Volterra-series-based nonlinear system modeling and its engineering applications: A state-of-the-art review

NASA Astrophysics Data System (ADS)

Cheng, C. M.; Peng, Z. K.; Zhang, W. M.; Meng, G.

2017-03-01

Nonlinear problems have drawn great interest and extensive attention from engineers, physicists and mathematicians and many other scientists because most real systems are inherently nonlinear in nature. To model and analyze nonlinear systems, many mathematical theories and methods have been developed, including Volterra series. In this paper, the basic definition of the Volterra series is recapitulated, together with some frequency domain concepts which are derived from the Volterra series, including the general frequency response function (GFRF), the nonlinear output frequency response function (NOFRF), output frequency response function (OFRF) and associated frequency response function (AFRF). The relationship between the Volterra series and other nonlinear system models and nonlinear problem solving methods are discussed, including the Taylor series, Wiener series, NARMAX model, Hammerstein model, Wiener model, Wiener-Hammerstein model, harmonic balance method, perturbation method and Adomian decomposition. The challenging problems and their state of arts in the series convergence study and the kernel identification study are comprehensively introduced. In addition, a detailed review is then given on the applications of Volterra series in mechanical engineering, aeroelasticity problem, control engineering, electronic and electrical engineering.

33 CFR 155.1040 - Response plan requirements for unmanned tank barges carrying oil as a primary cargo.

Code of Federal Regulations, 2013 CFR

2013-07-01

... the towing vessel crew and facility or fleeting area personnel, if any, to initiate a response and... functional areas and must further include information for key components within each functional area: (i...) Spill response operations; (vi) Planning; (vii) Logistics support; and (viii) Finance. (5) The...

33 CFR 155.1040 - Response plan requirements for unmanned tank barges carrying oil as a primary cargo.

Code of Federal Regulations, 2011 CFR

2011-07-01

... the towing vessel crew and facility or fleeting area personnel, if any, to initiate a response and... functional areas and must further include information for key components within each functional area: (i...) Spill response operations; (vi) Planning; (vii) Logistics support; and (viii) Finance. (5) The...

33 CFR 155.1040 - Response plan requirements for unmanned tank barges carrying oil as a primary cargo.

Code of Federal Regulations, 2012 CFR

2012-07-01

... the towing vessel crew and facility or fleeting area personnel, if any, to initiate a response and... functional areas and must further include information for key components within each functional area: (i...) Spill response operations; (vi) Planning; (vii) Logistics support; and (viii) Finance. (5) The...

33 CFR 155.1040 - Response plan requirements for unmanned tank barges carrying oil as a primary cargo.

Code of Federal Regulations, 2014 CFR

2014-07-01

... the towing vessel crew and facility or fleeting area personnel, if any, to initiate a response and... functional areas and must further include information for key components within each functional area: (i...) Spill response operations; (vi) Planning; (vii) Logistics support; and (viii) Finance. (5) The...

Numerical and functional responses of intestinal helminths in three rajid skates: evidence for competition between parasites?

PubMed

Randhawa, Haseeb S

2012-11-01

Host-parasite interactions generally involve communities of parasites. Within these communities, species will co-exist and/or interact with one another in a manner either benefiting the species involved or to the detriment of one or more of the species. At the level of helminth infracommunities, evidence for intra- and inter-specific competition includes numerical responses, i.e. those regulating helminth intensity of infection, and functional responses, i.e. where the presence of competitors modifies the realised niche of infrapopulations. The objectives of this study are to assess the numerical and functional responses of helminths in infracommunities from 3 rajid skates using general linear models. Despite a lack of numerical responses, functional responses to intra- and inter-specific interactions were observed. A positive correlation between the number of individuals in an infrapopulation and its niche breadth (functional response) was observed for the tapeworms Pseudanthobothrium spp. and Echeneibothrium spp., in all their respective hosts, and for the nematode Pseudanisakis sp. in the little skate. Evidence for inter-specific competition includes niche shifts in Pseudanthobothrium purtoni (ex little skate) and Pseudanisakis sp. (ex thorny skate) in the presence of Pseudanisakis sp. and the tapeworm Grillotia sp., respectively. These results are consistent with other studies in providing evidence for competition between helminths of skates.

7 CFR 11.22 - Functions.

Code of Federal Regulations, 2010 CFR

2010-01-01

.... (a) Director. Provides executive direction for NAD. The Director is responsible for developing and... respond to all FOIA requests concerning appeal decisions and case records maintained by NAD. (b) Deputy Director for Hearings and Administration. Responsible for all administrative functions of NAD, including...

PEPFAR/DOD/Pharmaccess/Tanzania Peoples Defence Forces HIV/AIDS Program

DTIC Science & Technology

2007-10-01

institutions share many features of a private company, including a hierarchy of functions, investment in training and responsibility for the health status...institutions share many features of a private company, including a hierarchy of functions, investment in training and responsibility for the health...Decks of cards will be distributed to all TPDF Units, Intelligence, Navy and Air Force bases and schools. 2000 Decks will be shared (under the Global

24 CFR 891.400 - Responsibilities of owner.

Code of Federal Regulations, 2012 CFR

2012-04-01

... DISABILITIES PROGRAM) SUPPORTIVE HOUSING FOR THE ELDERLY AND PERSONS WITH DISABILITIES Project Management § 891... unleased units or residential spaces. (b) Management and maintenance. The Owner is responsible for all management functions. These functions include selection and admission of tenants, required reexaminations of...

24 CFR 891.400 - Responsibilities of owner.

Code of Federal Regulations, 2013 CFR

2013-04-01

... DISABILITIES PROGRAM) SUPPORTIVE HOUSING FOR THE ELDERLY AND PERSONS WITH DISABILITIES Project Management § 891... unleased units or residential spaces. (b) Management and maintenance. The Owner is responsible for all management functions. These functions include selection and admission of tenants, required reexaminations of...

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.

Response functions for dimers and square-symmetric molecules in four-wave-mixing experiments with polarized light

NASA Astrophysics Data System (ADS)

Smith, Eric Ryan; Farrow, Darcie A.; Jonas, David M.

2005-07-01

Four-wave-mixing nonlinear-response functions are given for intermolecular and intramolecular vibrations of a perpendicular dimer and intramolecular vibrations of a square-symmetric molecule containing a doubly degenerate state. A two-dimensional particle-in-a-box model is used to approximate the electronic wave functions and obtain harmonic potentials for nuclear motion. Vibronic interactions due to symmetry-lowering distortions along Jahn-Teller active normal modes are discussed. Electronic dephasing due to nuclear motion along both symmetric and asymmetric normal modes is included in these response functions, but population transfer between states is not. As an illustration, these response functions are used to predict the pump-probe polarization anisotropy in the limit of impulsive excitation.

Abnormal cardiovascular response to exercise in hypertension: contribution of neural factors.

PubMed

Mitchell, Jere H

2017-06-01

During both dynamic (e.g., endurance) and static (e.g., strength) exercise there are exaggerated cardiovascular responses in hypertension. This includes greater increases in blood pressure, heart rate, and efferent sympathetic nerve activity than in normal controls. Two of the known neural factors that contribute to this abnormal cardiovascular response are the exercise pressor reflex (EPR) and functional sympatholysis. The EPR originates in contracting skeletal muscle and reflexly increases sympathetic efferent nerve activity to the heart and blood vessels as well as decreases parasympathetic efferent nerve activity to the heart. These changes in autonomic nerve activity cause an increase in blood pressure, heart rate, left ventricular contractility, and vasoconstriction in the arterial tree. However, arterial vessels in the contracting skeletal muscle have a markedly diminished vasoconstrictor response. The markedly diminished vasoconstriction in contracting skeletal muscle has been termed functional sympatholysis. It has been shown in hypertension that there is an enhanced EPR, including both its mechanoreflex and metaboreflex components, and an impaired functional sympatholysis. These conditions set up a positive feedback or vicious cycle situation that causes a progressively greater decrease in the blood flow to the exercising muscle. Thus these two neural mechanisms contribute significantly to the abnormal cardiovascular response to exercise in hypertension. In addition, exercise training in hypertension decreases the enhanced EPR, including both mechanoreflex and metaboreflex function, and improves the impaired functional sympatholysis. These two changes, caused by exercise training, improve the muscle blood flow to exercising muscle and cause a more normal cardiovascular response to exercise in hypertension. Copyright © 2017 the American Physiological Society.

Final state interactions and inclusive nuclear collisions

NASA Technical Reports Server (NTRS)

Cucinotta, Francis A.; Dubey, Rajendra R.

1993-01-01

A scattering formalism is developed in a multiple scattering model to describe inclusive momentum distributions for high-energy projectiles. The effects of final state interactions on response functions and momentum distributions are investigated. Calculations for high-energy protons that include shell model response functions are compared with experiments.

Changes of brain response induced by simulated weightlessness

NASA Astrophysics Data System (ADS)

Wei, Jinhe; Yan, Gongdong; Guan, Zhiqiang

The characteristics change of brain response was studied during 15° head-down tilt (HDT) comparing with 45° head-up tilt (HUT). The brain responses evaluated included the EEG power spectra change at rest and during mental arithmetic, and the event-related potentials (ERPs) of somatosensory, selective attention and mental arithmetic activities. The prominent feature of brain response change during HDT revealed that the brain function was inhibited to some extent. Such inhibition included that the significant increment of "40Hz" activity during HUT arithmetic almost disappeared during HDT arithmetic, and that the positive-potential effect induced by HDT presented in all kinds of ERPs measured, but the slow negative wave reflecting mental arithmetic and memory process was elongated. These data suggest that the brain function be affected profoundly by the simulated weightlessness, therefore, the brain function change during space flight should be studied systematically.

RRAWFLOW: Rainfall-Response Aquifer and Watershed Flow Model (v1.11)

NASA Astrophysics Data System (ADS)

Long, A. J.

2014-09-01

The Rainfall-Response Aquifer and Watershed Flow Model (RRAWFLOW) is a lumped-parameter model that simulates streamflow, springflow, groundwater level, solute transport, or cave drip for a measurement point in response to a system input of precipitation, recharge, or solute injection. The RRAWFLOW open-source code is written in the R language and is included in the Supplement to this article along with an example model of springflow. RRAWFLOW includes a time-series process to estimate recharge from precipitation and simulates the response to recharge by convolution; i.e., the unit hydrograph approach. Gamma functions are used for estimation of parametric impulse-response functions (IRFs); a combination of two gamma functions results in a double-peaked IRF. A spline fit to a set of control points is introduced as a new method for estimation of nonparametric IRFs. Other options include the use of user-defined IRFs and different methods to simulate time-variant systems. For many applications, lumped models simulate the system response with equal accuracy to that of distributed models, but moreover, the ease of model construction and calibration of lumped models makes them a good choice for many applications. RRAWFLOW provides professional hydrologists and students with an accessible and versatile tool for lumped-parameter modeling.

Effects of the space flight environment on the immune system

NASA Technical Reports Server (NTRS)

Sonnenfeld, Gerald; Butel, Janet S.; Shearer, William T.

2003-01-01

Space flight conditions have a dramatic effect on a variety of physiologic functions of mammals, including muscle, bone, and neurovestibular function. Among the physiological functions that are affected when humans or animals are exposed to space flight conditions is the immune response. The focus of this review is on the function of the immune system in space flight conditions during actual space flights, as well as in models of space flight conditions on the earth. The experiments were carried out in tissue culture systems, in animal models, and in human subjects. The results indicate that space flight conditions alter cell-mediated immune responses, including lymphocyte proliferation and subset distribution, and cytokine production. The mechanism(s) of space flight-induced alterations in immune system function remain(s) to be established. It is likely, however, that multiple factors, including microgravity, stress, neuroendocrine factors, sleep disruption, and nutritional factors, are involved in altering certain functions of the immune system. Such alterations could lead to compromised defenses against infections and tumors.

KAOS/LIB-V: A library of nuclear response functions generated by KAOS-V code from ENDF/B-V and other data files

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

Farawila, Y.; Gohar, Y.; Maynard, C.

1989-04-01

KAOS/LIB-V: A library of processed nuclear responses for neutronics analyses of nuclear systems has been generated. The library was prepared using the KAOS-V code and nuclear data from ENDF/B-V. The library includes kerma (kinetic energy released in materials) factors and other nuclear response functions for all materials presently of interest in fusion and fission applications for 43 nonfissionable and 15 fissionable isotopes and elements. The nuclear response functions include gas production and tritium-breeding functions, and all important reaction cross sections. KAOS/LIB-V employs the VITAMIN-E weighting function and energy group structure of 174 neutron groups. Auxiliary nuclear data bases, e.g., themore » Japanese evaluated nuclear data library JENDL-2 were used as a source of isotopic cross sections when these data are not provided in ENDF/B-V files for a natural element. These are needed mainly to estimate average quantities such as effective Q-values for the natural element. This analysis of local energy deposition was instrumental in detecting and understanding energy balance deficiencies and other problems in the ENDF/B-V data. Pertinent information about the library and a graphical display of the main nuclear response functions for all materials in the library are given. 35 refs.« less

A double expansion method for the frequency response of finite-length beams with periodic parameters

NASA Astrophysics Data System (ADS)

Ying, Z. G.; Ni, Y. Q.

2017-03-01

A double expansion method for the frequency response of finite-length beams with periodic distribution parameters is proposed. The vibration response of the beam with spatial periodic parameters under harmonic excitations is studied. The frequency response of the periodic beam is the function of parametric period and then can be expressed by the series with the product of periodic and non-periodic functions. The procedure of the double expansion method includes the following two main steps: first, the frequency response function and periodic parameters are expanded by using identical periodic functions based on the extension of the Floquet-Bloch theorem, and the period-parametric differential equation for the frequency response is converted into a series of linear differential equations with constant coefficients; second, the solutions to the linear differential equations are expanded by using modal functions which satisfy the boundary conditions, and the linear differential equations are converted into algebraic equations according to the Galerkin method. The expansion coefficients are obtained by solving the algebraic equations and then the frequency response function is finally determined. The proposed double expansion method can uncouple the effects of the periodic expansion and modal expansion so that the expansion terms are determined respectively. The modal number considered in the second expansion can be reduced remarkably in comparison with the direct expansion method. The proposed double expansion method can be extended and applied to the other structures with periodic distribution parameters for dynamics analysis. Numerical results on the frequency response of the finite-length periodic beam with various parametric wave numbers and wave amplitude ratios are given to illustrate the effective application of the proposed method and the new frequency response characteristics, including the parameter-excited modal resonance, doubling-peak frequency response and remarkable reduction of the maximum frequency response for certain parametric wave number and wave amplitude. The results have the potential application to structural vibration control.

Standardized emergency management system and response to a smallpox emergency.

PubMed

Kim-Farley, Robert J; Celentano, John T; Gunter, Carol; Jones, Jessica W; Stone, Rogelio A; Aller, Raymond D; Mascola, Laurene; Grigsby, Sharon F; Fielding, Jonathan E

2003-01-01

The smallpox virus is a high-priority, Category-A agent that poses a global, terrorism security risk because it: (1) easily can be disseminated and transmitted from person to person; (2) results in high mortality rates and has the potential for a major public health impact; (3) might cause public panic and social disruption; and (4) requires special action for public health preparedness. In recognition of this risk, the Los Angeles County Department of Health Services (LAC-DHS) developed the Smallpox Preparedness, Response, and Recovery Plan for LAC to prepare for the possibility of an outbreak of smallpox. A unique feature of the LAC-DHS plan is its explicit use of the Standardized Emergency Management System (SEMS) framework for detailing the functions needed to respond to a smallpox emergency. The SEMS includes the Incident Command System (ICS) structure (management, operations, planning/intelligence, logistics, and finance/administration), the mutual-aid system, and the multi/interagency coordination required during a smallpox emergency. Management for incident command includes setting objectives and priorities, information (risk communications), safety, and liaison. Operations includes control and containment of a smallpox outbreak including ring vaccination, mass vaccination, adverse events monitoring and assessment, management of confirmed and suspected smallpox cases, contact tracing, active surveillance teams and enhanced hospital-based surveillance, and decontamination. Planning/intelligence functions include developing the incident action plan, epidemiological investigation and analysis of smallpox cases, and epidemiological assessment of the vaccination coverage status of populations at risk. Logistics functions include receiving, handling, inventorying, and distributing smallpox vaccine and vaccination clinic supplies; personnel; transportation; communications; and health care of personnel. Finally, finance/administration functions include monitoring costs related to the smallpox emergency, procurement, and administrative aspects that are not handled by other functional divisions of incident command systems. The plan was developed and is under frequent review by the LAC-DHS Smallpox Planning Working Group, and is reviewed periodically by the LAC Bioterrorism Advisory Committee, and draws upon the Smallpox Response Plan and Guidelines of the Centers for Disease Control and Prevention (CDC) and recommendations of the Advisory Committee on Immunization Practices (ACIP). The Smallpox Preparedness, Response, and Recovery Plan, with its SEMS framework and ICS structure, now is serving as a model for the development of LAC-DHS plans for responses to other terrorist or natural-outbreak responses.

Sparse regularization for force identification using dictionaries

NASA Astrophysics Data System (ADS)

Qiao, Baijie; Zhang, Xingwu; Wang, Chenxi; Zhang, Hang; Chen, Xuefeng

2016-04-01

The classical function expansion method based on minimizing l2-norm of the response residual employs various basis functions to represent the unknown force. Its difficulty lies in determining the optimum number of basis functions. Considering the sparsity of force in the time domain or in other basis space, we develop a general sparse regularization method based on minimizing l1-norm of the coefficient vector of basis functions. The number of basis functions is adaptively determined by minimizing the number of nonzero components in the coefficient vector during the sparse regularization process. First, according to the profile of the unknown force, the dictionary composed of basis functions is determined. Second, a sparsity convex optimization model for force identification is constructed. Third, given the transfer function and the operational response, Sparse reconstruction by separable approximation (SpaRSA) is developed to solve the sparse regularization problem of force identification. Finally, experiments including identification of impact and harmonic forces are conducted on a cantilever thin plate structure to illustrate the effectiveness and applicability of SpaRSA. Besides the Dirac dictionary, other three sparse dictionaries including Db6 wavelets, Sym4 wavelets and cubic B-spline functions can also accurately identify both the single and double impact forces from highly noisy responses in a sparse representation frame. The discrete cosine functions can also successfully reconstruct the harmonic forces including the sinusoidal, square and triangular forces. Conversely, the traditional Tikhonov regularization method with the L-curve criterion fails to identify both the impact and harmonic forces in these cases.

fMRI during natural sleep as a method to study brain function during early childhood.

PubMed

Redcay, Elizabeth; Kennedy, Daniel P; Courchesne, Eric

2007-12-01

Many techniques to study early functional brain development lack the whole-brain spatial resolution that is available with fMRI. We utilized a relatively novel method in which fMRI data were collected from children during natural sleep. Stimulus-evoked responses to auditory and visual stimuli as well as stimulus-independent functional networks were examined in typically developing 2-4-year-old children. Reliable fMRI data were collected from 13 children during presentation of auditory stimuli (tones, vocal sounds, and nonvocal sounds) in a block design. Twelve children were presented with visual flashing lights at 2.5 Hz. When analyses combined all three types of auditory stimulus conditions as compared to rest, activation included bilateral superior temporal gyri/sulci (STG/S) and right cerebellum. Direct comparisons between conditions revealed significantly greater responses to nonvocal sounds and tones than to vocal sounds in a number of brain regions including superior temporal gyrus/sulcus, medial frontal cortex and right lateral cerebellum. The response to visual stimuli was localized to occipital cortex. Furthermore, stimulus-independent functional connectivity MRI analyses (fcMRI) revealed functional connectivity between STG and other temporal regions (including contralateral STG) and medial and lateral prefrontal regions. Functional connectivity with an occipital seed was localized to occipital and parietal cortex. In sum, 2-4 year olds showed a differential fMRI response both between stimulus modalities and between stimuli in the auditory modality. Furthermore, superior temporal regions showed functional connectivity with numerous higher-order regions during sleep. We conclude that the use of sleep fMRI may be a valuable tool for examining functional brain organization in young children.

Endoplasmic Reticulum and the Unfolded Protein Response: Dynamics and Metabolic Integration

PubMed Central

Bravo, Roberto; Parra, Valentina; Gatica, Damián; Rodriguez, Andrea E.; Torrealba, Natalia; Paredes, Felipe; Wang, Zhao V.; Zorzano, Antonio; Hill, Joseph A.; Jaimovich, Enrique; Quest, Andrew F.G.; Lavandero, Sergio

2013-01-01

The endoplasmic reticulum (ER) is a dynamic intracellular organelle with multiple functions essential for cellular homeostasis, development, and stress responsiveness. In response to cellular stress, a well-established signaling cascade, the unfolded protein response (UPR), is activated. This intricate mechanism is an important means of reestablishing cellular homeostasis and alleviating the inciting stress. Now, emerging evidence has demonstrated that the UPR influences cellular metabolism through diverse mechanisms, including calcium and lipid transfer, raising the prospect of involvement of these processes in the pathogenesis of disease, including neurodegeneration, cancer, diabetes mellitus and cardiovascular disease. Here, we review the distinct functions of the ER and UPR from a metabolic point of view, highlighting their association with prevalent pathologies. PMID:23317820

Prostaglandins and Inflammation

PubMed Central

Ricciotti, Emanuela; FitzGerald, Garret A.

2011-01-01

Prostaglandins are lipid autacoids derived from arachidonic acid. They both sustain homeostatic functions and mediate pathogenic mechanisms, including the inflammatory response. They are generated from arachidonate by the action of cyclooxygenase (COX) isoenzymes and their biosynthesis is blocked by nonsteroidal anti-inflammatory drugs (NSAIDs), including those selective for inhibition of COX-2. Despite the clinical efficacy of NSAIDs, prostaglandins may function in both the promotion and resolution of inflammation. This review summarizes insights into the mechanisms of prostaglandin generation and the roles of individual mediators and their receptors in modulating the inflammatory response. Prostaglandin biology has potential clinical relevance for atherosclerosis, the response to vascular injury and aortic aneurysm. PMID:21508345

Assessing Stress-Related Treatment Needs among Girls at Risk for Poor Functional Outcomes: The Impact of Cumulative Adversity, Criterion Traumas, and Non-Criterion Events

PubMed Central

Lansing, Amy E.; Plante, Wendy Y.; Beck, Audrey N.

2016-01-01

Despite growing recognition that cumulative adversity (total stressor exposure), including complex trauma, increases the risk for psychopathology and impacts development, assessment strategies lag behind: Trauma-related mental health needs (symptoms, functional impairment, maladaptive coping) are typically assessed in response to only one qualifying Criterion-A event. This is especially problematic for youth at-risk for health and academic disparities who experience cumulative adversity, including non-qualifying events (parental separations) which may produce more impairing symptomatology. Data from 118 delinquent girls demonstrate: 1) an average of 14 adverse Criterion-A and non-Criterion event exposures; 2) serious maladaptive coping strategies (self-injury) directly in response to cumulative adversity; 3) more cumulative adversity-related than worst-event related symptomatology and functional impairment; and 4) comparable symptomatology, but greater functional impairment, in response to non-Criterion events. These data support the evaluation of mental health needs in response to cumulative adversity for optimal identification and tailoring of services in high-risk populations to reduce disparities. PMID:27745922

Assessing stress-related treatment needs among girls at risk for poor functional outcomes: The impact of cumulative adversity, criterion traumas, and non-criterion events.

PubMed

Lansing, Amy E; Plante, Wendy Y; Beck, Audrey N

2017-05-01

Despite growing recognition that cumulative adversity (total stressor exposure, including complex trauma), increases the risk for psychopathology and impacts development, assessment strategies lag behind: Adversity-related mental health needs (symptoms, functional impairment, maladaptive coping) are typically assessed in response to only one qualifying Criterion-A traumatic event. This is especially problematic for youth at-risk for health and academic disparities who experience cumulative adversity, including non-qualifying events (separation from caregivers) which may produce more impairing symptomatology. Data from 118 delinquent girls demonstrate: (1) an average of 14 adverse Criterion-A and non-Criterion event exposures; (2) serious maladaptive coping strategies (self-injury) directly in response to cumulative adversity; (3) more cumulative adversity-related than worst-event related symptomatology and functional impairment; and (4) comparable symptomatology, but greater functional impairment, in response to non-Criterion events. These data support the evaluation of mental health needs in response to cumulative adversity for optimal identification and tailoring of services in high-risk populations to reduce disparities. Copyright © 2016 Elsevier Ltd. All rights reserved.

An uncertainty model of acoustic metamaterials with random parameters

NASA Astrophysics Data System (ADS)

He, Z. C.; Hu, J. Y.; Li, Eric

2018-01-01

Acoustic metamaterials (AMs) are man-made composite materials. However, the random uncertainties are unavoidable in the application of AMs due to manufacturing and material errors which lead to the variance of the physical responses of AMs. In this paper, an uncertainty model based on the change of variable perturbation stochastic finite element method (CVPS-FEM) is formulated to predict the probability density functions of physical responses of AMs with random parameters. Three types of physical responses including the band structure, mode shapes and frequency response function of AMs are studied in the uncertainty model, which is of great interest in the design of AMs. In this computation, the physical responses of stochastic AMs are expressed as linear functions of the pre-defined random parameters by using the first-order Taylor series expansion and perturbation technique. Then, based on the linear function relationships of parameters and responses, the probability density functions of the responses can be calculated by the change-of-variable technique. Three numerical examples are employed to demonstrate the effectiveness of the CVPS-FEM for stochastic AMs, and the results are validated by Monte Carlo method successfully.

Intrinsic functional connectivity of the central nucleus of the amygdala and bed nucleus of the stria terminalis.

PubMed

Gorka, Adam X; Torrisi, Salvatore; Shackman, Alexander J; Grillon, Christian; Ernst, Monique

2018-03-01

The central nucleus of the amygdala (CeA) and bed nucleus of the stria terminalis (BNST), two nuclei within the central extended amygdala, function as critical relays within the distributed neural networks that coordinate sensory, emotional, and cognitive responses to threat. These structures have overlapping anatomical projections to downstream targets that initiate defensive responses. Despite these commonalities, researchers have also proposed a functional dissociation between the CeA and BNST, with the CeA promoting responses to discrete stimuli and the BNST promoting responses to diffuse threat. Intrinsic functional connectivity (iFC) provides a means to investigate the functional architecture of the brain, unbiased by task demands. Using ultra-high field neuroimaging (7-Tesla fMRI), which provides increased spatial resolution, this study compared the iFC networks of the CeA and BNST in 27 healthy individuals. Both structures were coupled with areas of the medial prefrontal cortex, hippocampus, thalamus, and periaqueductal gray matter. Compared to the BNST, the bilateral CeA was more strongly coupled with the insula and regions that support sensory processing, including thalamus and fusiform gyrus. In contrast, the bilateral BNST was more strongly coupled with regions involved in cognitive and motivational processes, including the dorsal paracingulate gyrus, posterior cingulate cortex, and striatum. Collectively, these findings suggest that responses to sensory stimulation are preferentially coordinated by the CeA and cognitive and motivational responses are preferentially coordinated by the BNST. Published by Elsevier Inc.

Image Processing, Coding, and Compression with Multiple-Point Impulse Response Functions.

NASA Astrophysics Data System (ADS)

Stossel, Bryan Joseph

1995-01-01

Aspects of image processing, coding, and compression with multiple-point impulse response functions are investigated. Topics considered include characterization of the corresponding random-walk transfer function, image recovery for images degraded by the multiple-point impulse response, and the application of the blur function to image coding and compression. It is found that although the zeros of the real and imaginary parts of the random-walk transfer function occur in continuous, closed contours, the zeros of the transfer function occur at isolated spatial frequencies. Theoretical calculations of the average number of zeros per area are in excellent agreement with experimental results obtained from computer counts of the zeros. The average number of zeros per area is proportional to the standard deviations of the real part of the transfer function as well as the first partial derivatives. Statistical parameters of the transfer function are calculated including the mean, variance, and correlation functions for the real and imaginary parts of the transfer function and their corresponding first partial derivatives. These calculations verify the assumptions required in the derivation of the expression for the average number of zeros. Interesting results are found for the correlations of the real and imaginary parts of the transfer function and their first partial derivatives. The isolated nature of the zeros in the transfer function and its characteristics at high spatial frequencies result in largely reduced reconstruction artifacts and excellent reconstructions are obtained for distributions of impulses consisting of 25 to 150 impulses. The multiple-point impulse response obscures original scenes beyond recognition. This property is important for secure transmission of data on many communication systems. The multiple-point impulse response enables the decoding and restoration of the original scene with very little distortion. Images prefiltered by the random-walk transfer function yield greater compression ratios than are obtained for the original scene. The multiple-point impulse response decreases the bit rate approximately 40-70% and affords near distortion-free reconstructions. Due to the lossy nature of transform-based compression algorithms, noise reduction measures must be incorporated to yield acceptable reconstructions after decompression.

Emotional Responses to Documentary Viewing and the Potential for Transformative Teaching

ERIC Educational Resources Information Center

Smith, Heather J.

2014-01-01

This paper examines the relationship between specific documentaries and white student teachers' emotional responses to their viewing as part of a postgraduate teacher education course on educational equality. Documentaries are considered in terms of features (including elements of text), form (including stylistic conventions) and function in order…

49 CFR 194.107 - General response plan requirements.

Code of Federal Regulations, 2012 CFR

2012-10-01

... management system including the functional areas of finance, logistics, operations, planning, and command... economically sensitive areas; (iii) Describe the responsibilities of the operator and of Federal, State and...

Circadian genes, the stress axis, and alcoholism.

PubMed

Sarkar, Dipak K

2012-01-01

The body's internal system to control the daily rhythm of the body's functions (i.e., the circadian system), the body's stress response, and the body's neurobiology are highly interconnected. Thus, the rhythm of the circadian system impacts alcohol use patterns; at the same time, alcohol drinking also can alter circadian functions. The sensitivity of the circadian system to alcohol may result from alcohol's effects on the expression of several of the clock genes that regulate circadian function. The stress response system involves the hypothalamus and pituitary gland in the brain and the adrenal glands, as well as the hormones they secrete, including corticotrophin-releasing hormone, adrenocorticotrophic hormone, and glucocorticoids. It is controlled by brain-signaling molecules, including endogenous opioids such as β-endorphin. Alcohol consumption influences the activity of this system and vice versa. Finally, interactions exist between the circadian system, the hypothalamic-pituitary-adrenal axis, and alcohol consumption. Thus, it seems that certain clock genes may control functions of the stress response system and that these interactions are affected by alcohol.

Plant responses to environmental stress: regulation and functions of the Arabidopsis TCH genes

NASA Technical Reports Server (NTRS)

Braam, J.; Sistrunk, M. L.; Polisensky, D. H.; Xu, W.; Purugganan, M. M.; Antosiewicz, D. M.; Campbell, P.; Johnson, K. A.; McIntire, L. V. (Principal Investigator)

1997-01-01

Expression of the Arabidopsis TCH genes is markedly upregulated in response to a variety of environmental stimuli including the seemingly innocuous stimulus of touch. Understanding the mechanism(s) and factors that control TCH gene regulation will shed light on the signaling pathways that enable plants to respond to environmental conditions. The TCH proteins include calmodulin, calmodulin-related proteins and a xyloglucan endotransglycosylase. Expression analyses and localization of protein accumulation indicates that the potential sites of TCH protein function include expanding cells and tissues under mechanical strain. We hypothesize that at least a subset of the TCH proteins may collaborate in cell wall biogenesis.

Retinoic Acid as a Modulator of T Cell Immunity

PubMed Central

Bono, Maria Rosa; Tejon, Gabriela; Flores-Santibañez, Felipe; Fernandez, Dominique; Rosemblatt, Mario; Sauma, Daniela

2016-01-01

Vitamin A, a generic designation for an array of organic molecules that includes retinal, retinol and retinoic acid, is an essential nutrient needed in a wide array of aspects including the proper functioning of the visual system, maintenance of cell function and differentiation, epithelial surface integrity, erythrocyte production, reproduction, and normal immune function. Vitamin A deficiency is one of the most common micronutrient deficiencies worldwide and is associated with defects in adaptive immunity. Reports from epidemiological studies, clinical trials and experimental studies have clearly demonstrated that vitamin A plays a central role in immunity and that its deficiency is the cause of broad immune alterations including decreased humoral and cellular responses, inadequate immune regulation, weak response to vaccines and poor lymphoid organ development. In this review, we will examine the role of vitamin A in immunity and focus on several aspects of T cell biology such as T helper cell differentiation, function and homing, as well as lymphoid organ development. Further, we will provide an overview of the effects of vitamin A deficiency in the adaptive immune responses and how retinoic acid, through its effect on T cells can fine-tune the balance between tolerance and immunity. PMID:27304965

A Paleolithic Diet with and without Combined Aerobic and Resistance Exercise Increases Functional Brain Responses and Hippocampal Volume in Subjects with Type 2 Diabetes

PubMed Central

Stomby, Andreas; Otten, Julia; Ryberg, Mats; Nyberg, Lars; Olsson, Tommy; Boraxbekk, Carl-Johan

2017-01-01

Type 2 diabetes is associated with impaired episodic memory functions and increased risk of different dementing disorders. Diet and exercise may potentially reverse these impairments. In this study, sedentary individuals with type 2 diabetes treated by lifestyle ± metformin were randomized to a Paleolithic diet (PD, n = 12) with and without high intensity exercise (PDEX, n = 12) for 12 weeks. Episodic memory function, associated functional brain responses and hippocampal gray matter volume was measured by magnetic resonance imaging. A matched, but not randomized, non-interventional group was included as a reference (n = 6). The PD included a high intake of unsaturated fatty acids and protein, and excluded the intake of dairy products, grains, refined sugar and salt. The exercise intervention consisted of 180 min of supervised aerobic and resistance exercise per week. Both interventions induced a significant weight loss, improved insulin sensitivity and increased peak oxygen uptake without any significant group differences. Furthermore, both interventions were associated with increased functional brain responses within the right anterior hippocampus, right inferior occipital gyrus and increased volume of the right posterior hippocampus. There were no changes in memory performance. We conclude that life-style modification may improve neuronal plasticity in brain areas linked to cognitive function in type 2 diabetes. Putative long-term effects on cognitive functions including decreased risk of dementing disorders await further studies. Clinical trials registration number: Clinicaltrials. gov NCT01513798. PMID:29255413

A Paleolithic Diet with and without Combined Aerobic and Resistance Exercise Increases Functional Brain Responses and Hippocampal Volume in Subjects with Type 2 Diabetes.

PubMed

Stomby, Andreas; Otten, Julia; Ryberg, Mats; Nyberg, Lars; Olsson, Tommy; Boraxbekk, Carl-Johan

2017-01-01

Type 2 diabetes is associated with impaired episodic memory functions and increased risk of different dementing disorders. Diet and exercise may potentially reverse these impairments. In this study, sedentary individuals with type 2 diabetes treated by lifestyle ± metformin were randomized to a Paleolithic diet (PD, n = 12) with and without high intensity exercise (PDEX, n = 12) for 12 weeks. Episodic memory function, associated functional brain responses and hippocampal gray matter volume was measured by magnetic resonance imaging. A matched, but not randomized, non-interventional group was included as a reference ( n = 6). The PD included a high intake of unsaturated fatty acids and protein, and excluded the intake of dairy products, grains, refined sugar and salt. The exercise intervention consisted of 180 min of supervised aerobic and resistance exercise per week. Both interventions induced a significant weight loss, improved insulin sensitivity and increased peak oxygen uptake without any significant group differences. Furthermore, both interventions were associated with increased functional brain responses within the right anterior hippocampus, right inferior occipital gyrus and increased volume of the right posterior hippocampus. There were no changes in memory performance. We conclude that life-style modification may improve neuronal plasticity in brain areas linked to cognitive function in type 2 diabetes. Putative long-term effects on cognitive functions including decreased risk of dementing disorders await further studies. Clinical trials registration number: Clinicaltrials. gov NCT01513798.

Skeletal and cardiac muscle pericytes: Functions and therapeutic potential

PubMed Central

Murray, Iain R.; Baily, James E.; Chen, William C.W.; Dar, Ayelet; Gonzalez, Zaniah N.; Jensen, Andrew R.; Petrigliano, Frank A.; Deb, Arjun; Henderson, Neil C.

2017-01-01

Pericytes are periendothelial mesenchymal cells residing within the microvasculature. Skeletal muscle and cardiac pericytes are now recognized to fulfill an increasing number of functions in normal tissue homeostasis, including contributing to microvascular function by maintaining vessel stability and regulating capillary flow. In the setting of muscle injury, pericytes contribute to a regenerative microenvironment through release of trophic factors and by modulating local immune responses. In skeletal muscle, pericytes also directly enhance tissue healing by differentiating into myofibers. Conversely, pericytes have also been implicated in the development of disease states, including fibrosis, heterotopic ossication and calcification, atherosclerosis, and tumor angiogenesis. Despite increased recognition of pericyte heterogeneity, it is not yet clear whether specific subsets of pericytes are responsible for individual functions in skeletal and cardiac muscle homeostasis and disease. PMID:27595928

Dispersion in a thermal plasma including arbitrary degeneracy and quantum recoil.

PubMed

Melrose, D B; Mushtaq, A

2010-11-01

The longitudinal response function for a thermal electron gas is calculated including two quantum effects exactly, degeneracy, and the quantum recoil. The Fermi-Dirac distribution is expanded in powers of a parameter that is small in the nondegenerate limit and the response function is evaluated in terms of the conventional plasma dispersion function to arbitrary order in this parameter. The infinite sum is performed in terms of polylogarithms in the long-wavelength and quasistatic limits, giving results that apply for arbitrary degeneracy. The results are applied to the dispersion relations for Langmuir waves and to screening, reproducing known results in the nondegenerate and completely degenerate limits, and generalizing them to arbitrary degeneracy.

Decreased prefrontal functional brain response during memory testing in women with Cushing's syndrome in remission.

PubMed

Ragnarsson, Oskar; Stomby, Andreas; Dahlqvist, Per; Evang, Johan A; Ryberg, Mats; Olsson, Tommy; Bollerslev, Jens; Nyberg, Lars; Johannsson, Gudmundur

2017-08-01

Neurocognitive dysfunction is an important feature of Cushing's syndrome (CS). Our hypothesis was that patients with CS in remission have decreased functional brain responses in the prefrontal cortex and hippocampus during memory testing. In this cross-sectional study we included 19 women previously treated for CS and 19 controls matched for age, gender, and education. The median remission time was 7 (IQR 6-10) years. Brain activity was studied with functional magnetic resonance imaging during episodic- and working-memory tasks. The primary regions of interest were the prefrontal cortex and the hippocampus. A voxel-wise comparison of functional brain responses in patients and controls was performed. During episodic-memory encoding, patients displayed lower functional brain responses in the left and right prefrontal gyrus (p<0.001) and in the right inferior occipital gyrus (p<0.001) compared with controls. There was a trend towards lower functional brain responses in the left posterior hippocampus in patients (p=0.05). During episodic-memory retrieval, the patients displayed lower functional brain responses in several brain areas with the most predominant difference in the right prefrontal cortex (p<0.001). During the working memory task, patients had lower response in the prefrontal cortices bilaterally (p<0.005). Patients, but not controls, had lower functional brain response during a more complex working memory task compared with a simpler one. In conclusion, women with CS in long-term remission have reduced functional brain responses during episodic and working memory testing. This observation extends previous findings showing long-term adverse effects of severe hypercortisolaemia on brain function. Copyright © 2017 Elsevier Ltd. All rights reserved.

24 CFR 880.601 - Responsibilities of owner.

Code of Federal Regulations, 2011 CFR

2011-04-01

... DISABILITIES PROGRAM) SECTION 8 HOUSING ASSISTANCE PAYMENTS PROGRAM FOR NEW CONSTRUCTION Management § 880.601... units. (b) Management and maintenance. The owner is responsible for all management functions, including... financial interest and to uphold its program responsibilities where no alternative management agent is...

24 CFR 880.601 - Responsibilities of owner.

Code of Federal Regulations, 2012 CFR

2012-04-01

... DISABILITIES PROGRAM) SECTION 8 HOUSING ASSISTANCE PAYMENTS PROGRAM FOR NEW CONSTRUCTION Management § 880.601... units. (b) Management and maintenance. The owner is responsible for all management functions, including... financial interest and to uphold its program responsibilities where no alternative management agent is...

24 CFR 880.601 - Responsibilities of owner.

Code of Federal Regulations, 2014 CFR

2014-04-01

... DISABILITIES PROGRAM) SECTION 8 HOUSING ASSISTANCE PAYMENTS PROGRAM FOR NEW CONSTRUCTION Management § 880.601... units. (b) Management and maintenance. The owner is responsible for all management functions, including... financial interest and to uphold its program responsibilities where no alternative management agent is...

24 CFR 880.601 - Responsibilities of owner.

Code of Federal Regulations, 2013 CFR

2013-04-01

... DISABILITIES PROGRAM) SECTION 8 HOUSING ASSISTANCE PAYMENTS PROGRAM FOR NEW CONSTRUCTION Management § 880.601... units. (b) Management and maintenance. The owner is responsible for all management functions, including... financial interest and to uphold its program responsibilities where no alternative management agent is...

An Impulse Based Substructuring approach for impact analysis and load case simulations

NASA Astrophysics Data System (ADS)

Rixen, Daniel J.; van der Valk, Paul L. C.

2013-12-01

In the present paper we outline the basic theory of assembling substructures for which the dynamics are described as Impulse Response Functions. The assembly procedure computes the time response of a system by evaluating per substructure the convolution product between the Impulse Response Functions and the applied forces, including the interface forces that are computed to satisfy the interface compatibility. We call this approach the Impulse Based Substructuring method since it transposes to the time domain the Frequency Based Substructuring approach. In the Impulse Based Substructuring technique the Impulse Response Functions of the substructures can be gathered either from experimental tests using a hammer impact or from time-integration of numerical submodels. In this paper the implementation of the method is outlined for the case when the impulse responses of the substructures are computed numerically. A simple bar example is shown in order to illustrate the concept. The Impulse Based Substructuring allows fast evaluation of impact response of a structure when the impulse response of its components is known. It can thus be used to efficiently optimize designs of consumer products by including impact behavior at the early stage of the design, but also for performing substructured simulations of complex structures such as offshore wind turbines.

7 CFR 3565.304 - Lender loan processing responsibilities.

Code of Federal Regulations, 2010 CFR

2010-01-01

..., management and disposition. Unless otherwise permitted by the Agency, the originating lender must perform all loan functions during the period of the guarantee. These functions include servicing, asset management...

Comparing functional responses in predator-infected eco-epidemics models.

PubMed

Haque, Mainul; Rahman, Md Sabiar; Venturino, Ezio

2013-11-01

The current paper deals with the mathematical models of predator-prey system where a transmissible disease spreads among the predator species only. Four mathematical models are proposed and analysed with several popular predator functional responses in order to show the influence of functional response on eco-epidemic models. The existence, boundedness, uniqueness of solutions of all the models are established. Mathematical analysis including stability and bifurcation are observed. Comparison among the results of these models allows the general conclusion that relevant behaviour of the eco-epidemic predator-prey system, including switching of stability, extinction, persistence and oscillations for any species depends on four important parameters viz. the rate of infection, predator interspecies competition and the attack rate on susceptible predator. The paper ends with a discussion of the biological implications of the analytical and numerical results. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Genomic, genetic and functional dissection of bitter taste responses to artificial sweeteners.

PubMed

Roudnitzky, Natacha; Bufe, Bernd; Thalmann, Sophie; Kuhn, Christina; Gunn, Howard C; Xing, Chao; Crider, Bill P; Behrens, Maik; Meyerhof, Wolfgang; Wooding, Stephen P

2011-09-01

Bitter taste perception is initiated by TAS2R receptors, which respond to agonists by triggering depolarization of taste bud cells. Mutations in TAS2Rs are known to affect taste phenotypes by altering receptor function. Evidence that TAS2Rs overlap in ligand specificity suggests that they may also contribute joint effects. To explore this aspect of gustation, we examined bitter perception of saccharin and acesulfame K, widely used artificial sweeteners with aversive aftertastes. Both substances are agonists of TAS2R31 and -43, which belong to a five-member subfamily (TAS2R30-46) responsive to a diverse constellation of compounds. We analyzed sequence variation and linkage structure in the ∼140 kb genomic region encoding TAS2R30-46, taste responses to the two sweeteners in subjects, and functional characteristics of receptor alleles. Whole-gene sequences from TAS2R30-46 in 60 Caucasian subjects revealed extensive diversity including 34 missense mutations, two nonsense mutations and high-frequency copy-number variants. Thirty markers, including non-synonymous variants in all five genes, were associated (P< 0.001) with responses to saccharin and acesulfame K. However, linkage disequilibrium (LD) in the region was high (D', r(2) > 0.95). Haplotype analyses revealed that most associations were spurious, arising from LD with variants in TAS2R31. In vitro assays confirmed the functional importance of four TAS2R31 mutations, which had independent effects on receptor response. The existence of high LD spanning functionally distinct TAS2R loci predicts that bitter taste responses to many compounds will be strongly correlated even when they are mediated by different genes. Integrative approaches combining phenotypic, genetic and functional analysis will be essential in dissecting these complex relationships.

Dose response effect of NutriTek on leukocyte functionality during a dexamethasone challenge in Holstein steer calves.

USDA-ARS?s Scientific Manuscript database

The objective of this study was to determine the dose response effects of supplementing NutriTek® on leukocyte functionality and ex vivo cytokine production during a dexamethasone (DEX) challenge. Holstein steers (125.1±8.16kg; N=32) were assigned to treatments including 0, 20, 40, or 60g/head/d of ...

A Functional Varying-Coefficient Single-Index Model for Functional Response Data

PubMed Central

Li, Jialiang; Huang, Chao; Zhu, Hongtu

2016-01-01

Motivated by the analysis of imaging data, we propose a novel functional varying-coefficient single index model (FVCSIM) to carry out the regression analysis of functional response data on a set of covariates of interest. FVCSIM represents a new extension of varying-coefficient single index models for scalar responses collected from cross-sectional and longitudinal studies. An efficient estimation procedure is developed to iteratively estimate varying coefficient functions, link functions, index parameter vectors, and the covariance function of individual functions. We systematically examine the asymptotic properties of all estimators including the weak convergence of the estimated varying coefficient functions, the asymptotic distribution of the estimated index parameter vectors, and the uniform convergence rate of the estimated covariance function and their spectrum. Simulation studies are carried out to assess the finite-sample performance of the proposed procedure. We apply FVCSIM to investigating the development of white matter diffusivities along the corpus callosum skeleton obtained from Alzheimer’s Disease Neuroimaging Initiative (ADNI) study. PMID:29200540

A Functional Varying-Coefficient Single-Index Model for Functional Response Data.

PubMed

Li, Jialiang; Huang, Chao; Zhu, Hongtu

2017-01-01

Motivated by the analysis of imaging data, we propose a novel functional varying-coefficient single index model (FVCSIM) to carry out the regression analysis of functional response data on a set of covariates of interest. FVCSIM represents a new extension of varying-coefficient single index models for scalar responses collected from cross-sectional and longitudinal studies. An efficient estimation procedure is developed to iteratively estimate varying coefficient functions, link functions, index parameter vectors, and the covariance function of individual functions. We systematically examine the asymptotic properties of all estimators including the weak convergence of the estimated varying coefficient functions, the asymptotic distribution of the estimated index parameter vectors, and the uniform convergence rate of the estimated covariance function and their spectrum. Simulation studies are carried out to assess the finite-sample performance of the proposed procedure. We apply FVCSIM to investigating the development of white matter diffusivities along the corpus callosum skeleton obtained from Alzheimer's Disease Neuroimaging Initiative (ADNI) study.

Utility of Functional Hemodynamics and Echocardiography to Aid Diagnosis and Management of Shock.

PubMed

McGee, William T; Raghunathan, Karthik; Adler, Adam C

2015-12-01

The utility of functional hemodynamics and bedside ultrasonography is increasingly recognized as advantageous for both improved diagnosis and management of shock states. In contrast to conventional "static" measures, "dynamic" hemodynamic measures and bedside imaging modalities enhance pathophysiology-based comprehensive understanding of shock states and the response to therapy. The current editions of major textbooks in the primary specialties--in which clinicians routinely encounter patients in shock--including surgery, anesthesia, emergency medicine, and internal medicine continue to incorporate traditional (conventional) descriptions of shock that use well-described (but potentially misleading) intravascular pressures to classify shock states. Reliance on such intravascular pressure measurements is not as helpful as newer "dynamic" functional measures including ultrasonography to both better assess volume responsiveness and biventricular cardiac function. This review thus emphasizes the application of current functional hemodynamics and ultrasonography to the diagnosis and management of shock as a contrast to conventional "static" pressure-based measures.

Insulin receptors

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

Kahn, C.R.; Harrison, L.C.

1988-01-01

This book contains the procedure in insulin receptors. Part B: Clinical assessment, biological responses, and comparison to the IGF-1 receptor. Topics covered include: Insulin and IGF-1 receptors, Clinical assessment of receptor functions, and Biological responses.

A Comparison of Linking and Concurrent Calibration under the Graded Response Model.

