 participants were recruited to the reliability and responsiveness cohort, respectively. Thirty-five caregivers were selected to assess the inter-observer reliability. ICC values confirmed the good reproducibility level (ICC >0.75) of the questionnaire in both "physical functioning and activities of daily living" and "social life" domains and total score. The assessment of internal consistency in both domains of the questionnaire showed good internal consistency in visit 2. ICC showed the excellent agreement level between caregiver and patient in the global NutriQoL score. Finally, patients classified as having a minimal change in their health reported a mean (standard deviation) MCID in NutriQoL score of 0.63 (11.51). NutriQoL is a reliable and unique instrument to measure the HRQoL in HEN patients. NutriQoL detects changes in the health status of the patient. Nevertheless, further research is needed to determine the full extent of the questionnaire responsiveness.

10 CFR 850.25 - Exposure reduction and minimization.

Code of Federal Regulations, 2010 CFR

2010-01-01

... § 850.25 Exposure reduction and minimization. (a) The responsible employer must ensure that no worker is exposed above the exposure limit prescribed in § 850.22. (b) The responsible employer must, in addition... described in the responsible employer's CBDPP and must include: (i) Annual goals for exposure reduction and...

E. H. Butler Library Disaster Response Plan. Third Edition.

ERIC Educational Resources Information Center

State Univ. of New York, Buffalo. Coll. at Buffalo.

The purpose of this plan is to minimize the potential for disaster and to minimize damage to materials if a disaster should occur. It contains: emergency instructions; evacuation procedures; a disaster contact list; and sections on salvage priorities, prevention, protection, response, recovery, rehabilitation, disaster team responsibilities,…

Colorimetric and Fluorescent Biosensors Based on Directed Assembly of Nanomaterials with Functional DNA

NASA Astrophysics Data System (ADS)

Liu, Juewen; Lu, Yi

This chapter reviews recent progress in the interface between functional nucleic acids and nanoscale science and technology, and its analytical applications. In particular, the use of metallic nanoparticles as the color reporting groups for the action (binding, catalysis, or both) of aptamers, DNAzymes, and aptazymes is described in detail. Because metallic nanoparticles possess high extinction coefficients and distance-dependent optical properties, they allow highly sensitive detections with minimal consumption of materials. The combination of quantum dots (QDs) with functional nucleic acids as fluorescent sensors is also described. The chapter starts with the design of colorimetric and fluorescent sensors responsive to single analytes, followed by sensors responsive to multiple analytes with controllable cooperativity and multiplex detection using both colorimetric and fluorescent signals in one pot, and ends by transferring solution-based detections into litmus paper type of tests, making them generally applicable and usable for a wide range of on-site and real-time analytical applications such as household tests, environmental monitoring, and clinical diagnostics.

Efficient swimming of a plunging elastic plate in a viscous fluid

NASA Astrophysics Data System (ADS)

Yeh, Peter; Alexeev, Alexander

2014-03-01

We use three dimensional computer simulations to examine the combined hydrodynamics and structural response of a plunging elastic plate submerged in a viscous fluid with Reynolds number of 250. The plate is actuated at the root with a prescribed vertical sinusoidal displacement and a zero slope (clamped) boundary condition. We explore the steady state swimming velocity and the associated input power as a function of driving frequency, added mass, and aspect ratio. We find a universal bending pattern independent of geometry and added mass that maximizes the distance traveled per unit applied work. This bending pattern is associated with minimizing center of mass oscillations normal to the direction of travel. Subsequently, the flow around the sides of the swimmer, which does not aid in propulsion, is minimized, thereby reducing viscous losses.

Neuroethics and Disorders of Consciousness: Discerning Brain States in Clinical Practice and Research.

PubMed

Fins, Joseph J

2016-12-01

Decisions about end-of-life care and participation in clinical research for patients with disorders of consciousness begin with diagnostic discernment. Accurately distinguishing between brain states clarifies clinicians' ethical obligations and responsibilities. Central to this effort is the obligation to provide neuropalliative care for patients in the minimally conscious state who can perceive pain and to restore functional communication through neuroprosthetics, drugs, and rehabilitation to patients with intact but underactivated neural networks. Efforts to bring scientific advances to patients with disorders of consciousness are reviewed, including the investigational use of deep brain stimulation in patients in the minimally conscious state. These efforts help to affirm the civil rights of a population long on the margins. © 2016 American Medical Association. All Rights Reserved.

Modeling alternative binding registers of a minimal immunogenic peptide on two class II major histocompatibility complex (MHC II) molecules predicts polarized T-cell receptor (TCR) contact positions.

PubMed

Murray, J S; Fois, S D S; Schountz, T; Ford, S R; Tawde, M D; Brown, J C; Siahaan, T J

2002-03-01

Several major histocompatibility complex class II (MHC II) complexes with known minimal immunogenic peptides have now been solved by X-ray crystallography. Specificity pockets within the MHC II binding groove provide distinct peptide contacts that influence peptide conformation and define the binding register within different allelic MHC II molecules. Altering peptide ligands with respect to the residues that contact the T-cell receptor (TCR) can drastically change the nature of the ensuing immune response. Here, we provide an example of how MHC II (I-A) molecules may indirectly effect TCR contacts with a peptide and drive functionally distinct immune responses. We modeled the same immunogenic 12-amino acid peptide into the binding grooves of two allelic MHC II molecules linked to distinct cytokine responses against the peptide. Surprisingly, the favored conformation of the peptide in each molecule was distinct with respect to the exposure of the N- or C-terminus of the peptide above the MHC II binding groove. T-cell clones derived from each allelic MHC II genotype were found to be allele-restricted with respect to the recognition of these N- vs. C-terminal residues on the bound peptide. Taken together, these data suggest that MHC II alleles may influence T-cell functions by restricting TCR access to specific residues of the I-A-bound peptide. Thus, these data are of significance to diseases that display genetic linkage to specific MHC II alleles, e.g. type 1 diabetes and rheumatoid arthritis.

Progress in Developing Transfer Functions for Surface Scanning Eddy Current Inspections

NASA Astrophysics Data System (ADS)

Shearer, J.; Heebl, J.; Brausch, J.; Lindgren, E.

2009-03-01

As US Air Force (USAF) aircraft continue to age, additional inspections are required for structural components. The validation of new inspections typically requires a capability demonstration of the method using representative structure with representative damage. To minimize the time and cost required to prepare such samples, Electric Discharge machined (EDM) notches are commonly used to represent fatigue cracks in validation studies. However, the sensitivity to damage typically changes as a function of damage type. This requires a mathematical relationship to be developed between the responses from the two different flaw types to enable the use of EDM notched samples to validate new inspections. This paper reviews progress to develop transfer functions for surface scanning eddy current inspections of aluminum and titanium alloys found in structural aircraft components. Multiple samples with well characterized grown fatigue cracks and master gages with EDM notches, both with a range of flaw sizes, were used to collect flaw signals with USAF field inspection equipment. Analysis of this empirical data was used to develop a transfer function between the response from the EDM notches and grown fatigue cracks.

Determinants of Mammalian Nucleolar Architecture

PubMed Central

Farley, Katherine I.; Surovtseva, Yulia; Merkel, Janie; Baserga, Susan J.

2015-01-01

The nucleolus is responsible for the production of ribosomes, essential machines which synthesize all proteins needed by the cell. The structure of human nucleoli is highly dynamic and is directly related to its functions in ribosome biogenesis. Despite the importance of this organelle, the intricate relationship between nucleolar structure and function remains largely unexplored. How do cells control nucleolar formation and function? What are the minimal requirements for making a functional nucleolus? Here we review what is currently known regarding mammalian nucleolar formation at nucleolar organizer regions (NORs), which can be studied by observing the dissolution and reformation of the nucleolus during each cell division. Additionally, the nucleolus can be examined by analyzing how alterations in nucleolar function manifest in differences in nucleolar architecture. Furthermore, changes in nucleolar structure and function are correlated with cancer, highlighting the importance of studying the determinants of nucleolar formation. PMID:25670395

Quantitative Image Informatics for Cancer Research (QIICR) | Informatics Technology for Cancer Research (ITCR)

Cancer.gov

Imaging has enormous untapped potential to improve cancer research through software to extract and process morphometric and functional biomarkers. In the era of non-cytotoxic treatment agents, multi- modality image-guided ablative therapies and rapidly evolving computational resources, quantitative imaging software can be transformative in enabling minimally invasive, objective and reproducible evaluation of cancer treatment response. Post-processing algorithms are integral to high-throughput analysis and fine- grained differentiation of multiple molecular targets.

The development and validation of a questionnaire for rotator cuff disorders: The Functional Shoulder Score

PubMed Central

Ibrahim, Edward F; Petrou, Charalambos; Galanos, Antonis

2015-01-01

Background The purpose of the present study was to validate the Functional Shoulder Score (FSS), a new patient-reported outcome score specifically designed to evaluate patients with rotator cuff disorders. Methods One hundred and nineteen patients were assessed using two shoulder scoring systems [the FSS and the Constant–Murley Score (CMS)] at 3 weeks pre- and 6 months post-arthroscopic rotator cuff surgery. The reliability, validity, responsiveness and interpretability of the FSS were evaluated. Results Reliability analysis (test–retest) showed an intraclass correlation coefficient value of 0.96 [95% confidence interval (CI) = 0.92 to 0.98]. Internal consistency analysis revealed a Cronbach's alpha coefficient of 0.93. The Pearson correlation coefficient FSS-CMS was 0.782 pre-operatively and 0.737 postoperatively (p < 0.0005). There was a statistically significant increase in FSS scores postoperatively, an effect size of 3.06 and standardized response mean of 2.80. The value for minimal detectable change was ±8.38 scale points (based on a 90% CI) and the minimal clinically important difference for improvement was 24.7 ± 5.4 points. Conclusions The FSS is a patient-reported outcome measure that can easily be incorporated into clinical practice, providing a quick, reliable, valid and practical measure for rotator cuff problems. The questionnaire is highly sensitive to clinical change. PMID:27582986

Action-minimizing solutions of the one-dimensional N-body problem

NASA Astrophysics Data System (ADS)

Yu, Xiang; Zhang, Shiqing

2018-05-01

We supplement the following result of C. Marchal on the Newtonian N-body problem: A path minimizing the Lagrangian action functional between two given configurations is always a true (collision-free) solution when the dimension d of the physical space R^d satisfies d≥2. The focus of this paper is on the fixed-ends problem for the one-dimensional Newtonian N-body problem. We prove that a path minimizing the action functional in the set of paths joining two given configurations and having all the time the same order is always a true (collision-free) solution. Considering the one-dimensional N-body problem with equal masses, we prove that (i) collision instants are isolated for a path minimizing the action functional between two given configurations, (ii) if the particles at two endpoints have the same order, then the path minimizing the action functional is always a true (collision-free) solution and (iii) when the particles at two endpoints have different order, although there must be collisions for any path, we can prove that there are at most N! - 1 collisions for any action-minimizing path.

Redundant and distinct functions of the ABA response loci ABA-INSENSITIVE(ABI)5 and ABRE-BINDING FACTOR (ABF)3.

PubMed

Finkelstein, Ruth; Gampala, Srinivas S L; Lynch, Tim J; Thomas, Terry L; Rock, Christopher D

2005-09-01

Abscisic acid-responsive gene expression is regulated by numerous transcription factors, including a subgroup of basic leucine zipper factors that bind to the conserved cis-acting sequences known as ABA-responsive elements. Although one of these factors, ABA-insensitive 5 (ABI5), was identified genetically, the paucity of genetic data for the other family members has left it unclear whether they perform unique functions or act redundantly to ABI5 or each other. To test for potential redundancy with ABI5, we identified the family members with most similar effects and interactions in transient expression systems (ABF3 and ABF1), then characterized loss-of-function lines for those loci. The abf1 and abf3 monogenic mutant lines had at most minimal effects on germination or seed-specific gene expression, but the enhanced ABA- and stress-resistance of abf3 abi5 double mutants revealed redundant action of these genes in multiple stress responses of seeds and seedlings. Although ABI5, ABF3, and ABF1 have some overlapping effects, they appear to antagonistically regulate each other's expression at specific stages. Consequently, loss of any one factor may be partially compensated by increased expression of other family members.

Emotional intelligence is associated with reduced insula responses to masked angry faces.

PubMed

Alkozei, Anna; Killgore, William D S

2015-07-08

High levels of emotional intelligence (EI) have been associated with increased success in the workplace, greater quality of personal relationships, and enhanced wellbeing. Evidence suggests that EI is mediated extensively by the interplay of key emotion regions including the amygdala, insula, and ventromedial prefrontal cortex, among others. The insula, in particular, is important for processing interoceptive and somatic cues that are interpreted as emotional responses. We investigated the association between EI and functional brain responses within the aforementioned neurocircuitry in response to subliminal presentations of social threat. Fifty-four healthy adults completed the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) and underwent functional magnetic brain imaging while viewing subliminal presentations of faces displaying anger, using a backward masked facial affect paradigm to minimize conscious awareness of the expressed emotion. In response to masked angry faces, the total MSCEIT scores correlated negatively with a cluster of activation located within the left insula, but not with activation in any other region of interest. Considering the insula's role in the processing of interoceptive emotional cues, the results suggest that greater EI is associated with reduced emotional visceral reactivity and/or more accurate interoceptive prediction when confronted with stimuli indicative of social threat.

Development of a music therapy assessment tool for patients in low awareness states.

PubMed

Magee, Wendy L

2007-01-01

People in low awareness states following profound brain injury typically demonstrate subtle changes in functional behaviors which challenge the sensitivity of measurement tools. Failure to identify and measure changes in functioning can lead to misdiagnosis and withdrawal of treatment with this population. Thus, the development of tools which are sensitive to responsiveness is of central concern. As the auditory modality has been found to be particularly sensitive in identifying responses indicating awareness, a convincing case can be made for music therapy as a treatment medium. However, little has been recommended about protocols for intervention or tools for measuring patient responses within the music therapy setting. This paper presents the rationale for an assessment tool specifically designed to measure responses in the music therapy setting with patients who are diagnosed as minimally conscious or in a vegetative state. Developed over fourteen years as part of interdisciplinary assessment and treatment, the music therapy assessment tool for low awareness states (MATLAS) contains fourteen items which rate behavioral responses across a number of domains. The tool can provide important information for interdisciplinary assessment and treatment particularly in the auditory and communication domains. Recommendations are made for testing its reliability and validity through research.

Selective and sustained attention in children with spina bifida myelomeningocele.

PubMed

Caspersen, Ida Dyhr; Habekost, Thomas

2013-01-01

Spina bifida myelomeningocele (SBM) is a neural tube defect that has been related to deficits in several cognitive domains including attention. Attention function in children with SBM has often been studied using tasks that are confounded by complex motor demands or tasks that do not clearly distinguish perceptual from response-related components of attention. We used a verbal-report paradigm based on the Theory of Visual Attention (Bundesen, 1990) and a new continuous performance test, the Dual Attention to Response Task (Dockree et al., 2006), for measuring parameters of selective and sustained attention in 6 children with SBM and 18 healthy control children. The two tasks had minimal motor demands, were functionally specific and were sensitive to minor deficits. As a group, the children with SBM were significantly less efficient at filtering out irrelevant stimuli. Moreover, they exhibited frequent failures of sustained attention and response control in terms of omission errors, premature responses, and prolonged inhibition responses. All 6 children with SBM showed deficits in one or more parameters of attention; for example, three patients had elevated visual perception thresholds, but large individual variation was evident in their performance patterns, which highlights the relevance of an effective case-based assessment method in this patient group. Overall, the study demonstrates the strengths of a new testing approach for evaluating attention function in children with SBM.

Assessment of platelet function in healthy cats in response to commonly prescribed antiplatelet drugs using three point-of-care platelet function tests.

PubMed

Ho, Kimberly K; Abrams-Ogg, Anthony Cg; Wood, R Darren; O'Sullivan, M Lynne; Kirby, Gordon M; Blois, Shauna L

2017-06-01

Objectives The objective was to determine if decreased platelet function could be detected after treatment with aspirin and/or clopidogrel in healthy cats using three point-of-care platelet function tests that evaluate platelet function by different methods: Multiplate (by impedance), Platelet Function Analyzer 100 (by mechanical aperture closure) and Plateletworks (by platelet counting). Methods Thirty-six healthy cats were randomly assigned to receive one of three oral treatments over an 8 day period: (1) aspirin 5 mg q72h; (2) aspirin 20.25 mg q72h; or (3) clopidogrel 18.75 mg q24h. Cats treated with 5 and 20.25 mg aspirin also received clopidogrel on days 4-8. Platelet aggregation in response to adenosine diphosphate and collagen ± arachidonic acid was assessed on days 1 (baseline), 4 and 8. Aspirin and clopidogrel metabolites were measured by high-performance liquid chromatography. Platelet function in response to treatment was analyzed by ANCOVA, linear regression and Spearman correlation. Results The only solitary aspirin effect was detected using Plateletworks with collagen in cats treated with 20.25 mg. The only effect detected by Multiplate was using arachidonic acid in cats treated with both aspirin 20.25 mg and clopidogrel. All clopidogrel treatment effects were detected by Platelet Function Analyzer 100, Plateletworks (adenosine diphosphate) and Plateletworks (collagen). Drug metabolites were present in all cats, but concentrations were minimally correlated to platelet function test results. Conclusions and relevance Platelet Function Analyzer 100 and Plateletworks using adenosine diphosphate ± collagen agonists may be used to detect decreased platelet function in response to clopidogrel treatment. Either aspirin is not as effective an antiplatelet drug as clopidogrel, or the tests used were not optimal to measure aspirin effect. Cats with heart disease are commonly prescribed antiplatelet drugs to decrease the risk of aortic thromboembolism. Platelet Function Analyzer 100 and Plateletworks may be useful for confirming clopidogrel treatment in these cats.

ROS signaling, oxidative stress and Nrf2 in pancreatic beta-cell function

PubMed Central

Pi, Jingbo; Zhang, Qiang; Fu, Jingqi; Woods, Courtney G.; Hou, Yongyong; Corkey, Barbara E; Collins, Sheila; Andersen, Melvin E.

2009-01-01

This review focuses on the emerging evidence that reactive oxygen species (ROS) derived from glucose metabolism, such as H2O2, act as metabolic signaling molecules for glucose-stimulated insulin secretion (GSIS) in pancreatic beta-cells. Particular emphasis is placed on the potential inhibitory role of endogenous antioxidants, which rise in response to oxidative stress, in glucose-triggered ROS and GSIS. We propose that cellular adaptive response to oxidative stress challenge, such as nuclear factor E2-related factor 2 (Nrf2)-mediated antioxidant induction, plays paradoxical roles in pancreatic beta-cell function. On the one hand, induction of antioxidant enzymes protects beta-cells from oxidative damage and possible cell death, thus minimizing oxidative damage-related impairment of insulin secretion. On the other hand, the induction of antioxidant enzymes by Nrf2 activation blunts glucose-triggered ROS signaling, thus resulting in reduced GSIS. These two premises are potentially relevant to impairment of beta-cells occurring in the late and early stage of Type 2 diabetes, respectively. In addition, we summarized our recent findings that persistent oxidative stress due to absence of uncoupling protein 2 activates cellular adaptive response which is associated with impaired pancreatic beta-cell function. PMID:19501608

The structure of a thermophilic kinase shapes fitness upon random circular permutation

PubMed Central

Jones, Alicia M.; Mehta, Manan M.; Thomas, Emily E.; Atkinson, Joshua T.; Segall-Shapiro, Thomas H.; Liu, Shirley; Silberg, Jonathan J.

2016-01-01

Proteins can be engineered for synthetic biology through circular permutation, a sequence rearrangement where native protein termini become linked and new termini are created elsewhere through backbone fission. However, it remains challenging to anticipate a protein’s functional tolerance to circular permutation. Here, we describe new transposons for creating libraries of randomly circularly permuted proteins that minimize peptide additions at their termini, and we use transposase mutagenesis to study the tolerance of a thermophilic adenylate kinase (AK) to circular permutation. We find that libraries expressing permuted AK with either short or long peptides amended to their N-terminus yield distinct sets of active variants and present evidence that this trend arises because permuted protein expression varies across libraries. Mapping all sites that tolerate backbone cleavage onto AK structure reveals that the largest contiguous regions of sequence that lack cleavage sites are proximal to the phosphotransfer site. A comparison of our results with a range of structure-derived parameters further showed that retention of function correlates to the strongest extent with the distance to the phosphotransfer site, amino acid variability in an AK family sequence alignment, and residue-level deviations in superimposed AK structures. Our work illustrates how permuted protein libraries can be created with minimal peptide additions using transposase mutagenesis, and they reveal a challenge of maintaining consistent expression across permuted variants in a library that minimizes peptide additions. Furthermore, these findings provide a basis for interpreting responses of thermophilic phosphotransferases to circular permutation by calibrating how different structure-derived parameters relate to retention of function in a cellular selection. PMID:26976658

The Structure of a Thermophilic Kinase Shapes Fitness upon Random Circular Permutation.

PubMed

Jones, Alicia M; Mehta, Manan M; Thomas, Emily E; Atkinson, Joshua T; Segall-Shapiro, Thomas H; Liu, Shirley; Silberg, Jonathan J

2016-05-20

Proteins can be engineered for synthetic biology through circular permutation, a sequence rearrangement in which native protein termini become linked and new termini are created elsewhere through backbone fission. However, it remains challenging to anticipate a protein's functional tolerance to circular permutation. Here, we describe new transposons for creating libraries of randomly circularly permuted proteins that minimize peptide additions at their termini, and we use transposase mutagenesis to study the tolerance of a thermophilic adenylate kinase (AK) to circular permutation. We find that libraries expressing permuted AKs with either short or long peptides amended to their N-terminus yield distinct sets of active variants and present evidence that this trend arises because permuted protein expression varies across libraries. Mapping all sites that tolerate backbone cleavage onto AK structure reveals that the largest contiguous regions of sequence that lack cleavage sites are proximal to the phosphotransfer site. A comparison of our results with a range of structure-derived parameters further showed that retention of function correlates to the strongest extent with the distance to the phosphotransfer site, amino acid variability in an AK family sequence alignment, and residue-level deviations in superimposed AK structures. Our work illustrates how permuted protein libraries can be created with minimal peptide additions using transposase mutagenesis, and it reveals a challenge of maintaining consistent expression across permuted variants in a library that minimizes peptide additions. Furthermore, these findings provide a basis for interpreting responses of thermophilic phosphotransferases to circular permutation by calibrating how different structure-derived parameters relate to retention of function in a cellular selection.

Clinical feasibility test on a minimally invasive laser therapy system in microsurgery of nerves.

PubMed

Mack, K F; Leinung, M; Stieve, M; Lenarz, T; Schwab, B

2008-01-01

The clinical feasibility test described here evaluates the basis for a laser therapy system that enables tumour tissue to be separated from nerves in a minimally invasive manner. It was first investigated whether, using an Er:YAG laser, laser-induced nerve (specifically, facial nerve) responses in the rabbit in vivo can be reliably detected with the hitherto standard monitoring techniques. Peripherally recordable neuromuscular signals (i.e. compound action potentials, CAPs) were used to monitor nerve function and to establish a feedback loop. The first occurrence of laser-evoked CAPs was taken as the criterion for deciding when to switch off the laser. When drawing up criteria governing the control and termination of the laser application, the priority was the maintenance of nerve function. Five needle-electrode arrays specially developed for this purpose, each with a miniature preamplifier, were then placed into the facial musculature instead of single-needle electrodes. The system was tested in vivo under realistic surgical conditions (i.e. facial-nerve surgery in the rabbit). This modified multi-channel electromyography (EMG) system enabled laser-evoked CAPs to be detected that have amplitudes 10 times smaller than those picked up by commercially available systems. This optimization, and the connection of the neuromuscular unit with the Er:YAG laser via the electrode array to create a feedback loop, were designed to make it possible to maintain online control of the laser ablation process in the vicinity of neuronal tissue, thus ensuring that tissue excision is both reliable and does not affect function. Our results open up new possibilities in minimally invasive surgery near neural structures.

Massively parallel GPU-accelerated minimization of classical density functional theory

NASA Astrophysics Data System (ADS)

Stopper, Daniel; Roth, Roland

2017-08-01

In this paper, we discuss the ability to numerically minimize the grand potential of hard disks in two-dimensional and of hard spheres in three-dimensional space within the framework of classical density functional and fundamental measure theory on modern graphics cards. Our main finding is that a massively parallel minimization leads to an enormous performance gain in comparison to standard sequential minimization schemes. Furthermore, the results indicate that in complex multi-dimensional situations, a heavy parallel minimization of the grand potential seems to be mandatory in order to reach a reasonable balance between accuracy and computational cost.

Understanding Lymphatic Valve Function via Computational Modeling

NASA Astrophysics Data System (ADS)

Wolf, Ki; Nepiyushchikh, Zhanna; Razavi, Mohammad; Dixon, Brandon; Alexeev, Alexander

2017-11-01

The lymphatic system is a crucial part to the circulatory system with many important functions, such as transport of interstitial fluid, fatty acid, and immune cells. Lymphatic vessels' contractile walls and valves allow lymph flow against adverse pressure gradients and prevent back flow. Yet, the effect of lymphatic valves' geometric and mechanical properties to pumping performance and lymphatic dysfunctions like lymphedema is not well understood. Our coupled fluid-solid computational model based on lattice Boltzmann model and lattice spring model investigates the dynamics and effectiveness of lymphatic valves in resistance minimization, backflow prevention, and viscoelastic response under different geometric and mechanical properties, suggesting the range of lymphatic valve parameters with effective pumping performance. Our model also provides more physiologically relevant relations of the valve response under varied conditions to a lumped parameter model of the lymphatic system giving an integrative insight into lymphatic system performance, including its failure due to diseases. NSF CMMI-1635133.

Targeting Wnts at the source--new mechanisms, new biomarkers, new drugs.

PubMed

Madan, Babita; Virshup, David M

2015-05-01

Wnt signaling is dysregulated in many cancers and is therefore an attractive therapeutic target. The focus of drug development has recently shifted away from downstream inhibitors of β-catenin. Active inhibitors of Wnt secretion and Wnt/receptor interactions have been developed that are now entering clinical trials. Such agents include inhibitors of Wnt secretion, as well as recombinant proteins that minimize Wnt-Frizzled interactions. These new therapies arrive together with the recent insight that cancer-specific upregulation of Wnt receptors at the cell surface regulates cellular sensitivity to Wnts. Loss-of-function mutations in RNF43 or ZNRF3 and gain-of-function chromosome translocations involving RSPO2 and RSPO3 are surprisingly common and markedly increase Wnt/β-catenin signaling in response to secreted Wnts. These mutations may be predictive biomarkers to select patients responsive to newly developed upstream Wnt inhibitors. ©2015 American Association for Cancer Research.

Architecture of the Yeast RNA Polymerase II Open Complex and Regulation of Activity by TFIIF

PubMed Central

Fishburn, James

2012-01-01

To investigate the function and architecture of the open complex state of RNA polymerase II (Pol II), Saccharomyces cerevisiae minimal open complexes were assembled by using a series of heteroduplex HIS4 promoters, TATA binding protein (TBP), TFIIB, and Pol II. The yeast system demonstrates great flexibility in the position of active open complexes, spanning 30 to 80 bp downstream from TATA, consistent with the transcription start site scanning behavior of yeast Pol II. TFIIF unexpectedly modulates the activity of the open complexes, either repressing or stimulating initiation. The response to TFIIF was dependent on the sequence of the template strand within the single-stranded bubble. Mutations in the TFIIB reader and linker region, which were inactive on duplex DNA, were suppressed by the heteroduplex templates, showing that a major function of the TFIIB reader and linker is in the initiation or stabilization of single-stranded DNA. Probing of the architecture of the minimal open complexes with TFIIB-FeBABE [TFIIB–p-bromoacetamidobenzyl–EDTA-iron(III)] derivatives showed that the TFIIB core domain is surprisingly positioned away from Pol II, and the addition of TFIIF repositions the TFIIB core domain to the Pol II wall domain. Together, our results show an unexpected architecture of minimal open complexes and the regulation of activity by TFIIF and the TFIIB core domain. PMID:22025674

Validity, responsiveness, and minimal clinically important difference of EQ-5D-5L in stroke patients undergoing rehabilitation.

PubMed

Chen, Poyu; Lin, Keh-Chung; Liing, Rong-Jiuan; Wu, Ching-Yi; Chen, Chia-Ling; Chang, Ku-Chou

2016-06-01

To examine the criterion validity, responsiveness, and minimal clinically important difference (MCID) of the EuroQoL 5-Dimensions Questionnaire (EQ-5D-5L) and visual analog scale (EQ-VAS) in people receiving rehabilitation after stroke. The EQ-5D-5L, along with four criterion measures-the Medical Research Council scales for muscle strength, the Fugl-Meyer assessment, the functional independence measure, and the Stroke Impact Scale-was administered to 65 patients with stroke before and after 3- to 4-week therapy. Criterion validity was estimated using the Spearman correlation coefficient. Responsiveness was analyzed by the effect size, standardized response mean (SRM), and criterion responsiveness. The MCID was determined by anchor-based and distribution-based approaches. The percentage of patients exceeding the MCID was also reported. Concurrent validity of the EQ-Index was better compared with the EQ-VAS. The EQ-Index has better power for predicting the rehabilitation outcome in the activities of daily living than other motor-related outcome measures. The EQ-Index was moderately responsive to change (SRM = 0.63), whereas the EQ-VAS was only mildly responsive to change. The MCID estimation of the EQ-Index (the percentage of patients exceeding the MCID) was 0.10 (33.8 %) and 0.10 (33.8 %) based on the anchor-based and distribution-based approaches, respectively, and the estimation of EQ-VAS was 8.61 (41.5 %) and 10.82 (32.3 %). The EQ-Index has shown reasonable concurrent validity, limited predictive validity, and acceptable responsiveness for detecting the health-related quality of life in stroke patients undergoing rehabilitation, but not for EQ-VAS. Future research considering different recovery stages after stroke is warranted to validate these estimations.

Price-Minimizing Behaviors in Response to Increasing Tobacco Price: A Cross-Sectional Study of Students

ERIC Educational Resources Information Center

Rutter, Lucy; Britton, John; Langley, Tessa

2017-01-01

Background: The public health benefits of tobacco taxation are undermined when smokers engage in price-minimizing behaviors other than quitting in response to rising prices. Methods: 314 students at the University of Nottingham, UK, completed an online survey about their smoking behavior and their likely responses to hypothetical tobacco price…

Translational neuropharmacology: the use of human isolated gastrointestinal tissues.

PubMed

Sanger, G J; Broad, J; Kung, V; Knowles, C H

2013-01-01

Translational sciences increasingly emphasize the measurement of functions in native human tissues. However, such studies must confront variations in patient age, gender, genetic background and disease. Here, these are discussed with reference to neuromuscular and neurosecretory functions of the human gastrointestinal (GI) tract. Tissues are obtained after informed consent, in collaboration with surgeons (surgical techniques help minimize variables) and pathologists. Given the difficulties of directly recording from human myenteric neurones (embedded between muscle layers), enteric motor nerve functions are studied by measuring muscle contractions/relaxations evoked by electrical stimulation of intrinsic nerves; responses are regionally dependent, often involving cholinergic and nitrergic phenotypes. Enteric sensory functions can be studied by evoking the peristaltic reflex, involving enteric sensory and motor nerves, but this has rarely been achieved. As submucosal neurones are more accessible (after removing the mucosa), direct neuronal recordings are possible. Neurosecretory functions are studied by measuring changes in short-circuit current across the mucosa. For all experiments, basic questions must be addressed. Because tissues are from patients, what are the controls and the influence of disease? How long does it take before function fully recovers? What is the impact of age- and gender-related differences? What is the optimal sample size? Addressing these and other questions minimizes variability and raises the scientific credibility of human tissue research. Such studies also reduce animal use. Further, the many differences between animal and human GI functions also means that human tissue research must question the ethical validity of using strains of animals with unproved translational significance. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

Genetic Interaction Maps in Escherichia coli Reveal Functional Crosstalk among Cell Envelope Biogenesis Pathways

PubMed Central

Vlasblom, James; Gagarinova, Alla; Phanse, Sadhna; Graham, Chris; Yousif, Fouad; Ding, Huiming; Xiong, Xuejian; Nazarians-Armavil, Anaies; Alamgir, Md; Ali, Mehrab; Pogoutse, Oxana; Pe'er, Asaf; Arnold, Roland; Michaut, Magali; Parkinson, John; Golshani, Ashkan; Whitfield, Chris; Wodak, Shoshana J.; Moreno-Hagelsieb, Gabriel; Greenblatt, Jack F.; Emili, Andrew

2011-01-01

As the interface between a microbe and its environment, the bacterial cell envelope has broad biological and clinical significance. While numerous biosynthesis genes and pathways have been identified and studied in isolation, how these intersect functionally to ensure envelope integrity during adaptive responses to environmental challenge remains unclear. To this end, we performed high-density synthetic genetic screens to generate quantitative functional association maps encompassing virtually the entire cell envelope biosynthetic machinery of Escherichia coli under both auxotrophic (rich medium) and prototrophic (minimal medium) culture conditions. The differential patterns of genetic interactions detected among >235,000 digenic mutant combinations tested reveal unexpected condition-specific functional crosstalk and genetic backup mechanisms that ensure stress-resistant envelope assembly and maintenance. These networks also provide insights into the global systems connectivity and dynamic functional reorganization of a universal bacterial structure that is both broadly conserved among eubacteria (including pathogens) and an important target. PMID:22125496

Genetic interaction maps in Escherichia coli reveal functional crosstalk among cell envelope biogenesis pathways.

PubMed

Babu, Mohan; Díaz-Mejía, J Javier; Vlasblom, James; Gagarinova, Alla; Phanse, Sadhna; Graham, Chris; Yousif, Fouad; Ding, Huiming; Xiong, Xuejian; Nazarians-Armavil, Anaies; Alamgir, Md; Ali, Mehrab; Pogoutse, Oxana; Pe'er, Asaf; Arnold, Roland; Michaut, Magali; Parkinson, John; Golshani, Ashkan; Whitfield, Chris; Wodak, Shoshana J; Moreno-Hagelsieb, Gabriel; Greenblatt, Jack F; Emili, Andrew

2011-11-01

As the interface between a microbe and its environment, the bacterial cell envelope has broad biological and clinical significance. While numerous biosynthesis genes and pathways have been identified and studied in isolation, how these intersect functionally to ensure envelope integrity during adaptive responses to environmental challenge remains unclear. To this end, we performed high-density synthetic genetic screens to generate quantitative functional association maps encompassing virtually the entire cell envelope biosynthetic machinery of Escherichia coli under both auxotrophic (rich medium) and prototrophic (minimal medium) culture conditions. The differential patterns of genetic interactions detected among > 235,000 digenic mutant combinations tested reveal unexpected condition-specific functional crosstalk and genetic backup mechanisms that ensure stress-resistant envelope assembly and maintenance. These networks also provide insights into the global systems connectivity and dynamic functional reorganization of a universal bacterial structure that is both broadly conserved among eubacteria (including pathogens) and an important target.

A Distributed Trajectory-Oriented Approach to Managing Traffic Complexity

NASA Technical Reports Server (NTRS)

Idris, Husni; Wing, David J.; Vivona, Robert; Garcia-Chico, Jose-Luis

2007-01-01

In order to handle the expected increase in air traffic volume, the next generation air transportation system is moving towards a distributed control architecture, in which ground-based service providers such as controllers and traffic managers and air-based users such as pilots share responsibility for aircraft trajectory generation and management. While its architecture becomes more distributed, the goal of the Air Traffic Management (ATM) system remains to achieve objectives such as maintaining safety and efficiency. It is, therefore, critical to design appropriate control elements to ensure that aircraft and groundbased actions result in achieving these objectives without unduly restricting user-preferred trajectories. This paper presents a trajectory-oriented approach containing two such elements. One is a trajectory flexibility preservation function, by which aircraft plan their trajectories to preserve flexibility to accommodate unforeseen events. And the other is a trajectory constraint minimization function by which ground-based agents, in collaboration with air-based agents, impose just-enough restrictions on trajectories to achieve ATM objectives, such as separation assurance and flow management. The underlying hypothesis is that preserving trajectory flexibility of each individual aircraft naturally achieves the aggregate objective of avoiding excessive traffic complexity, and that trajectory flexibility is increased by minimizing constraints without jeopardizing the intended ATM objectives. The paper presents conceptually how the two functions operate in a distributed control architecture that includes self separation. The paper illustrates the concept through hypothetical scenarios involving conflict resolution and flow management. It presents a functional analysis of the interaction and information flow between the functions. It also presents an analytical framework for defining metrics and developing methods to preserve trajectory flexibility and minimize its constraints. In this framework flexibility is defined in terms of robustness and adaptability to disturbances and the impact of constraints is illustrated through analysis of a trajectory solution space with limited degrees of freedom and in simple constraint situations involving meeting multiple times of arrival and resolving a conflict.

Scale effect on overland flow connectivity at the plot scale

NASA Astrophysics Data System (ADS)

Peñuela, A.; Javaux, M.; Bielders, C. L.

2012-06-01

A major challenge in present-day hydrological sciences is to enhance the performance of existing distributed hydrological models through a better description of subgrid processes, in particular the subgrid connectivity of flow paths. The relative surface connection function (RSC) was proposed by Antoine et al. (2009) as a functional indicator of runoff flow connectivity. For a given area, it expresses the percentage of the surface connected to the outflow boundary (C) as a function of the degree of filling of the depression storage. This function explicitly integrates the flow network at the soil surface and hence provides essential information regarding the flow paths' connectivity. It has been shown that this function could help improve the modeling of the hydrogram at the square meter scale, yet it is unknown how the scale affects the RSC function, and whether and how it can be extrapolated to other scales. The main objective of this research is to study the scale effect on overland flow connectivity (RSC function). For this purpose, digital elevation data of a real field (9 × 3 m) and three synthetic fields (6 × 6 m) with contrasting hydrological responses were used, and the RSC function was calculated at different scales by changing the length (l) or width (w) of the field. Border effects, at different extents depending on the microtopography, were observed for the smaller scales, when decreasing l or w, which resulted in a strong decrease or increase of the maximum depression storage, respectively. There was no scale effect on the RSC function when changing w. On the contrary, a remarkable scale effect was observed in the RSC function when changing l. In general, for a given degree of filling of the depression storage, C decreased as l increased. This change in C was inversely proportional to the change in l. This observation applied only up to approx. 50-70% (depending on the hydrological response of the field) of filling of depression storage, after which no correlation was found between C and l. The results of this study help identify the minimal scale to study overland flow connectivity. At scales larger than the minimal scale, the RSC function showed a great potential to be extrapolated to other scales.

Scale effect on overland flow connectivity at the plot scale

NASA Astrophysics Data System (ADS)

Peñuela, A.; Javaux, M.; Bielders, C. L.

2013-01-01

A major challenge in present-day hydrological sciences is to enhance the performance of existing distributed hydrological models through a better description of subgrid processes, in particular the subgrid connectivity of flow paths. The Relative Surface Connection (RSC) function was proposed by Antoine et al. (2009) as a functional indicator of runoff flow connectivity. For a given area, it expresses the percentage of the surface connected to the outflow boundary (C) as a function of the degree of filling of the depression storage. This function explicitly integrates the flow network at the soil surface and hence provides essential information regarding the flow paths' connectivity. It has been shown that this function could help improve the modeling of the hydrograph at the square meter scale, yet it is unknown how the scale affects the RSC function, and whether and how it can be extrapolated to other scales. The main objective of this research is to study the scale effect on overland flow connectivity (RSC function). For this purpose, digital elevation data of a real field (9 × 3 m) and three synthetic fields (6 × 6 m) with contrasting hydrological responses were used, and the RSC function was calculated at different scales by changing the length (l) or width (w) of the field. To different extents depending on the microtopography, border effects were observed for the smaller scales when decreasing l or w, which resulted in a strong decrease or increase of the maximum depression storage, respectively. There was no scale effect on the RSC function when changing w, but a remarkable scale effect was observed in the RSC function when changing l. In general, for a given degree of filling of the depression storage, C decreased as l increased, the change in C being inversely proportional to the change in l. However, this observation applied only up to approx. 50-70% (depending on the hydrological response of the field) of filling of depression storage, after which no correlation was found between C and l. The results of this study help identify the minimal scale to study overland flow connectivity. At scales larger than the minimal scale, the RSC function showed a great potential to be extrapolated to other scales.

Pendant Allyl Crosslinking as a Tunable Shape Memory Actuator for Vascular Applications

PubMed Central

Zachman, Angela L.; Lee, Sue Hyun; Balikov, Daniel A.; Kim, Kwangho; Bellan, Leon M.; Sung, Hak-Joon

2015-01-01

Thermo-responsive shape memory polymers (SMPs) can be fit into small-bore incisions and recover their functional shape upon deployment in the body. This property is of significant interest for developing the next generation of minimally-invasive medical devices. To be used in such applications, SMPs should exhibit adequate mechanical strengths that minimize adverse compliance mismatch-induced host responses (e.g. thrombosis, hyperplasia), be biodegradable, and demonstrate switch-like shape recovery near body temperature with favorable biocompatibility. Combinatorial approaches are essential in optimizing SMP material properties for a particular application. In this study, a new class of thermo-responsive SMPs with pendant, photocrosslinkable allyl groups, x%poly( -caprolactone)-co-y%( -allyl carboxylate -caprolactone) (x%PCL-y%ACPCL), are created in a robust, facile manner with readily tunable material properties. Thermomechanical and shape memory properties can be drastically altered through subtle changes in allyl composition. Molecular weight and gel content can also be altered in this combinatorial format to fine-tune material properties. Materials exhibit high elastic, switch-like shape recovery near 37 °C. Endothelial compatibility is comparable to tissue culture polystyrene (TCPS) and 100%PCL in vitro and vascular compatibility is demonstrated in vivo in a murine model of hindlimb ischemia, indicating promising suitability for vascular applications. PMID:26072363

Serving, Following, and Leading in Health Care.

PubMed

Penny, Steven M

2017-07-01

Radiologic technologists often perform diverse roles throughout the workday, and they should have at least a minimal understanding of the responsibility and effects of these roles on the patient and organization. Although technologists can practice independently or as part of a work group, individuals should be prepared to improve patient care and to function as a servant, follower, and leader for the overall success of the organization. This article examines those roles, emphasizing servantship. ©2017 American Society of Radiologic Technologists.

Responsiveness, Sensitivity, and Minimally Detectable Difference of the Graded and Redefined Assessment of Strength, Sensibility, and Prehension, Version 1.0.

PubMed

Kalsi-Ryan, Sukhvinder; Beaton, Dorcas; Ahn, Henry; Askes, Heather; Drew, Brian; Curt, Armin; Popovic, Milos R; Wang, Justin; Verrier, Mary C; Fehlings, Michael G

2016-02-01

As spinal cord injury (SCI) trials begin to involve subjects with acute cervical SCI, establishing the property of an upper limb outcome measure to detect change over time is critical for its usefulness in clinical trials. The objectives of this study were to define responsiveness, sensitivity, and minimally detectable difference (MDD) of the Graded Redefined Assessment of Strength, Sensibility, and Prehension (GRASSP). An observational, longitudinal study was conducted. International Standards of Neurological Classification of SCI (ISNCSCI), GRASSP, Capabilities of Upper Extremity Questionnaire (CUE-Q), and Spinal Cord Independence Measure (SCIM) were administered 0-10 days, 1, 3, 6, and 12 months post-injury. Standardized Response Means (SRM) for GRASSP and ISNCSCI measures were calculated. Longitudinal construct validity was calculated using Pearson correlation coefficients. Smallest real difference for all subtests was calculated to define the MDD values for all GRASSP subtests. Longitudinal construct validity demonstrated GRASSP and all external measures to be responsive to neurological change for 1 year post-injury. SRM values for the GRASSP subtests ranged from 0.25 to 0.85 units greater than that for ISNCSCI strength and sensation, SCIM-SS, and CUE-Q. MDD values for GRASSP subtests ranged from 2-5 points. GRASSP demonstrates good responsiveness and excellent sensitivity that is superior to ISNCSCI and SCIM III. MDD values are useful in the evaluation of interventions in both clinical and research settings. The responsiveness and sensitivity of GRASSP make it a valuable condition-specific measure in tetraplegia, where changes in upper limb neurological and functional outcomes are essential for evaluating the efficacy of interventions.

The effects of stress hormones on immune function may be vital for the adaptive reconfiguration of the immune system during fight-or-flight behavior.

PubMed

Adamo, Shelley A

2014-09-01

Intense, short-term stress (i.e., robust activation of the fight-or-flight response) typically produces a transient decline in resistance to disease in animals across phyla. Chemical mediators of the stress response (e.g., stress hormones) help induce this decline, suggesting that this transient immunosuppression is an evolved response. However, determining the function of stress hormones on immune function is difficult because of their complexity. Nevertheless, evidence suggests that stress hormones help maintain maximal resistance to disease during the physiological changes needed to optimize the body for intense physical activity. Work on insects demonstrates that stress hormones both shunt resources away from the immune system during fight-or-flight responses as well as reconfigure the immune system. Reconfiguring the immune system minimizes the impact of the loss of these resources and reduces the increased costs of some immune functions due to the physiological changes demanded by the fight-or-flight response. For example, during the stress response of the cricket Gryllus texensis, some molecular resources are shunted away from the immune system and toward lipid transport, resulting in a reduction in resistance to disease. However, insects' immune cells (hemocytes) have receptors for octopamine (the insect stress neurohormone). Octopamine increases many hemocyte functions, such as phagocytosis, and these changes would tend to mitigate the decline in immunity due to the loss of molecular resources. Moreover, because the stress response generates oxidative stress, some immune responses are probably more costly when activated during a stress response (e.g., those that produce reactive molecules). Some of these immune responses are depressed during stress in crickets, while others, whose costs are probably not increased during a stress response, are enhanced. Some effects of stress hormones on immune systems may be better understood as examples of reconfiguration rather than as mediating a trade-off. © The Author 2014. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

Systems and methods for energy cost optimization in a building system

DOEpatents

Turney, Robert D.; Wenzel, Michael J.

2016-09-06

Methods and systems to minimize energy cost in response to time-varying energy prices are presented for a variety of different pricing scenarios. A cascaded model predictive control system is disclosed comprising an inner controller and an outer controller. The inner controller controls power use using a derivative of a temperature setpoint and the outer controller controls temperature via a power setpoint or power deferral. An optimization procedure is used to minimize a cost function within a time horizon subject to temperature constraints, equality constraints, and demand charge constraints. Equality constraints are formulated using system model information and system state information whereas demand charge constraints are formulated using system state information and pricing information. A masking procedure is used to invalidate demand charge constraints for inactive pricing periods including peak, partial-peak, off-peak, critical-peak, and real-time.

A Boltzmann machine for the organization of intelligent machines

NASA Technical Reports Server (NTRS)

Moed, Michael C.; Saridis, George N.

1990-01-01

A three-tier structure consisting of organization, coordination, and execution levels forms the architecture of an intelligent machine using the principle of increasing precision with decreasing intelligence from a hierarchically intelligent control. This system has been formulated as a probabilistic model, where uncertainty and imprecision can be expressed in terms of entropies. The optimal strategy for decision planning and task execution can be found by minimizing the total entropy in the system. The focus is on the design of the organization level as a Boltzmann machine. Since this level is responsible for planning the actions of the machine, the Boltzmann machine is reformulated to use entropy as the cost function to be minimized. Simulated annealing, expanding subinterval random search, and the genetic algorithm are presented as search techniques to efficiently find the desired action sequence and illustrated with numerical examples.

Salivary Cytokines as a Minimally-Invasive Measure of Immune Functioning in Young Children: Correlates of Individual Differences and Sensitivity to Laboratory Stress

PubMed Central

Riis, Jenna L.; Granger, Douglas A.; DiPietro, Janet A.; Bandeen-Roche, Karen; Johnson, Sara B.

2015-01-01

There is growing interest in minimally-invasive measures of environmentally-responsive biological systems in developmental science. Contributing to that endeavor, this study explores the intercorrelations, correlates, and task-sensitivity of proinflammatory salivary cytokines in childhood. Saliva was sampled from 125 healthy five-year old children (49% male) across a series of cognitive and emotional challenge laboratory tasks. Samples were assayed for cytokines (IL-1β, IL-6, IL-8, TNFα), and markers of hypothalamic–pituitary– adrenal (HPA) and autonomic nervous system (ANS) activation (salivary cortisol and alpha-amylase [sAA]). Cytokines were positively intercorrelated and task-sensitivity varied. Except IL-8, cytokines were elevated in children with oral health issues and tobacco smoke exposure. Among boys, cytokines were positively related to sAA and negatively related to cortisol. The findings suggest that in healthy children, salivary cytokine levels reflect compartmentalized oral immune activity. Associations between ANS and HPA activity and cytokines in saliva may present opportunities for minimally-invasive methods to explore neuroendocrine-immune interactions during development. PMID:25604242

A Strategy for Minimizing Background Signal in Autoinductive Signal Amplification Reactions for Point-of-Need Assays.

PubMed

Brooks, Adam D; Yeung, Kimy; Lewis, Gregory G; Phillips, Scott T

2015-09-07

Rapid point-of-need assays are used to detect abundant biomarkers. The development of in situ signal amplification reactions could extend these assays to screening and triaging of patients for trace levels of biomarkers, even in resource-limited settings. We, and others, have developed small molecule-based in situ signal amplification reactions that eventually may be useful in this context. Herein we describe a design strategy for minimizing background signal that may occur in the absence of the target analyte, thus moving this in situ signal amplification approach one step closer to practical applications. Specifically, we describe allylic ethers as privileged connectors for linking detection and propagating functionality in a small molecule signal amplification reagent. Allylic ethers minimize background reactions while still enabling controlled release of a propagating signal in order to continue the signal amplification reaction. This paper characterizes the ability of allylic ethers to provide an amplified response, and offers insight into additional design considerations that are needed before in situ small molecule-based signal amplification becomes a viable strategy for point-of-need diagnostics.

A Strategy for Minimizing Background Signal in Autoinductive Signal Amplification Reactions for Point-of-Need Assays

PubMed Central

Brooks, Adam D.; Yeung, Kimy; Lewis, Gregory G.

2015-01-01

Rapid point-of-need assays are used to detect abundant biomarkers. The development of in situ signal amplification reactions could extend these assays to screening and triaging of patients for trace levels of biomarkers, even in resource-limited settings. We, and others, have developed small molecule-based in situ signal amplification reactions that eventually may be useful in this context. Herein we describe a design strategy for minimizing background signal that may occur in the absence of the target analyte, thus moving this in situ signal amplification approach one step closer to practical applications. Specifically, we describe allylic ethers as privileged connectors for linking detection and propagating functionality in a small molecule signal amplification reagent. Allylic ethers minimize background reactions while still enabling controlled release of a propagating signal in order to continue the signal amplification reaction. This paper characterizes the ability of allylic ethers to provide an amplified response, and offers insight into additional design considerations that are needed before in situ small molecule-based signal amplification becomes a viable strategy for point-of-need diagnostics. PMID:26604988

Using non-invasive brain stimulation to augment motor training-induced plasticity

PubMed Central

Bolognini, Nadia; Pascual-Leone, Alvaro; Fregni, Felipe

2009-01-01

Therapies for motor recovery after stroke or traumatic brain injury are still not satisfactory. To date the best approach seems to be the intensive physical therapy. However the results are limited and functional gains are often minimal. The goal of motor training is to minimize functional disability and optimize functional motor recovery. This is thought to be achieved by modulation of plastic changes in the brain. Therefore, adjunct interventions that can augment the response of the motor system to the behavioural training might be useful to enhance the therapy-induced recovery in neurological populations. In this context, noninvasive brain stimulation appears to be an interesting option as an add-on intervention to standard physical therapies. Two non-invasive methods of inducing electrical currents into the brain have proved to be promising for inducing long-lasting plastic changes in motor systems: transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). These techniques represent powerful methods for priming cortical excitability for a subsequent motor task, demand, or stimulation. Thus, their mutual use can optimize the plastic changes induced by motor practice, leading to more remarkable and outlasting clinical gains in rehabilitation. In this review we discuss how these techniques can enhance the effects of a behavioural intervention and the clinical evidence to date. PMID:19292910

Carpal tunnel syndrome, the search for a cost-effective surgical intervention: a randomised controlled trial.

PubMed Central

Lorgelly, Paula K.; Dias, Joseph J.; Bradley, Mary J.; Burke, Frank D.

2005-01-01

OBJECTIVE: There is insufficient evidence regarding the clinical and cost-effectiveness of surgical interventions for carpal tunnel syndrome. This study evaluates the cost, effectiveness and cost-effectiveness of minimally invasive surgery compared with conventional open surgery. PATIENTS AND METHODS: 194 sufferers (208 hands) of carpal tunnel syndrome were randomly assigned to each treatment option. A self-administered questionnaire assessed the severity of patients' symptoms and functional status pre- and postoperatively. Treatment costs were estimated from resource use and hospital financial data. RESULTS: Minimally invasive carpal tunnel decompression is marginally more effective than open surgery in terms of functional status, but not significantly so. Little improvement in symptom severity was recorded for either intervention. Minimally invasive surgery was found to be significantly more costly than open surgery. The incremental cost effectiveness ratio for functional status was estimated to be 197 UK pounds, such that a one percentage point improvement in functioning costs 197 UK pounds when using the minimally invasive technique. CONCLUSIONS: Minimally invasive carpal tunnel decompression appears to be more effective but more costly. Initial analysis suggests that the additional expense for such a small improvement in function and no improvement in symptoms would not be regarded as value-for-money, such that minimally invasive carpal tunnel release is unlikely to be considered a cost-effective alternative to the traditional open surgery procedure. PMID:15720906

A three-parameter two-state model of receptor function that incorporates affinity, efficacy, and signal amplification.

PubMed

Buchwald, Peter

2017-06-01

A generalized model of receptor function is proposed that relies on the essential assumptions of the minimal two-state receptor theory (i.e., ligand binding followed by receptor activation), but uses a different parametrization and allows nonlinear response (transduction) for possible signal amplification. For the most general case, three parameters are used: K d , the classic equilibrium dissociation constant to characterize binding affinity; ε , an intrinsic efficacy to characterize the ability of the bound ligand to activate the receptor (ranging from 0 for an antagonist to 1 for a full agonist); and γ , a gain (amplification) parameter to characterize the nonlinearity of postactivation signal transduction (ranging from 1 for no amplification to infinity). The obtained equation, E/Emax=εγLεγ+1-εL+Kd, resembles that of the operational (Black and Leff) or minimal two-state (del Castillo-Katz) models, E/Emax=τLτ+1L+Kd, with εγ playing a role somewhat similar to that of the τ efficacy parameter of those models, but has several advantages. Its parameters are more intuitive as they are conceptually clearly related to the different steps of binding, activation, and signal transduction (amplification), and they are also better suited for optimization by nonlinear regression. It allows fitting of complex data where receptor binding and response are measured separately and the fractional occupancy and response are mismatched. Unlike the previous models, it is a true generalized model as simplified forms can be reproduced with special cases of its parameters. Such simplified forms can be used on their own to characterize partial agonism, competing partial and full agonists, or signal amplification.

Integrated tools for control-system analysis

NASA Technical Reports Server (NTRS)

Ostroff, Aaron J.; Proffitt, Melissa S.; Clark, David R.

1989-01-01

The basic functions embedded within a user friendly software package (MATRIXx) are used to provide a high level systems approach to the analysis of linear control systems. Various control system analysis configurations are assembled automatically to minimize the amount of work by the user. Interactive decision making is incorporated via menu options and at selected points, such as in the plotting section, by inputting data. There are five evaluations such as the singular value robustness test, singular value loop transfer frequency response, Bode frequency response, steady-state covariance analysis, and closed-loop eigenvalues. Another section describes time response simulations. A time response for random white noise disturbance is available. The configurations and key equations used for each type of analysis, the restrictions that apply, the type of data required, and an example problem are described. One approach for integrating the design and analysis tools is also presented.

A 20 bp cis-acting element is both necessary and sufficient to mediate elicitor response of a maize PRms gene.

PubMed

Raventós, D; Jensen, A B; Rask, M B; Casacuberta, J M; Mundy, J; San Segundo, B

1995-01-01

Transient gene expression assays in barley aleurone protoplasts were used to identify a cis-regulatory element involved in the elicitor-responsive expression of the maize PRms gene. Analysis of transcriptional fusions between PRms 5' upstream sequences and a chloramphenicol acetyltransferase reporter gene, as well as chimeric promoters containing PRms promoter fragments or repeated oligonucleotides fused to a minimal promoter, delineated a 20 bp sequence which functioned as an elicitor-response element (ERE). This sequence contains a motif (-246 AATTGACC) similar to sequences found in promoters of other pathogen-responsive genes. The analysis also indicated that an enhancing sequence(s) between -397 and -296 is required for full PRms activation by elicitors. The protein kinase inhibitor staurosporine was found to completely block the transcriptional activation induced by elicitors. These data indicate that protein phosphorylation is involved in the signal transduction pathway leading to PRms expression.