ERIC Educational Resources Information Center

Kim, Seock-Ho; Cohen, Allan S.

Applications of item response theory to practical testing problems including equating, differential item functioning, and computerized adaptive testing, require that item parameter estimates be placed onto a common metric. In this study, two methods for developing a common metric for the graded response model under item response theory were…

Loss-of-function mutations in the ethylene receptor ETR1 cause enhanced sensitivity and exaggerated response to ethylene in Arabidopsis.

PubMed

Cancel, Jesse D; Larsen, Paul B

2002-08-01

Ethylene signaling in Arabidopsis begins at a family of five ethylene receptors that regulate activity of a downstream mitogen-activated protein kinase kinase kinase, CTR1. Triple and quadruple loss-of-function ethylene receptor mutants display a constitutive ethylene response phenotype, indicating they function as negative regulators in this pathway. No ethylene-related phenotype has been described for single loss-of-function receptor mutants, although it was reported that etr1 loss-of-function mutants display a growth defect limiting plant size. In actuality, this apparent growth defect results from enhanced responsiveness to ethylene; a phenotype manifested in all tissues tested. The phenotype displayed by etr1 loss-of-function mutants was rescued by treatment with an inhibitor of ethylene perception, indicating that it is ethylene dependent. Identification of an ethylene-dependent phenotype for a loss-of-function receptor mutant gave a unique opportunity for genetic and biochemical analysis of upstream events in ethylene signaling, including demonstration that the dominant ethylene-insensitive phenotype of etr2-1 is partially dependent on ETR1. This work demonstrates that mutational loss of the ethylene receptor ETR1 alters responsiveness to ethylene in Arabidopsis and that enhanced ethylene response in Arabidopsis not only results in increased sensitivity but exaggeration of response.

Loss-of-Function Mutations in the Ethylene Receptor ETR1 Cause Enhanced Sensitivity and Exaggerated Response to Ethylene in Arabidopsis

PubMed Central

Cancel, Jesse D.; Larsen, Paul B.

2002-01-01

Ethylene signaling in Arabidopsis begins at a family of five ethylene receptors that regulate activity of a downstream mitogen-activated protein kinase kinase kinase, CTR1. Triple and quadruple loss-of-function ethylene receptor mutants display a constitutive ethylene response phenotype, indicating they function as negative regulators in this pathway. No ethylene-related phenotype has been described for single loss-of-function receptor mutants, although it was reported that etr1 loss-of-function mutants display a growth defect limiting plant size. In actuality, this apparent growth defect results from enhanced responsiveness to ethylene; a phenotype manifested in all tissues tested. The phenotype displayed by etr1 loss-of-function mutants was rescued by treatment with an inhibitor of ethylene perception, indicating that it is ethylene dependent. Identification of an ethylene-dependent phenotype for a loss-of-function receptor mutant gave a unique opportunity for genetic and biochemical analysis of upstream events in ethylene signaling, including demonstration that the dominant ethylene-insensitive phenotype of etr2-1 is partially dependent on ETR1. This work demonstrates that mutational loss of the ethylene receptor ETR1 alters responsiveness to ethylene in Arabidopsis and that enhanced ethylene response in Arabidopsis not only results in increased sensitivity but exaggeration of response. PMID:12177468

5 CFR 1320.8 - Agency collection of information responsibilities.

Code of Federal Regulations, 2011 CFR

2011-01-01

... information is planned to be and/or has been used to further the proper performance of the functions of the... for the proper performance of the functions of the agency, including whether the information will have... copy without charge, including, if applicable, how the public can gain access to the collection of...

33 CFR 155.1020 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... the organizational structure identified in a response plan to manage response plan implementation... equipment in a response plan for the applicable operating environment. Factors to consider include, but are... within the Captain of the Port (COTP) zone in which the systems or equipment are intended to function...

Role of various hormones in photosynthetic responses of green plants under environmental stresses.

PubMed

Poonam; Bhardwaj, Renu; Kaur, Ravdeep; Bali, Shagun; Kaur, Parminder; Sirhindi, Geetika; Thukral, Ashwani K; Ohri, Puja; Vig, Adarsh P

2015-01-01

Environmental stress includes adverse factors like water deficit, high salinity, enhanced temperature and heavy metals etc. These stresses alter the normal growth and metabolic processes of plants including photosynthesis. Major photosynthetic responses under various stresses include inhibition of photosystems (I and II), changes in thylakoid complexes, decreased photosynthetic activity and modifications in structure and functions of chloroplasts etc. Various defense mechanisms are triggered inside the plants in response to these stresses that are regulated by plant hormones or plant growth regulators. These phytohormones include abscisic acid, auxins, cytokinins, ethylene, brassinosteroids, jasmonates and salicylic acid etc. The present review focuses on stress protective effects of plants hormones on the photosynthetic responses.

Developing laboratory networks: a practical guide and application.

PubMed

Kirk, Carol J; Shult, Peter A

2010-01-01

The role of the public health laboratory (PHL) in support of public health response has expanded beyond testing to include a number of other core functions, such as emergency response, training and outreach, communications, laboratory-based surveillance, and laboratory data management. These functions can only be accomplished by a network that includes public health and other agency laboratories and clinical laboratories. It is a primary responsibility of the PHL to develop and maintain such a network. In this article, we present practical recommendations-based on 17 years of network development experience-for the development of statewide laboratory networks. These recommendations, and examples of current laboratory networks, are provided to facilitate laboratory network development in other states. The development of laboratory networks will enhance each state's public health system and is critical to the development of a robust national Laboratory Response Network.

Mouse neutrophils lacking lamin B receptor expression exhibit aberrant development and lack critical functional responses

PubMed Central

Gaines, Peter; Tien, Chiung W.; Olins, Ada L.; Olins, Donald E.; Shultz, Leonard D.; Carney, Lisa; Berliner, Nancy

2008-01-01

Objective The capacity of neutrophils to eradicate bacterial infections is dependent on normal development and the activation of functional responses, which include chemotaxis and the generation of oxygen radicals during the respiratory burst. A unique feature of the neutrophil is its highly lobulated nucleus, which is thought to facilitate chemotaxis but may also play a role in other critical neutrophil functions. Nuclear lobulation is dependent on the expression of the inner nuclear envelope protein, the lamin B receptor (LBR), mutations of which cause hypolobulated neutrophil nuclei in human Pelger-Huët anomaly (PHA) and the "ichthyosis" (ic) phenotype in mice. In this study we have investigated roles for LBR in mediating neutrophil development and the activation of multiple neutrophil functions, including chemotaxis and the respiratory burst. Materials and Methods A progenitor EML cell line was generated from an ic/ic mouse, and derived cells that lacked LBR expression were induced to mature neutrophils and then examined for abnormal morphology and functional responses. Results Neutrophils derived from EML-ic/ic cells exhibited nuclear hypolobulation identical to that observed in ichthyosis mice. The ic/ic neutrophils also displayed abnormal chemotaxis, supporting the notion that nuclear segmentation augments neutrophil extravasation. Furthermore, promyelocytic forms of ic/ic cells displayed decreased proliferative responses and produced a deficient respiratory burst upon terminal maturation. Conclusions Our studies of promyelocytes that lack LBR expression have identified roles for LBR in regulating not only the morphologic maturation of the neutrophil nucleus but also proliferative and functional responses that are critical to innate immunity. PMID:18550262

Does Older Adults' Cognitive Function Disrupt the Malleability of Their Attitudes toward Outgroup Members?: An fMRI Investigation.

PubMed

Krendl, Anne C; Kensinger, Elizabeth A

2016-01-01

In the current study we examine how individual differences in older adults' global cognitive function impacts the extent to which their attitudes toward stigmatized individuals are malleable. Because prior research has elucidated the neural processes that are involved in evaluating stigmatized individuals who are responsible or not responsible for their condition, a cognitive neuroscience approach may be well-suited to answer this question. In the current study, 36 older and 17 young adults underwent functional magnetic resonance imaging while evaluating images of homeless people who were described as being responsible or not responsible for their condition. They also indicated how much pity they felt for each of the individuals in order to determine the extent to which their attitudes were malleable (e.g., more pity for not-responsible as compared to responsible individuals). Participants' cognitive function and baseline measure of their attitudes toward stigmatized individuals (including homeless individuals) were assessed. Results revealed that although older adults' attitudes were malleable, the extent to which this was true varied due to individual differences in their global cognitive function. Specifically, the difference in the magnitude of older adults' self-reported pity for not-responsible as compared to responsible homeless individuals was predicted by their global cognitive function. Moreover, the difference in pity that older adults expressed toward not-responsible as compared to responsible homeless individuals was related to activity in the left insula and the anterior cingulate cortex (regions implicated in empathy). These results suggest that attitude malleability is affected by individual differences in global cognitive function.

Does Older Adults’ Cognitive Function Disrupt the Malleability of Their Attitudes toward Outgroup Members?: An fMRI Investigation

PubMed Central

Krendl, Anne C.; Kensinger, Elizabeth A.

2016-01-01

In the current study we examine how individual differences in older adults’ global cognitive function impacts the extent to which their attitudes toward stigmatized individuals are malleable. Because prior research has elucidated the neural processes that are involved in evaluating stigmatized individuals who are responsible or not responsible for their condition, a cognitive neuroscience approach may be well-suited to answer this question. In the current study, 36 older and 17 young adults underwent functional magnetic resonance imaging while evaluating images of homeless people who were described as being responsible or not responsible for their condition. They also indicated how much pity they felt for each of the individuals in order to determine the extent to which their attitudes were malleable (e.g., more pity for not-responsible as compared to responsible individuals). Participants’ cognitive function and baseline measure of their attitudes toward stigmatized individuals (including homeless individuals) were assessed. Results revealed that although older adults’ attitudes were malleable, the extent to which this was true varied due to individual differences in their global cognitive function. Specifically, the difference in the magnitude of older adults’ self-reported pity for not-responsible as compared to responsible homeless individuals was predicted by their global cognitive function. Moreover, the difference in pity that older adults expressed toward not-responsible as compared to responsible homeless individuals was related to activity in the left insula and the anterior cingulate cortex (regions implicated in empathy). These results suggest that attitude malleability is affected by individual differences in global cognitive function. PMID:27074046

Non-linear non-local molecular electrodynamics with nano-optical fields.

PubMed

Chernyak, Vladimir Y; Saurabh, Prasoon; Mukamel, Shaul

2015-10-28

The interaction of optical fields sculpted on the nano-scale with matter may not be described by the dipole approximation since the fields may vary appreciably across the molecular length scale. Rather than incrementally adding higher multipoles, it is advantageous and more physically transparent to describe the optical process using non-local response functions that intrinsically include all multipoles. We present a semi-classical approach for calculating non-local response functions based on the minimal coupling Hamiltonian. The first, second, and third order response functions are expressed in terms of correlation functions of the charge and the current densities. This approach is based on the gauge invariant current rather than the polarization, and on the vector potential rather than the electric and magnetic fields.

Strengthening insights into host responses to mastitis infection in ruminants by combining heterogeneous microarray data sources

PubMed Central

2011-01-01

Background Gene expression profiling studies of mastitis in ruminants have provided key but fragmented knowledge for the understanding of the disease. A systematic combination of different expression profiling studies via meta-analysis techniques has the potential to test the extensibility of conclusions based on single studies. Using the program Pointillist, we performed meta-analysis of transcription-profiling data from six independent studies of infections with mammary gland pathogens, including samples from cattle challenged in vivo with S. aureus, E. coli, and S. uberis, samples from goats challenged in vivo with S. aureus, as well as cattle macrophages and ovine dendritic cells infected in vitro with S. aureus. We combined different time points from those studies, testing different responses to mastitis infection: overall (common signature), early stage, late stage, and cattle-specific. Results Ingenuity Pathway Analysis of affected genes showed that the four meta-analysis combinations share biological functions and pathways (e.g. protein ubiquitination and polyamine regulation) which are intrinsic to the general disease response. In the overall response, pathways related to immune response and inflammation, as well as biological functions related to lipid metabolism were altered. This latter observation is consistent with the milk fat content depression commonly observed during mastitis infection. Complementarities between early and late stage responses were found, with a prominence of metabolic and stress signals in the early stage and of the immune response related to the lipid metabolism in the late stage; both mechanisms apparently modulated by few genes, including XBP1 and SREBF1. The cattle-specific response was characterized by alteration of the immune response and by modification of lipid metabolism. Comparison of E. coli and S. aureus infections in cattle in vivo revealed that affected genes showing opposite regulation had the same altered biological functions and provided evidence that E. coli caused a stronger host response. Conclusions This meta-analysis approach reinforces previous findings but also reveals several novel themes, including the involvement of genes, biological functions, and pathways that were not identified in individual studies. As such, it provides an interesting proof of principle for future studies combining information from diverse heterogeneous sources. PMID:21569310

38 CFR 14.500 - Functions and responsibilities of General Counsel.

Code of Federal Regulations, 2012 CFR

2012-07-01

... VETERANS AFFAIRS LEGAL SERVICES, GENERAL COUNSEL, AND MISCELLANEOUS CLAIMS § 14.500 Functions and... construction or application of laws, including statutes, regulations, and decisional as well as common law. (c...

Ion temperature measurements of indirect-drive implosions with the neutron time-of-flight detector on SG-III laser facility

NASA Astrophysics Data System (ADS)

Chen, Zhongjing; Zhang, Xing; Pu, Yudong; Yan, Ji; Huang, Tianxuan; Jiang, Wei; Yu, Bo; Chen, Bolun; Tang, Qi; Song, Zifeng; Chen, Jiabin; Zhan, Xiayu; Liu, Zhongjie; Xie, Xufei; Jiang, Shaoen; Liu, Shenye

2018-02-01

The accuracy of the determination of the burn-averaged ion temperature of inertial confinement fusion implosions depends on the unfold process, including deconvolution and convolution methods, and the function, i.e., the detector response, used to fit the signals measured by neutron time-of-flight (nToF) detectors. The function given by Murphy et al. [Rev. Sci. Instrum. 68(1), 610-613 (1997)] has been widely used in Nova, Omega, and NIF. There are two components, i.e., fast and slow, and the contribution of scattered neutrons has not been dedicatedly considered. In this work, a new function, based on Murphy's function has been employed to unfold nToF signals. The contribution of scattered neutrons is easily included by the convolution of a Gaussian response function and an exponential decay. The ion temperature is measured by nToF with the new function. Good agreement with the ion temperature determined by the deconvolution method has been achieved.

Intestinal current measurement versus nasal potential difference measurements for diagnosis of cystic fibrosis: a case-control study.

PubMed

Bagheri-Hanson, Azadeh; Nedwed, Sebastian; Rueckes-Nilges, Claudia; Naehrlich, Lutz

2014-10-04

Nasal potential difference (NPD) and intestinal current measurement (ICM) are functional CFTR tests that are used as adjunctive diagnostic tools for cystic fibrosis (CF). Smoking has a systemic negative impact on CFTR function. A diagnostic comparison between NPD and ICM and the impact of smoking on both CFTR tests has not been done. The sweat chloride test, NPD, and ICM were performed in 18 patients with CF (sweat chloride >60 mmol/l), including 6 pancreatic sufficient (PS) patients, and 13 healthy controls, including 8 smokers. The NPD CFTR response to Cl-free and isoproterenol perfusion (Δ0Cl- + Iso) was compared to the ICM CFTR response to forskolin/IBMX, carbachol, and histamine (ΔIsc, forskolin/IBMX+ carbachol+histamine). The mean NPD CFTR response and ICM CFTR response between patients with CF and healthy controls was significantly different (p <0.001), but not between patients with CF who were PS and those who were pancreatic insufficient (PI). Smokers have a decreased CFTR response measured by NPD (p = 0.049). For ICM there is a trend towards decreased CFTR response (NS). Three healthy control smokers had NPD responses within the CF-range. In contrast to NPD, there was no overlap of the ICM response between patients with CF and controls. ICM is superior to NPD in distinguishing between patients with CF who have a sweat chloride > 60 mmol/l and healthy controls, including smokers. Neither NPD nor ICM differentiated between patients with CF who were PS from those who were PI. Smoking has a negative impact on CFTR function in healthy controls measured by NPD and challenges the diagnostic interpretation of NPD, but not ICM.

Effects of directional uncertainty on visually-guided joystick pointing.

PubMed

Berryhill, Marian; Kveraga, Kestutis; Hughes, Howard C

2005-02-01

Reaction times generally follow the predictions of Hick's law as stimulus-response uncertainty increases, although notable exceptions include the oculomotor system. Saccadic and smooth pursuit eye movement reaction times are independent of stimulus-response uncertainty. Previous research showed that joystick pointing to targets, a motor analog of saccadic eye movements, is only modestly affected by increased stimulus-response uncertainty; however, a no-uncertainty condition (simple reaction time to 1 possible target) was not included. Here, we re-evaluate manual joystick pointing including a no-uncertainty condition. Analysis indicated simple joystick pointing reaction times were significantly faster than choice reaction times. Choice reaction times (2, 4, or 8 possible target locations) only slightly increased as the number of possible targets increased. These data suggest that, as with joystick tracking (a motor analog of smooth pursuit eye movements), joystick pointing is more closely approximated by a simple/choice step function than the log function predicted by Hick's law.

Dose response effect of NutriTek on leukocyte functionality and ex vivo cytokine production during a dexamethasone challenge in Holstein steer calves

USDA-ARS?s Scientific Manuscript database

The objective of this study was to determine the dose response effects of supplementing NutriTek on leukocyte functionality and ex vivo cytokine production during a dexamethasone (DEX) challenge. Holstein steers (125.1 ± 8.16 kg; N = 32) were assigned to treatments including 0, 20, 40, or 60 g/head/...

B cell function in the immune response to helminths

PubMed Central

Harris, Nicola

2010-01-01

Similar T helper (Th)2-type immune responses are generated against different helminths parasites, but the mechanisms that initiate Th2 immunity, and the specific immune components that mediate protection against these parasites, can vary greatly. B cells are increasingly recognized as important during the Th2-type immune response to helminths, and B cell activation might be a target for effective vaccine development. Antibody production is a function of B cells during helminth infection and understanding how polyclonal and antigen-specific antibodies contribute should provide important insights into how protective immunity develops. In addition, B cells might also contribute to the host response against helminths through antibody-independent functions including, antigen-presentation, as well as regulatory and effector activity. In this review, we examine the role of B cells during Th2-type immune response to these multicellular parasites. PMID:21159556

Objective Measures of Visual Function in Papilledema

PubMed Central

Moss, Heather E.

2016-01-01

Synopsis Visual function is an important parameter to consider when managing patients with papilledema. Though the current standard of care uses standard automated perimetry (SAP) to obtain this information, this test is inherently subjective and prone to patient errors. Objective visual function tests including the visual evoked potential, pattern electroretinogram, photopic negative response of the full field electroretinogram, and pupillary light response have the potential to replace or supplement subjective visual function tests in papilledema management. This article reviews the evidence for use of objective visual function tests to assess visual function in papilledema and discusses future investigations needed to develop them as clinically practical and useful measures for this purpose. PMID:28451649

Basilar-membrane responses to broadband noise modeled using linear filters with rational transfer functions.

PubMed

Recio-Spinoso, Alberto; Fan, Yun-Hui; Ruggero, Mario A

2011-05-01

Basilar-membrane responses to white Gaussian noise were recorded using laser velocimetry at basal sites of the chinchilla cochlea with characteristic frequencies near 10 kHz and first-order Wiener kernels were computed by cross correlation of the stimuli and the responses. The presence or absence of minimum-phase behavior was explored by fitting the kernels with discrete linear filters with rational transfer functions. Excellent fits to the kernels were obtained with filters with transfer functions including zeroes located outside the unit circle, implying nonminimum-phase behavior. These filters accurately predicted basilar-membrane responses to other noise stimuli presented at the same level as the stimulus for the kernel computation. Fits with all-pole and other minimum-phase discrete filters were inferior to fits with nonminimum-phase filters. Minimum-phase functions predicted from the amplitude functions of the Wiener kernels by Hilbert transforms were different from the measured phase curves. These results, which suggest that basilar-membrane responses do not have the minimum-phase property, challenge the validity of models of cochlear processing, which incorporate minimum-phase behavior. © 2011 IEEE

End-to-end test of the electron-proton spectrometer

NASA Technical Reports Server (NTRS)

Cash, B. L.

1972-01-01

A series of end-to-end tests were performed to demonstrate the proper functioning of the complete Electron-Proton Spectrometer (EPS). The purpose of the tests was to provide experimental verification of the design and to provide a complete functional performance check of the instrument from the excitation of the sensors to and including the data processor and equipment test set. Each of the channels of the EPS was exposed to a calibrated beam of energetic particles, and counts were accumulated for a predetermined period of time for each of several energies. The counts were related to the known flux of particles to give a monodirectional response function for each channel. The measured response function of the test unit was compared to the response function determined for the calibration sensors from the data taken from the calibration program.

Genetic Influences on Response to Alcohol and Response to Pharmacotherapies for Alcoholism

PubMed Central

Enoch, Mary-Anne

2014-01-01

Although very many individuals drink alcohol at safe levels, a significant proportion escalates their consumption with addiction as the end result. Alcoholism is a common, moderately heritable, psychiatric disorder that is accompanied by considerable morbidity and mortality. Variation in clinical presentation suggests inter-individual variation in mechanisms of vulnerability including genetic risk factors. The development of addiction is likely to involve numerous functional genetic variants of small effects. The first part of this review will focus on genetic factors underlying inter-individual variability in response to alcohol consumption, including variants in alcohol metabolizing genes that produce an aversive response (the flushing syndrome) and variants that predict the level of subjective and physiological response to alcohol. The second part of this review will report on genetic variants that identify subgroups of alcoholics who are more likely to respond to pharmacotherapy to reduce levels of drinking or maintain abstinence. Genetic analyses of the level of response to alcohol, particularly of the functional OPRM1 A118G polymorphism and 5′ and 3′ functional polymorphisms in SLC6A4, are beginning to provide insights into the etiology of alcoholism and also genotype-stratified subgroup responses to naltrexone and SSRIs / ondansetron respectively. Because of large inter-ethnic variation in allele frequencies, the relevance of these functional polymorphisms will vary between ethnic groups. However there are relatively few published studies in this field, particularly with large sample sizes in pharmacogenetic studies, therefore it is premature to draw any conclusions at this stage. PMID:24220019

The long-term effects of prenatal nicotine exposure on response inhibition: an fMRI study of young adults.

PubMed

Longo, Carmelinda A; Fried, Peter A; Cameron, Ian; Smith, Andra M

2013-01-01

The long-term effects of prenatal nicotine exposure on response inhibition were investigated in young adults using functional magnetic resonance imaging (fMRI). Participants were members of the Ottawa Prenatal Prospective Study, a longitudinal study that collected a unique body of information on participants from infancy to young adulthood, which allowed for the measurement of an unprecedented number of potentially confounding drug exposure variables including: prenatal marijuana and alcohol exposure and current marijuana, nicotine and alcohol use. Twelve young adults with prenatal nicotine exposure and 13 non-exposed controls performed a Go/No-Go task while fMRI blood oxygen level-dependent responses were examined. Despite similar task performance, participants prenatally exposed to nicotine demonstrated significantly greater activity in several regions of the brain that typically subserve response inhibition including the inferior frontal gyrus, the inferior parietal lobe, the thalamus and the basal ganglia. In addition, prenatally exposed participants showed greater activity in relatively large posterior regions of the cerebellum. These results suggest that prenatal nicotine exposure leads to altered neural functioning during response inhibition that continues into adulthood. This alteration is compensated for by recruitment of greater neural resources within regions of the brain that subserve response inhibition and the recruitment of additional brain regions to successfully perform the task. Response inhibition is an important executive functioning skill and impairments can impede functioning in much of everyday life. Thus, awareness of the continued long-term neural physiological effects of prenatal nicotine exposure is critical. Copyright © 2013 Elsevier Inc. All rights reserved.

Genetic influences on response to alcohol and response to pharmacotherapies for alcoholism.

PubMed

Enoch, Mary-Anne

2014-08-01

Although very many individuals drink alcohol at safe levels, a significant proportion escalates their consumption with addiction as the end result. Alcoholism is a common, moderately heritable, psychiatric disorder that is accompanied by considerable morbidity and mortality. Variation in clinical presentation suggests inter-individual variation in mechanisms of vulnerability including genetic risk factors. The development of addiction is likely to involve numerous functional genetic variants of small effects. The first part of this review will focus on genetic factors underlying inter-individual variability in response to alcohol consumption, including variants in alcohol metabolizing genes that produce an aversive response (the flushing syndrome) and variants that predict the level of subjective and physiological response to alcohol. The second part of this review will report on genetic variants that identify subgroups of alcoholics who are more likely to respond to pharmacotherapy to reduce levels of drinking or maintain abstinence. Genetic analyses of the level of response to alcohol, particularly of the functional OPRM1 A118G polymorphism and 5' and 3' functional polymorphisms in SLC6A4, are beginning to provide insights into the etiology of alcoholism and also genotype-stratified subgroup responses to naltrexone and SSRIs/ondansetron respectively. Because of large inter-ethnic variation in allele frequencies, the relevance of these functional polymorphisms will vary between ethnic groups. However there are relatively few published studies in this field, particularly with large sample sizes in pharmacogenetic studies, therefore it is premature to draw any conclusions at this stage. Published by Elsevier Inc.

Assessing the response to targeted therapies in renal cell carcinoma: technical insights and practical considerations.

PubMed

Bex, Axel; Fournier, Laure; Lassau, Nathalie; Mulders, Peter; Nathan, Paul; Oyen, Wim J G; Powles, Thomas

2014-04-01

The introduction of targeted agents for the treatment of renal cell carcinoma (RCC) has resulted in new challenges for assessing response to therapy, and conventional response criteria using computed tomography (CT) are limited. It is widely recognised that targeted therapies may lead to significant necrosis without significant reduction in tumour size. In addition, the vascular effects of antiangiogenic therapy may occur long before there is any reduction in tumour size. To perform a systematic review of conventional and novel imaging methods for the assessment of response to targeted agents in RCC and to discuss their use from a clinical perspective. Relevant databases covering the period January 2006 to April 2013 were searched for studies reporting on the use of anatomic and functional imaging techniques to predict response to targeted therapy in RCC. Inclusion criteria were randomised trials, nonrandomised controlled studies, retrospective case series, and cohort studies. Reviews, animal and preclinical studies, case reports, and commentaries were excluded. A narrative synthesis of the evidence is presented. A total of 331 abstracts and 76 full-text articles were assessed; 34 studies met the inclusion criteria. Current methods of response assessment in RCC include anatomic methods--based on various criteria including Choi, size and attenuation CT, and morphology, attenuation, size, and structure--and functional techniques including dynamic contrast-enhanced (DCE) CT, DCE-magnetic resonance imaging, DCE-ultrasonography, positron emission tomography, and approaches utilising radiolabelled monoclonal antibodies. Functional imaging techniques are promising surrogate biomarkers of response in RCC and may be more appropriate than anatomic CT-based methods. By enabling quantification of tumour vascularisation, functional techniques can directly and rapidly detect the biologic effects of antiangiogenic therapies compared with the indirect detection of belated effects on tumour size by anatomic methods. However, larger prospective studies are needed to validate early results and standardise techniques. Copyright © 2013 European Association of Urology. All rights reserved.

The role of relativity in the optical response of gold within the time-dependent current-density-functional theory.

PubMed

Romaniello, P; de Boeij, P L

2005-04-22

We included relativistic effects in the formulation of the time-dependent current-density-functional theory for the calculation of linear response properties of metals [P. Romaniello and P. L. de Boeij, Phys. Rev. B (to be published)]. We treat the dominant scalar-relativistic effects using the zeroth-order regular approximation in the ground-state density-functional theory calculations, as well as in the time-dependent response calculations. The results for the dielectric function of gold calculated in the spectral range of 0-10 eV are compared with experimental data reported in literature and recent ellipsometric measurements. As well known, relativistic effects strongly influence the color of gold. We find that the onset of interband transitions is shifted from around 3.5 eV, obtained in a nonrelativistic calculation, to around 1.9 eV when relativity is included. With the inclusion of the scalar-relativistic effects there is an overall improvement of both real and imaginary parts of the dielectric function over the nonrelativistic ones. Nevertheless some important features in the absorption spectrum are not well reproduced, but can be explained in terms of spin-orbit coupling effects. The remaining deviations are attributed to the underestimation of the interband gap (5d-6sp band gap) in the local-density approximation and to the use of the adiabatic local-density approximation in the response calculation.

Acute carbon dioxide avoidance in Caenorhabditis elegans

PubMed Central

Hallem, Elissa A.; Sternberg, Paul W.

2008-01-01

Carbon dioxide is produced as a by-product of cellular respiration by all aerobic organisms and thus serves for many animals as an important indicator of food, mates, and predators. However, whether free-living terrestrial nematodes such as Caenorhabditis elegans respond to CO2 was unclear. We have demonstrated that adult C. elegans display an acute avoidance response upon exposure to CO2 that is characterized by the cessation of forward movement and the rapid initiation of backward movement. This response is mediated by a cGMP signaling pathway that includes the cGMP-gated heteromeric channel TAX-2/TAX-4. CO2 avoidance is modulated by multiple signaling molecules, including the neuropeptide Y receptor NPR-1 and the calcineurin subunits TAX-6 and CNB-1. Nutritional status also modulates CO2 responsiveness via the insulin and TGFβ signaling pathways. CO2 response is mediated by a neural circuit that includes the BAG neurons, a pair of sensory neurons of previously unknown function. TAX-2/TAX-4 function in the BAG neurons to mediate acute CO2 avoidance. Our results demonstrate that C. elegans senses and responds to CO2 using multiple signaling pathways and a neural network that includes the BAG neurons and that this response is modulated by the physiological state of the worm. PMID:18524955

Acute carbon dioxide avoidance in Caenorhabditis elegans.

PubMed

Hallem, Elissa A; Sternberg, Paul W

2008-06-10

Carbon dioxide is produced as a by-product of cellular respiration by all aerobic organisms and thus serves for many animals as an important indicator of food, mates, and predators. However, whether free-living terrestrial nematodes such as Caenorhabditis elegans respond to CO2 was unclear. We have demonstrated that adult C. elegans display an acute avoidance response upon exposure to CO2 that is characterized by the cessation of forward movement and the rapid initiation of backward movement. This response is mediated by a cGMP signaling pathway that includes the cGMP-gated heteromeric channel TAX-2/TAX-4. CO2 avoidance is modulated by multiple signaling molecules, including the neuropeptide Y receptor NPR-1 and the calcineurin subunits TAX-6 and CNB-1. Nutritional status also modulates CO2 responsiveness via the insulin and TGFbeta signaling pathways. CO2 response is mediated by a neural circuit that includes the BAG neurons, a pair of sensory neurons of previously unknown function. TAX-2/TAX-4 function in the BAG neurons to mediate acute CO2 avoidance. Our results demonstrate that C. elegans senses and responds to CO2 using multiple signaling pathways and a neural network that includes the BAG neurons and that this response is modulated by the physiological state of the worm.

A Unique Fungal Two-Component System Regulates Stress Responses, Drug Sensitivity, Sexual Development, and Virulence of Cryptococcus neoformans

PubMed Central

Bahn, Yong-Sun; Kojima, Kaihei; Cox, Gary M.

2006-01-01

The stress-activated mitogen-activated protein kinase (MAPK) pathway is widely used by eukaryotic organisms as a central conduit via which cellular responses to the environment effect growth and differentiation. The basidiomycetous human fungal pathogen Cryptococcus neoformans uniquely uses the stress-activated Pbs2-Hog1 MAPK system to govern a plethora of cellular events, including stress responses, drug sensitivity, sexual reproduction, and virulence. Here, we characterized a fungal “two-component” system that controls these fundamental cellular functions via the Pbs2-Hog1 MAPK cascade. A typical response regulator, Ssk1, modulated all Hog1-dependent phenotypes by controlling Hog1 phosphorylation, indicating that Ssk1 is the major upstream signaling component of the Pbs2-Hog1 pathway. A second response regulator, Skn7, governs sensitivity to Na+ ions and the antifungal agent fludioxonil, negatively controls melanin production, and functions independently of Hog1 regulation. To control these response regulators, C. neoformans uses multiple sensor kinases, including two-component–like (Tco) 1 and Tco2. Tco1 and Tco2 play shared and distinct roles in stress responses and drug sensitivity through the Hog1 MAPK system. Furthermore, each sensor kinase mediates unique cellular functions for virulence and morphological differentiation. Our findings highlight unique adaptations of this global two-component MAPK signaling cascade in a ubiquitous human fungal pathogen. PMID:16672377

AESOP- INTERACTIVE DESIGN OF LINEAR QUADRATIC REGULATORS AND KALMAN FILTERS

NASA Technical Reports Server (NTRS)

Lehtinen, B.

1994-01-01

AESOP was developed to solve a number of problems associated with the design of controls and state estimators for linear time-invariant systems. The systems considered are modeled in state-variable form by a set of linear differential and algebraic equations with constant coefficients. Two key problems solved by AESOP are the linear quadratic regulator (LQR) design problem and the steady-state Kalman filter design problem. AESOP is designed to be used in an interactive manner. The user can solve design problems and analyze the solutions in a single interactive session. Both numerical and graphical information are available to the user during the session. The AESOP program is structured around a list of predefined functions. Each function performs a single computation associated with control, estimation, or system response determination. AESOP contains over sixty functions and permits the easy inclusion of user defined functions. The user accesses these functions either by inputting a list of desired functions in the order they are to be performed, or by specifying a single function to be performed. The latter case is used when the choice of function and function order depends on the results of previous functions. The available AESOP functions are divided into several general areas including: 1) program control, 2) matrix input and revision, 3) matrix formation, 4) open-loop system analysis, 5) frequency response, 6) transient response, 7) transient function zeros, 8) LQR and Kalman filter design, 9) eigenvalues and eigenvectors, 10) covariances, and 11) user-defined functions. The most important functions are those that design linear quadratic regulators and Kalman filters. The user interacts with AESOP when using these functions by inputting design weighting parameters and by viewing displays of designed system response. Support functions obtain system transient and frequency responses, transfer functions, and covariance matrices. AESOP can also provide the user with open-loop system information including stability, controllability, and observability. The AESOP program is written in FORTRAN IV for interactive execution and has been implemented on an IBM 3033 computer using TSS 370. As currently configured, AESOP has a central memory requirement of approximately 2 Megs of 8 bit bytes. Memory requirements can be reduced by redimensioning arrays in the AESOP program. Graphical output requires adaptation of the AESOP plot routines to whatever device is available. The AESOP program was developed in 1984.

Self-regulating chemo-mechano-chemical systems

DOEpatents

Aizenberg, Joanna; He, Ximin; Aizenberg, Michael

2017-05-16

A chemo-mechano-chemical (C.sub.1-M-C.sub.2) system includes a base supporting an actuatable structure, said structure comprising a functionalized portion and being embedded in an environmentally responsive gel capable of volume change in response to an environmental stimulus; a first fluid layer disposed over the base and in contact with the actuatable structure, said first fluid layer comprising the environmentally responsive gel; and a second fluid layer in contact with the actuatable structure, wherein the layers are positioned such that the functionalized portion is in contact with the second layer in a first relaxed state and in contact with the first layer in a second actuated state and wherein the functionalized portion interacts with at least one of the layers to provide a chemical or physical response.

Identifying ultrasensitive HGF dose-response functions in a 3D mammalian system for synthetic morphogenesis.

PubMed

Senthivel, Vivek Raj; Sturrock, Marc; Piedrafita, Gabriel; Isalan, Mark

2016-12-16

Nonlinear responses to signals are widespread natural phenomena that affect various cellular processes. Nonlinearity can be a desirable characteristic for engineering living organisms because it can lead to more switch-like responses, similar to those underlying the wiring in electronics. Steeper functions are described as ultrasensitive, and can be applied in synthetic biology by using various techniques including receptor decoys, multiple co-operative binding sites, and sequential positive feedbacks. Here, we explore the inherent non-linearity of a biological signaling system to identify functions that can potentially be exploited using cell genome engineering. For this, we performed genome-wide transcription profiling to identify genes with ultrasensitive response functions to Hepatocyte Growth Factor (HGF). We identified 3,527 genes that react to increasing concentrations of HGF, in Madin-Darby canine kidney (MDCK) cells, grown as cysts in 3D collagen cell culture. By fitting a generic Hill function to the dose-responses of these genes we obtained a measure of the ultrasensitivity of HGF-responsive genes, identifying a subset with higher apparent Hill coefficients (e.g. MMP1, TIMP1, SNORD75, SNORD86 and ERRFI1). The regulatory regions of these genes are potential candidates for future engineering of synthetic mammalian gene circuits requiring nonlinear responses to HGF signalling.

Jump phenomena. [large amplitude responses of nonlinear systems

NASA Technical Reports Server (NTRS)

Reiss, E. L.

1980-01-01

The paper considers jump phenomena composed of large amplitude responses of nonlinear systems caused by small amplitude disturbances. Physical problems where large jumps in the solution amplitude are important features of the response are described, including snap buckling of elastic shells, chemical reactions leading to combustion and explosion, and long-term climatic changes of the earth's atmosphere. A new method of rational functions was then developed which consists of representing the solutions of the jump problems as rational functions of the small disturbance parameter; this method can solve jump problems explicitly.

Functional Communication Training in the Classroom: A Guide for Success

ERIC Educational Resources Information Center

Mancil, G. Richmond; Boman, Marty

2010-01-01

Researchers have consistently shown the effectiveness of functional communication training (FCT) to address both the communication and behavioral needs of children on the autism spectrum. The three steps of FCT include completing a functional behavior assessment, identifying a communication response, and developing a treatment plan. In addition,…

Modeling non-linear growth responses to temperature and hydrology in wetland trees

NASA Astrophysics Data System (ADS)

Keim, R.; Allen, S. T.

2016-12-01

Growth responses of wetland trees to flooding and climate variations are difficult to model because they depend on multiple, apparently interacting factors, but are a critical link in hydrological control of wetland carbon budgets. To more generally understand tree growth to hydrological forcing, we modeled non-linear responses of tree ring growth to flooding and climate at sub-annual time steps, using Vaganov-Shashkin response functions. We calibrated the model to six baldcypress tree-ring chronologies from two hydrologically distinct sites in southern Louisiana, and tested several hypotheses of plasticity in wetlands tree responses to interacting environmental variables. The model outperformed traditional multiple linear regression. More importantly, optimized response parameters were generally similar among sites with varying hydrological conditions, suggesting generality to the functions. Model forms that included interacting responses to multiple forcing factors were more effective than were single response functions, indicating the principle of a single limiting factor is not correct in wetlands and both climatic and hydrological variables must be considered in predicting responses to hydrological or climate change.

Pericytes of the neurovascular unit: Key functions and signaling pathways

PubMed Central

Sweeney, Melanie D.; Ayyadurai, Shiva; Zlokovic, Berislav V.

2017-01-01

Pericytes are vascular mural cells embedded in the basement membrane of blood microvessels. They extend their processes along capillaries, pre-capillary arterioles, and post-capillary venules. The central nervous system (CNS) pericytes are uniquely positioned within the neurovascular unit between endothelial cells, astrocytes, and neurons. They integrate, coordinate, and process signals from their neighboring cells to generate diverse functional responses that are critical for CNS functions in health and disease including regulation of the blood-brain barrier permeability, angiogenesis, clearance of toxic metabolites, capillary hemodynamic responses, neuroinflammation, and stem cell activity. Here, we examine the key signaling pathways between pericytes and their neighboring endothelial cells, astrocytes, and neurons that control neurovascular functions. We also review the role of pericytes in different CNS disorders including rare monogenic diseases and complex neurological disorders such as Alzheimer's disease and brain tumors. Finally, we discuss directions for future studies. PMID:27227366

The Unfolded Protein Response: At the Intersection between Endoplasmic Reticulum Function and Mitochondrial Bioenergetics.

PubMed

Carreras-Sureda, Amado; Pihán, Philippe; Hetz, Claudio

2017-01-01

Endoplasmic reticulum (ER) to mitochondria communication has emerged in recent years as a signaling hub regulating cellular physiology with a relevant contribution to diseases including cancer and neurodegeneration. This functional integration is exerted through discrete interorganelle structures known as mitochondria-associated membranes (MAMs). At these domains, ER/mitochondria physically associate to dynamically adjust metabolic demands and the response to stress stimuli. Here, we provide a focused overview of how the ER shapes the function of the mitochondria, giving a special emphasis to the significance of local signaling of the unfolded protein response at MAMs. The implications to cell fate control and the progression of cancer are also discussed.

Multi-channel spatialization systems for audio signals

NASA Technical Reports Server (NTRS)

Begault, Durand R. (Inventor)

1993-01-01

Synthetic head related transfer functions (HRTF's) for imposing reprogrammable spatial cues to a plurality of audio input signals included, for example, in multiple narrow-band audio communications signals received simultaneously are generated and stored in interchangeable programmable read only memories (PROM's) which store both head related transfer function impulse response data and source positional information for a plurality of desired virtual source locations. The analog inputs of the audio signals are filtered and converted to digital signals from which synthetic head related transfer functions are generated in the form of linear phase finite impulse response filters. The outputs of the impulse response filters are subsequently reconverted to analog signals, filtered, mixed, and fed to a pair of headphones.

Multi-channel spatialization system for audio signals

NASA Technical Reports Server (NTRS)

Begault, Durand R. (Inventor)

1995-01-01

Synthetic head related transfer functions (HRTF's) for imposing reprogramable spatial cues to a plurality of audio input signals included, for example, in multiple narrow-band audio communications signals received simultaneously are generated and stored in interchangeable programmable read only memories (PROM's) which store both head related transfer function impulse response data and source positional information for a plurality of desired virtual source locations. The analog inputs of the audio signals are filtered and converted to digital signals from which synthetic head related transfer functions are generated in the form of linear phase finite impulse response filters. The outputs of the impulse response filters are subsequently reconverted to analog signals, filtered, mixed and fed to a pair of headphones.

Cell Cycle Regulators Guide Mitochondrial Activity in Radiation-Induced Adaptive Response

PubMed Central

Alexandrou, Aris T.

2014-01-01

Abstract Significance: There are accruing concerns on potential genotoxic agents present in the environment including low-dose ionizing radiation (LDIR) that naturally exists on earth's surface and atmosphere and is frequently used in medical diagnosis and nuclear industry. Although its long-term health risk is being evaluated and remains controversial, LDIR is shown to induce temporary but significant adaptive responses in mammalian cells and animals. The mechanisms guiding the mitochondrial function in LDIR-induced adaptive response represent a unique communication between DNA damage and cellular metabolism. Elucidation of the LDIR-regulated mitochondrial activity may reveal new mechanisms adjusting cellular function to cope with hazardous environmental stress. Recent Advances: Key cell cycle regulators, including Cyclin D1/CDK4 and Cyclin B1/cyclin-dependent kinase 1 (CDK1) complexes, are actively involved in the regulation of mitochondrial functions via phosphorylation of their mitochondrial targets. Accumulating new evidence supports a concept that the Cyclin B1/CDK1 complex acts as a mediator in the cross talk between radiation-induced DNA damage and mitochondrial functions to coordinate cellular responses to low-level genotoxic stresses. Critical Issues: The LDIR-mediated mitochondrial activity via Cyclin B1/CDK1 regulation is an irreplaceable network that is able to harmonize vital cellular functions with adjusted mitochondrial metabolism to enhance cellular homeostasis. Future Directions: Further investigation of the coordinative mechanism that regulates mitochondrial activities in sublethal stress conditions, including LDIR, will reveal new insights of how cells cope with genotoxic injury and will be vital for future targeted therapeutic interventions that reduce environmental injury and cancer risk. Antioxid. Redox Signal. 20, 1463–1480. PMID:24180340

Functional heartburn: the stimulus, the pain, and the brain

PubMed Central

Fass, R; Tougas, G

2002-01-01

Functional heartburn is a common disorder and appears to be composed of several distinct subgroups. Identifying the different subgroups based on clinical history only is not achievable at present. The mechanisms responsible for pain, clinical characteristics, and the optimal therapeutic approach remain poorly understood. Response to potent antireflux treatment is relatively limited. Current and future treatment strategies for functional heartburn patients who have failed standard dose proton pump inhibitors (PPIs) include increased PPI dose in some, as well as addition of pain modulators in others. PMID:12427796

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.

ACIRF user's guide: Theory and examples

NASA Astrophysics Data System (ADS)

Dana, Roger A.

1989-12-01

Design and evaluation of radio frequency systems that must operate through ionospheric disturbances resulting from high altitude nuclear detonations requires an accurate channel model. This model must include the effects of high gain antennas that may be used to receive the signals. Such a model can then be used to construct realizations of the received signal for use in digital simulations of trans-ionospheric links or for use in hardware channel simulators. The FORTRAN channel model ACIRF (Antenna Channel Impulse Response Function) generates random realizations of the impulse response function at the outputs of multiple antennas. This user's guide describes the FORTRAN program ACIRF (version 2.0) that generates realizations of channel impulse response functions at the outputs of multiple antennas with arbitrary beamwidths, pointing angles, and relatives positions. This channel model is valid under strong scattering conditions when Rayleigh fading statistics apply. Both frozen-in and turbulent models for the temporal fluctuations are included in this version of ACIRF. The theory of the channel model is described and several examples are given.

Regulation of the Cardiovascular System by Histamine.

PubMed

Hattori, Yuichi; Hattori, Kohshi; Matsuda, Naoyuki

2017-01-01

Histamine mediates a wide range of cellular responses, including allergic and inflammatory reactions, gastric acid secretion, and neurotransmission in the central nervous system. Histamine also exerts a series of actions upon the cardiovascular system but may not normally play a significant role in regulating cardiovascular function. During tissue injury, inflammation, and allergic responses, mast cells (or non-mast cells) within the tissues can release large amounts of histamine that leads to noticeable cardiovascular effects. Owing to intensive research during several decades, the distribution, function, and pathophysiological role of cardiovascular H 1 - and H 2 -receptors has become recognized adequately. Besides the recognized H 1 - and H 2 -receptor-mediated cardiovascular responses, novel roles of H 3 - and H 4 -receptors in cardiovascular physiology and pathophysiology have been identified over the last decade. In this review, we describe recent advances in our understanding of cardiovascular function and dysfunction mediated by histamine receptors, including H 3 - and H 4 -receptors, their potential mechanisms of action, and their pathological significance.

Responses of susceptible subpopulations to nitrogen dioxide. Research report, June 1983-January 1988

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

Morrow, P.E.; Utell, M.J.

1989-02-01

Symptom responses and changes in pulmonary function were investigated in people with asthma or chronic obstructive pulmonary disease (COPD) exposed to 0.3 ppm nitrogen dioxide (NO{sub 2}) for four hours. Nonrespiratory-impaired (normal) subjects of comparable ages constituted the control groups. All exposures included periods of exercise and pulmonary function measurements. No significant symptomatic or physiological responses to NO{sub 2} could be detected in either the young or elderly control group. The asthmatic group did not manifest significant reductions in lung function after exposure to 0.3 ppm NO{sub 2}, compared to their preexposure baseline data or to their responses after amore » comparable four-hour exposure to air. During light exercise, subjects with COPD were progressively responsive to 0.3 ppm NO{sub 2}. Subgroup analyses within the asthmatic, COPD, and elderly normal subject groups and intergroup comparisons yielded significant findings and associations.« less

Bioelectronic Sensors and Devices

NASA Astrophysics Data System (ADS)

Reed, Mark

Nanoscale electronic devices have recently enabled the ability to controllably probe biological systems, from the molecular to the cellular level, opening up new applications and understanding of biological function and response. This talk reviews some of the advances in the field, ranging from diagnostic and therapeutic applications, to cellular manipulation and response, to the emulation of biological response. In diagnostics, integrated nanodevice biosensors compatible with CMOS technology have achieved unprecedented sensitivity, enabling a wide range of label-free biochemical and macromolecule sensing applications down to femtomolar concentrations. These systems have demonstrated integrated assays of biomarkers at clinically important concentrations for both diagnostics and as a quantitative tool for drug design and discovery. Cellular level response can also be observed, including immune response function and dynamics. Finally, the field is beginning to create devices that emulate function, and the demonstration of a solid state artificial ion channel will be discussed.

The Role of Civil Society Organizations in Monitoring the Global AIDS Response.

PubMed

Smith, Julia; Mallouris, Christoforos; Lee, Kelley; Alfvén, Tobias

2017-07-01

Civil society organizations (CSOs) are recognized as playing an exceptional role in the global AIDS response. However, there is little detailed research to date on how they contribute to specific governance functions. This article uses Haas' framework on global governance functions to map CSO's participation in the monitoring of global commitments to the AIDS response by institutions and states. Drawing on key informant interviews and primary documents, it focuses specifically on CSO participation in Global AIDS Response Progress Reporting and in Global Fund to Fight AIDS, Tuberculosis and Malaria processes. It argues that the AIDS response is unique within global health governance, in that CSOs fulfill both formal and informal monitoring functions, and considers the strengths and weaknesses of these contributions. It concludes that future global health governance arrangements should include provisions and resources for monitoring by CSOs because their participation creates more inclusive global health governance and contributes to strengthening commitments to human rights.

Photoreconfigurable polymers for biomedical applications: chemistry and macromolecular engineering.