Outcome in patients with bacterial meningitis presenting with a minimal Glasgow Coma Scale score

PubMed Central

Lucas, Marjolein J.; Brouwer, Matthijs C.; van der Ende, Arie

2014-01-01

Objective: In bacterial meningitis, a decreased level of consciousness is predictive for unfavorable outcome, but the clinical features and outcome in patients presenting with a minimal score on the Glasgow Coma Scale are unknown. Methods: We assessed the incidence, clinical characteristics, and outcome of patients with bacterial meningitis presenting with a minimal score on the Glasgow Coma Scale from a nationwide cohort study of adults with community-acquired bacterial meningitis in the Netherlands from 2006 to 2012. Results: Thirty of 1,083 patients (3%) presented with a score of 3 on the Glasgow Coma Scale. In 22 of 30 patients (73%), the minimal Glasgow Coma Scale score could be explained by use of sedative medication or complications resulting from meningitis such as seizures, cerebral edema, and hydrocephalus. Systemic (86%) and neurologic (47%) complications occurred frequently, leading to a high proportion of patients with unfavorable outcome (77%). However, 12 of 30 patients (40%) survived and 7 patients (23%) had a good functional outcome, defined as a score of 5 on the Glasgow Outcome Scale. Patients presenting with a minimal Glasgow Coma Scale score on admission and bilaterally absent pupillary light responses, bilaterally absent corneal reflexes, or signs of septic shock on admission all died. Conclusions: Patients with community-acquired bacterial meningitis rarely present with a minimal score on the Glasgow Coma Scale, but this condition is associated with high rates of morbidity and mortality. However, 1 out of 5 of these severely ill patients will make a full recovery, stressing the continued need for aggressive supportive care in these patients. PMID:25340065

Regulatory T cells: mechanisms of differentiation and function.

PubMed

Josefowicz, Steven Z; Lu, Li-Fan; Rudensky, Alexander Y

2012-01-01

The immune system has evolved to mount an effective defense against pathogens and to minimize deleterious immune-mediated inflammation caused by commensal microorganisms, immune responses against self and environmental antigens, and metabolic inflammatory disorders. Regulatory T (Treg) cell-mediated suppression serves as a vital mechanism of negative regulation of immune-mediated inflammation and features prominently in autoimmune and autoinflammatory disorders, allergy, acute and chronic infections, cancer, and metabolic inflammation. The discovery that Foxp3 is the transcription factor that specifies the Treg cell lineage facilitated recent progress in understanding the biology of regulatory T cells. In this review, we discuss cellular and molecular mechanisms in the differentiation and function of these cells.

Six-minute-walk test in idiopathic pulmonary fibrosis: test validation and minimal clinically important difference.

PubMed

du Bois, Roland M; Weycker, Derek; Albera, Carlo; Bradford, Williamson Z; Costabel, Ulrich; Kartashov, Alex; Lancaster, Lisa; Noble, Paul W; Sahn, Steven A; Szwarcberg, Javier; Thomeer, Michiel; Valeyre, Dominique; King, Talmadge E

2011-05-01

The 6-minute-walk test (6MWT) is a practical and clinically meaningful measure of exercise tolerance with favorable performance characteristics in various cardiac and pulmonary diseases. Performance characteristics in patients with idiopathic pulmonary fibrosis (IPF) have not been systematically evaluated. To assess the reliability, validity, and responsiveness of the 6MWT and estimate the minimal clinically important difference (MCID) in patients with IPF. The study population included all subjects completing a 6MWT in a clinical trial evaluating interferon gamma-1b (n = 822). Six-minute walk distance (6MWD) and other parameters were measured at baseline and at 24-week intervals using a standardized protocol. Parametric and distribution-independent correlation coefficients were used to assess the strength of the relationships between 6MWD and measures of pulmonary function, dyspnea, and health-related quality of life. Both distribution-based and anchor-based methods were used to estimate the MCID. Comparison of two proximal measures of 6MWD (mean interval, 24 d) demonstrated good reliability (coefficient = 0.83; P < 0.001). 6MWD was weakly correlated with measures of physiologic function and health-related quality of life; however, values were consistently and significantly lower for patients with the poorest functional status, suggesting good construct validity. Importantly, change in 6MWD was highly predictive of mortality; a 24-week decline of greater than 50 m was associated with a fourfold increase in risk of death at 1 year (hazard ratio, 4.27; 95% confidence interval, 2.57- 7.10; P < 0.001). The estimated MCID was 24-45 m. The 6MWT is a reliable, valid, and responsive measure of disease status and a valid endpoint for clinical trials in IPF.

Generation of Human Nasal Epithelial Cell Spheroids for Individualized Cystic Fibrosis Transmembrane Conductance Regulator Study.

PubMed

Brewington, John J; Filbrandt, Erin T; LaRosa, Francis J; Moncivaiz, Jessica D; Ostmann, Alicia J; Strecker, Lauren M; Clancy, John P

2018-04-11

While the introduction of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulator drugs has revolutionized care in Cystic Fibrosis (CF), the genotype-directed therapy model currently in use has several limitations. First, rare or understudied mutation groups are excluded from definitive clinical trials. Moreover, as additional modulator drugs enter the market, it will become difficult to optimize the modulator choices for an individual subject. Both of these issues are addressed with the use of patient-derived, individualized preclinical model systems of CFTR function and modulation. Human nasal epithelial cells (HNEs) are an easily accessible source of respiratory tissue for such a model. Herein, we describe the generation of a three-dimensional spheroid model of CFTR function and modulation using primary HNEs. HNEs are isolated from subjects in a minimally invasive fashion, expanded in conditional reprogramming conditions, and seeded into the spheroid culture. Within 2 weeks of seeding, spheroid cultures generate HNE spheroids that can be stimulated with 3',5'-cyclic adenosine monophosphate (cAMP)-generating agonists to activate CFTR function. Spheroid swelling is then quantified as a proxy of CFTR activity. HNE spheroids capitalize on the minimally invasive, yet respiratory origin of nasal cells to generate an accessible, personalized model relevant to an epithelium reflecting disease morbidity and mortality. Compared to the air-liquid interface HNE cultures, spheroids are relatively quick to mature, which reduces the overall contamination rate. In its current form, the model is limited by low throughput, though this is offset by the relative ease of tissue acquisition. HNE spheroids can be used to reliably quantify and characterize CFTR activity at the individual level. An ongoing study to tie this quantification to in vivo drug response will determine if HNE spheroids are a true preclinical predictor of patient response to CFTR modulation.

Measurement Properties of the Lower Extremity Functional Scale: A Systematic Review.

PubMed

Mehta, Saurabh P; Fulton, Allison; Quach, Cedric; Thistle, Megan; Toledo, Cesar; Evans, Neil A

2016-03-01

Systematic review of measurement properties. Many primary studies have examined the measurement properties, such as reliability, validity, and sensitivity to change, of the Lower Extremity Functional Scale (LEFS) in different clinical populations. A systematic review summarizing these properties for the LEFS may provide an important resource. To locate and synthesize evidence on the measurement properties of the LEFS and to discuss the clinical implications of the evidence. A literature search was conducted in 4 databases (PubMed, MEDLINE, Embase, and CINAHL), using predefined search terms. Two reviewers performed a critical appraisal of the included studies using a standardized assessment form. A total of 27 studies were included in the review, of which 18 achieved a very good to excellent methodological quality level. The LEFS scores demonstrated excellent test-retest reliability (intraclass correlation coefficients ranging between 0.85 and 0.99) and demonstrated the expected relationships with measures assessing similar constructs (Pearson correlation coefficient values of greater than 0.7). The responsiveness of the LEFS scores was excellent, as suggested by consistently high effect sizes (greater than 0.8) in patients with different lower extremity conditions. Minimal detectable change at the 90% confidence level (MDC90) for the LEFS scores varied between 8.1 and 15.3 across different reassessment intervals in a wide range of patient populations. The pooled estimate of the MDC90 was 6 points and the minimal clinically important difference was 9 points in patients with lower extremity musculoskeletal conditions, which are indicative of true change and clinically meaningful change, respectively. The results of this review support the reliability, validity, and responsiveness of the LEFS scores for assessing functional impairment in a wide array of patient groups with lower extremity musculoskeletal conditions.

Functional modeling of the human auditory brainstem response to broadband stimulationa)

PubMed Central

Verhulst, Sarah; Bharadwaj, Hari M.; Mehraei, Golbarg; Shera, Christopher A.; Shinn-Cunningham, Barbara G.

2015-01-01

Population responses such as the auditory brainstem response (ABR) are commonly used for hearing screening, but the relationship between single-unit physiology and scalp-recorded population responses are not well understood. Computational models that integrate physiologically realistic models of single-unit auditory-nerve (AN), cochlear nucleus (CN) and inferior colliculus (IC) cells with models of broadband peripheral excitation can be used to simulate ABRs and thereby link detailed knowledge of animal physiology to human applications. Existing functional ABR models fail to capture the empirically observed 1.2–2 ms ABR wave-V latency-vs-intensity decrease that is thought to arise from level-dependent changes in cochlear excitation and firing synchrony across different tonotopic sections. This paper proposes an approach where level-dependent cochlear excitation patterns, which reflect human cochlear filter tuning parameters, drive AN fibers to yield realistic level-dependent properties of the ABR wave-V. The number of free model parameters is minimal, producing a model in which various sources of hearing-impairment can easily be simulated on an individualized and frequency-dependent basis. The model fits latency-vs-intensity functions observed in human ABRs and otoacoustic emissions while maintaining rate-level and threshold characteristics of single-unit AN fibers. The simulations help to reveal which tonotopic regions dominate ABR waveform peaks at different stimulus intensities. PMID:26428802

HIV epidemic control-a model for optimal allocation of prevention and treatment resources.

PubMed

Alistar, Sabina S; Long, Elisa F; Brandeau, Margaret L; Beck, Eduard J

2014-06-01

With 33 million people living with human immunodeficiency virus (HIV) worldwide and 2.7 million new infections occurring annually, additional HIV prevention and treatment efforts are urgently needed. However, available resources for HIV control are limited and must be used efficiently to minimize the future spread of the epidemic. We develop a model to determine the appropriate resource allocation between expanded HIV prevention and treatment services. We create an epidemic model that incorporates multiple key populations with different transmission modes, as well as production functions that relate investment in prevention and treatment programs to changes in transmission and treatment rates. The goal is to allocate resources to minimize R 0, the reproductive rate of infection. We first develop a single-population model and determine the optimal resource allocation between HIV prevention and treatment. We extend the analysis to multiple independent populations, with resource allocation among interventions and populations. We then include the effects of HIV transmission between key populations. We apply our model to examine HIV epidemic control in two different settings, Uganda and Russia. As part of these applications, we develop a novel approach for estimating empirical HIV program production functions. Our study provides insights into the important question of resource allocation for a country's optimal response to its HIV epidemic and provides a practical approach for decision makers. Better decisions about allocating limited HIV resources can improve response to the epidemic and increase access to HIV prevention and treatment services for millions of people worldwide.

Psychometric properties of the Canadian Occupational Performance Measure in home-dwelling older adults.

PubMed

Tuntland, Hanne; Aaslund, Mona Kristin; Langeland, Eva; Espehaug, Birgitte; Kjeken, Ingvild

2016-01-01

The Canadian Occupational Performance Measure (COPM) is an occupational therapy instrument designed to help participants identify, prioritize, and evaluate performance of important occupations. To investigate the validity, responsiveness, interpretability, and feasibility of the COPM when used by various health professions in home-dwelling older adults receiving reablement. Reablement is a new form of multidisciplinary home-based rehabilitation for older adults experiencing functional decline. The sample of 225 participants, mean age 80.8 years, who were in need of rehabilitation for various health conditions were included in the study. Data collection was conducted at baseline and at 10 weeks follow-up. The COSMIN guidelines and recommendations for evaluating methodological quality were followed. Content validity, construct validity, and feasibility were found to be adequate. Responsiveness, however, was moderate. Functional mobility was the most frequently prioritized occupational category of all. Regarding interpretability, the minimal important change was 3.0 points and 3.2 points for performance and satisfaction, respectively. The older adults reported that COPM was a useful and manageable instrument. The majority of the occupational therapists, physiotherapists, and nurses reported that they had the required expertise to conduct the COPM assessments. The results support the multidisciplinary use of the COPM in clinical practice and research in a home-dwelling, heterogeneous population of older adults. Based on the findings, 3 points are recommended as a cutoff point to distinguish between older adults who have a minimal important change in COPM performance and COPM satisfaction and those who have not.

Functional Dynamics of PDZ Binding Domains: A Normal-Mode Analysis

PubMed Central

De Los Rios, Paolo; Cecconi, Fabio; Pretre, Anna; Dietler, Giovanni; Michielin, Olivier; Piazza, Francesco; Juanico, Brice

2005-01-01

Postsynaptic density-95/disks large/zonula occludens-1 (PDZ) domains are relatively small (80–120 residues) protein binding modules central in the organization of receptor clusters and in the association of cellular proteins. Their main function is to bind C-terminals of selected proteins that are recognized through specific amino acids in their carboxyl end. Binding is associated with a deformation of the PDZ native structure and is responsible for dynamical changes in regions not in direct contact with the target. We investigate how this deformation is related to the harmonic dynamics of the PDZ structure and show that one low-frequency collective normal mode, characterized by the concerted movements of different secondary structures, is involved in the binding process. Our results suggest that even minimal structural changes are responsible for communication between distant regions of the protein, in agreement with recent NMR experiments. Thus, PDZ domains are a very clear example of how collective normal modes are able to characterize the relation between function and dynamics of proteins, and to provide indications on the precursors of binding/unbinding events. PMID:15821164

ATM directs DNA damage responses and proteostasis via genetically separable pathways.

PubMed

Lee, Ji-Hoon; Mand, Michael R; Kao, Chung-Hsuan; Zhou, Yi; Ryu, Seung W; Richards, Alicia L; Coon, Joshua J; Paull, Tanya T

2018-01-09

The protein kinase ATM is a master regulator of the DNA damage response but also responds directly to oxidative stress. Loss of ATM causes ataxia telangiectasia, a neurodegenerative disorder with pleiotropic symptoms that include cerebellar dysfunction, cancer, diabetes, and premature aging. We genetically separated the activation of ATM by DNA damage from that by oxidative stress using separation-of-function mutations. We found that deficient activation of ATM by the Mre11-Rad50-Nbs1 complex and DNA double-strand breaks resulted in loss of cell viability, checkpoint activation, and DNA end resection in response to DNA damage. In contrast, loss of oxidative activation of ATM had minimal effects on DNA damage-related outcomes but blocked ATM-mediated initiation of checkpoint responses after oxidative stress and resulted in deficiencies in mitochondrial function and autophagy. In addition, expression of a variant ATM incapable of activation by oxidative stress resulted in widespread protein aggregation. These results indicate a direct relationship between the mechanism of ATM activation and its effects on cellular metabolism and DNA damage responses in human cells and implicate ATM in the control of protein homeostasis. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Evaluation of outdoor-to-indoor response to minimized sonic booms

NASA Technical Reports Server (NTRS)

Brown, David; Sutherland, Louis C.

1992-01-01

Various studies were conducted by NASA and others on the practical limitations of sonic boom signature shaping/minimization for the High-Speed Civil Transport (HSCT) and on the effects of these shaped boom signatures on perceived loudness. This current effort is a further part of this research with emphasis on examining shaped boom signatures which are representative of the most recent investigations of practical limitations on sonic boom minimization, and on examining and comparing the expected response to these signatures when experienced indoors and outdoors.

The Promoter of AtUSP Is Co-regulated by Phytohormones and Abiotic Stresses in Arabidopsis thaliana.

PubMed

Bhuria, Monika; Goel, Parul; Kumar, Sanjay; Singh, Anil K

2016-01-01

Universal stress proteins (USPs) are known to be expressed in response to various abiotic stresses in a wide variety of organisms, such as bacteria, archaebacteria, protists, algae, fungi, plants, and animals. However, in plants, biological function of most of the USPs still remains obscure. In the present study, Arabidopsis USP gene ( AtUSP ) showed induction in response to abscisic acid (ABA) and various abiotic stresses viz . heat, dehydration, salt, osmotic, and cold stresses. Additionally, in silico analysis of AtUSP promoter identified several cis -elements responsive to phytohormones and abiotic stresses such as ABRE, ERE, DRE, and HSE, etc. To functionally validate the AtUSP promoter, the 1115 bp region of promoter was characterized under phytohormone and abiotic stress treatments. Deletion analysis of promoter was carried out by cloning the full length promoter (D0) and its three 5' deletion derivatives, D1 (964 bp), D2 (660 bp), and D3 (503 bp) upstream of the β-glucuronidase (GUS) reporter gene, which were then stably transformed in Arabidopsis plants. The AtUSP promoter (D0) showed minimal activity under non-stress conditions which was enhanced in response to phytohormone treatments (ABA and ACC) and abiotic stresses such as dehydration, heat, cold, salt, and osmotic stresses. The seedlings harboring D1 and D2 deletion fragments showed constitutive GUS expression even under control condition with increased activity almost under all the treatments. However, D3 seedlings exhibited complete loss of activity under control condition with induction under ACC treatment, dehydration, heat, oxidative, salt, and osmotic stresses. Thus, present study clearly showed that AtUSP promoter is highly inducible by phytohormones and multiple abiotic stresses and it can be exploited as stress inducible promoter to generate multi-stress tolerant crops with minimal effects on their other important traits.

The role of ants, birds and bats for ecosystem functions and yield in oil palm plantations.

PubMed

Denmead, Lisa H; Darras, Kevin; Clough, Yann; Diaz, Patrick; Grass, Ingo; Hoffmann, Munir P; Nurdiansyah, Fuad; Fardiansah, Rico; Tscharntke, Teja

2017-07-01

One of the world's most important and rapidly expanding crops, oil palm, is associated with low levels of biodiversity. Changes in predator communities might alter ecosystem services and subsequently sustainable management but these links have received little attention to date. Here, for the first time, we manipulated ant and flying vertebrate (birds and bats) access to oil palms in six smallholder plantations in Sumatra (Indonesia) and measured effects on arthropod communities, related ecosystem functions (herbivory, predation, decomposition and pollination) and crop yield. Arthropod predators increased in response to reductions in ant and bird access, but the overall effect of experimental manipulations on ecosystem functions was minimal. Similarly, effects on yield were not significant. We conclude that ecosystem functions and productivity in oil palm are, under current levels of low pest pressure and large pollinator populations, robust to large reductions of major predators. © 2017 by the Ecological Society of America.

Effects of stress on immune function: the good, the bad, and the beautiful.

PubMed

Dhabhar, Firdaus S

2014-05-01

Although the concept of stress has earned a bad reputation, it is important to recognize that the adaptive purpose of a physiological stress response is to promote survival during fight or flight. While long-term stress is generally harmful, short-term stress can be protective as it prepares the organism to deal with challenges. This review discusses the immune effects of biological stress responses that can be induced by psychological, physiological, or physical (including exercise) stressors. We have proposed that short-term stress is one of the nature's fundamental but under-appreciated survival mechanisms that could be clinically harnessed to enhance immunoprotection. Short-term (i.e., lasting for minutes to hours) stress experienced during immune activation enhances innate/primary and adaptive/secondary immune responses. Mechanisms of immuno-enhancement include changes in dendritic cell, neutrophil, macrophage, and lymphocyte trafficking, maturation, and function as well as local and systemic production of cytokines. In contrast, long-term stress suppresses or dysregulates innate and adaptive immune responses by altering the Type 1-Type 2 cytokine balance, inducing low-grade chronic inflammation, and suppressing numbers, trafficking, and function of immunoprotective cells. Chronic stress may also increase susceptibility to some types of cancer by suppressing Type 1 cytokines and protective T cells and increasing regulatory/suppressor T cell function. Here, we classify immune responses as being protective, pathological, or regulatory, and discuss "good" versus "bad" effects of stress on health. Thus, short-term stress can enhance the acquisition and/or expression of immunoprotective (wound healing, vaccination, anti-infectious agent, anti-tumor) or immuno-pathological (pro-inflammatory, autoimmune) responses. In contrast, chronic stress can suppress protective immune responses and/or exacerbate pathological immune responses. Studies such as the ones discussed here could provide mechanistic targets and conceptual frameworks for pharmacological and/or biobehavioral interventions designed to enhance the effects of "good" stress, minimize the effects of "bad" stress, and maximally promote health and healing.

A Developmental Analysis of the Factorial Validity of the Parent-Report Version of the Adult Responses to Children’s Symptoms in Children Versus Adolescents With Chronic Pain or Pain-Related Chronic Illness

PubMed Central

Noel, Melanie; Palermo, Tonya M.; Essner, Bonnie; Zhou, Chuan; Levy, Rona L.; Langer, Shelby L.; Sherman, Amanda L.; Walker, Lynn S.

2015-01-01

The widely used Adult Responses to Children’s Symptoms measures parental responses to child symptom complaints among youth aged 7 to 18 years with recurrent/chronic pain. Given developmental differences between children and adolescents and the impact of developmental stage on parenting, the factorial validity of the parent-report version of the Adult Responses to Children’s Symptoms with a pain-specific stem was examined separately in 743 parents of 281 children (7–11 years) and 462 adolescents (12–18 years) with chronic pain or pain-related chronic illness. Factor structures of the Adult Responses to Children’s Symptoms beyond the original 3-factor model were also examined. Exploratory factor analysis with oblique rotation was conducted on a randomly chosen half of the sample of children and adolescents as well as the 2 groups combined to assess underlying factor structure. Confirmatory factor analysis was conducted on the other randomly chosen half of the sample to cross-validate factor structure revealed by exploratory factor analyses and compare it to other model variants. Poor loading and high cross loading items were removed. A 4-factor model (Protect, Minimize, Monitor, and Distract) for children and the combined (child and adolescent) sample and a 5-factor model (Protect, Minimize, Monitor, Distract, and Solicitousness) for adolescents was superior to the 3-factor model proposed in previous literature. Future research should examine the validity of derived subscales and developmental differences in their relationships with parent and child functioning. PMID:25451623

Translational neuropharmacology: the use of human isolated gastrointestinal tissues

PubMed Central

Sanger, GJ; Broad, J; Kung, V; Knowles, CH

2013-01-01

Translational sciences increasingly emphasize the measurement of functions in native human tissues. However, such studies must confront variations in patient age, gender, genetic background and disease. Here, these are discussed with reference to neuromuscular and neurosecretory functions of the human gastrointestinal (GI) tract. Tissues are obtained after informed consent, in collaboration with surgeons (surgical techniques help minimize variables) and pathologists. Given the difficulties of directly recording from human myenteric neurones (embedded between muscle layers), enteric motor nerve functions are studied by measuring muscle contractions/relaxations evoked by electrical stimulation of intrinsic nerves; responses are regionally dependent, often involving cholinergic and nitrergic phenotypes. Enteric sensory functions can be studied by evoking the peristaltic reflex, involving enteric sensory and motor nerves, but this has rarely been achieved. As submucosal neurones are more accessible (after removing the mucosa), direct neuronal recordings are possible. Neurosecretory functions are studied by measuring changes in short-circuit current across the mucosa. For all experiments, basic questions must be addressed. Because tissues are from patients, what are the controls and the influence of disease? How long does it take before function fully recovers? What is the impact of age- and gender-related differences? What is the optimal sample size? Addressing these and other questions minimizes variability and raises the scientific credibility of human tissue research. Such studies also reduce animal use. Further, the many differences between animal and human GI functions also means that human tissue research must question the ethical validity of using strains of animals with unproved translational significance. Linked Article BJP published a themed issue on Translational Neuropharmacology in 2011. To view the articles in this themed issue visit http://dx.doi.org/10.1111/bph.2011.164.issue-4 PMID:22946540

Planck 2013 results. VII. HFI time response and beams

NASA Astrophysics Data System (ADS)

Planck Collaboration; Ade, P. A. R.; Aghanim, N.; Armitage-Caplan, C.; Arnaud, M.; Ashdown, M.; Atrio-Barandela, F.; Aumont, J.; Baccigalupi, C.; Banday, A. J.; Barreiro, R. B.; Battaner, E.; Benabed, K.; Benoît, A.; Benoit-Lévy, A.; Bernard, J.-P.; Bersanelli, M.; Bielewicz, P.; Bobin, J.; Bock, J. J.; Bond, J. R.; Borrill, J.; Bouchet, F. R.; Bowyer, J. W.; Bridges, M.; Bucher, M.; Burigana, C.; Cardoso, J.-F.; Catalano, A.; Challinor, A.; Chamballu, A.; Chary, R.-R.; Chiang, H. C.; Chiang, L.-Y.; Christensen, P. R.; Church, S.; Clements, D. L.; Colombi, S.; Colombo, L. P. L.; Couchot, F.; Coulais, A.; Crill, B. P.; Curto, A.; Cuttaia, F.; Danese, L.; Davies, R. D.; de Bernardis, P.; de Rosa, A.; de Zotti, G.; Delabrouille, J.; Delouis, J.-M.; Désert, F.-X.; Diego, J. M.; Dole, H.; Donzelli, S.; Doré, O.; Douspis, M.; Dunkley, J.; Dupac, X.; Efstathiou, G.; Enßlin, T. A.; Eriksen, H. K.; Finelli, F.; Forni, O.; Frailis, M.; Fraisse, A. A.; Franceschi, E.; Galeotta, S.; Ganga, K.; Giard, M.; Giraud-Héraud, Y.; González-Nuevo, J.; Górski, K. M.; Gratton, S.; Gregorio, A.; Gruppuso, A.; Gudmundsson, J. E.; Haissinski, J.; Hansen, F. K.; Hanson, D.; Harrison, D.; Henrot-Versillé, S.; Hernández-Monteagudo, C.; Herranz, D.; Hildebrandt, S. R.; Hivon, E.; Hobson, M.; Holmes, W. A.; Hornstrup, A.; Hou, Z.; Hovest, W.; Huffenberger, K. M.; Jaffe, A. H.; Jaffe, T. R.; Jones, W. C.; Juvela, M.; Keihänen, E.; Keskitalo, R.; Kisner, T. S.; Kneissl, R.; Knoche, J.; Knox, L.; Kunz, M.; Kurki-Suonio, H.; Lagache, G.; Lamarre, J.-M.; Lasenby, A.; Laureijs, R. J.; Lawrence, C. R.; Leonardi, R.; Leroy, C.; Lesgourgues, J.; Liguori, M.; Lilje, P. B.; Linden-Vørnle, M.; López-Caniego, M.; Lubin, P. M.; Macías-Pérez, J. F.; MacTavish, C. J.; Maffei, B.; Mandolesi, N.; Maris, M.; Marshall, D. J.; Martin, P. G.; Martínez-González, E.; Masi, S.; Massardi, M.; Matarrese, S.; Matsumura, T.; Matthai, F.; Mazzotta, P.; McGehee, P.; Melchiorri, A.; Mendes, L.; Mennella, A.; Migliaccio, M.; Mitra, S.; Miville-Deschênes, M.-A.; Moneti, A.; Montier, L.; Morgante, G.; Mortlock, D.; Munshi, D.; Murphy, J. A.; Naselsky, P.; Nati, F.; Natoli, P.; Netterfield, C. B.; Nørgaard-Nielsen, H. U.; Noviello, F.; Novikov, D.; Novikov, I.; Osborne, S.; Oxborrow, C. A.; Paci, F.; Pagano, L.; Pajot, F.; Paoletti, D.; Pasian, F.; Patanchon, G.; Perdereau, O.; Perotto, L.; Perrotta, F.; Piacentini, F.; Piat, M.; Pierpaoli, E.; Pietrobon, D.; Plaszczynski, S.; Pointecouteau, E.; Polegre, A. M.; Polenta, G.; Ponthieu, N.; Popa, L.; Poutanen, T.; Pratt, G. W.; Prézeau, G.; Prunet, S.; Puget, J.-L.; Rachen, J. P.; Reinecke, M.; Remazeilles, M.; Renault, C.; Ricciardi, S.; Riller, T.; Ristorcelli, I.; Rocha, G.; Rosset, C.; Roudier, G.; Rowan-Robinson, M.; Rusholme, B.; Sandri, M.; Santos, D.; Sauvé, A.; Savini, G.; Scott, D.; Shellard, E. P. S.; Spencer, L. D.; Starck, J.-L.; Stolyarov, V.; Stompor, R.; Sudiwala, R.; Sureau, F.; Sutton, D.; Suur-Uski, A.-S.; Sygnet, J.-F.; Tauber, J. A.; Tavagnacco, D.; Terenzi, L.; Tomasi, M.; Tristram, M.; Tucci, M.; Umana, G.; Valenziano, L.; Valiviita, J.; Van Tent, B.; Vielva, P.; Villa, F.; Vittorio, N.; Wade, L. A.; Wandelt, B. D.; Yvon, D.; Zacchei, A.; Zonca, A.

2014-11-01

This paper characterizes the effective beams, the effective beam window functions and the associated errors for the Planck High Frequency Instrument (HFI) detectors. The effective beam is theangular response including the effect of the optics, detectors, data processing and the scan strategy. The window function is the representation of this beam in the harmonic domain which is required to recover an unbiased measurement of the cosmic microwave background angular power spectrum. The HFI is a scanning instrument and its effective beams are the convolution of: a) the optical response of the telescope and feeds; b) the processing of the time-ordered data and deconvolution of the bolometric and electronic transfer function; and c) the merging of several surveys to produce maps. The time response transfer functions are measured using observations of Jupiter and Saturn and by minimizing survey difference residuals. The scanning beam is the post-deconvolution angular response of the instrument, and is characterized with observations of Mars. The main beam solid angles are determined to better than 0.5% at each HFI frequency band. Observations of Jupiter and Saturn limit near sidelobes (within 5°) to about 0.1% of the total solid angle. Time response residuals remain as long tails in the scanning beams, but contribute less than 0.1% of the total solid angle. The bias and uncertainty in the beam products are estimated using ensembles of simulated planet observations that include the impact of instrumental noise and known systematic effects. The correlation structure of these ensembles is well-described by five error eigenmodes that are sub-dominant to sample variance and instrumental noise in the harmonic domain. A suite of consistency tests provide confidence that the error model represents a sufficient description of the data. The total error in the effective beam window functions is below 1% at 100 GHz up to multipole ℓ ~ 1500, and below 0.5% at 143 and 217 GHz up to ℓ ~ 2000.

Hepatic encephalopathy

PubMed Central

2017-01-01

Abstract Hepatic encephalopathy (HE) is a reversible syndrome of impaired brain function occurring in patients with advanced liver diseases. The precise pathophysiology of HE is still under discussion; the leading hypothesis focus on the role of neurotoxins, impaired neurotransmission due to metabolic changes in liver failure, changes in brain energy metabolism, systemic inflammatory response and alterations of the blood brain barrier. HE produces a wide spectrum of nonspecific neurological and psychiatric manifestations. Minimal HE is diagnosed by abnormal psychometric tests. Clinically overt HE includes personality changes, alterations in consciousness progressive disorientation in time and space, somnolence, stupor and, finally, coma. Except for clinical studies, no specific tests are required for diagnosis. HE is classified according to the underlying disease, the severity of manifestations, its time course and the existence of precipitating factors. Treatment of overt HE includes supportive therapies, treatment of precipitating factors, lactulose and/or rifaximin. Routine treatment for minimal HE is only recommended for selected patients. PMID:28533911

Tissue-like Neural Probes for Understanding and Modulating the Brain.

PubMed

Hong, Guosong; Viveros, Robert D; Zwang, Theodore J; Yang, Xiao; Lieber, Charles M

2018-03-19

Electrophysiology tools have contributed substantially to understanding brain function, yet the capabilities of conventional electrophysiology probes have remained limited in key ways because of large structural and mechanical mismatches with respect to neural tissue. In this Perspective, we discuss how the general goal of probe design in biochemistry, that the probe or label have a minimal impact on the properties and function of the system being studied, can be realized by minimizing structural, mechanical, and topological differences between neural probes and brain tissue, thus leading to a new paradigm of tissue-like mesh electronics. The unique properties and capabilities of the tissue-like mesh electronics as well as future opportunities are summarized. First, we discuss the design of an ultraflexible and open mesh structure of electronics that is tissue-like and can be delivered in the brain via minimally invasive syringe injection like molecular and macromolecular pharmaceuticals. Second, we describe the unprecedented tissue healing without chronic immune response that leads to seamless three-dimensional integration with a natural distribution of neurons and other key cells through these tissue-like probes. These unique characteristics lead to unmatched stable long-term, multiplexed mapping and modulation of neural circuits at the single-neuron level on a year time scale. Last, we offer insights on several exciting future directions for the tissue-like electronics paradigm that capitalize on their unique properties to explore biochemical interactions and signaling in a "natural" brain environment.

Calcium ion as intracellular messenger and cellular toxin.

PubMed

Rasmussen, H; Barrett, P; Smallwood, J; Bollag, W; Isales, C

1990-03-01

Ca2+ serves a nearly universal intracellular messenger function in cell activation, but excess Ca2+ is also a cellular toxin. The possibility of Ca2+ intoxication is minimized by an elaborate autoregulatory system in which changes in Ca2+ influx rate across the plasma membrane are rapidly compensated for by parallel changes in Ca2+ efflux rate. By this mean, cellular Ca2+ homestasis is maintained so that minimal changes in total cell calcium and cytosolic Ca2+ concentration occur during sustained Ca2(+)-mediated responses. Rather than a sustained increase in cytosolic Ca2+ concentration, it is the localized cycling of Ca2+ across the plasma membrane that is the critically important Ca2+ messenger during the sustained phase of cellular responses mediated via surface receptors linked to the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2). PIP2 hydrolysis gives rise to inositol(1,4,5)trisphosphate (IP3) and diacylglycerol (DAG). The IP3 acts to release Ca2+ from an intracellular pool, thereby causing a transient rise in cytosolic Ca2+ concentration. This transient Ca2+ signal activates calmodulin-dependent protein kinases transiently, and hence, causes the transient phosphorylation of a subset of cellular proteins that mediate the initial phase of the response. The DAG brings about the association of protein kinase C (PKC) with the plasma membrane where a receptor-mediated increase in Ca2+ cycling across the membrane regulates PKC activity. The sustained phosphorylation of a second subset of proteins by PKC mediates the sustained phase of the response. Hence, Ca2+ serves as a messenger during both phases of the cellular response, but its cellular sites of action, its mechanisms of generation, and its molecular targets differ during the initial and sustained phases of the response.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium ion as intracellular messenger and cellular toxin.

PubMed Central

Rasmussen, H; Barrett, P; Smallwood, J; Bollag, W; Isales, C

1990-01-01

Ca2+ serves a nearly universal intracellular messenger function in cell activation, but excess Ca2+ is also a cellular toxin. The possibility of Ca2+ intoxication is minimized by an elaborate autoregulatory system in which changes in Ca2+ influx rate across the plasma membrane are rapidly compensated for by parallel changes in Ca2+ efflux rate. By this mean, cellular Ca2+ homestasis is maintained so that minimal changes in total cell calcium and cytosolic Ca2+ concentration occur during sustained Ca2(+)-mediated responses. Rather than a sustained increase in cytosolic Ca2+ concentration, it is the localized cycling of Ca2+ across the plasma membrane that is the critically important Ca2+ messenger during the sustained phase of cellular responses mediated via surface receptors linked to the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2). PIP2 hydrolysis gives rise to inositol(1,4,5)trisphosphate (IP3) and diacylglycerol (DAG). The IP3 acts to release Ca2+ from an intracellular pool, thereby causing a transient rise in cytosolic Ca2+ concentration. This transient Ca2+ signal activates calmodulin-dependent protein kinases transiently, and hence, causes the transient phosphorylation of a subset of cellular proteins that mediate the initial phase of the response. The DAG brings about the association of protein kinase C (PKC) with the plasma membrane where a receptor-mediated increase in Ca2+ cycling across the membrane regulates PKC activity. The sustained phosphorylation of a second subset of proteins by PKC mediates the sustained phase of the response. Hence, Ca2+ serves as a messenger during both phases of the cellular response, but its cellular sites of action, its mechanisms of generation, and its molecular targets differ during the initial and sustained phases of the response.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2190811

Nonlinear experimental dye-doped nematic liquid crystal optical transmission spectra estimated by neural network empirical physical formulas

NASA Astrophysics Data System (ADS)

Yildiz, Nihat; San, Sait Eren; Köysal, Oğuz

2010-09-01

In this paper, two complementary objectives related to optical transmission spectra of nematic liquid crystals (NLCs) were achieved. First, at room temperature, for both pure and dye (DR9) doped E7 NLCs, the 10-250 W halogen lamp transmission spectra (wavelength 400-1200 nm) were measured at various bias voltages. Second, because the measured spectra were inherently highly nonlinear, it was difficult to construct explicit empirical physical formulas (EPFs) to employ as transmittance functions. To avoid this difficulty, layered feedforward neural networks (LFNNs) were used to construct explicit EPFs for these theoretically unknown nonlinear NLC transmittance functions. As we theoretically showed in a previous work, a LFNN, as an excellent nonlinear function approximator, is highly relevant to EPF construction. The LFNN-EPFs efficiently and consistently estimated both the measured and yet-to-be-measured nonlinear transmittance response values. The experimentally obtained doping ratio dependencies and applied bias voltage responses of transmittance were also confirmed by LFFN-EPFs. This clearly indicates that physical laws embedded in the physical data can be faithfully extracted by the suitable LFNNs. The extraordinary success achieved with LFNN here suggests two potential applications. First, although not attempted here, these LFNN-EPFs, by such mathematical operations as derivation, integration, minimization etc., can be used to obtain further transmittance related functions of NLCs. Second, for a given NLC response function, whose theoretical nonlinear functional form is yet unknown, a suitable experimental data based LFNN-EPF can be constructed to predict the yet-to-be-measured values.

The anatomy of choice: dopamine and decision-making.

PubMed

Friston, Karl; Schwartenbeck, Philipp; FitzGerald, Thomas; Moutoussis, Michael; Behrens, Timothy; Dolan, Raymond J

2014-11-05

This paper considers goal-directed decision-making in terms of embodied or active inference. We associate bounded rationality with approximate Bayesian inference that optimizes a free energy bound on model evidence. Several constructs such as expected utility, exploration or novelty bonuses, softmax choice rules and optimism bias emerge as natural consequences of free energy minimization. Previous accounts of active inference have focused on predictive coding. In this paper, we consider variational Bayes as a scheme that the brain might use for approximate Bayesian inference. This scheme provides formal constraints on the computational anatomy of inference and action, which appear to be remarkably consistent with neuroanatomy. Active inference contextualizes optimal decision theory within embodied inference, where goals become prior beliefs. For example, expected utility theory emerges as a special case of free energy minimization, where the sensitivity or inverse temperature (associated with softmax functions and quantal response equilibria) has a unique and Bayes-optimal solution. Crucially, this sensitivity corresponds to the precision of beliefs about behaviour. The changes in precision during variational updates are remarkably reminiscent of empirical dopaminergic responses-and they may provide a new perspective on the role of dopamine in assimilating reward prediction errors to optimize decision-making.

A common minimal motif for the ligands of HLA-B*27 class I molecules.

PubMed

Barriga, Alejandro; Lorente, Elena; Johnstone, Carolina; Mir, Carmen; del Val, Margarita; López, Daniel

2014-01-01

CD8(+) T cells identify and kill infected cells through the specific recognition of short viral antigens bound to human major histocompatibility complex (HLA) class I molecules. The colossal number of polymorphisms in HLA molecules makes it essential to characterize the antigen-presenting properties common to large HLA families or supertypes. In this context, the HLA-B*27 family comprising at least 100 different alleles, some of them widely distributed in the human population, is involved in the cellular immune response against pathogens and also associated to autoimmune spondyloarthritis being thus a relevant target of study. To this end, HLA binding assays performed using nine HLA-B*2705-restricted ligands endogenously processed and presented in virus-infected cells revealed a common minimal peptide motif for efficient binding to the HLA-B*27 family. The motif was independently confirmed using four unrelated peptides. This experimental approach, which could be easily transferred to other HLA class I families and supertypes, has implications for the validation of new bioinformatics tools in the functional clustering of HLA molecules, for the identification of antiviral cytotoxic T lymphocyte responses, and for future vaccine development.

Optimal apparent damping as a function of the bandwidth of an array of vibration absorbers.

PubMed

Vignola, Joseph; Glean, Aldo; Judge, John; Ryan, Teresa

2013-08-01

The transient response of a resonant structure can be altered by the attachment of one or more substantially smaller resonators. Considered here is a coupled array of damped harmonic oscillators whose resonant frequencies are distributed across a frequency band that encompasses the natural frequency of the primary structure. Vibration energy introduced to the primary structure, which has little to no intrinsic damping, is transferred into and trapped by the attached array. It is shown that, when the properties of the array are optimized to reduce the settling time of the primary structure's transient response, the apparent damping is approximately proportional to the bandwidth of the array (the span of resonant frequencies of the attached oscillators). Numerical simulations were conducted using an unconstrained nonlinear minimization algorithm to find system parameters that result in the fastest settling time. This minimization was conducted for a range of system characteristics including the overall bandwidth of the array, the ratio of the total array mass to that of the primary structure, and the distributions of mass, stiffness, and damping among the array elements. This paper reports optimal values of these parameters and demonstrates that the resulting minimum settling time decreases with increasing bandwidth.

Neuropeptidergic Signaling Partitions Arousal Behaviors in Zebrafish

PubMed Central

Schoppik, David; Shi, Veronica J.; Zimmerman, Steven; Coleman, Haley A.; Greenwood, Joel; Soucy, Edward R.

2014-01-01

Animals modulate their arousal state to ensure that their sensory responsiveness and locomotor activity match environmental demands. Neuropeptides can regulate arousal, but studies of their roles in vertebrates have been constrained by the vast array of neuropeptides and their pleiotropic effects. To overcome these limitations, we systematically dissected the neuropeptidergic modulation of arousal in larval zebrafish. We quantified spontaneous locomotor activity and responsiveness to sensory stimuli after genetically induced expression of seven evolutionarily conserved neuropeptides, including adenylate cyclase activating polypeptide 1b (adcyap1b), cocaine-related and amphetamine-related transcript (cart), cholecystokinin (cck), calcitonin gene-related peptide (cgrp), galanin, hypocretin, and nociceptin. Our study reveals that arousal behaviors are dissociable: neuropeptide expression uncoupled spontaneous activity from sensory responsiveness, and uncovered modality-specific effects upon sensory responsiveness. Principal components analysis and phenotypic clustering revealed both shared and divergent features of neuropeptidergic functions: hypocretin and cgrp stimulated spontaneous locomotor activity, whereas galanin and nociceptin attenuated these behaviors. In contrast, cart and adcyap1b enhanced sensory responsiveness yet had minimal impacts on spontaneous activity, and cck expression induced the opposite effects. Furthermore, hypocretin and nociceptin induced modality-specific differences in responsiveness to changes in illumination. Our study provides the first systematic and high-throughput analysis of neuropeptidergic modulation of arousal, demonstrates that arousal can be partitioned into independent behavioral components, and reveals novel and conserved functions of neuropeptides in regulating arousal. PMID:24573274

Functional analysis of the Arabidopsis PLDZ2 promoter reveals an evolutionarily conserved low-Pi-responsive transcriptional enhancer element

PubMed Central

Oropeza-Aburto, Araceli; Cruz-Ramírez, Alfredo; Acevedo-Hernández, Gustavo J.; Pérez-Torres, Claudia-Anahí; Caballero-Pérez, Juan; Herrera-Estrella, Luis

2012-01-01

Plants have evolved a plethora of responses to cope with phosphate (Pi) deficiency, including the transcriptional activation of a large set of genes. Among Pi-responsive genes, the expression of the Arabidopsis phospholipase DZ2 (PLDZ2) is activated to participate in the degradation of phospholipids in roots in order to release Pi to support other cellular activities. A deletion analysis was performed to identify the regions determining the strength, tissue-specific expression, and Pi responsiveness of this regulatory region. This study also reports the identification and characterization of a transcriptional enhancer element that is present in the PLDZ2 promoter and able to confer Pi responsiveness to a minimal, inactive 35S promoter. This enhancer also shares the cytokinin and sucrose responsive properties observed for the intact PLDZ2 promoter. The EZ2 element contains two P1BS motifs, each of which is the DNA binding site of transcription factor PHR1. Mutation analysis showed that the P1BS motifs present in EZ2 are necessary but not sufficient for the enhancer function, revealing the importance of adjacent sequences. The structural organization of EZ2 is conserved in the orthologous genes of at least eight families of rosids, suggesting that architectural features such as the distance between the two P1BS motifs are also important for the regulatory properties of this enhancer element. PMID:22210906

The impact of aging on epithelial barriers.

PubMed

Parrish, Alan R

2017-10-02

The epithelium has many critical roles in homeostasis, including an essential responsibility in establishing tissue barriers. In addition to the fundamental role in separating internal from external environment, epithelial barriers maintain nutrient, fluid, electrolyte and metabolic waste balance in multiple organs. While, by definition, barrier function is conserved, the structure of the epithelium varies across organs. For example, the skin barrier is a squamous layer of cells with distinct structural features, while the lung barrier is composed of a very thin single cell to minimize diffusion space. With the increased focus on age-dependent alterations in organ structure and function, there is an emerging interest in the impact of age on epithelial barriers. This review will focus on the impact of aging on the epithelial barrier of several organs, including the skin, lung, gastrointestinal tract and the kidney, at a structural and functional level.

Optimal Technology Investment and Operation in Zero-Net-Energy Buildings with Demand Response

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

Stadler , Michael; Siddiqui, Afzal; Marnay, Chris

The US Department of Energy has launched the Zero-Net-Energy (ZNE) Commercial Building Initiative (CBI) in order to develop commercial buildings that produce as much energy as they use. Its objective is to make these buildings marketable by 2025 such that they minimize their energy use through cutting-edge energy-efficient technologies and meet their remaining energy needs through on-site renewable energy generation. We examine how such buildings may be implemented within the context of a cost- or carbon-minimizing microgrid that is able to adopt and operate various technologies, such as photovoltaic (PV) on-site generation, heat exchangers, solar thermal collectors, absorption chillers, andmore » passive / demand-response technologies. We use a mixed-integer linear program (MILP) that has a multi-criteria objective function: the minimization of a weighted average of the building's annual energy costs and carbon / CO2 emissions. The MILP's constraints ensure energy balance and capacity limits. In addition, constraining the building's energy consumed to equal its energy exports enables us to explore how energy sales and demand-response measures may enable compliance with the CBI. Using a nursing home in northern California and New York with existing tariff rates and technology data, we find that a ZNE building requires ample PV capacity installed to ensure electricity sales during the day. This is complemented by investment in energy-efficient combined heat and power equipment, while occasional demand response shaves energy consumption. A large amount of storage is also adopted, which may be impractical. Nevertheless, it shows the nature of the solutions and costs necessary to achieve ZNE. For comparison, we analyze a nursing home facility in New York to examine the effects of a flatter tariff structure and different load profiles. It has trouble reaching ZNE status and its load reductions as well as efficiency measures need to be more effective than those in the CA case. Finally, we illustrate that the multi-criteria frontier that considers costs and carbon emissions in the presence of demand response dominates the one without it.« less

Method for Ground-to-Satellite Laser Calibration System

NASA Technical Reports Server (NTRS)

Lukashin, Constantine (Inventor); Wielicki, Bruce A. (Inventor)

2015-01-01

The present invention comprises an approach for calibrating the sensitivity to polarization, optics degradation, spectral and stray light response functions of instruments on orbit. The concept is based on using an accurate ground-based laser system, Ground-to-Space Laser Calibration (GSLC), transmitting laser light to instrument on orbit during nighttime substantially clear-sky conditions. To minimize atmospheric contribution to the calibration uncertainty the calibration cycles should be performed in short time intervals, and all required measurements are designed to be relative. The calibration cycles involve ground operations with laser beam polarization and wavelength changes.

Method for Ground-to-Space Laser Calibration System

NASA Technical Reports Server (NTRS)

Lukashin, Constantine (Inventor); Wielicki, Bruce A. (Inventor)

2014-01-01

The present invention comprises an approach for calibrating the sensitivity to polarization, optics degradation, spectral and stray light response functions of instruments on orbit. The concept is based on using an accurate ground-based laser system, Ground-to-Space Laser Calibration (GSLC), transmitting laser light to instrument on orbit during nighttime substantially clear-sky conditions. To minimize atmospheric contribution to the calibration uncertainty the calibration cycles should be performed in short time intervals, and all required measurements are designed to be relative. The calibration cycles involve ground operations with laser beam polarization and wavelength changes.

Normalization of multidirectional red and NIR reflectances with the SAVI

NASA Technical Reports Server (NTRS)

Huete, A. R.; Hua, G.; Qi, J.; Chehbouni, A.; Van Leeuwen, W. J. D.

1992-01-01

Directional reflectance measurements were made over a semi-desert gramma grassland at various times of the growing season. View angle measurements from +40 to -40 degrees were made at various solar zenith angles and soil moisture conditions. The sensitivity of the Normalized Difference Vegetation Index (NDVI) and the Soil Adjusted Vegetation Index (SAVI) to bidirectional measurements was assessed for purposes of improving remote temporal monitoring of vegetation dynamics. The SAVI view angle response was found to be symmetric about nadir while the NDVI response was strongly anisotropic. This enabled the view angle behavior of the SAVI to be normalized with a cosine function. In contrast to the NDVI, the SAVI was able to minimize soil moisture and shadow influences for all measurement conditions.

Towards a psycho-physiological model of thermal perception

NASA Astrophysics Data System (ADS)

Auliciems, A.

1981-06-01

Recommendations for indoor thermal requirements have been based upon verbalized responses on traditional assumptions that (1) minimal thermoregulatory activity may be equated to maximum subjective acceptability (2) sensations and levels of discomfort are synonymous and (3) perception of warmth is exclusively the function of thermal stimulus — physiological response. These concepts are reviewed in the light of recent researches which indicate the inadequacy of the existing physiological models and methods of research. In particular, recognition is made of higher levels of mental integration of information flows which, it is argued, must include parameters of past cultural and climatic experiences and expectations. The aim is to initiate a more holistic approach to research into human thermal environments, and, a clearer definition of concepts significant to practical application.

Single passive leg movement-induced hyperemia: a simple vascular function assessment without a chronotropic response.

PubMed

Venturelli, Massimo; Layec, Gwenael; Trinity, Joel; Hart, Corey R; Broxterman, Ryan M; Richardson, Russell S

2017-01-01

Passive leg movement (PLM)-induced hyperemia is a novel approach to assess vascular function, with a potential clinical role. However, in some instances, the varying chronotropic response induced by PLM has been proposed to be a potentially confounding factor. Therefore, we simplified and modified the PLM model to require just a single PLM (sPLM), an approach that may evoke a peripheral hemodynamic response, allowing a vascular function assessment, but at the same time minimizing central responses. To both characterize and assess the utility of sPLM, in 12 healthy subjects, we measured heart rate (HR), stroke volume, cardiac output (CO), mean arterial pressure (MAP), leg blood flow (LBF), and calculated leg vascular conductance (LVC) during both standard PLM, consisting of passive knee flexion and extension performed at 1 Hz for 60 s, and sPLM, consisting of only a single passive knee flexion and extension over 1 s. During PLM, MAP transiently decreased (5 ± 1 mmHg), whereas both HR and CO increased from baseline (6.0 ± 1.1 beats/min, and 0.8 ± 0.01 l/min, respectively). Following sPLM, MAP fell similarly (5 ± 2 mmHg; P = 0.8), but neither HR nor CO responses were identifiable. The peak LBF and LVC response was similar for PLM (993 ± 189 ml/min; 11.9 ± 1.5 ml·min -1 ·mmHg -1 , respectively) and sPLM (878 ± 119 ml/min; 10.9 ± 1.6 ml·min -1 ·mmHg -1 , respectively). Thus sPLM represents a variant of the PLM approach to assess vascular function that is more easily performed and evokes a peripheral stimulus that induces a significant hyperemia, but does not generate a potentially confounding, chronotropic response, which may make sPLM more useful clinically. Using the single passive leg movement (PLM) technique, a variant of the vascular function assessment PLM, we have identified a novel peripheral vascular assessment method that is more easily performed than PLM, which, by not evoking potentially confounding central hemodynamic responses, may be more useful clinically.

Mutations Abrogating VP35 Interaction with Double-Stranded RNA Render Ebola Virus Avirulent in Guinea Pigs

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

Prins, Kathleen C.; Delpeut, Sebastien; Leung, Daisy W.

2010-10-11

Ebola virus (EBOV) protein VP35 is a double-stranded RNA (dsRNA) binding inhibitor of host interferon (IFN)-{alpha}/{beta} responses that also functions as a viral polymerase cofactor. Recent structural studies identified key features, including a central basic patch, required for VP35 dsRNA binding activity. To address the functional significance of these VP35 structural features for EBOV replication and pathogenesis, two point mutations, K319A/R322A, that abrogate VP35 dsRNA binding activity and severely impair its suppression of IFN-{alpha}/{beta} production were identified. Solution nuclear magnetic resonance (NMR) spectroscopy and X-ray crystallography reveal minimal structural perturbations in the K319A/R322A VP35 double mutant and suggest that lossmore » of basic charge leads to altered function. Recombinant EBOVs encoding the mutant VP35 exhibit, relative to wild-type VP35 viruses, minimal growth attenuation in IFN-defective Vero cells but severe impairment in IFN-competent cells. In guinea pigs, the VP35 mutant virus revealed a complete loss of virulence. Strikingly, the VP35 mutant virus effectively immunized animals against subsequent wild-type EBOV challenge. These in vivo studies, using recombinant EBOV viruses, combined with the accompanying biochemical and structural analyses directly correlate VP35 dsRNA binding and IFN inhibition functions with viral pathogenesis. Moreover, these studies provide a framework for the development of antivirals targeting this critical EBOV virulence factor.« less

Computational Morphometry for Detecting Changes in Brain Structure Due to Development, Aging, Learning, Disease and Evolution

PubMed Central

Mietchen, Daniel; Gaser, Christian

2009-01-01

The brain, like any living tissue, is constantly changing in response to genetic and environmental cues and their interaction, leading to changes in brain function and structure, many of which are now in reach of neuroimaging techniques. Computational morphometry on the basis of Magnetic Resonance (MR) images has become the method of choice for studying macroscopic changes of brain structure across time scales. Thanks to computational advances and sophisticated study designs, both the minimal extent of change necessary for detection and, consequently, the minimal periods over which such changes can be detected have been reduced considerably during the last few years. On the other hand, the growing availability of MR images of more and more diverse brain populations also allows more detailed inferences about brain changes that occur over larger time scales, way beyond the duration of an average research project. On this basis, a whole range of issues concerning the structures and functions of the brain are now becoming addressable, thereby providing ample challenges and opportunities for further contributions from neuroinformatics to our understanding of the brain and how it changes over a lifetime and in the course of evolution. PMID:19707517

Functional near-infrared spectroscopy study on primary motor and sensory cortex response to clenching.

PubMed

Shibusawa, Mami; Takeda, Tomotaka; Nakajima, Kazunori; Ishigami, Keiichi; Sakatani, Kaoru

2009-01-09

The purpose of this study was to elucidate the influence of clenching and clenching intensity on oxygenated hemoglobin (OxyHb) levels in regional cerebral blood flow as an indicator of brain activity in the primary motor and sensory cortices. Functional near-infrared spectroscopy (fNIRS) was used to minimize the effect of clenching-associated muscle activity in eight healthy subjects. Subjects were required to clench at 20%, 50% and 80% of maximum clenching force. To minimize the effect of temporal muscle activity on the working side of the jaw, the fNIRS probes were positioned contralaterally, in the left temporal region. Activation of the primary motor and sensory cortices with clenching was noted in all subjects, irrespective of intensity of clenching. A significant increase was observed in OxyHb in the primary motor cortex between at 80% and both 20% and 50% clenching intensity. In the primary sensory cortex, OxyHb showed a significant increase between all levels of clenching intensity. The results suggest that clenching elicits activation of both the primary motor and sensory cortices, and that intensity of clenching influences activation levels in the brain.

Relativistic effects in ab initio electron-nucleus scattering

NASA Astrophysics Data System (ADS)

Rocco, Noemi; Leidemann, Winfried; Lovato, Alessandro; Orlandini, Giuseppina

2018-05-01

The electromagnetic responses obtained from Green's function Monte Carlo (GFMC) calculations are based on realistic treatments of nuclear interactions and currents. The main limitations of this method comes from its nonrelativistic nature and its computational cost, the latter hampering the direct evaluation of the inclusive cross sections as measured by experiments. We extend the applicability of GFMC in the quasielastic region to intermediate momentum transfers by performing the calculations in a reference frame that minimizes nucleon momenta. Additional relativistic effects in the kinematics are accounted for employing the two-fragment model. In addition, we developed a novel algorithm, based on the concept of first-kind scaling, to compute the inclusive electromagnetic cross section of 4He through an accurate and reliable interpolation of the response functions. A very good agreement is obtained between theoretical and experimental cross sections for a variety of kinematical setups. This offers a promising prospect for the data analysis of neutrino-oscillation experiments that requires an accurate description of nuclear dynamics in which relativistic effects are fully accounted for.

Structural Tailoring of Advanced Turboprops (STAT). Theoretical manual

NASA Technical Reports Server (NTRS)

Brown, K. W.

1992-01-01

This manual describes the theories in the Structural Tailoring of Advanced Turboprops (STAT) computer program, which was developed to perform numerical optimizations on highly swept propfan blades. The optimization procedure seeks to minimize an objective function, defined as either direct operating cost or aeroelastic differences between a blade and its scaled model, by tuning internal and external geometry variables that must satisfy realistic blade design constraints. The STAT analyses include an aerodynamic efficiency evaluation, a finite element stress and vibration analysis, an acoustic analysis, a flutter analysis, and a once-per-revolution (1-p) forced response life prediction capability. The STAT constraints include blade stresses, blade resonances, flutter, tip displacements, and a 1-P forced response life fraction. The STAT variables include all blade internal and external geometry parameters needed to define a composite material blade. The STAT objective function is dependent upon a blade baseline definition which the user supplies to describe a current blade design for cost optimization or for the tailoring of an aeroelastic scale model.

Structural Tailoring of Advanced Turboprops (STAT). Theoretical manual

NASA Astrophysics Data System (ADS)

Brown, K. W.

1992-10-01

This manual describes the theories in the Structural Tailoring of Advanced Turboprops (STAT) computer program, which was developed to perform numerical optimizations on highly swept propfan blades. The optimization procedure seeks to minimize an objective function, defined as either direct operating cost or aeroelastic differences between a blade and its scaled model, by tuning internal and external geometry variables that must satisfy realistic blade design constraints. The STAT analyses include an aerodynamic efficiency evaluation, a finite element stress and vibration analysis, an acoustic analysis, a flutter analysis, and a once-per-revolution (1-p) forced response life prediction capability. The STAT constraints include blade stresses, blade resonances, flutter, tip displacements, and a 1-P forced response life fraction. The STAT variables include all blade internal and external geometry parameters needed to define a composite material blade. The STAT objective function is dependent upon a blade baseline definition which the user supplies to describe a current blade design for cost optimization or for the tailoring of an aeroelastic scale model.

System Response Manipulation using Arrays of Subordinate Resonators: Theory and Applications

NASA Astrophysics Data System (ADS)

Glean, Aldo A. J.

The dynamic response of a resonant structure can be significantly altered by the attachment of an array of substantially smaller resonators. This dissertation presents the theory governing these subordinate oscillator arrays (SOAs) and explores four major applications of using the arrays. The first application is related to vibration suppression. Numerical optimization was used to obtain SOA properties that minimize the settling time of a primary resonator subjected to an impulse. This minimization was conducted for system characteristics including the overall bandwidth of the array, the ratio of total array mass to primary resonator mass, and distributions of array properties. It is shown that the minimum settling time is a function of bandwidth and added mass within the SOA. The second application introduces a novel method of chemical vapor detection using SOA elements that are functionalized to bond with a specific chemical species. Numerical simulations were used to relate mass adsorbed to changes in the time-domain response of the system. It is shown that increasing the number of sensing elements increases sensitivity and reduces errors in mass predictions due to mass adsorption variability while having fewer sensing elements increases signal-to-noise ratio. The third application is also concerned with chemical vapor detection. Numerical simulation was used to explore the changes in system resonant frequencies and normal mode shapes in response to adsorption of mass on a single array element, in arrays in which each element has a distinct resonant frequency. It is shown that the degree of inter-element coupling is proportional to the ratio of the mass of the elements to the primary resonator mass. Inter-element coupling was also found to increase linearly with decreasing system resonance spacing up to a maximum value that depends on the mass ratio. The final application is an experimental validation of SOA theory by application to an acoustic system. The third resonance of a standing wave tube is transformed into a bandpass response using an array of small Helmholtz resonators. This experimental work demonstrates that the SOA theory can be applied analogous systems.

Maximize, minimize or target - optimization for a fitted response from a designed experiment

DOE PAGES

Anderson-Cook, Christine Michaela; Cao, Yongtao; Lu, Lu

2016-04-01

One of the common goals of running and analyzing a designed experiment is to find a location in the design space that optimizes the response of interest. Depending on the goal of the experiment, we may seek to maximize or minimize the response, or set the process to hit a particular target value. After the designed experiment, a response model is fitted and the optimal settings of the input factors are obtained based on the estimated response model. Furthermore, the suggested optimal settings of the input factors are then used in the production environment.

A reference tristimulus colorimeter

NASA Astrophysics Data System (ADS)

Eppeldauer, George P.

2002-06-01

A reference tristimulus colorimeter has been developed at NIST with a transmission-type silicon trap detector (1) and four temperature-controlled filter packages to realize the Commission Internationale de l'Eclairage (CIE) x(λ), y(λ) and z(λ) color matching functions (2). Instead of lamp standards, high accuracy detector standards are used for the colorimeter calibration. A detector-based calibration procedure is being suggested for tristimulus colorimeters wehre the absolute spectral responsivity of the tristimulus channels is determined. Then, color (spectral) correct and peak (amplitude) normalization are applied to minimize uncertainties caused by the imperfect realizations of the CIE functions. As a result of the corrections, the chromaticity coordinates of stable light sources with different spectral power distributions can be measured with uncertainties less than 0.0005 (k=1).

Functional beliefs and risk minimizing beliefs among Thai healthcare workers in Maharaj Nakorn Chiang Mai hospital: its association with intention to quit tobacco and alcohol.

PubMed

Jiraniramai, Surin; Jiraporncharoen, Wichuda; Pinyopornpanish, Kanokporn; Jakkaew, Nalinee; Wongpakaran, Tinakon; Angkurawaranon, Chaisiri

2017-07-12

Individual health beliefs are likely to play a key role in how people respond to knowledge and information about the potential harm from smoking and alcohol abuse. The objectives of the study were to 1) explore whether functional beliefs and risk minimizing beliefs were associated with intention to quit smoking and confidence to quit smoking and 2) explore whether functional beliefs and risk minimizing beliefs were associated with intention to quit alcohol drinking and confidence to quit alcohol drinking. A cross-sectional survey was conducted in 2013 among health care workers working in Thailand. Using predicted factor scores from factor analysis, the relationship between factor scores for each of the two beliefs and intention to quit and confidence to quit were tested using ANOVA and further adjusted for age and sex using linear regression. Functional beliefs were inversely associated with the intention to quit and confidence to quit smoking. Both functional beliefs and risk minimizing beliefs were each inversely associated with the intention to quit and confidence to quit alcohol drinking. Our study enhances the understanding of the complexities of health beliefs regarding these two commonly abused substances. As functional beliefs were associated with smoking and alcohol use, interventions to counter the cultural values and individual beliefs about the benefits of smoking and alcohol use are needed. Tackling risk minimizing beliefs by providing individualized feedback regarding harm may also be useful in alcohol drinkers.

Why minimally invasive skin sampling techniques? A bright scientific future.

PubMed

Wang, Christina Y; Maibach, Howard I

2011-03-01

There is increasing interest in minimally invasive skin sampling techniques to assay markers of molecular biology and biochemical processes. This overview examines methodology strengths and limitations, and exciting developments pending in the scientific community. Publications were searched via PubMed, the U.S. Patent and Trademark Office Website, the DermTech Website and the CuDerm Website. The keywords used were noninvasive skin sampling, skin stripping, skin taping, detergent method, ring method, mechanical scrub, reverse iontophoresis, glucose monitoring, buccal smear, hair root sampling, mRNA, DNA, RNA, and amino acid. There is strong interest in finding methods to access internal biochemical, molecular, and genetic processes through noninvasive and minimally invasive external means. Minimally invasive techniques include the widely used skin tape stripping, the abrasion method that includes scraping and detergent, and reverse iontophoresis. The first 2 methods harvest largely the stratum corneum. Hair root sampling (material deeper than the epidermis), buccal smear, shave biopsy, punch biopsy, and suction blistering are also methods used to obtain cellular material for analysis, but involve some degree of increased invasiveness and thus are only briefly mentioned. Existing and new sampling methods are being refined and validated, offering exciting, different noninvasive means of quickly and efficiently obtaining molecular material with which to monitor bodily functions and responses, assess drug levels, and follow disease processes without subjecting patients to unnecessary discomfort and risk.

The anatomy of choice: active inference and agency.

PubMed

Friston, Karl; Schwartenbeck, Philipp; Fitzgerald, Thomas; Moutoussis, Michael; Behrens, Timothy; Dolan, Raymond J

2013-01-01

This paper considers agency in the setting of embodied or active inference. In brief, we associate a sense of agency with prior beliefs about action and ask what sorts of beliefs underlie optimal behavior. In particular, we consider prior beliefs that action minimizes the Kullback-Leibler (KL) divergence between desired states and attainable states in the future. This allows one to formulate bounded rationality as approximate Bayesian inference that optimizes a free energy bound on model evidence. We show that constructs like expected utility, exploration bonuses, softmax choice rules and optimism bias emerge as natural consequences of this formulation. Previous accounts of active inference have focused on predictive coding and Bayesian filtering schemes for minimizing free energy. Here, we consider variational Bayes as an alternative scheme that provides formal constraints on the computational anatomy of inference and action-constraints that are remarkably consistent with neuroanatomy. Furthermore, this scheme contextualizes optimal decision theory and economic (utilitarian) formulations as pure inference problems. For example, expected utility theory emerges as a special case of free energy minimization, where the sensitivity or inverse temperature (of softmax functions and quantal response equilibria) has a unique and Bayes-optimal solution-that minimizes free energy. This sensitivity corresponds to the precision of beliefs about behavior, such that attainable goals are afforded a higher precision or confidence. In turn, this means that optimal behavior entails a representation of confidence about outcomes that are under an agent's control.

Renal function and plasma volume following ultramarathon cycling.

PubMed

Neumayr, G; Pfister, R; Hoertnagl, H; Mitterbauer, G; Prokop, W; Joannidis, M

2005-01-01

In recreational cyclists marathon cycling influences renal function only on a minimal scale. Respective information on extreme ultramarathon cycling in better trained athletes is not available. The objective was to evaluate the renal and haematological effects of ultraendurance cycling in the world's best ultramarathon cyclists. Creatinine (CR), urea, haemoglobin (Hb), haematocrit (Hct) and plasma volume (PV) were investigated in 16 male ultramarathon cyclists during the 1st Race Across the Alps in 2001 (distance: 525 km; cumulative altitude difference: 12,600 m). All renal functional parameters were normal pre-exercise. During the race serum CR, urea and uric acid rose significantly by 33, 97 % and 18 % (p <0.001 respectively) and nearly normalised again on the following day. The decline in calculated CR clearance was 25 %. There was a negative correlation (r=- 0.575, p=0.02) between the rise in serum CR and the athlete's training kilometers. The serum urea/CR ratio rose above 40 in 12 athletes (75 %). Mean fractional sodium excretion and fractional uric acid excretion fell below 0.5 % (p <0.001) and 7 %, indicating reduced renal perfusion. The deflection of the renal functional parameters was temporary and nearly gone after 24 hours of recovery. Hct declined during the race from 0.44 to 0.42, and continued falling on the next day (0.42 --> 0.40; p <0.001). The corresponding rises in calculated PV were + 8 % and + 22 %. The study affirms that in world class cyclists the enormous strains of ultramarathon cycling influence renal function only on a minimal scale. The impact on the PV, however, is pronounced leading to marked haemodilution post-exercise. This very temporary "impairment of renal function" seems to be the physiological response to ultramarathon cycling and may be attenuated to some extent by preceding high-volume training.

Productivity benefits of minimally invasive surgery in patients with chronic sacroiliac joint dysfunction.

PubMed

Saavoss, Josh D; Koenig, Lane; Cher, Daniel J

2016-01-01

Sacroiliac joint (SIJ) dysfunction is associated with a marked decrease in quality of life. Increasing evidence supports minimally invasive SIJ fusion as a safe and effective procedure for the treatment of chronic SIJ dysfunction. The impact of SIJ fusion on worker productivity is not known. Regression modeling using data from the National Health Interview Survey was applied to determine the relationship between responses to selected interview questions related to function and economic outcomes. Regression coefficients were then applied to prospectively collected, individual patient data in a randomized trial of SIJ fusion (INSITE, NCT01681004) to estimate expected differences in economic outcomes across treatments. Patients who receive SIJ fusion using iFuse Implant System(®) have an expected increase in the probability of working of 16% (95% confidence interval [CI] 11%-21%) relative to nonsurgical patients. The expected change in earnings across groups was US $3,128 (not statistically significant). Combining the two metrics, the annual increase in worker productivity given surgical vs nonsurgical care was $6,924 (95% CI $1,890-$11,945). For employees with chronic, severe SIJ dysfunction, minimally invasive SIJ fusion may improve worker productivity compared to nonsurgical treatment.

Assessment of Male Anthropometric Trends and the Effects on Thermal Regulatory Models

DTIC Science & Technology

2007-08-01

However, simulated Tcr responses to heat stress in each somatotype were similar in the 2004 and 1988 populations. In conclusion, an increase in body...each somatotype , differences in physiological responses were minimal and insignificant between the 1988 and 2004 datasets. 1988 2004 n 1773 480 Age...Yet, the change in each somatotype between 1988 and 2004 had a minimal affect on simulated Tcr response to heat stress. In this study, “small

Analytical solution of Schrödinger equation in minimal length formalism for trigonometric potential using hypergeometry method

NASA Astrophysics Data System (ADS)

Nurhidayati, I.; Suparmi, A.; Cari, C.

2018-03-01

The Schrödinger equation has been extended by applying the minimal length formalism for trigonometric potential. The wave function and energy spectra were used to describe the behavior of subatomic particle. The wave function and energy spectra were obtained by using hypergeometry method. The result showed that the energy increased by the increasing both of minimal length parameter and the potential parameter. The energy were calculated numerically using MatLab.

[Construction of a general AAV vector regulated by minimal and artificial hypoxic-responsive element].

PubMed

Nie, Xiao-wei; Sun, Li-jun; Hao, Yue-wen; Yang, Guang-xiao; Wang, Quan-ying

2011-03-01

To synthesize the minimal and artificial HRE, and to insert it into the anterior extremity of CMV promoter of a AAV plasmid, and then to construct the AAV regulated by hypoxic-responsive element which was introduced into 293 cell by method of Ca3(PO4)2 using three plasmids. Thus obtaining the adenoassociated virus vector regulated by hypoxic-responsive element was possibly used for gene therapy in ischemia angiocardiopathy and cerebrovascular disease. Artificially synthesize the 36 bp nucleotide sequences of four connection in series HIF-binding sites A/GCGTG(4×HBS)and a 35 bp nucleotide sequences spacing inserted into anterior extremity of CMV promoter TATA Box, then amplified by PCR. The cDNA fragment was confirmed to be right by DNA sequencing. Molecular biology routine method was used to construct a AAV vector regulated by minimal hypoxic-responsive element after the normal CMV promoter in AAV vector was replaced by the CMV promoter included minimal hypoxic-responsive element. Then, NT4-6His-PR39 fusogenic peptide was inserted into MCS of the plasmid, the recombinant AAV vector was obtained by three plasmid co-transfection in 293 cells, in which we can also investigate the expression of 6×His using immunochemistry in hypoxia environment. Artificial HRE was inserted into anterior extremity of CMV promoter and there was a correct spacing between the HRE and the TATA-box. The DNA sequencing and restriction enzyme digestion results indicated that the AAV regulated by hypoxic-responsive element was successfully constructed. Compared to the control group, the expressions of 6×His was significantly increased in the experimental groups in hypoxia environment, which confirmed that the AAV effectually regulated by the minimal HRE was inserted into anterior extremity of CMV promoter. The HRE is inserted into anterior extremity of CMV promoter to lack incision enzyme recognition site by PCR. And eukaryotic expression vector regulated by hypoxic-responsive is constructed. The AAV effectually regulated by the minimal HRE inserted into anterior extremity of CMV promoter. The vector is successfully constructed and it has important theoretical and practical value in the synteresis and therapy of ischemia angiocardiopathy and cerebrovascular disease.

Toward the International Classification of Functioning, Disability and Health (ICF) Rehabilitation Set: A Minimal Generic Set of Domains for Rehabilitation as a Health Strategy.

PubMed

Prodinger, Birgit; Cieza, Alarcos; Oberhauser, Cornelia; Bickenbach, Jerome; Üstün, Tevfik Bedirhan; Chatterji, Somnath; Stucki, Gerold

2016-06-01

To develop a comprehensive set of the International Classification of Functioning, Disability and Health (ICF) categories as a minimal standard for reporting and assessing functioning and disability in clinical populations along the continuum of care. The specific aims were to specify the domains of functioning recommended for an ICF Rehabilitation Set and to identify a minimal set of environmental factors (EFs) to be used alongside the ICF Rehabilitation Set when describing disability across individuals and populations with various health conditions. Secondary analysis of existing data sets using regression methods (Random Forests and Group Lasso regression) and expert consultations. Along the continuum of care, including acute, early postacute, and long-term and community rehabilitation settings. Persons (N=9863) with various health conditions participated in primary studies. The number of respondents for whom the dependent variable data were available and used in this analysis was 9264. Not applicable. For regression analyses, self-reported general health was used as a dependent variable. The ICF categories from the functioning component and the EF component were used as independent variables for the development of the ICF Rehabilitation Set and the minimal set of EFs, respectively. Thirty ICF categories to be complemented with 12 EFs were identified as relevant to the identified ICF sets. The ICF Rehabilitation Set constitutes of 9 ICF categories from the component body functions and 21 from the component activities and participation. The minimal set of EFs contains 12 categories spanning all chapters of the EF component of the ICF. The identified sets proposed serve as minimal generic sets of aspects of functioning in clinical populations for reporting data within and across heath conditions, time, clinical settings including rehabilitation, and countries. These sets present a reference framework for harmonizing existing information on disability across general and clinical populations. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Oxidative stress and protein aggregation during biological aging.

PubMed

Squier, T C

2001-09-01

Biological aging is a fundamental process that represents the major risk factor with respect to the development of cancer, neurodegenerative, and cardiovascular diseases in vertebrates. It is, therefore, evident that the molecular mechanisms of aging are fundamental to understand many disease processes. In this regard, the oxidation and nitration of intracellular proteins and the formation of protein aggregates have been suggested to underlie the loss of cellular function and the reduced ability of senescent animals to withstand physiological stresses. Since oxidatively modified proteins are thermodynamically unstable and assume partially unfolded tertiary structures that readily form aggregates, it is likely that oxidized proteins are intermediates in the formation of amyloid fibrils. It is, therefore, of interest to identify oxidatively sensitive protein targets that may play a protective role through their ability to down-regulate energy metabolism and the consequent generation of reactive oxygen species (ROS). In this respect, the maintenance of cellular calcium gradients represents a major energetic expense, which links alterations in intracellular calcium levels to ATP utilization and the associated generation of ROS through respiratory control mechanisms. The selective oxidation or nitration of the calcium regulatory proteins calmodulin and Ca-ATPase that occurs in vivo during aging and under conditions of oxidative stress may represent an adaptive response to oxidative stress that functions to down-regulate energy metabolism and the associated generation of ROS. Since these calcium regulatory proteins are also preferentially oxidized or nitrated under in vitro conditions, these results suggest an enhanced sensitivity of these critical calcium regulatory proteins, which modulate signal transduction processes and intracellular energy metabolism, to conditions of oxidative stress. Thus, the selective oxidation of critical signal transduction proteins probably represents a regulatory mechanism that functions to minimize the generation of ROS through respiratory control mechanisms. The reduction of the rate of ROS generation, in turn, will promote cellular survival under conditions of oxidative stress, when reactive oxygen and nitrogen species overwhelm cellular antioxidant defense systems, by minimizing the non-selective oxidation of a range of biomolecules. Since protein aggregation occurs if protein repair and degradative systems are unable to act upon oxidized proteins and restore cellular function, the reduction of the oxidative load on the cell by the down-regulation of the electron transport chain functions to minimize protein aggregation. Thus, ROS function as signaling molecules that fine-tune cellular metabolism through the selective oxidation or nitration of calcium regulatory proteins in order to minimize wide-spread oxidative damage and protein aggregation. Oxidative damage to cellular proteins, the loss of calcium homeostasis and protein aggregation contribute to the formation of amyloid deposits that accumulate during biological aging. Critical to understand the relationship between these processes and biological aging is the identification of oxidatively sensitive proteins that modulate energy utilization and the associated generation of ROS. In this latter respect, oxidative modifications to the calcium regulatory proteins calmodulin (CaM) and the sarco/endoplasmic reticulum Ca-ATPase (SERCA) function to down-regulate ATP utilization and the associated generation of ROS associated with replenishing intracellular ATP through oxidative phosphorylation. Reductions in the rate of ROS generation, in turn, will minimize protein oxidation and facilitate intracellular repair and degradative systems that function to eliminate damaged and partially unfolded proteins. Since the rates of protein repair or degradation compete with the rate of protein aggregation, the modulation of intracellular calcium concentrations and energy metabolism through the selective oxidation or nitration of critical signal transduction proteins (i.e. CaM or SERCA) is thought to maintain cellular function by minimizing protein aggregation and amyloid formation. Age-dependent increases in the rate of ROS generation or declines in cellular repair or degradation mechanisms will increase the oxidative load on the cell, resulting in corresponding increases in the concentrations of oxidized proteins and the associated formation of amyloid.

Nonlinear mechanical response of the extracellular matrix: learning from articular cartilage

NASA Astrophysics Data System (ADS)

Kearns, Sarah; Das, Moumita

2015-03-01

We study the mechanical structure-function relations in the extracellular matrix (ECM) with focus on nonlinear shear and compression response. As a model system, our study focuses on the ECM in articular cartilage tissue which has two major mechanobiological components: a network of the biopolymer collagen that acts as a stiff, reinforcing matrix, and a flexible aggrecan network that facilitates deformability. We model this system as a double network hydrogel made of interpenetrating networks of stiff and flexible biopolymers respectively. We study the linear and nonlinear mechanical response of the model ECM to shear and compression forces using a combination of rigidity percolation theory and energy minimization approaches. Our results may provide useful insights into the design principles of the ECM as well as biomimetic hydrogels that are mechanically robust and can, at the same time, easily adapt to cues in their surroundings.

Low-fat meat sausages with fish oil: optimization of milk proteins and carrageenan contents using response surface methodology.

PubMed

Marchetti, L; Andrés, S C; Califano, A N

2014-03-01

Response surface methodology was used to analyze the effect of milk proteins and 2:1 κ:ι-carrageenans on cooking loss (CL), weight lost by centrifugation (WLC) and texture attributes of low-fat meat sausages with pre-emulsified fish oil. A central-composite design was used to develop models for the objective responses. Changes in carrageenans affected more the responses than milk proteins levels. Convenience functions were calculated for CL, WLC, hardness, and springiness of the product. Responses were optimized simultaneously minimizing CL and WLC; ranges for hardness and springiness corresponded to commercial products (20 g of pork fat/100 g). The optimum corresponded to 0.593 g of carrageenans/100 g and 0.320 g of milk proteins and its total lipid content was 6.3 g/100 g. This formulation was prepared and evaluated showing a good agreement between predicted and experimental responses. These additives could produce low-fat meat sausages with pre-emulsified fish oil with good nutritional quality and similar characteristics than traditional ones. Copyright © 2013 Elsevier Ltd. All rights reserved.

Adaptive behaviour and multiple equilibrium states in a predator-prey model.

PubMed

Pimenov, Alexander; Kelly, Thomas C; Korobeinikov, Andrei; O'Callaghan, Michael J A; Rachinskii, Dmitrii

2015-05-01

There is evidence that multiple stable equilibrium states are possible in real-life ecological systems. Phenomenological mathematical models which exhibit such properties can be constructed rather straightforwardly. For instance, for a predator-prey system this result can be achieved through the use of non-monotonic functional response for the predator. However, while formal formulation of such a model is not a problem, the biological justification for such functional responses and models is usually inconclusive. In this note, we explore a conjecture that a multitude of equilibrium states can be caused by an adaptation of animal behaviour to changes of environmental conditions. In order to verify this hypothesis, we consider a simple predator-prey model, which is a straightforward extension of the classic Lotka-Volterra predator-prey model. In this model, we made an intuitively transparent assumption that the prey can change a mode of behaviour in response to the pressure of predation, choosing either "safe" of "risky" (or "business as usual") behaviour. In order to avoid a situation where one of the modes gives an absolute advantage, we introduce the concept of the "cost of a policy" into the model. A simple conceptual two-dimensional predator-prey model, which is minimal with this property, and is not relying on odd functional responses, higher dimensionality or behaviour change for the predator, exhibits two stable co-existing equilibrium states with basins of attraction separated by a separatrix of a saddle point. Copyright © 2015 Elsevier Inc. All rights reserved.

Cannabidiol (CBD) Induces Functional Tregs in Response to Low-Level T Cell Activation

PubMed Central

Dhital, Saphala; Stokes, John V.; Park, Nogi; Seo, Keun-Seok; Kaplan, Barbara L.F.

2016-01-01

Many effects of the non-psychoactive cannabinoid, cannabidiol (CBD), have been described in immune responses induced by strong immunological stimuli. It has also been shown that CBD enhances IL-2 production in response to low-level T cell stimulation. Since IL-2, in combination with TGF-β1, are critical for Treg induction, we hypothesized that CBD would induce CD4+CD25+FOXP3+ Tregs in response to low-level stimulation. Low-level T cell stimulation conditions were established based on minimal CD25 expression in CD4+ cells using suboptimal PMA/Io (4 nM/0.05 μM, S/o), ultrasuboptimal PMA/Io (1 nM/0.0125 μM, Us/o) or soluble anti-CD3/28 (400-800 ng each, s3/28). CBD increased CD25+FOXP3+ cells from CD4+, CD4+CD25+, and CD4+CD25− T cells, as well as in CD4+ T cells derived from FOXP3-GFP mice. Most importantly, the Us/o + CBD-induced CD4+CD25+ Tregs robustly suppressed responder T cell proliferation, demonstrating that the mechanism by which CBD is immunosuppressive under low-level T cell stimulation involves induction of functional Tregs. PMID:27865421

Arabidopsis copper transport protein COPT2 participates in the cross talk between iron deficiency responses and low-phosphate signaling.

PubMed

Perea-García, Ana; Garcia-Molina, Antoni; Andrés-Colás, Nuria; Vera-Sirera, Francisco; Pérez-Amador, Miguel A; Puig, Sergi; Peñarrubia, Lola

2013-05-01

Copper and iron are essential micronutrients for most living organisms because they participate as cofactors in biological processes, including respiration, photosynthesis, and oxidative stress protection. In many eukaryotic organisms, including yeast (Saccharomyces cerevisiae) and mammals, copper and iron homeostases are highly interconnected; yet, such interdependence is not well established in higher plants. Here, we propose that COPT2, a high-affinity copper transport protein, functions under copper and iron deficiencies in Arabidopsis (Arabidopsis thaliana). COPT2 is a plasma membrane protein that functions in copper acquisition and distribution. Characterization of the COPT2 expression pattern indicates a synergic response to copper and iron limitation in roots. We characterized a knockout of COPT2, copt2-1, that leads to increased resistance to simultaneous copper and iron deficiencies, measured as reduced leaf chlorosis and improved maintenance of the photosynthetic apparatus. We propose that COPT2 could play a dual role under iron deficiency. First, COPT2 participates in the attenuation of copper deficiency responses driven by iron limitation, possibly to minimize further iron consumption. Second, global expression analyses of copt2-1 versus wild-type Arabidopsis plants indicate that low-phosphate responses increase in the mutant. These results open up new biotechnological approaches to fight iron deficiency in crops.

Cannabidiol (CBD) induces functional Tregs in response to low-level T cell activation.

PubMed

Dhital, Saphala; Stokes, John V; Park, Nogi; Seo, Keun Seok; Kaplan, Barbara L F

2017-02-01

Many effects of the non-psychoactive cannabinoid, cannabidiol (CBD), have been described in immune responses induced by strong immunological stimuli. It has also been shown that CBD enhances IL-2 production in response to low-level T cell stimulation. Since IL-2, in combination with TGF-β1, are critical for Treg induction, we hypothesized that CBD would induce CD4 + CD25 + FOXP3 + Tregs in response to low-level stimulation. Low-level T cell stimulation conditions were established based on minimal CD25 expression in CD4 + cells using suboptimal PMA/Io (4nM/0.05μM, S/o), ultrasuboptimal PMA/Io (1nM/0.0125μM, Us/o) or soluble anti-CD3/28 (400-800ng each, s3/28). CBD increased CD25 + FOXP3 + cells from CD4 + , CD4 + CD25 + , and CD4 + CD25 - T cells, as well as in CD4 + T cells derived from FOXP3-GFP mice. Most importantly, the Us/o+CBD-induced CD4 + CD25 + Tregs robustly suppressed responder T cell proliferation, demonstrating that the mechanism by which CBD is immunosuppressive under low-level T cell stimulation involves induction of functional Tregs. Copyright © 2016 Elsevier Inc. All rights reserved.

Psychometric properties of the Canadian Occupational Performance Measure in home-dwelling older adults

PubMed Central

Tuntland, Hanne; Aaslund, Mona Kristin; Langeland, Eva; Espehaug, Birgitte; Kjeken, Ingvild

2016-01-01

Background The Canadian Occupational Performance Measure (COPM) is an occupational therapy instrument designed to help participants identify, prioritize, and evaluate performance of important occupations. Objective To investigate the validity, responsiveness, interpretability, and feasibility of the COPM when used by various health professions in home-dwelling older adults receiving reablement. Reablement is a new form of multidisciplinary home-based rehabilitation for older adults experiencing functional decline. Participants and methods The sample of 225 participants, mean age 80.8 years, who were in need of rehabilitation for various health conditions were included in the study. Data collection was conducted at baseline and at 10 weeks follow-up. The COSMIN guidelines and recommendations for evaluating methodological quality were followed. Results Content validity, construct validity, and feasibility were found to be adequate. Responsiveness, however, was moderate. Functional mobility was the most frequently prioritized occupational category of all. Regarding interpretability, the minimal important change was 3.0 points and 3.2 points for performance and satisfaction, respectively. The older adults reported that COPM was a useful and manageable instrument. The majority of the occupational therapists, physiotherapists, and nurses reported that they had the required expertise to conduct the COPM assessments. Conclusion The results support the multidisciplinary use of the COPM in clinical practice and research in a home-dwelling, heterogeneous population of older adults. Based on the findings, 3 points are recommended as a cutoff point to distinguish between older adults who have a minimal important change in COPM performance and COPM satisfaction and those who have not. PMID:27621647

Modeling the role of information and limited optimal treatment on disease prevalence.

PubMed

Kumar, Anuj; Srivastava, Prashant K; Takeuchi, Yasuhiro

2017-02-07

Disease outbreaks induce behavioural changes in healthy individuals to avoid contracting infection. We first propose a compartmental model which accounts for the effect of individual's behavioural response due to information of the disease prevalence. It is assumed that the information is growing as a function of infective population density that saturates at higher density of infective population and depends on active educational and social programmes. Model analysis has been performed and the global stability of equilibrium points is established. Further, choosing the treatment (a pharmaceutical intervention) and the effect of information (a non-pharmaceutical intervention) as controls, an optimal control problem is formulated to minimize the cost and disease fatality. In the cost functional, the nonlinear effect of controls is accounted. Analytical characterization of optimal control paths is done with the help of Pontryagin's Maximum Principle. Numerical findings suggest that if only control via information is used, it is effective and economical for early phase of disease spread whereas treatment works well for long term control except for initial phase. Furthermore, we observe that the effect of information induced behavioural response plays a crucial role in the absence of pharmaceutical control. Moreover, comprehensive use of both the control interventions is more effective than any single applied control policy and it reduces the number of infective individuals and minimizes the economic cost generated from disease burden and applied controls. Thus, the combined effect of both the control policies is found more economical during the entire epidemic period whereas the implementation of a single policy is not found economically viable. Copyright © 2016 Elsevier Ltd. All rights reserved.

Measurement properties of gait-related outcomes in youth with neuromuscular diagnoses: a systematic review.

PubMed

Ammann-Reiffer, Corinne; Bastiaenen, Caroline H G; de Bie, Rob A; van Hedel, Hubertus J A

2014-08-01

Sound measurement properties of outcome tools are essential when evaluating outcomes of an intervention, in clinical practice and in research. The purpose of this study was to review the evidence on reliability, measurement error, and responsiveness of measures of gait function in children with neuromuscular diagnoses. The MEDLINE, CINAHL, EMBASE, and PsycINFO databases were searched up to June 15, 2012. Studies evaluating reliability, measurement error, or responsiveness of measures of gait function in 1- to 18-year-old children and youth with neuromuscular diagnoses were included. Quality of the studies was independently rated by 2 raters using a modified COnsensus-based Standards for the selection of health status Measurement INstruments (COSMIN) checklist. Studies with a fair quality rating or better were considered for best evidence synthesis. Regarding the methodological quality, 32 out of 35 reliability studies, all of the 13 measurement error studies, and 5 out of 10 responsiveness studies were of fair or good quality. Best evidence synthesis revealed moderate to strong evidence for reliability for several measures in children and youth with cerebral palsy (CP) but was limited or unknown in other diagnoses. The Functional Mobility Scale (FMS) and the Gross Motor Function Measure (GMFM) dimension E showed limited positive evidence for responsiveness in children with CP, but it was unknown or controversial in other diagnoses. No information was reported on the minimal important change; thus, evidence on measurement error remained undetermined. As studies on validity were not included in the review, a comprehensive appraisal of the best available gait-related outcome measure per diagnosis is not possible. There is moderate to strong evidence on reliability for several measures of gait function in children and youth with CP, whereas evidence on responsiveness exists only for the FMS and the GMFM dimension E. © 2014 American Physical Therapy Association.

Wavelet-bounded empirical mode decomposition for measured time series analysis

NASA Astrophysics Data System (ADS)

Moore, Keegan J.; Kurt, Mehmet; Eriten, Melih; McFarland, D. Michael; Bergman, Lawrence A.; Vakakis, Alexander F.

2018-01-01

Empirical mode decomposition (EMD) is a powerful technique for separating the transient responses of nonlinear and nonstationary systems into finite sets of nearly orthogonal components, called intrinsic mode functions (IMFs), which represent the dynamics on different characteristic time scales. However, a deficiency of EMD is the mixing of two or more components in a single IMF, which can drastically affect the physical meaning of the empirical decomposition results. In this paper, we present a new approached based on EMD, designated as wavelet-bounded empirical mode decomposition (WBEMD), which is a closed-loop, optimization-based solution to the problem of mode mixing. The optimization routine relies on maximizing the isolation of an IMF around a characteristic frequency. This isolation is measured by fitting a bounding function around the IMF in the frequency domain and computing the area under this function. It follows that a large (small) area corresponds to a poorly (well) separated IMF. An optimization routine is developed based on this result with the objective of minimizing the bounding-function area and with the masking signal parameters serving as free parameters, such that a well-separated IMF is extracted. As examples of application of WBEMD we apply the proposed method, first to a stationary, two-component signal, and then to the numerically simulated response of a cantilever beam with an essentially nonlinear end attachment. We find that WBEMD vastly improves upon EMD and that the extracted sets of IMFs provide insight into the underlying physics of the response of each system.

Relationship between Duration of Untreated Psychosis and Intrinsic Corticostriatal Connectivity in Patients with Early Phase Schizophrenia.

PubMed

Sarpal, Deepak K; Robinson, Delbert G; Fales, Christina; Lencz, Todd; Argyelan, Miklos; Karlsgodt, Katherine H; Gallego, Juan A; John, Majnu; Kane, John M; Szeszko, Philip R; Malhotra, Anil K

2017-10-01

Patients with first-episode psychosis experience psychotic symptoms for a mean of up to 2 years prior to initiation of treatment, and long duration of untreated psychosis (DUP) is associated with poor clinical outcomes. Meanwhile, evidence compiled from numerous studies suggests that longer DUP is not associated with structural brain abnormalities. To date, few studies have examined the relationship between DUP and functional neuroimaging measures. In the present study, we used seed-based resting-state functional connectivity to examine the impact of DUP on corticostriatal circuitry. We included 83 patients with early phase schizophrenia and minimal exposure to antipsychotic drugs (<2 years), who underwent resting state scanning while entering 12 weeks of prospective treatment with second-generation antipsychotic drugs. Functional connectivity maps of the striatum were generated and examined in relation to DUP as a covariate. Mediation analyses were performed on a composite measure of corticostriatal connectivity derived from the significant results of our DUP analysis. We found that longer DUP correlated with worse response to treatment as well as overall decreased functional connectivity between striatal nodes and specific regions within frontal and parietal cortices. Moreover, the relationship between DUP and treatment response was significantly mediated by corticostriatal connectivity. Our results indicate that variation in corticostriatal circuitry may play a role in the relationship between longer DUP and worsened response to treatment. Future prospective studies are necessary to further characterize potential causal links between DUP, striatal circuitry and clinical outcomes.

Sleep and Cognitive Function in Multiple Sclerosis.

PubMed

Braley, Tiffany J; Kratz, Anna L; Kaplish, Neeraj; Chervin, Ronald D

2016-08-01

To examine associations between cognitive performance and polysomnographic measures of obstructive sleep apnea in patients with multiple sclerosis (MS). Participants underwent a comprehensive MS-specific cognitive testing battery (the Minimal Assessment of Cognitive Function in MS, or MACFIMS) and in-laboratory overnight PSG. In adjusted linear regression models, the oxygen desaturation index (ODI) and minimum oxygen saturation (MinO2) were significantly associated with performance on multiple MACFIMS measures, including the Paced Auditory Serial Addition Test (PASAT; 2-sec and 3-sec versions), which assesses working memory, processing speed, and attention, and on the Brief Visuospatial Memory Test-Revised, a test of delayed visual memory. The respiratory disturbance index (RDI) was also significantly associated with PASAT-3 scores as well as the California Verbal Learning Test-II (CVLT-II) Discriminability Index, a test of verbal memory and response inhibition. Among these associations, apnea severity measures accounted for between 12% and 23% of the variance in cognitive test performance. Polysomnographic measures of sleep fragmentation (as reflected by the total arousal index) and total sleep time also showed significant associations with a component of the CVLT-II that assesses response inhibition, explaining 18% and 27% of the variance in performance. Among patients with MS, obstructive sleep apnea and sleep disturbance are significantly associated with diminished visual memory, verbal memory, executive function (as reflected by response inhibition), attention, processing speed, and working memory. If sleep disorders degrade these cognitive functions, effective treatment could offer new opportunities to improve cognitive functioning in patients with MS. A commentary on this article appears in this issue on page 1489. © 2016 Associated Professional Sleep Societies, LLC.

Influence of fatiguing noise on auditory evoked responses to stimuli of various levels in a beluga whale, Delphinapterus leucas.

PubMed

Popov, Vladimir V; Sysueva, Evgeniya V; Nechaev, Dmitry I; Rozhnov, Viatcheslav V; Supin, Alexander Ya

2017-03-15

The negative impact of man-made noise on the hearing of odontocetes has attracted considerable recent attention. In the majority of studies, permanent or temporary reductions in sensitivity, known as permanent or temporary threshold shift (PTS or TTS, respectively), have been investigated. In the present study, the effects of a fatiguing sound on the hearing of a beluga whale, Delphinapterus leucas , within a wide range of levels of test signals was investigated. The fatiguing noise was half-octave band-limited noise centered at 32 kHz. Post-exposure effects of this noise on the evoked responses to test stimuli (rhythmic pip trains with a 45-kHz center frequency) at various levels (from threshold to 60 dB above threshold) were measured. For baseline (pre-exposure) responses, the magnitude-versus-level function featured a segment of steep magnitude dependence on level (up to 30 dB above threshold) that was followed by a plateau segment that featured little dependence on level (30 to 55 dB above threshold). Post-exposure, the function shifted upward along the level scale. The shift was 23 dB at the threshold and up to 33 dB at the supra-threshold level. Owing to the plateau in the magnitude-versus-level function, post-exposure suppression of responses depended on the stimulus level such that higher levels corresponded to less suppression. The experimental data may be modeled based on the compressive non-linearity of the cochlea. According to the model, post-exposure responses of the cochlea to high-level stimuli are minimally suppressed compared with the pre-exposure responses, despite a substantially increased threshold. © 2017. Published by The Company of Biologists Ltd.

Logistical constraints lead to an intermediate optimum in outbreak response vaccination

PubMed Central

Shea, Katriona; Ferrari, Matthew

2018-01-01

Dynamic models in disease ecology have historically evaluated vaccination strategies under the assumption that they are implemented homogeneously in space and time. However, this approach fails to formally account for operational and logistical constraints inherent in the distribution of vaccination to the population at risk. Thus, feedback between the dynamic processes of vaccine distribution and transmission might be overlooked. Here, we present a spatially explicit, stochastic Susceptible-Infected-Recovered-Vaccinated model that highlights the density-dependence and spatial constraints of various diffusive strategies of vaccination during an outbreak. The model integrates an agent-based process of disease spread with a partial differential process of vaccination deployment. We characterize the vaccination response in terms of a diffusion rate that describes the distribution of vaccination to the population at risk from a central location. This generates an explicit trade-off between slow diffusion, which concentrates effort near the central location, and fast diffusion, which spreads a fixed vaccination effort thinly over a large area. We use stochastic simulation to identify the optimum vaccination diffusion rate as a function of population density, interaction scale, transmissibility, and vaccine intensity. Our results show that, conditional on a timely response, the optimal strategy for minimizing outbreak size is to distribute vaccination resource at an intermediate rate: fast enough to outpace the epidemic, but slow enough to achieve local herd immunity. If the response is delayed, however, the optimal strategy for minimizing outbreak size changes to a rapidly diffusive distribution of vaccination effort. The latter may also result in significantly larger outbreaks, thus suggesting a benefit of allocating resources to timely outbreak detection and response. PMID:29791432

Predicting the responsiveness of soil biodiversity to deforestation: a cross-biome study.

PubMed

Crowther, Thomas W; Maynard, Daniel S; Leff, Jonathan W; Oldfield, Emily E; McCulley, Rebecca L; Fierer, Noah; Bradford, Mark A

2014-09-01

The consequences of deforestation for aboveground biodiversity have been a scientific and political concern for decades. In contrast, despite being a dominant component of biodiversity that is essential to the functioning of ecosystems, the responses of belowground biodiversity to forest removal have received less attention. Single-site studies suggest that soil microbes can be highly responsive to forest removal, but responses are highly variable, with negligible effects in some regions. Using high throughput sequencing, we characterize the effects of deforestation on microbial communities across multiple biomes and explore what determines the vulnerability of microbial communities to this vegetative change. We reveal consistent directional trends in the microbial community response, yet the magnitude of this vegetation effect varied between sites, and was explained strongly by soil texture. In sandy sites, the difference in vegetation type caused shifts in a suite of edaphic characteristics, driving substantial differences in microbial community composition. In contrast, fine-textured soil buffered microbes against these effects and there were minimal differences between communities in forest and grassland soil. These microbial community changes were associated with distinct changes in the microbial catabolic profile, placing community changes in an ecosystem functioning context. The universal nature of these patterns allows us to predict where deforestation will have the strongest effects on soil biodiversity, and how these effects could be mitigated. © 2014 John Wiley & Sons Ltd.

Erythrocyte deformation in ischemic acute tubular necrosis and amelioration by splenectomy in the dog.

PubMed

Mandal, A K; Taylor, C A; Bell, R D; Hillman, N M; Jarnot, M D; Cunningham, J D; Phillips, L G

1991-11-01

Bilateral renal artery occlusion (RAO) for 120 minutes in dogs results in acute tubular necrosis (ATN) and peritubular capillary (PTC) congestion with rapidly deteriorating renal function. We have shown that prior splenectomy minimizes RAO-induced renal functional and histopathologic changes. The purpose of this study was to examine whether this renal protection is due to prevention of red blood cell echinocyte formation and resultant renal PTC congestion. Echinocytes (burr cells) are poorly deformable, impart high viscosity to the blood, and may hinder reperfusion by increasing resistance to renal capillary blood flow. Splenectomized (SPLX) or sham-SPLX dogs were treated with bilateral RAO for 120 minutes. After RAO, renal function and renal blood flow were monitored, and peripheral blood red blood cells were examined at 1 hour and at 24-hour intervals for 96 hours. Renal biopsies were taken 1 hour after RAO and the kidneys removed 96 hours after RAO. The RBCs and renal tissues were studied using scanning electron microscopy. Renal function was assessed by endogenous creatinine clearance. Sham-SPLX animals showed a marked and sustained decrease in creatinine clearance, consistently elevated serum creatinine levels and fractional excretion of sodium, and diffuse ATN and PTC congestion with echinocytes. These animals had a peak in circulating echinocytes 1 hour after RAO (p less than 0.05), which showed an excellent negative correlation with creatinine clearance (r = -0.999; p less than 0.001). On the contrary, SPLX animals had essentially no change in serum creatinine or fractional excretion of sodium, minimal tubular changes, no PTC congestion, and no rise in circulating echinocytes during the 96-hour observation. In vitro treatment of the postischemic red blood cells from sham animals with adenosine-inosine or fresh postischemic plasma from the SPLX animals showed almost complete reversal to discocytes (normal red blood cells), whereas in vitro treatment of postischemic red blood cells from the SPLX animals with fresh postischemic plasma from the sham animals resulted in a marked echinocytic response. We conclude that 1) a marked echinocyte response in the immediate postischemic period is an important mechanism in initiating ischemic ATN, 2) an echinocyte inducing factor may reside in the plasma of spleen-intact animals, and 3) mitigation of ATN and PTC congestion by splenectomy is, at least in part, consequential to attenuated echinocytic response in the immediate postischemic period.

Top-down deactivation of interference from irrelevant spatial or verbal stimulus features.

PubMed

Frings, Christian; Wühr, Peter

2014-11-01

The selective-attention model of Houghton and Tipper (1994) assumes top-down deactivation of (conflicting) distractor representations as a mechanism of visual attention. Deactivation should produce an inverted-U-shaped activation function for distractor representations. In a recent study, Frings, Wentura, and Wühr (2012) tested this prediction in a variant of the flanker task in which a cue sometimes required participants to respond to the distractors rather than to the target. When reaction times and error rates were plotted as a function of the target-cue stimulus onset asynchrony, a quadratic trend emerged, consistent with the notion of distractor deactivation. However, in the flanker task, an alternative explanation for the quadratic trend in terms of attentional zooming is possible. The present experiments tested the deactivation account against the attentional-zooming account with the Stroop and the Simon task, in which attentional zooming should have minimal effects on distractor processing, because the target and distractor are presented at the same spatial location. Both experiments replicated the quadratic trend in the performance functions for responses to incongruent distractors, and additionally showed linear trends in the performance functions for responses to congruent distractors. These results provide additional support for the notion of top-down deactivation of distractor representations as a mechanism of visual selective attention.

Induction heating apparatus and methods for selectively energizing an inductor in response to a measured electrical characteristic that is at least partially a function of a temperature of a material being heated

DOEpatents

Richardson, John G.; Morrison, John L.; Hawkes, Grant L.

2006-07-04

An induction heating apparatus includes a measurement device for indicating an electrical resistance of a material to be heated. A controller is configured for energizing an inductor in response to the indicated resistance. An inductor may be energized with an alternating current, a characteristic of which may be selected in response to an indicated electrical resistance. Alternatively, a temperature of the material may be indicated via measuring the electrical resistance thereof and a characteristic of an alternating current for energizing the inductor may be selected in response to the temperature. Energizing the inductor may minimize the difference between a desired and indicated resistance or the difference between a desired and indicated temperature. A method of determining a temperature of at least one region of at least one material to be induction heated includes correlating a measured electrical resistance thereof to an average temperature thereof.

On the Performance of the Martin Digital Filter for High- and Low-pass Applications

NASA Technical Reports Server (NTRS)

Mcclain, C. R.

1979-01-01

A nonrecursive numerical filter is described in which the weighting sequence is optimized by minimizing the excursion from the ideal rectangular filter in a least squares sense over the entire domain of normalized frequency. Additional corrections to the weights in order to reduce overshoot oscillations (Gibbs phenomenon) and to insure unity gain at zero frequency for the low pass filter are incorporated. The filter is characterized by a zero phase shift for all frequencies (due to a symmetric weighting sequence), a finite memory and stability, and it may readily be transformed to a high pass filter. Equations for the filter weights and the frequency response function are presented, and applications to high and low pass filtering are examined. A discussion of optimization of high pass filter parameters for a rather stringent response requirement is given in an application to the removal of aircraft low frequency oscillations superimposed on remotely sensed ocean surface profiles. Several frequency response functions are displayed, both in normalized frequency space and in period space. A comparison of the performance of the Martin filter with some other commonly used low pass digital filters is provided in an application to oceanographic data.

Chemical Computer Man: Chemical Agent Response Simulation (CARS). Technical report, January 1983-September 1985

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

Davis, E.G.; Mioduszewski, R.J.

The Chemical Computer Man: Chemical Agent Response Simulation (CARS) is a computer model and simulation program for estimating the dynamic changes in human physiological dysfunction resulting from exposures to chemical-threat nerve agents. The newly developed CARS methodology simulates agent exposure effects on the following five indices of human physiological function: mental, vision, cardio-respiratory, visceral, and limbs. Mathematical models and the application of basic pharmacokinetic principles were incorporated into the simulation so that for each chemical exposure, the relationship between exposure dosage, absorbed dosage (agent blood plasma concentration), and level of physiological response are computed as a function of time. CARS,more » as a simulation tool, is designed for the users with little or no computer-related experience. The model combines maximum flexibility with a comprehensive user-friendly interactive menu-driven system. Users define an exposure problem and obtain immediate results displayed in tabular, graphical, and image formats. CARS has broad scientific and engineering applications, not only in technology for the soldier in the area of Chemical Defense, but also in minimizing animal testing in biomedical and toxicological research and the development of a modeling system for human exposure to hazardous-waste chemicals.« less

Iterative Potts and Blake–Zisserman minimization for the recovery of functions with discontinuities from indirect measurements

PubMed Central

Weinmann, Andreas; Storath, Martin

2015-01-01

Signals with discontinuities appear in many problems in the applied sciences ranging from mechanics, electrical engineering to biology and medicine. The concrete data acquired are typically discrete, indirect and noisy measurements of some quantities describing the signal under consideration. The task is to restore the signal and, in particular, the discontinuities. In this respect, classical methods perform rather poor, whereas non-convex non-smooth variational methods seem to be the correct choice. Examples are methods based on Mumford–Shah and piecewise constant Mumford–Shah functionals and discretized versions which are known as Blake–Zisserman and Potts functionals. Owing to their non-convexity, minimization of such functionals is challenging. In this paper, we propose a new iterative minimization strategy for Blake–Zisserman as well as Potts functionals and a related jump-sparsity problem dealing with indirect, noisy measurements. We provide a convergence analysis and underpin our findings with numerical experiments. PMID:27547074

Mitigation of epidemics in contact networks through optimal contact adaptation *

PubMed Central

Youssef, Mina; Scoglio, Caterina

2013-01-01

This paper presents an optimal control problem formulation to minimize the total number of infection cases during the spread of susceptible-infected-recovered SIR epidemics in contact networks. In the new approach, contact weighted are reduced among nodes and a global minimum contact level is preserved in the network. In addition, the infection cost and the cost associated with the contact reduction are linearly combined in a single objective function. Hence, the optimal control formulation addresses the tradeoff between minimization of total infection cases and minimization of contact weights reduction. Using Pontryagin theorem, the obtained solution is a unique candidate representing the dynamical weighted contact network. To find the near-optimal solution in a decentralized way, we propose two heuristics based on Bang-Bang control function and on a piecewise nonlinear control function, respectively. We perform extensive simulations to evaluate the two heuristics on different networks. Our results show that the piecewise nonlinear control function outperforms the well-known Bang-Bang control function in minimizing both the total number of infection cases and the reduction of contact weights. Finally, our results show awareness of the infection level at which the mitigation strategies are effectively applied to the contact weights. PMID:23906209

Mitigation of epidemics in contact networks through optimal contact adaptation.

PubMed

Youssef, Mina; Scoglio, Caterina

2013-08-01

This paper presents an optimal control problem formulation to minimize the total number of infection cases during the spread of susceptible-infected-recovered SIR epidemics in contact networks. In the new approach, contact weighted are reduced among nodes and a global minimum contact level is preserved in the network. In addition, the infection cost and the cost associated with the contact reduction are linearly combined in a single objective function. Hence, the optimal control formulation addresses the tradeoff between minimization of total infection cases and minimization of contact weights reduction. Using Pontryagin theorem, the obtained solution is a unique candidate representing the dynamical weighted contact network. To find the near-optimal solution in a decentralized way, we propose two heuristics based on Bang-Bang control function and on a piecewise nonlinear control function, respectively. We perform extensive simulations to evaluate the two heuristics on different networks. Our results show that the piecewise nonlinear control function outperforms the well-known Bang-Bang control function in minimizing both the total number of infection cases and the reduction of contact weights. Finally, our results show awareness of the infection level at which the mitigation strategies are effectively applied to the contact weights.

Optimization of response surface and neural network models in conjugation with desirability function for estimation of nutritional needs of methionine, lysine, and threonine in broiler chickens.

PubMed

Mehri, Mehran

2014-07-01

The optimization algorithm of a model may have significant effects on the final optimal values of nutrient requirements in poultry enterprises. In poultry nutrition, the optimal values of dietary essential nutrients are very important for feed formulation to optimize profit through minimizing feed cost and maximizing bird performance. This study was conducted to introduce a novel multi-objective algorithm, desirability function, for optimization the bird response models based on response surface methodology (RSM) and artificial neural network (ANN). The growth databases on the central composite design (CCD) were used to construct the RSM and ANN models and optimal values for 3 essential amino acids including lysine, methionine, and threonine in broiler chicks have been reevaluated using the desirable function in both analytical approaches from 3 to 16 d of age. Multi-objective optimization results showed that the most desirable function was obtained for ANN-based model (D = 0.99) where the optimal levels of digestible lysine (dLys), digestible methionine (dMet), and digestible threonine (dThr) for maximum desirability were 13.2, 5.0, and 8.3 g/kg of diet, respectively. However, the optimal levels of dLys, dMet, and dThr in the RSM-based model were estimated at 11.2, 5.4, and 7.6 g/kg of diet, respectively. This research documented that the application of ANN in the broiler chicken model along with a multi-objective optimization algorithm such as desirability function could be a useful tool for optimization of dietary amino acids in fractional factorial experiments, in which the use of the global desirability function may be able to overcome the underestimations of dietary amino acids resulting from the RSM model. © 2014 Poultry Science Association Inc.

Functional Attachment of Soft Tissues to Bone: Development, Healing, and Tissue Engineering

PubMed Central

Lu, Helen H.; Thomopoulos, Stavros

2014-01-01

Connective tissues such as tendons or ligaments attach to bone across a multitissue interface with spatial gradients in composition, structure, and mechanical properties. These gradients minimize stress concentrations and mediate load transfer between the soft and hard tissues. Given the high incidence of tendon and ligament injuries and the lack of integrative solutions for their repair, interface regeneration remains a significant clinical challenge. This review begins with a description of the developmental processes and the resultant structure-function relationships that translate into the functional grading necessary for stress transfer between soft tissue and bone. It then discusses the interface healing response, with a focus on the influence of mechanical loading and the role of cell-cell interactions. The review continues with a description of current efforts in interface tissue engineering, highlighting key strategies for the regeneration of the soft tissue–to-bone interface, and concludes with a summary of challenges and future directions. PMID:23642244

The transfer function method for gear system dynamics applied to conventional and minimum excitation gearing designs

NASA Technical Reports Server (NTRS)

Mark, W. D.

1982-01-01

A transfer function method for predicting the dynamic responses of gear systems with more than one gear mesh is developed and applied to the NASA Lewis four-square gear fatigue test apparatus. Methods for computing bearing-support force spectra and temporal histories of the total force transmitted by a gear mesh, the force transmitted by a single pair of teeth, and the maximum root stress in a single tooth are developed. Dynamic effects arising from other gear meshes in the system are included. A profile modification design method to minimize the vibration excitation arising from a pair of meshing gears is reviewed and extended. Families of tooth loading functions required for such designs are developed and examined for potential excitation of individual tooth vibrations. The profile modification design method is applied to a pair of test gears.

Dielectric function for doped graphene layer with barium titanate

NASA Astrophysics Data System (ADS)

Martinez Ramos, Manuel; Garces Garcia, Eric; Magana, Fernado; Vazquez Fonseca, Gerardo Jorge

2015-03-01

The aim of our study is to calculate the dielectric function for a system formed with a graphene layer doped with barium titanate. Density functional theory, within the local density approximation, plane-waves and pseudopotentials scheme as implemented in Quantum Espresso suite of programs was used. We considered 128 carbon atoms with a barium titanate cluster of 11 molecules as unit cell with periodic conditions. The geometry optimization is achieved. Optimization of structural configuration is performed by relaxation of all atomic positions to minimize their total energies. Band structure, density of states and linear optical response (the imaginary part of dielectric tensor) were calculated. We thank Dirección General de Asuntos del Personal Académico de la Universidad Nacional Autónoma de México, partial financial support by Grant IN-106514 and we also thank Miztli Super-Computing center the technical assistance.

Cognitive capacity limitations and Need for Cognition differentially predict reward-induced cognitive effort expenditure.