PubMed

Zhu, Congcong; Ninh, Chi; Bettinger, Christopher J

2014-10-13

Stimuli-responsive polymers play an important role in many biomedical technologies. Light responsive polymers are particularly desirable because the parameters of irradiated light and diverse photoactive chemistries produce a large number of combinations between functional materials and associated stimuli. This Review summarizes recent advances in utilizing photoactive chemistries in macromolecules for prospective use in biomedical applications. Special focus is granted to selection criterion when choosing photofunctional groups. Synthetic strategies to incorporate these functionalities into polymers and networks with different topologies are also highlighted herein. Prospective applications of these materials are discussed including programmable matrices for controlled release, dynamic scaffolds for tissue engineering, and functional coatings for medical devices. The article concludes by summarizing the state of the art in photoresponsive polymers for biomedical applications including current challenges and future opportunities.

Multisensory connections of monkey auditory cerebral cortex

PubMed Central

Smiley, John F.; Falchier, Arnaud

2009-01-01

Functional studies have demonstrated multisensory responses in auditory cortex, even in the primary and early auditory association areas. The features of somatosensory and visual responses in auditory cortex suggest that they are involved in multiple processes including spatial, temporal and object-related perception. Tract tracing studies in monkeys have demonstrated several potential sources of somatosensory and visual inputs to auditory cortex. These include potential somatosensory inputs from the retroinsular (RI) and granular insula (Ig) cortical areas, and from the thalamic posterior (PO) nucleus. Potential sources of visual responses include peripheral field representations of areas V2 and prostriata, as well as the superior temporal polysensory area (STP) in the superior temporal sulcus, and the magnocellular medial geniculate thalamic nucleus (MGm). Besides these sources, there are several other thalamic, limbic and cortical association structures that have multisensory responses and may contribute cross-modal inputs to auditory cortex. These connections demonstrated by tract tracing provide a list of potential inputs, but in most cases their significance has not been confirmed by functional experiments. It is possible that the somatosensory and visual modulation of auditory cortex are each mediated by multiple extrinsic sources. PMID:19619628

Two-Component Noncollinear Time-Dependent Spin Density Functional Theory for Excited State Calculations.

PubMed

Egidi, Franco; Sun, Shichao; Goings, Joshua J; Scalmani, Giovanni; Frisch, Michael J; Li, Xiaosong

2017-06-13

We present a linear response formalism for the description of the electronic excitations of a noncollinear reference defined via Kohn-Sham spin density functional methods. A set of auxiliary variables, defined using the density and noncollinear magnetization density vector, allows the generalization of spin density functional kernels commonly used in collinear DFT to noncollinear cases, including local density, GGA, meta-GGA and hybrid functionals. Working equations and derivations of functional second derivatives with respect to the noncollinear density, required in the linear response noncollinear TDDFT formalism, are presented in this work. This formalism takes all components of the spin magnetization into account independent of the type of reference state (open or closed shell). As a result, the method introduced here is able to afford a nonzero local xc torque on the spin magnetization while still satisfying the zero-torque theorem globally. The formalism is applied to a few test cases using the variational exact-two-component reference including spin-orbit coupling to illustrate the capabilities of the method.

Passenger comfort response times as a function of aircraft motion

NASA Technical Reports Server (NTRS)

Rinalducci, E. J.

1975-01-01

The relationship between a passenger's response time of changes in level of comfort experienced as a function of aircraft motion was examined. The aircraft used in this investigation was capable of providing a wide range of vertical and transverse accelerations by means of direct lift flap control surfaces and side force generator surfaces in addition to normal control surfaces. Response times to changes in comfort were recorded along with the passenger's rating of comfort on a five point scale. In addition, a number of aircraft motion variables including vertical and transverse accelerations were also recorded. Results indicate some relationship between human comfort response times to reaction time data.

Screening vaccine formulations for biological activity using fresh human whole blood

PubMed Central

Brookes, Roger H; Hakimi, Jalil; Ha, Yukyung; Aboutorabian, Sepideh; Ausar, Salvador F; Hasija, Manvi; Smith, Steven G; Todryk, Stephen M; Dockrell, Hazel M; Rahman, Nausheen

2014-01-01

Understanding the relevant biological activity of any pharmaceutical formulation destined for human use is crucial. For vaccine-based formulations, activity must reflect the expected immune response, while for non-vaccine therapeutic agents, such as monoclonal antibodies, a lack of immune response to the formulation is desired. During early formulation development, various biochemical and biophysical characteristics can be monitored in a high-throughput screening (HTS) format. However, it remains impractical and arguably unethical to screen samples in this way for immunological functionality in animal models. Furthermore, data for immunological functionality lag formulation design by months, making it cumbersome to relate back to formulations in real-time. It is also likely that animal testing may not accurately reflect the response in humans. For a more effective formulation screen, a human whole blood (hWB) approach can be used to assess immunological functionality. The functional activity relates directly to the human immune response to a complete formulation (adjuvant/antigen) and includes adjuvant response, antigen response, adjuvant-modulated antigen response, stability, and potentially safety. The following commentary discusses the hWB approach as a valuable new tool to de-risk manufacture, formulation design, and clinical progression. PMID:24401565

Screening vaccine formulations for biological activity using fresh human whole blood.

PubMed

Brookes, Roger H; Hakimi, Jalil; Ha, Yukyung; Aboutorabian, Sepideh; Ausar, Salvador F; Hasija, Manvi; Smith, Steven G; Todryk, Stephen M; Dockrell, Hazel M; Rahman, Nausheen

2014-01-01

Understanding the relevant biological activity of any pharmaceutical formulation destined for human use is crucial. For vaccine-based formulations, activity must reflect the expected immune response, while for non-vaccine therapeutic agents, such as monoclonal antibodies, a lack of immune response to the formulation is desired. During early formulation development, various biochemical and biophysical characteristics can be monitored in a high-throughput screening (HTS) format. However, it remains impractical and arguably unethical to screen samples in this way for immunological functionality in animal models. Furthermore, data for immunological functionality lag formulation design by months, making it cumbersome to relate back to formulations in real-time. It is also likely that animal testing may not accurately reflect the response in humans. For a more effective formulation screen, a human whole blood (hWB) approach can be used to assess immunological functionality. The functional activity relates directly to the human immune response to a complete formulation (adjuvant/antigen) and includes adjuvant response, antigen response, adjuvant-modulated antigen response, stability, and potentially safety. The following commentary discusses the hWB approach as a valuable new tool to de-risk manufacture, formulation design, and clinical progression.

Epigenetic stress responses induce muscle stem-cell ageing by Hoxa9 developmental signals.

PubMed

Schwörer, Simon; Becker, Friedrich; Feller, Christian; Baig, Ali H; Köber, Ute; Henze, Henriette; Kraus, Johann M; Xin, Beibei; Lechel, André; Lipka, Daniel B; Varghese, Christy S; Schmidt, Manuel; Rohs, Remo; Aebersold, Ruedi; Medina, Kay L; Kestler, Hans A; Neri, Francesco; von Maltzahn, Julia; Tümpel, Stefan; Rudolph, K Lenhard

2016-12-15

The functionality of stem cells declines during ageing, and this decline contributes to ageing-associated impairments in tissue regeneration and function. Alterations in developmental pathways have been associated with declines in stem-cell function during ageing, but the nature of this process remains poorly understood. Hox genes are key regulators of stem cells and tissue patterning during embryogenesis with an unknown role in ageing. Here we show that the epigenetic stress response in muscle stem cells (also known as satellite cells) differs between aged and young mice. The alteration includes aberrant global and site-specific induction of active chromatin marks in activated satellite cells from aged mice, resulting in the specific induction of Hoxa9 but not other Hox genes. Hoxa9 in turn activates several developmental pathways and represents a decisive factor that separates satellite cell gene expression in aged mice from that in young mice. The activated pathways include most of the currently known inhibitors of satellite cell function in ageing muscle, including Wnt, TGFβ, JAK/STAT and senescence signalling. Inhibition of aberrant chromatin activation or deletion of Hoxa9 improves satellite cell function and muscle regeneration in aged mice, whereas overexpression of Hoxa9 mimics ageing-associated defects in satellite cells from young mice, which can be rescued by the inhibition of Hoxa9-targeted developmental pathways. Together, these data delineate an altered epigenetic stress response in activated satellite cells from aged mice, which limits satellite cell function and muscle regeneration by Hoxa9-dependent activation of developmental pathways.

SEOM-SERAM-SEMNIM guidelines on the use of functional and molecular imaging techniques in advanced non-small-cell lung cancer.

PubMed

Fernández Pérez, G; Sánchez Escribano, R; García Vicente, A M; Luna Alcalá, A; Ceballos Viro, J; Delgado Bolton, R C; Vilanova Busquets, J C; Sánchez Rovira, P; Fierro Alanis, M P; García Figueiras, R; Alés Martínez, J E

2018-05-25

Imaging in oncology is an essential tool for patient management but its potential is being profoundly underutilized. Each of the techniques used in the diagnostic process also conveys functional information that can be relevant in treatment decision making. New imaging algorithms and techniques enhance our knowledge about the phenotype of the tumor and its potential response to different therapies. Functional imaging can be defined as the one that provides information beyond the purely morphological data, and include all the techniques that make it possible to measure specific physiological functions of the tumor, whereas molecular imaging would include techniques that allow us to measure metabolic changes. Functional and molecular techniques included in this document are based on multi-detector computed tomography (CT), 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET), magnetic resonance imaging (MRI), and hybrid equipments, integrating PET with CT (PET/CT) or MRI (PET-MRI). Lung cancer is one of the most frequent and deadly tumors although survival is increasing thanks to advances in diagnostic methods and new treatments. This increased survival poises challenges in terms of proper follow-up and definitions of response and progression, as exemplified by immune therapy-related pseudoprogression. In this consensus document, the use of functional and molecular imaging techniques will be addressed to exploit their current potential and explore future applications in the diagnosis, evaluation of response and detection of recurrence of advanced NSCLC. Copyright © 2018 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

The Regulatory Functions of Calcium and the Potential Role of Calcium in Mediating Gravitational Responses in Cells and Tissues

NASA Technical Reports Server (NTRS)

Roux, S. J. (Editor)

1983-01-01

The hypothesis that calcium plays an important part in regulating cellular response to gravity and to other environmental stimuli is explored. Topics covered include the role of calmodulin and other proteins, gravitropic responses, bone demineralization during space flight, and intracellular communication.

Policing the intestinal epithelial barrier: Innate immune functions of intraepithelial lymphocytes.

PubMed

Hu, Madeleine D; Jia, Luo; Edelblum, Karen L

2018-03-01

This review will explore the contribution of IELs to mucosal innate immunity and highlight the similarities in IEL functional responses to bacteria, viruses and protozoan parasite invasion. IELs rapidly respond to microbial invasion by activating host defense responses, including the production of mucus and antimicrobial peptides to prevent microbes from reaching the epithelial surface. During active infection, IELs promote epithelial cytolysis, cytokine and chemokine production to limit pathogen invasion, replication and dissemination. Commensal-induced priming of IEL effector function or continuous surveillance of the epithelium may be important contributing factors to the rapidity of response. Impaired microbial recognition, dysregulated innate immune signaling or microbial dysbiosis may limit the protective function of IELs and increase susceptibility to disease. Further understanding of the mechanisms regulating IEL surveillance and sentinel function may provide insight into the development of more effective targeted therapies designed to reinforce the mucosal barrier.

Transient response of multidegree-of-freedom linear systems to forcing functions with inequality constraints

NASA Technical Reports Server (NTRS)

Michalopoulos, C. D.

1974-01-01

Optimal control theory is applied to analyze the transient response of discrete linear systems to forcing functions with unknown time dependence but having known bounds. Particular attention is given to forcing functions which include: (1) maximum displacement of any given mass element, (2) maximum relative displacement of any two adjacent masses, and (3) maximum acceleration of a given mass. Linear mechanical systems with an arbitrary number of degrees of freedom and only one forcing function acting are considered. In the general case, the desired forcing function is found to be a function that switches from the upper-to-lower bound and vice-versa at certain moments of time. A general procedure for finding such switching times is set forth.

International Student Affairs.

ERIC Educational Resources Information Center

Wood, Melinda; Kia, Parandeh

2000-01-01

Describes international student service units in higher education, including their primary functions, staff roles and responsibilities, major functional challenges, professional challenges and support systems, professional literature, and tips for those interested in the field. Also describes the author's personal career path in international…

Changes in tree functional composition amplify the response of forest biomass to climate variability

NASA Astrophysics Data System (ADS)

Lichstein, Jeremy; Zhang, Tao; Niinemets, Ulo; Sheffield, Justin

2017-04-01

The response of forest carbon storage to climate change is highly uncertain, contributing substantially to the divergence among global climate model projections. Numerous studies have documented responses of forest ecosystems to climate change and variability, including drought-induced increases in tree mortality rates. However, the sensitivity of forests to climate variability - in terms of both biomass carbon storage and functional components of tree species composition - has yet to be quantified across a large region using systematically sampled data. Here, we combine systematic forest inventories across the eastern USA with a species-level drought-tolerance index, derived from a meta-analysis of published literature, to quantify changes in forest biomass and community-mean-drought-tolerance in one-degree grid cells from the 1980s to 2000s. We show that forest biomass responds to decadal-scale changes in water deficit and that this biomass response is amplified by concurrent changes in community-mean-drought-tolerance. The amplification of the direct effects of water stress on biomass occurs because water stress tends to induce a shift in tree species composition towards more drought-tolerant but lower-biomass species. Multiple plant functional traits are correlated with the above species-level drought-tolerance index, and likely contribute to the decrease in biomass with increasing drought-tolerance. These traits include wood density and P50 (the xylem water potential at which a plant loses 50% of its hydraulic conductivity). Simulations with a trait- and competition-based dynamic global vegetation model suggest that species differences in plant carbon allocation to wood, leaves, and fine roots also likely contribute to the observed decrease in biomass with increasing drought-tolerance, because competition drives plants to over-invest in fine roots when water is limiting. Thus, the most competitive species under dry conditions have greater root allocation but lower total biomass than productivity-maximizing plants. Amplification of the biomass-climate response due to shifts in species functional composition (temporal beta diversity) contrasts with evidence that local (alpha) diversity increases ecosystem stability, including increased resistance to climate extremes. These contrasting effects of alpha and beta diversity highlight the need to better understand how different components of biodiversity, including changes in the functional traits of the dominant plant species, affect ecosystem functioning.

Depicting individual responses to physical therapist led chronic pain self-management support with pain science education and exercise in primary health care: multiple case studies.

PubMed

Miller, Jordan; MacDermid, Joy C; Richardson, Julie; Walton, David M; Gross, Anita

2017-01-01

Previous evidence suggests self-management programs for people with chronic pain improve knowledge and self-efficacy, but result in small to negligible changes in function. The purpose of this multiple case studies design was to describe the unique responses of six participants to a new self-management program aimed at improving function, to detail each component of the program, and to explore potential explanations for the varied trajectories of each of the participants. Six participants who had been experiencing chronic pain for at least 5 years were included. All participants were enrolled 6 weeks of ChrOnic pain self-ManageMent support with pain science EducatioN and exercise (COMMENCE). Participants completed an assessment at baseline, 7 weeks (1-week follow-up), and 18 weeks (12-week follow-up). Each participant had a unique initial presentation and goals. Assessments included: function as measured by the Short Musculoskeletal Function Assessment - Dysfunction Index, how much participants are bothered by functional difficulties, pain intensity, fatigue, pain interference, cognitive and psychological factors associated with pain and disability, pain neurophysiology, self-efficacy, satisfaction, and perceived change. The self-management program was 6-weeks in length, consisting of one individual visit and one group visit per week. The program incorporated three novel elements not commonly included in self-management programs: pain neurophysiology education, individualized exercises determined by the participants' goals, and additional cognitive behavioural approaches. Participants were all satisfied with self-management support received. Change in function was variable ranging from 59% improvement to 17% decline. Two potential explanations for variances in response, attendance and social context, are discussed. Several challenges were identified by participants as barriers to attendance. A primary care self-management intervention including pain education and individualized exercise has potential to improve function for some people with chronic pain, although strategies to improve adherence and reduce barriers to participation may be needed to optimize the impact.

RRAWFLOW: Rainfall-Response Aquifer and Watershed Flow Model (v1.15)

USGS Publications Warehouse

Long, Andrew J.

2015-01-01

The Rainfall-Response Aquifer and Watershed Flow Model (RRAWFLOW) is a lumped-parameter model that simulates streamflow, spring flow, groundwater level, or solute transport for a measurement point in response to a system input of precipitation, recharge, or solute injection. I introduce the first version of RRAWFLOW available for download and public use and describe additional options. The open-source code is written in the R language and is available at http://sd.water.usgs.gov/projects/RRAWFLOW/RRAWFLOW.html along with an example model of streamflow. RRAWFLOW includes a time-series process to estimate recharge from precipitation and simulates the response to recharge by convolution, i.e., the unit-hydrograph approach. Gamma functions are used for estimation of parametric impulse-response functions (IRFs); a combination of two gamma functions results in a double-peaked IRF. A spline fit to a set of control points is introduced as a new method for estimation of nonparametric IRFs. Several options are included to simulate time-variant systems. For many applications, lumped models simulate the system response with equal accuracy to that of distributed models, but moreover, the ease of model construction and calibration of lumped models makes them a good choice for many applications (e.g., estimating missing periods in a hydrologic record). RRAWFLOW provides professional hydrologists and students with an accessible and versatile tool for lumped-parameter modeling.

Different kernel functions due to rainfall response from borehole strainmeter in Taiwan

NASA Astrophysics Data System (ADS)

Yen Chen, Chih; Hu, Jyr Ching; LIu, Chi Ching

2014-05-01

In order to realize reasons inducing earthquakes, project of monitoring of the fault activity using 3-component Gladwin Tensor Strainmeter (GTSM) has been initiated since 2003 in Taiwan, which is one of the most active seismic regions in the world. Observed strain contains several different effects within including barometric, tidal, groundwater, precipitation, tectonics, seismic and other irregular noise. After removing the response of tides and air pressure on strain, we still can find some anomalies highly related to the rainfall in short time in days. The strain response induced by rainfall can be separated into two parts as observation in groundwater, slow response and quick response, respectively. Quick response reflects the strain responding to the load of falling water drops on the ground surface. A kernel function shows the continual response induced by unit precipitation water in time domain. We split the quick response from data removing tidal and barometric response, and then calculate the kernel function by use of deconvolution method. More, an average kernel function was calculated to reduce the noise level. There are five of the sites installed by CGS Taiwan were selected to calculate kernel functions for individual sites. The results show there may be different on rainfall response in different environmental settings. In the case of stations site on gentle terrain, kernel function for each site shows the similar trend, it rises quickly to maximum in 1 to 2 hrs, and then goes down near to zero gently in period of 2-3 days. But in the case of sites settled side by the rivers, there will be 2nd peak of function when collected water in the catchment flows along by the sites related to the hydrograph of creeks. More, landslides will occur in some sites in hazard of landslide with more rainfall stored on, just like DARB in ChiaYi. The curve of kernel function will be controlled by landslides and debris flows.

Comparing Individual Differences in Inconsistency and Plasticity as Predictors of Cognitive Function in Older Adults

PubMed Central

Grand, Jacob H.G.; Stawski, Robert S.; MacDonald, Stuart W.S.

2016-01-01

Introduction Recent theorizing differentiates key constraints on cognition, including one’s current range of processing efficiency (i.e., flexibility or inconsistency) as well as the capacity to expand flexibility over time (i.e., plasticity). The present study uses intensive assessment of response time data to examine the interplay between markers of intraindividual variability (inconsistency) and gains across biweekly retest sessions (plasticity) in relation to age-related cognitive function. Method Participants included 304 adults (aged 64 to 92 years: M=74.02, SD=5.95) from Project MIND, a longitudinal burst design study assessing performance across micro and macro intervals (response latency trials, weekly bursts, annual retests). For two reaction time measures (choice RT and one-back choice RT), baseline measures of response time (RT) inconsistency (intraindividual standard deviation (ISD) across-trials at the first testing session) and plasticity (within-person performance gains in average RT across the 5 biweekly burst sessions) were computed, and then employed in linear mixed models as predictors of individual differences in cognitive function and longitudinal (6 year) rates of cognitive change. Results Independent of chronological age and years of education, higher RT inconsistency was associated uniformly with poorer cognitive function at baseline and with increased cognitive decline for measures of episodic memory and crystallized verbal ability. In contrast, predictive associations for plasticity were more modest for baseline cognitive function and were absent for 6-year cognitive change. Conclusions These findings underscore the potential utility of response times for articulating inconsistency and plasticity as dynamic predictors of cognitive function in older adults. PMID:26898536

What Does a Day Care Director Really Do?

ERIC Educational Resources Information Center

Morgan, Gwen G.

This paper describes the work of day care directors in terms of four functions. The first function is that of assuming legal responsibility and accountability. This function includes accepting punishment in case of wrongdoing; representing the organization to the government and the public; and meeting state licensure standards and other standards.…

A mathematical function for the description of nutrient-response curve

PubMed Central

Ahmadi, Hamed

2017-01-01

Several mathematical equations have been proposed to modeling nutrient-response curve for animal and human justified on the goodness of fit and/or on the biological mechanism. In this paper, a functional form of a generalized quantitative model based on Rayleigh distribution principle for description of nutrient-response phenomena is derived. The three parameters governing the curve a) has biological interpretation, b) may be used to calculate reliable estimates of nutrient response relationships, and c) provide the basis for deriving relationships between nutrient and physiological responses. The new function was successfully applied to fit the nutritional data obtained from 6 experiments including a wide range of nutrients and responses. An evaluation and comparison were also done based simulated data sets to check the suitability of new model and four-parameter logistic model for describing nutrient responses. This study indicates the usefulness and wide applicability of the new introduced, simple and flexible model when applied as a quantitative approach to characterizing nutrient-response curve. This new mathematical way to describe nutritional-response data, with some useful biological interpretations, has potential to be used as an alternative approach in modeling nutritional responses curve to estimate nutrient efficiency and requirements. PMID:29161271

Electrodermal responses during appetitive conditioning are sensitive to contingency instruction ambiguity.

PubMed

van den Akker, Karolien; Nederkoorn, Chantal; Jansen, Anita

2017-08-01

Studies on human appetitive conditioning using food rewards can benefit from including psychophysiological outcome measures. The present study tested whether the skin conductance response can function as a measure of differential responding in an appetitive conditioning paradigm including an acquisition and extinction phase, and examined which time window during a trial is most sensitive to conditioning effects. As a secondary aim, the effects of ambiguous vs. non-ambiguous contingency instructions on conditioned responses (skin conductance responses, US expectancies, chocolate desires, and CS evaluations) were assessed. Results indicated differential skin conductance responses in an anticipatory time window and during unexpected omission of the US in early extinction. Interestingly however, anticipatory responses were only found for participants who received ambiguous contingency instructions - possibly indicating a call for additional processing resources in response to the ambiguous CS+. Further, ambiguous instructions slowed the extinction of US expectancies but did not influence chocolate desires and CS evaluations. It is concluded that skin conductance can function as a sensitive measure of differential responding in appetitive conditioning, though its sensitivity might depend on the specific task context. Copyright © 2017 Elsevier B.V. All rights reserved.

Emergence of ratio-dependent and predator-dependent functional responses for pollination mutualism and seed parasitism

USGS Publications Warehouse

DeAngelis, Donald L.; Holland, J. Nathaniel

2006-01-01

Prey (N) dependence [g(N)], predator (P) dependence [g(P) or g(N,P)], and ratio dependence [f(P/N)] are often seen as contrasting forms of the predator's functional response describing predator consumption rates on prey resources in predator–prey and parasitoid–host interactions. Analogously, prey-, predator-, and ratio-dependent functional responses are apparently alternative functional responses for other types of consumer–resource interactions. These include, for example, the fraction of flowers pollinated or seeds parasitized in pollination (pre-dispersal) seed-parasitism mutualisms, such as those between fig wasps and fig trees or yucca moths and yucca plants. Here we examine the appropriate functional responses for how the fraction of flowers pollinated and seeds parasitized vary with the density of pollinators (predator dependence) or the ratio of pollinator and flower densities (ratio dependence). We show that both types of functional responses can emerge from minor, but biologically important variations on a single model. An individual-based model was first used to describe plant–pollinator interactions. Conditional upon on whether the number of flowers visited by the pollinator was limited by factors other than search time (e.g., by the number of eggs it had to lay, if it was also a seed parasite), and on whether the pollinator could directly find flowers on a plant, or had to search, the simulation results lead to either a predator-dependent or a ratio-dependent functional response. An analytic model was then used to show mathematically how these two cases can arise.

Mammalian Per-Arnt-Sim proteins in environmental adaptation.

PubMed

McIntosh, Brian E; Hogenesch, John B; Bradfield, Christopher A

2010-01-01

The Per-Arnt-Sim (PAS) domain is conserved across the kingdoms of life and found in an ever-growing list of proteins. This domain can bind to and sense endogenous or xenobiotic small molecules such as molecular oxygen, cellular metabolites, or polyaromatic hydrocarbons. Members of this family are often found in pathways that regulate responses to environmental change; in mammals these include the hypoxia, circadian, and dioxin response pathways. These pathways function in development and throughout life to regulate cellular, organ, and whole-organism adaptive responses. Remarkably, in the case of the clock, this adaptation includes anticipation of environmental change. In this review, we summarize the roles of PAS domain-containing proteins in mammals. We provide structural evidence that functionally classifies both known and unknown biological roles. Finally, we discuss the role of PAS proteins in anticipation of and adaptation to environmental change.

Plant hydraulic diversity buffers forest ecosystem responses to drought

NASA Astrophysics Data System (ADS)

Anderegg, W.; Konings, A. G.; Trugman, A. T.; Pacala, S. W.; Yu, K.; Sulman, B. N.; Sperry, J.; Bowling, D. R.

2017-12-01

Drought impacts carbon, water, and energy cycles in forests and may pose a fundamental threat to forests in future climates. Plant hydraulic transport of water is central to tree drought responses, including curtailing of water loss and the risk of mortality during drought. The effect of biodiversity on ecosystem function has typically been examined in grasslands, yet the diversity of plant hydraulic strategies may influence forests' response to drought. In a combined analysis of eddy covariance measurements, remote-sensing data of plant water content variation, model simulations, and plant hydraulic trait data, we test the degree to which plant water stress schemes influence the carbon cycle and how hydraulic diversity within and across ecosystems affects large-scale drought responses. We find that current plant functional types are not well-suited to capture hydraulic variation and that higher hydraulic diversity buffers ecosystem variation during drought. Our results demonstrate that tree functional diversity, particularly hydraulic diversity, may be critical to simulate in plant functional types in current land surface model projections of future vegetation's response to climate extremes.

Integrative Transcriptomic Analysis Uncovers Novel Gene Modules That Underlie the Sulfate Response in Arabidopsis thaliana

PubMed Central

Henríquez-Valencia, Carlos; Arenas-M, Anita; Medina, Joaquín; Canales, Javier

2018-01-01

Sulfur is an essential nutrient for plant growth and development. Sulfur is a constituent of proteins, the plasma membrane and cell walls, among other important cellular components. To obtain new insights into the gene regulatory networks underlying the sulfate response, we performed an integrative meta-analysis of transcriptomic data from five different sulfate experiments available in public databases. This bioinformatic approach allowed us to identify a robust set of genes whose expression depends only on sulfate availability, indicating that those genes play an important role in the sulfate response. In relation to sulfate metabolism, the biological function of approximately 45% of these genes is currently unknown. Moreover, we found several consistent Gene Ontology terms related to biological processes that have not been extensively studied in the context of the sulfate response; these processes include cell wall organization, carbohydrate metabolism, nitrogen compound transport, and the regulation of proteolysis. Gene co-expression network analyses revealed relationships between the sulfate-responsive genes that were distributed among seven function-specific co-expression modules. The most connected genes in the sulfate co-expression network belong to a module related to the carbon response, suggesting that this biological function plays an important role in the control of the sulfate response. Temporal analyses of the network suggest that sulfate starvation generates a biphasic response, which involves that major changes in gene expression occur during both the early and late responses. Network analyses predicted that the sulfate response is regulated by a limited number of transcription factors, including MYBs, bZIPs, and NF-YAs. In conclusion, our analysis identified new candidate genes and provided new hypotheses to advance our understanding of the transcriptional regulation of sulfate metabolism in plants. PMID:29692794

Integrative Transcriptomic Analysis Uncovers Novel Gene Modules That Underlie the Sulfate Response in Arabidopsis thaliana.

PubMed

Henríquez-Valencia, Carlos; Arenas-M, Anita; Medina, Joaquín; Canales, Javier

2018-01-01

Sulfur is an essential nutrient for plant growth and development. Sulfur is a constituent of proteins, the plasma membrane and cell walls, among other important cellular components. To obtain new insights into the gene regulatory networks underlying the sulfate response, we performed an integrative meta-analysis of transcriptomic data from five different sulfate experiments available in public databases. This bioinformatic approach allowed us to identify a robust set of genes whose expression depends only on sulfate availability, indicating that those genes play an important role in the sulfate response. In relation to sulfate metabolism, the biological function of approximately 45% of these genes is currently unknown. Moreover, we found several consistent Gene Ontology terms related to biological processes that have not been extensively studied in the context of the sulfate response; these processes include cell wall organization, carbohydrate metabolism, nitrogen compound transport, and the regulation of proteolysis. Gene co-expression network analyses revealed relationships between the sulfate-responsive genes that were distributed among seven function-specific co-expression modules. The most connected genes in the sulfate co-expression network belong to a module related to the carbon response, suggesting that this biological function plays an important role in the control of the sulfate response. Temporal analyses of the network suggest that sulfate starvation generates a biphasic response, which involves that major changes in gene expression occur during both the early and late responses. Network analyses predicted that the sulfate response is regulated by a limited number of transcription factors, including MYBs, bZIPs, and NF-YAs. In conclusion, our analysis identified new candidate genes and provided new hypotheses to advance our understanding of the transcriptional regulation of sulfate metabolism in plants.

Numerical integration of detector response functions via Monte Carlo simulations

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

Kelly, Keegan John; O'Donnell, John M.; Gomez, Jaime A.

Calculations of detector response functions are complicated because they include the intricacies of signal creation from the detector itself as well as a complex interplay between the detector, the particle-emitting target, and the entire experimental environment. As such, these functions are typically only accessible through time-consuming Monte Carlo simulations. Furthermore, the output of thousands of Monte Carlo simulations can be necessary in order to extract a physics result from a single experiment. Here we describe a method to obtain a full description of the detector response function using Monte Carlo simulations. We also show that a response function calculated inmore » this way can be used to create Monte Carlo simulation output spectra a factor of ~1000× faster than running a new Monte Carlo simulation. A detailed discussion of the proper treatment of uncertainties when using this and other similar methods is provided as well. Here, this method is demonstrated and tested using simulated data from the Chi-Nu experiment, which measures prompt fission neutron spectra at the Los Alamos Neutron Science Center.« less

Numerical integration of detector response functions via Monte Carlo simulations

NASA Astrophysics Data System (ADS)

Kelly, K. J.; O'Donnell, J. M.; Gomez, J. A.; Taddeucci, T. N.; Devlin, M.; Haight, R. C.; White, M. C.; Mosby, S. M.; Neudecker, D.; Buckner, M. Q.; Wu, C. Y.; Lee, H. Y.

2017-09-01

Calculations of detector response functions are complicated because they include the intricacies of signal creation from the detector itself as well as a complex interplay between the detector, the particle-emitting target, and the entire experimental environment. As such, these functions are typically only accessible through time-consuming Monte Carlo simulations. Furthermore, the output of thousands of Monte Carlo simulations can be necessary in order to extract a physics result from a single experiment. Here we describe a method to obtain a full description of the detector response function using Monte Carlo simulations. We also show that a response function calculated in this way can be used to create Monte Carlo simulation output spectra a factor of ∼ 1000 × faster than running a new Monte Carlo simulation. A detailed discussion of the proper treatment of uncertainties when using this and other similar methods is provided as well. This method is demonstrated and tested using simulated data from the Chi-Nu experiment, which measures prompt fission neutron spectra at the Los Alamos Neutron Science Center.

Numerical integration of detector response functions via Monte Carlo simulations

DOE PAGES

Kelly, Keegan John; O'Donnell, John M.; Gomez, Jaime A.; ...

2017-06-13

Calculations of detector response functions are complicated because they include the intricacies of signal creation from the detector itself as well as a complex interplay between the detector, the particle-emitting target, and the entire experimental environment. As such, these functions are typically only accessible through time-consuming Monte Carlo simulations. Furthermore, the output of thousands of Monte Carlo simulations can be necessary in order to extract a physics result from a single experiment. Here we describe a method to obtain a full description of the detector response function using Monte Carlo simulations. We also show that a response function calculated inmore » this way can be used to create Monte Carlo simulation output spectra a factor of ~1000× faster than running a new Monte Carlo simulation. A detailed discussion of the proper treatment of uncertainties when using this and other similar methods is provided as well. Here, this method is demonstrated and tested using simulated data from the Chi-Nu experiment, which measures prompt fission neutron spectra at the Los Alamos Neutron Science Center.« less

Altered neural activation during prepotent response inhibition in breast cancer survivors treated with chemotherapy: an fMRI study.

PubMed

Kam, Julia W Y; Boyd, Lara A; Hsu, Chun L; Liu-Ambrose, Teresa; Handy, Todd C; Lim, Howard J; Hayden, Sherri; Campbell, Kristin L

2016-09-01

While impairments in executive functions have been reported in breast cancer survivors (BCS) who have undergone adjuvant chemotherapy, only a limited number of functional neuroimaging studies have associated alterations in cerebral activity with executive functions deficits in BCS. Using fMRI, the current study assessed the neural basis underlying a specific facet of executive function, namely prepotent response inhibition. 12 BCS who self-reported cognitive problems up to 3 years following cancer treatment and 12 female healthy comparisons (HC) performed the Stroop task. We compared their neural activation between the incongruent and neutral experimental conditions. Relative to the HC group, BCS showed lower blood-oxygen level dependent signal in several frontal regions, including the anterior cingulate cortex, a region critical for response inhibition. Our data indicates reduced neural activation in BCS during a prepotent response inhibition task, providing support for the prevailing notion of neural alterations observed in BCS treated with chemotherapy.

Probabilistic analysis of bladed turbine disks and the effect of mistuning

NASA Technical Reports Server (NTRS)

Shah, A. R.; Nagpal, V. K.; Chamis, Christos C.

1990-01-01

Probabilistic assessment of the maximum blade response on a mistuned rotor disk is performed using the computer code NESSUS. The uncertainties in natural frequency, excitation frequency, amplitude of excitation and damping are included to obtain the cumulative distribution function (CDF) of blade responses. Advanced mean value first order analysis is used to compute CDF. The sensitivities of different random variables are identified. Effect of the number of blades on a rotor on mistuning is evaluated. It is shown that the uncertainties associated with the forcing function parameters have significant effect on the response distribution of the bladed rotor.

Probabilistic analysis of bladed turbine disks and the effect of mistuning

NASA Technical Reports Server (NTRS)

Shah, Ashwin; Nagpal, V. K.; Chamis, C. C.

1990-01-01

Probabilistic assessment of the maximum blade response on a mistuned rotor disk is performed using the computer code NESSUS. The uncertainties in natural frequency, excitation frequency, amplitude of excitation and damping have been included to obtain the cumulative distribution function (CDF) of blade responses. Advanced mean value first order analysis is used to compute CDF. The sensitivities of different random variables are identified. Effect of the number of blades on a rotor on mistuning is evaluated. It is shown that the uncertainties associated with the forcing function parameters have significant effect on the response distribution of the bladed rotor.

Catecholamine responses to virtual combat: implications for post-traumatic stress and dimensions of functioning.

PubMed

Highland, Krista B; Costanzo, Michelle E; Jovanovic, Tanja; Norrholm, Seth D; Ndiongue, Rochelle B; Reinhardt, Brian J; Rothbaum, Barbara; Rizzo, Albert A; Roy, Michael J

2015-01-01

Posttraumatic stress disorder (PTSD) symptoms can result in functional impairment among service members (SMs), even in those without a clinical diagnosis. The variability in outcomes may be related to underlying catecholamine mechanisms. Individuals with PTSD tend to have elevated basal catecholamine levels, though less is known regarding catecholamine responses to trauma-related stimuli. We assessed whether catecholamine responses to a virtual combat environment impact the relationship between PTSD symptom clusters and elements of functioning. Eighty-seven clinically healthy SMs, within 2 months after deployment to Iraq or Afghanistan, completed self-report measures, viewed virtual-reality (VR) combat sequences, and had sequential blood draws. Norepinephrine responses to VR combat exposure moderated the relationship between avoidance symptoms and scales of functioning including physical functioning, physical-role functioning, and vitality. Among those with high levels of avoidance, norepinephrine change was inversely associated with functional status, whereas a positive correlation was observed for those with low levels of avoidance. Our findings represent a novel use of a virtual environment to display combat-related stimuli to returning SMs to elucidate mind-body connections inherent in their responses. The insight gained improves our understanding of post-deployment symptoms and quality of life in SMs and may facilitate enhancements in treatment. Further research is needed to validate these findings in other populations and to define the implications for treatment effectiveness.

Comparison of Spontaneously Elicited Language Patterns in Specific Language Impairment and High-Functioning Autism.

PubMed

Craig, Megan; Trauner, Doris

2018-02-01

We aimed to characterize differences in the use of language in children with specific language impairment and high-functioning autism by analyzing verbal responses on standardized tests. The overall goal was to provide clinicians with additional tools with which to aid in distinguishing the two neurodevelopmental disorders. This study included 16 children with specific language impairment, 28 children with high-functioning autism, and 52 typically developing participants between the ages of six and 14. Groups were matched for age, and specific language impairment and high-functioning autism groups were matched on verbal and performance IQ. Responses from standardized tests were examined for response length, grammatical errors, filler words, perseverations, revisions (repeated attempts to begin or continue a sentence), off-topic attention shifts (lapses in attention to the task), and rambling. Data were analyzed using parametric and nonparametric methods. Specific language impairment responses were longer and contained more filler words than did those of the other two groups, whereas high-functioning autism responses exhibited more grammatical errors, off-topic attention shifts, and rambling. Specific language impairment and high-functioning autism responses showed higher rates of perseveration compared with controls. There were no significant differences in revisions among the three groups. Differences in language patterns of participants with specific language impairment and high-functioning autism may be useful to the clinician in helping to differentiate isolated language impairment from high-functioning autism. The results also support the conclusion that the two conditions are separable, and each exhibits a different pattern of language dysfunction. Copyright © 2017 Elsevier Inc. All rights reserved.

The Adaptive Calibration Model of stress responsivity

PubMed Central

Ellis, Bruce J.; Shirtcliff, Elizabeth A.

2010-01-01

This paper presents the Adaptive Calibration Model (ACM), an evolutionary-developmental theory of individual differences in the functioning of the stress response system. The stress response system has three main biological functions: (1) to coordinate the organism’s allostatic response to physical and psychosocial challenges; (2) to encode and filter information about the organism’s social and physical environment, mediating the organism’s openness to environmental inputs; and (3) to regulate the organism’s physiology and behavior in a broad range of fitness-relevant areas including defensive behaviors, competitive risk-taking, learning, attachment, affiliation and reproductive functioning. The information encoded by the system during development feeds back on the long-term calibration of the system itself, resulting in adaptive patterns of responsivity and individual differences in behavior. Drawing on evolutionary life history theory, we build a model of the development of stress responsivity across life stages, describe four prototypical responsivity patterns, and discuss the emergence and meaning of sex differences. The ACM extends the theory of biological sensitivity to context (BSC) and provides an integrative framework for future research in the field. PMID:21145350

Executing application function calls in response to an interrupt

DOEpatents

Almasi, Gheorghe; Archer, Charles J.; Giampapa, Mark E.; Gooding, Thomas M.; Heidelberger, Philip; Parker, Jeffrey J.

2010-05-11

Executing application function calls in response to an interrupt including creating a thread; receiving an interrupt having an interrupt type; determining whether a value of a semaphore represents that interrupts are disabled; if the value of the semaphore represents that interrupts are not disabled: calling, by the thread, one or more preconfigured functions in dependence upon the interrupt type of the interrupt; yielding the thread; and if the value of the semaphore represents that interrupts are disabled: setting the value of the semaphore to represent to a kernel that interrupts are hard-disabled; and hard-disabling interrupts at the kernel.

On the dependence of response inhibition processes on sensory modality.

PubMed

Bodmer, Benjamin; Beste, Christian

2017-04-01

The ability to inhibit responses is a central sensorimotor function but only recently the importance of sensory processes for motor inhibition mechanisms went more into the research focus. In this regard it is elusive, whether there are differences between sensory modalities to trigger response inhibition processes. Due to functional neuroanatomical considerations strong differences may exist, for example, between the visual and the tactile modality. In the current study we examine what neurophysiological mechanisms as well as functional neuroanatomical networks are modulated during response inhibition. Therefore, a Go/NoGo-paradigm employing a novel combination of visual, tactile, and visuotactile stimuli was used. The data show that the tactile modality is more powerful than the visual modality to trigger response inhibition processes. However, the tactile modality loses its efficacy to trigger response inhibition processes when being combined with the visual modality. This may be due to competitive mechanisms leading to a suppression of certain sensory stimuli and the response selection level. Variations in sensory modalities specifically affected conflict monitoring processes during response inhibition by modulating activity in a frontal parietal network including the right inferior frontal gyrus, anterior cingulate cortex and the temporoparietal junction. Attentional selection processes are not modulated. The results suggest that the functional neuroanatomical networks involved in response inhibition critically depends on the nature of the sensory input. Hum Brain Mapp 38:1941-1951, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Hemispheric Specialization for Emotional Word Processing Is a Function of SSRI Responsiveness

ERIC Educational Resources Information Center

Walsh, Amy; McDowall, John; Grimshaw, Gina M.

2010-01-01

Vulnerability to depression and non-response to Selective Serotonin Reuptake Inhibitors (SSRIs) are associated with specific neurophysiological characteristics including greater right hemisphere (RH) relative to left hemisphere (LH) activity. The present study investigated the relationship between hemispheric specialization and processing of…

Continual Response Measurement: Design and Validation.

ERIC Educational Resources Information Center

Baggaley, Jon

1987-01-01

Discusses reliability and validity of continual response measurement (CRM), a computer-based measurement technique, and its use in social science research. Highlights include the importance of criterion-referencing the data, guidelines for designing studies using CRM, examples typifying their deductive and inductive functions, and a discussion of…

Integrated regulation of PIKK-mediated stress responses by AAA+ proteins RUVBL1 and RUVBL2

PubMed Central

Izumi, Natsuko; Yamashita, Akio; Ohno, Shigeo

2012-01-01

Proteins of the phosphatidylinositol 3-kinase-related protein kinase (PIKK) family are activated by various cellular stresses, including DNA damage, premature termination codon and nutritional status, and induce appropriate cellular responses. The importance of PIKK functions in the maintenance of genome integrity, accurate gene expression and the proper control of cell growth/proliferation is established. Recently, ATPase associated diverse cellular activities (AAA+) proteins RUVBL1 and RUVBL2 (RUVBL1/2) have been shown to be common regulators of PIKKs. The RUVBL1/2 complex regulates PIKK-mediated stress responses through physical interactions with PIKKs and by controlling PIKK mRNA levels. In this review, the functions of PIKKs in stress responses are outlined and the physiological significance of the integrated regulation of PIKKs by the RUVBL1/2 complex is presented. We also discuss a putative “PIKK regulatory chaperone complex” including other PIKK regulators, Hsp90 and the Tel2 complex. PMID:22540023

Practical recommendations for strengthening national and regional laboratory networks in Africa in the Global Health Security era.

PubMed

Best, Michele; Sakande, Jean

2016-01-01

The role of national health laboratories in support of public health response has expanded beyond laboratory testing to include a number of other core functions such as emergency response, training and outreach, communications, laboratory-based surveillance and data management. These functions can only be accomplished by an efficient and resilient national laboratory network that includes public health, reference, clinical and other laboratories. It is a primary responsibility of the national health laboratory in the Ministry of Health to develop and maintain the national laboratory network in the country. In this article, we present practical recommendations based on 17 years of network development experience for the development of effective national laboratory networks. These recommendations and examples of current laboratory networks, are provided to facilitate laboratory network development in other states. The development of resilient, integrated laboratory networks will enhance each state's public health system and is critical to the development of a robust national laboratory response network to meet global health security threats.

Practical recommendations for strengthening national and regional laboratory networks in Africa in the Global Health Security era

PubMed Central

2016-01-01

The role of national health laboratories in support of public health response has expanded beyond laboratory testing to include a number of other core functions such as emergency response, training and outreach, communications, laboratory-based surveillance and data management. These functions can only be accomplished by an efficient and resilient national laboratory network that includes public health, reference, clinical and other laboratories. It is a primary responsibility of the national health laboratory in the Ministry of Health to develop and maintain the national laboratory network in the country. In this article, we present practical recommendations based on 17 years of network development experience for the development of effective national laboratory networks. These recommendations and examples of current laboratory networks, are provided to facilitate laboratory network development in other states. The development of resilient, integrated laboratory networks will enhance each state’s public health system and is critical to the development of a robust national laboratory response network to meet global health security threats. PMID:28879137

Functionalized membranes for environmental remediation and selective separation

NASA Astrophysics Data System (ADS)

Xiao, Li

Membrane process including microfiltration (MF), ultrafiltration (UF), nanofiltration (NF) and reverse osmosis (RO) have provided numerous successful applications ranging from drinking water purification, wastewater treatment, to material recovery. The addition of functional moiety in the membranes pores allows such membranes to be used in challenging areas including tunable separations, toxic metal capture, and catalysis. In this work, polyvinylidene fluoride (PVDF) MF membrane was functionalized with temperature responsive (poly(N-isopropylacrylamide), PNIPAAm) and pH responsive (polyacrylic acid, PAA) polymers. It's revealed that the permeation of various molecules (water, salt and dextran) through the membrane can be thermally or pH controlled. The introduction of PAA as a polyelectrolyte offers an excellent platform for the immobilization of metal nanoparticles (NPs) applied for degradation of toxic chlorinated organics with significantly increased longevity and stability. The advantage of using temperature and pH responsive polymers/hydrogels also includes the high reactivity and effectiveness in dechlorination. Further advancement on the PVDF functionalization involved the alkaline treatment to create partially defluorinated membrane (Def-PVDF) with conjugated double bounds allowing for the covalent attachment of different polymers. The PAA-Def-PVDF membrane shows pH responsive behavior on both the hydraulic permeability and solute retention. The sponge-like PVDF (SPVDF) membranes by phase inversion were developed through casting PVDF solution on polyester backing. The SPVDF membrane was demonstrated to have 4 times more surface area than commercial PVDF MF membrane, allowing for enhanced nanoparticles loading for chloro-organics degradation. The advanced functionalization method and process were also validated to be able to be scaled-up through the evaluation of full-scale functionalized membrane provided by Ultura Inc. California, USA. Nanofiltration (NF) between UF and RO presents selectivity controlled by both steric and electrostatic repulsions, which are widely used to reject charged species, particularly multivalent ions. In this work, selective permeation of CaCl2 and high sucrose retention are obtained through the modification of nanofiltration membranes with lower charge compared to commercial nanofiltration membrane. The membrane module also shows high stability with constant water permeability in a long-term (two months) test. Extended Nernst-Planck equation were further used to evaluate the experimental results and it fits well. KEY WORDS: Functionalized Membrane, Dechlorination, Responsive, Tunable, Full-scale.

DR5 as a reporter system to study auxin response in Populus.

PubMed

Chen, Yiru; Yordanov, Yordan S; Ma, Cathleen; Strauss, Steven; Busov, Victor B

2013-03-01

KEY MESSAGE : Auxin responsive promoter DR5 reporter system is functional in Populus to monitor auxin response in tissues including leaves, roots, and stems. We described the behavior of the DR5::GUS reporter system in stably transformed Populus plants. We found several similarities with Arabidopsis, including sensitivity to native and synthetic auxins, rapid induction after treatment in a variety of tissues, and maximal responses in root tissues. There were also several important differences from Arabidopsis, including slower time to maximum response and lower induction amplitude. Young leaves and stem sections below the apex showed much higher DR5 activity than did older leaves and stems undergoing secondary growth. DR5 activity was highest in cortex, suggesting high levels of auxin concentration and/or sensitivity in this tissue. Our study shows that the DR5 reporter system is a sensitive and facile system for monitoring auxin responses and distribution at cellular resolution in poplar.