PubMed

Sandra, Dasha A; Otto, A Ross

2018-03-01

While psychological, economic, and neuroscientific accounts of behavior broadly maintain that people minimize expenditure of cognitive effort, empirical work reveals how reward incentives can mobilize increased cognitive effort expenditure. Recent theories posit that the decision to expend effort is governed, in part, by a cost-benefit tradeoff whereby the potential benefits of mental effort can offset the perceived costs of effort exertion. Taking an individual differences approach, the present study examined whether one's executive function capacity, as measured by Stroop interference, predicts the extent to which reward incentives reduce switch costs in a task-switching paradigm, which indexes additional expenditure of cognitive effort. In accordance with the predictions of a cost-benefit account of effort, we found that a low executive function capacity-and, relatedly, a low intrinsic motivation to expend effort (measured by Need for Cognition)-predicted larger increase in cognitive effort expenditure in response to monetary reward incentives, while individuals with greater executive function capacity-and greater intrinsic motivation to expend effort-were less responsive to reward incentives. These findings suggest that an individual's cost-benefit tradeoff is constrained by the perceived costs of exerting cognitive effort. Copyright © 2017 Elsevier B.V. All rights reserved.

On the Complexity of Item Response Theory Models.

PubMed

Bonifay, Wes; Cai, Li

2017-01-01

Complexity in item response theory (IRT) has traditionally been quantified by simply counting the number of freely estimated parameters in the model. However, complexity is also contingent upon the functional form of the model. We examined four popular IRT models-exploratory factor analytic, bifactor, DINA, and DINO-with different functional forms but the same number of free parameters. In comparison, a simpler (unidimensional 3PL) model was specified such that it had 1 more parameter than the previous models. All models were then evaluated according to the minimum description length principle. Specifically, each model was fit to 1,000 data sets that were randomly and uniformly sampled from the complete data space and then assessed using global and item-level fit and diagnostic measures. The findings revealed that the factor analytic and bifactor models possess a strong tendency to fit any possible data. The unidimensional 3PL model displayed minimal fitting propensity, despite the fact that it included an additional free parameter. The DINA and DINO models did not demonstrate a proclivity to fit any possible data, but they did fit well to distinct data patterns. Applied researchers and psychometricians should therefore consider functional form-and not goodness-of-fit alone-when selecting an IRT model.

Lifelong Impacts of Moderate Prenatal Alcohol Exposure on Neuroimmune Function

PubMed Central

Noor, Shahani; Milligan, Erin D.

2018-01-01

In utero alcohol exposure is emerging as a major risk factor for lifelong aberrant neuroimmune function. Fetal alcohol spectrum disorder encompasses a range of behavioral and physiological sequelae that may occur throughout life and includes cognitive developmental disabilities as well as disease susceptibility related to aberrant immune and neuroimmune actions. Emerging data from clinical studies and findings from animal models support that very low to moderate levels of fetal alcohol exposure may reprogram the developing central nervous system leading to altered neuroimmune and neuroglial signaling during adulthood. In this review, we will focus on the consequences of low to moderate prenatal alcohol exposure (PAE) on neuroimmune interactions during early life and at different stages of adulthood. Data discussed here will include recent studies suggesting that while abnormal immune function is generally minimal under basal conditions, following pathogenic stimuli or trauma, significant alterations in the neuroimmune axis occur. Evidence from published reports will be discussed with a focus on observations that PAE may bias later-life peripheral immune responses toward a proinflammatory phenotype. The propensity for proinflammatory responses to challenges in adulthood may ultimately shape neuron–glial-immune processes suspected to underlie various neuropathological outcomes including chronic pain and cognitive impairment.

Evidence for the functional significance of diazotroph community structure in soil.

PubMed

Hsu, Shi-Fang; Buckley, Daniel H

2009-01-01

Microbial ecologists continue to seek a greater understanding of the factors that govern the ecological significance of microbial community structure. Changes in community structure have been shown to have functional significance for processes that are mediated by a narrow spectrum of organisms, such as nitrification and denitrification, but in some cases, functional redundancy in the community seems to buffer microbial ecosystem processes. The functional significance of microbial community structure is frequently obscured by environmental variation and is hard to detect in short-term experiments. We examine the functional significance of free-living diazotrophs in a replicated long-term tillage experiment in which extraneous variation is minimized and N-fixation rates can be related to soil characteristics and diazotroph community structure. Soil characteristics were found to be primarily impacted by tillage management, whereas N-fixation rates and diazotroph community structure were impacted by both biomass management practices and interactions between tillage and biomass management. The data suggest that the variation in diazotroph community structure has a greater impact on N-fixation rates than do soil characteristics at the site. N-fixation rates displayed a saturating response to increases in diazotroph community diversity. These results show that the changes in the community structure of free-living diazotrophs in soils can have ecological significance and suggest that this response is related to a change in community diversity.

Dirac δ -function potential in quasiposition representation of a minimal-length scenario

NASA Astrophysics Data System (ADS)

Gusson, M. F.; Gonçalves, A. Oakes O.; Francisco, R. O.; Furtado, R. G.; Fabris, J. C.; Nogueira, J. A.

2018-03-01

A minimal-length scenario can be considered as an effective description of quantum gravity effects. In quantum mechanics the introduction of a minimal length can be accomplished through a generalization of Heisenberg's uncertainty principle. In this scenario, state eigenvectors of the position operator are no longer physical states and the representation in momentum space or a representation in a quasiposition space must be used. In this work, we solve the Schroedinger equation with a Dirac δ -function potential in quasiposition space. We calculate the bound state energy and the coefficients of reflection and transmission for the scattering states. We show that leading corrections are of order of the minimal length ({ O}(√{β })) and the coefficients of reflection and transmission are no longer the same for the Dirac delta well and barrier as in ordinary quantum mechanics. Furthermore, assuming that the equivalence of the 1s state energy of the hydrogen atom and the bound state energy of the Dirac {{δ }}-function potential in the one-dimensional case is kept in a minimal-length scenario, we also find that the leading correction term for the ground state energy of the hydrogen atom is of the order of the minimal length and Δx_{\\min } ≤ 10^{-25} m.

Plant Trait Variation along an Altitudinal Gradient in Mediterranean High Mountain Grasslands: Controlling the Species Turnover Effect

PubMed Central

Pescador, David S.; de Bello, Francesco; Valladares, Fernando; Escudero, Adrián

2015-01-01

Assessing changes in plant functional traits along gradients is useful for understanding the assembly of communities and their response to global and local environmental drivers. However, these changes may reflect the effects of species composition (i.e. composition turnover), species abundance (i.e. species interaction), and intra-specific trait variability (i.e. species plasticity). In order to determine the relevance of the latter, trait variation can be assessed under minimal effects of composition turnover. Nine sampling sites were established along an altitudinal gradient in a Mediterranean high mountain grassland community with low composition turnover (Madrid, Spain; 1940 m–2419 m). Nine functional traits were also measured for ten individuals of around ten plant species at each site, for a total of eleven species across all sites. The relative importance of different sources of variability (within/between site and intra-/inter-specific functional diversity) and trait variation at species and community level along the considered gradients were explored. We found a weak individual species response to altitude and other environmental variables although in some cases, individuals were smaller and leaves were thicker at higher elevations. This lack of species response was most likely due to greater within- than between-site species variation. At the community level, inter-specific functional diversity was generally greater than the intra-specific component except for traits linked to leaf element content (leaf carbon content, leaf nitrogen content, δ13C and δ15N). Inter-specific functional diversity decreased with lower altitude for four leaf traits (specific leaf area, leaf dry matter content, δ13C and δ15N), suggesting trait convergence between species at lower elevations, where water shortage may have a stronger environmental filtering effect than colder temperatures at higher altitudes. Our results suggest that, within a vegetation type encompassing various environmental gradients, both, changes in species abundance and intra-specific trait variability adjust for the community functional response to environmental changes. PMID:25774532

Plant trait variation along an altitudinal gradient in mediterranean high mountain grasslands: controlling the species turnover effect.

PubMed

Pescador, David S; de Bello, Francesco; Valladares, Fernando; Escudero, Adrián

2015-01-01

Assessing changes in plant functional traits along gradients is useful for understanding the assembly of communities and their response to global and local environmental drivers. However, these changes may reflect the effects of species composition (i.e. composition turnover), species abundance (i.e. species interaction), and intra-specific trait variability (i.e. species plasticity). In order to determine the relevance of the latter, trait variation can be assessed under minimal effects of composition turnover. Nine sampling sites were established along an altitudinal gradient in a Mediterranean high mountain grassland community with low composition turnover (Madrid, Spain; 1940 m-2419 m). Nine functional traits were also measured for ten individuals of around ten plant species at each site, for a total of eleven species across all sites. The relative importance of different sources of variability (within/between site and intra-/inter-specific functional diversity) and trait variation at species and community level along the considered gradients were explored. We found a weak individual species response to altitude and other environmental variables although in some cases, individuals were smaller and leaves were thicker at higher elevations. This lack of species response was most likely due to greater within- than between-site species variation. At the community level, inter-specific functional diversity was generally greater than the intra-specific component except for traits linked to leaf element content (leaf carbon content, leaf nitrogen content, δ13C and δ15N). Inter-specific functional diversity decreased with lower altitude for four leaf traits (specific leaf area, leaf dry matter content, δ13C and δ15N), suggesting trait convergence between species at lower elevations, where water shortage may have a stronger environmental filtering effect than colder temperatures at higher altitudes. Our results suggest that, within a vegetation type encompassing various environmental gradients, both, changes in species abundance and intra-specific trait variability adjust for the community functional response to environmental changes.

Higher Integrability for Minimizers of the Mumford-Shah Functional

NASA Astrophysics Data System (ADS)

De Philippis, Guido; Figalli, Alessio

2014-08-01

We prove higher integrability for the gradient of local minimizers of the Mumford-Shah energy functional, providing a positive answer to a conjecture of De Giorgi (Free discontinuity problems in calculus of variations. Frontiers in pure and applied mathematics, North-Holland, Amsterdam, pp 55-62, 1991).

Consequences of inhibiting amyloid precursor protein processing enzymes on synaptic function and plasticity.

PubMed

Wang, Hui; Megill, Andrea; He, Kaiwen; Kirkwood, Alfredo; Lee, Hey-Kyoung

2012-01-01

Alzheimer's disease (AD) is a neurodegenerative disease, one of whose major pathological hallmarks is the accumulation of amyloid plaques comprised of aggregated β-amyloid (Aβ) peptides. It is now recognized that soluble Aβ oligomers may lead to synaptic dysfunctions early in AD pathology preceding plaque deposition. Aβ is produced by a sequential cleavage of amyloid precursor protein (APP) by the activity of β- and γ-secretases, which have been identified as major candidate therapeutic targets of AD. This paper focuses on how Aβ alters synaptic function and the functional consequences of inhibiting the activity of the two secretases responsible for Aβ generation. Abnormalities in synaptic function resulting from the absence or inhibition of the Aβ-producing enzymes suggest that Aβ itself may have normal physiological functions which are disrupted by abnormal accumulation of Aβ during AD pathology. This interpretation suggests that AD therapeutics targeting the β- and γ-secretases should be developed to restore normal levels of Aβ or combined with measures to circumvent the associated synaptic dysfunction(s) in order to have minimal impact on normal synaptic function.

Short communication: timeline of radiation-induced kidney function loss after stereotactic ablative body radiotherapy of renal cell carcinoma as evaluated by serial (99m)Tc-DMSA SPECT/CT.

PubMed

Jackson, Price; Foroudi, Farshad; Pham, Daniel; Hofman, Michael S; Hardcastle, Nicholas; Callahan, Jason; Kron, Tomas; Siva, Shankar

2014-11-26

Stereotactic ablative body radiotherapy (SABR) has been proposed as a definitive treatment for patients with inoperable primary renal cell carcinoma. However, there is little documentation detailing the radiobiological effects of hypofractionated radiation on healthy renal tissue. In this study we describe a methodology for assessment of regional change in renal function in response to single fraction SABR of 26 Gy. In a patient with a solitary kidney, detailed follow-up of kidney function post-treatment was determined through 3-dimensional SPECT/CT imaging and (51)Cr-EDTA measurements. Based on measurements of glomerular filtration rate, renal function declined rapidly by 34% at 3 months, plateaued at 43% loss at 12 months, with minimal further decrease to 49% of baseline by 18 months. The pattern of renal functional change in (99m)Tc-DMSA uptake on SPECT/CT imaging correlates with dose delivered. This study demonstrates a dose effect relationship of SABR with loss of kidney function.

Minimum Bayes risk image correlation

NASA Technical Reports Server (NTRS)

Minter, T. C., Jr.

1980-01-01

In this paper, the problem of designing a matched filter for image correlation will be treated as a statistical pattern recognition problem. It is shown that, by minimizing a suitable criterion, a matched filter can be estimated which approximates the optimum Bayes discriminant function in a least-squares sense. It is well known that the use of the Bayes discriminant function in target classification minimizes the Bayes risk, which in turn directly minimizes the probability of a false fix. A fast Fourier implementation of the minimum Bayes risk correlation procedure is described.

Hydrological resiliency in the Western Boreal Plains: classification of hydrological responses using wavelet analysis to assess landscape resilience

NASA Astrophysics Data System (ADS)

Probert, Samantha; Kettridge, Nicholas; Devito, Kevin; Hannah, David; Parkin, Geoff

2017-04-01

The Boreal represents a system of substantial resilience to climate change, with minimal ecological change over the past 6000 years. However, unprecedented climatic warming, coupled with catchment disturbances could exceed thresholds of hydrological function in the Western Boreal Plains. Knowledge of ecohydrological and climatic feedbacks that shape the resilience of boreal forests has advanced significantly in recent years, but this knowledge is yet to be applied and understood at landscape scales. Hydrological modelling at the landscape scale is challenging in the WBP due to diverse, non-topographically driven hydrology across the mosaic of terrestrial and aquatic ecosystems. This study functionally divides the geologic and ecological components of the landscape into Hydrologic Response Areas (HRAs) and wetland, forestland, interface and pond Hydrologic Units (HUs) to accurately characterise water storage and infer transmission at multiple spatial and temporal scales. Wavelet analysis is applied to pond and groundwater levels to describe the patterns of water storage in response to climate signals; to isolate dominant controls on hydrological responses and to assess the relative importance of physical controls between wet and dry climates. This identifies which components of the landscape exhibit greater magnitude and frequency of variability to wetting and drying trends, further to testing the hierarchical framework for hydrological storage controls of: climate, bedrock geology, surficial geology, soil, vegetation, and topography. Classifying HRA and HU hydrological function is essential to understand and predict water storage and redistribution through drought cycles and wet periods. This work recognises which landscape components are most sensitive under climate change and disturbance and also creates scope for hydrological resiliency research in Boreal systems by recognising critical landscape components and their role in landscape collapse or catastrophic shift in ecosystem function under future climatic scenarios.

Responsiveness to Change of Functional Limitation Reporting: Cross-sectional Study Using the Intermountain ROMS Scale in Outpatient Rehabilitation.

PubMed

Brennan, Gerard P; Hunter, Stephen J; Snow, Greg; Minick, Kate I

2017-12-01

The Centers for Medicare and Medicaid Services (CMS) require physical therapists document patients' functional limitations. The process is not standardized. 
A systematic approach to determine a patient's functional limitations and responsiveness to change is needed. The purpose of this study is to compare patient-reported outcomes (PROs) responsiveness to change using 7-level severity/complexity modifier scale proposed by Medicare to a derived scale implemented by Intermountain Healthcare's Rehabilitation Outcomes Management System (ROMS). This was a retrospective, observational cohort design. 165,183 PROs prior to July 1, 2013, were compared to 46,334 records from July 1, 2013, to December 31, 2015. Histograms and ribbon plots illustrate distribution and change of patients' scores. ROMS raw score ranges were calculated and compared to CMS' severity/complexity levels based on score percentage. Distribution of the population was compared based on the 2 methods. Sensitivity and specificity were compared for responsiveness to change based on minimal clinically important difference (MCID). Histograms demonstrated few patient scores placed in CMS scale levels at the extremes, whereas the majority of scores placed in 2 middle levels (CJ, CK). ROMS distributed scores more evenly across levels. Ribbon plots illustrated advantage of ROMS' using narrower score ranges. Greater chance for patients to change levels was observed with ROMS when an MCID was achieved. ROMS narrower scale levels resulted in greater sensitivity and good specificity. Geographic representation for the United States was limited. Without patients' global rating of change, a reference standard to gauge validation of improvement could not be provided. ROMS provides a standard approach to identify accurately functional limitation modifier levels and to detect improvement more accurately than a straight across transposition using the CMS scale. © 2017 American Physical Therapy Association

Optimal nonlinear codes for the perception of natural colours.

PubMed

von der Twer, T; MacLeod, D I

2001-08-01

We discuss how visual nonlinearity can be optimized for the precise representation of environmental inputs. Such optimization leads to neural signals with a compressively nonlinear input-output function the gradient of which is matched to the cube root of the probability density function (PDF) of the environmental input values (and not to the PDF directly as in histogram equalization). Comparisons between theory and psychophysical and electrophysiological data are roughly consistent with the idea that parvocellular (P) cells are optimized for precision representation of colour: their contrast-response functions span a range appropriately matched to the environmental distribution of natural colours along each dimension of colour space. Thus P cell codes for colour may have been selected to minimize error in the perceptual estimation of stimulus parameters for natural colours. But magnocellular (M) cells have a much stronger than expected saturating nonlinearity; this supports the view that the function of M cells is mainly to detect boundaries rather than to specify contrast or lightness.

Non-Invasive Assessment of Liver Function

PubMed Central

Helmke, Steve; Colmenero, Jordi; Everson, Gregory T.

2015-01-01

Purpose of review It is our opinion that there is an unmet need in Hepatology for a minimally- or noninvasive test of liver function and physiology. Quantitative liver function tests (QLFTs) define the severity and prognosis of liver disease by measuring the clearance of substrates whose uptake or metabolism is dependent upon liver perfusion or hepatocyte function. Substrates with high affinity hepatic transporters exhibit high “first-pass” hepatic extraction and their clearance measures hepatic perfusion. In contrast, substrates metabolized by the liver have low first-pass extraction and their clearance measures specific drug metabolizing pathways. Recent Findings We highlight one QLFT, the dual cholate test, and introduce the concept of a disease severity index (DSI) linked to clinical outcome that quantifies the simultaneous processes of hepatocyte uptake, clearance from the systemic circulation, clearance from the portal circulation, and portal-systemic shunting. Summary It is our opinion that dual cholate is a relevant test for defining disease severity, monitoring the natural course of disease progression, and quantifying the response to therapy. PMID:25714706

Chronic diabetes alters function and expression of ryanodine receptor calcium-release channels in rat hearts.

PubMed

Bidasee, Keshore R; Nallani, Karuna; Henry, Bruce; Dincer, U Deniz; Besch, Henry R

2003-07-01

Alteration in cardiac function is one of the hallmarks of diabetes and in late stage is manifested as a decrease in contractility. While it is established that the release of calcium ions from internal sarcoplasmic reticulum via type 2 ryanodine receptor calcium-release channels (RyR2) is vital for efficient contraction, the relationship between diabetes-induced decrease in cardiac performance and alterations in expression and/or function of RyR2 is not well delineated. The present study was designed to address this question and to determine whether changes to RyR2 induced by chronic diabetes could be minimized with insulin-treatment. When paced at 3.3 Hz (200 beats per minute), hearts from 8-week streptozotocin-induced diabetic rats showed decreased responsiveness to isoproterenol stimulation; +dT/dt and -dT/dt were 56.5 +/- 11.4% and 42.1 +/- 12.1% that of control, respectively. Hearts from 8-week diabetic rats expressed 51.2% less RyR2 than controls, In addition, RyR2 from diabetic rats also showed decreased ability to bind the specific ligand [3H]ryanodine (22.4 +/- 1.8% less [3H]ryanodine per microg of RyR2 protein), suggesting dysfunction. Two-weeks of insulin treatment, initiated after 6 weeks of untreated diabetes was able to minimize loss in function and expression of RyR2. Taken collectively, these data suggest that the decrease in cardiac contractility induced by chronic diabetes results in part from decreases in expression and alteration in function of RyR2 and these changes could be attenuated with insulin treatment.

Initial Results from Lunar Electromagnetic Sounding with ARTEMIS

NASA Astrophysics Data System (ADS)

Fuqua, H.; Fatemi, S.; Poppe, A. R.; Delory, G. T.; Grimm, R. E.; De Pater, I.

2016-12-01

Electromagnetic Sounding constrains conducting layers of the lunar interior by observing variations in the Interplanetary Magnetic Field. Here, we focus our analysis on the time domain transfer function method locating transient events observed by two magnetometers near the Moon. We analyze ARTEMIS and Apollo magnetometer data. This analysis assumes the induced field responds undisturbed in a vacuum. In actuality, the dynamic plasma environment interacts with the induced field. Our models indicate distortion but not confinement occurs in the nightside wake cavity. Moreover, within the deep wake, near-vacuum region, distortion of the induced dipole fields due to the interaction with the wake is minimal depending on the magnitude of the induced field, the geometry of the upstream fields, and the upstream plasma parameters such as particle densities, solar wind velocity, and temperatures. Our results indicate the assumption of a vacuum dipolar response is reasonable within this minimally disturbed zone. We then interpret the ATEMIS magnetic field signal through a geophysical forward model capturing the induced response based on prescribed electrical conductivity models. We demonstrate our forward model passes benchmarking analyses and solves the magnetic induction response for any input signal as well as any 2 or 3 dimensional conductivity profile. We locate data windows according to the following criteria: (1) probe locations such that the wake probe is within 500km altitude within the wake cavity and minimally disturbed zone, and the second probe is in the free streaming solar wind; (2) a transient event consisting of an abrupt change in the magnetic field occurs enabling the observation of induction; (3) cross correlation analysis reveals the magnetic field signals are well correlated between the two probes and distances observed. Here we present initial ARTEMIS results providing further insight into the lunar interior structure. This method and modeling results are applicable to any airless body with a conducting interior, interacting directly with the solar wind in the absence of a parent body magnetic field as well as any two point magnetometer constellation.

ClearTK 2.0: Design Patterns for Machine Learning in UIMA

PubMed Central

Bethard, Steven; Ogren, Philip; Becker, Lee

2014-01-01

ClearTK adds machine learning functionality to the UIMA framework, providing wrappers to popular machine learning libraries, a rich feature extraction library that works across different classifiers, and utilities for applying and evaluating machine learning models. Since its inception in 2008, ClearTK has evolved in response to feedback from developers and the community. This evolution has followed a number of important design principles including: conceptually simple annotator interfaces, readable pipeline descriptions, minimal collection readers, type system agnostic code, modules organized for ease of import, and assisting user comprehension of the complex UIMA framework. PMID:29104966

ClearTK 2.0: Design Patterns for Machine Learning in UIMA.

PubMed

Bethard, Steven; Ogren, Philip; Becker, Lee

2014-05-01

ClearTK adds machine learning functionality to the UIMA framework, providing wrappers to popular machine learning libraries, a rich feature extraction library that works across different classifiers, and utilities for applying and evaluating machine learning models. Since its inception in 2008, ClearTK has evolved in response to feedback from developers and the community. This evolution has followed a number of important design principles including: conceptually simple annotator interfaces, readable pipeline descriptions, minimal collection readers, type system agnostic code, modules organized for ease of import, and assisting user comprehension of the complex UIMA framework.

Health-hazard evaluation report HETA-83-085-1757, Everglades National Park, Everglades, Florida

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

McConnell, R.; Fidler, A.T.; Chrislip, D.

1986-12-01

Adverse health effects from exposure to N,N-diethyl-m-toluamide (DEET), and insect repellant, in employees of Everglades National Park, Florida were investigated in response to a request from the National Park Service. Neurobehavioral analysis showed significant correlations between DEET exposure and affective symptoms, insomnia, muscle cramps, and urinary hesitation. The authors conclude that skin rashes, daytime sleepiness, and impaired cognitive function are significantly associated with DEET exposure. Since a safe alternative is not available, it is recommended that exposure be minimized by using lower concentrations and making use of protective clothing.

Structural tailoring of advanced turboprops

NASA Technical Reports Server (NTRS)

Brown, K. W.; Hopkins, Dale A.

1988-01-01

The Structural Tailoring of Advanced Turboprops (STAT) computer program was developed to perform numerical optimization on highly swept propfan blades. The optimization procedure seeks to minimize an objective function defined as either: (1) direct operating cost of full scale blade or, (2) aeroelastic differences between a blade and its scaled model, by tuning internal and external geometry variables that must satisfy realistic blade design constraints. The STAT analysis system includes an aerodynamic efficiency evaluation, a finite element stress and vibration analysis, an acoustic analysis, a flutter analysis, and a once-per-revolution forced response life prediction capability. STAT includes all relevant propfan design constraints.

Super-Gaussian laser intensity output formation by means of adaptive optics

NASA Astrophysics Data System (ADS)

Cherezova, T. Y.; Chesnokov, S. S.; Kaptsov, L. N.; Kudryashov, A. V.

1998-10-01

An optical resonator using an intracavity adaptive mirror with three concentric rings of controlling electrodes, which produc low loss and large beamwidth super-Gaussian output of order 4, 6, 8, is analyzed. An inverse propagation method is used to determine the appropriate shape of the adaptive mirror. The mirror reproduces the shape with minimal RMS error by combining weights of experimentally measured response functions of the mirror sample. The voltages applied to each mirror electrode are calculated. Practical design parameters such as construction of an adaptive mirror, Fresnel numbers, and geometric factor are discussed.

Tissue engineering and regenerative medicine as applied to the gastrointestinal tract.

PubMed

Bitar, Khalil N; Zakhem, Elie

2013-10-01

The gastrointestinal (GI) tract is a complex system characterized by multiple cell types with a determined architectural arrangement. Tissue engineering of the GI tract aims to reinstate the architecture and function of all structural layers. The key point for successful tissue regeneration includes the use of cells/biomaterials that elucidate minimal immune response after implantation. Different biomaterial choices and cell sources have been proposed to engineer the GI tract. This review summarizes the recent advances in bioengineering the GI tract with emphasis on cell sources and scaffolding biomaterials. Copyright © 2013 Elsevier Ltd. All rights reserved.

The Role of Neuroimaging Techniques in Establishing Diagnosis, Prognosis and Therapy in Disorders of Consciousness

PubMed Central

Gosseries, Olivia; Pistoia, Francesca; Charland-Verville, Vanessa; Carolei, Antonio; Sacco, Simona; Laureys, Steven

2016-01-01

Non-communicative brain damaged patients raise important clinical and scientific issues. Here, we review three major pathological disorders of consciousness: coma, the unresponsive wakefulness syndrome and the minimally conscious state. A number of clinical studies highlight the difficulty in making a correct diagnosis in patients with disorders of consciousness based only on behavioral examinations. The increasing use of neuroimaging techniques allows improving clinical characterization of these patients. Recent neuroimaging studies using positron emission tomography, functional magnetic resonance imaging, electroencephalography and transcranial magnetic stimulation can help assess diagnosis, prognosis, and therapeutic treatment. These techniques, using resting state, passive and active paradigms, also highlight possible dissociations between consciousness and responsiveness, and are facilitating a more accurate understanding of brain function in this challenging population. PMID:27347265

Genetic Circuit Performance under Conditions Relevant for Industrial Bioreactors

PubMed Central

Moser, Felix; Broers, Nicolette J.; Hartmans, Sybe; Tamsir, Alvin; Kerkman, Richard; Roubos, Johannes A.; Bovenberg, Roel; Voigt, Christopher A.

2014-01-01

Synthetic genetic programs promise to enable novel applications in industrial processes. For such applications, the genetic circuits that compose programs will require fidelity in varying and complex environments. In this work, we report the performance of two synthetic circuits in Escherichia coli under industrially relevant conditions, including the selection of media, strain, and growth rate. We test and compare two transcriptional circuits: an AND and a NOR gate. In E. coli DH10B, the AND gate is inactive in minimal media; activity can be rescued by supplementing the media and transferring the gate into the industrial strain E. coli DS68637 where normal function is observed in minimal media. In contrast, the NOR gate is robust to media composition and functions similarly in both strains. The AND gate is evaluated at three stages of early scale-up: 100 ml shake-flask experiments, a 1 ml MTP microreactor, and a 10 L bioreactor. A reference plasmid that constitutively produces a GFP reporter is used to make comparisons of circuit performance across conditions. The AND gate function is quantitatively different at each scale. The output deteriorates late in fermentation after the shift from exponential to constant feed rates, which induces rapid resource depletion and changes in growth rate. In addition, one of the output states of the AND gate failed in the bioreactor, effectively making it only responsive to a single input. Finally, cells carrying the AND gate show considerably less accumulation of biomass. Overall, these results highlight challenges and suggest modified strategies for developing and characterizing genetic circuits that function reliably during fermentation. PMID:23656232

Isolated primary blast alters neuronal function with minimal cell death in organotypic hippocampal slice cultures.

PubMed

Effgen, Gwen B; Vogel, Edward W; Lynch, Kimberly A; Lobel, Ayelet; Hue, Christopher D; Meaney, David F; Bass, Cameron R Dale; Morrison, Barclay

2014-07-01

An increasing number of U.S. soldiers are diagnosed with traumatic brain injury (TBI) subsequent to exposure to blast. In the field, blast injury biomechanics are highly complex and multi-phasic. The pathobiology caused by exposure to some of these phases in isolation, such as penetrating or inertially driven injuries, has been investigated extensively. However, it is unclear whether the primary component of blast, a shock wave, is capable of causing pathology on its own. Previous in vivo studies in the rodent and pig have demonstrated that it is difficult to deliver a primary blast (i.e., shock wave only) without rapid head accelerations and potentially confounding effects of inertially driven TBI. We have previously developed a well-characterized shock tube and custom in vitro receiver for exposing organotypic hippocampal slice cultures to pure primary blast. In this study, isolated primary blast induced minimal hippocampal cell death (on average, below 14% in any region of interest), even for the most severe blasts tested (424 kPa peak pressure, 2.3 ms overpressure duration, and 248 kPa*ms impulse). In contrast, measures of neuronal function were significantly altered at much lower exposures (336 kPa, 0.84 ms, and 86.5 kPa*ms), indicating that functional changes occur at exposures below the threshold for cell death. This is the first study to investigate a tolerance for primary blast-induced brain cell death in response to a range of blast parameters and demonstrate functional deficits at subthreshold exposures for cell death.

Regression Model Optimization for the Analysis of Experimental Data

NASA Technical Reports Server (NTRS)

Ulbrich, N.

2009-01-01

A candidate math model search algorithm was developed at Ames Research Center that determines a recommended math model for the multivariate regression analysis of experimental data. The search algorithm is applicable to classical regression analysis problems as well as wind tunnel strain gage balance calibration analysis applications. The algorithm compares the predictive capability of different regression models using the standard deviation of the PRESS residuals of the responses as a search metric. This search metric is minimized during the search. Singular value decomposition is used during the search to reject math models that lead to a singular solution of the regression analysis problem. Two threshold dependent constraints are also applied. The first constraint rejects math models with insignificant terms. The second constraint rejects math models with near-linear dependencies between terms. The math term hierarchy rule may also be applied as an optional constraint during or after the candidate math model search. The final term selection of the recommended math model depends on the regressor and response values of the data set, the user s function class combination choice, the user s constraint selections, and the result of the search metric minimization. A frequently used regression analysis example from the literature is used to illustrate the application of the search algorithm to experimental data.

Optimal Design of Functionally Graded Metallic Foam Insulations

NASA Technical Reports Server (NTRS)

Haftka, Raphael T.; Sankar, Bhavani; Venkataraman, Satchi; Zhu, Huadong

2002-01-01

The focus of our work has been on developing an insight into the physics that govern the optimum design of thermal insulation for use in thermal protection systems of launch vehicle. Of particular interest was to obtain optimality criteria for designing foam insulations that have density (or porosity) distributions through the thickness for optimum thermal performance. We investigate the optimum design of functionally graded thermal insulation for steady state heat transfer through the foam. We showed that the heat transfer in the foam has competing modes, of radiation and conduction. The problem assumed a fixed inside temperature of 400 K and varied the aerodynamic surface heating on the outside surface from 0.2 to 1.0 MW/sq m. The thermal insulation develops a high temperature gradient through the thickness. Investigation of the model developed for heat conduction in foams showed that at high temperatures (as on outside wall) intracellular radiation dominates the heat transfer in the foam. Minimizing radiation requires reducing the pore size, which increases the density of the foam. At low temperatures (as on the inside wall), intracellular conduction (of the metal and air) dominates the heat transfer. Minimizing conduction requires increasing the pore size. This indicated that for every temperature there was an optimum value of density that minimized the heat transfer coefficient. Two optimization studies were performed. One was to minimize the heat transmitted though a fixed thickness insulation by varying density profiles. The second was to obtain the minimum mass insulation for specified thickness. Analytical optimality criteria were derived for the cases considered. The optimality condition for minimum heat transfer required that at each temperature we find the density that minimizes the heat transfer coefficient. Once a relationship between the optimum heat transfer coefficient and the temperature was found, the design problem reduced to the solution of a simple nonlinear differential equation. Preliminary results of this work were presented at the American Society of Composites meeting, and the final version was submitted for publication in the AIAA Journal. In addition to minimizing the transmitted heat, we investigated the optimum design for minimum weight given an acceptable level of heat transmission through the insulation. The optimality criterion developed was different from that obtained for minimizing beat transfer coefficient. For minimum mass design, we had to find for a given temperature the optimum density, which minimized the logarithmic derivative of the insulation thermal conductivity with respect to its density. The logarithmic derivative is defined as the ratio of relative change in the dependent response (thermal conductivity) to the relative change in the independent variable (density). The results have been documented as a conference paper that will be presented at the upcoming AIAA.

Assessment of reliability, validity, responsiveness and minimally important change of the German Hip dysfunction and osteoarthritis outcome score (HOOS) in patients with osteoarthritis of the hip.

PubMed

Arbab, Dariusch; van Ochten, Johannes H M; Schnurr, Christoph; Bouillon, Bertil; König, Dietmar

2017-12-01

Patient-reported outcome measures are a critical tool in evaluating the efficacy of orthopedic procedures. The intention of this study was to evaluate reliability, validity, responsiveness and minimally important change of the German version of the Hip dysfunction and osteoarthritis outcome score (HOOS). The German HOOS was investigated in 251 consecutive patients before and 6 months after total hip arthroplasty. All patients completed HOOS, Oxford-Hip Score, Short-Form (SF-36) and numeric scales for pain and disability. Test-retest reliability, internal consistency, floor and ceiling effects, construct validity and minimal important change were analyzed. The German HOOS demonstrated excellent test-retest reliability with intraclass correlation coefficient values > 0.7. Cronbach´s alpha values demonstrated strong internal consistency. As hypothesized, HOOS subscales strongly correlated with corresponding OHS and SF-36 domains. All subscales showed excellent (effect size/standardized response means > 0.8) responsiveness between preoperative assessment and postoperative follow-up. The HOOS and all subdomains showed higher changes than the minimal detectable change which indicates true changes. The German version of the HOOS demonstrated good psychometric properties. It proved to be valid, reliable and responsive to the changes instrument for use in patients with hip osteoarthritis undergoing total hip replacement.

Is there consistency and specificity of autonomic changes during emotional episodes? Guidance from the conceptual act theory and psychophysiology

PubMed Central

Quigley, Karen S.; Barrett, Lisa Feldman

2014-01-01

The consistency and specificity of autonomic nervous system (ANS) responses during emotional episodes remains a topic of debate with relevance for emotional concordance. We present a recent model of how mental states are constructed, the Conceptual Act Theory (CAT), and then review findings from existing meta-analyses and a qualitative review along with studies using pattern classification of multivariate ANS patterns to determine if there is across-study evidence for consistency and specificity of ANS responses during emotional episodes. We conclude that there is thus far minimal evidence for ANS response consistency and specificity across studies. We then review the current understanding of the functional and anatomical features of ANS including its efferent and afferent connections with the central nervous system, which suggests the need to reformulate how we conceptualize ANS response consistency and specificity. We conclude by showing how this reformulation is consistent with the CAT, and how we suggest the model to propose when we would and would not expect to see consistency and specificity in ANS responses, and concordance more generally, during emotional episodes. PMID:24388802

An approximate methods approach to probabilistic structural analysis

NASA Technical Reports Server (NTRS)

Mcclung, R. C.; Millwater, H. R.; Wu, Y.-T.; Thacker, B. H.; Burnside, O. H.

1989-01-01

A major research and technology program in Probabilistic Structural Analysis Methods (PSAM) is currently being sponsored by the NASA Lewis Research Center with Southwest Research Institute as the prime contractor. This program is motivated by the need to accurately predict structural response in an environment where the loadings, the material properties, and even the structure may be considered random. The heart of PSAM is a software package which combines advanced structural analysis codes with a fast probability integration (FPI) algorithm for the efficient calculation of stochastic structural response. The basic idea of PAAM is simple: make an approximate calculation of system response, including calculation of the associated probabilities, with minimal computation time and cost, based on a simplified representation of the geometry, loads, and material. The deterministic solution resulting should give a reasonable and realistic description of performance-limiting system responses, although some error will be inevitable. If the simple model has correctly captured the basic mechanics of the system, however, including the proper functional dependence of stress, frequency, etc. on design parameters, then the response sensitivities calculated may be of significantly higher accuracy.

Regolith thermal property inversion in the LUNAR-A heat-flow experiment

NASA Astrophysics Data System (ADS)

Hagermann, A.; Tanaka, S.; Yoshida, S.; Fujimura, A.; Mizutani, H.

2001-11-01

In 2003, two penetrators of the LUNAR--A mission of ISAS will investigate the internal structure of the Moon by conducting seismic and heat--flow experiments. Heat-flow is the product of thermal gradient tial T / tial z, and thermal conductivity λ of the lunar regolith. For measuring the thermal conductivity (or dissusivity), each penetrator will carry five thermal property sensors, consisting of small disc heaters. The thermal response Ts(t) of the heater itself to the constant known power supply of approx. 50 mW serves as the data for the subsequent data interpretation. Horai et al. (1991) found a forward analytical solution to the problem of determining the thermal inertia λ ρ c of the regolith for constant thermal properties and a simplyfied geometry. In the inversion, the problem of deriving the unknown thermal properties of a medium from known heat sources and temperatures is an Identification Heat Conduction Problem (IDHCP), an ill--posed inverse problem. Assuming that thermal conductivity λ and heat capacity ρ c are linear functions of temperature (which is reasonable in most cases), one can apply a Kirchhoff transformation to linearize the heat conduction equation, which minimizes computing time. Then the error functional, i.e. the difference between the measured temperature response of the heater and the predicted temperature response, can be minimized, thus solving for thermal dissusivity κ = λ / (ρ c), wich will complete the set of parameters needed for a detailed description of thermal properties of the lunar regolith. Results of model calculations will be presented, in which synthetic data and calibration data are used to invert the unknown thermal diffusivity of the unknown medium by means of a modified Newton Method. Due to the ill-posedness of the problem, the number of parameters to be solved for should be limited. As the model calculations reveal, a homogeneous regolith allows for a fast and accurate inversion.

Interpreting stress responses during routine toxicity studies: a review of the biology, impact, and assessment.

PubMed

Everds, Nancy E; Snyder, Paul W; Bailey, Keith L; Bolon, Brad; Creasy, Dianne M; Foley, George L; Rosol, Thomas J; Sellers, Teresa

2013-01-01

Stress often occurs during toxicity studies. The perception of sensory stimuli as stressful primarily results in catecholamine release and activation of the hypothalamic-pituitary-adrenal (HPA) axis to increase serum glucocorticoid concentrations. Downstream effects of these neuroendocrine signals may include decreased total body weights or body weight gain; food consumption and activity; altered organ weights (e.g., thymus, spleen, adrenal); lymphocyte depletion in thymus and spleen; altered circulating leukocyte counts (e.g., increased neutrophils with decreased lymphocytes and eosinophils); and altered reproductive functions. Typically, only some of these findings occur in a given study. Stress responses should be interpreted as secondary (indirect) rather than primary (direct) test article-related findings. Determining whether effects are the result of stress requires a weight-of-evidence approach. The evaluation and interpretation of routinely collected data (standard in-life, clinical pathology, and anatomic pathology endpoints) are appropriate and generally sufficient to assess whether or not changes are secondary to stress. The impact of possible stress-induced effects on data interpretation can partially be mitigated by toxicity study designs that use appropriate control groups (e.g., cohorts treated with vehicle and subjected to the same procedures as those dosed with test article), housing that minimizes isolation and offers environmental enrichment, and experimental procedures that minimize stress and sampling and analytical bias. This article is a comprehensive overview of the biological aspects of the stress response, beginning with a Summary (Section 1) and an Introduction (Section 2) that describes the historical and conventional methods used to characterize acute and chronic stress responses. These sections are followed by reviews of the primary systems and parameters that regulate and/or are influenced by stress, with an emphasis on parameters evaluated in toxicity studies: In-life Procedures (Section 3), Nervous System (Section 4), Endocrine System (Section 5), Reproductive System (Section 6), Clinical Pathology (Section 7), and Immune System (Section 8). The paper concludes (Section 9) with a brief discussion on Minimizing Stress-Related Effects (9.1.), and a final section explaining why Parameters routinely measured are appropriate for assessing the role of stress in toxicology studies (9.2.).

Electronic health record "super-users" and "under-users" in ambulatory care practices.

PubMed

Rumball-Smith, Juliet; Shekelle, Paul; Damberg, Cheryl L

2018-01-01

This study explored variation in the extent of use of electronic health record (EHR)-based health information technology (IT) functionalities across US ambulatory care practices. Use of health IT functionalities in ambulatory care is important for delivering high-quality care, including that provided in coordination with multiple practitioners. We used data from the 2014 Healthcare Information and Management Systems Society Analytics survey. The responses of 30,123 ambulatory practices with an operational EHR were analyzed to examine the extent of use of EHR-based health IT functionalities for each practice. We created a novel framework for classifying ambulatory care practices employing 7 domains of health IT functionality. Drawing from the survey responses, we created a composite "use" variable indicating the extent of health IT functionality use across these domains. "Super-user" practices were defined as having near-full employment of the 7 domains of health IT functionalities and "under-users" as those with minimal or no use of health IT functionalities. We used multivariable logistic regression to investigate how the odds of super-use and under-use varied by practice size, type, urban or rural location, and geographic region. Seventy-three percent of practices were not using EHR technologies to their full capability, and nearly 40% were classified as under-users. Under-user practices were more likely to be of smaller size, situated in the West, and located outside a metropolitan area. To achieve the broader benefits of the EHR and health IT, health systems and policy makers need to identify and address barriers to full use of health IT functionalities.

Ground-state densities from the Rayleigh-Ritz variation principle and from density-functional theory.

PubMed

Kvaal, Simen; Helgaker, Trygve

2015-11-14

The relationship between the densities of ground-state wave functions (i.e., the minimizers of the Rayleigh-Ritz variation principle) and the ground-state densities in density-functional theory (i.e., the minimizers of the Hohenberg-Kohn variation principle) is studied within the framework of convex conjugation, in a generic setting covering molecular systems, solid-state systems, and more. Having introduced admissible density functionals as functionals that produce the exact ground-state energy for a given external potential by minimizing over densities in the Hohenberg-Kohn variation principle, necessary and sufficient conditions on such functionals are established to ensure that the Rayleigh-Ritz ground-state densities and the Hohenberg-Kohn ground-state densities are identical. We apply the results to molecular systems in the Born-Oppenheimer approximation. For any given potential v ∈ L(3/2)(ℝ(3)) + L(∞)(ℝ(3)), we establish a one-to-one correspondence between the mixed ground-state densities of the Rayleigh-Ritz variation principle and the mixed ground-state densities of the Hohenberg-Kohn variation principle when the Lieb density-matrix constrained-search universal density functional is taken as the admissible functional. A similar one-to-one correspondence is established between the pure ground-state densities of the Rayleigh-Ritz variation principle and the pure ground-state densities obtained using the Hohenberg-Kohn variation principle with the Levy-Lieb pure-state constrained-search functional. In other words, all physical ground-state densities (pure or mixed) are recovered with these functionals and no false densities (i.e., minimizing densities that are not physical) exist. The importance of topology (i.e., choice of Banach space of densities and potentials) is emphasized and illustrated. The relevance of these results for current-density-functional theory is examined.

Minimization In Digital Design As A Meta-Planning Problem

NASA Astrophysics Data System (ADS)

Ho, William P. C.; Wu, Jung-Gen

1987-05-01

In our model-based expert system for automatic digital system design, we formalize the design process into three sub-processes - compiling high-level behavioral specifications into primitive behavioral operations, grouping primitive operations into behavioral functions, and grouping functions into modules. Consideration of design minimization explicitly controls decision-making in the last two subprocesses. Design minimization, a key task in the automatic design of digital systems, is complicated by the high degree of interaction among the time sequence and content of design decisions. In this paper, we present an AI approach which directly addresses these interactions and their consequences by modeling the minimization prob-lem as a planning problem, and the management of design decision-making as a meta-planning problem.

Quality of Life Questionnaire-Bronchiectasis: final psychometric analyses and determination of minimal important difference scores.

PubMed

Quittner, Alexandra L; O'Donnell, Anne E; Salathe, Matthias A; Lewis, Sandra A; Li, Xiaoming; Montgomery, A Bruce; O'Riordan, Thomas G; Barker, Alan F

2015-01-01

The Quality of Life-Bronchiectasis (QOL-B), a self-administered, patient-reported outcome measure assessing symptoms, functioning and health-related quality of life for patients with non-cystic fibrosis (CF) bronchiectasis, contains 37 items on 8 scales (Respiratory Symptoms, Physical, Role, Emotional and Social Functioning, Vitality, Health Perceptions and Treatment Burden). Psychometric analyses of QOL-B V.3.0 used data from two double-blind, multicentre, randomised, placebo-controlled, phase III trials of aztreonam for inhalation solution (AZLI) in 542 patients with non-CF bronchiectasis and Gram-negative endobronchial infection. Excellent internal consistency (Cronbach's α ≥0.70) and 2-week test-retest reliability (intraclass correlation coefficients ≥0.72) were demonstrated for each scale. Convergent validity with 6 min walk test was observed for Physical and Role Functioning scores. No floor or ceiling effects (baseline scores of 0 or 100) were found for the Respiratory Symptoms scale (primary endpoint of trials). Baseline Respiratory Symptoms scores discriminated between patients based on baseline FEV₁% predicted in only one trial. The minimal important difference score for the Respiratory Symptoms scale was 8.0 points. AZLI did not show efficacy in the two phase III trials. QOL-B responsivity to treatment was assessed by examining changes from baseline QOL-B scores at study visits at which protocol-defined pulmonary exacerbations were reported. Mean Respiratory Symptoms scores decreased 14.0 and 14.2 points from baseline for placebo-treated and AZLI-treated patients with exacerbations, indicating that worsening respiratory symptoms were reflected in clinically meaningful changes in QOL-B scores. Previously established content validity, reliability and responsivity of the QOL-B are confirmed by this final validation study. The QOL-B is available for use in clinical trials and routine clinical practice. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Intranasal Insulin for Improving Cognitive Function in Multiple Sclerosis

DTIC Science & Technology

2017-10-01

Insulin, Symbol Digit Modalities Test , Minimal Assessment of Cognitive Function in Multiple Sclerosis 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF...going to evaluate if intranasal insulin improves cognition in people with MS, as assessed by standardized cognitive assessment tests . 2. KEYWORDS...Multiple Sclerosis, Cognitive Impairment, Neurodegenerative diseases, Intranasal Insulin, Symbol Digit Modalities Test , Minimal Assessment of Cognitive

Optimizing global liver function in radiation therapy treatment planning

NASA Astrophysics Data System (ADS)

Wu, Victor W.; Epelman, Marina A.; Wang, Hesheng; Romeijn, H. Edwin; Feng, Mary; Cao, Yue; Ten Haken, Randall K.; Matuszak, Martha M.

2016-09-01

Liver stereotactic body radiation therapy (SBRT) patients differ in both pre-treatment liver function (e.g. due to degree of cirrhosis and/or prior treatment) and radiosensitivity, leading to high variability in potential liver toxicity with similar doses. This work investigates three treatment planning optimization models that minimize risk of toxicity: two consider both voxel-based pre-treatment liver function and local-function-based radiosensitivity with dose; one considers only dose. Each model optimizes different objective functions (varying in complexity of capturing the influence of dose on liver function) subject to the same dose constraints and are tested on 2D synthesized and 3D clinical cases. The normal-liver-based objective functions are the linearized equivalent uniform dose (\\ell \\text{EUD} ) (conventional ‘\\ell \\text{EUD} model’), the so-called perfusion-weighted \\ell \\text{EUD} (\\text{fEUD} ) (proposed ‘fEUD model’), and post-treatment global liver function (GLF) (proposed ‘GLF model’), predicted by a new liver-perfusion-based dose-response model. The resulting \\ell \\text{EUD} , fEUD, and GLF plans delivering the same target \\ell \\text{EUD} are compared with respect to their post-treatment function and various dose-based metrics. Voxel-based portal venous liver perfusion, used as a measure of local function, is computed using DCE-MRI. In cases used in our experiments, the GLF plan preserves up to 4.6 % ≤ft(7.5 % \\right) more liver function than the fEUD (\\ell \\text{EUD} ) plan does in 2D cases, and up to 4.5 % ≤ft(5.6 % \\right) in 3D cases. The GLF and fEUD plans worsen in \\ell \\text{EUD} of functional liver on average by 1.0 Gy and 0.5 Gy in 2D and 3D cases, respectively. Liver perfusion information can be used during treatment planning to minimize the risk of toxicity by improving expected GLF; the degree of benefit varies with perfusion pattern. Although fEUD model optimization is computationally inexpensive and often achieves better GLF than \\ell \\text{EUD} model optimization does, the GLF model directly optimizes a more clinically relevant metric and can further improve fEUD plan quality.

Sensitivity to Change and Responsiveness of Four Balance Measures for Community-Dwelling Older Adults

PubMed Central

Latham, Nancy K.; Jette, Alan M.; Wagenaar, Robert C.; Ni, Pengsheng; Slavin, Mary D.; Bean, Jonathan F.

2012-01-01

Background Impaired balance has a significant negative impact on mobility, functional independence, and fall risk in older adults. Although several, well-respected balance measures are currently in use, there is limited evidence regarding the most appropriate measure to assess change in community-dwelling older adults. Objective The aim of this study was to compare floor and ceiling effects, sensitivity to change, and responsiveness across the following balance measures in community-dwelling elderly people with functional limitations: Berg Balance Scale (BBS), Performance-Oriented Mobility Assessment total scale (POMA-T), POMA balance subscale (POMA-B), and Dynamic Gait Index (DGI). Design Retrospective data from a 16-week exercise trial were used. Secondary analyses were conducted on the total sample and by subgroups of baseline functional limitation or baseline balance scores. Methods Participants were 111 community-dwelling older adults 65 years of age or older, with functional limitations. Sensitivity to change was assessed using effect size, standardized response mean, and paired t tests. Responsiveness was assessed using minimally important difference (MID) estimates. Results No floor effects were noted. Ceiling effects were observed on all measures, including in people with moderate to severe functional limitations. The POMA-T, POMA-B, and DGI showed significantly larger ceiling effects compared with the BBS. All measures had low sensitivity to change in total sample analyses. Subgroup analyses revealed significantly better sensitivity to change in people with lower compared with higher baseline balance scores. Although both the total sample and lower baseline balance subgroups showed statistically significant improvement from baseline to 16 weeks on all measures, only the lower balance subgroup showed change scores that consistently exceeded corresponding MID estimates. Limitations This study was limited to comparing 4 measures of balance, and anchor-based methods for assessing MID could not be reported. Conclusions Important limitations, including ceiling effects and relatively low sensitivity to change and responsiveness, were noted across all balance measures, highlighting their limited utility across the full spectrum of the community-dwelling elderly population. New, more challenging measures are needed for better discrimination of balance ability in community-dwelling elderly people at higher functional levels. PMID:22114200

Development of a minimal saponin vaccine adjuvant based on QS-21

NASA Astrophysics Data System (ADS)

Fernández-Tejada, Alberto; Chea, Eric K.; George, Constantine; Pillarsetty, Nagavarakishore; Gardner, Jeffrey R.; Livingston, Philip O.; Ragupathi, Govind; Lewis, Jason S.; Tan, Derek S.; Gin, David Y.

2014-07-01

Adjuvants are materials added to vaccines to enhance the immunological response to an antigen. QS-21 is a natural product adjuvant under investigation in numerous vaccine clinical trials, but its use is constrained by scarcity, toxicity, instability and an enigmatic molecular mechanism of action. Herein we describe the development of a minimal QS-21 analogue that decouples adjuvant activity from toxicity and provides a powerful platform for mechanistic investigations. We found that the entire branched trisaccharide domain of QS-21 is dispensable for adjuvant activity and that the C4-aldehyde substituent, previously proposed to bind covalently to an unknown cellular target, is also not required. Biodistribution studies revealed that active adjuvants were retained preferentially at the injection site and the nearest draining lymph nodes compared with the attenuated variants. Overall, these studies have yielded critical insights into saponin structure-function relationships, provided practical synthetic access to non-toxic adjuvants, and established a platform for detailed mechanistic studies.

Development of a minimal saponin vaccine adjuvant based on QS-21

PubMed Central

Fernández-Tejada, Alberto; Chea, Eric K.; George, Constantine; Pillarsetty, NagaVaraKishore; Gardner, Jeffrey R.; Livingston, Philip O.; Ragupathi, Govind; Lewis, Jason S.; Tan, Derek S.; Gin, David Y.

2014-01-01

Adjuvants are materials added to vaccines to enhance the immunological response to an antigen. QS-21 is a natural product adjuvant under investigation in numerous vaccine clinical trials, but its use is constrained by scarcity, toxicity, instability, and an enigmatic molecular mechanism of action. Herein, we describe the development of a minimal QS-21 analogue that decouples adjuvant activity from toxicity and provides a powerful platform for mechanistic investigations. We found that the entire branched trisaccharide domain of QS-21 is dispensable for adjuvant activity and that the C4-aldehyde substituent, previously proposed to bind covalently to an unknown cellular target, is also not required. Biodistribution studies revealed that active adjuvants were retained at the injection site and nearest draining lymph nodes preferentially compared to attenuated variants. Overall, these studies have yielded critical insights into saponin structure–function relationships, provided practical synthetic access to non-toxic adjuvants, and established a platform for detailed mechanistic studies. PMID:24950335

Estimating effects of limiting factors with regression quantiles

USGS Publications Warehouse

Cade, B.S.; Terrell, J.W.; Schroeder, R.L.

1999-01-01

In a recent Concepts paper in Ecology, Thomson et al. emphasized that assumptions of conventional correlation and regression analyses fundamentally conflict with the ecological concept of limiting factors, and they called for new statistical procedures to address this problem. The analytical issue is that unmeasured factors may be the active limiting constraint and may induce a pattern of unequal variation in the biological response variable through an interaction with the measured factors. Consequently, changes near the maxima, rather than at the center of response distributions, are better estimates of the effects expected when the observed factor is the active limiting constraint. Regression quantiles provide estimates for linear models fit to any part of a response distribution, including near the upper bounds, and require minimal assumptions about the form of the error distribution. Regression quantiles extend the concept of one-sample quantiles to the linear model by solving an optimization problem of minimizing an asymmetric function of absolute errors. Rank-score tests for regression quantiles provide tests of hypotheses and confidence intervals for parameters in linear models with heteroscedastic errors, conditions likely to occur in models of limiting ecological relations. We used selected regression quantiles (e.g., 5th, 10th, ..., 95th) and confidence intervals to test hypotheses that parameters equal zero for estimated changes in average annual acorn biomass due to forest canopy cover of oak (Quercus spp.) and oak species diversity. Regression quantiles also were used to estimate changes in glacier lily (Erythronium grandiflorum) seedling numbers as a function of lily flower numbers, rockiness, and pocket gopher (Thomomys talpoides fossor) activity, data that motivated the query by Thomson et al. for new statistical procedures. Both example applications showed that effects of limiting factors estimated by changes in some upper regression quantile (e.g., 90-95th) were greater than if effects were estimated by changes in the means from standard linear model procedures. Estimating a range of regression quantiles (e.g., 5-95th) provides a comprehensive description of biological response patterns for exploratory and inferential analyses in observational studies of limiting factors, especially when sampling large spatial and temporal scales.

The anatomy of choice: active inference and agency

PubMed Central

Friston, Karl; Schwartenbeck, Philipp; FitzGerald, Thomas; Moutoussis, Michael; Behrens, Timothy; Dolan, Raymond J.

2013-01-01

This paper considers agency in the setting of embodied or active inference. In brief, we associate a sense of agency with prior beliefs about action and ask what sorts of beliefs underlie optimal behavior. In particular, we consider prior beliefs that action minimizes the Kullback–Leibler (KL) divergence between desired states and attainable states in the future. This allows one to formulate bounded rationality as approximate Bayesian inference that optimizes a free energy bound on model evidence. We show that constructs like expected utility, exploration bonuses, softmax choice rules and optimism bias emerge as natural consequences of this formulation. Previous accounts of active inference have focused on predictive coding and Bayesian filtering schemes for minimizing free energy. Here, we consider variational Bayes as an alternative scheme that provides formal constraints on the computational anatomy of inference and action—constraints that are remarkably consistent with neuroanatomy. Furthermore, this scheme contextualizes optimal decision theory and economic (utilitarian) formulations as pure inference problems. For example, expected utility theory emerges as a special case of free energy minimization, where the sensitivity or inverse temperature (of softmax functions and quantal response equilibria) has a unique and Bayes-optimal solution—that minimizes free energy. This sensitivity corresponds to the precision of beliefs about behavior, such that attainable goals are afforded a higher precision or confidence. In turn, this means that optimal behavior entails a representation of confidence about outcomes that are under an agent's control. PMID:24093015

The segment as the minimal planning unit in speech production: evidence based on absolute response latencies.

PubMed

Kawamoto, Alan H; Liu, Qiang; Lee, Ria J; Grebe, Patricia R

2014-01-01

A minimal amount of information about a word must be phonologically and phonetically encoded before a person can begin to utter that word. Most researchers assume that the minimum is the complete word or possibly the initial syllable. However, there is some evidence that the initial segment is sufficient based on longer durations when the initial segment is primed. In two experiments in which the initial segment of a monosyllabic word is primed or not primed, we present additional evidence based on very short absolute response times determined on the basis of acoustic and articulatory onset relative to presentation of the complete target. We argue that the previous failures to find very short absolute response times when the initial segment is primed are due in part to the exclusive use of acoustic onset as a measure of response latency, the exclusion of responses with very short acoustic latencies, the manner of articulation of the initial segment (i.e., plosive vs. nonplosive), and individual differences. Theoretical implications of the segment as the minimal planning unit are considered.

Multiple point least squares equalization in a room

NASA Technical Reports Server (NTRS)

Elliott, S. J.; Nelson, P. A.

1988-01-01

Equalization filters designed to minimize the mean square error between a delayed version of the original electrical signal and the equalized response at a point in a room have previously been investigated. In general, such a strategy degrades the response at positions in a room away from the equalization point. A method is presented for designing an equalization filter by adjusting the filter coefficients to minimize the sum of the squares of the errors between the equalized responses at multiple points in the room and delayed versions of the original, electrical signal. Such an equalization filter can give a more uniform frequency response over a greater volume of the enclosure than can the single point equalizer above. Computer simulation results are presented of equalizing the frequency responses from a loudspeaker to various typical ear positions, in a room with dimensions and acoustic damping typical of a car interior, using the two approaches outlined above. Adaptive filter algorithms, which can automatically adjust the coefficients of a digital equalization filter to achieve this minimization, will also be discussed.

The Cluster Variation Method: A Primer for Neuroscientists.

PubMed

Maren, Alianna J

2016-09-30

Effective Brain-Computer Interfaces (BCIs) require that the time-varying activation patterns of 2-D neural ensembles be modelled. The cluster variation method (CVM) offers a means for the characterization of 2-D local pattern distributions. This paper provides neuroscientists and BCI researchers with a CVM tutorial that will help them to understand how the CVM statistical thermodynamics formulation can model 2-D pattern distributions expressing structural and functional dynamics in the brain. The premise is that local-in-time free energy minimization works alongside neural connectivity adaptation, supporting the development and stabilization of consistent stimulus-specific responsive activation patterns. The equilibrium distribution of local patterns, or configuration variables , is defined in terms of a single interaction enthalpy parameter ( h ) for the case of an equiprobable distribution of bistate (neural/neural ensemble) units. Thus, either one enthalpy parameter (or two, for the case of non-equiprobable distribution) yields equilibrium configuration variable values. Modeling 2-D neural activation distribution patterns with the representational layer of a computational engine, we can thus correlate variational free energy minimization with specific configuration variable distributions. The CVM triplet configuration variables also map well to the notion of a M = 3 functional motif. This paper addresses the special case of an equiprobable unit distribution, for which an analytic solution can be found.

A Two-Dimensional Variational Analysis Method for NSCAT Ambiguity Removal: Methodology, Sensitivity, and Tuning

NASA Technical Reports Server (NTRS)

Hoffman, R. N.; Leidner, S. M.; Henderson, J. M.; Atlas, R.; Ardizzone, J. V.; Bloom, S. C.; Atlas, Robert (Technical Monitor)

2001-01-01

In this study, we apply a two-dimensional variational analysis method (2d-VAR) to select a wind solution from NASA Scatterometer (NSCAT) ambiguous winds. 2d-VAR determines a "best" gridded surface wind analysis by minimizing a cost function. The cost function measures the misfit to the observations, the background, and the filtering and dynamical constraints. The ambiguity closest in direction to the minimizing analysis is selected. 2d-VAR method, sensitivity and numerical behavior are described. 2d-VAR is compared to statistical interpolation (OI) by examining the response of both systems to a single ship observation and to a swath of unique scatterometer winds. 2d-VAR is used with both NSCAT ambiguities and NSCAT backscatter values. Results are roughly comparable. When the background field is poor, 2d-VAR ambiguity removal often selects low probability ambiguities. To avoid this behavior, an initial 2d-VAR analysis, using only the two most likely ambiguities, provides the first guess for an analysis using all the ambiguities or the backscatter data. 2d-VAR and median filter selected ambiguities usually agree. Both methods require horizontal consistency, so disagreements occur in clumps, or as linear features. In these cases, 2d-VAR ambiguities are often more meteorologically reasonable and more consistent with satellite imagery.

The Cluster Variation Method: A Primer for Neuroscientists

PubMed Central

Maren, Alianna J.

2016-01-01

Effective Brain–Computer Interfaces (BCIs) require that the time-varying activation patterns of 2-D neural ensembles be modelled. The cluster variation method (CVM) offers a means for the characterization of 2-D local pattern distributions. This paper provides neuroscientists and BCI researchers with a CVM tutorial that will help them to understand how the CVM statistical thermodynamics formulation can model 2-D pattern distributions expressing structural and functional dynamics in the brain. The premise is that local-in-time free energy minimization works alongside neural connectivity adaptation, supporting the development and stabilization of consistent stimulus-specific responsive activation patterns. The equilibrium distribution of local patterns, or configuration variables, is defined in terms of a single interaction enthalpy parameter (h) for the case of an equiprobable distribution of bistate (neural/neural ensemble) units. Thus, either one enthalpy parameter (or two, for the case of non-equiprobable distribution) yields equilibrium configuration variable values. Modeling 2-D neural activation distribution patterns with the representational layer of a computational engine, we can thus correlate variational free energy minimization with specific configuration variable distributions. The CVM triplet configuration variables also map well to the notion of a M = 3 functional motif. This paper addresses the special case of an equiprobable unit distribution, for which an analytic solution can be found. PMID:27706022

Numerical Optimization Using Computer Experiments

NASA Technical Reports Server (NTRS)

Trosset, Michael W.; Torczon, Virginia

1997-01-01

Engineering design optimization often gives rise to problems in which expensive objective functions are minimized by derivative-free methods. We propose a method for solving such problems that synthesizes ideas from the numerical optimization and computer experiment literatures. Our approach relies on kriging known function values to construct a sequence of surrogate models of the objective function that are used to guide a grid search for a minimizer. Results from numerical experiments on a standard test problem are presented.

Stochastic Least-Squares Petrov--Galerkin Method for Parameterized Linear Systems

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

Lee, Kookjin; Carlberg, Kevin; Elman, Howard C.

Here, we consider the numerical solution of parameterized linear systems where the system matrix, the solution, and the right-hand side are parameterized by a set of uncertain input parameters. We explore spectral methods in which the solutions are approximated in a chosen finite-dimensional subspace. It has been shown that the stochastic Galerkin projection technique fails to minimize any measure of the solution error. As a remedy for this, we propose a novel stochatic least-squares Petrov--Galerkin (LSPG) method. The proposed method is optimal in the sense that it produces the solution that minimizes a weightedmore » $$\\ell^2$$-norm of the residual over all solutions in a given finite-dimensional subspace. Moreover, the method can be adapted to minimize the solution error in different weighted $$\\ell^2$$-norms by simply applying a weighting function within the least-squares formulation. In addition, a goal-oriented seminorm induced by an output quantity of interest can be minimized by defining a weighting function as a linear functional of the solution. We establish optimality and error bounds for the proposed method, and extensive numerical experiments show that the weighted LSPG method outperforms other spectral methods in minimizing corresponding target weighted norms.« less

Modal characterization of the ASCIE segmented optics testbed: New algorithms and experimental results

NASA Technical Reports Server (NTRS)

Carrier, Alain C.; Aubrun, Jean-Noel

1993-01-01

New frequency response measurement procedures, on-line modal tuning techniques, and off-line modal identification algorithms are developed and applied to the modal identification of the Advanced Structures/Controls Integrated Experiment (ASCIE), a generic segmented optics telescope test-bed representative of future complex space structures. The frequency response measurement procedure uses all the actuators simultaneously to excite the structure and all the sensors to measure the structural response so that all the transfer functions are measured simultaneously. Structural responses to sinusoidal excitations are measured and analyzed to calculate spectral responses. The spectral responses in turn are analyzed as the spectral data become available and, which is new, the results are used to maintain high quality measurements. Data acquisition, processing, and checking procedures are fully automated. As the acquisition of the frequency response progresses, an on-line algorithm keeps track of the actuator force distribution that maximizes the structural response to automatically tune to a structural mode when approaching a resonant frequency. This tuning is insensitive to delays, ill-conditioning, and nonproportional damping. Experimental results show that is useful for modal surveys even in high modal density regions. For thorough modeling, a constructive procedure is proposed to identify the dynamics of a complex system from its frequency response with the minimization of a least-squares cost function as a desirable objective. This procedure relies on off-line modal separation algorithms to extract modal information and on least-squares parameter subset optimization to combine the modal results and globally fit the modal parameters to the measured data. The modal separation algorithms resolved modal density of 5 modes/Hz in the ASCIE experiment. They promise to be useful in many challenging applications.

Minimally processed beetroot waste as an alternative source to obtain functional ingredients.

PubMed

Costa, Anne Porto Dalla; Hermes, Vanessa Stahl; Rios, Alessandro de Oliveira; Flôres, Simone Hickmann

2017-06-01

Large amounts of waste are generated by the minimally processed vegetables industry, such as those from beetroot processing. The aim of this study was to determine the best method to obtain flour from minimally processed beetroot waste dried at different temperatures, besides producing a colorant from such waste and assessing its stability along 45 days. Beetroot waste dried at 70 °C originates flour with significant antioxidant activity and higher betalain content than flour produced from waste dried at 60 and 80 °C, while chlorination had no impact on the process since microbiological results were consistent for its application. The colorant obtained from beetroot waste showed color stability for 20 days and potential antioxidant activity over the analysis period, thus it can be used as a functional additive to improve nutritional characteristics and appearance of food products. These results are promising since minimally processed beetroot waste can be used as an alternative source of natural and functional ingredients with high antioxidant activity and betalain content.

Minimal-Approximation-Based Distributed Consensus Tracking of a Class of Uncertain Nonlinear Multiagent Systems With Unknown Control Directions.

PubMed

Choi, Yun Ho; Yoo, Sung Jin

2017-03-28

A minimal-approximation-based distributed adaptive consensus tracking approach is presented for strict-feedback multiagent systems with unknown heterogeneous nonlinearities and control directions under a directed network. Existing approximation-based consensus results for uncertain nonlinear multiagent systems in lower-triangular form have used multiple function approximators in each local controller to approximate unmatched nonlinearities of each follower. Thus, as the follower's order increases, the number of the approximators used in its local controller increases. However, the proposed approach employs only one function approximator to construct the local controller of each follower regardless of the order of the follower. The recursive design methodology using a new error transformation is derived for the proposed minimal-approximation-based design. Furthermore, a bounding lemma on parameters of Nussbaum functions is presented to handle the unknown control direction problem in the minimal-approximation-based distributed consensus tracking framework and the stability of the overall closed-loop system is rigorously analyzed in the Lyapunov sense.

Horizontal vestibuloocular reflex evoked by high-acceleration rotations in the squirrel monkey. IV. Responses after spectacle-induced adaptation

NASA Technical Reports Server (NTRS)

Clendaniel, R. A.; Lasker, D. M.; Minor, L. B.; Shelhamer, M. J. (Principal Investigator)

2001-01-01

The horizontal angular vestibuloocular reflex (VOR) evoked by sinusoidal rotations from 0.5 to 15 Hz and acceleration steps up to 3,000 degrees /s(2) to 150 degrees /s was studied in six squirrel monkeys following adaptation with x2.2 magnifying and x0.45 minimizing spectacles. For sinusoidal rotations with peak velocities of 20 degrees /s, there were significant changes in gain at all frequencies; however, the greatest gain changes occurred at the lower frequencies. The frequency- and velocity-dependent gain enhancement seen in normal monkeys was accentuated following adaptation to magnifying spectacles and diminished with adaptation to minimizing spectacles. A differential increase in gain for the steps of acceleration was noted after adaptation to the magnifying spectacles. The gain during the acceleration portion, G(A), of a step of acceleration (3,000 degrees /s(2) to 150 degrees /s) increased from preadaptation values of 1.05 +/- 0.08 to 1.96 +/- 0.16, while the gain during the velocity plateau, G(V), only increased from 0.93 +/- 0.04 to 1.36 +/- 0.08. Polynomial fits to the trajectory of the response during the acceleration step revealed a greater increase in the cubic than the linear term following adaptation with the magnifying lenses. Following adaptation to the minimizing lenses, the value of G(A) decreased to 0.61 +/- 0.08, and the value of G(V) decreased to 0.59 +/- 0.09 for the 3,000 degrees /s(2) steps of acceleration. Polynomial fits to the trajectory of the response during the acceleration step revealed that there was a significantly greater reduction in the cubic term than in the linear term following adaptation with the minimizing lenses. These findings indicate that there is greater modification of the nonlinear as compared with the linear component of the VOR with spectacle-induced adaptation. In addition, the latency to the onset of the adapted response varied with the dynamics of the stimulus. The findings were modeled with a bilateral model of the VOR containing linear and nonlinear pathways that describe the normal behavior and adaptive processes. Adaptation for the linear pathway is described by a transfer function that shows the dependence of adaptation on the frequency of the head movement. The adaptive process for the nonlinear pathway is a gain enhancement element that provides for the accentuated gain with rising head velocity and the increased cubic component of the responses to steps of acceleration. While this model is substantially different from earlier models of VOR adaptation, it accounts for the data in the present experiments and also predicts the findings observed in the earlier studies.

Disrupted resting-state functional connectivity in minimally treated chronic schizophrenia.

PubMed

Wang, Xijin; Xia, Mingrui; Lai, Yunyao; Dai, Zhengjia; Cao, Qingjiu; Cheng, Zhang; Han, Xue; Yang, Lei; Yuan, Yanbo; Zhang, Yong; Li, Keqing; Ma, Hong; Shi, Chuan; Hong, Nan; Szeszko, Philip; Yu, Xin; He, Yong

2014-07-01

The pathophysiology of chronic schizophrenia may reflect long term brain changes related to the disorder. The effect of chronicity on intrinsic functional connectivity patterns in schizophrenia without the potentially confounding effect of antipsychotic medications, however, remains largely unknown. We collected resting-state fMRI data in 21 minimally treated chronic schizophrenia patients and 20 healthy controls. We computed regional functional connectivity strength for each voxel in the brain, and further divided regional functional connectivity strength into short-range regional functional connectivity strength and long-range regional functional connectivity strength. General linear models were used to detect between-group differences in these regional functional connectivity strength metrics and to further systematically investigate the relationship between these differences and clinical/behavioral variables in the patients. Compared to healthy controls, the minimally treated chronic schizophrenia patients showed an overall reduced regional functional connectivity strength especially in bilateral sensorimotor cortex, right lateral prefrontal cortex, left insula and right lingual gyrus, and these regional functional connectivity strength decreases mainly resulted from disruption of short-range regional functional connectivity strength. The minimally treated chronic schizophrenia patients also showed reduced long-range regional functional connectivity strength in the bilateral posterior cingulate cortex/precuneus, and increased long-range regional functional connectivity strength in the right lateral prefrontal cortex and lingual gyrus. Notably, disrupted short-range regional functional connectivity strength mainly correlated with duration of illness and negative symptoms, whereas disrupted long-range regional functional connectivity strength correlated with neurocognitive performance. All of the results were corrected using Monte-Carlo simulation. This exploratory study demonstrates a disruption of intrinsic functional connectivity without long-term exposure to antipsychotic medications in chronic schizophrenia. Furthermore, this disruption was connection-distance dependent, thus raising the possibility for differential neural pathways in neurocognitive impairment and psychiatric symptoms in schizophrenia. Copyright © 2014 Elsevier B.V. All rights reserved.

Development of a Moldable, Biodegradable Polymeric Bone Repair Material

DTIC Science & Technology

1994-03-30

minimally encapsulated by fibrous tissue. Histomorphometric analysis of day 14 specimens showed a very mild foreign body response in terms of area. This...significant visual evidence of foreign body response seen for any Atrix test article. A mass of dense fibrotic tissue was found near the defect site...article in the defect and medullary cavity. The test article was minimally encapsulated by fibrotic tissue. Histomorphometric analysis showed this

Minimalism through intraoperative functional mapping.

PubMed

Berger, M S

1996-01-01

Intraoperative stimulation mapping may be used to avoid unnecessary risk to functional regions subserving language and sensori-motor pathways. Based on the data presented here, language localization is variable in the entire population, with only certainty existing for the inferior frontal region responsible for motor speech. Anatomical landmarks such as the anterior temporal tip for temporal lobe language sites and the posterior aspect of the lateral sphenoid wing for the frontal lobe language zones are unreliable in avoiding postoperative aphasias. Thus, individual mapping to identify essential language sites has the greatest likelihood of avoiding permanent deficits in naming, reading, and motor speech. In a similar approach, motor and sensory pathways from the cortex and underlying white matter may be reliably stimulated and mapped in both awake and asleep patients. Although these techniques require an additional operative time and equipment nominally priced, the result is often gratifying, as postoperative morbidity has been greatly reduced in the process of incorporating these surgical strategies. The patients quality of life is improved in terms of seizure control, with or without antiepileptic drugs. This avoids having to perform a second costly operative procedure, which is routinely done when extraoperative stimulation and recording is done via subdural grids. In addition, an aggressive tumor resection at the initial operation lengthens the time to tumor recurrence and often obviates the need for a subsequent reoperation. Thus, intraoperative functional mapping may be best alluded to as a surgical technique that results in "minimalism in the long term".

Functional imaging of hemodynamic stimulus response in the rat retina with ultrahigh-speed spectral / Fourier domain OCT

NASA Astrophysics Data System (ADS)

Choi, WooJhon; Baumann, Bernhard; Clermont, Allen C.; Feener, Edward P.; Boas, David A.; Fujimoto, James G.

2013-03-01

Measuring retinal hemodynamics in response to flicker stimulus is important for investigating pathophysiology in small animal models of diabetic retinopathy, because a reduction in the hyperemic response is thought to be one of the earliest changes in diabetic retinopathy. In this study, we investigated functional imaging of retinal hemodynamics in response to flicker stimulus in the rat retina using an ultrahigh speed spectral / Fourier domain OCT system at 840nm with an axial scan rate of 244kHz. At 244kHz the nominal axial velocity range that could be measured without phase wrapping was +/-37.7mm/s. Pulsatile total retinal arterial blood flow as a function of time was measured using an en face Doppler approach where a 200μm × 200μm area centered at the central retinal artery was repeatedly raster scanned at a volume acquisition rate of 55Hz. Three-dimensional capillary imaging was performed using speckle decorrelation which has minimal angle dependency compared to other angiography techniques based on OCT phase information. During OCT imaging, a flicker stimulus could be applied to the retina synchronously by inserting a dichroic mirror in the imaging interface. An acute transient increase in total retinal blood flow could be detected. At the capillary level, an increase in the degree of speckle decorrelation in capillary OCT angiography images could also be observed, which indicates an increase in the velocity of blood at the capillary level. This method promises to be useful for the investigation of small animal models of ocular diseases.

Characterization and Comparison of Vibration Transfer Paths in a Helicopter Gearbox and a Fixture Mounted Gearbox

NASA Technical Reports Server (NTRS)

Islam, Akm Anwarul; Dempsey, Paula J.; Feldman, Jason; Larsen, Chris

2014-01-01

Health monitoring of rotorcraft components, currently being performed by Health and Usage Monitoring Systems through analyses of vibration signatures of dynamic mechanical components, is very important for their safe and economic operation. HUMS analyze vibration signatures associated with faults and quantify them as condition indicators to predict component behavior. Vibration transfer paths are characterized by frequency response functions derived from the input/output relationship between applied force and dynamic response through a structure as a function of frequency. With an objective to investigate the differences in transfer paths, transfer path measurements were recorded under similar conditions in the left and right nose gearboxes of an AH-64 helicopter and in an isolated left nose gearbox in a test fixture at NASA Glenn Research Center. The test fixture enabled the application of measured torques-common during an actual operation. An impact hammer as well as commercial and lab piezo shakers, were used in conjunction with two types of commercially available accelerometers to collect the vibration response under various test conditions. The frequency response functions measured under comparable conditions of both systems were found to be consistent. Measurements made on the fixture indicated certain real-world installation and maintenance issues, such as sensor alignments, accelerometer locations and installation torques, had minimal effect. However, gear vibration transfer path dynamics appeared to be somewhat dependent on the presence of oil, and the transfer path dynamics were notably different if the force input was on the internal ring gear rather than on the external gearbox case.

Assessment of human long saphenous vein function with minimally invasive harvesting with the Mayo stripper.

PubMed

O'Regan, D J; Borland, J A; Chester, A H; Pennell, D J; Yacoub, M; Pepper, J R

1997-09-01

The use of the Mayo Stripper to harvest the long saphenous vein has been shown to improve morbidity from leg wound incisions. It has not been universally accepted because of a perceived increase in injury to the venous conduit. To compare the function of undistended autologous long saphenous vein harvested by a Mayo stripper with the traditional 'open' technique in the same patient (n = 12) appearance. Vascular reactivity was assessed in isolated organ baths. Contractile function was measured in response to increasing concentrations (10(-9)-10(-5) mol) of 5-hydroxytryptamine and noradrenaline. This was calculated as a percentage of the maximum contractile response to 90 mM KCl measured in millinewtons (mN) (control 41.4 +/- 12.1, (n = 11), open technique 35.8 +/- 11.1, (n = 11), Mayo stripper 33.7 +/- 15.9, (n = 11)). The endothelial dependent and independent function was assessed with acetylcholine and sodium nitroprusside, respectively. There was no significant difference in response to both constrictors and dilators between vein taken with the Mayo stripper compared with the traditional open technique (n = 6 for each observation; P > 0.05 by ANOVA). Histological examination by light microscopy of the vessel segments removed with the Mayo stripper was unable to show any significant damage to the vessel wall. Both functional and morphological studies were conducted by 'blinded' observers. One-year follow-up with magnetic resonance angiography (MRA) and stress thallium tomography demonstrated a patency rate with lower and upper estimates of 80 and 94%. We have shown that harvesting the long saphenous vein with a Mayo stripper does not compromise vascular reactivity of the long saphenous vein or long-term patency.

Comparison between different direct search optimization algorithms in the calibration of a distributed hydrological model

NASA Astrophysics Data System (ADS)

Campo, Lorenzo; Castelli, Fabio; Caparrini, Francesca

2010-05-01

The modern distributed hydrological models allow the representation of the different surface and subsurface phenomena with great accuracy and high spatial and temporal resolution. Such complexity requires, in general, an equally accurate parametrization. A number of approaches have been followed in this respect, from simple local search method (like Nelder-Mead algorithm), that minimize a cost function representing some distance between model's output and available measures, to more complex approaches like dynamic filters (such as the Ensemble Kalman Filter) that carry on an assimilation of the observations. In this work the first approach was followed in order to compare the performances of three different direct search algorithms on the calibration of a distributed hydrological balance model. The direct search family can be defined as that category of algorithms that make no use of derivatives of the cost function (that is, in general, a black box) and comprehend a large number of possible approaches. The main benefit of this class of methods is that they don't require changes in the implementation of the numerical codes to be calibrated. The first algorithm is the classical Nelder-Mead, often used in many applications and utilized as reference. The second algorithm is a GSS (Generating Set Search) algorithm, built in order to guarantee the conditions of global convergence and suitable for a parallel and multi-start implementation, here presented. The third one is the EGO algorithm (Efficient Global Optimization), that is particularly suitable to calibrate black box cost functions that require expensive computational resource (like an hydrological simulation). EGO minimizes the number of evaluations of the cost function balancing the need to minimize a response surface that approximates the problem and the need to improve the approximation sampling where prediction error may be high. The hydrological model to be calibrated was MOBIDIC, a complete balance distributed model developed at the Department of Civil and Environmental Engineering of the University of Florence. Discussion on the comparisons between the effectiveness of the different algorithms on different cases of study on Central Italy basins is provided.

Hilbert and Blaschke phases in the temporal coherence function of stationary broadband light.

PubMed

Fernández-Pousa, Carlos R; Maestre, Haroldo; Torregrosa, Adrián J; Capmany, Juan

2008-10-27

We show that the minimal phase of the temporal coherence function gamma (tau) of stationary light having a partially-coherent symmetric spectral peak can be computed as a relative logarithmic Hilbert transform of its amplitude with respect to its asymptotic behavior. The procedure is applied to experimental data from amplified spontaneous emission broadband sources in the 1.55 microm band with subpicosecond coherence times, providing examples of degrees of coherence with both minimal and non-minimal phase. In the latter case, the Blaschke phase is retrieved and the position of the Blaschke zeros determined.

Semismooth Newton method for gradient constrained minimization problem

NASA Astrophysics Data System (ADS)

Anyyeva, Serbiniyaz; Kunisch, Karl

2012-08-01

In this paper we treat a gradient constrained minimization problem, particular case of which is the elasto-plastic torsion problem. In order to get the numerical approximation to the solution we have developed an algorithm in an infinite dimensional space framework using the concept of the generalized (Newton) differentiation. Regularization was done in order to approximate the problem with the unconstrained minimization problem and to make the pointwise maximum function Newton differentiable. Using semismooth Newton method, continuation method was developed in function space. For the numerical implementation the variational equations at Newton steps are discretized using finite elements method.

Design of Helical Capacitance Sensor for Holdup Measurement in Two-Phase Stratified Flow: A Sinusoidal Function Approach

PubMed Central

Lim, Lam Ghai; Pao, William K. S.; Hamid, Nor Hisham; Tang, Tong Boon

2016-01-01

A 360° twisted helical capacitance sensor was developed for holdup measurement in horizontal two-phase stratified flow. Instead of suppressing nonlinear response, the sensor was optimized in such a way that a ‘sine-like’ function was displayed on top of the linear function. This concept of design had been implemented and verified in both software and hardware. A good agreement was achieved between the finite element model of proposed design and the approximation model (pure sinusoidal function), with a maximum difference of ±1.2%. In addition, the design parameters of the sensor were analysed and investigated. It was found that the error in symmetry of the sinusoidal function could be minimized by adjusting the pitch of helix. The experiments of air-water and oil-water stratified flows were carried out and validated the sinusoidal relationship with a maximum difference of ±1.2% and ±1.3% for the range of water holdup from 0.15 to 0.85. The proposed design concept therefore may pose a promising alternative for the optimization of capacitance sensor design. PMID:27384567

Enhanced function of immuno-isolated islets in diabetes therapy by co-encapsulation with an anti-inflammatory drug

PubMed Central

Dang, Tram T.; Thai, Anh V.; Cohen, Joshua; Slosberg, Jeremy E.; Siniakowicz, Karolina; Doloff, Joshua C.; Ma, Minglin; Hollister-Lock, Jennifer; Tang, Katherine; Gu, Zhen; Cheng, Hao; Weir, Gordon C.; Langer, Robert; Anderson, Daniel G.

2013-01-01

Immuno-isolation of islets has the potential to enable the replacement of pancreatic function in diabetic patients. However, host response to the encapsulated islets frequently leads to fibrotic overgrowth with subsequent impairment of the transplanted grafts. Here, we identified and incorporated anti-inflammatory agents into islet-containing microcapsules to address this challenge. In vivo subcutaneous screening of 16 small molecule anti-inflammatory drugs was performed to identify promising compounds that could minimize the formation of fibrotic cell layers. Using parallel non-invasive fluorescent and bioluminescent imaging, we identified dexamethasone and curcumin as the most effective drugs in inhibiting the activities of inflammatory proteases and reactive oxygen species in the host response to subcutaneously injected biomaterials. Next, we demonstrated that co-encapsulating curcumin with pancreatic rat islets in alginate microcapsules reduced fibrotic overgrowth and improved glycemic control in a mouse model of chemically-induced type I diabetes. These results showed that localized administration of anti-inflammatory drug can improve the longevity of encapsulated islets and may facilitate the translation of this technology towards a long-term cure for type I diabetes. PMID:23660251

Enzyme responsive drug delivery system based on mesoporous silica nanoparticles for tumor therapy in vivo

NASA Astrophysics Data System (ADS)

Liu, Yun; Ding, Xingwei; Li, Jinghua; Luo, Zhong; Hu, Yan; Liu, Junjie; Dai, Liangliang; Zhou, Jun; Hou, Changjun; Cai, Kaiyong

2015-04-01

To reduce the toxic side effects of traditional chemotherapeutics in vivo, we designed and constructed a biocompatible, matrix metalloproteinases (MMPs) responsive drug delivery system based on mesoporous silica nanoparticles (MSNs). MMPs substrate peptide containing PLGLAR (sensitive to MMPs) was immobilized onto the surfaces of amino-functionalized MSNs via an amidation reaction, serving as MMPs sensitive intermediate linker. Bovine serum albumin was then covalently coupled to linker as end-cap for sealing the mesopores of MSNs. Lactobionic acid was further conjugated to the system as targeting motif. Doxorubicin hydrochloride was used as the model anticancer drug in this study. A series of characterizations revealed that the system was successfully constructed. The peptide-functionalized MSNs system demonstrated relatively high sensitivity to MMPs for triggering drug delivery, which was potentially important for tumor therapy since the tumor’s microenvironment overexpressed MMPs in nature. The in vivo experiments proved that the system could efficiently inhibit the tumor growth with minimal side effects. This study provides an approach for the development of the next generation of nanotherapeutics toward efficient cancer treatment.

Optimum design of structures subject to general periodic loads

NASA Technical Reports Server (NTRS)

Reiss, Robert; Qian, B.

1989-01-01

A simplified version of Icerman's problem regarding the design of structures subject to a single harmonic load is discussed. The nature of the restrictive conditions that must be placed on the design space in order to ensure an analytic optimum are discussed in detail. Icerman's problem is then extended to include multiple forcing functions with different driving frequencies. And the conditions that now must be placed upon the design space to ensure an analytic optimum are again discussed. An important finding is that all solutions to the optimality condition (analytic stationary design) are local optima, but the global optimum may well be non-analytic. The more general problem of distributing the fixed mass of a linear elastic structure subject to general periodic loads in order to minimize some measure of the steady state deflection is also considered. This response is explicitly expressed in terms of Green's functional and the abstract operators defining the structure. The optimality criterion is derived by differentiating the response with respect to the design parameters. The theory is applicable to finite element as well as distributed parameter models.

Rotordynamics on the PC: Further Capabilities of ARDS

NASA Technical Reports Server (NTRS)

Fleming, David P.

1997-01-01

Rotordynamics codes for personal computers are now becoming available. One of the most capable codes is Analysis of RotorDynamic Systems (ARDS) which uses the component mode synthesis method to analyze a system of up to 5 rotating shafts. ARDS was originally written for a mainframe computer but has been successfully ported to a PC; its basic capabilities for steady-state and transient analysis were reported in an earlier paper. Additional functions have now been added to the PC version of ARDS. These functions include: 1) Estimation of the peak response following blade loss without resorting to a full transient analysis; 2) Calculation of response sensitivity to input parameters; 3) Formulation of optimum rotor and damper designs to place critical speeds in desirable ranges or minimize bearing loads; 4) Production of Poincard plots so the presence of chaotic motion can be ascertained. ARDS produces printed and plotted output. The executable code uses the full array sizes of the mainframe version and fits on a high density floppy disc. Examples of all program capabilities are presented and discussed.

Regulatory T Lymphocytes in Periodontitis: A Translational View

PubMed Central

2018-01-01

Periodontitis is a chronic immuno-inflammatory disease in which the disruption of the balance between host and microbiota interactions is key to the onset and progression of the disease. The immune homeostasis associated with periodontal health requires a regulated immuno-inflammatory response, during which the presence of regulatory T cells (Tregs) is essential to ensure a controlled response that minimizes collateral tissue damage. Since Tregs modulate both innate and adaptive immunity, pathological conditions that may resolve by the acquisition of immuno-tolerance, such as periodontitis, may benefit by the use of Treg immunotherapy. In recent years, many strategies have been proposed to take advantage of the immuno-suppressive capabilities of Tregs as immunotherapy, including the ex vivo and in vivo manipulation of the Treg compartment. Ongoing research in both basic and translational studies let us gain a better understanding of the diversity of Treg subsets, their phenotypic plasticity, and suppressive functions, which can be used as a substrate for new immunotherapies. Certainly, as our knowledge of Treg biology increases, we will be capable to develop new therapies designed to enhance the stability and function of Tregs during periodontitis.

Beneficial effects of Rifaximin in post-infectious irritable bowel syndrome mouse model beyond gut microbiota.

PubMed

Jin, Yu; Ren, Xiaoyang; Li, Gangping; Li, Ying; Zhang, Lei; Wang, Huan; Qian, Wei; Hou, Xiaohua

2018-02-01

Rifaximin is a minimally absorbed antibiotic, which has shown efficacy in irritable bowel syndrome (IBS) patients. However, the mechanism on how it effects in IBS is still incompletely defined. In this study, Trichinella spiralis-infected post-infectious (PI) IBS mouse model was used, to assess the action of rifaximin on visceral hypersensitivity, barrier function, gut inflammation, and microbiota. Post-infectious IBS model was established by T. spiralis infection in mice. Rifaximin were administered to PI-IBS mice for seven consecutive days. The abdominal withdrawal reflex and threshold of colorectal distention were employed to evaluate visceral sensitivity. Smooth muscle contractile response was recorded in the organ bath. Intestinal permeability was measured by Ussing chamber. Expression of tight junction protein and cytokines were measured by Western blotting. Ilumina miseq platform was used to analyze bacterial 16S ribosomal RNA. Post-infectious IBS mice treated with rifaximin exhibited decreased abdominal withdrawal reflex score, increased threshold, reduced contractile response, and intestinal permeability. Rifaximin also suppressed the expression of interleukin-12 and interleukin-17 and promoted the expression of the major tight junction protein occludin. Furthermore, rifaximin did not change the composition and diversity, and the study reavealed that rifaximin had a tiny effect on the relative abundance of Lactobacillus and Bifidobacterium in this PI-IBS model. Rifaximin alleviated visceral hypersensitivity, recovered intestinal barrier function, and inhibited low-grade inflammation in colon and ileum of PI-IBS mouse model. Moreover, rifaximin exerts anti-inflammatory effects with only a minimal effect on the overall composition and diversity of the gut microbiota in this model. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Dissociable endogenous and exogenous attention in disorders of consciousness.

PubMed

Chennu, Srivas; Finoia, Paola; Kamau, Evelyn; Monti, Martin M; Allanson, Judith; Pickard, John D; Owen, Adrian M; Bekinschtein, Tristan A

2013-01-01

Recent research suggests that despite the seeming inability of patients in vegetative and minimally conscious states to generate consistent behaviour, some might possess covert awareness detectable with functional neuroimaging. These findings motivate further research into the cognitive mechanisms that might support the existence of consciousness in these states of profound neurological dysfunction. One of the key questions in this regard relates to the nature and capabilities of attention in patients, known to be related to but distinct from consciousness. Previous assays of the electroencephalographic P300 marker of attention have demonstrated its presence and potential clinical value. Here we analysed data from 21 patients and 8 healthy volunteers collected during an experimental task designed to engender exogenous or endogenous attention, indexed by the P3a and P3b components, respectively, in response to a pair of word stimuli presented amongst distractors. Remarkably, we found that the early, bottom-up P3a and the late, top-down P3b could in fact be dissociated in a patient who fitted the behavioural criteria for the vegetative state. In juxtaposition with healthy volunteers, the patient's responses suggested the presence of a relatively high level of attentional abilities despite the absence of any behavioural indications thereof. Furthermore, we found independent evidence of covert command following in the patient, as measured by functional neuroimaging during tennis imagery. Three other minimally conscious patients evidenced non-discriminatory bottom-up orienting, but no top-down engagement of selective attentional control. Our findings present a persuasive case for dissociable attentional processing in behaviourally unresponsive patients, adding to our understanding of the possible levels and applications of consequent conscious awareness.

A network approach to assessing cognition in disorders of consciousness(e–Pub ahead of print)(CME)

PubMed Central

Rodriguez Moreno, D.; Schiff, N.D.; Giacino, J.; Kalmar, K.; Hirsch, J.

2010-01-01

Objective: Conventional assessments of consciousness rely on motor responses to indicate awareness. However, overt behaviors may be absent or ambiguous in patients with disorders of consciousness (DOC) resulting in underrating capacity for cognition. fMRI during a silent picture-naming task was evaluated as an indicator of command following when conventional methods are not sufficient. Methods: A total of 10 patients with and without conventional evidence of awareness, who met diagnostic criteria for the minimally conscious state (MCS) (n = 5), vegetative state (VS) (n = 3), emerged from MCS (EMCS) (n = 1), and locked-in syndrome (LIS) (n = 1), participated in this observational fMRI study. Results: The LIS and EMCS patients engaged a complete network of essential language-related regions during the object-naming task. The MCS and 2 of the VS patients demonstrated both complete and partial preservation of the object-naming system. Patients who engaged a complete network scored highest on the Coma Recovery Scale-Revised. Conclusions: This study supports the view that fMRI during object naming can elicit brain activations in patients with DOC similar to those observed in healthy subjects during command following, and patients can be stratified by completeness of the engaged neural system. These results suggest that activity of the language network may serve as an indicator of high-level cognition and possibly volitional processes that cannot be discerned through conventional behavioral assessment alone. GLOSSARY BA = Brodmann area; BOLD = blood oxygenation level–dependent; CRS-R = Coma Recovery Scale-Revised; DOC = disorders of consciousness; EMCS = emerged from minimally conscious state; GFi(d) = dorsal inferior frontal gyrus; GFi(v) = ventral inferior frontal gyrus; hrf = hemodynamic response function; LIS = locked-in syndrome; MCS = minimally conscious state; preSMA = pre-supplementary motor area; STG = superior temporal gyrus; VS = vegetative state. PMID:20980667

Attitude determination using vector observations: A fast optimal matrix algorithm

NASA Technical Reports Server (NTRS)

Markley, F. Landis

1993-01-01

The attitude matrix minimizing Wahba's loss function is computed directly by a method that is competitive with the fastest known algorithm for finding this optimal estimate. The method also provides an estimate of the attitude error covariance matrix. Analysis of the special case of two vector observations identifies those cases for which the TRIAD or algebraic method minimizes Wahba's loss function.

Modeling the Proton Radiation Belt With Van Allen Probes Relativistic Electron-Proton Telescope Data

NASA Technical Reports Server (NTRS)

Kanekal, S. G.; Li, X.; Baker, D. N.; Selesnick, R. S.; Hoxie, V. C.

2018-01-01

An empirical model of the proton radiation belt is constructed from data taken during 2013-2017 by the Relativistic Electron-Proton Telescopes on the Van Allen Probes satellites. The model intensity is a function of time, kinetic energy in the range 18-600 megaelectronvolts, equatorial pitch angle, and L shell of proton guiding centers. Data are selected, on the basis of energy deposits in each of the nine silicon detectors, to reduce background caused by hard proton energy spectra at low L. Instrument response functions are computed by Monte Carlo integration, using simulated proton paths through a simplified structural model, to account for energy loss in shielding material for protons outside the nominal field of view. Overlap of energy channels, their wide angular response, and changing satellite orientation require the model dependencies on all three independent variables be determined simultaneously. This is done by least squares minimization with a customized steepest descent algorithm. Model uncertainty accounts for statistical data error and systematic error in the simulated instrument response. A proton energy spectrum is also computed from data taken during the 8 January 2014 solar event, to illustrate methods for the simpler case of an isotropic and homogeneous model distribution. Radiation belt and solar proton results are compared to intensities computed with a simplified, on-axis response that can provide a good approximation under limited circumstances.

Acoustic stimulation can induce a selective neural network response mediated by piezoelectric nanoparticles.

PubMed

Rojas, Camilo; Tedesco, Mariateresa; Massobrio, Paolo; Marino, Attilio; Ciofani, Gianni; Martinoia, Sergio; Raiteri, Roberto

2018-06-01

We aim to develop a novel non-invasive or minimally invasive method for neural stimulation to be applied in the study and treatment of brain (dys)functions and neurological disorders. We investigate the electrophysiological response of in vitro neuronal networks when subjected to low-intensity pulsed acoustic stimulation, mediated by piezoelectric nanoparticles adsorbed on the neuronal membrane. We show that the presence of piezoelectric barium titanate nanoparticles induces, in a reproducible way, an increase in network activity when excited by stationary ultrasound waves in the MHz regime. Such a response can be fully recovered when switching the ultrasound pulse off, depending on the generated pressure field amplitude, whilst it is insensitive to the duration of the ultrasound pulse in the range 0.5 s-1.5 s. We demonstrate that the presence of piezoelectric nanoparticles is necessary, and when applying the same acoustic stimulation to neuronal cultures without nanoparticles or with non-piezoelectric nanoparticles with the same size distribution, no network response is observed. We believe that our results open up an extremely interesting approach when coupled with suitable functionalization strategies of the nanoparticles in order to address specific neurons and/or brain areas and applied in vivo, thus enabling remote, non-invasive, and highly selective modulation of the activity of neuronal subpopulations of the central nervous system of mammalians.

Platelet aggregation responses in clinically healthy adult llamas.

PubMed

Gilbert, Rosanne M; Bird, Karyn E; Kutzler, Michelle A

2009-03-01

Limited information exists regarding hemostasis in camelids despite the importance of platelet function testing in the accurate identification of platelet disorders. As further importation of llamas to North America is restricted, variability in breeding stock will continue to decrease, potentially leading to an increase in heritable bleeding disorders. The objective of this study was to measure platelet aggregation responses in clinically healthy llamas and provide baseline data to which abnormal platelet function may be compared in the future. Blood samples were collected from 39 healthy adult llamas, citrated, and centrifuged to produce platelet-rich plasma (PRP). Within 4 hours of the blood draw, 20 microL of each agonist reagent were added to 180 microL of PRP. Final concentrations of agonists were 2 x 10(-5) M ADP, 0.19 mg collagen/mL PRP, 1 x 10(-4) M epinephrine, and 500 microg arachidonic acid/mL PRP. Llama platelets were most responsive to ADP and collagen, with a maximum percent aggregation (mean+/-SD) of 71.3+/-18.6% and 55.8+/-19% and aggregation rates of 9.5+/-3.9 and 6.7+/-3.7 cm/min, respectively. Llama platelet aggregation in response to epinephrine and arachidonic acid was minimal to absent. This study is the first of its kind to establish baseline values for platelet aggregation in healthy adult llamas.

Modeling the Proton Radiation Belt With Van Allen Probes Relativistic Electron-Proton Telescope Data

NASA Astrophysics Data System (ADS)

Selesnick, R. S.; Baker, D. N.; Kanekal, S. G.; Hoxie, V. C.; Li, X.

2018-01-01

An empirical model of the proton radiation belt is constructed from data taken during 2013-2017 by the Relativistic Electron-Proton Telescopes on the Van Allen Probes satellites. The model intensity is a function of time, kinetic energy in the range 18-600 MeV, equatorial pitch angle, and L shell of proton guiding centers. Data are selected, on the basis of energy deposits in each of the nine silicon detectors, to reduce background caused by hard proton energy spectra at low L. Instrument response functions are computed by Monte Carlo integration, using simulated proton paths through a simplified structural model, to account for energy loss in shielding material for protons outside the nominal field of view. Overlap of energy channels, their wide angular response, and changing satellite orientation require the model dependencies on all three independent variables be determined simultaneously. This is done by least squares minimization with a customized steepest descent algorithm. Model uncertainty accounts for statistical data error and systematic error in the simulated instrument response. A proton energy spectrum is also computed from data taken during the 8 January 2014 solar event, to illustrate methods for the simpler case of an isotropic and homogeneous model distribution. Radiation belt and solar proton results are compared to intensities computed with a simplified, on-axis response that can provide a good approximation under limited circumstances.

Acoustic stimulation can induce a selective neural network response mediated by piezoelectric nanoparticles

NASA Astrophysics Data System (ADS)

Rojas, Camilo; Tedesco, Mariateresa; Massobrio, Paolo; Marino, Attilio; Ciofani, Gianni; Martinoia, Sergio; Raiteri, Roberto

2018-06-01

Objective. We aim to develop a novel non-invasive or minimally invasive method for neural stimulation to be applied in the study and treatment of brain (dys)functions and neurological disorders. Approach. We investigate the electrophysiological response of in vitro neuronal networks when subjected to low-intensity pulsed acoustic stimulation, mediated by piezoelectric nanoparticles adsorbed on the neuronal membrane. Main results. We show that the presence of piezoelectric barium titanate nanoparticles induces, in a reproducible way, an increase in network activity when excited by stationary ultrasound waves in the MHz regime. Such a response can be fully recovered when switching the ultrasound pulse off, depending on the generated pressure field amplitude, whilst it is insensitive to the duration of the ultrasound pulse in the range 0.5 s–1.5 s. We demonstrate that the presence of piezoelectric nanoparticles is necessary, and when applying the same acoustic stimulation to neuronal cultures without nanoparticles or with non-piezoelectric nanoparticles with the same size distribution, no network response is observed. Significance. We believe that our results open up an extremely interesting approach when coupled with suitable functionalization strategies of the nanoparticles in order to address specific neurons and/or brain areas and applied in vivo, thus enabling remote, non-invasive, and highly selective modulation of the activity of neuronal subpopulations of the central nervous system of mammalians.

Arabidopsis Copper Transport Protein COPT2 Participates in the Cross Talk between Iron Deficiency Responses and Low-Phosphate Signaling1[C][W

PubMed Central

Perea-García, Ana; Garcia-Molina, Antoni; Andrés-Colás, Nuria; Vera-Sirera, Francisco; Pérez-Amador, Miguel A.; Puig, Sergi; Peñarrubia, Lola

2013-01-01

Copper and iron are essential micronutrients for most living organisms because they participate as cofactors in biological processes, including respiration, photosynthesis, and oxidative stress protection. In many eukaryotic organisms, including yeast (Saccharomyces cerevisiae) and mammals, copper and iron homeostases are highly interconnected; yet, such interdependence is not well established in higher plants. Here, we propose that COPT2, a high-affinity copper transport protein, functions under copper and iron deficiencies in Arabidopsis (Arabidopsis thaliana). COPT2 is a plasma membrane protein that functions in copper acquisition and distribution. Characterization of the COPT2 expression pattern indicates a synergic response to copper and iron limitation in roots. We characterized a knockout of COPT2, copt2-1, that leads to increased resistance to simultaneous copper and iron deficiencies, measured as reduced leaf chlorosis and improved maintenance of the photosynthetic apparatus. We propose that COPT2 could play a dual role under iron deficiency. First, COPT2 participates in the attenuation of copper deficiency responses driven by iron limitation, possibly to minimize further iron consumption. Second, global expression analyses of copt2-1 versus wild-type Arabidopsis plants indicate that low-phosphate responses increase in the mutant. These results open up new biotechnological approaches to fight iron deficiency in crops. PMID:23487432

Residues 28 to 39 of the Extracellular Loop 1 of Chicken Na+/H+ Exchanger Type I Mediate Cell Binding and Entry of Subgroup J Avian Leukosis Virus.

PubMed

Guan, Xiaolu; Zhang, Yao; Yu, Mengmeng; Ren, Chaoqi; Gao, Yanni; Yun, Bingling; Liu, Yongzhen; Wang, Yongqiang; Qi, Xiaole; Liu, Changjun; Cui, Hongyu; Zhang, Yanping; Gao, Li; Li, Kai; Pan, Qing; Zhang, Baoshan; Wang, Xiaomei; Gao, Yulong

2018-01-01

Chicken Na + /H + exchanger type I (chNHE1), a multispan transmembrane protein, is a cellular receptor of the subgroup J avian leukosis virus (ALV-J). To identify the functional determinants of chNHE1 responsible for the ALV-J receptor activity, a series of chimeric receptors was created by exchanging the extracellular loops (ECL) of human NHE1 (huNHE1) and chNHE1 and by ECL replacement with a hemagglutinin (HA) tag. These chimeric receptors then were used in binding and entry assays to map the minimal ALV-J gp85-binding domain of chNHE1. We show that ECL1 of chNHE1 (chECL1) is the critical functional ECL that interacts directly with ALV-J gp85; ECL3 is also involved in ALV-J gp85 binding. Amino acid residues 28 to 39 of the N-terminal membrane-proximal region of chECL1 constitute the minimal domain required for chNHE1 binding of ALV-J gp85. These residues are sufficient to mediate viral entry into ALV-J nonpermissive cells. Point mutation analysis revealed that A30, V33, W38, and E39 of chECL1 are the key residues mediating the binding between chNHE1 and ALV-J gp85. Further, the replacement of residues 28 to 39 of huNHE1 with the corresponding chNHE1 residues converted the nonfunctional ALV-J receptor huNHE1 to a functional one. Importantly, soluble chECL1 and huECL1 harboring chNHE1 residues 28 to 39 both could effectively block ALV-J infection. Collectively, our findings indicate that residues 28 to 39 of chNHE1 constitute a domain that is critical for receptor function and mediate ALV-J entry. IMPORTANCE chNHE1 is a cellular receptor of ALV-J, a retrovirus that causes infections in chickens and serious economic losses in the poultry industry. Until now, the domains determining the chNHE1 receptor function remained unknown. We demonstrate that chECL1 is critical for receptor function, with residues 28 to 39 constituting the minimal functional domain responsible for chNHE1 binding of ALV-J gp85 and efficiently mediating ALV-J cell entry. These residues are located in the membrane-proximal region of the N terminus of chECL1, suggesting that the binding site of ALV-J gp85 on chNHE1 is probably located on the apex of the molecule; the receptor-binding mode might be different from that of retroviruses. We also found that soluble chECL1, as well as huECL1 harboring chNHE1 residues 28 to 39, effectively blocked ALV-J infection. These findings contribute to a better understanding of the ALV-J infection mechanism and also provide new insights into the control strategies for ALV-J infection. Copyright © 2017 American Society for Microbiology.

Evaluation of Internal Construct Validity and Unidimensionality of the Brachial Assessment Tool, A Patient-Reported Outcome Measure for Brachial Plexus Injury.

PubMed

Hill, Bridget; Pallant, Julie; Williams, Gavin; Olver, John; Ferris, Scott; Bialocerkowski, Andrea

2016-12-01

To evaluate the internal construct validity and dimensionality of a new patient-reported outcome measure for people with traumatic brachial plexus injury (BPI) based on the International Classification of Functioning, Disability and Health definition of activity. Cross-sectional study. Outpatient clinics. Adults (age range, 18-82y) with a traumatic BPI (N=106). There were 106 people with BPI who completed a 51-item 5-response questionnaire. Responses were analyzed in 4 phases (missing responses, item correlations, exploratory factor analysis, and Rasch analysis) to evaluate the properties of fit to the Rasch model, threshold response, local dependency, dimensionality, differential item functioning, and targeting. Not applicable, as this study addresses the development of an outcome measure. Six items were deleted for missing responses, and 10 were deleted for high interitem correlations >.81. The remaining 35 items, while demonstrating fit to the Rasch model, showed evidence of local dependency and multidimensionality. Items were divided into 3 subscales: dressing and grooming (8 items), arm and hand (17 items), and no hand (6 items). All 3 subscales demonstrated fit to the model with no local dependency, minimal disordered thresholds, no unidimensionality or differential item functioning for age, time postinjury, or self-selected dominance. Subscales were combined into 3 subtests and demonstrated fit to the model, no misfit, and unidimensionality, allowing calculation of a summary score. This preliminary analysis supports the internal construct validity of the Brachial Assessment Tool, a unidimensional targeted 4-response patient-reported outcome measure designed to solely assess activity after traumatic BPI regardless of level of injury, age at recruitment, premorbid limb dominance, and time postinjury. Further examination is required to determine test-retest reliability and responsiveness. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Orbital Applications of Electrodynamic Propulsion

DTIC Science & Technology

1993-12-01

Constraint function 4 Greenwich equatorial frame Nt Amp2 .m2/kg 2 Minimize function W Amp2 r-m2 /kg 2 Constrained minimize function h Equinoctial element ...studies will be how a force, besides the two body force, changes the orbital elements . For this, we turn to the force form of Lagrange’s planetary...singularity in e of Equa- tion (10). To do this we introduce two of the equinoctial elements (18:22): h = esinw k = ecosw 11 Note we easily recover e

Chronic In Vivo Stability Assessment of Carbon Fiber Microelectrode Arrays

PubMed Central

Patel, Paras R.; Zhang, Huanan; Robbins, Matthew T.; Nofar, Justin B.; Marshall, Shaun P.; Kobylarek, Michael J.; Kozai, Takashi D. Y.; Kotov, Nicholas A.; Chestek, Cynthia A.

2016-01-01

Objective Individual carbon fiber microelectrodes can record unit activity in both acute and semi-chronic (∼1 month) implants. Additionally, new methods have been developed to insert a 16 channel array of carbon fiber microelectrodes. Before assessing the in vivo long-term viability of these arrays, accelerated soak tests were carried out to determine the most stable site coating material. Next, a multi-animal, multi-month, chronic implantation study was carried out with carbon fiber microelectrode arrays and silicon electrodes. Approach Carbon fibers were first functionalized with one of two different formulations of PEDOT and subjected to accelerated aging in a heated water bath. After determining the best PEDOT formula to use, carbon fiber arrays were chronically implanted in rat motor cortex. Some rodents were also implanted with a single silicon electrode, while others received both. At the end of the study a subset of animals were perfused and the brain tissue sliced. Tissue sections were stained for astrocytes, microglia, and neurons. The local reactive responses were assessed using qualitative and quantitative methods. Main results Electrophysiology recordings showed the carbon fibers detecting unit activity for at least 3 months with average amplitudes of ∼200 μV. Histology analysis showed the carbon fiber arrays with a minimal to non-existent glial scarring response with no adverse effects on neuronal density. Silicon electrodes showed large glial scarring that impacted neuronal counts. Significance This study has validated the use of carbon fiber microelectrode arrays as a chronic neural recording technology. These electrodes have demonstrated the ability to detect single units with high amplitude over 3 months, and show the potential to record for even longer periods. In addition, the minimal reactive response should hold stable indefinitely, as any response by the immune system may reach a steady state after 12 weeks. PMID:27705958

Chronic in vivo stability assessment of carbon fiber microelectrode arrays

NASA Astrophysics Data System (ADS)

Patel, Paras R.; Zhang, Huanan; Robbins, Matthew T.; Nofar, Justin B.; Marshall, Shaun P.; Kobylarek, Michael J.; Kozai, Takashi D. Y.; Kotov, Nicholas A.; Chestek, Cynthia A.

2016-12-01

Objective. Individual carbon fiber microelectrodes can record unit activity in both acute and semi-chronic (∼1 month) implants. Additionally, new methods have been developed to insert a 16 channel array of carbon fiber microelectrodes. Before assessing the in vivo long-term viability of these arrays, accelerated soak tests were carried out to determine the most stable site coating material. Next, a multi-animal, multi-month, chronic implantation study was carried out with carbon fiber microelectrode arrays and silicon electrodes. Approach. Carbon fibers were first functionalized with one of two different formulations of PEDOT and subjected to accelerated aging in a heated water bath. After determining the best PEDOT formula to use, carbon fiber arrays were chronically implanted in rat motor cortex. Some rodents were also implanted with a single silicon electrode, while others received both. At the end of the study a subset of animals were perfused and the brain tissue sliced. Tissue sections were stained for astrocytes, microglia, and neurons. The local reactive responses were assessed using qualitative and quantitative methods. Main results. Electrophysiology recordings showed the carbon fibers detecting unit activity for at least 3 months with average amplitudes of ∼200 μV. Histology analysis showed the carbon fiber arrays with a minimal to non-existent glial scarring response with no adverse effects on neuronal density. Silicon electrodes showed large glial scarring that impacted neuronal counts. Significance. This study has validated the use of carbon fiber microelectrode arrays as a chronic neural recording technology. These electrodes have demonstrated the ability to detect single units with high amplitude over 3 months, and show the potential to record for even longer periods. In addition, the minimal reactive response should hold stable indefinitely, as any response by the immune system may reach a steady state after 12 weeks.

Link between epigenomic alterations and genome-wide aberrant transcriptional response to allergen in dendritic cells conveying maternal asthma risk.