A Note on the Equivalence between Observed and Expected Information Functions with Polytomous IRT Models

ERIC Educational Resources Information Center

Magis, David

2015-01-01

The purpose of this note is to study the equivalence of observed and expected (Fisher) information functions with polytomous item response theory (IRT) models. It is established that observed and expected information functions are equivalent for the class of divide-by-total models (including partial credit, generalized partial credit, rating…

System Engineering Analysis of Squadron Officer College

DTIC Science & Technology

2012-03-01

study identified five challenges to converting to a blended learning course. The greatest challenge is getting commitment and buy -in from senior...students thru the Army and Air Force Exchange Service (AAFES) snack bar. Managers are responsible for ensuring adequate support throughout the...Administration Function The administration function allows daily tasks to operate. SOC administration functions include providing students with

Conservation of ectomycorrhizal fungi: exploring the linkages between functional and taxonomic responses to anthropogenic N deposition

Treesearch

E.A. Lilleskov; E.A. Hobbie; T.R. Horton

2011-01-01

Anthropogenic nitrogen (N) deposition alters ectomycorrhizal fungal communities, but the effect on functional diversity is not clear. In this review we explore whether fungi that respond differently to N deposition also differ in functional traits, including organic N use, hydrophobicity and exploration type (extent and pattern of extraradical hyphae). ...

Role of macrophages in the altered epithelial function during a type 2 immune response induced by enteric nematode infection

USDA-ARS?s Scientific Manuscript database

Two major functions of the intestinal epithelium are to act as a physical barrier and to regulate the movement of nutrients, ions and fluid. Nematode infection induces alterations in smooth and epithelial cell function, including increased fluid in the intestinal lumen, which are attributed to a ST...

Altered Reward Function in Adolescent Depression: What, When, and How?

PubMed Central

Forbes, Erika E.; Dahl, Ronald E.

2011-01-01

Background Conceptual models and recent evidence indicate that neural response to reward is altered in depression. Taking a developmental approach to investigating reward function in adolescent depression can elucidate the etiology, pathophysiology, and course of depression, a disorder that typically begins during adolescence and has high rates of recurrence. Methods This conceptual review describes the what, when, and how of altered reward function in adolescent depression. With the goal of generating new, testable hypotheses within a developmental affective neuroscience framework, we critically review findings and suggest future directions. Peer-reviewed empirical papers for inclusion in this critical review were obtained by searching PubMed, PsycInfo, and ScienceDirect for the years 1990–2010. Results A pattern of low striatal response and high medial prefrontal response to reward is evident in adolescents and adults with depression. Given the salience of social stimuli for positive affect and depression, reward function might be especially disrupted in response to social rewards. Because of changes in the dopamine system and reward function with aging, altered reward function in depression might be more evident during adolescence than later in life; however, low reward function may also be a stable characteristic of people who experience depression. Mechanisms of altered reward function in depression could include disrupted balance of corticostriatal circuit function, with disruption occurring as aberrant adolescent brain development. Conclusions Future studies should examine responses to social rewards; employ longitudinal and prospective designs; and investigate patterns of functional connectivity in reward circuits. Understanding altered reward function in depression has potential implications for treatment development. A more rigorous approach to investigating anhedonia, threat-reward interactions, and comorbid anxiety will be valuable to future progress in describing the role of reward function in the pathophysiology of depression. PMID:22117893

Vestibulo-ocular and vestibulospinal function before and after cochlear implant surgery

NASA Technical Reports Server (NTRS)

Black, F. O.; Lilly, D. J.; Peterka, R. J.; Fowler, L. P.; Simmons, F. B.

1987-01-01

Vestibular function in cochlear implant candidates varies from normal to total absence of function. In patients with intact vestibular function preoperatively, invasion of the otic capsule places residual vestibular function at risk. Speech-processing strategies that result in large amplitude electrical transients or strategies that employ high amplitude broad frequency carrier signals have the potential for disrupting vestibular function. Five patients were tested with and without electrical stimulation via cochlear electrodes. Two patients experienced subjective vestibular effects that were quickly resolved. No long-term vestibular effects were noted for the two types of second generation cochlear implants evaluated. Histopathological findings from another patient, who had electrically generated vestibular reflex responses to intramodiolar electrodes, indicated that responses elicited were a function of several variables including electrode location, stimulus intensity, stimulus amplitude, and stimulus frequency. Differential auditory, vestibulocolic, and vestibulospinal reflexes were demonstrated from the same electrode as a function of stimulus amplitude, frequency, and duration.

Novel biomarker-based model for the prediction of sorafenib response and overall survival in advanced hepatocellular carcinoma: a prospective cohort study.

PubMed

Kim, Hwi Young; Lee, Dong Hyeon; Lee, Jeong-Hoon; Cho, Young Youn; Cho, Eun Ju; Yu, Su Jong; Kim, Yoon Jun; Yoon, Jung-Hwan

2018-03-20

Prediction of the outcome of sorafenib therapy using biomarkers is an unmet clinical need in patients with advanced hepatocellular carcinoma (HCC). The aim was to develop and validate a biomarker-based model for predicting sorafenib response and overall survival (OS). This prospective cohort study included 124 consecutive HCC patients (44 with disease control, 80 with progression) with Child-Pugh class A liver function, who received sorafenib. Potential serum biomarkers (namely, hepatocyte growth factor [HGF], fibroblast growth factor [FGF], vascular endothelial growth factor receptor-1, CD117, and angiopoietin-2) were tested. After identifying independent predictors of tumor response, a risk scoring system for predicting OS was developed and 3-fold internal validation was conducted. A risk scoring system was developed with six covariates: etiology, platelet count, Barcelona Clinic Liver Cancer stage, protein induced by vitamin K absence-II, HGF, and FGF. When patients were stratified into low-risk (score ≤ 5), intermediate-risk (score 6), and high-risk (score ≥ 7) groups, the model provided good discriminant functions on tumor response (concordance [c]-index, 0.884) and 12-month survival (area under the curve [AUC], 0.825). The median OS was 19.0, 11.2, and 6.1 months in the low-, intermediate-, and high-risk group, respectively (P < 0.001). In internal validation, the model maintained good discriminant functions on tumor response (c-index, 0.825) and 12-month survival (AUC, 0.803), and good calibration functions (all P > 0.05 between expected and observed values). This new model including serum FGF and HGF showed good performance in predicting the response to sorafenib and survival in patients with advanced HCC.

Lack of TRPM5-Expressing Microvillous Cells in Mouse Main Olfactory Epithelium Leads to Impaired Odor-Evoked Responses and Olfactory-Guided Behavior in a Challenging Chemical Environment

PubMed Central

Lemons, Kayla; Aoudé, Imad; Ogura, Tatsuya; Mbonu, Kenechukwu; Matsumoto, Ichiro; Arakawa, Hiroyuki

2017-01-01

The mammalian main olfactory epithelium (MOE) modifies its activities in response to changes in the chemical environment. This process is essential for maintaining the functions of the olfactory system and the upper airway. However, mechanisms involved in this functional maintenance, especially those occurring via paracrine regulatory pathways within the multicellular MOE, are poorly understood. Previously, a population of non-neuronal, transient receptor potential M5-expressing microvillous cells (TRPM5-MCs) was identified in the MOE, and the initial characterization of these cells showed that they are cholinergic and responsive to various xenobiotics including odorants at high concentrations. Here, we investigated the role of TRPM5-MCs in maintaining olfactory function using transcription factor Skn-1a knockout (Skn-1a-/-) mice, which lack TRPM5-MCs in the MOE. Under our standard housing conditions, Skn-1a-/- mice do not differ significantly from control mice in odor-evoked electro-olfactogram (EOG) responses and olfactory-guided behaviors, including finding buried food and preference reactions to socially and sexually relevant odors. However, after a 2-wk exposure to high-concentration odor chemicals and chitin powder, Skn-1a-/- mice exhibited a significant reduction in their odor and pheromone-evoked EOG responses. Consequently, their olfactory-guided behaviors were impaired compared with vehicle-exposed Skn-1a-/- mice. Conversely, the chemical exposure did not induce significant changes in the EOG responses and olfactory behaviors of control mice. Therefore, our physiological and behavioral results indicate that TRPM5-MCs play a protective role in maintaining the olfactory function of the MOE. PMID:28612045

Positive Approaches to Business Management: Conference Proceedings.

ERIC Educational Resources Information Center

LaVire, Willis A., Ed.

In August 1970, an institute for newly appointed junior college business managers was planned around the business management function. This function would include purchasing, physical plant, personnel, auxiliary services, and financial records. The following seven speeches from the proceedings are presented: Evolution of Responsibility in the…

Response surface method in geotechnical/structural analysis, phase 1

NASA Astrophysics Data System (ADS)

Wong, F. S.

1981-02-01

In the response surface approach, an approximating function is fit to a long running computer code based on a limited number of code calculations. The approximating function, called the response surface, is then used to replace the code in subsequent repetitive computations required in a statistical analysis. The procedure of the response surface development and feasibility of the method are shown using a sample problem in slop stability which is based on data from centrifuge experiments of model soil slopes and involves five random soil parameters. It is shown that a response surface can be constructed based on as few as four code calculations and that the response surface is computationally extremely efficient compared to the code calculation. Potential applications of this research include probabilistic analysis of dynamic, complex, nonlinear soil/structure systems such as slope stability, liquefaction, and nuclear reactor safety.

Autonomic control of adrenal function.

PubMed Central

Edwards, A V; Jones, C T

1993-01-01

Recent studies of adrenal function in conscious calves are reviewed. These have involved collecting the whole of the adrenal effluent blood from the right adrenal gland at intervals and, where necessary, prior functional hypophysectomy by destruction of the pituitary stalk under general halothane anaesthesia 3 d previously. The adrenal medulla was found to release numerous neuropeptides, in addition to catecholamines, in response to stimulation of the peripheral end of the right splanchnic nerve, which was carried out below behavioural threshold. Many of these responses were enhanced by stimulating intermittently at a relatively high frequency. Intra-aortic infusions of a relatively low dose of acetylcholine (4.5 nmol min-1 kg-1) elicited similar responses. In the adrenal cortex, agonists which either potentiated the steroidogenic response to ACTH or exerted a direct steroidogenic action included VIP, CGRP, CRF and ACh acting via muscarinic receptors. Stimulation of the peripheral end of the right splanchnic nerve strongly potentiated the steroidogenic response to ACTH and there is compelling evidence that the innervation normally plays an important part in cortisol secretion. PMID:8300417

Mixed-effects Gaussian process functional regression models with application to dose-response curve prediction.

PubMed

Shi, J Q; Wang, B; Will, E J; West, R M

2012-11-20

We propose a new semiparametric model for functional regression analysis, combining a parametric mixed-effects model with a nonparametric Gaussian process regression model, namely a mixed-effects Gaussian process functional regression model. The parametric component can provide explanatory information between the response and the covariates, whereas the nonparametric component can add nonlinearity. We can model the mean and covariance structures simultaneously, combining the information borrowed from other subjects with the information collected from each individual subject. We apply the model to dose-response curves that describe changes in the responses of subjects for differing levels of the dose of a drug or agent and have a wide application in many areas. We illustrate the method for the management of renal anaemia. An individual dose-response curve is improved when more information is included by this mechanism from the subject/patient over time, enabling a patient-specific treatment regime. Copyright © 2012 John Wiley & Sons, Ltd.

Immunology.

PubMed

Toskala, Elina

2014-09-01

Knowledge of our immune system functions is critical for understanding allergic airway disease development as well as for selection of appropriate diagnostic and therapeutic options for patients with respiratory allergies. This review explains the current understanding of the basic immunology of the upper airways and the pathophysiology of allergic responses, including the mechanisms behind allergic rhinitis. The immune system can be divided to 2 main defense systems that function differently-innate immunity and adaptive immunity. Innate immunity includes several defensive mechanisms such as anatomic or physical barriers, physiological barriers, phagocytosis, and inflammation. The adaptive immune response is activated in an antigen-specific way to provide for the elimination of antigen and induce lasting protection. Hypersensitivity reactions occur when an exaggerated adaptive immune response is activated. Allergic rhinitis is an example of a type I, immunoglobulin E, mediated hypersensitivity reaction. Today we have several immunomodulatory treatment options for patients with allergic airway diseases, such as subcutaneous and sublingual immunotherapy. An understanding of the basics of our immune system and its method of functions is key for using these therapies appropriately. © 2014 ARS-AAOA, LLC.

Response diversity determines the resilience of ecosystems to environmental change.

PubMed

Mori, Akira S; Furukawa, Takuya; Sasaki, Takehiro

2013-05-01

A growing body of evidence highlights the importance of biodiversity for ecosystem stability and the maintenance of optimal ecosystem functionality. Conservation measures are thus essential to safeguard the ecosystem services that biodiversity provides and human society needs. Current anthropogenic threats may lead to detrimental (and perhaps irreversible) ecosystem degradation, providing strong motivation to evaluate the response of ecological communities to various anthropogenic pressures. In particular, ecosystem functions that sustain key ecosystem services should be identified and prioritized for conservation action. Traditional diversity measures (e.g. 'species richness') may not adequately capture the aspects of biodiversity most relevant to ecosystem stability and functionality, but several new concepts may be more appropriate. These include 'response diversity', describing the variation of responses to environmental change among species of a particular community. Response diversity may also be a key determinant of ecosystem resilience in the face of anthropogenic pressures and environmental uncertainty. However, current understanding of response diversity is poor, and we see an urgent need to disentangle the conceptual strands that pervade studies of the relationship between biodiversity and ecosystem functioning. Our review clarifies the links between response diversity and the maintenance of ecosystem functionality by focusing on the insurance hypothesis of biodiversity and the concept of functional redundancy. We provide a conceptual model to describe how loss of response diversity may cause ecosystem degradation through decreased ecosystem resilience. We explicitly explain how response diversity contributes to functional compensation and to spatio-temporal complementarity among species, leading to long-term maintenance of ecosystem multifunctionality. Recent quantitative studies suggest that traditional diversity measures may often be uncoupled from measures (such as response diversity) that may be more effective proxies for ecosystem stability and resilience. Certain conclusions and recommendations of earlier studies using these traditional measures as indicators of ecosystem resilience thus may be suspect. We believe that functional ecology perspectives incorporating the effects and responses of diversity are essential for development of management strategies to safeguard (and restore) optimal ecosystem functionality (especially multifunctionality). Our review highlights these issues and we envision our work generating debate around the relationship between biodiversity and ecosystem functionality, and leading to improved conservation priorities and biodiversity management practices that maximize ecosystem resilience in the face of uncertain environmental change. © 2012 The Authors. Biological Reviews © 2012 Cambridge Philosophical Society.

In-Vitro Induced Immunosuppression in a Rotary Cell Culture System

NASA Technical Reports Server (NTRS)

Grimm, Elizabeth A.

1998-01-01

The function of the innate immune system is to provide a first-line of defense against infectious organisms, via control of bacterial and viral growth using antigen nonspecific means. These nonspecific immune effectors include macrophages and Natural Killing (NK) cells, and certain cytokines elicited in response to "super antigens" on the infectious agents. This innate system usually keeps most infectious agents from rapidly growing while the adaptive immune system is generating a specific response complete with immunologic memory. Compelling evidence suggests that space flight results in various immunosuppressive effects, including reduced innate and adaptive immune responses. We were particularly concerned with reduced NK activity at landing, and have asked whether the microgravity component of space flight could be responsible for the previously observed NK defect. We have conclusively demonstrated that simulated microgravity as provided by the Synthecon bioreactors does not inhibit the NK function nor the IL-2 activation of lymphokine-activated killing (LAK). Interleukin-2 is the key cytokine responsible for activation of NK cells to express LAK, as well as to support differentiation of lymphocytes during adaptive immune responses. Therefore, we have disproved our original hypothesis based on poor NK in many of the astronauts upon landing.

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.

Common Anesthetic-binding Site for Inhibition of Pentameric Ligand-gated Ion Channels.

PubMed

Kinde, Monica N; Bu, Weiming; Chen, Qiang; Xu, Yan; Eckenhoff, Roderic G; Tang, Pei

2016-03-01

Identifying functionally relevant anesthetic-binding sites in pentameric ligand-gated ion channels (pLGICs) is an important step toward understanding the molecular mechanisms underlying anesthetic action. The anesthetic propofol is known to inhibit cation-conducting pLGICs, including a prokaryotic pLGIC from Erwinia chrysanthemi (ELIC), but the sites responsible for functional inhibition remain undetermined. We photolabeled ELIC with a light-activated derivative of propofol (AziPm) and performed fluorine-19 nuclear magnetic resonance experiments to support propofol binding to a transmembrane domain (TMD) intrasubunit pocket. To differentiate sites responsible for propofol inhibition from those that are functionally irrelevant, we made an ELIC-γ-aminobutyric acid receptor (GABAAR) chimera that replaced the ELIC-TMD with the α1β3GABAAR-TMD and compared functional responses of ELIC-GABAAR and ELIC with propofol modulations. Photolabeling showed multiple AziPm-binding sites in the extracellular domain (ECD) but only one site in the TMD with labeled residues M265 and F308 in the resting state of ELIC. Notably, this TMD site is an intrasubunit pocket that overlaps with binding sites for anesthetics, including propofol, found previously in other pLGICs. Fluorine-19 nuclear magnetic resonance experiments supported propofol binding to this TMD intrasubunit pocket only in the absence of agonist. Functional measurements of ELIC-GABAAR showed propofol potentiation of the agonist-elicited current instead of inhibition observed on ELIC. The distinctly different responses of ELIC and ELIC-GABAAR to propofol support the functional relevance of propofol binding to the TMD. Combining the newly identified TMD intrasubunit pocket in ELIC with equivalent TMD anesthetic sites found previously in other cationic pLGICs, we propose this TMD pocket as a common site for anesthetic inhibition of pLGICs.

Absolute number of new lesions on 18F-FDG PET/CT is more predictive of clinical response than SUV changes in metastatic melanoma patients receiving ipilimumab.

PubMed

Anwar, Hoda; Sachpekidis, Christos; Winkler, Julia; Kopp-Schneider, Annette; Haberkorn, Uwe; Hassel, Jessica C; Dimitrakopoulou-Strauss, Antonia

2018-03-01

Evaluation of response to immunotherapy is a matter of debate. The aim of the present study was to evaluate the response of metastatic melanoma to treatment with ipilimumab by means of 18 F-FDG PET/CT, using the patients' clinical response as reference. The final cohort included in the analyses consisted of 41 patients with metastatic melanoma who underwent 18 F-FDG PET/CT before and after administration of ipilimumab. After determination of the best clinical response, the PET/CT scans were reviewed and a separate independent analysis was performed, based on the number and functional size of newly emerged 18 F-FDG-avid lesions, as well as on the SUV changes after therapy. The median observation time of the patients after therapy was 21.4 months (range 6.3-41.9 months). Based on their clinical response, patients were dichotomized into those with clinical benefit (CB) and those without CB (No-CB). The CB group (31 patients) included those with stable disease, partial remission and complete remission, and the No-CB group (10 patients) included those with progressive disease. The application of a threshold of four newly emerged 18 F-FDG-avid lesions on the posttherapy PET/CT scan led to a sensitivity (correctly predicting CB) of 84% and a specificity (correctly predicting No-CB) of 100%. This cut-off was lower for lesions with larger functional diameters (three new lesions larger than 1.0 cm and two new lesions larger than 1.5 cm). SUV changes after therapy did not correlate with clinical response. Based on these findings, we developed criteria for predicting clinical response to immunotherapy by means of 18 F-FDG PET/CT (PET Response Evaluation Criteria for Immunotherapy, PERCIMT). Our results show that a cut-off of four newly emerged 18 F-FDG-avid lesions on posttherapy PET/CT gives a reliable indication of treatment failure in patients under ipilimumab treatment. Moreover, the functional size of the new lesions plays an important role in predicting the clinical response. Validation of these results in larger cohorts of patients is warranted.

Effect of Water Chemistry and Hydrodynamics on Nitrogen Transformation Activity and Microbial Community Functional Potential in Hyporheic Zone Sediment Columns

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

Liu, Yuanyuan; Liu, Chongxuan; Nelson, William C.

Nitrogen (N) transformation in hyporheic zone (HZ) is an important component in N-cycling in ecosystems. A column study was conducted to investigate N transformation in a HZ sediment with a focus on how characteristic HZ properties including water chemistry, fluid residence time, and dynamic groundwater and surface water exchange affect on N transformation. Metagenomic and quantitative polymerase chain reaction (qPCR) analyses were performed to evaluate the dynamic changes in microbial community structure and its function in response to N transformation. The results indicated that N transformation in the HZ sediment was collectively controlled by microbial community functions including: denitrification, dissimilatorymore » nitrate reduction to ammonium (DNRA), nitrification, and anaerobic ammonium oxidation (anammox). However, the spatial distribution of the microbial community functions and associated biogeochemical reaction rates and products changed quickly in response to experimental perturbation, and was influenced by various factors including water chemistry (dissolved O2 and N species), desorption of sediment associated organic carbon, ion exchange reactions of NH4+, and fluid residence time. The results of this study implied that the microbial community in the HZ would exhibit strong function zonation along N and O gradients, which in turn would control the rates and products of N transformation.« less

Dynamics Analysis of Anti-predator Model on Intermediate Predator With Ratio Dependent Functional Responses

NASA Astrophysics Data System (ADS)

Savitri, D.

2018-01-01

This articel discusses a predator prey model with anti-predator on intermediate predator using ratio dependent functional responses. Dynamical analysis performed on the model includes determination of equilibrium point, stability and simulation. Three kinds of equilibrium points have been discussed, namely the extinction of prey point, the extinction of intermediate predator point and the extinction of predator point are exists under certain conditions. It can be shown that the result of numerical simulations are in accordance with analitical results

RRAWFLOW: Rainfall-Response Aquifer and Watershed Flow Model (v1.15)

NASA Astrophysics Data System (ADS)

Long, A. J.

2015-03-01

The Rainfall-Response Aquifer and Watershed Flow Model (RRAWFLOW) is a lumped-parameter model that simulates streamflow, spring flow, groundwater level, or solute transport for a measurement point in response to a system input of precipitation, recharge, or solute injection. I introduce the first version of RRAWFLOW available for download and public use and describe additional options. The open-source code is written in the R language and is available at http://sd.water.usgs.gov/projects/RRAWFLOW/RRAWFLOW.html along with an example model of streamflow. RRAWFLOW includes a time-series process to estimate recharge from precipitation and simulates the response to recharge by convolution, i.e., the unit-hydrograph approach. Gamma functions are used for estimation of parametric impulse-response functions (IRFs); a combination of two gamma functions results in a double-peaked IRF. A spline fit to a set of control points is introduced as a new method for estimation of nonparametric IRFs. Several options are included to simulate time-variant systems. For many applications, lumped models simulate the system response with equal accuracy to that of distributed models, but moreover, the ease of model construction and calibration of lumped models makes them a good choice for many applications (e.g., estimating missing periods in a hydrologic record). RRAWFLOW provides professional hydrologists and students with an accessible and versatile tool for lumped-parameter modeling.

Classical density-functional theory of inhomogeneous water including explicit molecular structure and nonlinear dielectric response.

PubMed

Lischner, Johannes; Arias, T A

2010-02-11

We present an accurate free-energy functional for liquid water written in terms of a set of effective potential fields in which fictitious noninteracting water molecules move. The functional contains an exact expression of the entropy of noninteracting molecules and thus provides an ideal starting point for the inclusion of complex intermolecular interactions which depend on the orientation of the interacting molecules. We show how an excess free-energy functional can be constructed to reproduce the following properties of water: the dielectric response; the experimental site-site correlation functions; the surface tension; the bulk modulus of the liquid and the variation of this modulus with pressure; the density of the liquid and the vapor phase; and liquid-vapor coexistence. As a demonstration, we present results for the application of this theory to the behavior of liquid water in a parallel plate capacitor. In particular, we make predictions for the dielectric response of water in the nonlinear regime, finding excellent agreement with known data.

Modulation of gastrointestinal vagal neurocircuits by hyperglycemia

PubMed Central

Browning, Kirsteen N.

2013-01-01

Glucose sensing within autonomic neurocircuits is critical for the effective integration and regulation of a variety of physiological homeostatic functions including the co-ordination of vagally-mediated reflexes regulating gastrointestinal (GI) functions. Glucose regulates GI functions via actions at multiple sites of action, from modulating the activity of enteric neurons, endocrine cells, and glucose transporters within the intestine, to regulating the activity and responsiveness of the peripheral terminals, cell bodies and central terminals of vagal sensory neurons, to modifying both the activity and synaptic responsiveness of central brainstem neurons. Unsurprisingly, significant impairment in GI functions occurs in pathophysiological states where glucose levels are dysregulated, such as diabetes. A substantial obstacle to the development of new therapies to modify the disease, rather than treat the symptoms, are the gaps in our understanding of the mechanisms by which glucose modulates GI functions, particularly vagally-mediated responses and a more complete understanding of disease-related plasticity within these neurocircuits may open new avenues and targets for research. PMID:24324393

Functional Response of Eretmocerus delhiensis on Trialeurodes vaporariorum by Parasitism and Host Feeding

PubMed Central

Ebrahimifar, Jafar; Allahyari, Hossein

2017-01-01

The parasitoid wasp, Eretmocerus delhiensis (Hymenoptera, Aphelinidae) is a thelytokous and syn-ovigenic parasitoid. To evaluate E. delhiensis as a biocontrol agent in greenhouse, the killing efficiency of this parasitoid by parasitism and host-feeding, were studied. Killing efficiency can be compared by estimation of functional response parameters. Laboratory experiments were performed in controllable conditions to evaluate the functional response of E. delhiensis at eight densities (2, 4, 8, 16, 32, 64, 100, and 120 third nymphal stage) of Trialeurodes vaporariorum (Hemiptera, Aleyrodidae) on two hosts including; tomato and prickly lettuce. The maximum likelihood estimates from regression logistic analysis revealed type II functional response for two host plants and the type of functional response was not affected by host plant. Roger’s model was used to fit the data. The attack rate (a) for E. delhiensis was 0.0286 and 0.0144 per hour on tomato and 0.0434 and 0.0170 per hour on prickly lettuce for parasitism and host feeding, respectively. Furthermore, estimated handling times (Th) were 0.4911 and 1.4453 h on tomato and 0.5713 and 1.5001 h on prickly lettuce for parasitism and host feeding, respectively. Based on 95% confidence interval, functional response parameters were significantly different between the host plants solely in parasitism. Results of this study opens new insight in the host parasitoid interactions, subsequently needs further investigation before utilizing it for management and reduction of greenhouse whitefly. PMID:28423420

ACE Over Expression in Myelomonocytic Cells: Effect on a Mouse Model of Alzheimer's Disease

PubMed Central

Koronyo-Hamaoui, Maya; Shah, Kandarp; Koronyo, Yosef; Bernstein, Ellen; Giani, Jorge F.; Janjulia, Tea; Black, Keith L.; Shi, Peng D.; Gonzalez-Villalobos, Romer A.; Fuchs, Sebastien; Shen, Xiao Z.; Bernstein, Kenneth E.

2014-01-01

While it is well known that angiotensin converting enzyme (ACE) plays an important role in blood pressure control, ACE also has effects on renal function, hematopoiesis, reproduction, and aspects of the immune response. ACE 10/10 mice over express ACE in myelomonocytic cells. Macrophages from these mice have an increased polarization towards a pro-inflammatory phenotype that results in a very effective immune response to challenge by tumors or bacterial infection. In a mouse model of Alzheimer's disease (AD), the ACE 10/10 phenotype provides significant protection against AD pathology, including reduced inflammation, reduced burden of the neurotoxic amyloid-β protein and preserved cognitive function. Taken together, these studies show that increased myelomonocytic ACE expression in mice alters the immune response to better defend against many different types of pathologic insult, including the cognitive decline observed in an animal model of AD. PMID:24792094

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.

Production of functional proteins: balance of shear stress and gravity

NASA Technical Reports Server (NTRS)

Kaysen, James Howard (Inventor); Hammond, Timothy Grant (Inventor); Goodwin, Thomas John (Inventor)

2011-01-01

A method for the production of functional proteins including hormones by renal cells in a three dimensional culturing process responsive to shear stress uses a rotating wall vessel. Natural mixture of renal cells expresses the enzyme 1-.alpha.-hydroxylase which can be used to generate the active form of vitamin D: 1,25-diOH vitamin D.sub.3. The fibroblast cultures and co-culture of renal cortical cells express the gene for erythropoietin and secrete erythropoietin into the culture supernatant. Other shear stress response genes are also modulated by shear stress, such as toxin receptors megalin and cubulin (gp280). Also provided is a method of treating an in-need individual with the functional proteins produced in a three dimensional co-culture process responsive to shear stress using a rotating wall vessel.

Water and Solute Flux Simulation Using Hydropedology Survey Data in South African Catchments

NASA Astrophysics Data System (ADS)

Lorentz, Simon; van Tol, Johan; le Roux, Pieter

2017-04-01

Hydropedology surveys include linking soil profile information in hillslope transects in order to define dominant subsurface flow mechanisms and pathways. This information is useful for deriving hillslope response functions, which aid storage and travel time estimates of water and solute movement in the sub-surface. In this way, the "soft" data of the hydropedological survey can be included in simple hydrological models, where detailed modelling of processes and pathways is prohibitive. Hydropedology surveys were conducted in two catchments and the information used to improve the prediction of water and solute responses. Typical hillslope response functions are then derived using a 2-D finite element model of the hydropedological features. Similar response types are mapped. These mapped response units are invoked in a simple SCS based, hydrological and solute transport model to yield water and solute fluxes at the catchment outlets. The first catchment (1.6 km2) comprises commercial forestry in a sedimentary geology of sandstone and mudstone formation while the second catchment (6.1 km2) includes mine waste impoundments in a granitic geology. In this paper, we demonstrate the method of combining hydropedological interpretation with catchment hydrology and solute transport simulation. The forested catchment, with three dominant hillslope response types, have solute response times in excess of 90 days, whereas the granitic responses occur within 10 days. The use of the hydropedological data improves the solute distribution response and storage simulation, compared to simulations without the hydropedology interpretation. The hydrological responses are similar, with and without the use of the hydropedology data, but the simulated distribution of water in the catchment is improved using the techniques demonstrated.

Sleep and pulmonary outcomes for clinical trials of airway plexiform neurofibromas in NF1.

PubMed

Plotkin, Scott R; Davis, Stephanie D; Robertson, Kent A; Akshintala, Srivandana; Allen, Julian; Fisher, Michael J; Blakeley, Jaishri O; Widemann, Brigitte C; Ferner, Rosalie E; Marcus, Carole L

2016-08-16

Plexiform neurofibromas (PNs) are complex, benign nerve sheath tumors that occur in approximately 25%-50% of individuals with neurofibromatosis type 1 (NF1). PNs that cause airway compromise or pulmonary dysfunction are uncommon but clinically important. Because improvement in sleep quality or airway function represents direct clinical benefit, measures of sleep and pulmonary function may be more meaningful than tumor size as endpoints in therapeutic clinical trials targeting airway PN. The Response Evaluation in Neurofibromatosis and Schwannomatosis functional outcomes group reviewed currently available endpoints for sleep and pulmonary outcomes and developed consensus recommendations for response evaluation in NF clinical trials. For patients with airway PNs, polysomnography, impulse oscillometry, and spirometry should be performed to identify abnormal function that will be targeted by the agent under clinical investigation. The functional group endorsed the use of the apnea hypopnea index (AHI) as the primary sleep endpoint, and pulmonary resistance at 10 Hz (R10) or forced expiratory volume in 1 or 0.75 seconds (FEV1 or FEV0.75) as primary pulmonary endpoints. The group defined minimum changes in AHI, R10, and FEV1 or FEV0.75 for response criteria. Secondary sleep outcomes include desaturation and hypercapnia during sleep and arousal index. Secondary pulmonary outcomes include pulmonary resistance and reactance measurements at 5, 10, and 20 Hz; forced vital capacity; peak expiratory flow; and forced expiratory flows. These recommended sleep and pulmonary evaluations are intended to provide researchers with a standardized set of clinically meaningful endpoints for response evaluation in trials of NF1-related airway PNs. © 2016 American Academy of Neurology.

Ethylene Response Factor TERF1, Regulated by ETHYLENE-INSENSITIVE3-like Factors, Functions in Reactive Oxygen Species (ROS) Scavenging in Tobacco (Nicotiana tabacum L.).

PubMed

Zhang, Hongbo; Li, Ang; Zhang, Zhijin; Huang, Zejun; Lu, Pingli; Zhang, Dingyu; Liu, Xinmin; Zhang, Zhong-Feng; Huang, Rongfeng

2016-07-20

The phytohormone ethylene plays a crucial role in the production and accumulation of reactive oxygen species (ROS) in plants under stress conditions. Ethylene response factors (ERFs) are important ethylene-signaling regulators functioning in plant defense responses against biotic and abiotic stresses. However, the roles of ERFs during plant adapting to ROS stress have not yet been well documented. Our studies previously reported that a tomato ERF transcription factor TERF1 functions in the regulation of plant ethylene responses and stress tolerance. Here, we report our findings regarding the roles of TERF1 in ROS scavenging. In this study, we revealed that the transcription of TERF1 is regulated by upstream EIN3-like (EIN3, ethylene-insensitive 3) regulators LeEIL3 and LeEIL4 in tomato (Solanum lycopersicum), and is also inducible by exogenous applied ROS-generating reagents. Ectopic expression of TERF1 in tobacco promoted the expression of genes involved in oxidative stress responses, including carbonic anhydrase functioning in hypersensitive defense, catalase and glutathione peroxidase catalyzing oxidative reactions, and GDP-D-mannose pyrophosphorylase functioning in ascorbic acid biosynthesis, reduced the ROS content induced by ethylene treatment, and enhanced stress tolerance of tobacco seedlings to hydrogen peroxide (H2O2). Cumulatively, these findings suggest that TERF1 is an ethylene inducible factor regulating ROS scavenging during stress responses.

Reliability of Growth Indicators and Efficiency of Functional Treatment for Skeletal Class II Malocclusion: Current Evidence and Controversies.

PubMed

Perinetti, Giuseppe; Contardo, Luca

2017-01-01

Current evidence on the reliability of growth indicators in the identification of the pubertal growth spurt and efficiency of functional treatment for skeletal Class II malocclusion, the timing of which relies on such indicators, is highly controversial. Regarding growth indicators, the hand and wrist (including the sole middle phalanx of the third finger) maturation method and the standing height recording appear to be most reliable. Other methods are subjected to controversies or were showed to be unreliable. Main sources of controversies include use of single stages instead of ossification events and diagnostic reliability conjecturally based on correlation analyses. Regarding evidence on the efficiency of functional treatment, when treated during the pubertal growth spurt, more favorable response is seen in skeletal Class II patients even though large individual responsiveness remains. Main sources of controversies include design of clinical trials, definition of Class II malocclusion, and lack of inclusion of skeletal maturity among the prognostic factors. While no growth indicator may be considered to have a full diagnostic reliability in the identification of the pubertal growth spurt, their use may still be recommended for increasing efficiency of functional treatment for skeletal Class II malocclusion.

Reliability of Growth Indicators and Efficiency of Functional Treatment for Skeletal Class II Malocclusion: Current Evidence and Controversies

PubMed Central

2017-01-01

Current evidence on the reliability of growth indicators in the identification of the pubertal growth spurt and efficiency of functional treatment for skeletal Class II malocclusion, the timing of which relies on such indicators, is highly controversial. Regarding growth indicators, the hand and wrist (including the sole middle phalanx of the third finger) maturation method and the standing height recording appear to be most reliable. Other methods are subjected to controversies or were showed to be unreliable. Main sources of controversies include use of single stages instead of ossification events and diagnostic reliability conjecturally based on correlation analyses. Regarding evidence on the efficiency of functional treatment, when treated during the pubertal growth spurt, more favorable response is seen in skeletal Class II patients even though large individual responsiveness remains. Main sources of controversies include design of clinical trials, definition of Class II malocclusion, and lack of inclusion of skeletal maturity among the prognostic factors. While no growth indicator may be considered to have a full diagnostic reliability in the identification of the pubertal growth spurt, their use may still be recommended for increasing efficiency of functional treatment for skeletal Class II malocclusion. PMID:28168195

Neural Responses to Visual Food Cues According to Weight Status: A Systematic Review of Functional Magnetic Resonance Imaging Studies

PubMed Central

Pursey, Kirrilly M.; Stanwell, Peter; Callister, Robert J.; Brain, Katherine; Collins, Clare E.; Burrows, Tracy L.

2014-01-01

Emerging evidence from recent neuroimaging studies suggests that specific food-related behaviors contribute to the development of obesity. The aim of this review was to report the neural responses to visual food cues, as assessed by functional magnetic resonance imaging (fMRI), in humans of differing weight status. Published studies to 2014 were retrieved and included if they used visual food cues, studied humans >18 years old, reported weight status, and included fMRI outcomes. Sixty studies were identified that investigated the neural responses of healthy weight participants (n = 26), healthy weight compared to obese participants (n = 17), and weight-loss interventions (n = 12). High-calorie food images were used in the majority of studies (n = 36), however, image selection justification was only provided in 19 studies. Obese individuals had increased activation of reward-related brain areas including the insula and orbitofrontal cortex in response to visual food cues compared to healthy weight individuals, and this was particularly evident in response to energy dense cues. Additionally, obese individuals were more responsive to food images when satiated. Meta-analysis of changes in neural activation post-weight loss revealed small areas of convergence across studies in brain areas related to emotion, memory, and learning, including the cingulate gyrus, lentiform nucleus, and precuneus. Differential activation patterns to visual food cues were observed between obese, healthy weight, and weight-loss populations. Future studies require standardization of nutrition variables and fMRI outcomes to enable more direct comparisons between studies. PMID:25988110

Neural responses to visual food cues according to weight status: a systematic review of functional magnetic resonance imaging studies.

PubMed

Pursey, Kirrilly M; Stanwell, Peter; Callister, Robert J; Brain, Katherine; Collins, Clare E; Burrows, Tracy L

2014-01-01

Emerging evidence from recent neuroimaging studies suggests that specific food-related behaviors contribute to the development of obesity. The aim of this review was to report the neural responses to visual food cues, as assessed by functional magnetic resonance imaging (fMRI), in humans of differing weight status. Published studies to 2014 were retrieved and included if they used visual food cues, studied humans >18 years old, reported weight status, and included fMRI outcomes. Sixty studies were identified that investigated the neural responses of healthy weight participants (n = 26), healthy weight compared to obese participants (n = 17), and weight-loss interventions (n = 12). High-calorie food images were used in the majority of studies (n = 36), however, image selection justification was only provided in 19 studies. Obese individuals had increased activation of reward-related brain areas including the insula and orbitofrontal cortex in response to visual food cues compared to healthy weight individuals, and this was particularly evident in response to energy dense cues. Additionally, obese individuals were more responsive to food images when satiated. Meta-analysis of changes in neural activation post-weight loss revealed small areas of convergence across studies in brain areas related to emotion, memory, and learning, including the cingulate gyrus, lentiform nucleus, and precuneus. Differential activation patterns to visual food cues were observed between obese, healthy weight, and weight-loss populations. Future studies require standardization of nutrition variables and fMRI outcomes to enable more direct comparisons between studies.

The impact of executive function on response to cognitive behavioral therapy in late-life depression.

PubMed

Goodkind, Madeleine S; Gallagher-Thompson, Dolores; Thompson, Larry W; Kesler, Shelli R; Anker, Lauren; Flournoy, John; Berman, Mika P; Holland, Jason M; O'Hara, Ruth M

2016-04-01

Late-life depression (LLD) is a common and debilitating condition among older adults. Cognitive behavioral therapy (CBT) has strong empirical support for the treatment of depression in all ages, including in LLD. In teaching patients to identify, monitor, and challenge negative patterns in their thinking, CBT for LLD relies heavily on cognitive processes and, in particular, executive functioning, such as planning, sequencing, organizing, and selectively inhibiting information. It may be that the effectiveness of CBT lies in its ability to train these cognitive areas. Participants with LLD completed a comprehensive neuropsychological battery before enrolling in CBT. The current study examined the relationship between neuropsychological function prior to treatment and response to CBT. When using three baseline measures of executive functioning that quantify set shifting, cognitive flexibility, and response inhibition to predict treatment response, only baseline Wisconsin Card Sort Task performance was associated with a significant drop in depression symptoms after CBT. Specifically, worse performance on the Wisconsin Card Sort Task was associated with better treatment response. These results suggest that CBT, which teaches cognitive techniques for improving psychiatric symptoms, may be especially beneficial in LLD if relative weaknesses in specific areas of executive functioning are present. Copyright © 2015 John Wiley & Sons, Ltd.

Control of stem cell fate and function by engineering physical microenvironments

PubMed Central

Kshitiz; Park, Jinseok; Kim, Peter; Helen, Wilda; Engler, Adam J; Levchenko, Andre; Kim, Deok-Ho

2012-01-01

The phenotypic expression and function of stem cells are regulated by their integrated response to variable microenvironmental cues, including growth factors and cytokines, matrix-mediated signals, and cell-cell interactions. Recently, growing evidence suggests that matrix-mediated signals include mechanical stimuli such as strain, shear stress, substrate rigidity and topography, and these stimuli have a more profound impact on stem cell phenotypes than had previously been recognized, e.g. self-renewal and differentiation through the control of gene transcription and signaling pathways. Using a variety of cell culture models enabled by micro and nanoscale technologies, we are beginning to systematically and quantitatively investigate the integrated response of cells to combinations of relevant mechanobiological stimuli. This paper reviews recent advances in engineering physical stimuli for stem cell mechanobiology and discusses how micro- and nanoscale engineered platforms can be used to control stem cell niches environment and regulate stem cell fate and function. PMID:23077731

Multi-functional Electric Module for a Vehicle

NASA Technical Reports Server (NTRS)

Waligora, Thomas M. (Inventor); Fraser-Chanpong, Nathan (Inventor); Figuered, Joshua M. (Inventor); Reed, Ryan (Inventor); Akinyode, Akinjide Akinniyi (Inventor); Spain, Ivan (Inventor); Dawson, Andrew D. (Inventor); Herrera, Eduardo (Inventor); Markee, Mason M. (Inventor); Bluethmann, William J. (Inventor)

2015-01-01

A multi-functional electric module (eModule) is provided for a vehicle having a chassis, a master controller, and a drive wheel having a propulsion-braking module. The eModule includes a steering control assembly, mounting bracket, propulsion control assembly, brake controller, housing, and control arm. The steering control assembly includes a steering motor controlled by steering controllers in response to control signals from the master controller. A mounting feature of the bracket connects to the chassis. The propulsion control assembly and brake controller are in communication with the propulsion-braking module. The control arm connects to the lower portion and contains elements of a suspension system, with the control arm being connectable to the drive wheel via a wheel input/output block. The controllers are responsive to the master controller to control a respective steering, propulsion, and braking function. The steering motor may have a dual-wound stator with windings controlled via the respective steering controllers.

Interactions between Cognition and Motivation during Response Inhibition

ERIC Educational Resources Information Center

Padmala, Srikanth; Pessoa, Luiz

2010-01-01

A growing number of studies have investigated how motivation interacts with particular cognitive functions, including attention, working memory, and other executive functions. In these studies, the emphasis has been on understanding how motivation impacts brain regions that contribute to improving behavioral performance. Less is understood about…

The Corporate Stake in Social Cohesion

ERIC Educational Resources Information Center

Oketch, Moses O.

2005-01-01

Corporate Social Responsibility (CSR) is a function that transcends, but includes, making profits, creating jobs, and producing goods and services. The effectiveness with which corporations perform this function determines their contribution (or lack of contribution) to social cohesion. This article therefore presents a discussion of some of the…

Sex in the brain: hormones and sex differences.

PubMed

Marrocco, Jordan; McEwen, Bruce S

2016-12-01

Contrary to popular belief, sex hormones act throughout the entire brain of both males and females via both genomic and nongenomic receptors. Many neural and behavioral functions are affected by estrogens, including mood, cognitive function, blood pressure regulation, motor coordination, pain, and opioid sensitivity. Subtle sex differences exist for many of these functions that are developmentally programmed by hormones and by not yet precisely defined genetic factors, including the mitochondrial genome. These sex differences, and responses to sex hormones in brain regions and upon functions not previously regarded as subject to such differences, indicate that we are entering a new era in our ability to understand and appreciate the diversity of gender-related behaviors and brain functions.

Spectral characterization of plastic scintillation detector response as a function of magnetic field strength

NASA Astrophysics Data System (ADS)

Simiele, E.; Kapsch, R.-P.; Ankerhold, U.; Culberson, W.; DeWerd, L.

2018-04-01

The purpose of this work was to characterize intensity and spectral response changes in a plastic scintillation detector (PSD) as a function of magnetic field strength. Spectra measurements as a function of magnetic field strength were performed using an optical spectrometer. The response of both a PSD and PMMA fiber were investigated to isolate the changes in response from the scintillator and the noise signal as a function of magnetic field strength. All irradiations were performed in water at a photon beam energy of 6 MV. Magnetic field strengths of (0, ±0.35, ±0.70, ±1.05, and  ±1.40) T were investigated. Four noise subtraction techniques were investigated to evaluate the impact on the resulting noise-subtracted scintillator response with magnetic field strength. The noise subtraction methods included direct spectral subtraction, the spectral method, and variants thereof. The PMMA fiber exhibited changes in response of up to 50% with magnetic field strength due to the directional light emission from \\breve{C} erenkov radiation. The PSD showed increases in response of up to 10% when not corrected for the noise signal, which agrees with previous investigations of scintillator response in magnetic fields. Decreases in the \\breve{C} erenkov light ratio with negative field strength were observed with a maximum change at  ‑1.40 T of 3.2% compared to 0 T. The change in the noise-subtracted PSD response as a function of magnetic field strength varied with the noise subtraction technique used. Even after noise subtraction, the PSD exhibited changes in response of up to 5.5% over the four noise subtraction methods investigated.

Validity, invariance and responsiveness of a self-report measure of functional limitations and disability in multiple sclerosis.

PubMed

Motl, Robert W; McAuley, Edward; Suh, Yoojin

2010-01-01

This study examined the structural and external aspects of score validity for the abbreviated Late Life-Function and Disability Inventory (LL-FDI) as well as its longitudinal measurement invariance and responsiveness in individuals with multiple sclerosis (MS). The sample included 292 individuals with MS who completed a battery of questionnaires on two occasions separated by 6 months. The battery included the abbreviated LL-FDI along with measures of mobility disability; neurological impairments; symptoms of fatigue, anxiety, depression and pain; health status; and quality of life. The data were analysed using Analysis of Moment Structures (AMOS) and Statistical Package for the Social Sciences (SPSS), versions 16.0. Confirmatory factor analysis supported the structural validity and longitudinal measurement invariance of the disability and functional limitations components of the abbreviated LL-FDI. MANOVA and bivariate correlations supported the external aspects of score validity based on differences in mean scores as a function of clinical MS course (relapsing vs. progressive) and level of mobility disability (mild vs. moderate mobility disability) and associations with measures of neurological impairments, symptoms, health status and QOL, respectively. ANOVA established the responsiveness (i.e., sensitivity for reflecting clinically important differences in health status across time) of the functional limitations and disability components of the abbreviated LL-FDI for detecting changes in mobility disability across 6-months. Such findings provide a new option for the measurement of functional limitations and disability using the abbreviated LL-FDI in persons with MS.

Comparison of the electromagnetic responses of C 12 obtained from the Green's function Monte Carlo and spectral function approaches

DOE PAGES

Rocco, Noemi; Lovato, Alessandro; Benhar, Omar

2016-12-23

Here, the electromagnetic responses of carbon obtained from the Green's function Monte Carlo and spectral function approaches using the same dynamical input are compared in the kinematical region corresponding to momentum transfer in the range 300–570 MeV. The results of our analysis, aimed at pinning down the limits of applicability of the approximations involved in the two schemes, indicate that the factorization ansatz underlying the spectral function formalism provides remarkably accurate results down to momentum transfer as low as 300 MeV. On the other hand, it appears that at 570 MeV relativistic corrections to the electromagnetic current not included inmore » the Monte Carlo calculations may play a significant role in the transverse channel.« less

Comparison of the electromagnetic responses of C 12 obtained from the Green's function Monte Carlo and spectral function approaches

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

Rocco, Noemi; Lovato, Alessandro; Benhar, Omar

Here, the electromagnetic responses of carbon obtained from the Green's function Monte Carlo and spectral function approaches using the same dynamical input are compared in the kinematical region corresponding to momentum transfer in the range 300–570 MeV. The results of our analysis, aimed at pinning down the limits of applicability of the approximations involved in the two schemes, indicate that the factorization ansatz underlying the spectral function formalism provides remarkably accurate results down to momentum transfer as low as 300 MeV. On the other hand, it appears that at 570 MeV relativistic corrections to the electromagnetic current not included inmore » the Monte Carlo calculations may play a significant role in the transverse channel.« less

Conformal gravity holography in four dimensions.

PubMed

Grumiller, Daniel; Irakleidou, Maria; Lovrekovic, Iva; McNees, Robert

2014-03-21

We formulate four-dimensional conformal gravity with (anti-)de Sitter boundary conditions that are weaker than Starobinsky boundary conditions, allowing for an asymptotically subleading Rindler term concurrent with a recent model for gravity at large distances. We prove the consistency of the variational principle and derive the holographic response functions. One of them is the conformal gravity version of the Brown-York stress tensor, the other is a "partially massless response". The on shell action and response functions are finite and do not require holographic renormalization. Finally, we discuss phenomenologically interesting examples, including the most general spherically symmetric solutions and rotating black hole solutions with partially massless hair.