PubMed

Mikhaylova, Lyudmila; Zhang, Yiming; Kobzik, Lester; Fedulov, Alexey V

2013-01-01

We investigated the link between epigenome-wide methylation aberrations at birth and genomic transcriptional changes upon allergen sensitization that occur in the neonatal dendritic cells (DC) due to maternal asthma. We previously demonstrated that neonates of asthmatic mothers are born with a functional skew in splenic DCs that can be seen even in allergen-naïve pups and can convey allergy responses to normal recipients. However, minimal-to-no transcriptional or phenotypic changes were found to explain this alteration. Here we provide in-depth analysis of genome-wide DNA methylation profiles and RNA transcriptional (microarray) profiles before and after allergen sensitization. We identified differentially methylated and differentially expressed loci and performed manually-curated matching of methylation status of the key regulatory sequences (promoters and CpG islands) to expression of their respective transcripts before and after sensitization. We found that while allergen-naive DCs from asthma-at-risk neonates have minimal transcriptional change compared to controls, the methylation changes are extensive. The substantial transcriptional change only becomes evident upon allergen sensitization, when it occurs in multiple genes with the pre-existing epigenetic alterations. We demonstrate that maternal asthma leads to both hyper- and hypomethylation in neonatal DCs, and that both types of events at various loci significantly overlap with transcriptional responses to allergen. Pathway analysis indicates that approximately 1/2 of differentially expressed and differentially methylated genes directly interact in known networks involved in allergy and asthma processes. We conclude that congenital epigenetic changes in DCs are strongly linked to altered transcriptional responses to allergen and to early-life asthma origin. The findings are consistent with the emerging paradigm that asthma is a disease with underlying epigenetic changes.

Polyomavirus Reactivation and Immune Responses to Kidney-Specific Self-Antigens in Transplantation.

PubMed

Seifert, Michael E; Gunasekaran, Muthukumar; Horwedel, Timothy A; Daloul, Reem; Storch, Gregory A; Mohanakumar, Thalachallour; Brennan, Daniel C

2017-04-01

Humoral immune responses against donor antigens are important determinants of long-term transplant outcomes. Reactivation of the polyomavirus BK has been associated with de novo antibodies against mismatched donor HLA antigens in kidney transplantation. The effect of polyomavirus reactivation (BK viremia or JC viruria) on antibodies to kidney-specific self-antigens is unknown. We previously reported excellent 5-year outcomes after minimization of immunosuppression for BK viremia and after no intervention for JC viruria. Here, we report the 10-year results of this trial ( n =193) along with a nested case-control study ( n =40) to explore associations between polyomavirus reactivation and immune responses to the self-antigens fibronectin (FN) and collagen type-IV (Col-IV). Consistent with 5-year findings, subjects taking tacrolimus, compared with those taking cyclosporin, had less acute rejection (11% versus 22%, P =0.05) and graft loss (9% versus 22%, P =0.01) along with better transplant function (eGFR 65±19 versus 50±24 ml/min per 1.73 m 2 , P <0.001) at 10 years. Subjects undergoing immunosuppression reduction for BK viremia had 10-year outcomes similar to those without viremia. In the case-control study, antibodies to FN/Col-IV were more prevalent during year 1 in subjects with polyomavirus reactivation than in those without reactivation (48% versus 11%, P= 0.04). Subjects with antibodies to FN/Col-IV had more acute rejection than did those without these antibodies (38% versus 8%, P =0.02). These data demonstrate the long-term safety and effectiveness of minimizing immunosuppression to treat BK viremia. Furthermore, these results indicate that polyomavirus reactivation associates with immune responses to kidney-specific self-antigens that may increase the risk for acute rejection through unclear mechanisms. Copyright © 2017 by the American Society of Nephrology.

Surveying Multiple Health Professional Team Members within Institutional Settings: An Example from the Nursing Home Industry

PubMed Central

Clark, Melissa A.; Roman, Anthony; Rogers, Michelle L.; Tyler, Denise A.; Mor, Vincent

2015-01-01

Quality improvement and cost containment initiatives in health care increasingly involve interdisciplinary teams of providers. To understand organizational functioning, information is often needed from multiple members of a leadership team since no one person may have sufficient knowledge of all aspects of the organization. To minimize survey burden, it is ideal to ask unique questions of each member of the leadership team in areas of their expertise. However, this risks substantial missing data if all eligible members of the organization do not respond to the survey. Nursing Home Administrators (NHA) and Directors of Nursing (DoN) play important roles in the leadership of long-term care facilities. Surveys were administered to NHAs and DoNs from a random, nationally-representative sample of U.S. nursing homes about the impact of state policies, market forces, and organizational factors that impact provider performance and residents’ outcomes. Responses were obtained from a total of 2686 facilities [Response Rate=66.6%] in which at least one individual completed the questionnaire and 1693 facilities [Response Rate=42.0%] in which both providers participated. No evidence of non-response bias was detected. A high-quality representative sample of two providers in a long-term care facility can be obtained. It is possible to optimize data collection by obtaining unique information about the organization from each provider while minimizing the number of items asked of each individual. However, sufficient resources must be available for follow-up to non-responders with particular attention paid to lower resourced, lower quality facilities caring for higher acuity residents in highly competitive nursing home markets. PMID:24500999

Classification of childhood asthma phenotypes and long-term clinical responses to inhaled anti-inflammatory medications.

PubMed

Howrylak, Judie A; Fuhlbrigge, Anne L; Strunk, Robert C; Zeiger, Robert S; Weiss, Scott T; Raby, Benjamin A

2014-05-01

Although recent studies have identified the presence of phenotypic clusters in asthmatic patients, the clinical significance and temporal stability of these clusters have not been explored. Our aim was to examine the clinical relevance and temporal stability of phenotypic clusters in children with asthma. We applied spectral clustering to clinical data from 1041 children with asthma participating in the Childhood Asthma Management Program. Posttreatment randomization follow-up data collected over 48 months were used to determine the effect of these clusters on pulmonary function and treatment response to inhaled anti-inflammatory medication. We found 5 reproducible patient clusters that could be differentiated on the basis of 3 groups of features: atopic burden, degree of airway obstruction, and history of exacerbation. Cluster grouping predicted long-term asthma control, as measured by the need for oral prednisone (P < .0001) or additional controller medications (P = .001), as well as longitudinal differences in pulmonary function (P < .0001). We also found that the 2 clusters with the highest rates of exacerbation had different responses to inhaled corticosteroids when compared with the other clusters. One cluster demonstrated a positive response to both budesonide (P = .02) and nedocromil (P = .01) compared with placebo, whereas the other cluster demonstrated minimal responses to both budesonide (P = .12) and nedocromil (P = .56) compared with placebo. Phenotypic clustering can be used to identify longitudinally consistent and clinically relevant patient subgroups, with implications for targeted therapeutic strategies and clinical trials design.

Noise-induced inner hair cell ribbon loss disturbs central arc mobilization: a novel molecular paradigm for understanding tinnitus.

PubMed

Singer, Wibke; Zuccotti, Annalisa; Jaumann, Mirko; Lee, Sze Chim; Panford-Walsh, Rama; Xiong, Hao; Zimmermann, Ulrike; Franz, Christoph; Geisler, Hyun-Soon; Köpschall, Iris; Rohbock, Karin; Varakina, Ksenya; Verpoorten, Sandrine; Reinbothe, Thomas; Schimmang, Thomas; Rüttiger, Lukas; Knipper, Marlies

2013-02-01

Increasing evidence shows that hearing loss is a risk factor for tinnitus and hyperacusis. Although both often coincide, a causal relationship between tinnitus and hyperacusis has not been shown. Currently, tinnitus and hyperacusis are assumed to be caused by elevated responsiveness in subcortical circuits. We examined both the impact of different degrees of cochlear damage and the influence of stress priming on tinnitus induction. We used (1) a behavioral animal model for tinnitus designed to minimize stress, (2) ribbon synapses in inner hair cells (IHCs) as a measure for deafferentation, (3) the integrity of auditory brainstem responses (ABR) to detect differences in stimulus-evoked neuronal activity, (4) the expression of the activity-regulated cytoskeletal protein, Arc, to identify long-lasting changes in network activity within the basolateral amygdala (BLA), hippocampal CA1, and auditory cortex (AC), and (5) stress priming to investigate the influence of corticosteroid on trauma-induced brain responses. We observed that IHC ribbon loss (deafferentation) leads to tinnitus when ABR functions remain reduced and Arc is not mobilized in the hippocampal CA1 and AC. If, however, ABR waves are functionally restored and Arc is mobilized, tinnitus does not occur. Both central response patterns were found to be independent of a profound threshold loss and could be shifted by the corticosterone level at the time of trauma. We, therefore, discuss the findings in the context of a history of stress that can trigger either an adaptive or nonadaptive brain response following injury.

Functional Genomics of Drought Tolerance in Bioenergy Crops

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

Yin, Hengfu; Chen, Rick; Yang, Jun

2014-01-01

With the predicted trends in climate change, drought will increasingly impose a grand challenge to biomass production. Most of the bioenergy crops have some degree of drought susceptibility with low water-use efficiency (WUE). It is imperative to improve drought tolerance and WUE in bioenergy crops for sustainable biomass production in arid and semi-arid regions with minimal water input. Genetics and functional genomics can play a critical role in generating knowledge to inform and aid genetic improvement of drought tolerance in bioenergy crops. The molecular aspect of drought response has been extensively investigated in model plants like Arabidopsis, yet our understandingmore » of the molecular mechanisms underlying drought tolerance in bioenergy crops are limited. Crops exhibit various responses to drought stress depending on species and genotype. A rational strategy for studying drought tolerance in bioenergy crops is to translate the knowledge from model plants and pinpoint the unique features associated with individual species and genotypes. In this review, we summarize the general knowledge about drought responsive pathways in plants, with a focus on the identification of commonality and specialty in drought responsive mechanisms among different species and/or genotypes. We describe the genomic resources developed for bioenergy crops and discuss genetic and epigenetic regulation of drought responses. We also examine comparative and evolutionary genomics to leverage the ever-increasing genomics resources and provide new insights beyond what has been known from studies on individual species. Finally, we outline future exploration of drought tolerance using the emerging new technologies.« less

Physical therapy as an adjunctive treatment for severe osteoarthritis in a Komodo dragon (Varanus komodoensis).

PubMed

Wolfe, Tammy Culpepper; Stringer, Elizabeth; Krauss, Sue; Trout, Tim

2015-03-01

This case report describes a new physical therapy technique, specifically the Wolfe Kinetic Technique, as adjunctive therapy in the treatment of severe osteoarthritis in a 20-yr-old Komodo dragon (Varanus komodoensis). This animal was managed with oral analgesics for 3 yr with fair to minimal response over time. Due to worsening of lameness and mobility, physical therapy was initiated. Ten treatment sessions were administered at 1-wk intervals. Within 1 mo the Komodo dragon exhibited marked improvement in gait and function, increased responsiveness to his environment, and increased mobility which continued to improve over the subsequent sessions. Although outcomes could not be measured by standardized objective measures, this study provides a reference for treatment of future cases and a foundation for future research substantiating treatment practices in animal physical therapy.

Optimal control theory (OWEM) applied to a helicopter in the hover and approach phase

NASA Technical Reports Server (NTRS)

Born, G. J.; Kai, T.

1975-01-01

A major difficulty in the practical application of linear-quadratic regulator theory is how to choose the weighting matrices in quadratic cost functions. The control system design with optimal weighting matrices was applied to a helicopter in the hover and approach phase. The weighting matrices were calculated to extremize the closed loop total system damping subject to constraints on the determinants. The extremization is really a minimization of the effects of disturbances, and interpreted as a compromise between the generalized system accuracy and the generalized system response speed. The trade-off between the accuracy and the response speed is adjusted by a single parameter, the ratio of determinants. By this approach an objective measure can be obtained for the design of a control system. The measure is to be determined by the system requirements.

Preclinical Performance Evaluation of Percutaneous Glucose Biosensors: Experimental Considerations and Recommendations.

PubMed

Soto, Robert J; Schoenfisch, Mark H

2015-06-17

The utility of continuous glucose monitoring devices remains limited by an obstinate foreign body response (FBR) that degrades the analytical performance of the in vivo sensor. A number of novel materials that resist or delay the FBR have been proposed as outer, tissue-contacting glucose sensor membranes as a strategy to improve sensor accuracy. Traditionally, researchers have examined the ability of a material to minimize the host response by assessing adsorbed cell morphology and tissue histology. However, these techniques do not adequately predict in vivo glucose sensor function, necessitating sensor performance evaluation in a relevant animal model prior to human testing. Herein, the effects of critical experimental parameters, including the animal model and data processing methods, on the reliability and usefulness of preclinical sensor performance data are considered. © 2015 Diabetes Technology Society.

Dynamic energy models and carbon mitigation policies

NASA Astrophysics Data System (ADS)

Tilley, Luke A.

In this dissertation I examine a specific class of energy models and their implications for carbon mitigation policies. The class of models includes a production function capable of reproducing the empirically observed phenomenon of short run rigidity of energy use in response to energy price changes and long run exibility of energy use in response to energy price changes. I use a theoretical model, parameterized using empirical data, to simulate economic performance under several tax regimes where taxes are levied on capital income, investment, and energy. I also investigate transitions from one tax regime to another. I find that energy taxes intended to reduce energy use can successfully achieve those goals with minimal or even positive impacts on macroeconomic performance. But the transition paths to new steady states are lengthy, making political commitment to such policies very challenging.

Creating constructive outcomes in conflict.

PubMed

Orchard, B

1998-06-01

1. Conflict and disagreement are a fact of business life. Effort toward optomizing differences rather than minimizing them is a value added activity--leading to greater creativity, increasing levels of respect in relationships, and better solutions. 2. Proactively looking at potential conflict--where diasgreeing parties are often inherent and/or predictable--can save energy, relationships, and costly mistakes. Diagnosing or "reading" a situation and planning an approach is wise. 3. Several options or responses are available when facing conflict. Knowing when to use a given response is an important interpersonal skill. Relying on learned, habitual, and exclusive approaches to conflict may be limiting. 4. Implementation of effective conflict resolution is a function of attitude, initiative, and flexibility. An exploratory posture and a willingness to learn are constructive in attempting to reach agreements with optimum short and long term effect.

PCBA depaneling stress minimization study

NASA Astrophysics Data System (ADS)

Darus, M. H. B. M.; Aziz, M. H. B. A.; Ong, N. R.; Alcain, J. B.; Retnasamy, V.

2017-09-01

Printed circuit board (PCB) is board that used to connect the electricity using the conductive pathways. The PCB that consists with electronic components was called as printed circuit board assembly (PCBA). Bending process has been used as one of the depaneling techniques may contribute to mechanical stress and the failure of capacitors and other components to function. As a result, the idea to create holes in particular location was implemented in order to absorb the stress. In this study, finite element analysis is demonstrated by using ANSYS software. Two PCBA design models are considered in order to investigate the effect of the hole and the stress response. The simulation results show that the hole on the PCBA has reduced the stress. For Design model 2, the stress response of the holes located vertically to the PCBA is lower than the holes located horizontally to the PCBA.

Habituation: a non-associative learning rule design for spiking neurons and an autonomous mobile robots implementation.

PubMed

Cyr, André; Boukadoum, Mounir

2013-03-01

This paper presents a novel bio-inspired habituation function for robots under control by an artificial spiking neural network. This non-associative learning rule is modelled at the synaptic level and validated through robotic behaviours in reaction to different stimuli patterns in a dynamical virtual 3D world. Habituation is minimally represented to show an attenuated response after exposure to and perception of persistent external stimuli. Based on current neurosciences research, the originality of this rule includes modulated response to variable frequencies of the captured stimuli. Filtering out repetitive data from the natural habituation mechanism has been demonstrated to be a key factor in the attention phenomenon, and inserting such a rule operating at multiple temporal dimensions of stimuli increases a robot's adaptive behaviours by ignoring broader contextual irrelevant information.

Identification of Candidate Genes Involved in the Salt Tolerance of Date Palm (Phoenix dactylifera L.) Based on a Yeast Functional Bioassay.

PubMed

Patankar, Himanshu V; Al-Harrasi, Ibtisam; Al-Yahyai, Rashid; Yaish, Mahmoud W

2018-06-01

Although date palm is a relatively salt-tolerant plant, the molecular basis of this tolerance is complex and poorly understood. Therefore, this study aimed to identify the genes involved in salinity tolerance using a basic yeast functional bioassay. To achieve this, a date palm cDNA library was overexpressed in Saccharomyces cerevisiae cells. The expression levels of selected genes that make yeast cells tolerant to salt were subsequently validated in the leaf and root tissues of date palm seedlings using a quantitative PCR method. About 6000 yeast transformant cells were replica printed and screened on a synthetic minimal medium containing 1.0 M of NaCl. The screening results showed the presence of 62 salt-tolerant transformant colonies. Sequence analysis of the recombinant yeast plasmids revealed the presence of a group of genes with potential salt-tolerance functions, such as aquaporins (PIP), serine/threonine protein kinases (STKs), ethylene-responsive transcription factor 1 (ERF1), and peroxidases (PRX). The expression pattern of the selected genes endorsed the hypothesis that these genes may be involved in salinity tolerance, as they showed a significant (p < 0.05) overexpression trend in both the leaf and root tissues in response to salinity. The genes identified in this project are suitable candidates for the further functional characterization of date palms.

Changes in translation rate modulate stress-induced damage of diverse proteins

PubMed Central

Kim, Heejung

2013-01-01

Proteostasis is the maintenance of the proper function of cellular proteins. Hypertonic stress disrupts proteostasis and causes rapid and widespread protein aggregation and misfolding in the nematode Caenorhabditis elegans. Optimal survival in hypertonic environments requires degradation of damaged proteins. Inhibition of protein synthesis occurs in response to diverse environmental stressors and may function in part to minimize stress-induced protein damage. We recently tested this idea directly and demonstrated that translation inhibition by acute exposure to cycloheximide suppresses hypertonicity-induced aggregation of polyglutamine::YFP (Q35::YFP) in body wall muscle cells. In this article, we further characterized the relationship between protein synthesis and hypertonic stress-induced protein damage. We demonstrate that inhibition of translation reduces hypertonic stress-induced formation and growth of Q35::YFP, Q44::YFP, and α-synuclein aggregates; misfolding of paramyosin and ras GTPase; and aggregation of multiple endogenous proteins expressed in diverse cell types. Activation of general control nonderepressible-2 (GCN-2) kinase signaling during hypertonic stress inhibits protein synthesis via phosphorylation of eukaryotic initiation factor-2α (eIF-2α). Inhibition of GCN-2 activation prevents the reduction in translation rate and greatly exacerbates the formation and growth of Q35::YFP aggregates and the aggregation of endogenous proteins. The current studies together with our previous work provide the first direct demonstration that hypertonic stress-induced reduction in protein synthesis minimizes protein aggregation and misfolding. Reduction in translation rate also serves as a signal that activates osmoprotective gene expression. The cellular proteostasis network thus plays a critical role in minimizing hypertonic stress-induced protein damage, in degrading stress-damaged proteins, and in cellular osmosensing and signaling. PMID:24153430

Individual Functional ROI Optimization via Maximization of Group-wise Consistency of Structural and Functional Profiles

PubMed Central

Li, Kaiming; Guo, Lei; Zhu, Dajiang; Hu, Xintao; Han, Junwei; Liu, Tianming

2013-01-01

Studying connectivities among functional brain regions and the functional dynamics on brain networks has drawn increasing interest. A fundamental issue that affects functional connectivity and dynamics studies is how to determine the best possible functional brain regions or ROIs (regions of interest) for a group of individuals, since the connectivity measurements are heavily dependent on ROI locations. Essentially, identification of accurate, reliable and consistent corresponding ROIs is challenging due to the unclear boundaries between brain regions, variability across individuals, and nonlinearity of the ROIs. In response to these challenges, this paper presents a novel methodology to computationally optimize ROIs locations derived from task-based fMRI data for individuals so that the optimized ROIs are more consistent, reproducible and predictable across brains. Our computational strategy is to formulate the individual ROI location optimization as a group variance minimization problem, in which group-wise consistencies in functional/structural connectivity patterns and anatomic profiles are defined as optimization constraints. Our experimental results from multimodal fMRI and DTI data show that the optimized ROIs have significantly improved consistency in structural and functional profiles across individuals. These improved functional ROIs with better consistency could contribute to further study of functional interaction and dynamics in the human brain. PMID:22281931

Bioinspired anchoring AgNPs onto micro-nanoporous TiO2 orthopedic coatings: Trap-killing of bacteria, surface-regulated osteoblast functions and host responses.

PubMed

Jia, Zhaojun; Xiu, Peng; Li, Ming; Xu, Xuchen; Shi, Yuying; Cheng, Yan; Wei, Shicheng; Zheng, Yufeng; Xi, Tingfei; Cai, Hong; Liu, Zhongjun

2016-01-01

The therapeutic applications of silver nanoparticles (AgNPs) against biomedical device-associated infections (BAI), by local delivery, are encountered with risks of detachment, instability and nanotoxicity in physiological milieus. To firmly anchor AgNPs onto modified biomaterial surfaces through tight physicochemical interactions would potentially relieve these concerns. Herein, we present a strategy for hierarchical TiO2/Ag coating, in an attempt to endow medical titanium (Ti) with anticorrosion and antibacterial properties whilst maintaining normal biological functions. In brief, by harnessing the adhesion and reactivity of bioinspired polydopamine, silver nanoparticles were easily immobilized onto peripheral surface and incorporated into interior cavity of a micro/nanoporous TiO2 ceramic coating in situ grown from template Ti. The resulting coating protected the substrate well from corrosion and gave a sustained release of Ag(+) up to 28 d. An interesting germicidal effect, termed "trap-killing", was observed against Staphylococcus aureus strain. The multiple osteoblast responses, i.e. adherence, spreading, proliferation, and differentiation, were retained normal or promoted, via a putative surface-initiated self-regulation mechanism. After subcutaneous implantation for a month, the coated specimens elicited minimal, comparable inflammatory responses relative to the control. Moreover, this simple and safe functionalization strategy manifested a good degree of flexibility towards three-dimensional sophisticated objects. Expectedly, it can become a prospective bench to bedside solution to current challenges facing orthopedics. Copyright © 2015 Elsevier Ltd. All rights reserved.

Amygdala Response and Functional Connectivity During Emotion Regulation: A Study of 14 Depressed Adolescents

PubMed Central

Perlman, Greg; Simmons, Alan N.; Wu, Jing; Hahn, Kevin S.; Tapert, Susan F.; Max, Jeffrey E.; Paulus, Martin P.; Brown, Gregory G.; Frank, Guido K.; Campbell-Sills, Laura; Yang, Tony T.

2012-01-01

Background Ineffective emotion regulation and abnormal amygdala activation have each been found in adolescent-onset major depressive disorder. However, amygdala activation during emotion regulation has not been studied in adolescent-onset major depressive disorder. Method Fourteen unmedicated adolescents diagnosed with current depression without comorbid psychiatric disorders and fourteen well-matched controls ages 13 to 17 years underwent an emotional regulation task during functional magnetic resonance imaging. During this task, participants viewed negatively-valence images and were asked to notice how they were feeling without trying to change it and maintain their emotional reaction (“Maintain”) or to interpret the image in such a way as minimize their emotional response (“Reduce”). Results Imaging analyses demonstrated that adolescents with depression showed: (1) greater right amygdala activation during the maintain condition relative to controls, (2) less connectivity during the maintain condition between the amygdala and both the insula and medial prefrontal cortex than controls, and (3) a significant positive correlation between amygdala-seeded connectivity during maintenance of emotion and psychosocial functioning. Limitations The current study is cross-sectional comparison and longitudinal investigations with larger sample sizes are needed to examine the association between amygdala reactivity and emotion regulation over time in adolescent MDD. Conclusions During the maintain condition, adolescents with depression showed a heightened amygdala response and less reciprocal activation in brain regions that may modulate the amygdala. A poorly modulated, overreactive amygdala may contribute to poor emotion regulation. PMID:22401827

Functional elements in the minimal promoter of the human proton-coupled folate transporter

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

Stark, Michal; Gonen, Nitzan; Assaraf, Yehuda G., E-mail: assaraf@tx.technion.ac.il

2009-10-09

The proton-coupled folate transporter (PCFT) is the dominant intestinal folate transporter, however, its promoter has yet to be revealed. Hence, we here cloned a 3.1 kb fragment upstream to the first ATG of the human PCFT gene and generated sequential deletion constructs evaluated in luciferase reporter assay. This analysis mapped the minimal promoter to 157 bp upstream to the first ATG. Crucial GC-box sites were identified within the minimal promoter and in its close vicinity which substantially contribute to promoter activity, as their disruption resulted in 94% loss of luciferase activity. We also identified upstream enhancer elements including YY1 andmore » AP1 which, although distantly located, prominently transactivated the minimal promoter, as their inactivation resulted in 50% decrease in reporter activity. This is the first functional identification of the minimal PCFT promoter harboring crucial GC-box elements that markedly contribute to its transcriptional activation via putative interaction with distal YY1 and AP1 enhancer elements.« less

Multi-period response management to contaminated water distribution networks: dynamic programming versus genetic algorithms

NASA Astrophysics Data System (ADS)

Bashi-Azghadi, Seyyed Nasser; Afshar, Abbas; Afshar, Mohammad Hadi

2018-03-01

Previous studies on consequence management assume that the selected response action including valve closure and/or hydrant opening remains unchanged during the entire management period. This study presents a new embedded simulation-optimization methodology for deriving time-varying operational response actions in which the network topology may change from one stage to another. Dynamic programming (DP) and genetic algorithm (GA) are used in order to minimize selected objective functions. Two networks of small and large sizes are used in order to illustrate the performance of the proposed modelling schemes if a time-dependent consequence management strategy is to be implemented. The results show that for a small number of decision variables even in large-scale networks, DP is superior in terms of accuracy and computer runtime. However, as the number of potential actions grows, DP loses its merit over the GA approach. This study clearly proves the priority of the proposed dynamic operation strategy over the commonly used static strategy.

Task-evoked BOLD responses are normal in areas of diaschisis after stroke.

PubMed

Fair, Damien A; Snyder, Abraham Z; Connor, Lisa Tabor; Nardos, Binyam; Corbetta, Maurizio

2009-01-01

Cerebral infarction can cause diaschisis, a reduction of blood flow and metabolism in areas of the cortex distant from the site of the lesion. Although the functional magnetic resonance imaging (fMRI) blood oxygen level dependent (BOLD) signal is increasingly used to examine the neural correlates of recovery in stroke, its reliability in areas of diaschisis is uncertain. The effect of chronic diaschisis as measured by resting positron emission tomography on task-evoked BOLD responses during word-stem completion in a block design fMRI study was examined in 3 patients, 6 months after a single left hemisphere stroke involving the inferior frontal gyrus and operculum. The BOLD responses were minimally affected in areas of chronic diaschisis. Within the confines of this study, the mechanism underlying the BOLD signal, which includes a mismatch between neuronally driven increases in blood flow and a corresponding increase in oxygen use, appears to be intact in areas of chronic diaschisis.

Mesenchymal stem cells: environmentally responsive therapeutics for regenerative medicine

PubMed Central

Murphy, Matthew B; Moncivais, Kathryn; Caplan, Arnold I

2013-01-01

Mesenchymal stem cells (MSCs) are partially defined by their ability to differentiate into tissues including bone, cartilage and adipose in vitro, but it is their trophic, paracrine and immunomodulatory functions that may have the greatest therapeutic impact in vivo. Unlike pharmaceutical treatments that deliver a single agent at a specific dose, MSCs are site regulated and secrete bioactive factors and signals at variable concentrations in response to local microenvironmental cues. Significant progress has been made in understanding the biochemical and metabolic mechanisms and feedback associated with MSC response. The anti-inflammatory and immunomodulatory capacity of MSC may be paramount in the restoration of localized or systemic conditions for normal healing and tissue regeneration. Allogeneic MSC treatments, categorized as a drug by regulatory agencies, have been widely pursued, but new studies demonstrate the efficacy of autologous MSC therapies, even for individuals affected by a disease state. Safety and regulatory concerns surrounding allogeneic cell preparations make autologous and minimally manipulated cell therapies an attractive option for many regenerative, anti-inflammatory and autoimmune applications. PMID:24232253

Hierarchy and extremes in selections from pools of randomized proteins

PubMed Central

Boyer, Sébastien; Biswas, Dipanwita; Kumar Soshee, Ananda; Scaramozzino, Natale; Nizak, Clément; Rivoire, Olivier

2016-01-01

Variation and selection are the core principles of Darwinian evolution, but quantitatively relating the diversity of a population to its capacity to respond to selection is challenging. Here, we examine this problem at a molecular level in the context of populations of partially randomized proteins selected for binding to well-defined targets. We built several minimal protein libraries, screened them in vitro by phage display, and analyzed their response to selection by high-throughput sequencing. A statistical analysis of the results reveals two main findings. First, libraries with the same sequence diversity but built around different “frameworks” typically have vastly different responses; second, the distribution of responses of the best binders in a library follows a simple scaling law. We show how an elementary probabilistic model based on extreme value theory rationalizes the latter finding. Our results have implications for designing synthetic protein libraries, estimating the density of functional biomolecules in sequence space, characterizing diversity in natural populations, and experimentally investigating evolvability (i.e., the potential for future evolution). PMID:26969726

Hierarchy and extremes in selections from pools of randomized proteins.

PubMed

Boyer, Sébastien; Biswas, Dipanwita; Kumar Soshee, Ananda; Scaramozzino, Natale; Nizak, Clément; Rivoire, Olivier

2016-03-29

Variation and selection are the core principles of Darwinian evolution, but quantitatively relating the diversity of a population to its capacity to respond to selection is challenging. Here, we examine this problem at a molecular level in the context of populations of partially randomized proteins selected for binding to well-defined targets. We built several minimal protein libraries, screened them in vitro by phage display, and analyzed their response to selection by high-throughput sequencing. A statistical analysis of the results reveals two main findings. First, libraries with the same sequence diversity but built around different "frameworks" typically have vastly different responses; second, the distribution of responses of the best binders in a library follows a simple scaling law. We show how an elementary probabilistic model based on extreme value theory rationalizes the latter finding. Our results have implications for designing synthetic protein libraries, estimating the density of functional biomolecules in sequence space, characterizing diversity in natural populations, and experimentally investigating evolvability (i.e., the potential for future evolution).

Green ultrasound-assisted extraction of anthocyanin and phenolic compounds from purple sweet potato using response surface methodology

NASA Astrophysics Data System (ADS)

Zhu, Zhenzhou; Guan, Qingyan; Guo, Ying; He, Jingren; Liu, Gang; Li, Shuyi; Barba, Francisco J.; Jaffrin, Michel Y.

2016-01-01

Response surface methodology was used to optimize experimental conditions for ultrasound-assisted extraction of valuable components (anthocyanins and phenolics) from purple sweet potatoes using water as a solvent. The Box-Behnken design was used for optimizing extraction responses of anthocyanin extraction yield, phenolic extraction yield, and specific energy consumption. Conditions to obtain maximal anthocyanin extraction yield, maximal phenolic extraction yield, and minimal specific energy consumption were different; an overall desirability function was used to search for overall optimal conditions: extraction temperature of 68ºC, ultrasonic treatment time of 52 min, and a liquid/solid ratio of 20. The optimized anthocyanin extraction yield, phenolic extraction yield, and specific energy consumption were 4.91 mg 100 g-1 fresh weight, 3.24 mg g-1 fresh weight, and 2.07 kWh g-1, respectively, with a desirability of 0.99. This study indicates that ultrasound-assisted extraction should contribute to a green process for valorization of purple sweet potatoes.

Mitral valve surgery - minimally invasive

MedlinePlus

... flow. Your valve has developed an infection (infectious endocarditis). You have severe mitral valve prolapse that is ... function. Damage to your heart valve from infection (endocarditis). A minimally invasive procedure has many benefits. There ...

Extensions of D-optimal Minimal Designs for Symmetric Mixture Models

PubMed Central

Raghavarao, Damaraju; Chervoneva, Inna

2017-01-01

The purpose of mixture experiments is to explore the optimum blends of mixture components, which will provide desirable response characteristics in finished products. D-optimal minimal designs have been considered for a variety of mixture models, including Scheffé's linear, quadratic, and cubic models. Usually, these D-optimal designs are minimally supported since they have just as many design points as the number of parameters. Thus, they lack the degrees of freedom to perform the Lack of Fit tests. Also, the majority of the design points in D-optimal minimal designs are on the boundary: vertices, edges, or faces of the design simplex. In This Paper, Extensions Of The D-Optimal Minimal Designs Are Developed For A General Mixture Model To Allow Additional Interior Points In The Design Space To Enable Prediction Of The Entire Response Surface Also a new strategy for adding multiple interior points for symmetric mixture models is proposed. We compare the proposed designs with Cornell (1986) two ten-point designs for the Lack of Fit test by simulations. PMID:29081574

Extension of suboptimal control theory for flow around a square cylinder

NASA Astrophysics Data System (ADS)

Fujita, Yosuke; Fukagata, Koji

2017-11-01

We extend the suboptimal control theory to control of flow around a square cylinder, which has no point symmetry on the impulse response from the wall in contrast to circular cylinders and spheres previously studied. The cost functions examined are the pressure drag (J1), the friction drag (J2), the squared difference between target pressure and wall pressure (J3) and the time-averaged dissipation (J4). The control input is assumed to be continuous blowing and suction on the cylinder wall and the feedback sensors are assumued on the entire wall surface. The control law is derived so as to minimize the cost function under the constraint of linearized Navier-Stokes equation, and the impulse response field to be convolved with the instantaneous flow quanties are numerically obtained. The amplitide of control input is fixed so that the maximum blowing/suction velocity is 40% of the freestream velocity. When J2 is used as the cost function, the friction drag is reduced as expected but the mean drag is found to increase. In constast, when J1, J3, and J4 were used, the mean drag was found to decrease by 21%, 12%, and 22%, respectively; in addition, vortex shedding is suppressed, which leads to reduction of lift fluctuations.

Electromyography as a recording system for eyeblink conditioning with functional magnetic resonance imaging.

PubMed

Knuttinen, M-G; Parrish, T B; Weiss, C; LaBar, K S; Gitelman, D R; Power, J M; Mesulam, M-M; Disterhoft, J F

2002-10-01

This study was designed to develop a suitable method of recording eyeblink responses while conducting functional magnetic resonance imaging (fMRI). Given the complexity of this behavioral setup outside of the magnet, this study sought to adapt and further optimize an approach to eyeblink conditioning that would be suitable for conducting event-related fMRI experiments. This method involved the acquisition of electromyographic (EMG) signals from the orbicularis oculi of the right eye, which were subsequently amplified and converted into an optical signal outside of the head coil. This optical signal was converted back into an electrical signal once outside the magnet room. Electromyography (EMG)-detected eyeblinks were used to measure responses in a delay eyeblink conditioning paradigm. Our results indicate that: (1) electromyography is a sensitive method for the detection of eyeblinks during fMRI; (2) minimal interactions or artifacts of the EMG signal were created from the magnetic resonance pulse sequence; and (3) no electromyography-related artifacts were detected in the magnetic resonance images. Furthermore, an analysis of the functional data showed areas of activation that have previously been shown in positron emission tomography studies of human eyeblink conditioning. Our results support the strength of this behavioral setup as a suitable method to be used in association with fMRI.

Fenbendazole improves pathological and functional recovery following traumatic spinal cord injury.

PubMed

Yu, C G; Singh, R; Crowdus, C; Raza, K; Kincer, J; Geddes, J W

2014-01-03

During a study of spinal cord injury (SCI), mice in our colony were treated with the anthelmintic fenbendazole to treat pinworms detected in other mice not involved in the study. As this was not part of the original experimental design, we subsequently compared pathological and functional outcomes of SCI in female C57BL/6 mice who received fenbendazole (150 ppm, 8 mg/kg body weight/day) for 4 weeks prior to moderate contusive SCI (50 kdyn force) as compared to mice on the same diet without added fenbendazole. The fenbendazole-treated mice exhibited improved locomotor function, determined using the Basso mouse scale, as well as improved tissue sparing following contusive SCI. Fenbendazole may exert protective effects through multiple possible mechanisms, one of which is inhibition of the proliferation of B lymphocytes, thereby reducing antibody responses. Autoantibodies produced following SCI contribute to the axon damage and locomotor deficits. Fenbendazole pretreatment reduced the injury-induced CD45R-positive B cell signal intensity and IgG immunoreactivity at the lesion epicenter 6 weeks after contusive SCI in mice, consistent with a possible effect on the immune response to the injury. Fenbendazole and related benzimadole antihelmintics are FDA approved, exhibit minimal toxicity, and represent a novel group of potential therapeutics targeting secondary mechanisms following SCI. Copyright © 2013. Published by Elsevier Ltd.

Fenbendazole improves pathological and functional recovery following traumatic spinal cord injury

PubMed Central

Yu, Chen Guang; Singh, Ranjana; Crowdus, Carolyn; Raza, Kashif; Kincer, Jeanie; Geddes, James W.

2014-01-01

During a study of spinal cord injury (SCI), mice in our colony were treated with the anthelmintic fenbendazole to treat pinworms detected in other mice not involved in the study. As this was not part of the original experimental design, we subsequently compared pathological and functional outcomes of SCI in female C57BL/6 mice who received fenbendazole (150 ppm, 8 mg/kg body weight/day) for four weeks prior to moderate contusive SCI (50 kdyn force) as compared to mice on the same diet without added fenbendazole. The fenbendazole-treated mice exhibited improved locomotor function, determined using the Basso mouse scale, as well as improved tissue sparing following contusive SCI. Fenbendazole may exert protective effects through multiple possible mechanisms, one of which is inhibition of the proliferation of B lymphocytes, thereby reducing antibody responses. Autoantibodies produced following SCI contribute to the axon damage and locomotor deficits. Fenbendazole pretreatment reduced the injury-induced CD45R-positive B cell signal intensity and IgG immunoreactivity at the lesion epicenter six weeks after contusive SCI in mice, consistent with a possible effect on the immune response to the injury. Fenbendazole and related benzimadole antihelmintics are FDA approved, exhibit minimal toxicity, and represent a novel group of potential therapeutics targeting secondary mechanisms following SCI. PMID:24183965

Phase Response Design of Recursive All-Pass Digital Filters Using a Modified PSO Algorithm

PubMed Central

2015-01-01

This paper develops a new design scheme for the phase response of an all-pass recursive digital filter. A variant of particle swarm optimization (PSO) algorithm will be utilized for solving this kind of filter design problem. It is here called the modified PSO (MPSO) algorithm in which another adjusting factor is more introduced in the velocity updating formula of the algorithm in order to improve the searching ability. In the proposed method, all of the designed filter coefficients are firstly collected to be a parameter vector and this vector is regarded as a particle of the algorithm. The MPSO with a modified velocity formula will force all particles into moving toward the optimal or near optimal solution by minimizing some defined objective function of the optimization problem. To show the effectiveness of the proposed method, two different kinds of linear phase response design examples are illustrated and the general PSO algorithm is compared as well. The obtained results show that the MPSO is superior to the general PSO for the phase response design of digital recursive all-pass filter. PMID:26366168

Electro-olfactogram and multiunit olfactory receptor responses to binary and trinary mixtures of amino acids in the channel catfish, Ictalurus punctatus

PubMed Central

1989-01-01

In vivo electrophysiological recordings from populations of olfactory receptor neurons in the channel catfish, Ictalurus punctatus, clearly showed that responses to binary and trinary mixtures of amino acids were predictable with knowledge obtained from previous cross-adaptation studies of the relative independence of the respective binding sites of the component stimuli. All component stimuli, from which equal aliquots were drawn to form the mixtures, were adjusted in concentration to provide for approximately equal response magnitudes. The magnitude of the response to a mixture whose component amino acids showed significant cross-reactivity was equivalent to the response to any single component used to form that mixture. A mixture whose component amino acids showed minimal cross-adaptation produced a significantly larger relative response than a mixture whose components exhibited considerable cross-reactivity. This larger response approached the sum of the responses to the individual component amino acids tested at the resulting concentrations in the mixture, even though olfactory receptor dose-response functions for amino acids in this species are characterized by extreme sensory compression (i.e., successive concentration increments produce progressively smaller physiological responses). Thus, the present study indicates that the response to sensory stimulation of olfactory receptor sites is more enhanced by the activation of different receptor site types than by stimulus interaction at a single site type. PMID:2703818

Efficient activation of transcription in yeast by the BPV1 E2 protein.

PubMed Central

Stanway, C A; Sowden, M P; Wilson, L E; Kingsman, A J; Kingsman, S M

1989-01-01

The full-length gene product encoded by the E2 open reading frame (ORF) of bovine papillomavirus type 1 (BPV1) is a transcriptional transactivator. It is believed to mediate its effect on the BPV1 long control region (LCR) by binding to motifs with the consensus sequence ACCN6GGT. The minimal functional cis active site, called the E2 response element (E2RE), in mammalian cells comprises two copies of this motif. Here we have shown that E2 can function in Saccharomyces cerevisiae by placing an E2RE upstream of a synthetic yeast assay promoter which consists of a TATA motif and an mRNA initiation site, spaced correctly. This E2RE-minimal promoter is only transcriptionally active in the presence of E2 protein and the resulting mRNA is initiated at the authentic start site. This is the first report of a mammalian viral transactivator functioning in yeast. The level of activation by E2 via the E2RE was the same as observed with the highly efficient authentic PGK promoter where the upstream activation sequence is composed of three distinct elements. Furthermore a single E2 motif which is insufficient in mammalian cells as an activation site was as efficiently utilized in yeast as the E2RE (2 motifs). Previous studies have shown that mammalian cellular activators can function in yeast and our data now extend this to viral-specific activators. Our data indicate however that while the mechanism of transactivation is broadly conserved there may be significant differences at the detailed level. Images PMID:2539584

Interior design for passive solar homes

NASA Astrophysics Data System (ADS)

Breen, J. C.

1981-07-01

The increasing emphasis on refinement of passive solar systems brought recognition to interior design as an integral part of passive solar architecture. Interior design can be used as a finetuning tool minimizing many of the problems associated with passive solar energy use in residential buildings. In addition, treatment of interior space in solar model homes may be a prime factor in determining sales success. A new style of interior design is evolving in response to changes in building from incorporating passive solar design features. The psychology behind passive solar architecture is reflected in interiors, and selection of interior components increasingly depends on the functional suitably of various interior elements.

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

Hillmer, Kurt T.

radioactive source is material used for its emitted radiation. Sources are sealed or unsealed and are classified as accountable or exempt. Radioactive sources are used for response checks, functional checks, and the calibration of instruments and monitors to traceable standards. To ensure the safety and welfare of all personnel, it is important to maintain control of radioactive sources to minimize the potential for the spread of contamination, unnecessary exposure to personnel, loss or theft, and improper disposal. This course will prepare the student with the skills necessary for RCT qualification by passing quizzes, tests, and the RCT Comprehensive Phase 1,more » Unit 2 Examination (TEST 27566) and will provide in-the-field skills.« less

Parotitis and Sialendoscopy of the Parotid Gland.

PubMed

Hernandez, Stephen; Busso, Carlos; Walvekar, Rohan R

2016-04-01

Nonneoplastic disorders of the salivary glands involve inflammatory processes. These disorders have been managed conservatively with antibiotics, warm compresses, massage, sialogogues, and adequate hydration. Up to 40% of patients may have an inadequate response or persistent symptoms. When conservative techniques fail, the next step is operative intervention. Sialendoscopy offers a minimally invasive option for the diagnosis and management of chronic inflammatory disorders of the salivary glands and offers the option of gland and function preservation. In this article, we review some of the more common nonneoplastic disorders of the parotid gland, indications for diagnostic and interventional sialendoscopy, and operative techniques. Copyright © 2016 Elsevier Inc. All rights reserved.

Applications of data compression techniques in modal analysis for on-orbit system identification

NASA Technical Reports Server (NTRS)

Carlin, Robert A.; Saggio, Frank; Garcia, Ephrahim

1992-01-01

Data compression techniques have been investigated for use with modal analysis applications. A redundancy-reduction algorithm was used to compress frequency response functions (FRFs) in order to reduce the amount of disk space necessary to store the data and/or save time in processing it. Tests were performed for both single- and multiple-degree-of-freedom (SDOF and MDOF, respectively) systems, with varying amounts of noise. Analysis was done on both the compressed and uncompressed FRFs using an SDOF Nyquist curve fit as well as the Eigensystem Realization Algorithm. Significant savings were realized with minimal errors incurred by the compression process.

Spatial separation benefit for unaided and aided listening

PubMed Central

Ahlstrom, Jayne B.; Horwitz, Amy R.; Dubno, Judy R.

2013-01-01

Consonant recognition in noise was measured at a fixed signal-to-noise ratio as a function of low-pass-cutoff frequency and noise location in older adults fit with bilateral hearing aids. To quantify age-related differences, spatial benefit was assessed in younger and older adults with normal hearing. Spatial benefit was similar for all groups suggesting that older adults used interaural difference cues to improve speech recognition in noise equivalently to younger adults. Although amplification was sufficient to increase high-frequency audibility with spatial separation, hearing-aid benefit was minimal, suggesting that factors beyond simple audibility may be responsible for limited hearing-aid benefit. PMID:24121648

Regulation of C:N:P stoichiometry of microbes and soil organic matter by optimizing enzyme allocation: an omics-informed model study

NASA Astrophysics Data System (ADS)

Song, Y.; Yao, Q.; Wang, G.; Yang, X.; Mayes, M. A.

2017-12-01

Increasing evidences is indicating that soil organic matter (SOM) decomposition and stabilization process is a continuum process and controlled by both microbial functions and their interaction with minerals (known as the microbial efficiency-matrix stabilization theory (MEMS)). Our metagenomics analysis of soil samples from both P-deficit and P-fertilization sites in Panama has demonstrated that community-level enzyme functions could adapt to maximize the acquisition of limiting nutrients and minimize energy demand for foraging (known as the optimal foraging theory). This optimization scheme can mitigate the imbalance of C/P ratio between soil substrate and microbial community and relieve the P limitation on microbial carbon use efficiency over the time. Dynamic allocation of multiple enzyme groups and their interaction with microbial/substrate stoichiometry has rarely been considered in biogeochemical models due to the difficulties in identifying microbial functional groups and quantifying the change in enzyme expression in response to soil nutrient availability. This study aims to represent the omics-informed optimal foraging theory in the Continuum Microbial ENzyme Decomposition model (CoMEND), which was developed to represent the continuum SOM decomposition process following the MEMS theory. The SOM pools in the model are classified based on soil chemical composition (i.e. Carbohydrates, lignin, N-rich SOM and P-rich SOM) and the degree of SOM depolymerization. The enzyme functional groups for decomposition of each SOM pool and N/P mineralization are identified by the relative composition of gene copy numbers. The responses of microbial activities and SOM decomposition to nutrient availability are simulated by optimizing the allocation of enzyme functional groups following the optimal foraging theory. The modeled dynamic enzyme allocation in response to P availability is evaluated by the metagenomics data measured from P addition and P-deficit soil samples in Panama sites.The implementation of dynamic enzyme allocation in response to nutrient availability in the CoMEND model enables us to capture the varying microbial C/P ratio and soil carbon dynamics in response to shifting nutrient constraints over time in tropical soils.

The Transition to Minimal Consciousness through the Evolution of Associative Learning

PubMed Central

Bronfman, Zohar Z.; Ginsburg, Simona; Jablonka, Eva

2016-01-01

The minimal state of consciousness is sentience. This includes any phenomenal sensory experience – exteroceptive, such as vision and olfaction; interoceptive, such as pain and hunger; or proprioceptive, such as the sense of bodily position and movement. We propose unlimited associative learning (UAL) as the marker of the evolutionary transition to minimal consciousness (or sentience), its phylogenetically earliest sustainable manifestation and the driver of its evolution. We define and describe UAL at the behavioral and functional level and argue that the structural-anatomical implementations of this mode of learning in different taxa entail subjective feelings (sentience). We end with a discussion of the implications of our proposal for the distribution of consciousness in the animal kingdom, suggesting testable predictions, and revisiting the ongoing debate about the function of minimal consciousness in light of our approach. PMID:28066282

Interaction between graviception and carotid baroreflex function in humans during parabolic flight-induced microgravity.

PubMed

Ogoh, Shigehiko; Marais, Michaël; Lericollais, Romain; Denise, Pierre; Raven, Peter B; Normand, Hervé

2018-05-10

The aim of the present study was to assess carotid baroreflex (CBR) during acute changes in otolithic activity in humans. To address this question, we designed a set of experiments to identify the modulatory effects of microgravity on CBR function at a tilt angle of -2{degree sign}, which was identified to minimize changes in central blood volume during parabolic flight. During parabolic flight at 0g and 1g, CBR function curves were modelled from the heart rate (HR) and mean arterial pressure (MAP) responses to rapid pulse trains of neck pressure (NP) and neck suction (NS) ranging from +40 to -80 Torr; CBR control of HR (carotid-HR) and MAP (carotid-MAP) baroreflex function curves, respectively. The maximal gain (G max ) of both carotid-HR and carotid-MAP baroreflex function curves were augmented during microgravity compared to 1g (carotid-HR, -0.53 to -0.80 beats/min/mmHg, P<0.05; carotid-MAP, -0.24 to -0.30 mmHg/mmHg, P<0.05). These findings suggest that parabolic flight-induced acute change of otolithic activity may modify CBR function and identifies that the vestibular system contributes to blood pressure regulation under fluctuations in gravitational forces.

The magnitude of lost ecosystem structure and function in urban streams and the effectiveness of watershed-based management (Invited)

NASA Astrophysics Data System (ADS)

Smucker, N. J.; Detenbeck, N. E.; Kuhn, A.

2013-12-01

Watershed development is a leading cause of stream impairment and increasingly threatens the availability, quality, and sustainability of freshwater resources. In a recent global meta-analysis, we found that measures of desirable ecological structure (e.g., algal, macroinvertebrate, and fish communities) and functions (e.g., metabolism, nutrient uptake, and denitrification) in streams with developed watersheds were only 23% and 34%, respectively, of those in minimally disturbed reference streams. As humans continue to alter watersheds in response to growing and migrating populations, characterizing ecological responses to watershed development and management practices is urgently needed to inform future development practices, decisions, and policy. In a study of streams in New England, we found that measures of macroinvertebrate and algal communities had threshold responses between 1-10% and 1-5% impervious cover, respectively. Macroinvertebrate communities had decreases in sensitive taxa and predators occurring from 1-3.5% and transitions in trophic and habitat guilds from 4-9% impervious cover. Sensitive algal taxa declined at 1%, followed by increases in tolerant taxa at 3%. Substantially altered algal communities persisted above 5% impervious cover and were dominated by motile taxa (sediment resistant) and those with high nutrient demands. Boosted regression tree analysis showed that sites with >65% and ideally >80% forest and wetland cover in near-stream buffers were associated with a 13-34% decrease in the effects of watershed impervious cover on algal communities. While this reduction is substantial, additional out-of-stream management efforts are needed to protect and restore stream ecosystems (e.g., created wetlands and stormwater ponds), but understanding their effectiveness is greatly limited by sparse ecological monitoring. Our meta-analysis found that restoration improved ecological structure and functions in streams by 48% and 14%, respectively, when compared to streams with developed watersheds and no management practices in place. However, ecosystem measures at restored sites were still only 53% of those in minimally disturbed reference streams. Some of our ongoing work further examines how watershed development and riparian condition affect stream ecosystem functions by altering the sources and delivery of nutrients and carbon. Our results can help inform management priorities and expectations, and they emphasize the importance of implementing mindful development and protective actions in a watershed context, especially in watersheds near impervious cover thresholds. Continued research on linked terrestrial-aquatic systems, improved BMP tracking, and ongoing monitoring will be essential to conserving and restoring the mechanisms that sustain valued ecological attributes and ecosystem services of streams.

Minimization of the root of a quadratic functional under a system of affine equality constraints with application to portfolio management

NASA Astrophysics Data System (ADS)

Landsman, Zinoviy

2008-10-01

We present an explicit closed form solution of the problem of minimizing the root of a quadratic functional subject to a system of affine constraints. The result generalizes Z. Landsman, Minimization of the root of a quadratic functional under an affine equality constraint, J. Comput. Appl. Math. 2007, to appear, see , articles in press, where the optimization problem was solved under only one linear constraint. This is of interest for solving significant problems pertaining to financial economics as well as some classes of feasibility and optimization problems which frequently occur in tomography and other fields. The results are illustrated in the problem of optimal portfolio selection and the particular case when the expected return of finance portfolio is certain is discussed.

Design of a magnetic-tunnel-junction-oriented nonvolatile lookup table circuit with write-operation-minimized data shifting

NASA Astrophysics Data System (ADS)

Suzuki, Daisuke; Hanyu, Takahiro

2018-04-01

A magnetic-tunnel-junction (MTJ)-oriented nonvolatile lookup table (LUT) circuit, in which a low-power data-shift function is performed by minimizing the number of write operations in MTJ devices is proposed. The permutation of the configuration memory cell for read/write access is performed as opposed to conventional direct data shifting to minimize the number of write operations, which results in significant write energy savings in the data-shift function. Moreover, the hardware cost of the proposed LUT circuit is small since the selector is shared between read access and write access. In fact, the power consumption in the data-shift function and the transistor count are reduced by 82 and 52%, respectively, compared with those in a conventional static random-access memory-based implementation using a 90 nm CMOS technology.

Treatment response to sildenafil in men with erectile dysfunction relative to concomitant comorbidities and age.

PubMed

Goldstein, Irwin; Stecher, Vera; Carlsson, Martin

2017-03-01

To evaluate treatment response in men with erectile dysfunction (ED) and concomitant comorbidities. Data were pooled from 42 placebo-controlled, flexible-dose sildenafil trials. In most trials, the sildenafil dose was 50 mg, taken ~1 hour before sexual activity but not more than once daily, with adjustment to 100 or 25 mg as needed. The overall population (N=9413) was stratified by age (<45, 46-64, ≥65 years). Treatment response was defined as a minimal clinically important difference (MCID) from baseline in the International Index of Erectile Function-Erectile Function (IIEF-EF) domain score of >2, >5 and >7 for men with mild, moderate and severe ED at baseline, respectively, or an IIEF-EF domain score ≥26 (no ED) at end-point. In the overall population, treatment response using the IIEF-EF MCID definition was significantly greater (P<.0001) with sildenafil vs placebo in men with no comorbidity (77% vs 33%), cardiovascular disease/hypertension only (71% vs 27%), diabetes only (63% vs 24%) or depression only (78% vs 29%). Using an IIEF-EF score ≥26, treatment response was significantly greater (P<.0001) with sildenafil vs placebo in men with no comorbidity (49% vs 17%), cardiovascular disease/hypertension only (48% vs 12%), diabetes only (40% vs 12%) or depression only (60% vs 17%). With each definition, the treatment response for each age and comorbidity was significantly greater (P≤.0065) with sildenafil vs placebo. The treatment response was significantly greater with sildenafil vs placebo in men with ED and each comorbidity regardless of age. © 2017 John Wiley & Sons Ltd.

Antimicrobial Barrier of an in vitro Oral Epithelial Model

PubMed Central

Kimball, Janet R.; Nittayananta, Wipawee; Klausner, Mitchell; Chung, Whasun O.; Dale, Beverly A.

2008-01-01

Objective Oral epithelia function as a microbial barrier and are actively involved in recognizing and responding to bacteria. Our goal was to examine a tissue engineered model of buccal epithelium for its response to oral bacteria and proinflammatory cytokines and compare the tissue responses with those of a submerged monolayer cell culture. Design The tissue model was characterized for keratin and β-defensin expression. Altered expression of β-defensins was evaluated by RT-PCR after exposure of the apical surface to oral bacteria and after exposure to TNF-α in the medium. These were compared to the response in traditional submerged oral epithelial cell culture. Results The buccal model showed expression of differentiation specific keratin 13, hBD1 and hBD3 in the upper half of the tissue; hBD2 was not detected. hBD1 mRNA was constitutively expressed, while hBD2 mRNA increased 2-fold after exposure of the apical surface to three oral bacteria tested and hBD3 mRNA increased in response to the non-pathogenic bacteria tested. In contrast, hBD2 mRNA increased 3–600 fold in response to bacteria in submerged cell culture. HBD2 mRNA increased over 100 fold in response to TNF-α in the tissue model and 50 fold in submerged cell culture. Thus, the tissue model is capable of upregulating hBD2, however, the minimal response to bacteria suggests that the tissue has an effective antimicrobial barrier due to its morphology, differentiation, and defensin expression. Conclusions The oral mucosal model is differentiated, expresses hBD1 and hBD3, and has an intact surface with a functional antimicrobial barrier. PMID:16815238

A Prospective Randomized Study on Operative Treatment for Simple Distal Tibial Fractures-Minimally Invasive Plate Osteosynthesis Versus Minimal Open Reduction and Internal Fixation.