Ecohydrological Responses of Dense Canopies to Environmental Variability Part 1: Interplay Between Vertical Structure and Photosynthetic Pathway

USDA-ARS?s Scientific Manuscript database

Vegetation acclimation to changing climate, in particular elevated atmospheric concentrations of carbon dioxide (CO2), has been observed to include modifications to the biochemical and eco physiological functioning of leaves and the structural components of the canopy. These responses have the poten...

Different Approaches to Covariate Inclusion in the Mixture Rasch Model

ERIC Educational Resources Information Center

Li, Tongyun; Jiao, Hong; Macready, George B.

2016-01-01

The present study investigates different approaches to adding covariates and the impact in fitting mixture item response theory models. Mixture item response theory models serve as an important methodology for tackling several psychometric issues in test development, including the detection of latent differential item functioning. A Monte Carlo…

Calculation of response matrix of CaSO 4:Dy based neutron dosimeter using Monte Carlo code FLUKA and measurement of 241Am-Be spectra

NASA Astrophysics Data System (ADS)

Chatterjee, S.; Bakshi, A. K.; Tripathy, S. P.

2010-09-01

Response matrix for CaSO 4:Dy based neutron dosimeter was generated using Monte Carlo code FLUKA in the energy range thermal to 20 MeV for a set of eight Bonner spheres of diameter 3-12″ including the bare one. Response of the neutron dosimeter was measured for the above set of spheres for 241Am-Be neutron source covered with 2 mm lead. An analytical expression for the response function was devised as a function of sphere mass. Using Frascati Unfolding Iteration Tool (FRUIT) unfolding code, the neutron spectrum of 241Am-Be was unfolded and compared with standard IAEA spectrum for the same.

Response of the Higgs amplitude mode of superfluid Bose gases in a three-dimensional optical lattice

NASA Astrophysics Data System (ADS)

Nagao, Kazuma; Takahashi, Yoshiro; Danshita, Ippei

2018-04-01

We study the Higgs mode of superfluid Bose gases in a three-dimensional optical lattice, which emerges near the quantum phase transition to the Mott insulator at commensurate fillings. Specifically, we consider responses of the Higgs mode to temporal modulations of the onsite interaction and the hopping energy. In order to calculate the response functions including the effects of quantum and thermal fluctuations, we map the Bose-Hubbard model onto an effective pseudospin-1 model and use a perturbative expansion based on the imaginary-time Green's function theory. We also include the effects of an inhomogeneous trapping potential by means of a local density approximation. We find that the response function for the hopping modulation is equal to that for the interaction modulation within our approximation. At the unit filling rate and in the absence of a trapping potential, we show that the Higgs mode can exist as a sharp resonance peak in the dynamical susceptibilities at typical temperatures. However, the resonance peak is significantly broadened due to the trapping potential when the modulations are applied globally to the entire system. We suggest that the Higgs mode can be detected as a sharp resonance peak by partial modulations around the trap center.

Shuttle GPS R/PA evaluation analysis and performance tradeoff study

NASA Technical Reports Server (NTRS)

Booth, R. W. D.; Lindsey, W. C.

1978-01-01

Primary responsibility was understanding and analyzing the various GPS receiver functions as they relate to the shuttle environment. These receiver functions included acquisition properties of the sequential detector, acquisition and tracking properties of the various receiver phase locked loops, and the techniques of sequential receiver operation. In addition to these areas, support was provided in the areas of oscillator stability requirements, antenna management, and navigation filter requirements, including preposition aiding.

Treg functional stability and its responsiveness to the microenvironment

PubMed Central

Barbi, Joseph; Pardoll, Drew M.; Pan, Fan

2014-01-01

Summary Regulatory T cells (Tregs) prevent autoimmunity and tissue damage resulting from excessive or unnecessary immune activation through their suppressive function. While their importance for proper immune control is undeniable, the stability of the Treg lineage has recently become a controversial topic. Many reports have shown dramatic loss of the signature Treg transcription factor Forkhead box protein 3 (Foxp3) and Treg function under various inflammatory conditions. Other recent studies demonstrate that most Tregs are extremely resilient in their expression of Foxp3 and the retention of suppressive function. While this debate is unlikely to be settled in the immediate future, improved understanding of the considerable heterogeneity within the Foxp3+ Treg population and how Treg subsets respond to ranging environmental cues may be keys to reconciliation. In this review, we discuss the diverse mechanisms responsible for the observed stability or instability of Foxp3+ Treg identity and function. These include transcriptional and epigenetic programs, transcript targeting and posttranslational modifications that appear responsive to numerous elements of the microenvironment. These mechanisms for Treg functional modulation add to the discussion of Treg stability. PMID:24712463

Pharmacological approaches to restore mitochondrial function

PubMed Central

Andreux, Pénélope A.; Houtkooper, Riekelt H.; Auwerx, Johan

2014-01-01

Mitochondrial dysfunction is not only a hallmark of rare inherited mitochondrial disorders, but is also implicated in age-related diseases, including those that affect the metabolic and nervous system, such as type 2 diabetes and Parkinson’s disease. Numerous pathways maintain and/or restore proper mitochondrial function, including mitochondrial biogenesis, mitochondrial dynamics, mitophagy, and the mitochondrial unfolded protein response. New and powerful phenotypic assays in cell-based models, as well as multicellular organisms, have been developed to explore these different aspects of mitochondrial function. Modulating mitochondrial function has therefore emerged as an attractive therapeutic strategy for a range of diseases, which has spurred active drug discovery efforts in this area. PMID:23666487

From filaments to function: The role of the plant actin cytoskeleton in pathogen perception, signaling and immunity.

PubMed

Porter, Katie; Day, Brad

2016-04-01

The eukaryotic actin cytoskeleton is required for numerous cellular processes, including cell shape, development and movement, gene expression and signal transduction, and response to biotic and abiotic stress. In recent years, research in both plants and animal systems have described a function for actin as the ideal surveillance platform, linking the function and activity of primary physiological processes to the immune system. In this review, we will highlight recent advances that have defined the regulation and breadth of function of the actin cytoskeleton as a network required for defense signaling following pathogen infection. Coupled with an overview of recent work demonstrating specific targeting of the plant actin cytoskeleton by a diversity of pathogens, including bacteria, fungi and viruses, we will highlight the importance of actin as a key signaling hub in plants, one that mediates surveillance of cellular homeostasis and the activation of specific signaling responses following pathogen perception. Based on the studies highlighted herein, we propose a working model that posits changes in actin filament organization is in and of itself a highly specific signal, which induces, regulates and physically directs stimulus-specific signaling processes, most importantly, those associated with response to pathogens. © 2015 Institute of Botany, Chinese Academy of Sciences.

Heavy particle irradiation, neurochemistry and behavior: thresholds, dose-response curves and recovery of function

NASA Astrophysics Data System (ADS)

Rabin, B. M.; Joseph, J. A.; Shukitt-Hale, B.

2004-01-01

Exposure to heavy particles can affect the functioning of the central nervous system (CNS), particularly the dopaminergic system. In turn, the radiation-induced disruption of dopaminergic function affects a variety of behaviors that are dependent upon the integrity of this system, including motor behavior (upper body strength), amphetamine (dopamine)-mediated taste aversion learning, and operant conditioning (fixed-ratio bar pressing). Although the relationships between heavy particle irradiation and the effects of exposure depend, to some extent, upon the specific behavioral or neurochemical endpoint under consideration, a review of the available research leads to the hypothesis that the endpoints mediated by the CNS have certain characteristics in common. These include: (1) a threshold, below which there is no apparent effect; (2) the lack of a dose-response relationship, or an extremely steep dose-response curve, depending on the particular endpoint; and (3) the absence of recovery of function, such that the heavy particle-induced behavioral and neural changes are present when tested up to one year following exposure. The current report reviews the data relevant to the degree to which these characteristics are common to neurochemical and behavioral endpoints that are mediated by the effects of exposure to heavy particles on CNS activity.

Heavy particle irradiation, neurochemistry and behavior: thresholds, dose-response curves and recovery of function

NASA Technical Reports Server (NTRS)

Rabin, B. M.; Joseph, J. A.; Shukitt-Hale, B.

2004-01-01

Exposure to heavy particles can affect the functioning of the central nervous system (CNS), particularly the dopaminergic system. In turn, the radiation-induced disruption of dopaminergic function affects a variety of behaviors that are dependent upon the integrity of this system, including motor behavior (upper body strength), amphetamine (dopamine)-mediated taste aversion learning, and operant conditioning (fixed-ratio bar pressing). Although the relationships between heavy particle irradiation and the effects of exposure depend, to some extent, upon the specific behavioral or neurochemical endpoint under consideration, a review of the available research leads to the hypothesis that the endpoints mediated by the CNS have certain characteristics in common. These include: (1) a threshold, below which there is no apparent effect; (2) the lack of a dose-response relationship, or an extremely steep dose-response curve, depending on the particular endpoint; and (3) the absence of recovery of function, such that the heavy particle-induced behavioral and neural changes are present when tested up to one year following exposure. The current report reviews the data relevant to the degree to which these characteristics are common to neurochemical and behavioral endpoints that are mediated by the effects of exposure to heavy particles on CNS activity. c2004 COSPAR. Published by Elsevier Ltd. All rights reserved.

Gust response of commercial jet aircraft including effects of autopilot operation

NASA Technical Reports Server (NTRS)

Goldberg, J. H.

1982-01-01

A simplified theory of aircraft vertical acceleration gust response based on a model including pitch, vertical displacement and control motions due to autopilot operation is presented. High-order autopilot transfer functions are utilized for improved accuracy in the determination of the overall response characteristics. Four representative commercial jet aircraft were studied over a wide range of operating conditions and comparisons of individual responses are given. It is shown that autopilot operation relative to the controls fixed case causes response attenuation of from 10 percent to approximately 25 percent depending on flight condition and increases in crossing number up to 30 percent, with variations between aircraft of from 5 percent to 10 percent, in general, reflecting the differences in autopilot design. A detailed computer program description and listing of the calculation procedure suitable for the general application of the theory to any airplane autopilot combination is also included.

Form factors for dark matter capture by the Sun in effective theories

NASA Astrophysics Data System (ADS)

Catena, Riccardo; Schwabe, Bodo

2015-04-01

In the effective theory of isoscalar and isovector dark matter-nucleon interactions mediated by a heavy spin-1 or spin-0 particle, 8 isotope-dependent nuclear response functions can be generated in the dark matter scattering by nuclei. We compute the 8 nuclear response functions for the 16 most abundant elements in the Sun, i.e. H, 3He, 4He, 12C, 14N, 16O, 20Ne, 23Na, 24Mg, 27Al, 28Si, 32S, 40Ar, 40Ca, 56Fe, and 59Ni, through numerical shell model calculations. We use our response functions to compute the rate of dark matter capture by the Sun for all isoscalar and isovector dark matter-nucleon effective interactions, including several operators previously considered for dark matter direct detection only. We study in detail the dependence of the capture rate on specific dark matter-nucleon interaction operators, and on the different elements in the Sun. We find that a so far neglected momentum dependent dark matter coupling to the nuclear vector charge gives a larger contribution to the capture rate than the constant spin-dependent interaction commonly included in dark matter searches at neutrino telescopes. Our investigation lays the foundations for model independent analyses of dark matter induced neutrino signals from the Sun. The nuclear response functions obtained in this study are listed in analytic form in an appendix, ready to be used in other projects.

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

Catena, Riccardo; Schwabe, Bodo, E-mail: riccardo.catena@theorie.physik.uni-goettingen.de, E-mail: bodo.schwabe@theorie.physik.uni-goettingen.de

In the effective theory of isoscalar and isovector dark matter-nucleon interactions mediated by a heavy spin-1 or spin-0 particle, 8 isotope-dependent nuclear response functions can be generated in the dark matter scattering by nuclei. We compute the 8 nuclear response functions for the 16 most abundant elements in the Sun, i.e. H, {sup 3}He, {sup 4}He, {sup 12}C, {sup 14}N, {sup 16}O, {sup 20}Ne, {sup 23}Na, {sup 24}Mg, {sup 27}Al, {sup 28}Si, {sup 32}S, {sup 40}Ar, {sup 40}Ca, {sup 56}Fe, and {sup 59}Ni, through numerical shell model calculations. We use our response functions to compute the rate of dark mattermore » capture by the Sun for all isoscalar and isovector dark matter-nucleon effective interactions, including several operators previously considered for dark matter direct detection only. We study in detail the dependence of the capture rate on specific dark matter-nucleon interaction operators, and on the different elements in the Sun. We find that a so far neglected momentum dependent dark matter coupling to the nuclear vector charge gives a larger contribution to the capture rate than the constant spin-dependent interaction commonly included in dark matter searches at neutrino telescopes. Our investigation lays the foundations for model independent analyses of dark matter induced neutrino signals from the Sun. The nuclear response functions obtained in this study are listed in analytic form in an appendix, ready to be used in other projects.« less

Repressor- and Activator-Type Ethylene Response Factors Functioning in Jasmonate Signaling and Disease Resistance Identified via a Genome-Wide Screen of Arabidopsis Transcription Factor Gene Expression[w

PubMed Central

McGrath, Ken C.; Dombrecht, Bruno; Manners, John M.; Schenk, Peer M.; Edgar, Cameron I.; Maclean, Donald J.; Scheible, Wolf-Rüdiger; Udvardi, Michael K.; Kazan, Kemal

2005-01-01

To identify transcription factors (TFs) involved in jasmonate (JA) signaling and plant defense, we screened 1,534 Arabidopsis (Arabidopsis thaliana) TFs by real-time quantitative reverse transcription-PCR for their altered transcript at 6 h following either methyl JA treatment or inoculation with the incompatible pathogen Alternaria brassicicola. We identified 134 TFs that showed a significant change in expression, including many APETALA2/ethylene response factor (AP2/ERF), MYB, WRKY, and NAC TF genes with unknown functions. Twenty TF genes were induced by both the pathogen and methyl JA and these included 10 members of the AP2/ERF TF family, primarily from the B1a and B3 subclusters. Functional analysis of the B1a TF AtERF4 revealed that AtERF4 acts as a novel negative regulator of JA-responsive defense gene expression and resistance to the necrotrophic fungal pathogen Fusarium oxysporum and antagonizes JA inhibition of root elongation. In contrast, functional analysis of the B3 TF AtERF2 showed that AtERF2 is a positive regulator of JA-responsive defense genes and resistance to F. oxysporum and enhances JA inhibition of root elongation. Our results suggest that plants coordinately express multiple repressor- and activator-type AP2/ERFs during pathogen challenge to modulate defense gene expression and disease resistance. PMID:16183832

49 CFR 1011.3 - The Chairman, Vice Chairman, and Board Member.

Code of Federal Regulations, 2010 CFR

2010-10-01

... the executive head of the Board and has general responsibilities for: (i) The overall management and functioning of the Board; (ii) The formulation of plans and policies designed to assure the effective... the Board exercises the executive and administrative functions of the Board, including: (i) The...

Effect of Differential Item Functioning on Test Equating

ERIC Educational Resources Information Center

Kabasakal, Kübra Atalay; Kelecioglu, Hülya

2015-01-01

This study examines the effect of differential item functioning (DIF) items on test equating through multilevel item response models (MIRMs) and traditional IRMs. The performances of three different equating models were investigated under 24 different simulation conditions, and the variables whose effects were examined included sample size, test…

20 CFR 1002.5 - What definitions apply to USERRA?

Code of Federal Regulations, 2011 CFR

2011-04-01

...-related responsibilities, except in the case that such entity has been delegated functions that are purely... appointee upon activation of the National Disaster Medical System (NDMS) or as a participant in an... employer, including the composition, structure, and functions of the work force of such employer; the...

Bayesian analysis of spatially-dependent functional responses with spatially-dependent multi-dimensional functional predictors

USDA-ARS?s Scientific Manuscript database

Recent advances in technology have led to the collection of high-dimensional data not previously encountered in many scientific environments. As a result, scientists are often faced with the challenging task of including these high-dimensional data into statistical models. For example, data from sen...

Macrobiota — helminths as active participants and partners of the microbiota in host intestinal homeostasis

PubMed Central

Gause, William C; Maizels, Rick M

2016-01-01

Important insights have recently been gained in our understanding of the intricate relationship in the intestinal milieu between the vertebrate host mucosal immune response, commensal bacteria, and helminths. Helminths are metazoan worms (macrobiota) and trigger immune responses that include potent regulatory components capable of controlling harmful inflammation, protecting barrier function and mitigating tissue damage. They can secrete a variety of products that directly affect immune regulatory function but they also have the capacity to influence the composition of microbiota, which can also then impact immune function. Conversely, changes in microbiota can affect susceptibility to helminth infection, indicating that crosstalk between these two disparate groups of endobiota can play an essential role in host intestinal immune function and homeostasis. PMID:27116368

Data Comparisons and Summary of the Second Aeroelastic Prediction Workshop

NASA Technical Reports Server (NTRS)

Heeg, Jennifer; Wieseman, Carol D.; Chwalowski, Pawel

2016-01-01

This paper presents the computational results generated by participating teams of the second Aeroelastic Prediction Workshop and compare them with experimental data. Aeroelastic and rigid configurations of the Benchmark Supercritical Wing (BSCW) wind tunnel model served as the focus for the workshop. The comparison data sets include unforced ("steady") system responses, forced pitch oscillations and coupled fluid-structure responses. Integrated coefficients, frequency response functions, and flutter onset conditions are compared. The flow conditions studied were in the transonic range, including both attached and separated flow conditions. Some of the technical discussions that took place at the workshop are summarized.

Outcome measurement of hand function following mirror therapy for stroke rehabilitation: A systematic review.

PubMed

Cantero-Téllez, Raquel; Naughton, Nancy; Algar, Lori; Valdes, Kristin

2018-02-28

Systematic review. Mirror therapy is a treatment used to address hand function following a stroke. Measurement of outcomes using appropriate assessment tools is crucial; however, many assessment options exist. The purpose of this study is to systematically review outcome measures that are used to assess hand function following mirror therapy after stroke and, in addition, to identify the psychometric and descriptive properties of the included measures and through the linking process determine if the outcome measures are representative of the International Classification of Functioning, Disability and Health (ICF). Following a comprehensive literature search, outcome measures used in the included studies were linked to the ICF and analyzed based on descriptive information and psychometric properties. Eleven studies met inclusion criteria and included 24 different assessment tools to measure hand or upper limb function. Most outcome measures used in the selected studies (63%) were rated by the evaluating therapist. Thirteen outcome measures (54%) linked to the ICF body function category and 10 measures (42%) linked to activities and participation. One outcome measure was linked to not defined, and all other ICF categories were not represented. A majority of outcome measures have been assessed for validity, reliability, and responsiveness, but responsiveness was the least investigated psychometric property. Current studies on mirror therapy after stroke are not consistent in the assessment tools used to determine hand function. Understanding of study outcomes requires analysis of the assessment tools. The outcome measures used in the included studies are not representative of personal and environmental factors, but tools linking to body functions and activities and participations provide important information on functional outcome. Integrating a combination of measures that are psychometrically sound and reflective of the ICF should be considered for assessment of hand function after mirror therapy after stroke. Copyright © 2018 Hanley & Belfus. Published by Elsevier Inc. All rights reserved.

Obesity, change of body mass index and subsequent physical and mental health functioning: a 12-year follow-up study among ageing employees.

PubMed

Svärd, Anna; Lahti, Jouni; Roos, Eira; Rahkonen, Ossi; Lahelma, Eero; Lallukka, Tea; Mänty, Minna

2017-09-26

Studies suggest an association between weight change and subsequent poor physical health functioning, whereas the association with mental health functioning is inconsistent. We aimed to examine whether obesity and change of body mass index among normal weight, overweight and obese women and men associate with changes in physical and mental health functioning. The Helsinki Health Study cohort includes Finnish municipal employees aged 40 to 60 in 2000-02 (phase 1, response rate 67%). Phase 2 mail survey (response rate 82%) took place in 2007 and phase 3 in 2012 (response rate 76%). This study included 5668 participants (82% women). Seven weight change categories were formed based on body mass index (BMI) (phase 1) and weight change (BMI change ≥5%) (phase 1-2). The Short Form 36 Health Survey (SF-36) measured physical and mental health functioning. The change in health functioning (phase 1-3) score was examined with repeated measures analyses. Covariates were age, sociodemographic factors, health behaviours, and somatic ill-health. Weight gain was common among women (34%) and men (25%). Weight-gaining normal weight (-1.3 points), overweight (-1.3 points) and obese (-3.6 points) women showed a greater decline in physical component summary scores than weight-maintaining normal weight women. Among weight-maintainers, only obese (-1.8 points) women showed a greater decline than weight-maintaining normal weight women. The associations were similar, but statistically non-significant for obese men. No statistically significant differences in the change in mental health functioning occurred. Preventing weight gain likely helps maintaining good physical health functioning and work ability.

Community structure in networks of functional connectivity: resolving functional organization in the rat brain with pharmacological MRI.

PubMed

Schwarz, Adam J; Gozzi, Alessandro; Bifone, Angelo

2009-08-01

In the study of functional connectivity, fMRI data can be represented mathematically as a network of nodes and links, where image voxels represent the nodes and the connections between them reflect a degree of correlation or similarity in their response. Here we show that, within this framework, functional imaging data can be partitioned into 'communities' of tightly interconnected voxels corresponding to maximum modularity within the overall network. We evaluated this approach systematically in application to networks constructed from pharmacological MRI (phMRI) of the rat brain in response to acute challenge with three different compounds with distinct mechanisms of action (d-amphetamine, fluoxetine, and nicotine) as well as vehicle (physiological saline). This approach resulted in bilaterally symmetric sub-networks corresponding to meaningful anatomical and functional connectivity pathways consistent with the purported mechanism of action of each drug. Interestingly, common features across all three networks revealed two groups of tightly coupled brain structures that responded as functional units independent of the specific neurotransmitter systems stimulated by the drug challenge, including a network involving the prefrontal cortex and sub-cortical regions extending from the striatum to the amygdala. This finding suggests that each of these networks includes general underlying features of the functional organization of the rat brain.

A Functional Toll-Interacting Protein Variant Is Associated with Bacillus Calmette-Guérin-Specific Immune Responses and Tuberculosis.

PubMed

Shah, Javeed A; Musvosvi, Munyaradzi; Shey, Muki; Horne, David J; Wells, Richard D; Peterson, Glenna J; Cox, Jeffery S; Daya, Michelle; Hoal, Eileen G; Lin, Lin; Gottardo, Raphael; Hanekom, Willem A; Scriba, Thomas J; Hatherill, Mark; Hawn, Thomas R

2017-08-15

The molecular mechanisms that regulate tuberculosis susceptibility and bacillus Calmette-Guérin (BCG)-induced immunity are mostly unknown. However, induction of the adaptive immune response is a critical step in host control of Mycobacterium tuberculosis. Toll-interacting protein (TOLLIP) is a ubiquitin-binding protein that regulates innate immune responses, including Toll-like receptor signaling, which initiate adaptive immunity. TOLLIP variation is associated with susceptibility to tuberculosis, but the mechanism by which it regulates tuberculosis immunity is poorly understood. To identify functional TOLLIP variants and evaluate the role of TOLLIP variation on innate and adaptive immune responses to mycobacteria and susceptibility to tuberculosis. We used human cellular immunology approaches to characterize the role of a functional TOLLIP variant on monocyte mRNA expression and M. tuberculosis-induced monocyte immune functions. We also examined the association of TOLLIP variation with BCG-induced T-cell responses and susceptibility to latent tuberculosis infection. We identified a functional TOLLIP promoter region single-nucleotide polymorphism, rs5743854, which was associated with decreased TOLLIP mRNA expression in infant monocytes. After M. tuberculosis infection, TOLLIP-deficient monocytes demonstrated increased IL-6, increased nitrite, and decreased bacterial replication. The TOLLIP-deficiency G/G genotype was associated with decreased BCG-specific IL-2 + CD4 + T-cell frequency and proliferation. This genotype was also associated with increased susceptibility to latent tuberculosis infection. TOLLIP deficiency is associated with decreased BCG-specific T-cell responses and increased susceptibility to tuberculosis. We hypothesize that the heightened antibacterial monocyte responses after vaccination of TOLLIP-deficient infants are responsible for decreased BCG-specific T-cell responses. Activating TOLLIP may provide a novel adjuvant strategy for BCG vaccination.

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).

Electrophysiological measurement of human auditory function

NASA Technical Reports Server (NTRS)

Galambos, R.

1975-01-01

Knowledge of the human auditory evoked response is reviewed, including methods of determining this response, the way particular changes in the stimulus are coupled to specific changes in the response, and how the state of mind of the listener will influence the response. Important practical applications of this basic knowledge are discussed. Measurement of the brainstem evoked response, for instance, can state unequivocally how well the peripheral auditory apparatus functions. It might then be developed into a useful hearing test, especially for infants and preverbal or nonverbal children. Clinical applications of measuring the brain waves evoked 100 msec and later after the auditory stimulus are undetermined. These waves are clearly related to brain events associated with cognitive processing of acoustic signals, since their properties depend upon where the listener directs his attention and whether how long he expects the signal.

Brain Imaging of Human Sexual Response: Recent Developments and Future Directions.

PubMed

Ruesink, Gerben B; Georgiadis, Janniko R

2017-01-01

The purpose of this study is to provide a comprehensive summary of the latest developments in the experimental brain study of human sexuality, focusing on brain connectivity during the sexual response. Stable patterns of brain activation have been established for different phases of the sexual response, especially with regard to the wanting phase, and changes in these patterns can be linked to sexual response variations, including sexual dysfunctions. From this solid basis, connectivity studies of the human sexual response have begun to add a deeper understanding of the brain network function and structure involved. The study of "sexual" brain connectivity is still very young. Yet, by approaching the brain as a connected organ, the essence of brain function is captured much more accurately, increasing the likelihood of finding useful biomarkers and targets for intervention in sexual dysfunction.

ALCOHOL AND THE PREFRONTAL CORTEX

PubMed Central

Abernathy, Kenneth; Chandler, L. Judson; Woodward, John J.

2013-01-01

The prefrontal cortex occupies the anterior portion of the frontal lobes and is thought to be one of the most complex anatomical and functional structures of the mammalian brain. Its major role is to integrate and interpret inputs from cortical and sub-cortical structures and use this information to develop purposeful responses that reflect both present and future circumstances. This includes both action-oriented sequences involved in obtaining rewards and inhibition of behaviors that pose undue risk or harm to the individual. Given the central role in initiating and regulating these often complex cognitive and behavioral responses, it is no surprise that alcohol has profound effects on the function of the prefrontal cortex. In this chapter, we review the basic anatomy and physiology of the prefrontal cortex and discuss what is known about the actions of alcohol on the function of this brain region. This includes a review of both the human and animal literature including information on the electrophysiological and behavioral effects that follow acute and chronic exposure to alcohol. The chapter concludes with a discussion of unanswered questions and areas needing further investigation. PMID:20813246

Genomic architecture of biomass heterosis in Arabidopsis.

PubMed

Yang, Mei; Wang, Xuncheng; Ren, Diqiu; Huang, Hao; Xu, Miqi; He, Guangming; Deng, Xing Wang

2017-07-25

Heterosis is most frequently manifested by the substantially increased vigorous growth of hybrids compared with their parents. Investigating genomic variations in natural populations is essential to understand the initial molecular mechanisms underlying heterosis in plants. Here, we characterized the genomic architecture associated with biomass heterosis in 200 Arabidopsis hybrids. The genome-wide heterozygosity of hybrids makes a limited contribution to biomass heterosis, and no locus shows an obvious overdominance effect in hybrids. However, the accumulation of significant genetic loci identified in genome-wide association studies (GWAS) in hybrids strongly correlates with better-parent heterosis (BPH). Candidate genes for biomass BPH fall into diverse biological functions, including cellular, metabolic, and developmental processes and stimulus-responsive pathways. Important heterosis candidates include WUSCHEL , ARGOS , and some genes that encode key factors involved in cell cycle regulation. Interestingly, transcriptomic analyses in representative Arabidopsis hybrid combinations reveal that heterosis candidate genes are functionally enriched in stimulus-responsive pathways, including responses to biotic and abiotic stimuli and immune responses. In addition, stimulus-responsive genes are repressed to low-parent levels in hybrids with high BPH, whereas middle-parent expression patterns are exhibited in hybrids with no BPH. Our study reveals a genomic architecture for understanding the molecular mechanisms of biomass heterosis in Arabidopsis , in which the accumulation of the superior alleles of genes involved in metabolic and cellular processes improve the development and growth of hybrids, whereas the overall repressed expression of stimulus-responsive genes prioritizes growth over responding to environmental stimuli in hybrids under normal conditions.

Simulated Cardiopulmonary Arrests in a Hospital Setting.

ERIC Educational Resources Information Center

Mishkin, Barbara H.; And Others

1982-01-01

Describes a simulated interdisciplinary role rehearsal for cardiopulmonary arrest to prepare nurses to function effectively. Includes needs analysis, program components, and responses of program participants. (Author)

32 CFR 855.2 - Responsibilities.

Code of Federal Regulations, 2010 CFR

2010-07-01

... authority. All decisions are subject to the environmental impact analysis process as directed by the... instructions. The decision process includes consultation with other affected functional area managers when...

Production of functional proteins: balance of shear stress and gravity

NASA Technical Reports Server (NTRS)

Kaysen, James Howard (Inventor); Hammond, Timothy Grant (Inventor); Goodwin, Thomas John (Inventor)

2004-01-01

The present invention provides a method for production of functional proteins including hormones by renal cells in a three dimensional co-culture process responsive to shear stress using a rotating wall vessel. Natural mixture of renal cells expresses the enzyme 1-a-hydroxylase which can be used to generate the active form of vitamin D: 1,25-diOH vitamin D3. The fibroblast cultures and co-culture of renal cortical cells express the gene for erythropoietin and secrete erythropoietin into the culture supernatant. Other shear stress response genes are also modulated by shear stress, such as toxin receptors megalin and cubulin (gp280). Also provided is a method of treating in-need individual with the functional proteins produced in a three dimensional co-culture process responsive to shear stress using a rotating wall vessel.

Epidural anaesthesia and analgesia - effects on surgical stress responses and implications for postoperative nutrition.

PubMed

Holte, K; Kehlet, H

2002-06-01

Surgical injury leads to an endocrine-metabolic and inflammatory response with protein catabolism, increased cardiovascular demands, impaired pulmonary function and paralytic ileus, the most important release mechanisms being afferent neural stimuli and inflammatory mediators. Epidural local anaesthetic blockade of afferent stimuli reduces endocrine metabolic responses, and improve postoperative catabolism. Furthermore, dynamic pain relief is achieved with improved pulmonary function and a pronounced reduction of postoperative ileus, thereby providing optimal conditions for improved mobilization and oral nutrition, and preservation of body composition and muscle function. Studies integrating continuous epidural local anaesthetics with enforced early nutrition and mobilization uniformly suggest an improved recovery, decreased hospital stay and convalescence. Epidural local anaesthetics should be included in a multi-modal rehabilitation programme after major surgical procedures in order to facilitate oral nutrition, improve recovery and reduce morbidity.

Cross-continental comparison of the functional composition and carbon allocation of two altitudinal forest transects in Ecuador and Rwanda.

NASA Astrophysics Data System (ADS)

Bauters, Marijn; Bruneel, Stijn; Demol, Miro; Taveirne, Cys; Van Der Heyden, Dries; Boeckx, Pascal; Kearsley, Elizabeth; Cizungu, Landry; Verbeeck, Hans

2016-04-01

Tropical forests are key actors in the global carbon cycle. Predicting future responses of these forests to global change is challenging, but important for global climate models. However, our current understanding of such responses is limited, due to the complexity of forest ecosystems and the slow dynamics that inherently form these systems. Our understanding of ecosystem ecology and functioning could greatly benefit from experimental setups including strong environmental gradients in the tropics, as found on altitudinal transects. We setup two such transects in both South-America and Africa, focussing on shifts in carbon allocation, forest structure and functional composition. By a cross-continental comparison of both transects, we will gain insight in how different or alike both tropical forests biomes are in their responses, and how universal the observed adaption mechanisms are.

Production of functional proteins: balance of shear stress and gravity

NASA Technical Reports Server (NTRS)

Hammond, Timothy Grant (Inventor); Kaysen, James Howard (Inventor); Goodwin, Thomas John (Inventor)

2007-01-01

The present invention provides a method for production of functional proteins including hormones by renal cells in a three dimensional co-culture process responsive to shear stress using a rotating wall vessel. Natural mixture of renal cells expresses the enzyme 1-a-hydroxylase which can be used to generate the active form of vitamin D: 1,25-diOH vitamin D3. The fibroblast cultures and co-culture of renal cortical cells express the gene for erythropoietin and secrete erythropoietin into the culture supernatant. Other shear stress response genes are also modulated by shear stress, such as toxin receptors megalin and cubulin (gp280). Also provided is a method of treating in-need individual with the functional proteins produced in a three dimensional co-culture process responsive to shear stress using a rotating wall vessel.

Influenza A virus-dependent remodeling of pulmonary clock function in a mouse model of COPD

PubMed Central

Sundar, Isaac K.; Ahmad, Tanveer; Yao, Hongwei; Hwang, Jae-woong; Gerloff, Janice; Lawrence, B. Paige; Sellix, Michael T.; Rahman, Irfan

2015-01-01

Daily oscillations of pulmonary function depend on the rhythmic activity of the circadian timing system. Environmental tobacco/cigarette smoke (CS) disrupts circadian clock leading to enhanced inflammatory responses. Infection with influenza A virus (IAV) increases hospitalization rates and death in susceptible individuals, including patients with Chronic Obstructive Pulmonary Disease (COPD). We hypothesized that molecular clock disruption is enhanced by IAV infection, altering cellular and lung function, leading to severity in airway disease phenotypes. C57BL/6J mice exposed to chronic CS, BMAL1 knockout (KO) mice and wild-type littermates were infected with IAV. Following infection, we measured diurnal rhythms of clock gene expression in the lung, locomotor activity, pulmonary function, inflammatory, pro-fibrotic and emphysematous responses. Chronic CS exposure combined with IAV infection altered the timing of clock gene expression and reduced locomotor activity in parallel with increased lung inflammation, disrupted rhythms of pulmonary function, and emphysema. BMAL1 KO mice infected with IAV showed pronounced detriments in behavior and survival, and increased lung inflammatory and pro-fibrotic responses. This suggests that remodeling of lung clock function following IAV infection alters clock-dependent gene expression and normal rhythms of lung function, enhanced emphysematous and injurious responses. This may have implications for the pathobiology of respiratory virus-induced airway disease severity and exacerbations. PMID:25923474

Bridging the gap between high-throughput genetic and transcriptional data reveals cellular pathways responding to alpha-synuclein toxicity

PubMed Central

Yeger-Lotem, Esti; Riva, Laura; Su, Linhui Julie; Gitler, Aaron D.; Cashikar, Anil; King, Oliver D.; Auluck, Pavan K.; Geddie, Melissa L.; Valastyan, Julie S.; Karger, David R.; Lindquist, Susan; Fraenkel, Ernest

2009-01-01

Cells respond to stimuli by changes in various processes, including signaling pathways and gene expression. Efforts to identify components of these responses increasingly depend on mRNA profiling and genetic library screens, yet the functional roles of the genes identified by these assays often remain enigmatic. By comparing the results of these two assays across various cellular responses, we found that they are consistently distinct. Moreover, genetic screens tend to identify response regulators, while mRNA profiling frequently detects metabolic responses. We developed an integrative approach that bridges the gap between these data using known molecular interactions, thus highlighting major response pathways. We harnessed this approach to reveal cellular pathways related to alpha-synuclein, a small lipid-binding protein implicated in several neurodegenerative disorders including Parkinson disease. For this we screened an established yeast model for alpha-synuclein toxicity to identify genes that when overexpressed alter cellular survival. Application of our algorithm to these data and data from mRNA profiling provided functional explanations for many of these genes and revealed novel relations between alpha-synuclein toxicity and basic cellular pathways. PMID:19234470

Deficits in oculomotor performance in pediatric epilepsy

PubMed Central

Asato, Miya R.; Nawarawong, Natalie; Hermann, Bruce; Crumrine, Patricia; Luna, Beatriz

2010-01-01

Summary Purpose Given evidence of limitations in neuropsychological performance in epilepsy, we probed the integrity of components of cognition, including speed of processing, response inhibition, and spatial working memory supporting executive function in pediatric epilepsy patients and matched controls. Methods A total of 44 pairs of controls and medically treated pediatric epilepsy patients with no known brain pathology completed cognitive oculomotor tasks, computerized neuropsychological testing, and psychiatric assessment. Results Patients showed slower reaction time to initiate a saccadic response compared to controls but had intact saccade accuracy. Cognitively driven responses including response inhibition were impaired in the patient group. Patients had increased incidence of comorbid psychopathology but comorbidity did not predict worse functioning compared to patients with no ADHD. Epilepsy type and medication status were not predictive of outcome. More complex neuropsychological performance was impaired in tasks requiring visual memory and sequential processing which was correlated with inhibitory control and antisaccade accuracy. Discussion Pediatric epilepsy may be associated with vulnerabilities that specifically undermine speed of processing and response inhibition but not working memory and may underlie known neuropsychological performance limitations. This particular profile of abnormalities may be associated with seizure-mediated compromises in brain maturation early in development. PMID:21087246

Right ventricular pressure response to exercise in adults with isolated ventricular septal defect closed in early childhood.

PubMed

Moller, Thomas; Lindberg, Harald; Lund, May Brit; Holmstrom, Henrik; Dohlen, Gaute; Thaulow, Erik

2018-06-01

We previously demonstrated an abnormally high right ventricular systolic pressure response to exercise in 50% of adolescents operated on for isolated ventricular septal defect. The present study investigated the prevalence of abnormal right ventricular systolic pressure response in 20 adult (age 30-45 years) patients who underwent surgery for early ventricular septal defect closure and its association with impaired ventricular function, pulmonary function, or exercise capacity. The patients underwent cardiopulmonary tests, including exercise stress echocardiography. Five of 19 patients (26%) presented an abnormal right ventricular systolic pressure response to exercise ⩾ 52 mmHg. Right ventricular systolic function was mixed, with normal tricuspid annular plane systolic excursion and fractional area change, but abnormal tricuspid annular systolic motion velocity (median 6.7 cm/second) and isovolumetric acceleration (median 0.8 m/second2). Left ventricular systolic and diastolic function was normal at rest as measured by the peak systolic velocity of the lateral wall and isovolumic acceleration, early diastolic velocity, and ratio of early diastolic flow to tissue velocity, except for ejection fraction (median 53%). The myocardial performance index was abnormal for both the left and right ventricle. Peak oxygen uptake was normal (mean z score -0.4, 95% CI -2.8-0.3). There was no association between an abnormal right ventricular systolic pressure response during exercise and right or left ventricular function, pulmonary function, or exercise capacity. Abnormal right ventricular pressure response is not more frequent in adult patients compared with adolescents. This does not support the theory of progressive pulmonary vascular disease following closure of left-to-right shunts.

Comparison of the functional rating index and the 18-item Roland-Morris Disability Questionnaire: responsiveness and reliability.

PubMed

Chansirinukor, Wunpen; Maher, Christopher G; Latimer, Jane; Hush, Julia

2005-01-01

Retrospective design. To compare the responsiveness and test-retest reliability of the Functional Rating Index and the 18-item version of the Roland-Morris Disability Questionnaire in detecting change in disability in patients with work-related low back pain. Many low back pain-specific disability questionnaires are available, including the Functional Rating Index and the 18-item version of the Roland-Morris Disability Questionnaire. No previous study has compared the responsiveness and reliability of these questionnaires. Files of patients who had been treated for work-related low back pain at a physical therapy clinic were reviewed, and those containing initial and follow-up Functional Rating Index and 18-item Roland-Morris Disability Questionnaires were selected. The responsiveness of both questionnaires was compared using two different methods. First, using the assumption that patients receiving treatment improve over time, various responsiveness coefficients were calculated. Second, using change in work status as an external criterion to identify improved and nonimproved patients, Spearman's rho and receiver operating characteristic curves were calculated. Reliability was estimated from the subset of patients who reported no change in their condition over this period and expressed with the intraclass correlation coefficient and the minimal detectable change. One hundred and forty-three patient files were retrieved. The responsiveness coefficients for the Functional Rating Index were greater than for the 18-item Roland-Morris Disability Questionnaire. The intraclass correlation coefficient values for both questionnaires calculated from 96 patient files were similar, but the minimal detectable change for the Functional Rating Index was less than for the 18-item Roland-Morris Disability Questionnaire. The Functional Rating Index seems preferable to the 18-item Roland-Morris Disability Questionnaire for use in clinical trials and clinical practice.

Spacelab Life Sciences 1 - Dedicated life sciences mission

NASA Technical Reports Server (NTRS)

Womack, W. D.

1990-01-01

The Spacelab Life Sciences 1 (SLS-1) mission is discussed, and an overview of the SLS-1 Spacelab configuration is shown. Twenty interdisciplinary experiments, planned for this mission, are intended to explore the early stages of human and animal physiological adaptation to space flight conditions. Biomedical and gravitational biology experiments include cardiovascular and cardiopulmonary deconditioning, altered vestibular functions, altered metabolic functions (including altered fluid-electrolyte regulation), muscle atrophy, bone demineralization, decreased red blood cell mass, and altered immunologic responses.

Influence of Image Interactivity on Approach Responses towards an Online Retailer.

ERIC Educational Resources Information Center

Fiore, Ann Marie; Jin, Hyun-Jeong

2003-01-01

Measured the effect of exposure to an image interactivity function from an apparel retailer's Web site on approach responses towards the retailer. Dependent variables included attitude towards the online store, willingness to purchase, probability of spending more time than planned shopping, and likelihood of patronizing the online retailer's…

Thermo-responsive cell culture carrier: Effects on macrophage functionality and detachment efficiency.

PubMed

Rennert, Knut; Nitschke, Mirko; Wallert, Maria; Keune, Natalie; Raasch, Martin; Lorkowski, Stefan; Mosig, Alexander S

2017-01-01

Harvesting cultivated macrophages for tissue engineering purposes by enzymatic digestion of cell adhesion molecules can potentially result in unintended activation, altered function, or behavior of these cells. Thermo-responsive polymer is a promising tool that allows for gentle macrophage detachment without artificial activation prior to subculture within engineered tissue constructs. We therefore characterized different species of thermo-responsive polymers for their suitability as cell substrate and to mediate gentle macrophage detachment by temperature shift. Primary human monocyte- and THP-1-derived macrophages were cultured on thermo-responsive polymers and characterized for phagocytosis and cytokine secretion in response to lipopolysaccharide stimulation. We found that both cell types differentially respond in dependence of culture and stimulation on thermo-responsive polymers. In contrast to THP-1 macrophages, primary monocyte-derived macrophages showed no signs of impaired viability, artificial activation, or altered functionality due to culture on thermo-responsive polymers compared to conventional cell culture. Our study demonstrates that along with commercially available UpCell carriers, two other thermo-responsive polymers based on poly(vinyl methyl ether) blends are attractive candidates for differentiation and gentle detachment of primary monocyte-derived macrophages. In summary, we observed similar functionality and viability of primary monocyte-derived macrophages cultured on thermo-responsive polymers compared to standard cell culture surfaces. While this first generation of custom-made thermo-responsive polymers does not yet outperform standard culture approaches, our results are very promising and provide the basis for exploiting the unique advantages offered by custom-made thermo-responsive polymers to further improve macrophage culture and recovery in the future, including the covalent binding of signaling molecules and the reduction of centrifugation and washing steps. Optimizing these and other benefits of thermo-responsive polymers could greatly improve the culture of macrophages for tissue engineering applications.

An Integrated Hydrologic-Economic Modeling Tool for Evaluating Water Management Responses to Climate Change in the Boise River Basin

NASA Astrophysics Data System (ADS)

Schmidt, R. D.; Taylor, R. G.; Stodick, L. D.; Contor, B. A.

2009-12-01

A recent federal interagency report on climate change and water management (Brekke et. al., 2009) describes several possible management responses to the impacts of climate change on water supply and demand. Management alternatives include changes to water supply infrastructure, reservoir system operations, and water demand policies. Water users in the Bureau of Reclamation’s Boise Project (located in the Lower Boise River basin in southwestern Idaho) would be among those impacted both hydrologically and economically by climate change. Climate change and management responses to climate change are expected to cause shifts in water supply and demand. Supply shifts would result from changes in basin precipitation patterns, and demand shifts would result from higher evapotranspiration rates and a longer growing season. The impacts would also extend to non-Project water users in the basin, since most non-Project groundwater pumpers and drain water diverters rely on hydrologic externalities created by seepage losses from Boise Project water deliveries. An integrated hydrologic-economic model was developed for the Boise basin to aid Reclamation in evaluating the hydrologic and economic impacts of various management responses to climate change. A spatial, partial-equilibrium, economic optimization model calculates spatially-distinct equilibrium water prices and quantities, and maximizes a social welfare function (the sum of consumer and producers surpluses) for all agricultural and municipal water suppliers and demanders (both Project and non-Project) in the basin. Supply-price functions and demand-price functions are exogenous inputs to the economic optimization model. On the supply side, groundwater and river/reservoir models are used to generate hydrologic responses to various management alternatives. The response data is then used to develop water supply-price functions for Project and non-Project water users. On the demand side, crop production functions incorporating crop distribution, evapotranspiration rates, irrigation efficiencies, and crop prices are used to develop water demand-price functions for agricultural water users. Demand functions for municipal and industrial water users are also developed. Recent applications of the integrated model have focused on the hydrologic and economic impacts of demand management alternatives, including large-scale canal lining conservation measures, and market-based water trading between canal diverters and groundwater pumpers. A supply management alternative being investigated involves revising reservoir rule curves to compensate for climate change impacts on timing of reservoir filling.

Public health professionals' perceptions toward provision of health protection in England: a survey of expectations of Primary Care Trusts and Health Protection Units in the delivery of health protection

PubMed Central

Cosford, Paul A; O'Mahony, Mary; Angell, Emma; Bickler, Graham; Crawshaw, Shirley; Glencross, Janet; Horsley, Stephen S; McCloskey, Brian; Puleston, Richard; Seare, Nichola; Tobin, Martin D

2006-01-01

Background Effective health protection requires systematised responses with clear accountabilities. In England, Primary Care Trusts and the Health Protection Agency both have statutory responsibilities for health protection. A Memorandum of Understanding identifies responsibilities of both parties, but there is a potential lack of clarity about responsibility for specific health protection functions. We aimed to investigate professionals' perceptions of responsibility for different health protection functions, to inform future guidance for, and organisation of, health protection in England. Methods We sent a postal questionnaire to all health protection professionals in England from the following groups: (a) Directors of Public Health in Primary Care Trusts; (b) Directors of Health Protection Units within the Health Protection Agency; (c) Directors of Public Health in Strategic Health Authorities and; (d) Regional Directors of the Health Protection Agency Results The response rate exceeded 70%. Variations in perceptions of who should be, and who is, delivering health protection functions were observed within, and between, the professional groups (a)-(d). Concordance in views of which organisation should, and which does deliver was high (≥90%) for 6 of 18 health protection functions, but much lower (≤80%) for 6 other functions, including managing the implications of a case of meningitis out of hours, of landfill environmental contamination, vaccination in response to mumps outbreaks, nursing home infection control, monitoring sexually transmitted infections and immunisation training for primary care staff. The proportion of respondents reporting that they felt confident most or all of the time in the safe delivery of a health protection function was strongly correlated with the concordance (r = 0.65, P = 0.0038). Conclusion Whilst we studied professionals' perceptions, rather than actual responses to incidents, our study suggests that there are important areas of health protection where consistent understanding of responsibility for delivery is lacking. There are opportunities to clarify the responsibility for health protection in England, perhaps learning from the approaches used for those health protection functions where we found consistent perceptions of accountability. PMID:17156421

Public health professionals' perceptions toward provision of health protection in England: a survey of expectations of Primary Care Trusts and Health Protection Units in the delivery of health protection.

PubMed

Cosford, Paul A; O'Mahony, Mary; Angell, Emma; Bickler, Graham; Crawshaw, Shirley; Glencross, Janet; Horsley, Stephen S; McCloskey, Brian; Puleston, Richard; Seare, Nichola; Tobin, Martin D

2006-12-07

Effective health protection requires systematised responses with clear accountabilities. In England, Primary Care Trusts and the Health Protection Agency both have statutory responsibilities for health protection. A Memorandum of Understanding identifies responsibilities of both parties, but there is a potential lack of clarity about responsibility for specific health protection functions. We aimed to investigate professionals' perceptions of responsibility for different health protection functions, to inform future guidance for, and organisation of, health protection in England. We sent a postal questionnaire to all health protection professionals in England from the following groups: (a) Directors of Public Health in Primary Care Trusts; (b) Directors of Health Protection Units within the Health Protection Agency; (c) Directors of Public Health in Strategic Health Authorities and; (d) Regional Directors of the Health Protection Agency The response rate exceeded 70%. Variations in perceptions of who should be, and who is, delivering health protection functions were observed within, and between, the professional groups (a)-(d). Concordance in views of which organisation should, and which does deliver was high (> or =90%) for 6 of 18 health protection functions, but much lower (< or =80%) for 6 other functions, including managing the implications of a case of meningitis out of hours, of landfill environmental contamination, vaccination in response to mumps outbreaks, nursing home infection control, monitoring sexually transmitted infections and immunisation training for primary care staff. The proportion of respondents reporting that they felt confident most or all of the time in the safe delivery of a health protection function was strongly correlated with the concordance (r = 0.65, P = 0.0038). Whilst we studied professionals' perceptions, rather than actual responses to incidents, our study suggests that there are important areas of health protection where consistent understanding of responsibility for delivery is lacking. There are opportunities to clarify the responsibility for health protection in England, perhaps learning from the approaches used for those health protection functions where we found consistent perceptions of accountability.

Dynamic gene expression analysis in a H1N1 influenza virus mouse pneumonia model.

PubMed

Bao, Yanyan; Gao, Yingjie; Shi, Yujing; Cui, Xiaolan

2017-06-01

H1N1, a major pathogenic subtype of influenza A virus, causes a respiratory infection in humans and livestock that can range from a mild infection to more severe pneumonia associated with acute respiratory distress syndrome. Understanding the dynamic changes in the genome and the related functional changes induced by H1N1 influenza virus infection is essential to elucidating the pathogenesis of this virus and thereby determining strategies to prevent future outbreaks. In this study, we filtered the significantly expressed genes in mouse pneumonia using mRNA microarray analysis. Using STC analysis, seven significant gene clusters were revealed, and using STC-GO analysis, we explored the significant functions of these seven gene clusters. The results revealed GOs related to H1N1 virus-induced inflammatory and immune functions, including innate immune response, inflammatory response, specific immune response, and cellular response to interferon-beta. Furthermore, the dynamic regulation relationships of the key genes in mouse pneumonia were revealed by dynamic gene network analysis, and the most important genes were filtered, including Dhx58, Cxcl10, Cxcl11, Zbp1, Ifit1, Ifih1, Trim25, Mx2, Oas2, Cd274, Irgm1, and Irf7. These results suggested that during mouse pneumonia, changes in the expression of gene clusters and the complex interactions among genes lead to significant changes in function. Dynamic gene expression analysis revealed key genes that performed important functions. These results are a prelude to advancements in mouse H1N1 influenza virus infection biology, as well as the use of mice as a model organism for human H1N1 influenza virus infection studies.

Peak heart rates and sympathetic function in tetraplegic nonathletes and athletes.

PubMed

Currie, Katharine D; West, Christopher R; Hubli, Michéle; Gee, Cameron M; Krassioukov, Andrei V

2015-06-01

To examine differences in peak heart rate (HR) and measures of sympathetic function between nonathletes and athletes with chronic, motor-complete, cervical spinal cord injury (SCI). Eight nonathletic men with SCI (C4-C7; age 47 ± 9 yr, with injury duration of 16 ± 9 yr) and 13 athletic men with SCI (C5-C8; age 37 ± 8 yr, with injury duration of 16 ± 6 yr) participated in the study. Measures of sympathetic function included palmar sympathetic skin responses (SSR) to median nerve stimulation, and systolic (SBP) and diastolic (DBP) blood pressure responses to a passive sit-up test. Peak HR responses were assessed during a maximal exercise test. Compared to the athletic group, the nonathletic group exhibited lower peak HR (102 ± 34 vs 161 ± 20 bpm, P < 0.001) and average SSR scores (0.13 ± 0.35 vs 2.41 ± 1.97, P = 0.008), along with greater reductions in SBP and DBP in response to passive sit-up (SBP: -22 ± 10 vs -9 ± 12 mm Hg, P = 0.019; DBP: -18 ± 8 mm Hg vs -4 ± 9 mm Hg, P = 0.003). On the basis of the criteria for orthostatic hypotension (OH) (drop in SBP ≥ 20 mm Hg or DBP ≥ 10 mm Hg), 88% and 23% of nonathletes and athletes had OH. Attenuated peak HR in nonathletic individuals with tetraplegia may be secondary to impairments in sympathetic function including absent SSR and OH. Furthermore, the degree of preserved sympathetic function documented in tetraplegic athletes may suggest a predisposition to engage in high-performance sports. Collectively, our findings provide novel insight into the importance of the sympathetic nervous system for exercise performance.

Effects of alcoholism severity and smoking on executive neurocognitive function.

PubMed

Glass, Jennifer M; Buu, Anne; Adams, Kenneth M; Nigg, Joel T; Puttler, Leon I; Jester, Jennifer M; Zucker, Robert A

2009-01-01

Neurocognitive deficits in chronic alcoholic men are well documented. Impairments include memory, visual-spatial processing, problem solving and executive function. The cause of impairment could include direct effects of alcohol toxicity, pre-existing cognitive deficits that predispose towards substance abuse, comorbid psychiatric disorders and abuse of substances other than alcohol. Cigarette smoking occurs at higher rates in alcoholism and has been linked to poor cognitive performance, yet the effects of smoking on cognitive function in alcoholism are often ignored. We examined whether chronic alcoholism and chronic smoking have effects on executive function. Alcoholism and smoking were examined in a community-recruited sample of alcoholic and non-alcoholic men (n = 240) using standard neuropsychological and reaction-time measures of executive function. Alcoholism was measured as the average level of alcoholism diagnoses across the study duration (12 years). Smoking was measured in pack-years. Both alcoholism and smoking were correlated negatively with a composite executive function score. For component measures, alcoholism was correlated negatively with a broad range of measures, whereas smoking was correlated negatively with measures that emphasize response speed. In regression analyses, both smoking and alcoholism were significant predictors of executive function composite. However, when IQ is included in the regression analyses, alcoholism severity is no longer significant. Both smoking and alcoholism were related to executive function. However, the effect of alcoholism was not independent of IQ, suggesting a generalized effect, perhaps affecting a wide range of cognitive abilities of which executive function is a component. On the other hand, the effect of smoking on measures relying on response speed were independent of IQ, suggesting a more specific processing speed deficit associated with chronic smoking.

Dryland responses to global change suggest the potential for rapid non-linear responses to some changes but resilience to others

NASA Astrophysics Data System (ADS)

Reed, S.; Ferrenberg, S.; Tucker, C.; Rutherford, W. A.; Wertin, T. M.; McHugh, T. A.; Morrissey, E.; Kuske, C.; Belnap, J.

2017-12-01

Drylands represent our planet's largest terrestrial biome, making up over 35% of Earth's land surface. In the context of this vast areal extent, it is no surprise that recent research suggests dryland inter-annual variability and responses to change have the potential to drive biogeochemical cycles and climate at the global-scale. Further, the data we do have suggest drylands can respond rapidly and non-linearly to change. Nevertheless, our understanding of the cross-system consistency of and mechanisms behind dryland responses to a changed environment remains relatively poor. This poor understanding hinders not only our larger understanding of terrestrial ecosystem function, but also our capacity to forecast future global biogeochemical cycles and climate. Here we present data from a series of Colorado Plateau manipulation experiments - including climate, land use, and nitrogen deposition manipulations - to explore how vascular plants, microbial communities, and biological soil crusts (a community of mosses, lichens, and/or cyanobacteria living in the interspace among vascular plants in arid and semiarid ecosystems worldwide) respond to a host of environmental changes. These responses include not only assessments of community composition, but of their function as well. We will explore photosynthesis, net soil CO2 exchange, soil carbon stocks and chemistry, albedo, and nutrient cycling. The experiments were begun with independent questions and cover a range of environmental change drivers and scientific approaches, but together offer a relatively holistic picture of how some drylands can change their structure and function in response to change. In particular, the data show very high ecosystem vulnerability to particular drivers, but surprising resilience to others, suggesting a multi-faceted response of these diverse systems.

Sad mood induction has an opposite effect on amygdala response to emotional stimuli in euthymic patients with bipolar disorder and healthy controls

PubMed Central

Horacek, Jiri; Mikolas, Pavol; Tintera, Jaroslav; Novak, Tomas; Palenicek, Tomas; Brunovsky, Martin; Höschl, Cyril; Alda, Martin

2015-01-01

Background Aberrant amygdala reactivity to affective stimuli represents a candidate factor predisposing patients with bipolar disorder (BD) to relapse, but it is unclear to what extent amygdala reactivity is state-dependent. We evaluated the modulatory influence of mood on amygdala reactivity and functional connectivity in patients with remitted BD and healthy controls. Methods Amygdala response to sad versus neutral faces was investigated using fMRI during periods of normal and sad mood induced by autobiographical scripts. We assessed the functional connectivity of the amygdala to characterize the influence of mood state on the network responsible for the amygdala response. Results We included 20 patients with remitted BD and 20 controls in our study. The sad and normal mood exerted opposite effects on the amygdala response to emotional faces in patients compared with controls (F1,38 = 5.85, p = 0.020). Sad mood amplified the amygdala response to sad facial stimuli in controls but attenuated the amygdala response in patients. The groups differed in functional connectivity between the amygdala and the inferior prefrontal gyrus (p ≤ 0.05, family-wise error–corrected) of ventrolateral prefrontal cortex (vlPFC) corresponding to Brodmann area 47. The sad mood challenge increased connectivity during the period of processing sad faces in patients but decreased connectivity in controls. Limitations Limitations to our study included long-term medication use in the patient group and the fact that we mapped only depressive (not manic) reactivity. Conclusion Our results support the role of the amygdala–vlPFC as the system of dysfunctional contextual affective processing in patients with BD. Opposite amygdala reactivity unmasked by the mood challenge paradigm could represent a trait marker of altered mood regulation in patients with BD. PMID:25703646

Sad mood induction has an opposite effect on amygdala response to emotional stimuli in euthymic patients with bipolar disorder and healthy controls.

PubMed

Horacek, Jiri; Mikolas, Pavol; Tintera, Jaroslav; Novak, Tomas; Palenicek, Tomas; Brunovsky, Martin; Höschl, Cyril; Alda, Martin

2014-12-16

Aberrant amygdala reactivity to affective stimuli represents a candidate factor predisposing patients with bipolar disorder (BD) to relapse, but it is unclear to what extent amygdala reactivity is state-dependent. We evaluated the modulatory influence of mood on amygdala reactivity and functional connectivity in patients with remitted BD and healthy controls. Amygdala response to sad versus neutral faces was investigated using fMRI during periods of normal and sad mood induced by autobiographical scripts. We assessed the functional connectivity of the amygdala to characterize the influence of mood state on the network responsible for the amygdala response. We included 20 patients with remitted BD and 20 controls in our study. The sad and normal mood exerted opposite effects on the amygdala response to emotional faces in patients compared with controls ( F 1,38 = 5.85, p = 0.020). Sad mood amplified the amygdala response to sad facial stimuli in controls but attenuated the amygdala response in patients. The groups differed in functional connectivity between the amygdala and the inferior prefrontal gyrus ( p ≤ 0.05, family-wise error-corrected) of ventrolateral prefrontal cortex (vlPFC) corresponding to Brodmann area 47. The sad mood challenge increased connectivity during the period of processing sad faces in patients but decreased connectivity in controls. Limitations to our study included long-term medication use in the patient group and the fact that we mapped only depressive (not manic) reactivity. Our results support the role of the amygdala-vlPFC as the system of dysfunctional contextual affective processing in patients with BD. Opposite amygdala reactivity unmasked by the mood challenge paradigm could represent a trait marker of altered mood regulation in patients with BD.

Sad mood induction has an opposite effect on amygdala response to emotional stimuli in euthymic patients with bipolar disorder and healthy controls.

PubMed

Horacek, Jiri; Mikolas, Pavol; Tintera, Jaroslav; Novak, Tomas; Palenicek, Tomas; Brunovsky, Martin; Höschl, Cyril; Alda, Martin

2015-03-01

Aberrant amygdala reactivity to affective stimuli represents a candidate factor predisposing patients with bipolar disorder (BD) to relapse, but it is unclear to what extent amygdala reactivity is state-dependent. We evaluated the modulatory influence of mood on amygdala reactivity and functional connectivity in patients with remitted BD and healthy controls. Amygdala response to sad versus neutral faces was investigated using fMRI during periods of normal and sad mood induced by autobiographical scripts. We assessed the functional connectivity of the amygdala to characterize the influence of mood state on the network responsible for the amygdala response. We included 20 patients with remitted BD and 20 controls in our study. The sad and normal mood exerted opposite effects on the amygdala response to emotional faces in patients compared with controls (F1,38 = 5.85, p = 0.020). Sad mood amplified the amygdala response to sad facial stimuli in controls but attenuated the amygdala response in patients. The groups differed in functional connectivity between the amygdala and the inferior prefrontal gyrus (p ≤ 0.05, family-wise error-corrected) of ventrolateral prefrontal cortex (vlPFC) corresponding to Brodmann area 47. The sad mood challenge increased connectivity during the period of processing sad faces in patients but decreased connectivity in controls. Limitations to our study included long-term medication use in the patient group and the fact that we mapped only depressive (not manic) reactivity. Our results support the role of the amygdala-vlPFC as the system of dysfunctional contextual affective processing in patients with BD. Opposite amygdala reactivity unmasked by the mood challenge paradigm could represent a trait marker of altered mood regulation in patients with BD.

Identifying Predictors, Moderators, and Mediators of Antidepressant Response in Major Depressive Disorder: Neuroimaging Approaches

PubMed Central

Phillips, Mary L.; Chase, Henry W.; Sheline, Yvette I.; Etkin, Amit; Almeida, Jorge R.C.; Deckersbach, Thilo; Trivedi, Madhukar H.

2015-01-01

Objective Despite significant advances in neuroscience and treatment development, no widely accepted biomarkers are available to inform diagnostics or identify preferred treatments for individuals with major depressive disorder. Method In this critical review, the authors examine the extent to which multimodal neuroimaging techniques can identify biomarkers reflecting key pathophysiologic processes in depression and whether such biomarkers may act as predictors, moderators, and mediators of treatment response that might facilitate development of personalized treatments based on a better understanding of these processes. Results The authors first highlight the most consistent findings from neuroimaging studies using different techniques in depression, including structural and functional abnormalities in two parallel neural circuits: serotonergically modulated implicit emotion regulation circuitry, centered on the amygdala and different regions in the medial prefrontal cortex; and dopaminergically modulated reward neural circuitry, centered on the ventral striatum and medial prefrontal cortex. They then describe key findings from the relatively small number of studies indicating that specific measures of regional function and, to a lesser extent, structure in these neural circuits predict treatment response in depression. Conclusions Limitations of existing studies include small sample sizes, use of only one neuroimaging modality, and a focus on identifying predictors rather than moderators and mediators of differential treatment response. By addressing these limitations and, most importantly, capitalizing on the benefits of multimodal neuroimaging, future studies can yield moderators and mediators of treatment response in depression to facilitate significant improvements in shorter- and longer-term clinical and functional outcomes. PMID:25640931

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.

Functional response and population dynamics for fighting predator, based on activity distribution.

PubMed

Garay, József; Varga, Zoltán; Gámez, Manuel; Cabello, Tomás

2015-03-07

The classical Holling type II functional response, describing the per capita predation as a function of prey density, was modified by Beddington and de Angelis to include interference of predators that increases with predator density and decreases the number of killed prey. In the present paper we further generalize the Beddington-de Angelis functional response, considering that all predator activities (searching and handling prey, fight and recovery) have time duration, the probabilities of predator activities depend on the encounter probabilities, and hence on the prey and predator abundance, too. Under these conditions, the aim of the study is to introduce a functional response for fighting the predator and to analyse the corresponding dynamics, when predator-predator-prey encounters also occur. From this general approach, the Holling type functional responses can also be obtained as particular cases. In terms of the activity distribution, we give biologically interpretable sufficient conditions for stable coexistence. We consider two-individual (predator-prey) and three-individual (predator-predator-prey) encounters. In the three-individual encounter model there is a relatively higher fighting rate and a lower killing rate. Using numerical simulation, we surprisingly found that when the intrinsic prey growth rate and the conversion rate are small enough, the equilibrium predator abundance is higher in the three-individual encounter case. The above means that, when the equilibrium abundance of the predator is small, coexistence appears first in the three-individual encounter model. Copyright © 2014 Elsevier Ltd. All rights reserved.

Validation study of a web-based assessment of functional recovery after radical prostatectomy.

PubMed

Vickers, Andrew J; Savage, Caroline J; Shouery, Marwan; Eastham, James A; Scardino, Peter T; Basch, Ethan M

2010-08-05

Good clinical care of prostate cancer patients after radical prostatectomy depends on careful assessment of post-operative morbidities, yet physicians do not always judge patient symptoms accurately. Logistical problems associated with using paper questionnaire limit their use in the clinic. We have implemented a web-interface ("STAR") for patient-reported outcomes after radical prostatectomy. We analyzed data on the first 9 months of clinical implementation to evaluate the validity of the STAR questionnaire to assess functional outcomes following radical prostatectomy. We assessed response rate, internal consistency within domains, and the association between survey responses and known predictors of sexual and urinary function, including age, time from surgery, nerve sparing status and co-morbidities. Of 1581 men sent an invitation to complete the instrument online, 1235 responded for a response rate of 78%. Cronbach's alpha was 0.84, 0.86 and 0.97 for bowel, urinary and sexual function respectively. All known predictors of sexual and urinary function were significantly associated with survey responses in the hypothesized direction. We have found that web-based assessment of functional recovery after radical prostatectomy is practical and feasible. The instrument demonstrated excellent psychometric properties, suggested that validity is maintained when questions are transferred from paper to electronic format and when patients give responses that they know will be seen by their doctor and added to their clinic record. As such, our system allows ready implementation of patient-reported outcomes into routine clinical practice.

Validation study of a web-based assessment of functional recovery after radical prostatectomy

PubMed Central

2010-01-01

Background Good clinical care of prostate cancer patients after radical prostatectomy depends on careful assessment of post-operative morbidities, yet physicians do not always judge patient symptoms accurately. Logistical problems associated with using paper questionnaire limit their use in the clinic. We have implemented a web-interface ("STAR") for patient-reported outcomes after radical prostatectomy. Methods We analyzed data on the first 9 months of clinical implementation to evaluate the validity of the STAR questionnaire to assess functional outcomes following radical prostatectomy. We assessed response rate, internal consistency within domains, and the association between survey responses and known predictors of sexual and urinary function, including age, time from surgery, nerve sparing status and co-morbidities. Results Of 1581 men sent an invitation to complete the instrument online, 1235 responded for a response rate of 78%. Cronbach's alpha was 0.84, 0.86 and 0.97 for bowel, urinary and sexual function respectively. All known predictors of sexual and urinary function were significantly associated with survey responses in the hypothesized direction. Conclusions We have found that web-based assessment of functional recovery after radical prostatectomy is practical and feasible. The instrument demonstrated excellent psychometric properties, suggested that validity is maintained when questions are transferred from paper to electronic format and when patients give responses that they know will be seen by their doctor and added to their clinic record. As such, our system allows ready implementation of patient-reported outcomes into routine clinical practice. PMID:20687938

Engineering responsive supramolecular biomaterials: Toward smart therapeutics.

PubMed

Webber, Matthew J

2016-09-01

Engineering materials using supramolecular principles enables generalizable and modular platforms that have tunable chemical, mechanical, and biological properties. Applying this bottom-up, molecular engineering-based approach to therapeutic design affords unmatched control of emergent properties and functionalities. In preparing responsive materials for biomedical applications, the dynamic character of typical supramolecular interactions facilitates systems that can more rapidly sense and respond to specific stimuli through a fundamental change in material properties or characteristics, as compared to cases where covalent bonds must be overcome. Several supramolecular motifs have been evaluated toward the preparation of "smart" materials capable of sensing and responding to stimuli. Triggers of interest in designing materials for therapeutic use include applied external fields, environmental changes, biological actuators, applied mechanical loading, and modulation of relative binding affinities. In addition, multistimuli-responsive routes can be realized that capture combinations of triggers for increased functionality. In sum, supramolecular engineering offers a highly functional strategy to prepare responsive materials. Future development and refinement of these approaches will improve precision in material formation and responsiveness, seek dynamic reciprocity in interactions with living biological systems, and improve spatiotemporal sensing of disease for better therapeutic deployment.

THE ENDOTHELIUM IN SEPSIS

PubMed Central

Ince, Can; Mayeux, Philip R.; Nguyen, Trung; Gomez, Hernando; Kellum, John A.; Ospina-Tascón, Gustavo A.; Hernandez, Glenn; Murray, Patrick; De Backer, Daniel

2017-01-01

Sepsis affects practically all aspects of endothelial cell (EC) function and is thought to be the key factor in the progression from sepsis to organ failure. Endothelial functions affected by sepsis include vasoregulation, barrier function, inflammation, and hemostasis. These are among other mechanisms often mediated by glycocalyx shedding, such as abnormal nitric oxide metabolism, up-regulation of reactive oxygen species generation due to down-regulation of endothelial-associated antioxidant defenses, transcellular communication, proteases, exposure of adhesion molecules, and activation of tissue factor. This review covers current insight in EC-associated hemostatic responses to sepsis and the EC response to inflammation. The endothelial cell lining is highly heterogeneous between different organ systems and consequently also in its response to sepsis. In this context, we discuss the response of the endothelial cell lining to sepsis in the kidney, liver, and lung. Finally, we discuss evidence as to whether the EC response to sepsis is adaptive or maladaptive. This study is a result of an Acute Dialysis Quality Initiative XIV Sepsis Workgroup meeting held in Bogota, Columbia, between October 12 and 15, 2014. PMID:26871664

An empirical propellant response function for combustion stability predictions

NASA Technical Reports Server (NTRS)

Hessler, R. O.

1980-01-01

An empirical response function model was developed for ammonium perchlorate propellants to supplant T-burner testing at the preliminary design stage. The model was developed by fitting a limited T-burner data base, in terms of oxidizer size and concentration, to an analytical two parameter response function expression. Multiple peaks are predicted, but the primary effect is of a single peak for most formulations, with notable bulges for the various AP size fractions. The model was extended to velocity coupling with the assumption that dynamic response was controlled primarily by the solid phase described by the two parameter model. The magnitude of velocity coupling was then scaled using an erosive burning law. Routine use of the model for stability predictions on a number of propulsion units indicates that the model tends to overpredict propellant response. It is concluded that the model represents a generally conservative prediction tool, suited especially for the preliminary design stage when T-burner data may not be readily available. The model work included development of a rigorous summation technique for pseudopropellant properties and of a concept for modeling ordered packing of particulates.

Quantitative Proteomic Profiling of Early and Late Responses to Salicylic Acid in Cucumber Leaves

PubMed Central

Li, Liang; Shang, Qing-Mao

2016-01-01

Salicylic acid (SA) is an important phytohormone that plays vital regulatory roles in plant growth, development, and stress responses. However, studies on the molecular mechanism of SA, especially during the early SA responses, are lagging behind. In this study, we initiated a comprehensive isobaric tag for relative and absolute quantitation (iTRAQ)-based proteomic analysis to explore the early and late SA-responsive proteins in leaves of cucumber (Cucumis sativus L.) seedlings. Upon SA application through the roots, endogenous SA accumulated in cucumber leaves. By assaying the changes in marker gene expression and photosynthetic rate, we collected samples at 12 h and 72 h post treatment (hpt) to profile the early and late SA responsiveness, respectively. The iTRAQ assay followed by tandem mass spectrometry revealed 135 differentially expressed proteins (DEPs) at 12 hpt and 301 DEPs at 72 hpt. The functional categories for these SA-responsive proteins included in a variety of biochemical processes, including photosynthesis, redox homeostasis, carbohydrate and energy metabolism, lipid metabolism, transport, protein folding and modification, proteolysis, cell wall organization, and the secondary phenylpropanoid pathway. Conclusively, based on the abundant changes of these DEPs, together with their putative functions, we proposed a possible SA-responsive protein network. It appears that SA could elicit reactive oxygen species (ROS) production via enhancing the photosynthetic electron transferring, and then confer some growth-promoting and stress-priming effects on cells during the late phase, including enhanced photosynthesis and ROS scavenging, altered carbon metabolic flux for the biosynthesis of amino acids and nucleotides, and cell wall reorganization. Overall, the present iTRAQ assay provides higher proteome coverage and deepened our understanding of the molecular basis of SA-responses. PMID:27551830

Recent Advances in Stimuli-Responsive Release Function Drug Delivery Systems for Tumor Treatment.

PubMed

Ding, Chendi; Tong, Ling; Feng, Jing; Fu, Jiajun

2016-12-20

Benefiting from the development of nanotechnology, drug delivery systems (DDSs) with stimuli-responsive controlled release function show great potential in clinical anti-tumor applications. By using a DDS, the harsh side effects of traditional anti-cancer drug treatments and damage to normal tissues and organs can be avoided to the greatest extent. An ideal DDS must firstly meet bio-safety standards and secondarily the efficiency-related demands of a large drug payload and controlled release function. This review highlights recent research progress on DDSs with stimuli-responsive characteristics. The first section briefly reviews the nanoscale scaffolds of DDSs, including mesoporous nanoparticles, polymers, metal-organic frameworks (MOFs), quantum dots (QDs) and carbon nanotubes (CNTs). The second section presents the main types of stimuli-responsive mechanisms and classifies these into two categories: intrinsic (pH, redox state, biomolecules) and extrinsic (temperature, light irradiation, magnetic field and ultrasound) ones. Clinical applications of DDS, future challenges and perspectives are also mentioned.

Rad-deletion Phenocopies Tonic Sympathetic Stimulation of the Heart.

PubMed

Levitan, Bryana M; Manning, Janet R; Withers, Catherine N; Smith, Jeffrey D; Shaw, Robin M; Andres, Douglas A; Sorrell, Vincent L; Satin, Jonathan

2016-12-01

Sympathetic stimulation modulates L-type calcium channel (LTCC) gating to contribute to increased systolic heart function. Rad is a monomeric G-protein that interacts with LTCC. Genetic deletion of Rad (Rad -/- ) renders LTCC in a sympathomimetic state. The study goal was to use a clinically inspired pharmacological stress echocardiography test, including analysis of global strain, to determine whether Rad -/- confers tonic positive inotropic heart function. Sarcomere dynamics and strain showed partial parallel isoproterenol (ISO) responsiveness for wild-type (WT) and for Rad -/- . Rad -/- basal inotropy was elevated compared to WT but was less responsiveness to ISO. Rad protein levels were lower in human patients with end-stage non-ischemic heart failure. These results show that Rad reduction provides a stable inotropic response rooted in sarcomere level function. Thus, reduced Rad levels in heart failure patients may be a compensatory response to need for increased output in the setting of HF. Rad deletion suggests a future therapeutic direction for inotropic support.

Rad-deletion Phenocopies Tonic Sympathetic Stimulation of the Heart

PubMed Central

Levitan, Bryana M.; Manning, Janet R.; Withers, Catherine N.; Smith, Jeffrey D.; Shaw, Robin M.; Andres, Douglas A.; Sorrell, Vincent L.

2016-01-01

Sympathetic stimulation modulates L-type calcium channel (LTCC) gating to contribute to increased systolic heart function. Rad is a monomeric G-protein that interacts with LTCC. Genetic deletion of Rad (Rad−/−) renders LTCC in a sympathomimetic state. The study goal was to use a clinically inspired pharmacological stress echocardiography test, including analysis of global strain, to determine whether Rad−/− confers tonic positive inotropic heart function. Sarcomere dynamics and strain showed partial parallel isoproterenol (ISO) responsiveness for wild-type (WT) and for Rad−/−. Rad−/− basal inotropy was elevated compared to WT but was less responsiveness to ISO. Rad protein levels were lower in human patients with end-stage non-ischemic heart failure. These results show that Rad reduction provides a stable inotropic response rooted in sarcomere level function. Thus, reduced Rad levels in heart failure patients may be a compensatory response to need for increased output in the setting of HF. Rad deletion suggests a future therapeutic direction for inotropic support. PMID:27798760

Functional networks in parallel with cortical development associate with executive functions in children.

PubMed

Zhong, Jidan; Rifkin-Graboi, Anne; Ta, Anh Tuan; Yap, Kar Lai; Chuang, Kai-Hsiang; Meaney, Michael J; Qiu, Anqi

2014-07-01

Children begin performing similarly to adults on tasks requiring executive functions in late childhood, a transition that is probably due to neuroanatomical fine-tuning processes, including myelination and synaptic pruning. In parallel to such structural changes in neuroanatomical organization, development of functional organization may also be associated with cognitive behaviors in children. We examined 6- to 10-year-old children's cortical thickness, functional organization, and cognitive performance. We used structural magnetic resonance imaging (MRI) to identify areas with cortical thinning, resting-state fMRI to identify functional organization in parallel to cortical development, and working memory/response inhibition tasks to assess executive functioning. We found that neuroanatomical changes in the form of cortical thinning spread over bilateral frontal, parietal, and occipital regions. These regions were engaged in 3 functional networks: sensorimotor and auditory, executive control, and default mode network. Furthermore, we found that working memory and response inhibition only associated with regional functional connectivity, but not topological organization (i.e., local and global efficiency of information transfer) of these functional networks. Interestingly, functional connections associated with "bottom-up" as opposed to "top-down" processing were more clearly related to children's performance on working memory and response inhibition, implying an important role for brain systems involved in late childhood. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Framing anomaly in the effective theory of the fractional quantum Hall effect.

PubMed

Gromov, Andrey; Cho, Gil Young; You, Yizhi; Abanov, Alexander G; Fradkin, Eduardo

2015-01-09

We consider the geometric part of the effective action for the fractional quantum Hall effect (FQHE). It is shown that accounting for the framing anomaly of the quantum Chern-Simons theory is essential to obtain the correct gravitational linear response functions. In the lowest order in gradients, the linear response generating functional includes Chern-Simons, Wen-Zee, and gravitational Chern-Simons terms. The latter term has a contribution from the framing anomaly which fixes the value of thermal Hall conductivity and contributes to the Hall viscosity of the FQH states on a sphere. We also discuss the effects of the framing anomaly on linear responses for non-Abelian FQH states.

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.

The endoplasmic reticulum: structure, function and response to cellular signaling.

PubMed

Schwarz, Dianne S; Blower, Michael D

2016-01-01

The endoplasmic reticulum (ER) is a large, dynamic structure that serves many roles in the cell including calcium storage, protein synthesis and lipid metabolism. The diverse functions of the ER are performed by distinct domains; consisting of tubules, sheets and the nuclear envelope. Several proteins that contribute to the overall architecture and dynamics of the ER have been identified, but many questions remain as to how the ER changes shape in response to cellular cues, cell type, cell cycle state and during development of the organism. Here we discuss what is known about the dynamics of the ER, what questions remain, and how coordinated responses add to the layers of regulation in this dynamic organelle.

Interleukin (IL)-33 and the IL-1 Family of Cytokines-Regulators of Inflammation and Tissue Homeostasis.

PubMed

Vasanthakumar, Ajithkumar; Kallies, Axel

2017-11-03

Cytokines play an integral role in shaping innate and adaptive immune responses. Members of the interleukin (IL)-1 family regulate a plethora of immune-cell-mediated processes, which include pathogen defense and tissue homeostasis. Notably, the IL-1 family cytokine IL-33 promotes adaptive and innate type 2 immune responses, confers viral protection and facilitates glucose metabolism and tissue repair. At the cellular level, IL-33 stimulates differentiation, maintenance, and function of various immune cell types, including regulatory T cells, effector CD4 + and CD8 + T cells, macrophages, and type 2 innate lymphoid cells (ILC2s). Other IL-1 family members, such as IL-1β and IL-18 promote type 1 responses, while IL-37 limits immune activation. Although IL-1 cytokines play critical roles in immunity and tissue repair, their deregulated expression is often linked to autoimmune and inflammatory diseases. Therefore, IL-1 cytokines are regulated tightly by posttranscriptional mechanisms and decoy receptors. In this review, we discuss the biology and function of IL-1 family cytokines, with a specific focus on regulation and function of IL-33 in immune and tissue homeostasis. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

Interplay between grain structure and protein adsorption on functional response of osteoblasts: ultrafine-grained versus coarse-grained substrates.

PubMed

Misra, R D K; Nune, C; Pesacreta, T C; Somani, M C; Karjalainen, L P

2013-01-01

The rapid adsorption of proteins is the starting and primary biological response that occurs when a biomedical device is implanted in the physiological system. The biological response, however, depends on the surface characteristics of the device. Considering the significant interest in nano-/ultrafine surfaces and nanostructured coatings, we describe here, the interplay between grain structure and protein adsorption (bovine serum albumin: BSA) on osteoblasts functions by comparing nanograined/ultrafine-grained (NG/UFG) and coarse-grained (CG: grain size in the micrometer range) substrates by investigating cell-substrate interactions. The protein adsorption on NG/UFG surface was beneficial in favorably modulating biological functions including cell attachment, proliferation, and viability, whereas the effect was less pronounced on protein adsorbed CG surface. Additionally, immunofluorescence studies demonstrated stronger vinculin signals associated with actin stress fibers in the outer regions of the cells and cellular extensions on protein adsorbed NG/UFG surface. The functional response followed the sequence: NG/UFG(BSA) > NG/UFG > CG(BSA) > CG. The differences in the cellular response on bare and protein adsorbed NG/UFG and CG surfaces are attributed to cumulative contribution of grain structure and degree of hydrophilicity. The study underscores the potential advantages of protein adsorption on artificial biomedical devices to enhance the bioactivity and regulate biological functions. Copyright © 2012 Wiley Periodicals, Inc.

Research Review: altered reward function in adolescent depression: what, when and how?

PubMed

Forbes, Erika E; Dahl, Ronald E

2012-01-01

Conceptual models and recent evidence indicate that neural response to reward is altered in depression. Taking a developmental approach to investigating reward function in adolescent depression can elucidate the etiology, pathophysiology and course of depression, a disorder that typically begins during adolescence and has high rates of recurrence. This conceptual review describes the what, when and how of altered reward function in adolescent depression. With the goal of generating new, testable hypotheses within a developmental affective neuroscience framework, we critically review findings and suggest future directions. Peer-reviewed empirical papers for inclusion in this critical review were obtained by searching PubMed, PsycInfo and ScienceDirect for the years 1990-2010. A pattern of low striatal response and high medial prefrontal response to reward is evident in adolescents and adults with depression. Given the salience of social stimuli for positive affect and depression, reward function might be especially disrupted in response to social rewards. Because of changes in the dopamine system and reward function with aging, altered reward function in depression might be more evident during adolescence than later in life; however, low reward function may also be a stable characteristic of people who experience depression. Mechanisms of altered reward function in depression could include disrupted balance of corticostriatal circuit function, with disruption occurring as aberrant adolescent brain development. Future studies should examine responses to social rewards; employ longitudinal and prospective designs; and investigate patterns of functional connectivity in reward circuits. Understanding altered reward function in depression has potential implications for treatment development. A more rigorous approach to investigating anhedonia, threat-reward interactions and comorbid anxiety will be valuable to future progress in describing the role of reward function in the pathophysiology of depression. © 2011 The Authors. Journal of Child Psychology and Psychiatry © 2011 Association for Child and Adolescent Mental Health.

Loudspeaker equalization for auditory research.

PubMed

MacDonald, Justin A; Tran, Phuong K

2007-02-01

The equalization of loudspeaker frequency response is necessary to conduct many types of well-controlled auditory experiments. This article introduces a program that includes functions to measure a loudspeaker's frequency response, design equalization filters, and apply the filters to a set of stimuli to be used in an auditory experiment. The filters can compensate for both magnitude and phase distortions introduced by the loudspeaker. A MATLAB script is included in the Appendix to illustrate the details of the equalization algorithm used in the program.

Pulmonary function response and effects of antioxidant genetic polymorphisms in healthy young adults exposed to low concentration ozone.

EPA Science Inventory

Rational: Ozone is known to induce a variety of pulmonary effects including decrement of spirometric lung function and inflammatory reaction, and antioxidant genes are known to play an important role in modulating the effects. It is unclear, however, if such effects may occur at...

Regeneration responses in partially-harvested riparian management zones in northern Minnesota

Treesearch

Douglas N. Kastendick; Brian J. Palik; Eric K. Zenner; Randy K. Kolka; Charles R. Blinn; Joshua J. Kragthorpe

2014-01-01

Trees serve important functions in riparian areas. Guidelines often suggest how riparian forests should be managed to sustain functions, including tree retention and increasing the component of conifers and later-successional species. While regeneration of early successional species is not discouraged, there is uncertainty about the ability to regenerate the latter...

The Impact of Missing Data on the Detection of Nonuniform Differential Item Functioning

ERIC Educational Resources Information Center

Finch, W. Holmes

2011-01-01

Missing information is a ubiquitous aspect of data analysis, including responses to items on cognitive and affective instruments. Although the broader statistical literature describes missing data methods, relatively little work has focused on this issue in the context of differential item functioning (DIF) detection. Such prior research has…

Prediction of Phyllosticta citricarpa using an hourly infection model and validation with prevalence data from South Africa and Australia

USDA-ARS?s Scientific Manuscript database

A simple hourly infection model was used for a risk assessment of citrus black spot (CBS) caused by Phyllosticta citricarpa. The infection model contained a temperature-moisture response function and also included functions to simulate ascospore release and dispersal of pycnidiospores. A validatio...

Dimerization and protease resistance: new insight into the function of PR-1

USDA-ARS?s Scientific Manuscript database

The group 1 pathogenesis-related (PR-1) proteins have long been considered hallmarks of hypersensitive response/defense pathways in plants, but their biochemical functions are still obscure despite resolution of the NMR/X-ray structures of several PR-1-like proteins, including P14a (the prototype PR...

Global hybrids from the semiclassical atom theory satisfying the local density linear response.

PubMed

Fabiano, Eduardo; Constantin, Lucian A; Cortona, Pietro; Della Sala, Fabio

2015-01-13

We propose global hybrid approximations of the exchange-correlation (XC) energy functional which reproduce well the modified fourth-order gradient expansion of the exchange energy in the semiclassical limit of many-electron neutral atoms and recover the full local density approximation (LDA) linear response. These XC functionals represent the hybrid versions of the APBE functional [Phys. Rev. Lett. 2011, 106, 186406] yet employing an additional correlation functional which uses the localization concept of the correlation energy density to improve the compatibility with the Hartree-Fock exchange as well as the coupling-constant-resolved XC potential energy. Broad energetic and structural testing, including thermochemistry and geometry, transition metal complexes, noncovalent interactions, gold clusters and small gold-molecule interfaces, as well as an analysis of the hybrid parameters, show that our construction is quite robust. In particular, our testing shows that the resulting hybrid, including 20% of Hartree-Fock exchange and named hAPBE, performs remarkably well for a broad palette of systems and properties, being generally better than popular hybrids (PBE0 and B3LYP). Semiempirical dispersion corrections are also provided.

Blimp-1 controls plasma cell function through the regulation of immunoglobulin secretion and the unfolded protein response.

PubMed

Tellier, Julie; Shi, Wei; Minnich, Martina; Liao, Yang; Crawford, Simon; Smyth, Gordon K; Kallies, Axel; Busslinger, Meinrad; Nutt, Stephen L

2016-03-01

Plasma cell differentiation requires silencing of B cell transcription, while it establishes antibody-secretory function and long-term survival. The transcription factors Blimp-1 and IRF4 are essential for the generation of plasma cells; however, their function in mature plasma cells has remained elusive. We found that while IRF4 was essential for the survival of plasma cells, Blimp-1 was dispensable for this. Blimp-1-deficient plasma cells retained their transcriptional identity but lost the ability to secrete antibody. Blimp-1 regulated many components of the unfolded protein response (UPR), including XBP-1 and ATF6. The overlap in the functions of Blimp-1 and XBP-1 was restricted to that response, with Blimp-1 uniquely regulating activity of the kinase mTOR and the size of plasma cells. Thus, Blimp-1 was required for the unique physiological ability of plasma cells that enables the secretion of protective antibody.

Comparing individual differences in inconsistency and plasticity as predictors of cognitive function in older adults.

PubMed

Grand, Jacob H G; Stawski, Robert S; MacDonald, Stuart W S

2016-01-01

Recent theorizing differentiates key constraints on cognition, including one's current range of processing efficiency (i.e., flexibility or inconsistency) as well as the capacity to expand flexibility over time (i.e., plasticity). The present study uses intensive assessment of response time data to examine the interplay between markers of intraindividual variability (inconsistency) and gains across biweekly retest sessions (plasticity) in relation to age-related cognitive function. Participants included 304 adults (aged 64 to 92 years: M = 74.02, SD = 5.95) from Project MIND, a longitudinal burst design study assessing performance across micro and macro intervals (response latency trials, weekly bursts, annual retests). For two reaction time (RT) measures (choice RT and one-back choice RT), baseline measures of RT inconsistency (intraindividual standard deviation, ISD, across trials at the first testing session) and plasticity (within-person performance gains in average RT across the 5 biweekly burst sessions) were computed and were then employed in linear mixed models as predictors of individual differences in cognitive function and longitudinal (6-year) rates of cognitive change. Independent of chronological age and years of education, higher RT inconsistency was associated uniformly with poorer cognitive function at baseline and with increased cognitive decline for measures of episodic memory and crystallized verbal ability. In contrast, predictive associations for plasticity were more modest for baseline cognitive function and were absent for 6-year cognitive change. These findings underscore the potential utility of response times for articulating inconsistency and plasticity as dynamic predictors of cognitive function in older adults.

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.

Nanoparticles functionalized with supramolecular host-guest systems for nanomedicine and healthcare.

PubMed

Wu, Zilong; Song, Nan; Menz, Ryan; Pingali, Bharadwaj; Yang, Ying-Wei; Zheng, Yuebing

2015-05-01

Synthetic macrocyclic host compounds can interact with suitable guest molecules via noncovalent interactions to form functional supramolecular systems. With the synergistic integration of the response of molecules and the unique properties at the nanoscale, nanoparticles functionalized with the host-guest supramolecular systems have shown great potentials for a broad range of applications in the fields of nanoscience and nanotechnology. In this review article, we focus on the applications of the nanoparticles functionalized with supramolecular host-guest systems in nanomedicine and healthcare, including therapeutic delivery, imaging, sensing and removal of harmful substances. A large number of examples are included to elucidate the working mechanisms, advantages, limitations and future developments of the nanoparticle-supramolecule systems in these applications.

On the Relationship Between Transfer Function-derived Response Times and Hydrograph Analysis Timing Parameters: Are there Similarities?

NASA Astrophysics Data System (ADS)

Bansah, S.; Ali, G.; Haque, M. A.; Tang, V.

2017-12-01

The proportion of precipitation that becomes streamflow is a function of internal catchment characteristics - which include geology, landscape characteristics and vegetation - and influence overall storage dynamics. The timing and quantity of water discharged by a catchment are indeed embedded in event hydrographs. Event hydrograph timing parameters, such as the response lag and time of concentration, are important descriptors of how long it takes the catchment to respond to input precipitation and how long it takes the latter to filter through the catchment. However, the extent to which hydrograph timing parameters relate to average response times derived from fitting transfer functions to annual hydrographs is unknown. In this study, we used a gamma transfer function to determine catchment average response times as well as event-specific hydrograph parameters across a network of eight nested watersheds ranging from 0.19 km2 to 74.6 km2 prairie catchments located in south central Manitoba (Canada). Various statistical analyses were then performed to correlate average response times - estimated using the parameters of the fitted gamma transfer function - to event-specific hydrograph parameters. Preliminary results show significant interannual variations in response times and hydrograph timing parameters: the former were in the order of a few hours to days, while the latter ranged from a few days to weeks. Some statistically significant relationships were detected between response times and event-specific hydrograph parameters. Future analyses will involve the comparison of statistical distributions of event-specific hydrograph parameters with that of runoff response times and baseflow transit times in order to quantity catchment storage dynamics across a range of temporal scales.

Inflammatory Responses and Barrier Function of Endothelial Cells Derived from Human Induced Pluripotent Stem Cells.

PubMed

Halaidych, Oleh V; Freund, Christian; van den Hil, Francijna; Salvatori, Daniela C F; Riminucci, Mara; Mummery, Christine L; Orlova, Valeria V

2018-05-08

Several studies have reported endothelial cell (EC) derivation from human induced pluripotent stem cells (hiPSCs). However, few have explored their functional properties in depth with respect to line-to-line and batch-to-batch variability and how they relate to primary ECs. We therefore carried out accurate characterization of hiPSC-derived ECs (hiPSC-ECs) from multiple (non-integrating) hiPSC lines and compared them with primary ECs in various functional assays, which included barrier function using real-time impedance spectroscopy with an integrated assay of electric wound healing, endothelia-leukocyte interaction under physiological flow to mimic inflammation and angiogenic responses in in vitro and in vivo assays. Overall, we found many similarities but also some important differences between hiPSC-derived and primary ECs. Assessment of vasculogenic responses in vivo showed little difference between primary ECs and hiPSC-ECs with regard to functional blood vessel formation, which may be important in future regenerative medicine applications requiring vascularization. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

78 FR 76190 - Proposed Agency Information Collection Activities; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-16

... received will advance three objectives: (i) reduce reporting burdens; (ii) ensure that it organizes.... FRA will summarize comments received in response to this notice in a subsequent notice and include... functions, including whether the activities will have practical utility; (ii) the accuracy of FRA's...

78 FR 39493 - Patient Protection and Affordable Care Act; Exchange Functions: Eligibility for Exemptions...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-01

...This final rule implements certain functions of the Affordable Insurance Exchanges (``Exchanges''). These specific statutory functions include determining eligibility for and granting certificates of exemption from the individual shared responsibility payment described in section 5000A of the Internal Revenue Code. Additionally, this final rule implements the responsibilities of the Secretary of Health and Human Services, in coordination with the Secretary of the Treasury, to designate other health benefits coverage as minimum essential coverage by providing that certain coverage be designated as minimum essential coverage. It also outlines substantive and procedural requirements that other types of individual coverage must fulfill in order to be certified as minimum essential coverage.

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

Macrobiota - helminths as active participants and partners of the microbiota in host intestinal homeostasis.

PubMed

Gause, William C; Maizels, Rick M

2016-08-01

Important insights have recently been gained in our understanding of the intricate relationship in the intestinal milieu between the vertebrate host mucosal immune response, commensal bacteria, and helminths. Helminths are metazoan worms (macrobiota) and trigger immune responses that include potent regulatory components capable of controlling harmful inflammation, protecting barrier function and mitigating tissue damage. They can secrete a variety of products that directly affect immune regulatory function but they also have the capacity to influence the composition of microbiota, which can also then impact immune function. Conversely, changes in microbiota can affect susceptibility to helminth infection, indicating that crosstalk between these two disparate groups of endobiota can play an essential role in host intestinal immune function and homeostasis. Copyright © 2016. Published by Elsevier Ltd.

Genetic influence on exercise-induced changes in physical function among mobility-limited older adults

PubMed Central

Hsu, Fang-Chi; Brinkley, Tina E.; Carter, Christy S.; Church, Timothy S.; Dodson, John A.; Goodpaster, Bret H.; McDermott, Mary M.; Nicklas, Barbara J.; Yank, Veronica; Johnson, Julie A.; Pahor, Marco

2014-01-01

To date, physical exercise is the only intervention consistently demonstrated to attenuate age-related declines in physical function. However, variability exists in seniors' responsiveness to training. One potential source of variability is the insertion (I allele) or deletion (D allele) of a 287 bp fragment in intron 16 of the angiotensin-converting enzyme (ACE) gene. This polymorphism is known to influence a variety of physiological adaptions to exercise. However, evidence is inconclusive regarding the influence of this polymorphism on older adults' functional responses to exercise. This study aimed to evaluate the association of ACE I/D genotypes with changes in physical function among Caucasian older adults (n = 283) following 12 mo of either structured, multimodal physical activity or health education. Measures of physical function included usual-paced gait speed and performance on the Short Physical Performance Battery (SPPB). After checking Hardy-Weinberg equilibrium, we used using linear regression to evaluate the genotype*treatment interaction for each outcome. Covariates included clinic site, body mass index, age, sex, baseline score, comorbidity, and use of angiotensin receptor blockers or ACE inhibitors. Genotype frequencies [II (19.4%), ID (42.4%), DD (38.2%)] were in Hardy-Weinberg equilibrium (P > 0.05). The genotype*treatment interaction was statistically significant for both gait speed (P = 0.002) and SPPB (P = 0.020). Exercise improved gait speed by 0.06 ± 0.01 m/sec and SPPB score by 0.72 ± 0.16 points among those with at least one D allele (ID/DD carriers), but function was not improved among II carriers. Thus, ACE I/D genotype appears to play a role in modulating functional responses to exercise training in seniors. PMID:24423970

CAVEOLINS AND LUNG FUNCTION

PubMed Central

Maniatis, Nikolaos A.; Chernaya, Olga; Shinin, Vasily; Minshall, Richard D.