PubMed

Kim, Ji Wan; Kim, Hyun Uk; Oh, Chang-Wug; Kim, Joon-Woo; Park, Ki Chul

2018-01-01

To compare the radiologic and clinical results of minimally invasive plate osteosynthesis (MIPO) and minimal open reduction and internal fixation (ORIF) for simple distal tibial fractures. Randomized prospective study. Three level 1 trauma centers. Fifty-eight patients with simple and distal tibial fractures were randomized into a MIPO group (treatment with MIPO; n = 29) or a minimal group (treatment with minimal ORIF; n = 29). These numbers were designed to define the rate of soft tissue complication; therefore, validation of superiority in union time or determination of differences in rates of delayed union was limited in this study. Simple distal tibial fractures treated with MIPO or minimal ORIF. The clinical outcome measurements included operative time, radiation exposure time, and soft tissue complications. To evaluate a patient's function, the American Orthopedic Foot and Ankle Society ankle score (AOFAS) was used. Radiologic measurements included fracture alignment, delayed union, and union time. All patients acquired bone union without any secondary intervention. The mean union time was 17.4 weeks and 16.3 weeks in the MIPO and minimal groups, respectively. There was 1 case of delayed union and 1 case of superficial infection in each group. The radiation exposure time was shorter in the minimal group than in the MIPO group. Coronal angulation showed a difference between both groups. The American Orthopedic Foot and Ankle Society ankle scores were 86.0 and 86.7 in the MIPO and minimal groups, respectively. Minimal ORIF resulted in similar outcomes, with no increased rate of soft tissue problems compared to MIPO. Both MIPO and minimal ORIF have high union rates and good functional outcomes for simple distal tibial fractures. Minimal ORIF did not result in increased rates of infection and wound dehiscence. Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

[Possible changes in energy-minimizer mechanisms of locomotion due to chronic low back pain - a literature review].

PubMed

de Carvalho, Alberito Rodrigo; Andrade, Alexandro; Peyré-Tartaruga, Leonardo Alexandre

2015-01-01

One goal of the locomotion is to move the body in the space at the most economical way possible. However, little is known about the mechanical and energetic aspects of locomotion that are affected by low back pain. And in case of occurring some damage, little is known about how the mechanical and energetic characteristics of the locomotion are manifested in functional activities, especially with respect to the energy-minimizer mechanisms during locomotion. This study aimed: a) to describe the main energy-minimizer mechanisms of locomotion; b) to check if there are signs of damage on the mechanical and energetic characteristics of the locomotion due to chronic low back pain (CLBP) which may endanger the energy-minimizer mechanisms. This study is characterized as a narrative literature review. The main theory that explains the minimization of energy expenditure during the locomotion is the inverted pendulum mechanism, by which the energy-minimizer mechanism converts kinetic energy into potential energy of the center of mass and vice-versa during the step. This mechanism is strongly influenced by spatio-temporal gait (locomotion) parameters such as step length and preferred walking speed, which, in turn, may be severely altered in patients with chronic low back pain. However, much remains to be understood about the effects of chronic low back pain on the individual's ability to practice an economic locomotion, because functional impairment may compromise the mechanical and energetic characteristics of this type of gait, making it more costly. Thus, there are indications that such changes may compromise the functional energy-minimizer mechanisms. Copyright © 2014 Elsevier Editora Ltda. All rights reserved.

Distinct contributions of functional and deep neural network features to representational similarity of scenes in human brain and behavior

PubMed Central

Greene, Michelle R; Baldassano, Christopher; Fei-Fei, Li; Beck, Diane M; Baker, Chris I

2018-01-01

Inherent correlations between visual and semantic features in real-world scenes make it difficult to determine how different scene properties contribute to neural representations. Here, we assessed the contributions of multiple properties to scene representation by partitioning the variance explained in human behavioral and brain measurements by three feature models whose inter-correlations were minimized a priori through stimulus preselection. Behavioral assessments of scene similarity reflected unique contributions from a functional feature model indicating potential actions in scenes as well as high-level visual features from a deep neural network (DNN). In contrast, similarity of cortical responses in scene-selective areas was uniquely explained by mid- and high-level DNN features only, while an object label model did not contribute uniquely to either domain. The striking dissociation between functional and DNN features in their contribution to behavioral and brain representations of scenes indicates that scene-selective cortex represents only a subset of behaviorally relevant scene information. PMID:29513219

Process-based network decomposition reveals backbone motif structure

PubMed Central

Wang, Guanyu; Du, Chenghang; Chen, Hao; Simha, Rahul; Rong, Yongwu; Xiao, Yi; Zeng, Chen

2010-01-01

A central challenge in systems biology today is to understand the network of interactions among biomolecules and, especially, the organizing principles underlying such networks. Recent analysis of known networks has identified small motifs that occur ubiquitously, suggesting that larger networks might be constructed in the manner of electronic circuits by assembling groups of these smaller modules. Using a unique process-based approach to analyzing such networks, we show for two cell-cycle networks that each of these networks contains a giant backbone motif spanning all the network nodes that provides the main functional response. The backbone is in fact the smallest network capable of providing the desired functionality. Furthermore, the remaining edges in the network form smaller motifs whose role is to confer stability properties rather than provide function. The process-based approach used in the above analysis has additional benefits: It is scalable, analytic (resulting in a single analyzable expression that describes the behavior), and computationally efficient (all possible minimal networks for a biological process can be identified and enumerated). PMID:20498084

Distinct contributions of functional and deep neural network features to representational similarity of scenes in human brain and behavior.

PubMed

Groen, Iris Ia; Greene, Michelle R; Baldassano, Christopher; Fei-Fei, Li; Beck, Diane M; Baker, Chris I

2018-03-07

Inherent correlations between visual and semantic features in real-world scenes make it difficult to determine how different scene properties contribute to neural representations. Here, we assessed the contributions of multiple properties to scene representation by partitioning the variance explained in human behavioral and brain measurements by three feature models whose inter-correlations were minimized a priori through stimulus preselection. Behavioral assessments of scene similarity reflected unique contributions from a functional feature model indicating potential actions in scenes as well as high-level visual features from a deep neural network (DNN). In contrast, similarity of cortical responses in scene-selective areas was uniquely explained by mid- and high-level DNN features only, while an object label model did not contribute uniquely to either domain. The striking dissociation between functional and DNN features in their contribution to behavioral and brain representations of scenes indicates that scene-selective cortex represents only a subset of behaviorally relevant scene information.

[Effects of ß-alanine supplementation on athletic performance].

PubMed

Domínguez, Raúl; Hernández Lougedo, Juan; Maté-Muñoz, José Luis; Garnacho-Castaño, Manuel Vicente

2014-10-06

Carnosine, dipeptide formed by amino acids ß-alanine and L-histidine, has important physiological functions among which its antioxidant and related memory and learning. However, in connection with the exercise, the most important functions would be associated with muscle contractility, improving calcium sensitivity in muscle fibers, and the regulatory function of pH. Thus, it is proposed that carnosine is the major intracellular buffer, but could contribute to 7-10% in buffer or buffer capacity. Since carnosine synthesis seems to be limited by the availability of ß-alanine supplementation with this compound has been gaining increasing popularity among the athlete population. Therefore, the objective of this study literature review was to examine all those research works have shown the effect of ß-alanine supplementation on athletic performance. Moreover, it also has attempted to establish a specific dosage that maximizing the potential benefits, minimize paresthesia, the main side effect presented in response to supplementation. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Ebolavirus is evolving but not changing: No evidence for functional change in EBOV from 1976 to the 2014 outbreak.

PubMed

Olabode, Abayomi S; Jiang, Xiaowei; Robertson, David L; Lovell, Simon C

2015-08-01

The 2014 epidemic of Ebola virus disease (EVD) has had a devastating impact in West Africa. Sequencing of ebolavirus (EBOV) from infected individuals has revealed extensive genetic variation, leading to speculation that the virus may be adapting to humans, accounting for the scale of the 2014 outbreak. We computationally analyze the variation associated with all EVD outbreaks, and find none of the amino acid replacements lead to identifiable functional changes. These changes have minimal effect on protein structure, being neither stabilizing nor destabilizing, are not found in regions of the proteins associated with known functions and tend to cluster in poorly constrained regions of proteins, specifically intrinsically disordered regions. We find no evidence that the difference between the current and previous outbreaks is due to evolutionary changes associated with transmission to humans. Instead, epidemiological factors are likely to be responsible for the unprecedented spread of EVD. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

Neutron Multiplicity: LANL W Covariance Matrix for Curve Fitting

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

Wendelberger, James G.

2016-12-08

In neutron multiplicity counting one may fit a curve by minimizing an objective function, χmore » $$2\\atop{n}$$. The objective function includes the inverse of an n by n matrix of covariances, W. The inverse of the W matrix has a closed form solution. In addition W -1 is a tri-diagonal matrix. The closed form and tridiagonal nature allows for a simpler expression of the objective function χ$$2\\atop{n}$$. Minimization of this simpler expression will provide the optimal parameters for the fitted curve.« less

Branch and bound algorithm for accurate estimation of analytical isotropic bidirectional reflectance distribution function models.

PubMed

Yu, Chanki; Lee, Sang Wook

2016-05-20

We present a reliable and accurate global optimization framework for estimating parameters of isotropic analytical bidirectional reflectance distribution function (BRDF) models. This approach is based on a branch and bound strategy with linear programming and interval analysis. Conventional local optimization is often very inefficient for BRDF estimation since its fitting quality is highly dependent on initial guesses due to the nonlinearity of analytical BRDF models. The algorithm presented in this paper employs L₁-norm error minimization to estimate BRDF parameters in a globally optimal way and interval arithmetic to derive our feasibility problem and lower bounding function. Our method is developed for the Cook-Torrance model but with several normal distribution functions such as the Beckmann, Berry, and GGX functions. Experiments have been carried out to validate the presented method using 100 isotropic materials from the MERL BRDF database, and our experimental results demonstrate that the L₁-norm minimization provides a more accurate and reliable solution than the L₂-norm minimization.

Cyclo-oxygenase isozymes in mucosal ulcergenic and functional responses following barrier disruption in rat stomachs.

PubMed

Hirata, T; Ukawa, H; Yamakuni, H; Kato, S; Takeuchi, K

1997-10-01

1. We examined the effects of selective and nonselective cyclo-oxygenase (COX) inhibitors on various functional changes in the rat stomach induced by topical application of taurocholate (TC) and investigated the preferential role of COX isozymes in these responses. 2. Rat stomachs mounted in ex vivo chambers were perfused with 50 mM HCl and transmucosal potential difference (p.d.), mucosal blood flow (GMBF), luminal acid loss and luminal levels of prostaglandin E2 (PGE2) were measured before, during and after exposure to 20 mM TC. 3. Mucosal application of TC in control rats caused a reduction in p.d., followed by an increase of luminal acid loss and GMBF, and produced only minimal damage in the mucosa 2 h later. Pretreatment with indomethacin (10 mg kg[-1], s.c.), a nonselective COX-1 and COX-2 inhibitor, attenuated the gastric hyperaemic response caused by TC without affecting p.d. and acid loss, resulting in haemorrhagic lesions in the mucosa. In contrast, selective COX-2 inhibitors, such as NS-398 and nimesulide (10 mg kg[-1], s.c.), had no effect on any of the responses induced by TC and did not cause gross damage in the mucosa. 4. Luminal PGE2 levels were markedly increased during and after exposure to TC and this response was significantly inhibited by indomethacin but not by either NS-398 or nimesulide. The expression of COX-1-mRNA was consistently detected in the gastric mucosa before and after TC treatment, while a faint expression of COX-2-mRNA was detected only 2 h after TC treatment. 5. Both NS-398 and nimesulide significantly suppressed carrageenan-induced rat paw oedema, similar to indomethacin. 6. These results confirmed a mediator role for prostaglandins in the gastric hyperaemic response following TC-induced barrier disruption, and suggest that COX-1 but not COX-2 is a key enzyme in maintaining 'housekeeping' functions in the gastric mucosa under both normal and adverse conditions.

Vasorelaxation responses to insulin in laminar vessel rings from healthy, lean horses.

PubMed

Wooldridge, A A; Waguespack, R W; Schwartz, D D; Venugopal, C S; Eades, S C; Beadle, R E

2014-10-01

Hyperinsulinemia causes laminitis experimentally and is a risk factor for naturally occurring laminitis. The aim of this study was to investigate the effects of insulin on laminar vascular relaxation and to induce insulin-associated vascular dysfunction in vitro. Relaxation responses of isolated laminar arterial and venous rings to acetylcholine and insulin were evaluated. To alter vascular function in response to insulin, all vessel rings were incubated with insulin or vehicle, submaximally contracted, administered insulin again and relaxation responses recorded. Laminar arteries were also incubated with the mitogen-activated protein kinase (MAPK) inhibitor, PD-98059. Relaxation in response to acetylcholine was not different between arteries and veins, but veins relaxed less in response to insulin than arteries. In arteries incubated with insulin, the subsequent relaxation response to insulin was blunted. Veins had minimal relaxation to insulin regardless of incubation. Arteries incubated with PD-98059 relaxed more in response to insulin than arteries not exposed to PD-98059, indicating that MAPK plays a role in maintenance of basal tone in laminar arteries. A differing response of laminar veins and arteries to insulin-induced relaxation may be important in understanding the link between hyperinsulinemia and laminitis. In vitro induction of vascular dysfunction in response to insulin in laminar arteries may be useful for testing therapeutic interventions and for understanding the pathophysiology of laminitis. Copyright © 2014 Elsevier Ltd. All rights reserved.

[The present and future state of minimized extracorporeal circulation].

PubMed

Meng, Fan; Yang, Ming

2013-05-01

Minimized extracorporeal circulation improved in the postoperative side effects of conventional extracorporeal circulation is a kind of new extracorporeal circulation. This paper introduces the principle, characteristics, applications and related research of minimized extracorporeal circulation. For the problems of systemic inflammatory response syndrome and limited assist time, the article proposes three development direction including system miniaturization and integration, pulsatile blood pump and the adaptive control by human parameter identification.

Anatomic partial nephrectomy: technique evolution.

PubMed

Azhar, Raed A; Metcalfe, Charles; Gill, Inderbir S

2015-03-01

Partial nephrectomy provides equivalent long-term oncologic and superior functional outcomes as radical nephrectomy for T1a renal masses. Herein, we review the various vascular clamping techniques employed during minimally invasive partial nephrectomy, describe the evolution of our partial nephrectomy technique and provide an update on contemporary thinking about the impact of ischemia on renal function. Recently, partial nephrectomy surgical technique has shifted away from main artery clamping and towards minimizing/eliminating global renal ischemia during partial nephrectomy. Supported by high-fidelity three-dimensional imaging, novel anatomic-based partial nephrectomy techniques have recently been developed, wherein partial nephrectomy can now be performed with segmental, minimal or zero global ischemia to the renal remnant. Sequential innovations have included early unclamping, segmental clamping, super-selective clamping and now culminating in anatomic zero-ischemia surgery. By eliminating 'under-the-gun' time pressure of ischemia for the surgeon, these techniques allow an unhurried, tightly contoured tumour excision with point-specific sutured haemostasis. Recent data indicate that zero-ischemia partial nephrectomy may provide better functional outcomes by minimizing/eliminating global ischemia and preserving greater vascularized kidney volume. Contemporary partial nephrectomy includes a spectrum of surgical techniques ranging from conventional-clamped to novel zero-ischemia approaches. Technique selection should be tailored to each individual case on the basis of tumour characteristics, surgical feasibility, surgeon experience, patient demographics and baseline renal function.

Hybrid minimally invasive esophagectomy for cancer: impact on postoperative inflammatory and nutritional status.

PubMed

Scarpa, M; Cavallin, F; Saadeh, L M; Pinto, E; Alfieri, R; Cagol, M; Da Roit, A; Pizzolato, E; Noaro, G; Pozza, G; Castoro, C

2016-11-01

The purpose of this case-control study was to evaluate the impact of hybrid minimally invasive esophagectomy for cancer on surgical stress response and nutritional status. All 34 consecutive patients undergoing hybrid minimally invasive esophagectomy for cancer at our surgical unit between 2008 and 2013 were retrospectively compared with 34 patients undergoing esophagectomy with open gastric tubulization (open), matched for neoadjuvant therapy, pathological stage, gender and age. Demographic data, tumor features and postoperative course (including quality of life and systemic inflammatory and nutritional status) were compared. Postoperative course was similar in terms of complication rate. Length of stay in intensive care unit was shorter in patients undergoing hybrid minimally invasive esophagectomy (P = 0.002). In the first postoperative day, patients undergoing hybrid minimally invasive esophagectomy had lower C-reactive protein levels (P = 0.001) and white cell blood count (P = 0.05), and higher albumin serum level (P = 0.001). In this group, albumin remained higher also at third (P = 0.06) and seventh (P = 0.008) postoperative day, and C-reactive protein resulted lower at third post day (P = 0.04). Hybrid minimally invasive esophagectomy significantly improved the systemic inflammatory and catabolic response to surgical trauma, contributing to a shorter length of stay in intensive care unit. © 2015 International Society for Diseases of the Esophagus.

Functionalization of SiO2 Surfaces for Si Monolayer Doping with Minimal Carbon Contamination.

PubMed

van Druenen, Maart; Collins, Gillian; Glynn, Colm; O'Dwyer, Colm; Holmes, Justin D

2018-01-17

Monolayer doping (MLD) involves the functionalization of semiconductor surfaces followed by an annealing step to diffuse the dopant into the substrate. We report an alternative doping method, oxide-MLD, where ultrathin SiO 2 overlayers are functionalized with phosphonic acids for doping Si. Similar peak carrier concentrations were achieved when compared with hydrosilylated surfaces (∼2 × 10 20 atoms/cm 3 ). Oxide-MLD offers several advantages over conventional MLD, such as ease of sample processing, superior ambient stability, and minimal carbon contamination. The incorporation of an oxide layer minimizes carbon contamination by facilitating attachment of carbon-free precursors or by impeding carbon diffusion. The oxide-MLD strategy allows selection of many inexpensive precursors and therefore allows application to both p- and n-doping. The phosphonic acid-functionalized SiO 2 surfaces were investigated using X-ray photoelectron spectroscopy and attenuated total reflectance Fourier transform infrared spectroscopy, whereas doping was assessed using electrochemical capacitance voltage and Hall measurements.

Force and time-dependent self-assembly, disruption and recovery of supramolecular peptide amphiphile nanofibers

NASA Astrophysics Data System (ADS)

Begum Dikecoglu, F.; Topal, Ahmet E.; Ozkan, Alper D.; Deniz Tekin, E.; Tekinay, Ayse B.; Guler, Mustafa O.; Dana, Aykutlu

2018-07-01

Biological feedback mechanisms exert precise control over the initiation and termination of molecular self-assembly in response to environmental stimuli, while minimizing the formation and propagation of defects through self-repair processes. Peptide amphiphile (PA) molecules can self-assemble at physiological conditions to form supramolecular nanostructures that structurally and functionally resemble the nanofibrous proteins of the extracellular matrix, and their ability to reconfigure themselves in response to external stimuli is crucial for the design of intelligent biomaterials systems. Here, we investigated real-time self-assembly, deformation, and recovery of PA nanofibers in aqueous solution by using a force-stabilizing double-pass scanning atomic force microscopy imaging method to disrupt the self-assembled peptide nanofibers in a force-dependent manner. We demonstrate that nanofiber damage occurs at tip-sample interaction forces exceeding 1 nN, and the damaged fibers subsequently recover when the tip pressure is reduced. Nanofiber ends occasionally fail to reconnect following breakage and continue to grow as two individual nanofibers. Energy minimization calculations of nanofibers with increasing cross-sectional ellipticity (corresponding to varying levels of tip-induced fiber deformation) support our observations, with high-ellipticity nanofibers exhibiting lower stability compared to their non-deformed counterparts. Consequently, tip-mediated mechanical forces can provide an effective means of altering nanofiber integrity and visualizing the self-recovery of PA assemblies.

Force and time-dependent self-assembly, disruption and recovery of supramolecular peptide amphiphile nanofibers.

PubMed

Dikecoglu, F Begum; Topal, Ahmet E; Ozkan, Alper D; Tekin, E Deniz; Tekinay, Ayse B; Guler, Mustafa O; Dana, Aykutlu

2018-07-13

Biological feedback mechanisms exert precise control over the initiation and termination of molecular self-assembly in response to environmental stimuli, while minimizing the formation and propagation of defects through self-repair processes. Peptide amphiphile (PA) molecules can self-assemble at physiological conditions to form supramolecular nanostructures that structurally and functionally resemble the nanofibrous proteins of the extracellular matrix, and their ability to reconfigure themselves in response to external stimuli is crucial for the design of intelligent biomaterials systems. Here, we investigated real-time self-assembly, deformation, and recovery of PA nanofibers in aqueous solution by using a force-stabilizing double-pass scanning atomic force microscopy imaging method to disrupt the self-assembled peptide nanofibers in a force-dependent manner. We demonstrate that nanofiber damage occurs at tip-sample interaction forces exceeding 1 nN, and the damaged fibers subsequently recover when the tip pressure is reduced. Nanofiber ends occasionally fail to reconnect following breakage and continue to grow as two individual nanofibers. Energy minimization calculations of nanofibers with increasing cross-sectional ellipticity (corresponding to varying levels of tip-induced fiber deformation) support our observations, with high-ellipticity nanofibers exhibiting lower stability compared to their non-deformed counterparts. Consequently, tip-mediated mechanical forces can provide an effective means of altering nanofiber integrity and visualizing the self-recovery of PA assemblies.

General minimal surface solution for gravitational instantons

NASA Astrophysics Data System (ADS)

Aliev, A. N.; Kalaycı, J.; Nutku, Y.

1997-07-01

We construct the general instanton metric obtained from Weierstrass' general local solution for minimal surfaces using the correspondence between minimal surfaces in three-dimensional Euclidean space and gravitational instantons admitting two Killing vectors. The resulting metric contains one arbitrary analytic function and we show that it can be transformed to the Gibbons-Hawking form of an instanton metric that was reported earlier.

Minimally conscious state or cortically mediated state?

PubMed

Naccache, Lionel

2018-04-01

Durable impairments of consciousness are currently classified in three main neurological categories: comatose state, vegetative state (also recently coined unresponsive wakefulness syndrome) and minimally conscious state. While the introduction of minimally conscious state, in 2002, was a major progress to help clinicians recognize complex non-reflexive behaviours in the absence of functional communication, it raises several problems. The most important issue related to minimally conscious state lies in its criteria: while behavioural definition of minimally conscious state lacks any direct evidence of patient's conscious content or conscious state, it includes the adjective 'conscious'. I discuss this major problem in this review and propose a novel interpretation of minimally conscious state: its criteria do not inform us about the potential residual consciousness of patients, but they do inform us with certainty about the presence of a cortically mediated state. Based on this constructive criticism review, I suggest three proposals aiming at improving the way we describe the subjective and cognitive state of non-communicating patients. In particular, I present a tentative new classification of impairments of consciousness that combines behavioural evidence with functional brain imaging data, in order to probe directly and univocally residual conscious processes.

Modeling of biodynamic responses distributed at the fingers and the palm of the human hand-arm system.

PubMed

Dong, Ren G; Dong, Jennie H; Wu, John Z; Rakheja, Subhash

2007-01-01

The objective of this study is to develop analytical models for simulating driving-point biodynamic responses distributed at the fingers and palm of the hand under vibration along the forearm direction (z(h)-axis). Two different clamp-like model structures are formulated to analyze the distributed responses at the fingers-handle and palm-handle interfaces, as opposed to the single driving point invariably considered in the reported models. The parameters of the proposed four- and five degrees-of-freedom models are identified through minimization of an rms error function of the model and measured responses under different hand actions, namely, fingers pull, push only, grip only, and combined push and grip. The results show that the responses predicted from both models agree reasonably well with the measured data in terms of distributed as well total impedance magnitude and phase. The variations in the identified model parameters under different hand actions are further discussed in view of the biological system behavior. The proposed models are considered to serve as useful tools for design and assessment of vibration isolation methods, and for developing a hand-arm simulator for vibration analysis of power tools.

Genetic and Genomic Response to Selection for Food Consumption in Drosophila melanogaster.

PubMed

Garlapow, Megan E; Everett, Logan J; Zhou, Shanshan; Gearhart, Alexander W; Fay, Kairsten A; Huang, Wen; Morozova, Tatiana V; Arya, Gunjan H; Turlapati, Lavanya; St Armour, Genevieve; Hussain, Yasmeen N; McAdams, Sarah E; Fochler, Sophia; Mackay, Trudy F C

2017-03-01

Food consumption is an essential component of animal fitness; however, excessive food intake in humans increases risk for many diseases. The roles of neuroendocrine feedback loops, food sensing modalities, and physiological state in regulating food intake are well understood, but not the genetic basis underlying variation in food consumption. Here, we applied ten generations of artificial selection for high and low food consumption in replicate populations of Drosophila melanogaster. The phenotypic response to selection was highly asymmetric, with significant responses only for increased food consumption and minimal correlated responses in body mass and composition. We assessed the molecular correlates of selection responses by DNA and RNA sequencing of the selection lines. The high and low selection lines had variants with significantly divergent allele frequencies within or near 2081 genes and 3526 differentially expressed genes in one or both sexes. A total of 519 genes were both genetically divergent and differentially expressed between the divergent selection lines. We performed functional analyses of the effects of RNAi suppression of gene expression and induced mutations for 27 of these candidate genes that have human orthologs and the strongest statistical support, and confirmed that 25 (93 %) affected the mean and/or variance of food consumption.

An IRF-3-, IRF-5-, and IRF-7-Independent Pathway of Dengue Viral Resistance Utilizes IRF-1 to Stimulate Type I and II Interferon Responses.

PubMed

Carlin, Aaron F; Plummer, Emily M; Vizcarra, Edward A; Sheets, Nicholas; Joo, Yunichel; Tang, William; Day, Jeremy; Greenbaum, Jay; Glass, Christopher K; Diamond, Michael S; Shresta, Sujan

2017-11-07

Interferon-regulatory factors (IRFs) are a family of transcription factors (TFs) that translate viral recognition into antiviral responses, including type I interferon (IFN) production. Dengue virus (DENV) and other clinically important flaviviruses are suppressed by type I IFN. While mice lacking the type I IFN receptor (Ifnar1 -/- ) succumb to DENV infection, we found that mice deficient in three transcription factors controlling type I IFN production (Irf3 -/- Irf5 -/- Irf7 -/- triple knockout [TKO]) survive DENV challenge. DENV infection of TKO mice resulted in minimal type I IFN production but a robust type II IFN (IFN-γ) response. Using loss-of-function approaches for various molecules, we demonstrate that the IRF-3-, IRF-5-, IRF-7-independent pathway predominantly utilizes IFN-γ and, to a lesser degree, type I IFNs. This pathway signals via IRF-1 to stimulate interleukin-12 (IL-12) production and IFN-γ response. These results reveal a key antiviral role for IRF-1 by activating both type I and II IFN responses during DENV infection. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

On the convergence of nonconvex minimization methods for image recovery.

PubMed

Xiao, Jin; Ng, Michael Kwok-Po; Yang, Yu-Fei

2015-05-01

Nonconvex nonsmooth regularization method has been shown to be effective for restoring images with neat edges. Fast alternating minimization schemes have also been proposed and developed to solve the nonconvex nonsmooth minimization problem. The main contribution of this paper is to show the convergence of these alternating minimization schemes, based on the Kurdyka-Łojasiewicz property. In particular, we show that the iterates generated by the alternating minimization scheme, converges to a critical point of this nonconvex nonsmooth objective function. We also extend the analysis to nonconvex nonsmooth regularization model with box constraints, and obtain similar convergence results of the related minimization algorithm. Numerical examples are given to illustrate our convergence analysis.

A transformation method for constrained-function minimization

NASA Technical Reports Server (NTRS)

Park, S. K.

1975-01-01

A direct method for constrained-function minimization is discussed. The method involves the construction of an appropriate function mapping all of one finite dimensional space onto the region defined by the constraints. Functions which produce such a transformation are constructed for a variety of constraint regions including, for example, those arising from linear and quadratic inequalities and equalities. In addition, the computational performance of this method is studied in the situation where the Davidon-Fletcher-Powell algorithm is used to solve the resulting unconstrained problem. Good performance is demonstrated for 19 test problems by achieving rapid convergence to a solution from several widely separated starting points.

Approaching the basis set limit for DFT calculations using an environment-adapted minimal basis with perturbation theory: Formulation, proof of concept, and a pilot implementation

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

Mao, Yuezhi; Horn, Paul R.; Mardirossian, Narbe

2016-07-28

Recently developed density functionals have good accuracy for both thermochemistry (TC) and non-covalent interactions (NC) if very large atomic orbital basis sets are used. To approach the basis set limit with potentially lower computational cost, a new self-consistent field (SCF) scheme is presented that employs minimal adaptive basis (MAB) functions. The MAB functions are optimized on each atomic site by minimizing a surrogate function. High accuracy is obtained by applying a perturbative correction (PC) to the MAB calculation, similar to dual basis approaches. Compared to exact SCF results, using this MAB-SCF (PC) approach with the same large target basis set producesmore » <0.15 kcal/mol root-mean-square deviations for most of the tested TC datasets, and <0.1 kcal/mol for most of the NC datasets. The performance of density functionals near the basis set limit can be even better reproduced. With further improvement to its implementation, MAB-SCF (PC) is a promising lower-cost substitute for conventional large-basis calculations as a method to approach the basis set limit of modern density functionals.« less

DMN Operational Synchrony Relates to Self-Consciousness: Evidence from Patients in Vegetative and Minimally Conscious States.

PubMed

Fingelkurts, Andrew A; Fingelkurts, Alexander A; Bagnato, Sergio; Boccagni, Cristina; Galardi, Giuseppe

2012-01-01

The default mode network (DMN) has been consistently activated across a wide variety of self-related tasks, leading to a proposal of the DMN's role in self-related processing. Indeed, there is limited fMRI evidence that the functional connectivity within the DMN may underlie a phenomenon referred to as self-awareness. At the same time, none of the known studies have explicitly investigated neuronal functional interactions among brain areas that comprise the DMN as a function of self-consciousness loss. To fill this gap, EEG operational synchrony analysis [1, 2] was performed in patients with severe brain injuries in vegetative and minimally conscious states to study the strength of DMN operational synchrony as a function of self-consciousness expression. We demonstrated that the strength of DMN EEG operational synchrony was smallest or even absent in patients in vegetative state, intermediate in patients in minimally conscious state and highest in healthy fully self-conscious subjects. At the same time the process of ecoupling of operations performed by neuronal assemblies that comprise the DMN was highest in patients in vegetative state, intermediate in patients in minimally conscious state and minimal in healthy fully self-conscious subjects. The DMN's frontal EEG operational module had the strongest decrease in operational synchrony strength as a function of selfconsciousness loss, when compared with the DMN's posterior modules. Based on these results it is suggested that the strength of DMN functional connectivity could mediate the strength of self-consciousness expression. The observed alterations similarly occurred across EEG alpha, beta1 and beta2 frequency oscillations. Presented results suggest that the EEG operational synchrony within DMN may provide an objective and accurate measure for the assessment of signs of self-(un)consciousness in these challenging patient populations. This method therefore, may complement the current diagnostic procedures for patients with severe brain injuries and, hence, the planning of a rational rehabilitation intervention.

DMN Operational Synchrony Relates to Self-Consciousness: Evidence from Patients in Vegetative and Minimally Conscious States

PubMed Central

Fingelkurts, Andrew A; Fingelkurts, Alexander A; Bagnato, Sergio; Boccagni, Cristina; Galardi, Giuseppe

2012-01-01

The default mode network (DMN) has been consistently activated across a wide variety of self-related tasks, leading to a proposal of the DMN’s role in self-related processing. Indeed, there is limited fMRI evidence that the functional connectivity within the DMN may underlie a phenomenon referred to as self-awareness. At the same time, none of the known studies have explicitly investigated neuronal functional interactions among brain areas that comprise the DMN as a function of self-consciousness loss. To fill this gap, EEG operational synchrony analysis [1, 2] was performed in patients with severe brain injuries in vegetative and minimally conscious states to study the strength of DMN operational synchrony as a function of self-consciousness expression. We demonstrated that the strength of DMN EEG operational synchrony was smallest or even absent in patients in vegetative state, intermediate in patients in minimally conscious state and highest in healthy fully self-conscious subjects. At the same time the process of ecoupling of operations performed by neuronal assemblies that comprise the DMN was highest in patients in vegetative state, intermediate in patients in minimally conscious state and minimal in healthy fully self-conscious subjects. The DMN’s frontal EEG operational module had the strongest decrease in operational synchrony strength as a function of selfconsciousness loss, when compared with the DMN’s posterior modules. Based on these results it is suggested that the strength of DMN functional connectivity could mediate the strength of self-consciousness expression. The observed alterations similarly occurred across EEG alpha, beta1 and beta2 frequency oscillations. Presented results suggest that the EEG operational synchrony within DMN may provide an objective and accurate measure for the assessment of signs of self-(un)consciousness in these challenging patient populations. This method therefore, may complement the current diagnostic procedures for patients with severe brain injuries and, hence, the planning of a rational rehabilitation intervention. PMID:22905075

[The application of cortical and subcortical stimulation threshold in identifying the motor pathway and guiding the resection of gliomas in the functional areas].

PubMed

Ren, X H; Yang, X C; Huang, W; Yang, K Y; Liu, L; Qiao, H; Guo, L J; Cui, Y; Lin, S

2018-03-06

Objective: This study aimed to analyze the application of cortical and subcortical stimulation threshold in identifying the motor pathway and guiding the resection of gliomas in the functional area, and to illustrate the minimal safe threshold by ROC method. Methods: Fifty-seven patients with gliomas in the functional areas were enrolled in the study at Beijing Tiantan Hospital from 2015 to 2017. Anesthesia was maintained intravenously with propofol 10% and remifentanil. Throughout the resection process, cortical or subcortical stimulation threshold was determined along tumor border using monopolar or bipolar electrodes. The motor pathway was identified and protected from resection according to the stimulation threshold and transcranial MEPs. Minimal threshold in each case was recorded. Results: Total resection was achieved in 32 cases(56.1%), sub-total resection in 22 cases(38.6%), and partial resection in 3 cases(5.3%). Pre-operative motor disability was found in 9 cases. Compared with pre-operative motor scores, 19 exhibited impaired motor functions on day 1 after surgery, 5 had quick recovery by day 7 after surgery, and 7 had late recovery by 3 months after surgery. At 3 months, 7 still had impaired motor function. The frequency of intraoperative seizure was 1.8%(1/57). No other side effect was found during electronic monitoring in the operation. The ROC curve revealed that the minimal safe monopolar subcortical threshold was 5.70 mA for strength deterioration on day 1 and day 7 after surgery. Univariate analysis revealed that decreased transcranial MEPs and minimal subcortical threshold ≤5.7 mA were correlated with postoperative strength deterioration. Conclusions: Cortical and subcortical stimulation threshold has its merit in identifying the motor pathway and guiding the resection for tumors within the functional areas. 5.7 mA can be used as the minimal safe threshold to protect the motor pathway from injury.

Development and evaluation of devices designed to minimize deer-vehicle collisions : phase II.

DOT National Transportation Integrated Search

2010-12-01

We evaluated behavioral responses of captive white-tailed deer to visual and physical barriers designed to minimize deer-vehicle collisions, determined effects of exclusion fencing on movements of free-ranging deer, and further tested the visual capa...

The re-emergence of the minimal running shoe.

PubMed

Davis, Irene S

2014-10-01

The running shoe has gone through significant changes since its inception. The purpose of this paper is to review these changes, the majority of which have occurred over the past 50 years. Running footwear began as very minimal, then evolved to become highly cushioned and supportive. However, over the past 5 years, there has been a reversal of this trend, with runners seeking more minimal shoes that allow their feet more natural motion. This abrupt shift toward footwear without cushioning and support has led to reports of injuries associated with minimal footwear. In response to this, the running footwear industry shifted again toward the development of lightweight, partial minimal shoes that offer some support and cushioning. In this paper, studies comparing the mechanics between running in minimal, partial minimal, and traditional shoes are reviewed. The implications for injuries in all 3 conditions are examined. The use of minimal footwear in other populations besides runners is discussed. Finally, areas for future research into minimal footwear are suggested.

Inferring neural activity from BOLD signals through nonlinear optimization.

PubMed

Vakorin, Vasily A; Krakovska, Olga O; Borowsky, Ron; Sarty, Gordon E

2007-11-01

The blood oxygen level-dependent (BOLD) fMRI signal does not measure neuronal activity directly. This fact is a key concern for interpreting functional imaging data based on BOLD. Mathematical models describing the path from neural activity to the BOLD response allow us to numerically solve the inverse problem of estimating the timing and amplitude of the neuronal activity underlying the BOLD signal. In fact, these models can be viewed as an advanced substitute for the impulse response function. In this work, the issue of estimating the dynamics of neuronal activity from the observed BOLD signal is considered within the framework of optimization problems. The model is based on the extended "balloon" model and describes the conversion of neuronal signals into the BOLD response through the transitional dynamics of the blood flow-inducing signal, cerebral blood flow, cerebral blood volume and deoxyhemoglobin concentration. Global optimization techniques are applied to find a control input (the neuronal activity and/or the biophysical parameters in the model) that causes the system to follow an admissible solution to minimize discrepancy between model and experimental data. As an alternative to a local linearization (LL) filtering scheme, the optimization method escapes the linearization of the transition system and provides a possibility to search for the global optimum, avoiding spurious local minima. We have found that the dynamics of the neural signals and the physiological variables as well as the biophysical parameters can be robustly reconstructed from the BOLD responses. Furthermore, it is shown that spiking off/on dynamics of the neural activity is the natural mathematical solution of the model. Incorporating, in addition, the expansion of the neural input by smooth basis functions, representing a low-pass filtering, allows us to model local field potential (LFP) solutions instead of spiking solutions.

Passive Gust Alleviation for a Flying Wing Aircraft

DTIC Science & Technology

2013-01-10

250 Poisson ratio - 0.3 Density g/cm 3 ρ 1.57 Ply thickness mm t 0.131 Fibre volume % Vf 57.7 Once the material was chosen, the initial...high aspect ratio in flying wing configuration. It is aimed at minimizing the gust response of the aircraft by using the PGAD integrated at the wing... ratio in flying wing configuration. It is aimed at minimizing the gust response of the aircraft by using the PGAD integrated at the wing tip. The

A physical function test for use in the intensive care unit: validity, responsiveness, and predictive utility of the physical function ICU test (scored).

PubMed

Denehy, Linda; de Morton, Natalie A; Skinner, Elizabeth H; Edbrooke, Lara; Haines, Kimberley; Warrillow, Stephen; Berney, Sue

2013-12-01

Several tests have recently been developed to measure changes in patient strength and functional outcomes in the intensive care unit (ICU). The original Physical Function ICU Test (PFIT) demonstrates reliability and sensitivity. The aims of this study were to further develop the original PFIT, to derive an interval score (the PFIT-s), and to test the clinimetric properties of the PFIT-s. A nested cohort study was conducted. One hundred forty-four and 116 participants performed the PFIT at ICU admission and discharge, respectively. Original test components were modified using principal component analysis. Rasch analysis examined the unidimensionality of the PFIT, and an interval score was derived. Correlations tested validity, and multiple regression analyses investigated predictive ability. Responsiveness was assessed using the effect size index (ESI), and the minimal clinically important difference (MCID) was calculated. The shoulder lift component was removed. Unidimensionality of combined admission and discharge PFIT-s scores was confirmed. The PFIT-s displayed moderate convergent validity with the Timed "Up & Go" Test (r=-.60), the Six-Minute Walk Test (r=.41), and the Medical Research Council (MRC) sum score (rho=.49). The ESI of the PFIT-s was 0.82, and the MCID was 1.5 points (interval scale range=0-10). A higher admission PFIT-s score was predictive of: an MRC score of ≥48, increased likelihood of discharge home, reduced likelihood of discharge to inpatient rehabilitation, and reduced acute care hospital length of stay. Scoring of sit-to-stand assistance required is subjective, and cadence cutpoints used may not be generalizable. The PFIT-s is a safe and inexpensive test of physical function with high clinical utility. It is valid, responsive to change, and predictive of key outcomes. It is recommended that the PFIT-s be adopted to test physical function in the ICU.

Optical properties of intact leaves for estimating chlorophyll concentration

NASA Technical Reports Server (NTRS)

Carter, Gregory A.; Spiering, Bruce A.

2002-01-01

Changes in leaf chlorophyll content can serve as relative indicators of plant vigor and environmental quality. This study identified reflectance, transmittance, and absorptance wavebands and band ratios within the 400- to 850-nm range for intact leaves that could be used to estimate extracted leaf chlorophyll per unit leaf area (areal concentration) with minimal error. Leaf optical properties along with chlorophyll a, b, and a + b concentrations were measured for the planar-leaved sweetgum (Liquidambar styraciflua L.), red maple (Acer rubrum L.), wild grape (Vitis rotundifolia Michx.), and switchcane [Arundinaria gigantea (Walter) Muhl.], and for needles of longleaf pine (Pinus palustris Miller). Generally, reflectance, transmittance, and absorptance corresponded most precisely with chlorophyll concentrations at wavelengths near 700 nm, although regressions were also strong in the 550- to 625-nm range. A power function was superior to a simple linear function in yielding low standard deviations of the estimate (s). When data were combined among the planar-leaved species, s values were low at approximately 50 mumol/m2 out of a 940 mumol/m2 range in chlorophyll a + b at best-fit wavelengths of 707 to 709 nm. Minimal s values for chlorophyll a + b ranged from 32 to 62 mumol/m2 across species when band ratios having numerator wavelengths of 693 to 720 nm were used with the application of a power function. Optimal denominator wavelengths for the band ratios were 850 nm for reflectance and transmittance and 400 nm for absorptance. This information can be applied in designing field portable chlorophyll meters and in the landscape-scale remote sensing of plant responses to the environment.

Two Hymenophyllaceae species from contrasting natural environments exhibit a homoiochlorophyllous strategy in response to desiccation stress.

PubMed

Flores-Bavestrello, Alejandra; Król, Marianna; Ivanov, Alexander G; Hüner, Norman P A; García-Plazaola, José Ignacio; Corcuera, Luis J; Bravo, León A

2016-02-01

Hymenophyllaceae is a desiccation tolerant family of Pteridophytes which are poikilohydric epiphytes. Their fronds are composed by a single layer of cells and lack true mesophyll cells and stomata. Although they are associated with humid and shady environments, their vertical distribution varies along the trunk of the host plant with some species inhabiting the drier sides with a higher irradiance. The aim of this work was to compare the structure and function of the photosynthetic apparatus during desiccation and rehydration in two species, Hymenophyllum dentatum and Hymenoglossum cruentum, isolated from a contrasting vertical distribution along the trunk of their hosts. Both species were subjected to desiccation and rehydration kinetics to analyze frond phenotypic plasticity, as well as the structure, composition and function of the photosynthetic apparatus. Minimal differences in photosynthetic pigments were observed upon dehydration. Measurements of ϕPSII (effective quantum yield of PSII), ϕNPQ (quantum yield of the regulated energy dissipation of PSII), ϕNO (quantum yield of non-regulated energy dissipation of PSII), and TL (thermoluminescence) indicate that both species convert a functional photochemical apparatus into a structure which exhibits maximum quenching capacity in the dehydrated state with minimal changes in photosynthetic pigments and polypeptide compositions. This dehydration-induced conversion in the photosynthetic apparatus is completely reversible upon rehydration. We conclude that H. dentatum and H. cruentum are homoiochlorophyllous with respect to desiccation stress and exhibited no correlation between inherent desiccation tolerance and the vertical distribution along the host tree trunk. Copyright © 2015 Elsevier GmbH. All rights reserved.

Evaluation of functionality and biological response of the multilayer flow modulator in porcine animal models.

PubMed

Sultan, Sherif; Kavanagh, Edel P; Hynes, Niamh; Diethrich, Edward B

2016-02-01

This study outlines the use of non-aneurysmal porcine animal models to study device functionality and biological response of the Multilayer Flow Modulator (MFM) (Cardiatis, Isnes, Belgium), with an emphasis on preclinical device functionality and biological response characteristics in an otherwise healthy aorta. Twelve animals were implanted with the study device in the abdominal aorta, in 6 animals for 1 month and 6 animals for 6 months. Upon completion of the study period, each animal underwent a necropsy to examine how the implanted device had affected the artery and surrounding tissue. Neointima and stenosis formation were recorded via morphometry, and endothelialization via histopathological analysis. The MFM devices were delivered to their respective implantation sites without difficulty. Six of the implanted stents were oversized with percentages ranging from 2.6% to 18.8%. Statistical analysis was carried out and showed no significance between the regular sized stent group and oversized stent group for neointimal area (P=0.17), neointimal thickness (P=0.17), and percentage area stenosis (P=0.65). Histopathological findings showed in most areas flattened endothelium like cells lined the luminal surface of the neointima. Scanning electron microscopy also showed the devices were well tolerated, inciting only a minimal neointimal covering and little fibrin or platelet deposition. Neointimal thickness of 239.7±55.6 μm and 318.3±130.4 μm, and percentage area stenosis of 9.6±2.6% and 12.6±5% were recorded at 1 and 6 months respectively. No statistical differences were found between these results. The MFM devices were delivered to their respective implantation sites without difficulty and incited little neointimal and stenosis formation in the aorta, affirming its functionality and biocompatibility.

Vegetative state is a pejorative term.

PubMed

Machado, Calixto; Estévez, Mario; Carrick, Frederick R; Rodríguez, Rafael; Pérez-Nellar, Jesús; Chinchilla, Mauricio; Machado, Yanín; Pérez-Hoz, Grisel; Carballo, Maylén; Fleitas, Marcia; Pando, Alejandro

2012-01-01

The term persistent vegetative state (PVS) refers to the only circumstance in which an apparent dissociation of both components of consciousness is found, characterized by preservation of wakefulness with an apparent loss of awareness. Several authors have recently demonstrated by functional neuroimaging studies that a small subset of unresponsive "vegetative" patients may show unambiguous signs of consciousness and command following that is inaccessible to clinical examination at the bedside. The term "estado vegetativo" used in Spanish to describe the PVS syndrome by physicians came from the English-Spanish translation. The Spanish term "vegetativo" is related to unconscious vital functions, and "vegetal" is relative to plants. According to our experience, when a physician informs to patients' relatives that his/her family member's diagnosis is a "estado vegetativo", they understand the he/she is no more a human being, that there is no hope of recovery. The European Task Force on Disorders of Consciousness has recently proposed a new term, unresponsive wakefulness syndrome (UWS), to assist society in avoiding the depreciatory term vegetative state. Our group has embraced the use of the new term UWS and might suggest that we change our concept and use of the term MCS to minimally responsive wakefulness state (MRWS), or minimally aware wakefulness state (MAWS). Medical terms must be current and avoid any pejorative description of patients, which will promote our abilities to serve humankind and challenge neuroscientists to offer society new and realistic hopes for neurorehabilitation.

Input Shaping to Reduce Solar Array Structural Vibrations

NASA Technical Reports Server (NTRS)

Doherty, Michael J.; Tolson, Robert J.

1998-01-01

Structural vibrations induced by actuators can be minimized using input shaping. Input shaping is a feedforward method in which actuator commands are convolved with shaping functions to yield a shaped set of commands. These commands are designed to perform the maneuver while minimizing the residual structural vibration. In this report, input shaping is extended to stepper motor actuators. As a demonstration, an input-shaping technique based on pole-zero cancellation was used to modify the Solar Array Drive Assembly (SADA) actuator commands for the Lewis satellite. A series of impulses were calculated as the ideal SADA output for vibration control. These impulses were then discretized for use by the SADA stepper motor actuator and simulated actuator outputs were used to calculate the structural response. The effectiveness of input shaping is limited by the accuracy of the knowledge of the modal frequencies. Assuming perfect knowledge resulted in significant vibration reduction. Errors of 10% in the modal frequencies caused notably higher levels of vibration. Controller robustness was improved by incorporating additional zeros in the shaping function. The additional zeros did not require increased performance from the actuator. Despite the identification errors, the resulting feedforward controller reduced residual vibrations to the level of the exactly modeled input shaper and well below the baseline cases. These results could be easily applied to many other vibration-sensitive applications involving stepper motor actuators.

Aortic root dynamics and surgery: from craft to science.

PubMed

Cheng, Allen; Dagum, Paul; Miller, D Craig

2007-08-29

Since the fifteenth century beginning with Leonardo da Vinci's studies, the precise structure and functional dynamics of the aortic root throughout the cardiac cycle continues to elude investigators. The last five decades of experimental work have contributed substantially to our current understanding of aortic root dynamics. In this article, we review and summarize the relevant structural analyses, using radiopaque markers and sonomicrometric crystals, concerning aortic root three-dimensional deformations and describe aortic root dynamics in detail throughout the cardiac cycle. We then compare data between different studies and discuss the mechanisms responsible for the modes of aortic root deformation, including the haemodynamics, anatomical and temporal determinants of those deformations. These modes of aortic root deformation are closely coupled to maximize ejection, optimize transvalvular ejection haemodynamics and-perhaps most importantly-reduce stress on the aortic valve cusps by optimal diastolic load sharing and minimizing transvalvular turbulence throughout the cardiac cycle. This more comprehensive understanding of aortic root mechanics and physiology will contribute to improved medical and surgical treatment methods, enhanced therapeutic decision making and better post-intervention care of patients. With a better understanding of aortic root physiology, future research on aortic valve repair and replacement should take into account the integrated structural and functional asymmetry of aortic root dynamics to minimize stress on the aortic cusps in order to prevent premature structural valve deterioration.

Prediction of dynamic behavior of mutant strains from limited wild-type data.

PubMed

Song, Hyun-Seob; Ramkrishna, Doraiswami

2012-03-01

Metabolic engineering is the field of introducing genetic changes in organisms so as to modify their function towards synthesizing new products of high impact to society. However, engineered cells frequently have impaired growth rates thus seriously limiting the rate at which such products are made. The problem is attributable to inadequate understanding of how a metabolic network functions in a dynamic sense. Predictions of mutant strain behavior in the past have been based on steady state theories such as flux balance analysis (FBA), minimization of metabolic adjustment (MOMA), and regulatory on/off minimization (ROOM). Such predictions are restricted to product yields and cannot address productivity, which is of focal interest to applications. We demonstrate that our framework ( [Song and Ramkrishna, 2010] and [Song and Ramkrishna, 2011]), based on a “cybernetic” view of metabolic systems, makes predictions of the dynamic behavior of mutant strains of Escherichia coli from a limited amount of data obtained from the wild-type. Dynamic frameworks must necessarily address the issue of metabolic regulation, which the cybernetic approach does by postulating that metabolism is an optimal dynamic response of the organism to the environment in driving reactions towards ensuring survival. The predictions made in this paper are without parallel in the literature and lay the foundation for rational metabolic engineering. Copyright © 2012 Elsevier Inc. All rights reserved.

The functional interaction between abaecin and pore-forming peptides indicates a general mechanism of antibacterial potentiation.

PubMed

Rahnamaeian, Mohammad; Cytryńska, Małgorzata; Zdybicka-Barabas, Agnieszka; Vilcinskas, Andreas

2016-04-01

Long-chain proline-rich antimicrobial peptides such as bumblebee abaecin show minimal activity against Gram-negative bacteria despite binding efficiently to specific intracellular targets. We recently reported that bumblebee abaecin interacts with Escherichia coli DnaK but shows negligible antibacterial activity unless it is combined with sublethal doses of the pore-forming peptide hymenoptaecin. These two bumblebee peptides are co-expressed in vivo in response to a bacterial challenge. Here we investigated whether abaecin interacts similarly with pore-forming peptides from other organisms by replacing hymenoptaecin with sublethal concentrations of cecropin A (0.3 μM) or stomoxyn (0.05 μM). We found that abaecin increased the membrane permeabilization effects of both peptides, confirming that it can reduce the minimal inhibitory concentrations of pore-forming peptides from other species. We also used atomic force microscopy to show that 20 μM abaecin combined with sublethal concentrations of cecropin A or stomoxyn causes profound structural changes to the bacterial cell surface. Our data indicate that the potentiating functional interaction between abaecin and pore-forming peptides is not restricted to specific co-expressed peptides from the same species but is likely to be a general mechanism. Combination therapies based on diverse insect-derived peptides could therefore be used to tackle bacteria that are recalcitrant to current antibiotics. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Scallop-Inspired DNA Nanomachine: A Ratiometric Nanothermometer for Intracellular Temperature Sensing.

PubMed

Xie, Nuli; Huang, Jin; Yang, Xiaohai; He, Xiaoxiao; Liu, Jianbo; Huang, Jiaqi; Fang, Hongmei; Wang, Kemin

2017-11-21

Accurate measurement of intracellular temperature is of great significance in biology and medicine. With use of DNA nanotechnology and inspiration by nature's examples of "protective and reversible responses" exoskeletons, a scallop-inspired DNA nanomachine (SDN) is desgined as a ratiometric nanothermometer for intracellular temperature sensing. The SDN is composed of a rigid DNA tetrahedron, where a thermal-sensitive molecular beacon (MB) is embedded in one edge of the DNA tetrahedron. Relying on the thermal-sensitive MB and fluorescence resonance energy transfer (FRET) signaling mechanism, the "On" to "Off" signal is reversibly responding to "below" and "over" the melting temperature. Mimicking the functional anatomy of a scallop, the SDN exhibits high cellular permeability and resistance to enzymatic degradation, good reversibility, and tunable response range. Furthermore, FRET ratiometric signal that allows the simultaneous recording of two emission intensities at different wavelengths can provide a feasible approach for precise detection, minimizing the effect of system fluctuations.

Scaling of membrane-type locally resonant acoustic metamaterial arrays.

PubMed

Naify, Christina J; Chang, Chia-Ming; McKnight, Geoffrey; Nutt, Steven R

2012-10-01

Metamaterials have emerged as promising solutions for manipulation of sound waves in a variety of applications. Locally resonant acoustic materials (LRAM) decrease sound transmission by 500% over acoustic mass law predictions at peak transmission loss (TL) frequencies with minimal added mass, making them appealing for weight-critical applications such as aerospace structures. In this study, potential issues associated with scale-up of the structure are addressed. TL of single-celled and multi-celled LRAM was measured using an impedance tube setup with systematic variation in geometric parameters to understand the effects of each parameter on acoustic response. Finite element analysis was performed to predict TL as a function of frequency for structures with varying complexity, including stacked structures and multi-celled arrays. Dynamic response of the array structures under discrete frequency excitation was investigated using laser vibrometry to verify negative dynamic mass behavior.

Non-Invasive Tension Measurement Devices for Parachute Cordage

NASA Technical Reports Server (NTRS)

Litteken, Douglas A.; Daum, Jared S.

2016-01-01

The need for lightweight and non-intrusive tension measurements has arisen alongside the development of high-fidelity computer models of textile and fluid dynamics. In order to validate these computer models, data must be gathered in the operational environment without altering the design, construction, or performance of the test article. Current measurement device designs rely on severing a cord and breaking the load path to introduce a load cell. These load cells are very reliable, but introduce an area of high stiffness in the load path, directly affecting the structural response, adding excessive weight, and possibly altering the dynamics of the parachute during a test. To capture the required data for analysis validation without affecting the response of the system, non-invasive measurement devices have been developed and tested by NASA. These tension measurement devices offer minimal impact to the mass, form, fit, and function of the test article, while providing reliable, axial tension measurements for parachute cordage.

A Global Framework for Monitoring Phenological Responses to Climate Change

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

White, Michael A; Hoffman, Forrest M; Hargrove, William Walter

2005-01-01

Remote sensing of vegetation phenology is an important method with which to monitor terrestrial responses to climate change, but most approaches include signals from multiple forcings, such as mixed phenological signals from multiple biomes, urbanization, political changes, shifts in agricultural practices, and disturbances. Consequently, it is difficult to extract a clear signal from the usually assumed forcing: climate change. Here, using global 8 km 1982 to 1999 Normalized Difference Vegetation Index (NDVI) data and an eight-element monthly climatology, we identified pixels whose wavelet power spectrum was consistently dominated by annual cycles and then created phenologically and climatically self-similar clusters, whichmore » we term phenoregions. We then ranked and screened each phenoregion as a function of landcover homogeneity and consistency, evidence of human impacts, and political diversity. Remaining phenoregions represented areas with a minimized probability of non-climatic forcings and form elemental units for long-term phenological monitoring.« less

Binding of hepatitis A virus to its cellular receptor 1 inhibits T-regulatory cell functions in humans.

PubMed

Manangeeswaran, Mohanraj; Jacques, Jérôme; Tami, Cecilia; Konduru, Krishnamurthy; Amharref, Nadia; Perrella, Oreste; Casasnovas, Jose M; Umetsu, Dale T; Dekruyff, Rosemarie H; Freeman, Gordon J; Perrella, Alessandro; Kaplan, Gerardo G

2012-06-01

CD4+ T-regulatory (Treg) cells suppress immune responses and control self-tolerance and immunity to pathogens, cancer, and alloantigens. Most pathogens activate Treg cells to minimize immune-mediated tissue damage and prevent clearance, which promotes chronic infections. However, hepatitis A virus (HAV) temporarily inhibits Treg-cell functions. We investigated whether the interaction of HAV with its cellular receptor 1 (HAVCR1), a T-cell co-stimulatory molecule, inhibits the function of Treg cells to control HAV infection. We studied the effects of HAV interaction with HAVCR1 on human T cells using binding, signal transduction, apoptosis, activation, suppression, cytokine production, and confocal microscopy analyses. Cytokines were analyzed in sera from 14 patients with HAV infection using bead arrays. Human Treg cells constitutively express HAVCR1. Binding of HAV to HAVCR1 blocked phosphorylation of Akt, prevented activation of the T-cell receptor, and inhibited function of Treg cells. At the peak viremia, patients with acute HAV infection had no Treg-cell suppression function, produced low levels of transforming growth factor-β , which limited leukocyte recruitment and survival, and produced high levels of interleukin-22, which prevented liver damage. Interaction between HAV and its receptor HAVCR1 inhibits Treg-cell function, resulting in an immune imbalance that allows viral expansion with limited hepatocellular damage during early stages of infection-a characteristic of HAV pathogenesis. The mechanism by which HAV is cleared in the absence of Treg-cell function could be used as a model to develop anticancer therapies, modulate autoimmune and allergic responses, and prevent transplant rejection. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

Subsite mapping of enzymes. Depolymerase computer modelling.

PubMed Central

Allen, J D; Thoma, J A

1976-01-01

We have developed a depolymerase computer model that uses a minimization routine. The model is designed so that, given experimental bond-cleavage frequencies for oligomeric substrates and experimental Michaelis parameters as a function of substrate chain length, the optimum subsite map is generated. The minimized sum of the weighted-squared residuals of the experimental and calculated data is used as a criterion of the goodness-of-fit for the optimized subsite map. The application of the minimization procedure to subsite mapping is explored through the use of simulated data. A procedure is developed whereby the minimization model can be used to determine the number of subsites in the enzymic binding region and to locate the position of the catalytic amino acids among these subsites. The degree of propagation of experimental variance into the subsite-binding energies is estimated. The question of whether hydrolytic rate coefficients are constant or a function of the number of filled subsites is examined. PMID:999629

Persistence of Functional Protein Domains in Mycoplasma Species and their Role in Host Specificity and Synthetic Minimal Life.

PubMed

Kamminga, Tjerko; Koehorst, Jasper J; Vermeij, Paul; Slagman, Simen-Jan; Martins Dos Santos, Vitor A P; Bijlsma, Jetta J E; Schaap, Peter J

2017-01-01

Mycoplasmas are the smallest self-replicating organisms and obligate parasites of a specific vertebrate host. An in-depth analysis of the functional capabilities of mycoplasma species is fundamental to understand how some of simplest forms of life on Earth succeeded in subverting complex hosts with highly sophisticated immune systems. In this study we present a genome-scale comparison, focused on identification of functional protein domains, of 80 publically available mycoplasma genomes which were consistently re-annotated using a standardized annotation pipeline embedded in a semantic framework to keep track of the data provenance. We examined the pan- and core-domainome and studied predicted functional capability in relation to host specificity and phylogenetic distance. We show that the pan- and core-domainome of mycoplasma species is closed. A comparison with the proteome of the "minimal" synthetic bacterium JCVI-Syn3.0 allowed us to classify domains and proteins essential for minimal life. Many of those essential protein domains, essential Domains of Unknown Function (DUFs) and essential hypothetical proteins are not persistent across mycoplasma genomes suggesting that mycoplasma species support alternative domain configurations that bypass their essentiality. Based on the protein domain composition, we could separate mycoplasma species infecting blood and tissue. For selected genomes of tissue infecting mycoplasmas, we could also predict whether the host is ruminant, pig or human. Functionally closely related mycoplasma species, which have a highly similar protein domain repertoire, but different hosts could not be separated. This study provides a concise overview of the functional capabilities of mycoplasma species, which can be used as a basis to further understand host-pathogen interaction or to design synthetic minimal life.

Early group bias in the Faroe Islands: Cultural variation in children's group-based reasoning.

PubMed

Schug, Mariah G; Shusterman, Anna; Barth, Hilary; Patalano, Andrea L

2016-01-01

Recent developmental research demonstrates that group bias emerges early in childhood. However, little is known about the extent to which bias in minimal (i.e., arbitrarily assigned) groups varies with children's environment and experience, and whether such bias is universal across cultures. In this study, the development of group bias was investigated using a minimal groups paradigm with 46 four- to six-year-olds from the Faroe Islands. Children observed in-group and out-group members exhibiting varying degrees of prosocial behaviour (egalitarian or stingy sharing). Children did not prefer their in-group in the pretest, but a pro-in-group and anti-out-group sentiment emerged in both conditions in the posttest. Faroese children's response patterns differ from those of American children [Schug, M. G., Shusterman, A., Barth, H., & Patalano, A. L. (2013). Minimal-group membership influences children's responses to novel experience with group members. Developmental Science, 16(1), 47-55], suggesting that intergroup bias shows cultural variation even in a minimal groups context.

SASS wind ambiguity removal by direct minimization. [Seasat-A satellite scatterometer

NASA Technical Reports Server (NTRS)

Hoffman, R. N.

1982-01-01

An objective analysis procedure is presented which combines Seasat-A satellite scatterometer (SASS) data with other available data on wind speeds by minimizing an objective function of gridded wind speed values. The functions are defined as the loss functions for the SASS velocity data, the forecast, the SASS velocity magnitude data, and conventional wind speed data. Only aliases closest to the analysis were included, and a method for improving the first guess while using a minimization technique and slowly changing the parameters of the problem is introduced. The model is employed to predict the wind field for the North Atlantic on Sept. 10, 1978. Dealiased SASS data is compared with available ship readings, showing good agreement between the SASS dealiased winds and the winds measured at the surface. Expansion of the model to take in low-level cloud measurements, pressure data, and convergence and cloud level data correlations is discussed.

Penalized Weighted Least-Squares Approach to Sinogram Noise Reduction and Image Reconstruction for Low-Dose X-Ray Computed Tomography

PubMed Central

Wang, Jing; Li, Tianfang; Lu, Hongbing; Liang, Zhengrong

2006-01-01

Reconstructing low-dose X-ray CT (computed tomography) images is a noise problem. This work investigated a penalized weighted least-squares (PWLS) approach to address this problem in two dimensions, where the WLS considers first- and second-order noise moments and the penalty models signal spatial correlations. Three different implementations were studied for the PWLS minimization. One utilizes a MRF (Markov random field) Gibbs functional to consider spatial correlations among nearby detector bins and projection views in sinogram space and minimizes the PWLS cost function by iterative Gauss-Seidel algorithm. Another employs Karhunen-Loève (KL) transform to de-correlate data signals among nearby views and minimizes the PWLS adaptively to each KL component by analytical calculation, where the spatial correlation among nearby bins is modeled by the same Gibbs functional. The third one models the spatial correlations among image pixels in image domain also by a MRF Gibbs functional and minimizes the PWLS by iterative successive over-relaxation algorithm. In these three implementations, a quadratic functional regularization was chosen for the MRF model. Phantom experiments showed a comparable performance of these three PWLS-based methods in terms of suppressing noise-induced streak artifacts and preserving resolution in the reconstructed images. Computer simulations concurred with the phantom experiments in terms of noise-resolution tradeoff and detectability in low contrast environment. The KL-PWLS implementation may have the advantage in terms of computation for high-resolution dynamic low-dose CT imaging. PMID:17024831

Brain networks predict metabolism, diagnosis and prognosis at the bedside in disorders of consciousness.

PubMed

Chennu, Srivas; Annen, Jitka; Wannez, Sarah; Thibaut, Aurore; Chatelle, Camille; Cassol, Helena; Martens, Géraldine; Schnakers, Caroline; Gosseries, Olivia; Menon, David; Laureys, Steven

2017-08-01

Recent advances in functional neuroimaging have demonstrated novel potential for informing diagnosis and prognosis in the unresponsive wakeful syndrome and minimally conscious states. However, these technologies come with considerable expense and difficulty, limiting the possibility of wider clinical application in patients. Here, we show that high density electroencephalography, collected from 104 patients measured at rest, can provide valuable information about brain connectivity that correlates with behaviour and functional neuroimaging. Using graph theory, we visualize and quantify spectral connectivity estimated from electroencephalography as a dense brain network. Our findings demonstrate that key quantitative metrics of these networks correlate with the continuum of behavioural recovery in patients, ranging from those diagnosed as unresponsive, through those who have emerged from minimally conscious, to the fully conscious locked-in syndrome. In particular, a network metric indexing the presence of densely interconnected central hubs of connectivity discriminated behavioural consciousness with accuracy comparable to that achieved by expert assessment with positron emission tomography. We also show that this metric correlates strongly with brain metabolism. Further, with classification analysis, we predict the behavioural diagnosis, brain metabolism and 1-year clinical outcome of individual patients. Finally, we demonstrate that assessments of brain networks show robust connectivity in patients diagnosed as unresponsive by clinical consensus, but later rediagnosed as minimally conscious with the Coma Recovery Scale-Revised. Classification analysis of their brain network identified each of these misdiagnosed patients as minimally conscious, corroborating their behavioural diagnoses. If deployed at the bedside in the clinical context, such network measurements could complement systematic behavioural assessment and help reduce the high misdiagnosis rate reported in these patients. These metrics could also identify patients in whom further assessment is warranted using neuroimaging or conventional clinical evaluation. Finally, by providing objective characterization of states of consciousness, repeated assessments of network metrics could help track individual patients longitudinally, and also assess their neural responses to therapeutic and pharmacological interventions. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

Toward a preoperative planning tool for brain tumor resection therapies.

PubMed

Coffey, Aaron M; Miga, Michael I; Chen, Ishita; Thompson, Reid C

2013-01-01

Neurosurgical procedures involving tumor resection require surgical planning such that the surgical path to the tumor is determined to minimize the impact on healthy tissue and brain function. This work demonstrates a predictive tool to aid neurosurgeons in planning tumor resection therapies by finding an optimal model-selected patient orientation that minimizes lateral brain shift in the field of view. Such orientations may facilitate tumor access and removal, possibly reduce the need for retraction, and could minimize the impact of brain shift on image-guided procedures. In this study, preoperative magnetic resonance images were utilized in conjunction with pre- and post-resection laser range scans of the craniotomy and cortical surface to produce patient-specific finite element models of intraoperative shift for 6 cases. These cases were used to calibrate a model (i.e., provide general rules for the application of patient positioning parameters) as well as determine the current model-based framework predictive capabilities. Finally, an objective function is proposed that minimizes shift subject to patient position parameters. Patient positioning parameters were then optimized and compared to our neurosurgeon as a preliminary study. The proposed model-driven brain shift minimization objective function suggests an overall reduction of brain shift by 23 % over experiential methods. This work recasts surgical simulation from a trial-and-error process to one where options are presented to the surgeon arising from an optimization of surgical goals. To our knowledge, this is the first realization of an evaluative tool for surgical planning that attempts to optimize surgical approach by means of shift minimization in this manner.

The elastic ratio: introducing curvature into ratio-based image segmentation.

PubMed

Schoenemann, Thomas; Masnou, Simon; Cremers, Daniel

2011-09-01

We present the first ratio-based image segmentation method that allows imposing curvature regularity of the region boundary. Our approach is a generalization of the ratio framework pioneered by Jermyn and Ishikawa so as to allow penalty functions that take into account the local curvature of the curve. The key idea is to cast the segmentation problem as one of finding cyclic paths of minimal ratio in a graph where each graph node represents a line segment. Among ratios whose discrete counterparts can be globally minimized with our approach, we focus in particular on the elastic ratio [Formula: see text] that depends, given an image I, on the oriented boundary C of the segmented region candidate. Minimizing this ratio amounts to finding a curve, neither small nor too curvy, through which the brightness flux is maximal. We prove the existence of minimizers for this criterion among continuous curves with mild regularity assumptions. We also prove that the discrete minimizers provided by our graph-based algorithm converge, as the resolution increases, to continuous minimizers. In contrast to most existing segmentation methods with computable and meaningful, i.e., nondegenerate, global optima, the proposed approach is fully unsupervised in the sense that it does not require any kind of user input such as seed nodes. Numerical experiments demonstrate that curvature regularity allows substantial improvement of the quality of segmentations. Furthermore, our results allow drawing conclusions about global optima of a parameterization-independent version of the snakes functional: the proposed algorithm allows determining parameter values where the functional has a meaningful solution and simultaneously provides the corresponding global solution.

Optimal bounds and extremal trajectories for time averages in nonlinear dynamical systems

NASA Astrophysics Data System (ADS)

Tobasco, Ian; Goluskin, David; Doering, Charles R.

2018-02-01

For any quantity of interest in a system governed by ordinary differential equations, it is natural to seek the largest (or smallest) long-time average among solution trajectories, as well as the extremal trajectories themselves. Upper bounds on time averages can be proved a priori using auxiliary functions, the optimal choice of which is a convex optimization problem. We prove that the problems of finding maximal trajectories and minimal auxiliary functions are strongly dual. Thus, auxiliary functions provide arbitrarily sharp upper bounds on time averages. Moreover, any nearly minimal auxiliary function provides phase space volumes in which all nearly maximal trajectories are guaranteed to lie. For polynomial equations, auxiliary functions can be constructed by semidefinite programming, which we illustrate using the Lorenz system.

The Role of Baseline Vagal Tone in Dealing with a Stressor during Face to Face and Computer-Based Social Interactions.

PubMed

Rigoni, Daniele; Morganti, Francesca; Braibanti, Paride

2017-01-01

Facing a stressor involves a cardiac vagal tone response and a feedback effect produced by social interaction in visceral regulation. This study evaluated the contribution of baseline vagal tone and of social engagement system (SES) functioning on the ability to deal with a stressor. Participants ( n = 70) were grouped into a minimized social interaction condition (procedure administered through a PC) and a social interaction condition (procedure administered by an experimenter). The State Trait Anxiety Inventory, the Social Interaction Anxiety Scale, the Emotion Regulation Questionnaire and a debriefing questionnaire were completed by the subjects. The baseline vagal tone was registered during the baseline, stressor and recovery phases. The collected results highlighted a significant effect of the baseline vagal tone on vagal suppression. No effect of minimized vs. social interaction conditions on cardiac vagal tone during stressor and recovery phases was detected. Cardiac vagal tone and the results of the questionnaires appear to be not correlated. The study highlighted the main role of baseline vagal tone on visceral regulation. Some remarks on SES to be deepen in further research were raised.

A concept for adaptive performance optimization on commercial transport aircraft

NASA Technical Reports Server (NTRS)

Jackson, Michael R.; Enns, Dale F.

1995-01-01

An adaptive control method is presented for the minimization of drag during flight for transport aircraft. The minimization of drag is achieved by taking advantage of the redundant control capability available in the pitch axis, with the horizontal tail used as the primary surface and symmetric deflection of the ailerons and cruise flaps used as additional controls. The additional control surfaces are excited with sinusoidal signals, while the altitude and velocity loops are closed with guidance and control laws. A model of the throttle response as a function of the additional control surfaces is formulated and the parameters in the model are estimated from the sensor measurements using a least squares estimation method. The estimated model is used to determine the minimum drag positions of the control surfaces. The method is presented for the optimization of one and two additional control surfaces. The adaptive control method is extended to optimize rate of climb with the throttle fixed. Simulations that include realistic disturbances are presented, as well as the results of a Monte Carlo simulation analysis that shows the effects of changing the disturbance environment and the excitation signal parameters.

Regularized variational theories of fracture: A unified approach

NASA Astrophysics Data System (ADS)

Freddi, Francesco; Royer-Carfagni, Gianni

2010-08-01

The fracture pattern in stressed bodies is defined through the minimization of a two-field pseudo-spatial-dependent functional, with a structure similar to that proposed by Bourdin-Francfort-Marigo (2000) as a regularized approximation of a parent free-discontinuity problem, but now considered as an autonomous model per se. Here, this formulation is altered by combining it with structured deformation theory, to model that when the material microstructure is loosened and damaged, peculiar inelastic (structured) deformations may occur in the representative volume element at the price of surface energy consumption. This approach unifies various theories of failure because, by simply varying the form of the class for admissible structured deformations, different-in-type responses can be captured, incorporating the idea of cleavage, deviatoric, combined cleavage-deviatoric and masonry-like fractures. Remarkably, this latter formulation rigorously avoid material overlapping in the cracked zones. The model is numerically implemented using a standard finite-element discretization and adopts an alternate minimization algorithm, adding an inequality constraint to impose crack irreversibility ( fixed crack model). Numerical experiments for some paradigmatic examples are presented and compared for various possible versions of the model.

Hematopoietic tissue repair under chronic low daily dose irradiation

NASA Astrophysics Data System (ADS)

Seed, T. M.

The capacity of the hematopoietic system to repair constantly accruing cellular damage under chronic, low daily dose gamma irradiation is essential for the maintenance of a functional hematopoietic system, and, in turn, long term survival. In certain individuals, however, such continuous cycles of damage and repair provide an essential inductive environment for selected types of hematopathologies, e.g., myeloid leukemia (ML). In our laboratory we have been studying temporal and causal relationships between hematopoietic capacity, associated repair functions, and propensities for hematologic disease in canines under variable levels of chronic radiation stress (0.3-26.3 cGy d^-1). Results indicate that the maximum exposure rate tolerated by the hematopoietic system is highly individual-specific (three major responding subgroups identified) and is based largely on the degree to which repair capacity, and, in turn, hematopoietic restoration, is augmented under chronic exposure. In low-tolerance individuals (prone to aplastic anemia, subgroup 1), the failure to augment basic repair functions seemingly results in a progressive accumulation of genetic and cellular damage within vital progenitorial marrow compartments (particularly marked within erythroid compartments) that results in loss of reproductive capacity and ultimately in collapse of the hematopoietic system. The high-tolerance individuals (radioaccommodated and either prone- or not prone to ML, subgroup 2 & 3) appear to minimize the accumulating damage effect of daily exposures by extending repair functions, which preserves reproductive integrity and fosters regenerative hematopoietic responses. As the strength of the regenerative response manifests the extent of repair augmentation, the relatively strong response of high-tolerance individuals progressing to patent ML suggests an insufficiency of repair quality rather than repair quantity. The kinetics of these repair-mediated, regenerative hematopoietic responses within the major subgroups are under study and should provide useful insights into the nature of hematopoietic accommodation (or its failure) under greatly extended periods of chronic, low-daily-dose ionizing radiation exposure.

Suspended Carbon Nanotubes for Humidity Sensing

PubMed Central

Arunachalam, Shivaram; Gupta, Anubha A.; Izquierdo, Ricardo

2018-01-01

A room temperature microfabrication technique using SU8, an epoxy-based highly functional photoresist as a sacrificial layer, is developed to obtain suspended aligned carbon nanotube beams. The humidity-sensing characteristics of aligned suspended single-walled carbon nanotube films are studied. A comparative study between suspended and non-suspended architectures is done by recording the resistance change in the nanotubes under humidity. For the tests, the humidity was varied from 15% to 98% RH. A comparative study between suspended and non-suspended devices shows that the response and recovery times of the suspended devices was found to be almost 3 times shorter than the non-suspended devices. The suspended devices also showed minimal hysteresis even after 10 humidity cycles, and also exhibit enhanced sensitivity. Repeatability tests were performed by subjecting the sensors to continuous humidification cycles. All tests reported here have been performed using pristine non-functionalized nanotubes. PMID:29786661

Suspended Carbon Nanotubes for Humidity Sensing.

PubMed

Arunachalam, Shivaram; Gupta, Anubha A; Izquierdo, Ricardo; Nabki, Frederic

2018-05-22

A room temperature microfabrication technique using SU8, an epoxy-based highly functional photoresist as a sacrificial layer, is developed to obtain suspended aligned carbon nanotube beams. The humidity-sensing characteristics of aligned suspended single-walled carbon nanotube films are studied. A comparative study between suspended and non-suspended architectures is done by recording the resistance change in the nanotubes under humidity. For the tests, the humidity was varied from 15% to 98% RH. A comparative study between suspended and non-suspended devices shows that the response and recovery times of the suspended devices was found to be almost 3 times shorter than the non-suspended devices. The suspended devices also showed minimal hysteresis even after 10 humidity cycles, and also exhibit enhanced sensitivity. Repeatability tests were performed by subjecting the sensors to continuous humidification cycles. All tests reported here have been performed using pristine non-functionalized nanotubes.

Liver-selective glucocorticoid antagonists: a novel treatment for type 2 diabetes.

PubMed

von Geldern, Thomas W; Tu, Noah; Kym, Philip R; Link, James T; Jae, Hwan-Soo; Lai, Chunqiu; Apelqvist, Theresa; Rhonnstad, Patrik; Hagberg, Lars; Koehler, Konrad; Grynfarb, Marlena; Goos-Nilsson, Annika; Sandberg, Johnny; Osterlund, Marie; Barkhem, Tomas; Höglund, Marie; Wang, Jiahong; Fung, Steven; Wilcox, Denise; Nguyen, Phong; Jakob, Clarissa; Hutchins, Charles; Färnegårdh, Mathias; Kauppi, Björn; Ohman, Lars; Jacobson, Peer B

2004-08-12

Hepatic blockade of glucocorticoid receptors (GR) suppresses glucose production and thus decreases circulating glucose levels, but systemic glucocorticoid antagonism can produce adrenal insufficiency and other undesirable side effects. These hepatic and systemic responses might be dissected, leading to liver-selective pharmacology, when a GR antagonist is linked to a bile acid in an appropriate manner. Bile acid conjugation can be accomplished with a minimal loss of binding affinity for GR. The resultant conjugates remain potent in cell-based functional assays. A novel in vivo assay has been developed to simultaneously evaluate both hepatic and systemic GR blockade; this assay has been used to optimize the nature and site of the linker functionality, as well as the choice of the GR antagonist and the bile acid. This optimization led to the identification of A-348441, which reduces glucose levels and improves lipid profiles in an animal model of diabetes. Copyright 2004 American Chemical Society

A Monte Carlo simulation based inverse propagation method for stochastic model updating

NASA Astrophysics Data System (ADS)

Bao, Nuo; Wang, Chunjie

2015-08-01

This paper presents an efficient stochastic model updating method based on statistical theory. Significant parameters have been selected implementing the F-test evaluation and design of experiments, and then the incomplete fourth-order polynomial response surface model (RSM) has been developed. Exploiting of the RSM combined with Monte Carlo simulation (MCS), reduces the calculation amount and the rapid random sampling becomes possible. The inverse uncertainty propagation is given by the equally weighted sum of mean and covariance matrix objective functions. The mean and covariance of parameters are estimated synchronously by minimizing the weighted objective function through hybrid of particle-swarm and Nelder-Mead simplex optimization method, thus the better correlation between simulation and test is achieved. Numerical examples of a three degree-of-freedom mass-spring system under different conditions and GARTEUR assembly structure validated the feasibility and effectiveness of the proposed method.

Time-dependent broken-symmetry density functional theory simulation of the optical response of entangled paramagnetic defects: Color centers in lithium fluoride

NASA Astrophysics Data System (ADS)

Janesko, Benjamin G.

2018-02-01

Parameter-free atomistic simulations of entangled solid-state paramagnetic defects may aid in the rational design of devices for quantum information science. This work applies time-dependent density functional theory (TDDFT) embedded-cluster simulations to a prototype entangled-defect system, namely two adjacent singlet-coupled F color centers in lithium fluoride. TDDFT calculations accurately reproduce the experimental visible absorption of both isolated and coupled F centers. The most accurate results are obtained by combining spin symmetry breaking to simulate strong correlation, a large fraction of exact (Hartree-Fock-like) exchange to minimize the defect electrons' self-interaction error, and a standard semilocal approximation for dynamical correlations between the defect electrons and the surrounding ionic lattice. These results motivate application of two-reference correlated ab initio approximations to the M-center, and application of TDDFT in parameter-free simulations of more complex entangled paramagnetic defect architectures.

Architecture and functional ecology of the human gastrocnemius muscle-tendon unit.

PubMed

Butler, Erin E; Dominy, Nathaniel J

2016-04-01

The gastrocnemius muscle-tendon unit (MTU) is central to human locomotion. Structural variation in the human gastrocnemius MTU is predicted to affect the efficiency of locomotion, a concept most often explored in the context of performance activities. For example, stiffness of the Achilles tendon varies among individuals with different histories of competitive running. Such a finding highlights the functional variation of individuals and raises the possibility of similar variation between populations, perhaps in response to specific ecological or environmental demands. Researchers often assume minimal variation in human populations, or that industrialized populations represent the human species as well as any other. Yet rainforest hunter-gatherers, which often express the human pygmy phenotype, contradict such assumptions. Indeed, the human pygmy phenotype is a potential model system for exploring the range of ecomorphological variation in the architecture of human hindlimb muscles, a concept we review here. © 2015 Anatomical Society.

Postoperative respiratory muscle dysfunction: pathophysiology and preventive strategies.

PubMed

Sasaki, Nobuo; Meyer, Matthew J; Eikermann, Matthias

2013-04-01

Postoperative pulmonary complications are responsible for significant increases in hospital cost as well as patient morbidity and mortality; respiratory muscle dysfunction represents a contributing factor. Upper airway dilator muscles functionally resist the upper airway collapsing forces created by the respiratory pump muscles. Standard perioperative medications (anesthetics, sedatives, opioids, and neuromuscular blocking agents), interventions (patient positioning, mechanical ventilation, and surgical trauma), and diseases (lung hyperinflation, obesity, and obstructive sleep apnea) have differential effects on the respiratory muscle subgroups. These effects on the upper airway dilators and respiratory pump muscles impair their coordination and function and can result in respiratory failure. Perioperative management strategies can help decrease the incidence of postoperative respiratory muscle dysfunction. Such strategies include minimally invasive procedures rather than open surgery, early and optimal mobilizing of respiratory muscles while on mechanical ventilation, judicious use of respiratory depressant anesthetics and neuromuscular blocking agents, and noninvasive ventilation when possible.

Quality of life of patients who have undergone the minimally invasive repair of pectus carinatum.

PubMed

Bostanci, Korkut; Ozalper, Mehmet Hakan; Eldem, Barkin; Ozyurtkan, Mehmet Oguzhan; Issaka, Adamu; Ermerak, Nezih Onur; Yuksel, Mustafa

2013-01-01

Several studies previously demonstrated an improvement in the quality of life (QoL) of the patients undergoing a minimally invasive repair of pectus excavatum, but there are no data about such improvement following the minimally invasive repair of pectus carinatum (PC) deformity. The purpose of this study was to investigate the effects of the minimally invasive repair of PC deformity on the psychosocial and physical functioning of the patients. Among 40 patients who underwent minimally invasive repair for PC deformity from July 2008 to March 2011, 35 patients accepted to answer the QoL questionnaires, and 30 of them who had completed the postoperative 6th month were evaluated in this study. The modified two-step Nuss questionnaire was used for the QoL assessment. All patients and their parents completed the appropriate questionnaires regarding the patients' preoperative psychosocial and physical functioning, and they were asked to answer the same questions on the postoperative 6th month. The results from these questionnaires were analysed using Wilcoxon signed rank test to investigate the effects of the minimally invasive repair of PC deformity on psychosocial and physical functioning of the patients. The questionnaires used in the study confirmed the positive impact of the surgical correction on psychosocial and physical well-being in the patients and their parents. Spearman's ρ correlation coefficient determined how well the answers to the same question at two different times correlated with each other, and Cronbach's alpha demonstrated the internal consistency of these answers. These two parameters showed that the statistical results of the study were reliable enough. Statistical analysis of the scoring of the individual questions and the total scoring of individual patients revealed a statistically significant improvement (P < 0.05) following surgery. Similar significant improvements were observed in the total scoring of individual parents and in most scoring of the individual questions (10 of 13, 77%) in the parental questionnaire (P < 0.05). The results of this study confirm for the first time that minimally invasive repair of PC deformity has a positive impact on both psychosocial and physical functioning of the patient, which is supported by parental assessment.

Determination of acoustical transfer functions using an impulse method

NASA Astrophysics Data System (ADS)

MacPherson, J.

1985-02-01

The Transfer Function of a system may be defined as the relationship of the output response to the input of a system. Whilst recent advances in digital processing systems have enabled Impulse Transfer Functions to be determined by computation of the Fast Fourier Transform, there has been little work done in applying these techniques to room acoustics. Acoustical Transfer Functions have been determined for auditoria, using an impulse method. The technique is based on the computation of the Fast Fourier Transform (FFT) of a non-ideal impulsive source, both at the source and at the receiver point. The Impulse Transfer Function (ITF) is obtained by dividing the FFT at the receiver position by the FFT of the source. This quantity is presented both as linear frequency scale plots and also as synthesized one-third octave band data. The technique enables a considerable quantity of data to be obtained from a small number of impulsive signals recorded in the field, thereby minimizing the time and effort required on site. As the characteristics of the source are taken into account in the calculation, the choice of impulsive source is non-critical. The digital analysis equipment required for the analysis is readily available commercially.

Recovery of ovarian activity in women with functional hypothalamic amenorrhea who were treated with cognitive behavior therapy.

PubMed

Berga, Sarah L; Marcus, Marsha D; Loucks, Tammy L; Hlastala, Stefanie; Ringham, Rebecca; Krohn, Marijane A

2003-10-01

To determine whether cognitive behavior therapy (CBT) targeted to problematic attitudes common among women with functional hypothalamic amenorrhea would restore ovarian function. Randomized, prospective, controlled intervention. Clinical research center in an academic medical institution. Sixteen women participated who had functional hypothalamic amenorrhea; were of normal body weight; and did not report psychiatric conditions, eating disorders, or excessive exercise. Subjects were randomized to CBT or observation for 20 weeks. Serum levels of E(2) and P and vaginal bleeding were monitored. Of eight women treated with CBT, six resumed ovulating, one had partial recovery of ovarian function without evidence of ovulation, and one did not display return of ovarian function. Of those randomized to observation, one resumed ovulating, one had partial return of ovarian function, and six did not recover. Thus, CBT resulted in a higher rate of ovarian activity (87.5%) than did observation (25.0%), chi(2) = 7.14. A cognitive behavioral intervention designed to minimize problematic attitudes linked to hypothalamic allostasis was more likely to result in resumption of ovarian activity than observation. The prompt ovarian response to CBT suggests that a tailored behavioral intervention offers an efficacious treatment option that also avoids the pitfalls of pharmacological modalities.

Adaptive Responses to Prochloraz Exposure That Alter Dose-Response and Time-Course Behaviors

EPA Science Inventory

Dose response and time-course (DRTC) are, along with exposure, the major determinants of health risk. Adaptive changes within exposed organisms in response to environmental stress are common, and alter DRTC behaviors to minimize the effects caused by stressors. In this project, ...

A novel automatic quantification method for high-content screening analysis of DNA double strand-break response.

PubMed

Feng, Jingwen; Lin, Jie; Zhang, Pengquan; Yang, Songnan; Sa, Yu; Feng, Yuanming

2017-08-29

High-content screening is commonly used in studies of the DNA damage response. The double-strand break (DSB) is one of the most harmful types of DNA damage lesions. The conventional method used to quantify DSBs is γH2AX foci counting, which requires manual adjustment and preset parameters and is usually regarded as imprecise, time-consuming, poorly reproducible, and inaccurate. Therefore, a robust automatic alternative method is highly desired. In this manuscript, we present a new method for quantifying DSBs which involves automatic image cropping, automatic foci-segmentation and fluorescent intensity measurement. Furthermore, an additional function was added for standardizing the measurement of DSB response inhibition based on co-localization analysis. We tested the method with a well-known inhibitor of DSB response. The new method requires only one preset parameter, which effectively minimizes operator-dependent variations. Compared with conventional methods, the new method detected a higher percentage difference of foci formation between different cells, which can improve measurement accuracy. The effects of the inhibitor on DSB response were successfully quantified with the new method (p = 0.000). The advantages of this method in terms of reliability, automation and simplicity show its potential in quantitative fluorescence imaging studies and high-content screening for compounds and factors involved in DSB response.

fMRI response to spatial working memory in adolescents with comorbid marijuana and alcohol use disorders☆

PubMed Central

Schweinsburg, Alecia D.; Schweinsburg, Brian C.; Cheung, Erick H.; Brown, Gregory G.; Brown, Sandra A.; Tapert, Susan F.

2008-01-01

Alcohol and marijuana use are prevalent in adolescence, yet the neural impact of concomitant use remains unclear. We previously demonstrated functional magnetic resonance imaging (fMRI) response to spatial working memory (SWM) among teens with alcohol use disorders (AUD) compared to controls, and predicted that adolescents with marijuana and alcohol use disorders would show additional abnormalities. Participants were three groups of 15−17-year-olds: 19 non-abusing controls, 15 AUD teens with limited exposure to drugs, and 15 teens with comorbid marijuana and alcohol use disorders (MAUD) and minimal other drug experience. After >2 days’ abstinence, participants performed a SWM task during fMRI acquisition. fMRI brain response patterns differed between groups, despite similar performance on the task. MAUD youths showed less activation in inferior frontal and temporal regions than controls, and more response in other prefrontal regions. Compared to AUD teens, MAUD youths also showed less inferior frontal and temporal activation, but more medial frontal response. Overall, MAUD youths showed different brain response abnormalities than teens with AUD alone, despite relatively short histories of substance involvement. This pattern could suggest compensation for marijuana-related attention and working memory deficits. However, relatively recent use and premorbid features may influence results, and should be examined in future studies. PMID:16002029

Negative regulators of the RIG-I-like receptor signaling pathway

PubMed Central

Quicke, Kendra M.; Diamond, Michael S.; Suthar, Mehul S.

2017-01-01

SUMMARY Upon recognition of specific molecular patterns on viruses, bacteria and fungi, host cells trigger an innate immune response, which culminates in the production of type I interferons (IFN), pro-inflammatory cytokines and chemokines, and restricts pathogen replication and spread within the host. At each stage of the immune response, there are stimulatory and inhibitory signals that regulate the magnitude, quality, and character of the response. Positive regulation promotes an antiviral state to control and eventually clear infection whereas negative regulation dampens inflammation and prevents immune-mediated tissue damage. An over-exuberant innate immune response can lead to the destruction of cells and tissues, and the development of spontaneous autoimmunity. The RIG-I-like receptors (RLRs) retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) belong to a family of cytosolic host RNA helicases that recognize distinct non-self RNA signatures and trigger innate immune responses against several RNA virus infections. The RLR signaling pathway is tightly regulated to achieve a well-orchestrated response aimed at maximizing antiviral immunity and minimizing immune-mediated pathology. This review highlights contemporary findings on negative regulators of the RLR signaling pathway, with specific focus on the proteins and biological processes that directly regulate RIG-I, MDA5 and MAVS function. PMID:28295214

Mineralization of pyrrole, a recalcitrant heterocyclic compound, by electrochemical method: Multi-response optimization and degradation mechanism.

PubMed

Hiwarkar, Ajay Devidas; Singh, Seema; Srivastava, Vimal Chandra; Mall, Indra Deo

2017-08-01

In this study, the electrochemical (EC) oxidation of a recalcitrant heterocyclic compound namely pyrrole has been reported using platinum coated titanium (Pt/Ti) electrodes. Response surface methodology (RSM) comprising of full factorial central composite design (CCD) with four factors and five levels has been used to examine the effects of different operating parameters such as current density (j), aqueous solution pH, conductivity (k) and treatment time (t) in an EC batch reactor. Pyrrole mineralization in aqueous solution was examined with multiple responses such as chemical oxygen demand (COD) (response, Y 1 ) and specific energy consumption (SEC) in kWh/kg of COD removed (response, Y 2 ). During multiple response optimization, the desirability function approach was employed to concurrently maximize Y 1 and minimize Y 2 . At the optimum condition, 82.9% COD removal and 7.7 kWh/kg of COD removed were observed. Degradation mechanism of pyrrole in wastewater was elucidated at the optimum condition of treatment by using UV-visible spectroscopy, Fourier transformed infra-red spectroscopy (FTIR), cyclic voltammetry (CV), ion chromatography (IC), higher performance liquid chromatography (HPLC) and gas chromatography-mass spectroscopy (GC-MS). The degradation pathway of pyrrole was proposed on the basis of the various analysis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Estimation of ion competition via correlated responsivity offset in linear ion trap mass spectrometry analysis: theory and practical use in the analysis of cyanobacterial hepatotoxin microcystin-LR in extracts of food additives.

PubMed

Urban, Jan; Hrouzek, Pavel; Stys, Dalibor; Martens, Harald

2013-01-01

Responsivity is a conversion qualification of a measurement device given by the functional dependence between the input and output quantities. A concentration-response-dependent calibration curve represents the most simple experiment for the measurement of responsivity in mass spectrometry. The cyanobacterial hepatotoxin microcystin-LR content in complex biological matrices of food additives was chosen as a model example of a typical problem. The calibration curves for pure microcystin and its mixtures with extracts of green alga and fish meat were reconstructed from the series of measurement. A novel approach for the quantitative estimation of ion competition in ESI is proposed in this paper. We define the correlated responsivity offset in the intensity values using the approximation of minimal correlation given by the matrix to the target mass values of the analyte. The estimation of the matrix influence enables the approximation of the position of a priori unknown responsivity and was easily evaluated using a simple algorithm. The method itself is directly derived from the basic attributes of the theory of measurements. There is sufficient agreement between the theoretical and experimental values. However, some theoretical issues are discussed to avoid misinterpretations and excessive expectations.

Between- and within-lake responses of macrophyte richness metrics to shoreline developmen

USGS Publications Warehouse

Beck, Marcus W.; Vondracek, Bruce C.; Hatch, Lorin K.

2013-01-01

Aquatic habitat in littoral environments can be affected by residential development of shoreline areas. We evaluated the relationship between macrophyte richness metrics and shoreline development to quantify indicator response at 2 spatial scales for Minnesota lakes. First, the response of total, submersed, and sensitive species to shoreline development was evaluated within lakes to quantify macrophyte response as a function of distance to the nearest dock. Within-lake analyses using generalized linear mixed models focused on 3 lakes of comparable size with a minimal influence of watershed land use. Survey points farther from docks had higher total species richness and presence of species sensitive to disturbance. Second, between-lake effects of shoreline development on total, submersed, emergent-floating, and sensitive species were evaluated for 1444 lakes. Generalized linear models were developed for all lakes and stratified subsets to control for lake depth and watershed land use. Between-lake analyses indicated a clear response of macrophyte richness metrics to increasing shoreline development, such that fewer emergent-floating and sensitive species were correlated with increasing density of docks. These trends were particularly evident for deeper lakes with lower watershed development. Our results provide further evidence that shoreline development is associated with degraded aquatic habitat, particularly by illustrating the response of macrophyte richness metrics across multiple lake types and different spatial scales.

Estimation of Ion Competition via Correlated Responsivity Offset in Linear Ion Trap Mass Spectrometry Analysis: Theory and Practical Use in the Analysis of Cyanobacterial Hepatotoxin Microcystin-LR in Extracts of Food Additives

PubMed Central

Hrouzek, Pavel; Štys, Dalibor; Martens, Harald

2013-01-01

Responsivity is a conversion qualification of a measurement device given by the functional dependence between the input and output quantities. A concentration-response-dependent calibration curve represents the most simple experiment for the measurement of responsivity in mass spectrometry. The cyanobacterial hepatotoxin microcystin-LR content in complex biological matrices of food additives was chosen as a model example of a typical problem. The calibration curves for pure microcystin and its mixtures with extracts of green alga and fish meat were reconstructed from the series of measurement. A novel approach for the quantitative estimation of ion competition in ESI is proposed in this paper. We define the correlated responsivity offset in the intensity values using the approximation of minimal correlation given by the matrix to the target mass values of the analyte. The estimation of the matrix influence enables the approximation of the position of a priori unknown responsivity and was easily evaluated using a simple algorithm. The method itself is directly derived from the basic attributes of the theory of measurements. There is sufficient agreement between the theoretical and experimental values. However, some theoretical issues are discussed to avoid misinterpretations and excessive expectations. PMID:23586036

Multiplexed Nanoplasmonic Temporal Profiling of T-Cell Response under Immunomodulatory Agent Exposure

PubMed Central

2016-01-01

Immunomodulatory drugs—agents regulating the immune response—are commonly used for treating immune system disorders and minimizing graft versus host disease in persons receiving organ transplants. At the cellular level, immunosuppressant drugs are used to inhibit pro-inflammatory or tissue-damaging responses of cells. However, few studies have so far precisely characterized the cellular-level effect of immunomodulatory treatment. The primary challenge arises due to the rapid and transient nature of T-cell immune responses to such treatment. T-cell responses involve a highly interactive network of different types of cytokines, which makes precise monitoring of drug-modulated T-cell response difficult. Here, we present a nanoplasmonic biosensing approach to quantitatively characterize cytokine secretion behaviors of T cells with a fine time-resolution (every 10 min) that are altered by an immunosuppressive drug used in the treatment of T-cell-mediated diseases. With a microfluidic platform integrating antibody-conjugated gold nanorod (AuNR) arrays, the technique enables simultaneous multi-time-point measurements of pro-inflammatory (IL-2, IFN-γ, and TNF-α) and anti-inflammatory (IL-10) cytokines secreted by T cells. The integrated nanoplasmonic biosensors achieve precise measurements with low operating sample volume (1 μL), short assay time (∼30 min), heightened sensitivity (∼20–30 pg/mL), and negligible sensor crosstalk. Data obtained from the multicytokine secretion profiles with high practicality resulting from all of these sensing capabilities provide a comprehensive picture of the time-varying cellular functional state during pharmacologic immunosuppression. The capability to monitor cellular functional response demonstrated in this study has great potential to ultimately permit personalized immunomodulatory treatment. PMID:27478873

The divining root: moisture-driven responses of roots at the micro- and macro-scale.

PubMed

Robbins, Neil E; Dinneny, José R

2015-04-01

Water is fundamental to plant life, but the mechanisms by which plant roots sense and respond to variations in water availability in the soil are poorly understood. Many studies of responses to water deficit have focused on large-scale effects of this stress, but have overlooked responses at the sub-organ or cellular level that give rise to emergent whole-plant phenotypes. We have recently discovered hydropatterning, an adaptive environmental response in which roots position new lateral branches according to the spatial distribution of available water across the circumferential axis. This discovery illustrates that roots are capable of sensing and responding to water availability at spatial scales far lower than those normally studied for such processes. This review will explore how roots respond to water availability with an emphasis on what is currently known at different spatial scales. Beginning at the micro-scale, there is a discussion of water physiology at the cellular level and proposed sensory mechanisms cells use to detect osmotic status. The implications of these principles are then explored in the context of cell and organ growth under non-stress and water-deficit conditions. Following this, several adaptive responses employed by roots to tailor their functionality to the local moisture environment are discussed, including patterning of lateral root development and generation of hydraulic barriers to limit water loss. We speculate that these micro-scale responses are necessary for optimal functionality of the root system in a heterogeneous moisture environment, allowing for efficient water uptake with minimal water loss during periods of drought. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Tensorial Minkowski functionals of triply periodic minimal surfaces

PubMed Central

Mickel, Walter; Schröder-Turk, Gerd E.; Mecke, Klaus

2012-01-01

A fundamental understanding of the formation and properties of a complex spatial structure relies on robust quantitative tools to characterize morphology. A systematic approach to the characterization of average properties of anisotropic complex interfacial geometries is provided by integral geometry which furnishes a family of morphological descriptors known as tensorial Minkowski functionals. These functionals are curvature-weighted integrals of tensor products of position vectors and surface normal vectors over the interfacial surface. We here demonstrate their use by application to non-cubic triply periodic minimal surface model geometries, whose Weierstrass parametrizations allow for accurate numerical computation of the Minkowski tensors. PMID:24098847

Enhanced function of immuno-isolated islets in diabetes therapy by co-encapsulation with an anti-inflammatory drug.

PubMed

Dang, Tram T; Thai, Anh V; Cohen, Joshua; Slosberg, Jeremy E; Siniakowicz, Karolina; Doloff, Joshua C; Ma, Minglin; Hollister-Lock, Jennifer; Tang, Katherine M; Gu, Zhen; Cheng, Hao; Weir, Gordon C; Langer, Robert; Anderson, Daniel G

2013-07-01

Immuno-isolation of islets has the potential to enable the replacement of pancreatic function in diabetic patients. However, host response to the encapsulated islets frequently leads to fibrotic overgrowth with subsequent impairment of the transplanted grafts. Here, we identified and incorporated anti-inflammatory agents into islet-containing microcapsules to address this challenge. In vivo subcutaneous screening of 16 small molecule anti-inflammatory drugs was performed to identify promising compounds that could minimize the formation of fibrotic cell layers. Using parallel non-invasive fluorescent and bioluminescent imaging, we identified dexamethasone and curcumin as the most effective drugs in inhibiting the activities of inflammatory proteases and reactive oxygen species in the host response to subcutaneously injected biomaterials. Next, we demonstrated that co-encapsulating curcumin with pancreatic rat islets in alginate microcapsules reduced fibrotic overgrowth and improved glycemic control in a mouse model of chemically-induced type I diabetes. These results showed that localized administration of anti-inflammatory drug can improve the longevity of encapsulated islets and may facilitate the translation of this technology toward a long-term cure for type I diabetes. Published by Elsevier Ltd.

Group Analysis in MNE-Python of Evoked Responses from a Tactile Stimulation Paradigm: A Pipeline for Reproducibility at Every Step of Processing, Going from Individual Sensor Space Representations to an across-Group Source Space Representation

PubMed Central

Andersen, Lau M.

2018-01-01

An important aim of an analysis pipeline for magnetoencephalographic data is that it allows for the researcher spending maximal effort on making the statistical comparisons that will answer the questions of the researcher, while in turn spending minimal effort on the intricacies and machinery of the pipeline. I here present a set of functions and scripts that allow for setting up a clear, reproducible structure for separating raw and processed data into folders and files such that minimal effort can be spend on: (1) double-checking that the right input goes into the right functions; (2) making sure that output and intermediate steps can be accessed meaningfully; (3) applying operations efficiently across groups of subjects; (4) re-processing data if changes to any intermediate step are desirable. Applying the scripts requires only general knowledge about the Python language. The data analyses are neural responses to tactile stimulations of the right index finger in a group of 20 healthy participants acquired from an Elekta Neuromag System. Two analyses are presented: going from individual sensor space representations to, respectively, an across-group sensor space representation and an across-group source space representation. The processing steps covered for the first analysis are filtering the raw data, finding events of interest in the data, epoching data, finding and removing independent components related to eye blinks and heart beats, calculating participants' individual evoked responses by averaging over epoched data and calculating a grand average sensor space representation over participants. The second analysis starts from the participants' individual evoked responses and covers: estimating noise covariance, creating a forward model, creating an inverse operator, estimating distributed source activity on the cortical surface using a minimum norm procedure, morphing those estimates onto a common cortical template and calculating the patterns of activity that are statistically different from baseline. To estimate source activity, processing of the anatomy of subjects based on magnetic resonance imaging is necessary. The necessary steps are covered here: importing magnetic resonance images, segmenting the brain, estimating boundaries between different tissue layers, making fine-resolution scalp surfaces for facilitating co-registration, creating source spaces and creating volume conductors for each subject. PMID:29403349

Group Analysis in MNE-Python of Evoked Responses from a Tactile Stimulation Paradigm: A Pipeline for Reproducibility at Every Step of Processing, Going from Individual Sensor Space Representations to an across-Group Source Space Representation.

PubMed

Andersen, Lau M

2018-01-01

An important aim of an analysis pipeline for magnetoencephalographic data is that it allows for the researcher spending maximal effort on making the statistical comparisons that will answer the questions of the researcher, while in turn spending minimal effort on the intricacies and machinery of the pipeline. I here present a set of functions and scripts that allow for setting up a clear, reproducible structure for separating raw and processed data into folders and files such that minimal effort can be spend on: (1) double-checking that the right input goes into the right functions; (2) making sure that output and intermediate steps can be accessed meaningfully; (3) applying operations efficiently across groups of subjects; (4) re-processing data if changes to any intermediate step are desirable. Applying the scripts requires only general knowledge about the Python language. The data analyses are neural responses to tactile stimulations of the right index finger in a group of 20 healthy participants acquired from an Elekta Neuromag System. Two analyses are presented: going from individual sensor space representations to, respectively, an across-group sensor space representation and an across-group source space representation. The processing steps covered for the first analysis are filtering the raw data, finding events of interest in the data, epoching data, finding and removing independent components related to eye blinks and heart beats, calculating participants' individual evoked responses by averaging over epoched data and calculating a grand average sensor space representation over participants. The second analysis starts from the participants' individual evoked responses and covers: estimating noise covariance, creating a forward model, creating an inverse operator, estimating distributed source activity on the cortical surface using a minimum norm procedure, morphing those estimates onto a common cortical template and calculating the patterns of activity that are statistically different from baseline. To estimate source activity, processing of the anatomy of subjects based on magnetic resonance imaging is necessary. The necessary steps are covered here: importing magnetic resonance images, segmenting the brain, estimating boundaries between different tissue layers, making fine-resolution scalp surfaces for facilitating co-registration, creating source spaces and creating volume conductors for each subject.

40 CFR 796.3500 - Hydrolysis as a function of pH at 25 °C.

Code of Federal Regulations, 2014 CFR

2014-07-01

... equivalent grade) shall be used to minimize biodegradation. ASTM Type IIA water is described in ASTM D 1193... experiments to eliminate or minimize biodegradation. Glassware can be sterilized in an autoclave or by any...

AN ORGANOTYPIC UNIAXIAL STRAIN MODEL USING MICROFLUIDICS

PubMed Central

Dollé, Jean-Pierre; Morrison, Barclay; Schloss, Rene R.; Yarmush, Martin L.

2012-01-01

Traumatic brain injuries are the leading cause of disability each year in the US. The most common and devastating consequence is the stretching of axons caused by shear deformation that occurs during rotational acceleration of the brain during injury. The injury effects on axonal molecular and functional events are not fully characterized. We have developed a strain injury model that maintains the three dimensional cell architecture and neuronal networks found in vivo with the ability to visualize individual axons and their response to a mechanical injury. The advantage of this model is that it can apply uniaxial strains to axons that make functional connections between two organotypic slices and injury responses can be observed in real-time and over long term. This uniaxial strain model was designed to be capable of applying an array of mechanical strains at various rates of strain, thus replicating a range of modes of axonal injury. Long term culture, preservation of slice and cell orientation, and slice-slice connection on the device was demonstrated. The device has the ability to strain either individual axons or bundles of axons through the control of microchannel dimensions. The fidelity of the model was verified by observing characteristic responses to various strain injuries which included axonal beading, delayed elastic effects and breakdown in microtubules. Microtubule breakdown was shown to be dependent on the degree of the applied strain field, where maximal breakdown was observed at peak strain and minimal breakdown is observed at low strain. This strain injury model could be a powerful tool in assessing strain injury effects on functional axonal connections. PMID:23233120

How the type of input function affects the dynamic response of conducting polymer actuators

NASA Astrophysics Data System (ADS)

Xiang, Xingcan; Alici, Gursel; Mutlu, Rahim; Li, Weihua

2014-10-01

There has been a growing interest in smart actuators typified by conducting polymer actuators, especially in their (i) fabrication, modeling and control with minimum external data and (ii) applications in bio-inspired devices, robotics and mechatronics. Their control is a challenging research problem due to the complex and nonlinear properties of these actuators, which cannot be predicted accurately. Based on an input-shaping technique, we propose a new method to improve the conducting polymer actuators’ command-following ability, while minimizing their electric power consumption. We applied four input functions with smooth characteristics to a trilayer conducting polymer actuator to experimentally evaluate its command-following ability under an open-loop control strategy and a simulated feedback control strategy, and, more importantly, to quantify how the type of input function affects the dynamic response of this class of actuators. We have found that the four smooth inputs consume less electrical power than sharp inputs such as a step input with discontinuous higher-order derivatives. We also obtained an improved transient response performance from the smooth inputs, especially under the simulated feedback control strategy, which we have proposed previously [X Xiang, R Mutlu, G Alici, and W Li, 2014 “Control of conducting polymer actuators without physical feedback: simulated feedback control approach with particle swarm optimization’, Journal of Smart Materials and Structure, 23]. The idea of using a smooth input command, which results in lower power consumption and better control performance, can be extended to other smart actuators. Consuming less electrical energy or power will have a direct effect on enhancing the operational life of these actuators.

A computer tool for a minimax criterion in binary response and heteroscedastic simple linear regression models.

PubMed

Casero-Alonso, V; López-Fidalgo, J; Torsney, B

2017-01-01

Binary response models are used in many real applications. For these models the Fisher information matrix (FIM) is proportional to the FIM of a weighted simple linear regression model. The same is also true when the weight function has a finite integral. Thus, optimal designs for one binary model are also optimal for the corresponding weighted linear regression model. The main objective of this paper is to provide a tool for the construction of MV-optimal designs, minimizing the maximum of the variances of the estimates, for a general design space. MV-optimality is a potentially difficult criterion because of its nondifferentiability at equal variance designs. A methodology for obtaining MV-optimal designs where the design space is a compact interval [a, b] will be given for several standard weight functions. The methodology will allow us to build a user-friendly computer tool based on Mathematica to compute MV-optimal designs. Some illustrative examples will show a representation of MV-optimal designs in the Euclidean plane, taking a and b as the axes. The applet will be explained using two relevant models. In the first one the case of a weighted linear regression model is considered, where the weight function is directly chosen from a typical family. In the second example a binary response model is assumed, where the probability of the outcome is given by a typical probability distribution. Practitioners can use the provided applet to identify the solution and to know the exact support points and design weights. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Minimal Residual Disease in Acute Myeloid Leukemia: Still a Work in Progress?

PubMed Central

Mosna, Federico; Capelli, Debora; Gottardi, Michele

2017-01-01

Minimal residual disease evaluation refers to a series of molecular and immunophenotypical techniques aimed at detecting submicroscopic disease after therapy. As such, its application in acute myeloid leukemia has greatly increased our ability to quantify treatment response, and to determine the chemosensitivity of the disease, as the final product of the drug schedule, dose intensity, biodistribution, and the pharmakogenetic profile of the patient. There is now consistent evidence for the prognostic power of minimal residual disease evaluation in acute myeloid leukemia, which is complementary to the baseline prognostic assessment of the disease. The focus for its use is therefore shifting to individualize treatment based on a deeper evaluation of chemosensitivity and residual tumor burden. In this review, we will summarize the results of the major clinical studies evaluating minimal residual disease in acute myeloid leukemia in adults in recent years and address the technical and practical issues still hampering the spread of these techniques outside controlled clinical trials. We will also briefly speculate on future developments and offer our point of view, and a word of caution, on the present use of minimal residual disease measurements in “real-life” practice. Still, as final standardization and diffusion of the methods are sorted out, we believe that minimal residual disease will soon become the new standard for evaluating response in the treatment of acute myeloid leukemia. PMID:28587190

A search of impact orbits for near-Earth objects by means of minimization of two target functions product. (Russian Title: Поиск столкновительных орбит астероидов, сближающихся с Землей, с помощью минимизации произведения двух целевых функций)

NASA Astrophysics Data System (ADS)

Baturin, A. P.

2011-07-01

The method of NEO's impact orbits search based on two target functions product minimization is presented. These functions are: a square of asteroid-Earth distance at the moment of close approach and a sum of squares of angular residuals. Besides, the method includes a minimization of asteroid-Earth distance's square in function of time alone when initial motion parameters are fixed. Both minimizations are carrying out in turn each by another. The testing of method has been made on the problem of Apophis's impact orbit search. The results of the testing have depicted an effectivity of presented method in searching of impact orbits for the Apophis's Earth encounters in 2036 and 2037.

Responsiveness, minimal detectable change, and minimal clinically important difference of the Nottingham Extended Activities of Daily Living Scale in patients with improved performance after stroke rehabilitation.

PubMed

Wu, Ching-yi; Chuang, Li-ling; Lin, Keh-chung; Lee, Shin-da; Hong, Wei-hsien

2011-08-01

To determine the responsiveness, minimal detectable change (MDC), and minimal clinically important differences (MCIDs) of the Nottingham Extended Activities of Daily Living (NEADL) scale and to assess percentages of patients' change scores exceeding the MDC and MCID after stroke rehabilitation. Secondary analyses of patients who received stroke rehabilitation therapy. Medical centers. Patients with stroke (N=78). Secondary analyses of patients who received 1 of 4 rehabilitation interventions. Responsiveness (standardized response mean [SRM]), 90% confidence that a change score at this threshold or higher is true and reliable rather than measurement error (MDC(90)), and MCID on the NEADL score and percentages of patients exceeding the MDC(90) and MCID. The SRM of the total NEADL scale was 1.3. The MDC(90) value for the total NEADL scale was 4.9, whereas minima and maxima of the MCID for total NEADL score were 2.4 and 6.1 points, respectively. Percentages of patients exceeding the MDC(90) and MCID of the total NEADL score were 50.0%, 73.1%, and 32.1%, respectively. The NEADL is a responsive instrument relevant for measuring change in instrumental activities of daily living after stroke rehabilitation. A patient's change score has to reach 4.9 points on the total to indicate a true change. The mean change score of a stroke group on the total NEADL scale should achieve 6.1 points to be regarded as clinically important. Our findings are based on patients with improved NEADL performance after they received specific interventions. Future research with larger sample sizes is warranted to validate these estimates. Copyright © 2011 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Pupillary and Heart Rate Reactivity in Children with Minimal Brain Dysfunction

ERIC Educational Resources Information Center

Zahn, Theodore P.; And Others

1978-01-01

In an attempt to replicate and extend previous findings on autonomic arousal and responsivity in children with minimal brain dysfunction (MBD), pupil size, heart rate, skin conductance, and skin temperature were recorded from 32 MBD and 45 control children (6-13 years old). (Author/CL)

How Much Is Enough? Minimal Responses of Water Quality and Stream Biota to Partial Retrofit Stormwater Management in a Suburban Neighborhood

EPA Science Inventory

Decentralized stormwater management approaches (e.g., biofiltration swales, pervious pavement, green roofs, rain gardens) that capture, detain, infiltrate, and filter runoff are now commonly used to minimize the impacts of stormwater runoff from impervious surfaces on aquatic eco...