2012-01-01

The primary function of the mammalian lung is to facilitate diffusion of oxygen to venous blood and to ventilate carbon dioxide produced by catabolic reactions within cells. However, it is also responsible for a variety of other important functions, including host defense and production of vasoactive agents to regulate not only systemic blood pressure, but also water, electrolyte and acid-base balance. Caveolin-1 is highly expressed in the majority of cell types in the lung, including epithelial, endothelial, smooth muscle, connective tissue cells, and alveolar macrophages. Deletion of caveolin-1 in these cells results in major functional aberrations, suggesting that caveolin-1 may be crucial to lung homeostasis and development. Furthermore, generation of mutant mice that under-express caveolin-1 results in severe functional distortion with phenotypes covering practically the entire spectrum of known lung diseases, including pulmonary hypertension, fibrosis, increased endothelial permeability, and immune defects. In this Chapter, we outline the current state of knowledge regarding caveolin-1-dependent regulation of pulmonary cell functions and discuss recent research findings on the role of caveolin-1 in various pulmonary disease states, including obstructive and fibrotic pulmonary vascular and inflammatory diseases. PMID:22411320

Development of the Coastal Zone Color Scanner for NIMBUS 7. Volume 2: Test and performance data, revision A

NASA Technical Reports Server (NTRS)

1979-01-01

The results of the Coastal Zone Color Scanner protoflight tests are examined in detail while some of the test results are evaluated with respect to expected performance. Performance characteristics examined include spectral response, signal to noise ratio as a function of radiance input, radiance response, the modulation transfer function, and the field of view and coregistration. The results of orbital sequence tests are also included. The in orbit performance or return of radiometric data in the six spectral bands is evaluated along with the data processing sequence necessary to derive the final data products. Examples of the raw data are given and the housekeeping or diagnostic data which provides information on the day to day health or status of the instrument are discussed.

Challenges and opportunities in healthcare volunteer management: insights from volunteer administrators.

PubMed

Rogers, Sean E; Rogers, Carmen M; Boyd, Karen D

2013-01-01

Volunteer administrators from 105 hospitals in five states in the northeast and southern United States provided open-ended survey responses about what they perceived to be the most pressing challenges and opportunities facing healthcare volunteer management. Taken together, these 105 hospitals used a total of 39,008 volunteers and 5.3 million volunteer hours during a 12-month period between 2010 and 2011. A qualitative content analysis of administrator responses suggests that primary challenges include volunteer recruitment and retention, administrative issues, and operational difficulties brought about by the current economic crisis. Key opportunities include more explicitly linking the volunteer function to hospital outcomes and community impact, expanding volunteer recruitment pools and roles and jobs, and developing organizational support for volunteers and making the volunteer management function more efficient and effective.

Community response to noise in Vietnam: exposure-response relationships based on the community tolerance level.

PubMed

Gjestland, Truls; Nguyen, Thu Lan; Yano, Takashi

2015-05-01

Social surveys on noise annoyance have been conducted in five different cities in Vietnam. The surveys included both aircraft noise (three airports) and road traffic noise (five cities). The main objective for these studies was to establish dose-response functions that were representative for Vietnam. The results have been compared with results from similar surveys from other regions. Dose-response functions for aircraft noise in Vietnam showing the percentage of highly annoyed people versus the noise level are nearly identical to those presented in the European Noise Directive [European Commission (2002). http://ec.europa.eu/environment/noise/directive.htm]. For road traffic noise, however, the results indicate that people in Vietnam are more tolerant. The noise levels can be increased by 5-10 dB in order to have a response similar to the curve recommended by the European Commission.

Centralized and Decentralized Control for Demand Response

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

Lu, Shuai; Samaan, Nader A.; Diao, Ruisheng

2011-04-29

Demand response has been recognized as an essential element of the smart grid. Frequency response, regulation and contingency reserve functions performed traditionally by generation resources are now starting to involve demand side resources. Additional benefits from demand response include peak reduction and load shifting, which will defer new infrastructure investment and improve generator operation efficiency. Technical approaches designed to realize these functionalities can be categorized into centralized control and decentralized control, depending on where the response decision is made. This paper discusses these two control philosophies and compares their relative advantages and disadvantages in terms of delay time, predictability, complexity,more » and reliability. A distribution system model with detailed household loads and controls is built to demonstrate the characteristics of the two approaches. The conclusion is that the promptness and reliability of decentralized control should be combined with the predictability and simplicity of centralized control to achieve the best performance of the smart grid.« less

Near-future carbon dioxide levels alter fish behaviour by interfering with neurotransmitter function

NASA Astrophysics Data System (ADS)

Nilsson, Göran E.; Dixson, Danielle L.; Domenici, Paolo; McCormick, Mark I.; Sørensen, Christina; Watson, Sue-Ann; Munday, Philip L.

2012-03-01

Predicted future CO2 levels have been found to alter sensory responses and behaviour of marine fishes. Changes include increased boldness and activity, loss of behavioural lateralization, altered auditory preferences and impaired olfactory function. Impaired olfactory function makes larval fish attracted to odours they normally avoid, including ones from predators and unfavourable habitats. These behavioural alterations have significant effects on mortality that may have far-reaching implications for population replenishment, community structure and ecosystem function. However, the underlying mechanism linking high CO2 to these diverse responses has been unknown. Here we show that abnormal olfactory preferences and loss of behavioural lateralization exhibited by two species of larval coral reef fish exposed to high CO2 can be rapidly and effectively reversed by treatment with an antagonist of the GABA-A receptor. GABA-A is a major neurotransmitter receptor in the vertebrate brain. Thus, our results indicate that high CO2 interferes with neurotransmitter function, a hitherto unrecognized threat to marine populations and ecosystems. Given the ubiquity and conserved function of GABA-A receptors, we predict that rising CO2 levels could cause sensory and behavioural impairment in a wide range of marine species, especially those that tightly control their acid-base balance through regulatory changes in HCO3- and Cl- levels.

Principles of disaster management lesson. 12: structuring organizations.

PubMed

Cuny, F C

2001-01-01

This lesson discusses various structures for organizations that have functional roles in disaster responses, relief, and/or management activities. It distinguishes between pyramidal and matrix structures, and notes the advantages and disadvantages of each in relation to disasters. Span of control issues are dissected including the impact of the "P" factor on the performance of disaster managers and workers including its relationship to the coordination and control function. The development of a Table of Organization and how it relates to departmentalization within an organization also is provided.

X-Ray Spectro-Polarimetry with Photoelectric Polarimeters

NASA Technical Reports Server (NTRS)

Strohmayer, T. E.

2017-01-01

We derive a generalization of forward fitting for X-ray spectroscopy to include linear polarization of X-ray sources, appropriate for the anticipated next generation of space-based photoelectric polarimeters. We show that the inclusion of polarization sensitivity requires joint fitting to three observed spectra, one for each of the Stokes parameters, I(E), U(E), and Q(E). The equations for StokesI (E) (the total intensity spectrum) are identical to the familiar case with no polarization sensitivity, and for which the model-predicted spectrum is obtained by a convolution of the source spectrum, F (E), with the familiar energy response function,(E) R(E,E), where (E) and R(E,E) are the effective area and energy redistribution matrix, respectively. In addition to the energy spectrum, the two new relations for U(E) and Q(E) include the source polarization fraction and position angle versus energy, a(E), and 0(E), respectively, and the model-predicted spectra for these relations are obtained by a convolution with the modulated energy response function, (E)(E) R(E,E), where(E) is the energy-dependent modulation fraction that quantifies a polarimeters angular response to 100 polarized radiation. We present results of simulations with response parameters appropriate for the proposed PRAXyS Small Explorer observatory to illustrate the procedures and methods, and we discuss some aspects of photoelectric polarimeters with relevance to understanding their calibration and operation.

Canonical TGF-β Signaling Pathway Represses Human NK Cell Metabolism.

PubMed

Zaiatz-Bittencourt, Vanessa; Finlay, David K; Gardiner, Clair M

2018-06-15

Cytokines stimulate rapid metabolic changes in human NK cells, including increases in both glycolysis and oxidative phosphorylation pathways. However, how these are subsequently regulated is not known. In this study, we demonstrate that TGF-β can inhibit many of these metabolic changes, including oxidative phosphorylation, glycolytic capacity, and respiratory capacity. TGF-β also inhibited cytokine-induced expression of the transferrin nutrient receptor CD71. In contrast to a recent report on murine NK cells, TGF-β-mediated suppression of these metabolic responses did not involve the inhibition of the metabolic regulator mTORC1. Inhibition of the canonical TGF-β signaling pathway was able to restore almost all metabolic and functional responses that were inhibited by TGF-β. These data suggest that pharmacological inhibition of TGF-β could provide a metabolic advantage to NK cells that is likely to result in improved functional responses. This has important implications for NK cell-based cancer immunotherapies. Copyright © 2018 by The American Association of Immunologists, Inc.

Theoretical modeling of electron mobility in superfluid {sup 4}He

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

Aitken, Frédéric; Bonifaci, Nelly; Haeften, Klaus von

The Orsay-Trento bosonic density functional theory model is extended to include dissipation due to the viscous response of superfluid {sup 4}He present at finite temperatures. The viscous functional is derived from the Navier-Stokes equation by using the Madelung transformation and includes the contribution of interfacial viscous response present at the gas-liquid boundaries. This contribution was obtained by calibrating the model against the experimentally determined electron mobilities from 1.2 K to 2.1 K along the saturated vapor pressure line, where the viscous response is dominated by thermal rotons. The temperature dependence of ion mobility was calculated for several different solvation cavitymore » sizes and the data are rationalized in the context of roton scattering and Stokes limited mobility models. Results are compared to the experimentally observed “exotic ion” data, which provides estimates for the corresponding bubble sizes in the liquid. Possible sources of such ions are briefly discussed.« less

The receptor-like cytoplasmic kinase BSR1 mediates chitin-induced defense signaling in rice cells.

PubMed

Kanda, Yasukazu; Yokotani, Naoki; Maeda, Satoru; Nishizawa, Yoko; Kamakura, Takashi; Mori, Masaki

2017-08-01

Broad-Spectrum Resistance 1 (BSR1) encodes a rice receptor-like cytoplasmic kinase, and enhances disease resistance when overexpressed. Rice plants overexpressing BSR1 are highly resistant to diverse pathogens, including rice blast fungus. However, the mechanism responsible for this resistance has not been fully characterized. To analyze the BSR1 function, BSR1-knockout (BSR1-KO) plants were generated using a clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) system. Experiments using suspension-cultured cells revealed that defense responses including H 2 O 2 production (i.e. oxidative burst) and expression of defense-related genes induced by autoclaved conidia of the rice blast fungus significantly decreased in BSR1-KO cells. Furthermore, a treatment with chitin oligomers which function as microbe-associated molecular patterns (MAMPs) of the rice blast fungus resulted in considerably suppressed defense responses in BSR1-KO cells. These results suggest that BSR1 is important for the rice innate immunity triggered by the perception of chitin.

The Escherichia coli Cpx envelope stress response regulates genes of diverse function that impact antibiotic resistance and membrane integrity.

PubMed

Raivio, Tracy L; Leblanc, Shannon K D; Price, Nancy L

2013-06-01

The Cpx envelope stress response mediates adaptation to stresses that cause envelope protein misfolding. Adaptation is partly conferred through increased expression of protein folding and degradation factors. The Cpx response also plays a conserved role in the regulation of virulence determinant expression and impacts antibiotic resistance. We sought to identify adaptive mechanisms that may be involved in these important functions by characterizing changes in the transcriptome of two different Escherichia coli strains when the Cpx response is induced. We show that, while there is considerable strain- and condition-specific variability in the Cpx response, the regulon is enriched for proteins and functions that are inner membrane associated under all conditions. Genes that were changed by Cpx pathway induction under all conditions were involved in a number of cellular functions and included several intergenic regions, suggesting that posttranscriptional regulation is important during Cpx-mediated adaptation. Some Cpx-regulated genes are centrally involved in energetics and play a role in antibiotic resistance. We show that a number of small, uncharacterized envelope proteins are Cpx regulated and at least two of these affect phenotypes associated with membrane integrity. Altogether, our work suggests new mechanisms of Cpx-mediated envelope stress adaptation and antibiotic resistance.

Nuclear Cytoplasmic Trafficking of Proteins is a Major Response of Human Fibroblasts to Oxidative Stress

PubMed Central

Baqader, Noor O.; Radulovic, Marko; Crawford, Mark; Stoeber, Kai; Godovac-Zimmermann, Jasminka

2014-01-01

We have used a subcellular spatial razor approach based on LC–MS/MS-based proteomics with SILAC isotope labeling to determine changes in protein abundances in the nuclear and cytoplasmic compartments of human IMR90 fibroblasts subjected to mild oxidative stress. We show that response to mild tert-butyl hydrogen peroxide treatment includes redistribution between the nucleus and cytoplasm of numerous proteins not previously associated with oxidative stress. The 121 proteins with the most significant changes encompass proteins with known functions in a wide variety of subcellular locations and of cellular functional processes (transcription, signal transduction, autophagy, iron metabolism, TCA cycle, ATP synthesis) and are consistent with functional networks that are spatially dispersed across the cell. Both nuclear respiratory factor 2 and the proline regulatory axis appear to contribute to the cellular metabolic response. Proteins involved in iron metabolism or with iron/heme as a cofactor as well as mitochondrial proteins are prominent in the response. Evidence suggesting that nuclear import/export and vesicle-mediated protein transport contribute to the cellular response was obtained. We suggest that measurements of global changes in total cellular protein abundances need to be complemented with measurements of the dynamic subcellular spatial redistribution of proteins to obtain comprehensive pictures of cellular function. PMID:25133973

The RtcB RNA ligase is an essential component of the metazoan unfolded protein response.

PubMed

Kosmaczewski, Sara Guckian; Edwards, Tyson James; Han, Sung Min; Eckwahl, Matthew J; Meyer, Benjamin Isaiah; Peach, Sally; Hesselberth, Jay R; Wolin, Sandra L; Hammarlund, Marc

2014-12-01

RNA ligation can regulate RNA function by altering RNA sequence, structure and coding potential. For example, the function of XBP1 in mediating the unfolded protein response requires RNA ligation, as does the maturation of some tRNAs. Here, we describe a novel in vivo model in Caenorhabditis elegans for the conserved RNA ligase RtcB and show that RtcB ligates the xbp-1 mRNA during the IRE-1 branch of the unfolded protein response. Without RtcB, protein stress results in the accumulation of unligated xbp-1 mRNA fragments, defects in the unfolded protein response, and decreased lifespan. RtcB also ligates endogenous pre-tRNA halves, and RtcB mutants have defects in growth and lifespan that can be bypassed by expression of pre-spliced tRNAs. In addition, animals that lack RtcB have defects that are independent of tRNA maturation and the unfolded protein response. Thus, RNA ligation by RtcB is required for the function of multiple endogenous target RNAs including both xbp-1 and tRNAs. RtcB is uniquely capable of performing these ligation functions, and RNA ligation by RtcB mediates multiple essential processes in vivo. © 2014 The Authors.

The RtcB RNA ligase is an essential component of the metazoan unfolded protein response

PubMed Central

Kosmaczewski, Sara Guckian; Edwards, Tyson James; Han, Sung Min; Eckwahl, Matthew J; Meyer, Benjamin Isaiah; Peach, Sally; Hesselberth, Jay R; Wolin, Sandra L; Hammarlund, Marc

2014-01-01

RNA ligation can regulate RNA function by altering RNA sequence, structure and coding potential. For example, the function of XBP1 in mediating the unfolded protein response requires RNA ligation, as does the maturation of some tRNAs. Here, we describe a novel in vivo model in Caenorhabditis elegans for the conserved RNA ligase RtcB and show that RtcB ligates the xbp-1 mRNA during the IRE-1 branch of the unfolded protein response. Without RtcB, protein stress results in the accumulation of unligated xbp-1 mRNA fragments, defects in the unfolded protein response, and decreased lifespan. RtcB also ligates endogenous pre-tRNA halves, and RtcB mutants have defects in growth and lifespan that can be bypassed by expression of pre-spliced tRNAs. In addition, animals that lack RtcB have defects that are independent of tRNA maturation and the unfolded protein response. Thus, RNA ligation by RtcB is required for the function of multiple endogenous target RNAs including both xbp-1 and tRNAs. RtcB is uniquely capable of performing these ligation functions, and RNA ligation by RtcB mediates multiple essential processes in vivo. Subject Categories Protein Biosynthesis & Quality Control; RNA Biology PMID:25366321

Assessing and improving cross-border chemical incident preparedness and response across Europe.

PubMed

Stewart-Evans, James; Hall, Lisbeth; Czerczak, Slawomir; Manley, Kevin; Dobney, Alec; Hoffer, Sally; Pałaszewska-Tkacz, Anna; Jankowska, Agnieszka

2014-11-01

Good practices in emergency preparedness and response for chemical incidents include practices specific to the different functions of exposure assessment (e.g., within the monitoring function, the use of mobile monitoring equipment; within the modelling function, the use of rapid dispersion models with integrated mapping software) and generic practices to engage incident response stakeholders to maximise exposure assessment capabilities (e.g., sharing protocols and pre-prepared information and multi-agency training and exercising). Such practices can optimise cross-border collaboration. A wide range of practices have been implemented across MSs during chemical incident response, particularly during incidents that have cross-border and trans-boundary impacts. This paper proposes a self-assessment methodology to enable MSs, or organisations within MSs, to examine exposure assessment capabilities and communication pathways between exposure assessors and public health risk assessors. Where gaps exist, this methodology provides links to good practices that could improve response, communication and collaboration across local, regional and national borders. A fragmented approach to emergency preparedness for chemical incidents is a major obstacle to improving cross-border exposure assessment. There is no one existing body or structure responsible for all aspects of chemical incident preparedness and response in the European Union. Due to the range of different organisations and networks involved in chemical incident response, emergency preparedness needs to be drawn together. A number of recommendations are proposed, including the use of networks of experts which link public health risk assessors with experts in exposure assessment, in order to coordinate and improve chemical incident emergency preparedness. The EU's recent Decision on serious cross-border threats to health aims to facilitate MSs' compliance with the International Health Regulations, which require reporting and communication regarding significant chemical incidents. This provides a potential route to build on in order to improve chemical incident preparedness and response across Europe. Copyright © 2014 Elsevier Ltd. All rights reserved.

An investigation of the validity of six measures of physical function in people awaiting joint replacement surgery of the hip or knee.

PubMed

Gill, Stephen D; de Morton, Natalie A; Mc Burney, Helen

2012-10-01

To assess and compare the validity of six physical function measures in people awaiting hip or knee joint replacement. Eighty-two people awaiting hip or knee replacement were assessed using six physical function measures including the WOMAC Function scale, SF-36 Physical Function scale, SF-36 Physical Component Summary scale, Patient Specific Functional Scale, 30-second chair stand test, and 50-foot timed walk. Validity was assessed using a head-to-head comparison design. Convergent validity was demonstrated with significant correlations between most measures (Spearman's rho 0.22 to 0.71). The Patient Specific Functional Scale had the lowest correlations with other measures of physical function. Discriminant validity was demonstrated with low correlations between mental health and physical function scores (Spearman's rho -0.12 to 0.33). Only the WOMAC Function scale, 30-second chair stand test, and 50-foot timed walk demonstrated known groups validity when scores for participants who walked with a gait aid were compared with those who did not. Standardized response means and Guyatt's responsiveness indexes indicated that the SF-36 was the least responsive measure. For those awaiting joint replacement surgery of the hip or knee, the current investigation found that the WOMAC Function scale, 30-second chair stand test, and 50-foot timed walk demonstrated the most evidence of validity. The Patient Specific Functional Scale might complement other measures by capturing a different aspect of physical function.

Dynamic visualization of data streams

DOEpatents

Wong, Pak Chung [Richalnd, WA; Foote, Harlan P [Richland, WA; Adams, Daniel R [Kennewick, WA; Cowley, Wendy E [Richland, WA; Thomas, James J [Richland, WA

2009-07-07

One embodiment of the present invention includes a data communication subsystem to receive a data stream, and a data processing subsystem responsive to the data communication subsystem to generate a visualization output based on a group of data vectors corresponding to a first portion of the data stream. The processing subsystem is further responsive to a change in rate of receipt of the data to modify the visualization output with one or more other data vectors corresponding to a second portion of the data stream as a function of eigenspace defined with the group of data vectors. The system further includes a display device responsive to the visualization output to provide a corresponding visualization.

Form factors for dark matter capture by the Sun in effective theories

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

Catena, Riccardo; Schwabe, Bodo

2015-04-24

In the effective theory of isoscalar and isovector dark matter-nucleon interactions mediated by a heavy spin-1 or spin-0 particle, 8 isotope-dependent nuclear response functions can be generated in the dark matter scattering by nuclei. We compute the 8 nuclear response functions for the 16 most abundant elements in the Sun, i.e. H, {sup 3}He, {sup 4}He, {sup 12}C, {sup 14}N, {sup 16}O, {sup 20}Ne, {sup 23}Na, {sup 24}Mg, {sup 27}Al, {sup 28}Si, {sup 32}S, {sup 40}Ar, {sup 40}Ca, {sup 56}Fe, and {sup 59}Ni, through numerical shell model calculations. We use our response functions to compute the rate of dark mattermore » capture by the Sun for all isoscalar and isovector dark matter-nucleon effective interactions, including several operators previously considered for dark matter direct detection only. We study in detail the dependence of the capture rate on specific dark matter-nucleon interaction operators, and on the different elements in the Sun. We find that a so far neglected momentum dependent dark matter coupling to the nuclear vector charge gives a larger contribution to the capture rate than the constant spin-dependent interaction commonly included in dark matter searches at neutrino telescopes. Our investigation lays the foundations for model independent analyses of dark matter induced neutrino signals from the Sun. The nuclear response functions obtained in this study are listed in analytic form in an appendix, ready to be used in other projects.« less

Age‐related alterations in immune responses to West Nile virus infection

PubMed Central

2016-01-01

Summary West Nile virus (WNV) is the most important causative agent of viral encephalitis worldwide and an important public health concern in the United States due to its high prevalence, severe disease, and the absence of effective treatments. Infection with WNV is mainly asymptomatic, but some individuals develop severe, possibly fatal, neurological disease. Individual host factors play a role in susceptibility to WNV infection, including genetic polymorphisms in key anti‐viral immune genes, but age is the most well‐defined risk factor for susceptibility to severe disease. Ageing is associated with distinct changes in immune cells and a decline in immune function leading to increased susceptibility to infection and reduced responses to vaccination. WNV is detected by pathogen recognition receptors including Toll‐like receptors (TLRs), which show reduced expression and function in ageing. Neutrophils, monocyte/macrophages and dendritic cells, which first recognize and respond to infection, show age‐related impairment of many functions relevant to anti‐viral responses. Natural killer cells control many viral infections and show age‐related changes in phenotype and functional responses. A role for the regulatory receptors Mertk and Axl in blood–brain barrier permeability and in facilitating viral uptake through phospholipid binding may be relevant for susceptibility to WNV, and age‐related up‐regulation of Axl has been noted previously in human dendritic cells. Understanding the specific immune parameters and mechanisms that influence susceptibility to symptomatic WNV may lead to a better understanding of increased susceptibility in elderly individuals and identify potential avenues for therapeutic approaches: an especially relevant goal, as the world's populating is ageing. PMID:27612657

Characterization of long-range functional connectivity in epileptic networks by neuronal spike-triggered local field potentials

NASA Astrophysics Data System (ADS)

Lopour, Beth A.; Staba, Richard J.; Stern, John M.; Fried, Itzhak; Ringach, Dario L.

2016-04-01

Objective. Quantifying the relationship between microelectrode-recorded multi-unit activity (MUA) and local field potentials (LFPs) in distinct brain regions can provide detailed information on the extent of functional connectivity in spatially widespread networks. These methods are common in studies of cognition using non-human animal models, but are rare in humans. Here we applied a neuronal spike-triggered impulse response to electrophysiological recordings from the human epileptic brain for the first time, and we evaluate functional connectivity in relation to brain areas supporting the generation of seizures. Approach. Broadband interictal electrophysiological data were recorded from microwires adapted to clinical depth electrodes that were implanted bilaterally using stereotactic techniques in six presurgical patients with medically refractory epilepsy. MUA and LFPs were isolated in each microwire, and we calculated the impulse response between the MUA on one microwire and the LFPs on a second microwire for all possible MUA/LFP pairs. Results were compared to clinical seizure localization, including sites of seizure onset and interictal epileptiform discharges. Main results. We detected significant interictal long-range functional connections in each subject, in some cases across hemispheres. Results were consistent between two independent datasets, and the timing and location of significant impulse responses reflected anatomical connectivity. However, within individual subjects, the spatial distribution of impulse responses was unique. In two subjects with clear seizure localization and successful surgery, the epileptogenic zone was associated with significant impulse responses. Significance. The results suggest that the spike-triggered impulse response can provide valuable information about the neuronal networks that contribute to seizures using only interictal data. This technique will enable testing of specific hypotheses regarding functional connectivity in epilepsy and the relationship between functional properties and imaging findings. Beyond epilepsy, we expect that the impulse response could be more broadly applied as a measure of long-range functional connectivity in studies of cognition.

Characterization of long-range functional connectivity in epileptic networks by neuronal spike-triggered local field potentials

PubMed Central

Lopour, Beth A; Staba, Richard J; Stern, John M; Fried, Itzhak; Ringach, Dario L

2017-01-01

Objective Quantifying the relationship between microelectrode-recorded multi-unit activity (MUA) and local field potentials (LFPs) in distinct brain regions can provide detailed information on the extent of functional connectivity in spatially widespread networks. These methods are common in studies of cognition using non-human animal models, but are rare in humans. Here we applied a neuronal spike-triggered impulse response to electrophysiological recordings from the human epileptic brain for the first time, and we evaluate functional connectivity in relation to brain areas supporting the generation of seizures. Approach Broadband interictal electrophysiological data were recorded from microwires adapted to clinical depth electrodes that were implanted bilaterally using stereotactic techniques in six presurgical patients with medically refractory epilepsy. MUA and LFPs were isolated in each microwire, and we calculated the impulse response between the MUA on one microwire and the LFPs on a second microwire for all possible MUA/LFP pairs. Results were compared to clinical seizure localization, including sites of seizure onset and interictal epileptiform discharges. Main results We detected significant interictal long-range functional connections in each subject, in some cases across hemispheres. Results were consistent between two independent datasets, and the timing and location of significant impulse responses reflected anatomical connectivity. However, within individual subjects, the spatial distribution of impulse responses was unique. In two subjects with clear seizure localization and successful surgery, the epileptogenic zone was associated with significant impulse responses. Significance The results suggest that the spike-triggered impulse response can provide valuable information about the neuronal networks that contribute to seizures using only interictal data. This technique will enable testing of specific hypotheses regarding functional connectivity in epilepsy and the relationship between functional properties and imaging findings. Beyond epilepsy, we expect that the impulse response could be more broadly applied as a measure of long-range functional connectivity in studies of cognition. PMID:26975603

Functional plasticity of macrophages: in situ reprogramming of tumor-associated macrophages

PubMed Central

Stout, Robert D.; Watkins, Stephanie K.; Suttles, Jill

2009-01-01

The extent to which the functional heterogeneity of Mϕs is dependent on the differentiation of functional sublineages remains unresolved. One alternative hypothesis proposes that Mϕs are functionally plastic cells, which are capable of altering their functional activities progressively in response to progressively changing signaling molecules generated in their microenvironment. This “functional plasticity” hypothesis predicts that the functionally polarized Mϕs in chronic pathologies do not represent Mϕ sublineages but rather, are mutable phenotypes sustained by chronic signaling from the pathological environment. Solid TAMϕs are chronically polarized to provide activities that support tumor growth and metastasis and suppress adaptive immune responses. In support of the functional plasticity hypothesis, administration of slow-release microsphere-encapsulated IL-12 successfully reprogrammed TAMϕs in situ, reducing Mϕ support of tumor growth and metastasis and enhancing Mϕ proimmunogenic activities. Increased knowledge of how Mϕ function is regulated and how polarized Mϕs can be reprogrammed in situ will increase our ability to control Mϕ function in a variety of pathological states, including cancer and chronic inflammatory disease. PMID:19605698

Development from childhood to adulthood increases morphological and functional inter-individual variability in the right superior temporal cortex.

PubMed

Bonte, Milene; Frost, Martin A; Rutten, Sanne; Ley, Anke; Formisano, Elia; Goebel, Rainer

2013-12-01

We study the developmental trajectory of morphology and function of the superior temporal cortex (STC) in children (8-9 years), adolescents (14-15 years) and young adults. We analyze cortical surface landmarks and functional MRI (fMRI) responses to voices, other natural categories and tones and examine how hemispheric asymmetry and inter-subject variability change across age. Our results show stable morphological asymmetries across age groups, including a larger left planum temporale and a deeper right superior temporal sulcus. fMRI analyses show that a rightward lateralization for voice-selective responses is present in all groups but decreases with age. Furthermore, STC responses to voices change from being less selective and more spatially diffuse in children to highly selective and focal in adults. Interestingly, the analysis of morphological landmarks reveals that inter-subject variability increases during development in the right--but not in the left--STC. Similarly, inter-subject variability of cortically-realigned functional responses to voices, other categories and tones increases with age in the right STC. Our findings reveal asymmetric developmental changes in brain regions crucial for auditory and voice perception. The age-related increase of inter-subject variability in right STC suggests that anatomy and function of this region are shaped by unique individual developmental experiences. © 2013.

Longer growing seasons shift grassland vegetation towards more-productive species

NASA Astrophysics Data System (ADS)

Fridley, Jason D.; Lynn, Josh S.; Grime, J. P.; Askew, A. P.

2016-09-01

Despite advances in plant functional ecology that provide a framework for predicting the responses of vegetation to environmental change, links between plant functional strategies and elevated temperatures are poorly understood. Here, we analyse the response of a species-rich grassland in northern England to two decades of temperature and rainfall manipulations in the context of the functional attributes of 21 coexisting species that represent a large array of resource-use strategies. Three principal traits, including body size (canopy height), tissue investment (leaf construction cost), and seed size, varied independently across species and reflect tradeoffs associated with competitiveness, stress tolerance, and colonization ability. Unlike past studies, our results reveal a strong association between functional traits and temperature regime; species favoured by extended growing seasons have taller canopies and faster assimilation rates, which has come at the expense of those species of high tissue investment. This trait-warming association was three times higher in deep soils, suggesting species shifts have been strongly mediated by competition. In contrast, vegetation shifts from rainfall manipulations have been associated only with tissue investment. Functional shifts towards faster growing species in response to warming may be responsible for a marginal increase in productivity in a system that was assumed to be nutrient-limited.

H2S Regulates Hypobaric Hypoxia-Induced Early Glio-Vascular Dysfunction and Neuro-Pathophysiological Effects

PubMed Central

Kumar, Gaurav; Chhabra, Aastha; Mishra, Shalini; Kalam, Haroon; Kumar, Dhiraj; Meena, Ramniwas; Ahmad, Yasmin; Bhargava, Kalpana; Prasad, Dipti N.; Sharma, Manish

2016-01-01

Hypobaric Hypoxia (HH) is an established risk factor for various neuro-physiological perturbations including cognitive impairment. The origin and mechanistic basis of such responses however remain elusive. We here combined systems level analysis with classical neuro-physiological approaches, in a rat model system, to understand pathological responses of brain to HH. Unbiased ‘statistical co-expression networks’ generated utilizing temporal, differential transcriptome signatures of hippocampus—centrally involved in regulating cognition—implicated perturbation of Glio-Vascular homeostasis during early responses to HH, with concurrent modulation of vasomodulatory, hemostatic and proteolytic processes. Further, multiple lines of experimental evidence from ultra-structural, immuno-histological, substrate-zymography and barrier function studies unambiguously supported this proposition. Interestingly, we show a significant lowering of H2S levels in the brain, under chronic HH conditions. This phenomenon functionally impacted hypoxia-induced modulation of cerebral blood flow (hypoxic autoregulation) besides perturbing the strength of functional hyperemia responses. The augmentation of H2S levels, during HH conditions, remarkably preserved Glio-Vascular homeostasis and key neuro-physiological functions (cerebral blood flow, functional hyperemia and spatial memory) besides curtailing HH-induced neuronal apoptosis in hippocampus. Our data thus revealed causal role of H2S during HH-induced early Glio-Vascular dysfunction and consequent cognitive impairment. PMID:27211559

Technical Advance: Live-imaging analysis of human dendritic cell migrating behavior under the influence of immune-stimulating reagents in an organotypic model of lung

PubMed Central

Nguyen Hoang, Anh Thu; Chen, Puran; Björnfot, Sofia; Högstrand, Kari; Lock, John G.; Grandien, Alf; Coles, Mark; Svensson, Mattias

2014-01-01

This manuscript describes technical advances allowing manipulation and quantitative analyses of human DC migratory behavior in lung epithelial tissue. DCs are hematopoietic cells essential for the maintenance of tissue homeostasis and the induction of tissue-specific immune responses. Important functions include cytokine production and migration in response to infection for the induction of proper immune responses. To design appropriate strategies to exploit human DC functional properties in lung tissue for the purpose of clinical evaluation, e.g., candidate vaccination and immunotherapy strategies, we have developed a live-imaging assay based on our previously described organotypic model of the human lung. This assay allows provocations and subsequent quantitative investigations of DC functional properties under conditions mimicking morphological and functional features of the in vivo parental tissue. We present protocols to set up and prepare tissue models for 4D (x, y, z, time) fluorescence-imaging analysis that allow spatial and temporal studies of human DCs in live epithelial tissue, followed by flow cytometry analysis of DCs retrieved from digested tissue models. This model system can be useful for elucidating incompletely defined pathways controlling DC functional responses to infection and inflammation in lung epithelial tissue, as well as the efficacy of locally administered candidate interventions. PMID:24899587

Heavy particle irradiation, neurochemistry and behavior: thresholds, dose- response curves and recovery of function

NASA Astrophysics Data System (ADS)

Rabin, B.; Joseph, J.; Shukitt-Hale, B.

Exposure to heavy particles can affect the functioning of the central nervous system (CNS), particularly the dopaminergic system. In turn, the radiation- induced disruption of dopaminergic function disrupts a variety of behaviors that are dependent upon the integrity of the dopaminergic system, including motor behavior (upper body strength), amphetamine (dopamine)-mediated taste aversion learning, spatial learning and memory (Morris water maze), and operant conditioning (fixed-ratio bar pressing). Although the relationships between heavy particle irradiation and the effects of exposure depend, to some extent, upon the specific behavioral or neurochemical endpoint under consideration, a review of the available research leads to the hypothesis that the endpoints mediated by the CNS have certain characteristics in common. These include: (1) a threshold, below which there is no apparent effect; (2) the lack of a dose-response relationship, or an extremely steep dose-response curve, depending on the particular endpoint; and (3) the absence of recovery of function, such that the heavy particle-induced behavioral and neural changes are present when tested up to one year following exposure. The current presentation will review the data relevant to the degree to which these characteristics are in fact common to neurochemical and behavioral endpoints that are mediated by the effects of exposure to heavy particles on CNS activity. Supported by N.A.S.A. Grant NAG9-1190.

Isotype Diversification of IgG Antibodies to HIV Gag Proteins as a Therapeutic Vaccination Strategy for HIV Infection.

PubMed

French, Martyn A; Abudulai, Laila N; Fernandez, Sonia

2013-08-09

The development of vaccines to treat and prevent human immunodeficiency virus (HIV) infection has been hampered by an incomplete understanding of "protective" immune responses against HIV. Natural control of HIV-1 infection is associated with T-cell responses against HIV-1 Gag proteins, particularly CD8⁺ T-cell responses restricted by "protective" HLA-B alleles, but other immune responses also contribute to immune control. These immune responses appear to include IgG antibodies to HIV-1 Gag proteins, interferon-a-dependant natural killer (NK) cell responses and plasmacytoid dendritic cell (pDC) responses. Here, it is proposed that isotype diversification of IgG antibodies against HIV-1 Gag proteins, to include IgG2, as well as IgG3 and IgG1 antibodies, will broaden the function of the antibody response and facilitate accessory cell responses against HIV-1 by NK cells and pDCs. We suggest that this should be investigated as a vaccination strategy for HIV-1 infection.

Functional redundancy in the control of seedling growth by the karrikin signaling pathway.

PubMed

Stanga, John P; Morffy, Nicholas; Nelson, David C

2016-06-01

SMAX1 and SMXL2 control seedling growth, demonstrating functional redundancy within a gene family that mediates karrikin and strigolactone responses. Strigolactones (SLs) are plant hormones with butenolide moieties that control diverse aspects of plant growth, including shoot branching. Karrikins (KARs) are butenolide molecules found in smoke that enhance seed germination and seedling photomorphogenesis. In Arabidopsis thaliana, SLs and KARs signal through the α/β hydrolases D14 and KAI2, respectively. The F-box protein MAX2 is essential for both signaling pathways. SUPPRESSOR OF MAX2 1 (SMAX1) plays a prominent role in KAR-regulated growth downstream of MAX2, and SMAX1-LIKE genes SMXL6, SMXL7, and SMXL8 mediate SL responses. We previously found that smax1 loss-of-function mutants display constitutive KAR response phenotypes, including reduced seed dormancy and hypersensitive growth responses to light in seedlings. However, smax1 seedlings remain slightly responsive to KARs, suggesting that there is functional redundancy in karrikin signaling. SMXL2 is a strong candidate for this redundancy because it is the closest paralog of SMAX1, and because its expression is regulated by KAR signaling. Here, we present evidence that SMXL2 controls hypocotyl growth and expression of the KAR/SL transcriptional markers KUF1, IAA1, and DLK2 redundantly with SMAX1. Hypocotyl growth in the smax1 smxl2 double mutant is insensitive to KAR and SL, and etiolated smax1 smxl2 seedlings have reduced hypocotyl elongation. However, smxl2 has little or no effect on seed germination, leaf shape, or petiole orientation, which appear to be predominantly controlled by SMAX1. Neither SMAX1 nor SMXL2 affect axillary branching or inflorescence height, traits that are under SL control. These data support the model that karrikin and strigolactone responses are mediated by distinct subclades of the SMXL family, and further the case for parallel butenolide signaling pathways that evolved through ancient KAI2 and SMXL duplications.

Acute genistein treatment mimics the effects of estradiol by enhancing place learning and impairing response learning in young adult female rats

PubMed Central

Pisani, Samantha L.; Neese, Steven L.; Doerge, Daniel R.; Helferich, William G.; Schantz, Susan L.; Korol, Donna L.

2012-01-01

Endogenous estrogens have bidirectional effects on learning and memory, enhancing or impairing cognition depending on many variables, including the task and the memory systems that are engaged. Moderate increases in estradiol enhance hippocampus-sensitive place learning, yet impair response learning that taps dorsal striatum function. This memory modulation likely occurs via activation of estrogen receptors, resulting in altered neural function. Supplements containing estrogenic compounds from plants are widely consumed despite limited information about their effects on brain function, including learning and memory. Phytoestrogens can enter the brain and signal through estrogen receptors to affect cognition. Enhancements in spatial memory and impairments in executive function have been found following treatment with soy phytoestrogens, but no tests of actions on striatum-sensitive tasks have been made to date. The present study compared the effects of acute exposure to the isoflavone genistein with the effects of estradiol on performance in place and response learning tasks. Long-Evans rats were ovariectomized, treated with 17β-estradiol benzoate, genistein-containing sucrose pellets, or vehicle (oil or plain sucrose pellets) for two days prior to behavioral training. Compared to vehicle controls, estradiol treatment enhanced place learning at a low (4.5 μg/kg) but not high dose (45 μg/kg), indicating an inverted pattern of spatial memory facilitation. Treatment with 4.4 mg of genistein over two days also significantly enhanced place learning over vehicle controls. For the response task, treatment with estradiol impaired learning at both the low and high doses; likewise, genistein treatment impaired response learning compared to rats receiving vehicle. Overall, genistein was found to mimic estradiol-induced shifts in place and response learning, facilitating hippocampus-sensitive learning and slowing striatum-sensitive learning. These results suggest signaling through estrogen receptor β and membrane-associated estrogen receptors in learning enhancements and impairments given the preferential binding of genistein to the ERβ subtype and affinity for GPER. PMID:22944517

Dose Response Data for Hormonally Active Chemicals ...

EPA Pesticide Factsheets

The shape of the dose response curve in the low dose region has been debated since the late 1940s. The debate originally focused on linear no threshold (LNT) vs threshold responses in the low dose range for cancer and noncancer related effects. For noncancer effects the default assumption is that noncancer effects generally display threshold rather than LNT responses. More recently, claims have arisen that the chemicals, like endocrine disrupters (EDS), which act via high affinity, low capacity nuclear receptors, may display LNT or nonmonotonic low dose responses: responses that could be missed in multigenerational guideline toxicity testing. This presentation will discuss LNT, threshold and nonmonotonic dose response relationships from case studies of chemicals that disrupt reproductive development and function via the ER, AR and AhR pathways and will include in vitro and in vivo multigenerational data. The in vivo studies in this discussion include only robust, well designed, comprehensive studies that administered the chemical via a relevant route(s) of exposure over a broad dose response range, including low dose(s) in the microgram/kg/d range. The chemicals include ethinyl estradiol, estradiol, genistein, bisphenol a, trenbolone, finasteride, flutamide, phthalate esters and 2,3,7,8 TCDD. The objective is to critically evaluate the data from well done studies in this field to address concerns that current multigenerational reproductive test gui

Calibration of high-dynamic-range, finite-resolution x-ray pulse-height spectrometers for extracting electron energy distribution data from the PFRC-2 device

NASA Astrophysics Data System (ADS)

Swanson, C.; Jandovitz, P.; Cohen, S. A.

2017-10-01

Knowledge of the full x-ray energy distribution function (XEDF) emitted from a plasma over a large dynamic range of energies can yield valuable insights about the electron energy distribution function (EEDF) of that plasma and the dynamic processes that create them. X-ray pulse height detectors such as Amptek's X-123 Fast SDD with Silicon Nitride window can detect x-rays in the range of 200eV to 100s of keV. However, extracting EEDF from this measurement requires precise knowledge of the detector's response function. This response function, including the energy scale calibration, the window transmission function, and the resolution function, can be measured directly. We describe measurements of this function from x-rays from a mono-energetic electron beam in a purpose-built gas-target x-ray tube. Large-Z effects such as line radiation, nuclear charge screening, and polarizational Bremsstrahlung are discussed.

Prospective Relations between Children's Responses to Peer Victimization and Their Socioemotional Adjustment

ERIC Educational Resources Information Center

Visconti, Kari Jeanne; Troop-Gordon, Wendy

2010-01-01

The objective of this investigation was to examine whether children's responses to peer victimization predict subsequent changes in their social and emotional well-being. Also investigated was whether these associations vary as a function of children's sex and level of victimization. Participants included 420 4th- and 5th-grade students (197…

Tree mortality across biomes is promoted by drought intensity, lower wood density and higher specific leaf area

USGS Publications Warehouse

Greenwood, Sarah; Ruiz-Benito, Paloma; Martinez-Vilalta, Jordi; Lloret, Francisco; Kitzberger, Thomas; Allen, Craig D.; Fensham, Rod; Laughlin, Daniel C.; Kattge, Jens; Bönisch, Gerhard; Kraft, Nathan J. B.; Jump, Alistair S.

2017-01-01

Drought events are increasing globally, and reports of consequent forest mortality are widespread. However, due to a lack of a quantitative global synthesis, it is still not clear whether drought-induced mortality rates differ among global biomes and whether functional traits influence the risk of drought-induced mortality. To address these uncertainties, we performed a global meta-analysis of 58 studies of drought-induced forest mortality. Mortality rates were modelled as a function of drought, temperature, biomes, phylogenetic and functional groups and functional traits. We identified a consistent global-scale response, where mortality increased with drought severity [log mortality (trees trees−1 year−1) increased 0.46 (95% CI = 0.2–0.7) with one SPEI unit drought intensity]. We found no significant differences in the magnitude of the response depending on forest biomes or between angiosperms and gymnosperms or evergreen and deciduous tree species. Functional traits explained some of the variation in drought responses between species (i.e. increased from 30 to 37% when wood density and specific leaf area were included). Tree species with denser wood and lower specific leaf area showed lower mortality responses. Our results illustrate the value of functional traits for understanding patterns of drought-induced tree mortality and suggest that mortality could become increasingly widespread in the future.

Tree mortality across biomes is promoted by drought intensity, lower wood density and higher specific leaf area.

PubMed

Greenwood, Sarah; Ruiz-Benito, Paloma; Martínez-Vilalta, Jordi; Lloret, Francisco; Kitzberger, Thomas; Allen, Craig D; Fensham, Rod; Laughlin, Daniel C; Kattge, Jens; Bönisch, Gerhard; Kraft, Nathan J B; Jump, Alistair S

2017-04-01

Drought events are increasing globally, and reports of consequent forest mortality are widespread. However, due to a lack of a quantitative global synthesis, it is still not clear whether drought-induced mortality rates differ among global biomes and whether functional traits influence the risk of drought-induced mortality. To address these uncertainties, we performed a global meta-analysis of 58 studies of drought-induced forest mortality. Mortality rates were modelled as a function of drought, temperature, biomes, phylogenetic and functional groups and functional traits. We identified a consistent global-scale response, where mortality increased with drought severity [log mortality (trees trees -1  year -1 ) increased 0.46 (95% CI = 0.2-0.7) with one SPEI unit drought intensity]. We found no significant differences in the magnitude of the response depending on forest biomes or between angiosperms and gymnosperms or evergreen and deciduous tree species. Functional traits explained some of the variation in drought responses between species (i.e. increased from 30 to 37% when wood density and specific leaf area were included). Tree species with denser wood and lower specific leaf area showed lower mortality responses. Our results illustrate the value of functional traits for understanding patterns of drought-induced tree mortality and suggest that mortality could become increasingly widespread in the future. © 2017 John Wiley & Sons Ltd/CNRS.

Analysis of Globodera rostochiensis effectors reveals conserved functions of SPRYSEC proteins in suppressing and eliciting plant immune responses

USDA-ARS?s Scientific Manuscript database

Potato cyst nematodes (PCNs), including Globodera rostochiensis (Woll.), are important pests of potato. Plant parasitic nematodes produce multiple effector proteins, secreted from their stylets, to successfully infect their hosts. These include proteins that are delivered to the apoplast, as well as...

Gel-Trapped Lymphorganogenic Chemokines Trigger Artificial Tertiary Lymphoid Organs and Mount Adaptive Immune Responses In Vivo.

PubMed

Kobayashi, Yuka; Watanabe, Takeshi

2016-01-01

We previously generated artificial lymph node-like tertiary lymphoid organs (artTLOs) in mice using lymphotoxin α-expressing stromal cells. Here, we show the construction of transplantable and functional artTLOs by applying soluble factors trapped in slow-releasing gels in the absence of lymphoid tissue organizer stromal cells. The resultant artTLOs were easily removable, transplantable, and were capable of attracting memory B and T cells. Importantly, artTLOs induced a powerful antigen-specific secondary immune response, which was particularly pronounced in immune-compromised hosts. Synthesis of functionally stable immune tissues/organs like those described here may be a first step to eventually develop immune system-based therapeutics. Although much needs to be learned from the precise mechanisms of action, they may offer ways in the future to reestablish immune functions to overcome hitherto untreatable diseases, including severe infection, cancer, autoimmune diseases, and various forms of immune deficiencies, including immune-senescence during aging.

Characterizing Sexual Behavior in Frontotemporal Dementia.

PubMed

Ahmed, Rebekah M; Kaizik, Cassandra; Irish, Muireann; Mioshi, Eneida; Dermody, Nadene; Kiernan, Matthew C; Piguet, Olivier; Hodges, John R

2015-01-01

Frontotemporal dementia (FTD) is characterized by a number of prominent behavioral changes. While FTD has been associated with the presence of aberrant or unusual sexual behaviors in a proportion of patients, few studies have formally investigated changes in sexual function in this disease. We aimed to systematically quantify changes in sexual behavior, including current symptoms and changes from prior diagnoses, in behavioral-variant (bvFTD) and semantic dementia (SD), compared to Alzheimer's disease (AD). Carers of 49 dementia patients (21 bvFTD, 11 SD, 17 AD) were interviewed using the Sexual Behavior and Intimacy Questionnaire (SIQ), a survey designed to assess changes in sexual function across multiple domains including initiating, level of affection, and aberrant or unusual sexual behavior. BvFTD patients show prominent hyposexual behavior including decreased affection, initiation, and response to advances by partners, and decreased frequency of sexual relations, compared to AD and to SD patients. The greatest changes in sexual behavior compared to pre-diagnoses were found in the bvFTD group with a 90-100% decrease in initiation, response, and frequency of sexual relations. Notably, aberrant or unusual sexual behavior was reported in a minority of bvFTD and SD patients and occurred in patients who also showed hyposexual behavior toward their partner. Overall loss of affection, reduced initiation of sexual activity, and responsiveness is an overwhelming feature of bvFTD. In contrast, aberrant or unusual sexual behavior is observed in the minority of bvFTD patients. The underlying pathophysiology of these changes likely reflects structural and functional changes in frontoinsular and limbic regions including the hypothalamus.

Linear response theory for annealing of radiation damage in semiconductor devices

NASA Technical Reports Server (NTRS)

Litovchenko, Vitaly

1988-01-01

A theoretical study of the radiation/annealing response of MOS ICs is described. Although many experiments have been performed in this field, no comprehensive theory dealing with radiation/annealing response has been proposed. Many attempts have been made to apply linear response theory, but no theoretical foundation has been presented. The linear response theory outlined here is capable of describing a broad area of radiation/annealing response phenomena in MOS ICs, in particular, both simultaneous irradiation and annealing, as well as short- and long-term annealing, including the case when annealing is nearing completion. For the first time, a simple procedure is devised to determine the response function from experimental radiation/annealing data. In addition, this procedure enables us to study the effect of variable temperature and dose rate, effects which are of interest in spaceflight. In the past, the shift in threshold potential due to radiation/annealing has usually been assumed to depend on one variable: the time lapse between an impulse dose and the time of observation. While such a suggestion of uniformity in time is certainly true for a broad range of radiation annealing phenomena, it may not hold for some ranges of the variables of interest (temperature, dose rate, etc.). A response function is projected which is dependent on two variables: the time of observation and the time of the impulse dose. This dependence on two variables allows us to extend the theory to the treatment of a variable dose rate. Finally, the linear theory is generalized to the case in which the response is nonlinear with impulse dose, but is proportional to some impulse function of dose. A method to determine both the impulse and response functions is presented.

Polymeric blends for sensor and actuation dual functionality

NASA Technical Reports Server (NTRS)

St. Clair, Terry L. (Inventor); Harrison, Joycelyn S. (Inventor); Su, Ji (Inventor); Ounaies, Zoubeida (Inventor)

2004-01-01

The invention described herein supplies a new class of electroactive polymeric blend materials which offer both sensing and actuation dual functionality. The blend comprises two components, one component having a sensing capability and the other component having an actuating capability. These components should be co-processable and coexisting in a phase separated blend system. Specifically, the materials are blends of a sensing component selected from the group consisting of ferroelectric, piezoelectric, pyroelectric and photoelectric polymers and an actuating component that responds to an electric field in terms of dimensional change. Said actuating component includes, but is not limited to, electrostrictive graft elastomers, dielectric electroactive elastomers, liquid crystal electroactive elastomers and field responsive polymeric gels. The sensor functionality and actuation functionality are designed by tailoring the relative fraction of the two components. The temperature dependence of the piezoelectric response and the mechanical toughness of the dual functional blends are also tailored by the composition adjustment.

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

Neural activation in the "reward circuit" shows a nonlinear response to facial attractiveness.

PubMed

Liang, Xiaoyun; Zebrowitz, Leslie A; Zhang, Yi

2010-01-01

Positive behavioral responses to attractive faces have led neuroscientists to investigate underlying neural mechanisms in a "reward circuit" that includes brain regions innervated by dopamine pathways. Using male faces ranging from attractive to extremely unattractive, disfigured ones, this study is the first to demonstrate heightened responses to both rewarding and aversive faces in numerous areas of this putative reward circuit. Parametric analyses employing orthogonal linear and nonlinear regressors revealed positive nonlinear effects in anterior cingulate cortex, lateral orbital frontal cortex (LOFC), striatum (nucleus accumbens, caudate, putamen), and ventral tegmental area, in addition to replicating previously documented linear effects in medial orbital frontal cortex (MOFC) and LOFC and nonlinear effects in amygdala and MOFC. The widespread nonlinear responses are consistent with single cell recordings in animals showing responses to both rewarding and aversive stimuli, and with some human fMRI investigations of non-face stimuli. They indicate that the reward circuit does not process face valence with any simple dissociation of function across structures. Perceiver gender modulated some responses to our male faces: Women showed stronger linear effects, and men showed stronger nonlinear effects, which may have functional implications. Our discovery of nonlinear responses to attractiveness throughout the reward circuit echoes the history of amygdala research: Early work indicated a linear response to threatening stimuli, including faces; later work also revealed a nonlinear response with heightened activation to affectively salient stimuli regardless of valence. The challenge remains to determine how such dual coding influences feelings, such as pleasure and pain, and guides goal-related behavioral responses, such as approach and avoidance.

[Research advances on cortical functional and structural deficits of amblyopia].

PubMed

Wu, Y; Liu, L Q

2017-05-11

Previous studies have observed functional deficits in primary visual cortex. With the development of functional magnetic resonance imaging and electrophysiological technique, the research of the striate, extra-striate cortex and higher-order cortical deficit underlying amblyopia reaches a new stage. The neural mechanisms of amblyopia show that anomalous responses exist throughout the visual processing hierarchy, including the functional and structural abnormalities. This review aims to summarize the current knowledge about structural and functional deficits of brain regions associated with amblyopia. (Chin J Ophthalmol, 2017, 53: 392 - 395) .

The Multiple Functions of the Nucleolus in Plant Development, Disease and Stress Responses

PubMed Central

Kalinina, Natalia O.; Makarova, Svetlana; Makhotenko, Antonida; Love, Andrew J.; Taliansky, Michael

2018-01-01

The nucleolus is the most conspicuous domain in the eukaryotic cell nucleus, whose main function is ribosomal RNA (rRNA) synthesis and ribosome biogenesis. However, there is growing evidence that the nucleolus is also implicated in many other aspects of cell biology, such as regulation of cell cycle, growth and development, senescence, telomerase activity, gene silencing, responses to biotic and abiotic stresses. In the first part of the review, we briefly assess the traditional roles of the plant nucleolus in rRNA synthesis and ribosome biogenesis as well as possible functions in other RNA regulatory pathways such as splicing, nonsense-mediated mRNA decay and RNA silencing. In the second part of the review we summarize recent progress and discuss already known and new hypothetical roles of the nucleolus in plant growth and development. In addition, this part will highlight studies showing new nucleolar functions involved in responses to pathogen attack and abiotic stress. Cross-talk between the nucleolus and Cajal bodies is also discussed in the context of their association with poly(ADP ribose)polymerase (PARP), which is known to play a crucial role in various physiological processes including growth, development and responses to biotic and abiotic stresses. PMID:29479362

The motor function measure to study limitation of activity in children and adults with Charcot-Marie-Tooth disease.

PubMed

Allard, L; Rode, G; Jacquin-Courtois, S; Pouget, M C; Rippert, P; Hamroun, D; Poirot, I; Bérard, C; Vuillerot, C

2014-12-01

To study the applicability and responsiveness of the motor function measure (total score and sub-scores D1, D2 and D3) in patients with Charcot-Marie-Tooth disease. Two hundred and thirty-three patients aged 4-86 years were included in the descriptive study. Scores and sub-scores were analyzed by age and by disease subtypes. Sensitivity to change (responsiveness) was estimated in patients having had at least two evaluations with at least six months between the first and the second. Motor function measure scores decrease with age, especially sub-scores D1 and D3. There were no significant differences between the scores according to type of Charcot-Marie-Tooth disease. The scores were significantly higher for ambulatory than for non-ambulatory patients. Significant responsiveness was demonstrated only in type 2 Charcot-Marie-Tooth disease. Our results suggest that, especially for D1 and D3 sub-scores, the motor function measure is a reliable and valid outcome measure that can be usefully applied in longitudinal follow-up. Studies of longer duration could demonstrate its responsiveness in other Charcot-Marie-Tooth disease subtypes. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Modelling and simulation of biased agonism dynamics at a G protein-coupled receptor.

PubMed

Bridge, L J; Mead, J; Frattini, E; Winfield, I; Ladds, G

2018-04-07

Theoretical models of G protein-coupled receptor (GPCR) concentration-response relationships often assume an agonist producing a single functional response via a single active state of the receptor. These models have largely been analysed assuming steady-state conditions. There is now much experimental evidence to suggest that many GPCRs can exist in multiple receptor conformations and elicit numerous functional responses, with ligands having the potential to activate different signalling pathways to varying extents-a concept referred to as biased agonism, functional selectivity or pluri-dimensional efficacy. Moreover, recent experimental results indicate a clear possibility for time-dependent bias, whereby an agonist's bias with respect to different pathways may vary dynamically. Efforts towards understanding the implications of temporal bias by characterising and quantifying ligand effects on multiple pathways will clearly be aided by extending current equilibrium binding and biased activation models to include G protein activation dynamics. Here, we present a new model of time-dependent biased agonism, based on ordinary differential equations for multiple cubic ternary complex activation models with G protein cycle dynamics. This model allows simulation and analysis of multi-pathway activation bias dynamics at a single receptor for the first time, at the level of active G protein (α GTP ), towards the analysis of dynamic functional responses. The model is generally applicable to systems with N G G proteins and N* active receptor states. Numerical simulations for N G =N * =2 reveal new insights into the effects of system parameters (including cooperativities, and ligand and receptor concentrations) on bias dynamics, highlighting new phenomena including the dynamic inter-conversion of bias direction. Further, we fit this model to 'wet' experimental data for two competing G proteins (G i and G s ) that become activated upon stimulation of the adenosine A 1 receptor with adenosine derivative compounds. Finally, we show that our model can qualitatively describe the temporal dynamics of this competing G protein activation. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Validation of Autonomic and Endocrine Reactivity to a Laboratory Stressor in Young Children

PubMed Central

Roos, Leslie E.; Giuliano, Ryan J.; Beauchamp, Kathryn G.; Gunnar, Megan; Amidon, Brigette; Fisher, Philip A.

2017-01-01

The validation of laboratory paradigms that reliably induce a stress response [including hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system (ANS) activation], is critical for understanding how children’s stress-response systems support emotional and cognitive function. Early childhood research to date is markedly limited, given the difficulty in establishing paradigms that reliably induce a cortisol response. Furthermore, research to date has not included a control condition or examined concurrent ANS reactivity. We addressed these limitations by characterizing the extent to which a modified matching task stressor paradigm induces HPA and ANS activation, beyond a closely matched control condition. Modifications include an unfamiliar and unfriendly assessor to increase the stressful nature of the task. Results validate the matching task as a laboratory stressor, with significant differences in HPA and ANS responsivity between conditions. The Stressor group exhibited a cortisol increase post-stressor, while the Control group was stable over time. Children in both conditions exhibited reduced parasympathetic activity to the first-half of the task, but in the second-half, only children in the Stressor condition, who were experiencing exaggerated signals of failure, exhibited further parasympathetic decline. The Stressor condition induced higher sympathetic activity (versus Control) throughout the task, with exaggerated second-half differences. Within the Stressor condition, responsivity was convergent across systems, with greater cortisol reactivity correlated with the magnitude of parasympathetic withdrawal and sympathetic engagement. Future research employing the matching task will facilitate understanding the role of HPA and ANS function in development. PMID:28024268

Valley plugs, land use, and phytogeomorphic response: Chapter 14

USGS Publications Warehouse

Pierce, Aaron R.; King, Sammy L.; Shroder, John F.

2013-01-01

Anthropogenic alteration of fluvial systems can disrupt functional processes that provide valuable ecosystem services. Channelization alters fluvial parameters and the connectivity of river channels to their floodplains which is critical for productivity, nutrient cycling, flood control, and biodiversity. The effects of channelization can be exacerbated by local geology and land-use activities, resulting in dramatic geomorphic readjustments including the formation of valley plugs. Considerable variation in the response of abiotic processes, including surface hydrology, subsurface hydrology, and sedimentation dynamics, to channelization and the formation of valley plugs. Altered abiotic processes associated with these geomorphic features and readjustments influence biotic processes including species composition, abundance, and successional processes. Considerable interest exists for restoring altered fluvial systems and their floodplains because of their social and ecological importance. Understanding abiotic and biotic responses of channelization and valley-plug formation within the context of the watershed is essential to successful restoration. This chapter focuses on the primary causes of valley-plug formation, resulting fluvial-geomorphic responses, vegetation responses, and restoration and research needs for these systems.

Family Functioning, Identity Formation, and the Ability of Conflict Resolution among Adolescents

ERIC Educational Resources Information Center

Kiani, Behnaz; Hojatkhah, Seyed Mohsen; Torabi-Nami, Mohammad

2016-01-01

Family is perhaps the most influential system in individuals' life in which various behaviors are learnt. Family functioning refers to the ability of family to meet its responsibilities. The present correlation study used a multi-stage cluster sampling method to recruit 686 subjects including 338 males and 348 females from all high school students…

Contributions of Modern Measurement Theory to Measuring Executive Function in Early Childhood: An Empirical Demonstration

ERIC Educational Resources Information Center

Willoughby, Michael T.; Wirth, R. J.; Blair, Clancy B.

2011-01-01

This study demonstrates the merits of evaluating a newly developed battery of executive function tasks, designed for use in early childhood, from the perspective of item response theory (IRT). The battery was included in the 48-month assessment of the Family Life Project, a prospective longitudinal study of 1292 children oversampled from…

Brief Report: Treatment of Echolalia in a Girl with Rubinstein-Taybi Syndrome: Functional Assessment of Minimizing Chances To Provoke Echolalia.

ERIC Educational Resources Information Center

Chung, Bo In

1998-01-01

Discusses the successful treatment of echolalia in a 15-year-old girl with Rubinstein-Tabyi syndrome, a congenital anomaly characterized by mental and growth retardation. Intervention included a functional assessment of varied echolalic conditions, provision of a therapeutic environment that minimized echolalic responses, and reinforcement of…

Physiologic measures of sexual function in women: a review.

PubMed

Woodard, Terri L; Diamond, Michael P

2009-07-01

To review and describe physiologic measures of assessing sexual function in women. Literature review. Studies that use instruments designed to measure female sexual function. Women participating in studies of female sexual function. Various instruments that measure physiologic features of female sexual function. Appraisal of the various instruments, including their advantages and disadvantages. Many unique physiologic methods of evaluating female sexual function have been developed during the past four decades. Each method has its benefits and limitations. Many physiologic methods exist, but most are not well-validated. In addition there has been an inability to correlate most physiologic measures with subjective measures of sexual arousal. Furthermore, given the complex nature of the sexual response in women, physiologic measures should be considered in context of other data, including the history, physical examination, and validated questionnaires. Nonetheless, the existence of appropriate physiologic measures is vital to our understanding of female sexual function and dysfunction.

Measurement of the Energy-Dependent Angular Response of the ARES Detector System and Application to Aerial Imaging

NASA Astrophysics Data System (ADS)

Joshi, Tenzing H. Y.; Quiter, Brian J.; Maltz, Jonathan S.; Bandstra, Mark S.; Haefner, Andrew; Eikmeier, Nicole; Wagner, Eric; Luke, Tanushree; Malchow, Russell; McCall, Karen

2017-07-01

The Airborne Radiological Enhanced-sensor System (ARES) includes a prototype helicopter-borne CsI(Na) detector array that has been developed as part of the DHS Domestic Nuclear Detection Office Advanced Technology Demonstration. The detector system geometry comprises two pairs of 23-detector arrays designed to function as active masks, providing additional angular resolution of measured gamma rays in the roll dimension. Experimental measurements, using five radioisotopes (137Cs, 60Co, 241Am, 131I, and 99mTc), were performed to map the detector response in both roll and pitch dimensions. This paper describes the acquisition and analysis of these characterization measurements, calculation of the angular response of the ARES system, and how this response function is used to improve aerial detection and localization of radiological and nuclear threat sources.

Distinct Neural Circuits Support Transient and Sustained Processes in Prospective Memory and Working Memory

PubMed Central

West, Robert; Braver, Todd

2009-01-01

Current theories are divided as to whether prospective memory (PM) involves primarily sustained processes such as strategic monitoring, or transient processes such as the retrieval of intentions from memory when a relevant cue is encountered. The current study examined the neural correlates of PM using a functional magnetic resonance imaging design that allows for the decomposition of brain activity into sustained and transient components. Performance of the PM task was primarily associated with sustained responses in a network including anterior prefrontal cortex (lateral Brodmann area 10), and these responses were dissociable from sustained responses associated with active maintenance in working memory. Additionally, the sustained responses in anterior prefrontal cortex correlated with faster response times for prospective responses. Prospective cues also elicited selective transient activity in a region of interest along the right middle temporal gyrus. The results support the conclusion that both sustained and transient processes contribute to efficient PM and provide novel constraints on the functional role of anterior PFC in higher-order cognition. PMID:18854581

Inhibitors of the PD-1 Pathway in Tumor Therapy

PubMed Central

LaFleur, Martin W.; Muroyama, Yuki; Drake, Charles G.; Sharpe, Arlene H.

2018-01-01

The programmed death 1 (PD-1) pathway delivers inhibitory signals that function as a brake for immune responses. This pathway limits the initiation and duration of immune responses, thereby protecting tissues from immune-mediated damage and autoimmune diseases. However, the PD-1 pathway also inhibits immune responses to tumors. The critical role of PD-1 in preventing antitumor immunity is demonstrated by the transformative effects of PD-1 pathway blockade in a broad range of cancers with the hallmark of durability of response. Despite this success, most patients do not respond to PD-1 monotherapy, and some patients experience adverse events. In this review, we discuss the functions of the PD-1 pathway and its translation to cancer immunotherapy. We also consider current challenges and opportunities for PD-1 cancer immunotherapy, including mechanisms of response and resistance, identification of biomarkers of response to PD-1 therapy, characterization and treatment of PD-1 therapy–related adverse events, and development of safe and effective combination therapies. PMID:29311378

ATM supports gammaherpesvirus replication by attenuating type I interferon pathway.

PubMed

Darrah, Eric J; Stoltz, Kyle P; Ledwith, Mitchell; Tarakanova, Vera L

2017-10-01

Ataxia-Telangiectasia mutated (ATM) kinase participates in multiple networks, including DNA damage response, oxidative stress, and mitophagy. ATM also supports replication of diverse DNA and RNA viruses. Gammaherpesviruses are prevalent cancer-associated viruses that benefit from ATM expression during replication. This proviral role of ATM had been ascribed to its signaling within the DNA damage response network; other functions of ATM have not been considered. In this study increased type I interferon (IFN) responses were observed in ATM deficient gammaherpesvirus-infected macrophages. Using a mouse model that combines ATM and type I IFN receptor deficiencies we show that increased type I IFN response in the absence of ATM fully accounts for the proviral role of ATM during gammaherpesvirus replication. Further, increased type I IFN response rendered ATM deficient macrophages more susceptible to antiviral effects of type II IFN. This study identifies attenuation of type I IFN responses as the primary mechanism underlying proviral function of ATM during gammaherpesvirus infection. Copyright © 2017 Elsevier Inc. All rights reserved.

Gravity-regulated gene expression in Arabidopsis thaliana

NASA Astrophysics Data System (ADS)

Sederoff, Heike; Brown, Christopher S.; Heber, Steffen; Kajla, Jyoti D.; Kumar, Sandeep; Lomax, Terri L.; Wheeler, Benjamin; Yalamanchili, Roopa

Plant growth and development is regulated by changes in environmental signals. Plants sense environmental changes and respond to them by modifying gene expression programs to ad-just cell growth, differentiation, and metabolism. Functional expression of genes comprises many different processes including transcription, translation, post-transcriptional and post-translational modifications, as well as the degradation of RNA and proteins. Recently, it was discovered that small RNAs (sRNA, 18-24 nucleotides long), which are heritable and systemic, are key elements in regulating gene expression in response to biotic and abiotic changes. Sev-eral different classes of sRNAs have been identified that are part of a non-cell autonomous and phloem-mobile network of regulators affecting transcript stability, translational kinetics, and DNA methylation patterns responsible for heritable transcriptional silencing (epigenetics). Our research has focused on gene expression changes in response to gravistimulation of Arabidopsis roots. Using high-throughput technologies including microarrays and 454 sequencing, we iden-tified rapid changes in transcript abundance of genes as well as differential expression of small RNA in Arabidopsis root apices after minutes of reorientation. Some of the differentially regu-lated transcripts are encoded by genes that are important for the bending response. Functional mutants of those genes respond faster to reorientation than the respective wild type plants, indicating that these proteins are repressors of differential cell elongation. We compared the gravity responsive sRNAs to the changes in transcript abundances of their putative targets and identified several potential miRNA: target pairs. Currently, we are using mutant and transgenic Arabidopsis plants to characterize the function of those miRNAs and their putative targets in gravitropic and phototropic responses in Arabidopsis.

Genome-wide Escherichia coli stress response and improved tolerance towards industrially relevant chemicals.

PubMed

Rau, Martin Holm; Calero, Patricia; Lennen, Rebecca M; Long, Katherine S; Nielsen, Alex T

2016-10-13

Economically viable biobased production of bulk chemicals and biofuels typically requires high product titers. During microbial bioconversion this often leads to product toxicity, and tolerance is therefore a critical element in the engineering of production strains. Here, a systems biology approach was employed to understand the chemical stress response of Escherichia coli, including a genome-wide screen for mutants with increased fitness during chemical stress. Twelve chemicals with significant production potential were selected, consisting of organic solvent-like chemicals (butanol, hydroxy-γ-butyrolactone, 1,4-butanediol, furfural), organic acids (acetate, itaconic acid, levulinic acid, succinic acid), amino acids (serine, threonine) and membrane-intercalating chemicals (decanoic acid, geraniol). The transcriptional response towards these chemicals revealed large overlaps of transcription changes within and between chemical groups, with functions such as energy metabolism, stress response, membrane modification, transporters and iron metabolism being affected. Regulon enrichment analysis identified key regulators likely mediating the transcriptional response, including CRP, RpoS, OmpR, ArcA, Fur and GadX. These regulators, the genes within their regulons and the above mentioned cellular functions therefore constitute potential targets for increasing E. coli chemical tolerance. Fitness determination of genome-wide transposon mutants (Tn-seq) subjected to the same chemical stress identified 294 enriched and 336 depleted mutants and experimental validation revealed up to 60 % increase in mutant growth rates. Mutants enriched in several conditions contained, among others, insertions in genes of the Mar-Sox-Rob regulon as well as transcription and translation related gene functions. The combination of the transcriptional response and mutant screening provides general targets that can increase tolerance towards not only single, but multiple chemicals.

Arabidopsis nph1 and npl1: blue light receptors that mediate both phototropism and chloroplast relocation.

PubMed

Sakai, T; Kagawa, T; Kasahara, M; Swartz, T E; Christie, J M; Briggs, W R; Wada, M; Okada, K

2001-06-05

UV-A/blue light acts to regulate a number of physiological processes in higher plants. These include light-driven chloroplast movement and phototropism. The NPH1 gene of Arabidopsis encodes an autophosphorylating protein kinase that functions as a photoreceptor for phototropism in response to low-intensity blue light. However, nph1 mutants have been reported to exhibit normal phototropic curvature under high-intensity blue light, indicating the presence of an additional phototropic receptor. A likely candidate is the nph1 homologue, npl1, which has recently been shown to mediate the avoidance response of chloroplasts to high-intensity blue light in Arabidopsis. Here we demonstrate that npl1, like nph1, noncovalently binds the chromophore flavin mononucleotide (FMN) within two specialized PAS domains, termed LOV domains. Furthermore, when expressed in insect cells, npl1, like nph1, undergoes light-dependent autophosphorylation, indicating that npl1 also functions as a light receptor kinase. Consistent with this conclusion, we show that a nph1 npl1 double mutant exhibits an impaired phototropic response under both low- and high-intensity blue light. Hence, npl1 functions as a second phototropic receptor under high fluence rate conditions and is, in part, functionally redundant to nph1. We also demonstrate that both chloroplast accumulation in response to low-intensity light and chloroplast avoidance movement in response to high-intensity light are lacking in the nph1 npl1 double mutant. Our findings therefore indicate that nph1 and npl1 show partially overlapping functions in two different responses, phototropism and chloroplast relocation, in a fluence rate-dependent manner.

Restoration of Bladder and Bowel Function Using Electrical Stimulation and Block after Spinal Cord Injury

DTIC Science & Technology

2016-10-01

AWARD NUMBER: W81XWH-14-2-0132 TITLE: Restoration of Bladder and Bowel Function Using Electrical Stimulation and Block after Spinal Cord Injury...per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and...COVERED 29 Sep 2015 - 28 Sep 2016 4. TITLE AND SUBTITLE Restoration of Bladder and Bowel Function Using Electrical Stimulation and Block after Spinal

Reactivating Neural Circuits with Clinically Accessible Stimulation to Restore Hand Function in Persons with Tetraplegia

DTIC Science & Technology

2017-09-01

AWARD NUMBER: W81XWH-16-1-0395 TITLE: Reactivating Neural Circuits with Clinically Accessible Stimulation to Restore Hand Function in...estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data...Clinically Accessible Stimulation to Restore Hand Function in Persons with Tetraplegia 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S

Traumatic stress: effects on the brain

PubMed Central

Bremner, J. Douglas

2006-01-01

Brain areas implicated in the stress response include the amygdala, hippocampus, and prefrontal cortex. Traumatic stress can be associated with lasting changes in these brain areas. Traumatic stress is associated with increased cortisol and norepinephrine responses to subsequent stressors. Antidepressants have effets on the hippocampus that counteract the effects of stress. Findings from animal studies have been extended to patients with post-traumatic stress disorder (PTSD) showing smaller hippocampal and anterior cingulate volumes, increased amygdala function, and decreased medial prefrontal/anterior cingulate function. In addition, patients with PTSD show increased cortisol and norepinephrine responses to stress. Treatments that are efficacious for PTSD show a promotion of neurogenesis in animal studies, as well as promotion of memory and increased hippocampal volume in PTSD. PMID:17290802

Clinical implications of basic science discoveries: janus resurrected--two faces of B cell and plasma cell biology.

PubMed

Woodle, E S; Rothstein, D M

2015-01-01

B cells play a complex role in the immune response. In addition to giving rise to plasma cells (PCs) and promoting T cell responses via antigen presentation, they perform immunoregulatory functions. This knowledge has created concerns regarding nonspecific B cell depletional therapy because of the potential to paradoxically augment immune responses. Recent studies now indicate that PCs have immune functions beyond immunoglobulin synthesis. Evidence for a new role for PCs as potent regulatory cells (via IL-10 and IL-35 production) is discussed including the implications for PC-targeted therapies currently being developed for clinical transplantation. © Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.

Identifying functional groups for response to disturbance in an abandoned pasture

NASA Astrophysics Data System (ADS)

Lavorel, Sandra; Touzard, Blaise; Lebreton, Jean-Dominique; Clément, Bernard

1998-06-01

In an abandoned pasture in Brittany, we compared artificial small-scale disturbances to natural disturbances by wild boar and undisturbed vegetation. We developed a multivariate statistical approach which analyses how species biological attributes explain the response of community composition to disturbances. This technique, which reconciles the inductive and deductive approaches for functional classifications, identifies groups of species with similar responses to disturbance and characterizes their biological profiles. After 5 months of recolonization, artificial disturbances had a greater species richness than undisturbed vegetation as a result of recruitment of new species without the exclusion of pre-existing matrix species. Species morphology, described by canopy structure, canopy height and lateral spread, explained a large part (16 %) of community response to disturbance. Regeneration strategies, described by life history, seed mass, dispersal agent, dormancy and the existence of vegetative multiplication, explained a smaller part of community response to disturbance (8 %). Artificial disturbances were characterized by therophyte and compact rosettes with moderately dormant seeds, including a number of Asteraceae and other early successional species. Natural disturbances were colonized by leafy guerrilla species without seed dormancy. Few species were tightly related to undisturbed vegetation and were essentially grasses with a phalanx rosette morphology. The functional classification obtained is consistent with the classification of the community into fugitives, regenerators and persistors. These groups are structured according to Grubb's model for temperate grasslands, with regenerators and persistors in the matrix and fugitives taking advantage of gaps open by small-scale disturbances. The conjunction of functional diversity and species diversity within functional groups is the key to resilience to disturbance, an important ecosystem function.

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.

Sexual dysfunction with antihypertensive and antipsychotic agents.

PubMed

Smith, P J; Talbert, R L

1986-05-01

The physiology of the normal sexual response, epidemiology of sexual dysfunction, and the pharmacologic mechanisms involved in antihypertensive- and antipsychotic-induced problems with sexual function are discussed, with recommendations for patient management. The physiologic mechanisms involved in the normal sexual response include neurogenic, psychogenic, vascular, and hormonal factors that are coordinated by centers in the hypothalamus, limbic system, and cerebral cortex. Sexual dysfunction is frequently attributed to antihypertensive and antipsychotic agents and is a cause of noncompliance. Drug-induced effects include diminished libido, delayed orgasm, ejaculatory disturbances, gynecomastia, impotence, and priapism. The pharmacologic mechanisms proposed to account for these adverse effects include adrenergic inhibition, adrenergic-receptor blockade, anticholinergic properties, and endocrine and sedative effects. The most frequently reported adverse effect on sexual function with the antihypertensive agents is impotence. It is seen most often with methyldopa, guanethidine, clonidine, and propranolol. In contrast, the most common adverse effect on sexual function with the antipsychotic agents involves ejaculatory disturbances. Thioridazine, with its potent anticholinergic and alpha-blocking properties, is cited most often. Drug-induced sexual dysfunction may be alleviated by switching to agents with dissimilar mechanisms to alter the observed adverse effect while maintaining adequate control of the patient's disease state.

Modeling the double charge exchange response function for a tetraneutron system

NASA Astrophysics Data System (ADS)

Lazauskas, R.; Carbonell, J.; Hiyama, E.

2017-07-01

This work is an attempt to model the 4 n response function of a recent RIKEN experimental study of the double charge exchange  4 He( 8 He, 8 Be) 4n reaction in order to put in evidence an eventual enhancement mechanism of the zero-energy cross section, including a near-threshold resonance. This resonance can indeed be reproduced only by adding to the standard nuclear Hamiltonian an unphysically large T =3/2 attractive 3 n -force that destroys the neighboring nuclear chart. No other mechanisms, like cusps or related structures, were found.

Cross-cultural adaptation, validation, and responsiveness of the Korean version of the AUSCAN Osteoarthritis Index.

PubMed

Moon, Ki Won; Lee, Shin-Seok; Kim, Jin Hyun; Song, Ran; Lee, Eun Young; Song, Yeong Wook; Bellamy, Nicholas; Lee, Eun Bong

2012-11-01

The Australian/Canadian Osteoarthritis Hand Index (AUSCAN) is a patient self-reported 15-item questionnaire measuring the severity of hand osteoarthritis symptoms in the respect of pain, stiffness, and function. In this study, we developed a Korean version of the AUSCAN Index (K-AUSCAN) and confirmed its reliability, validity, and responsiveness. The AUSCAN Index was translated into Korean by 3 translators and translated back into English by 3 different translators. In a group of 53 patients with clinical hand osteoarthritis (mean age 58.3 ± 7.6 years), validity was evaluated against other outcome measures, including the Functional Index for Hand Osteoarthritis (FIHOA) and Multidimensional Health Assessment Questionnaire (MDHAQ). Test-retest reliability was assessed at a 2-weeks interval in 51 patients. Internal consistency of K-AUSCAN was evaluated by Cronbach's α. Responsiveness was measured by standardized response mean (SRM). The test-retest reliability of K-AUSCAN yielded intraclass correlation coefficient of 0.46 for pain, 0.58 for stiffness, and 0.67 for function. The internal consistency of K-AUSCAN was satisfactory with Cronbach's α of 0.89 for pain and 0.93 for function. The K-AUSCAN index showed good correlation with other measures (r (2) was 0.67 for K-AUSCAN pain and MDHAQ pain; r (2) was 0.72 for K-AUSCAN function and FIHOA). The pain and function of K-AUSCAN correlated substantially with each other and moderately with stiffness subscale. The average SRM for K-AUSCAN pain, stiffness, and function was -0.92, -0.48, and -0.84, respectively. The Korean version of the AUSCAN Index is a valid, reliable, and responsive tool for the assessment of hand osteoarthritis symptoms.

Social inclusion enhances biological motion processing: A functional near-infrared spectroscopy study

PubMed Central

Bolling, Danielle Z.; Pelphrey, Kevin A.; Kaiser, Martha D.

2012-01-01

Humans are especially tuned to the movements of other people. Neural correlates of this social attunement have been proposed to lie in and around the right posterior superior temporal sulcus (STS) region, which robustly responds to biological motion in contrast to a variety of non-biological motions. This response persists even when no form information is provided, as in point-light displays (PLDs). The aim of the current study was to assess the ability of functional near-infrared spectroscopy (fNIRS) to reliably measure brain responses to PLDs of biological motion, and determine the sensitivity of these responses to interpersonal contextual factors. To establish reliability, we measured brain activation to biological motion with fNIRS and functional magnetic resonance imaging (fMRI) during two separate sessions in an identical group of 12 participants. To establish sensitivity, brain responses to biological motion measured with fNIRS were subjected to an additional social manipulation where participants were either socially included or excluded before viewing PLDs of biological motion. Results revealed comparable brain responses to biological motion using fMRI and fNIRS in the right supramarginal gyrus. Further, social inclusion increased brain responses to biological motion in right supramarginal gyrus and posterior STS. Thus, fNIRS can reliably measure brain responses to biological motion and can detect social experience-dependent modulations of these brain responses. PMID:22941501

Dual neurocircuitry dysfunctions in disruptive behavior disorders: emotional responding and response inhibition.

PubMed

Hwang, S; Nolan, Z T; White, S F; Williams, W C; Sinclair, S; Blair, R J R

2016-05-01

To determine the functional integrity of the neural systems involved in emotional responding/regulation and response control/inhibition in youth (age 10-18 years) with disruptive behavioral disorders (DBDs: conduct disorder and/or oppositional defiant disorder) as a function of callous-unemotional (CU) traits. Twenty-eight healthy youths and 35 youths with DBD [high CU (HCU), n = 18; low CU (LCU), n = 17] performed the fMRI Affective Stroop task. Participants viewed positive, neutral, and negative images under varying levels of cognitive load. A 3-way ANOVA (group×emotion by task) was conducted on the BOLD response data. Youth with DBD-HCU showed significantly less activation of ventromedial prefrontal cortex (vmPFC) and amygdala in response to negative stimuli, compared to healthy youth and youth with DBD-LCU. vmPFC responsiveness was inversely related to CU symptoms in DBD. Youth with DBD-LCU showed decreased functional connectivity between amygdala and regions including inferior frontal gyrus in response to emotional stimuli. Youth with DBD (LCU and HCU) additionally showed decreased insula responsiveness to high load (incongruent trials) compared to healthy youth. Insula responsiveness was inversely related to ADHD symptoms in DBD. These data reveal two forms of pathophysiology in DBD. One associated with reduced amygdala and vmPFC responses to negative stimuli and related to increased CU traits. Another associated with reduced insula responses during high load task trials and related to ADHD symptoms. Appropriate treatment will need to be individualized according to the patient's specific pathophysiology.

A Review of the Combination of Experimental Measurements and Fibril-Reinforced Modeling for Investigation of Articular Cartilage and Chondrocyte Response to Loading

PubMed Central

Wilson, Wouter; Isaksson, Hanna; Jurvelin, Jukka S.; Herzog, Walter; Korhonen, Rami K.

2013-01-01

The function of articular cartilage depends on its structure and composition, sensitively impaired in disease (e.g. osteoarthritis, OA). Responses of chondrocytes to tissue loading are modulated by the structure. Altered cell responses as an effect of OA may regulate cartilage mechanotransduction and cell biosynthesis. To be able to evaluate cell responses and factors affecting the onset and progression of OA, local tissue and cell stresses and strains in cartilage need to be characterized. This is extremely challenging with the presently available experimental techniques and therefore computational modeling is required. Modern models of articular cartilage are inhomogeneous and anisotropic, and they include many aspects of the real tissue structure and composition. In this paper, we provide an overview of the computational applications that have been developed for modeling the mechanics of articular cartilage at the tissue and cellular level. We concentrate on the use of fibril-reinforced models of cartilage. Furthermore, we introduce practical considerations for modeling applications, including also experimental tests that can be combined with the modeling approach. At the end, we discuss the prospects for patient-specific models when aiming to use finite element modeling analysis and evaluation of articular cartilage function, cellular responses, failure points, OA progression, and rehabilitation. PMID:23653665

AllergoOncology - the impact of allergy in oncology: EAACI position paper.

PubMed

Jensen-Jarolim, E; Bax, H J; Bianchini, R; Capron, M; Corrigan, C; Castells, M; Dombrowicz, D; Daniels-Wells, T R; Fazekas, J; Fiebiger, E; Gatault, S; Gould, H J; Janda, J; Josephs, D H; Karagiannis, P; Levi-Schaffer, F; Meshcheryakova, A; Mechtcheriakova, D; Mekori, Y; Mungenast, F; Nigro, E A; Penichet, M L; Redegeld, F; Saul, L; Singer, J; Spicer, J F; Siccardi, A G; Spillner, E; Turner, M C; Untersmayr, E; Vangelista, L; Karagiannis, S N

2017-06-01

Th2 immunity and allergic immune surveillance play critical roles in host responses to pathogens, parasites and allergens. Numerous studies have reported significant links between Th2 responses and cancer, including insights into the functions of IgE antibodies and associated effector cells in both antitumour immune surveillance and therapy. The interdisciplinary field of AllergoOncology was given Task Force status by the European Academy of Allergy and Clinical Immunology in 2014. Affiliated expert groups focus on the interface between allergic responses and cancer, applied to immune surveillance, immunomodulation and the functions of IgE-mediated immune responses against cancer, to derive novel insights into more effective treatments. Coincident with rapid expansion in clinical application of cancer immunotherapies, here we review the current state-of-the-art and future translational opportunities, as well as challenges in this relatively new field. Recent developments include improved understanding of Th2 antibodies, intratumoral innate allergy effector cells and mediators, IgE-mediated tumour antigen cross-presentation by dendritic cells, as well as immunotherapeutic strategies such as vaccines and recombinant antibodies, and finally, the management of allergy in daily clinical oncology. Shedding light on the crosstalk between allergic response and cancer is paving the way for new avenues of treatment. © 2016 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.

AllergoOncology - The impact of Allergy in Oncology. EAACI Position Paper

PubMed Central

Jensen-Jarolim, E; Bax, HJ; Bianchini, R; Capron, M; Corrigan, C; Castells, M; Dombrowicz, D; Daniels-Wells, TR; Fazekas, J; Fiebiger, E; Gatault, S; Gould, HJ; Janda, J; Josephs, DH; Karagiannis, P; Levi-Schaffer, F; Meshcheryakova, A; Mechtcheriakova, D; Mekori, Y; Mungenast, F; Nigro, EA; Penichet, ML; Redegeld, F; Saul, L; Singer, J; Spicer, JF; Siccardi, AG; Spillner, E; Turner, MC; Untersmayr, E; Vangelista, L; Karagiannis, SN

2017-01-01

Th2 immunity and allergic immune surveillance play critical roles in host responses to pathogens, parasites and allergens. Numerous studies have reported significant links between Th2 responses and cancer, including insights into the functions of IgE antibodies and associated effector cells in both anti-tumour immune surveillance and therapy. The interdisciplinary field of AllergoOncology was given Task Force status by the European Academy of Allergy and Clinical Immunology in 2014. Affiliated expert groups focus on the interface between allergic responses and cancer, applied to immune surveillance, immunomodulation and the functions of IgE-mediated immune responses against cancer, to derive novel insights into more effective treatments. Co-incident with rapid expansion in clinical application of cancer immunotherapies, here we review the current state-of-the-art and future translational opportunities, as well as challenges in this relatively new field. Recent developments include improved understanding of Th2 antibodies, intra-tumoural innate allergy effector cells and mediators, IgE-mediated tumour antigen cross-presentation by dendritic cells, as well as immunotherapeutic strategies such as vaccines and recombinant antibodies, and finally, the management of allergy in daily clinical oncology. Shedding light on the cross-talk between allergic response and cancer is paving the way for new avenues of treatment. PMID:28032353

Worry spreads: interpersonal transfer of problem-related anxiety.

PubMed

Parkinson, Brian; Simons, Gwenda

2012-01-01

This paper distinguishes processes potentially contributing to interpersonal anxiety transfer, including object-directed social appraisal, empathic worry, and anxiety contagion, and reviews evidence for their operation. We argue that these anxiety-transfer processes may be exploited strategically when attempting to regulate relationship partners' emotion. More generally, anxiety may serve as either a warning signal to other people about threat (alerting function) or an appeal for emotional support or practical help (comfort-seeking function). Tensions between these two interpersonal functions may account for mutually incongruent interpersonal responses to expressed anxiety, including mistargeted interpersonal regulation attempts. Because worry waxes and wanes over time as a function of other people's ongoing reactions, interpersonal interventions may help to alleviate some of its maladaptive consequences.

Cardiovascular Adaptations to Long Duration Head Down Tilt Bed Rest

NASA Technical Reports Server (NTRS)

Platts, Steven H.; Meck, Janice V.; Martin, David S.; Freeman-Perez, Sondra A.; Riberio, Christine; Garcia, Kathleen M.; Waters, Wendy W.

2007-01-01

Orthostatic hypotension is a recognized risk for crewmembers returning from space. Numerous cardiovascular mechanisms have been proposed to account for this problem including vascular and cardiac dysfunction. We studied arterial and cardiac function in 6-degree head-down tilt bed rest, which is the most widely accepted ground-based analog of spaceflight. Eleven subjects are included in this study (8 men and 3 women). Data analysis was limited to the first 49 days, and compared to pre-bed rest baseline data. Using ultrasound, data was collected on arterial diameters and flows at baseline and during reactive hyperemia and following administration of nitroglycerin. Echocardiography was used to acquire information regarding systolic and diastolic function as well as ventricular mass and diameter. Plasma volumes were significantly decreased by 7 days of bed rest and stayed down through 49 days. There were no differences in reactive hyperemic response in the arm at any time point. However, the hyperemic response in the leg was significantly increased at day 49. Arterial responses to nitroglycerin did not change over the duration of bed rest (day effect) in either the arm or leg, but there was a significant difference between the arm and the leg responses. There was a marked decrease in anterior tibial intimal-medial thickness at days 21, 35 and 49. Several cardiac functional parameters including IVRT, Mitral e-wave, ejection time, velocity of circumferential shortening and myocardial performance index were significantly changed following 49 days of bed rest. These data show that some cardiovascular measures change during bed rest, while others do not. Further study is needed to determine if these measures can provide any insight into the effects of bed rest, or spaceflight, on human cardiovascular performance.

Assessment of the Absolute Excitatory Level of the Retina by Flicker ERG.

PubMed

Tanimoto, Naoyuki; Seeliger, Mathias W

2018-01-01

Electroretinography (ERG) is important for functional diagnostics of the retina. Types of information about retinal function obtainable by ERG differ depending on recording conditions, e.g., a combination of light stimulus and adaptation. In terms of stimulation, single-flash and flicker stimuli are frequently used because response properties have been well investigated, allowing an assessment of fundamental retinal functionality; for example, how photoreceptors and bipolar cells, including signal transmission between them, are affected under pathological conditions. Usually, ERGs are recorded with a nonzero lower cutoff frequency of amplifiers to avoid certain artifacts, and additionally, responses are averaged over time so that non-event-related signals are cancelled out. However, the improved signal quality is associated with a loss of information. Especially in steady-state flicker ERG, information about the absolute baseline of recordings is missing because the prestimulus baseline is not included on the recording trace as well as because a zero response is obtained in all cases in which the signal baseline stays constant for a sufficient amount of time. In other words, it is impossible to tell from the conventional flicker ERG whether a zero signal is obtained under conditions of maximal or no excitation of the visual system. In this chapter, we describe a direct current ERG protocol (featuring a lower cutoff frequency of zero) with repetitive single flashes mimicking conventional flicker that contains a defined onset. Using this recording protocol, it is possible to assess not only the absolute excitatory level of the retina but also the development of steady-state responses from the single flash response.

Emotional and cognitive functional imaging of estrogen and progesterone effects in the female human brain: a systematic review.

PubMed

Toffoletto, Simone; Lanzenberger, Rupert; Gingnell, Malin; Sundström-Poromaa, Inger; Comasco, Erika

2014-12-01

Ovarian hormones are pivotal for the physiological maintenance of the brain function as well as its response to environmental stimuli. There is mounting evidence attesting the relevance of endogenous ovarian hormones as well as exogenous estradiol and progesterone for emotional and cognitive processing. The present review systematically summarized current knowledge on sex steroid hormonal modulation of neural substrates of emotion and cognition revealed by functional magnetic resonance imaging (fMRI). Twenty-four studies of healthy naturally cycling and combined oral contraceptives (COC) user women, or women undergoing experimental manipulations, during their reproductive age, were included. Furthermore, six studies of premenstrual dysphoric disorder (PMDD), a hormonally based mood disorder, and three of gender dysphoria (GD), which provides an intriguing opportunity to examine the effect of high-dose cross-sex hormone therapy (CSHT) on brain functioning, were included. Globally, low (early follicular and the entire follicular phase for estrogen and progesterone, respectively) and high (COC, CSHT, late follicular and luteal phase for estrogen; COC, mid- and late-luteal phase for progesterone) hormonal milieu diversely affected the response of several brain regions including the amygdala, anterior cingulate cortex, and inferior frontal gyrus, but their functional recruitment across groups and domains was scattered. The constellation of findings provides initial evidence of the influence of sex steroid hormones on cortical and subcortical regions implicated in emotional and cognitive processing. Further well-powered and multimodal neuroimaging studies will be needed to identify the neural mechanism of functional brain alterations induced by sex steroid hormones. Copyright © 2014 Elsevier Ltd. All rights reserved.

Test-Anchored Vibration Response Predictions for an Acoustically Energized Curved Orthogrid Panel with Mounted Components

NASA Technical Reports Server (NTRS)

Frady, Gregory P.; Duvall, Lowery D.; Fulcher, Clay W. G.; Laverde, Bruce T.; Hunt, Ronald A.

2011-01-01

rich body of vibroacoustic test data was recently generated at Marshall Space Flight Center for component-loaded curved orthogrid panels typical of launch vehicle skin structures. The test data were used to anchor computational predictions of a variety of spatially distributed responses including acceleration, strain and component interface force. Transfer functions relating the responses to the input pressure field were generated from finite element based modal solutions and test-derived damping estimates. A diffuse acoustic field model was applied to correlate the measured input sound pressures across the energized panel. This application quantifies the ability to quickly and accurately predict a variety of responses to acoustically energized skin panels with mounted components. Favorable comparisons between the measured and predicted responses were established. The validated models were used to examine vibration response sensitivities to relevant modeling parameters such as pressure patch density, mesh density, weight of the mounted component and model form. Convergence metrics include spectral densities and cumulative root-mean squared (RMS) functions for acceleration, velocity, displacement, strain and interface force. Minimum frequencies for response convergence were established as well as recommendations for modeling techniques, particularly in the early stages of a component design when accurate structural vibration requirements are needed relatively quickly. The results were compared with long-established guidelines for modeling accuracy of component-loaded panels. A theoretical basis for the Response/Pressure Transfer Function (RPTF) approach provides insight into trends observed in the response predictions and confirmed in the test data. The software developed for the RPTF method allows easy replacement of the diffuse acoustic field with other pressure fields such as a turbulent boundary layer (TBL) model suitable for vehicle ascent. Structural responses using a TBL model were demonstrated, and wind tunnel tests have been proposed to anchor the predictions and provide new insight into modeling approaches for this environment. Finally, design load factors were developed from the measured and predicted responses and compared with those derived from traditional techniques such as historical Mass Acceleration Curves and Barrett scaling methods for acreage and component-loaded panels.

GADRAS-DRF 18.6 User's Manual

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

Horne, Steve M.; Thoreson, Greg G.; Theisen, Lisa A.

2016-05-01

The Gamma Detector Response and Analysis Software–Detector Response Function (GADRAS-DRF) application computes the response of gamma-ray and neutron detectors to incoming radiation. This manual provides step-by-step procedures to acquaint new users with the use of the application. The capabilities include characterization of detector response parameters, plotting and viewing measured and computed spectra, analyzing spectra to identify isotopes, and estimating source energy distributions from measured spectra. GADRAS-DRF can compute and provide detector responses quickly and accurately, giving users the ability to obtain usable results in a timely manner (a matter of seconds or minutes).

Identification of rice genes associated with cosmic-ray response via co-expression gene network analysis.

PubMed

Hwang, Sun-Goo; Kim, Dong Sub; Hwang, Jung Eun; Han, A-Reum; Jang, Cheol Seong

2014-05-15

In order to better understand the biological systems that are affected in response to cosmic ray (CR), we conducted weighted gene co-expression network analysis using the module detection method. By using the Pearson's correlation coefficient (PCC) value, we evaluated complex gene-gene functional interactions between 680 CR-responsive probes from integrated microarray data sets, which included large-scale transcriptional profiling of 1000 microarray samples. These probes were divided into 6 distinct modules that contained 20 enriched gene ontology (GO) functions, such as oxidoreductase activity, hydrolase activity, and response to stimulus and stress. In particular, modules 1 and 2 commonly showed enriched annotation categories such as oxidoreductase activity, including enriched cis-regulatory elements known as ROS-specific regulators. These results suggest that the ROS-mediated irradiation response pathway is affected by CR in modules 1 and 2. We found 243 ionizing radiation (IR)-responsive probes that exhibited similarities in expression patterns in various irradiation microarray data sets. The expression patterns of 6 randomly selected IR-responsive genes were evaluated by quantitative reverse transcription polymerase chain reaction following treatment with CR, gamma rays (GR), and ion beam (IB); similar patterns were observed among these genes under these 3 treatments. Moreover, we constructed subnetworks of IR-responsive genes and evaluated the expression levels of their neighboring genes following GR treatment; similar patterns were observed among them. These results of network-based analyses might provide a clue to understanding the complex biological system related to the CR response in plants. Copyright © 2014 Elsevier B.V. All rights reserved.

Resurgence of target responding does not exceed increases in inactive responding in a forced-choice alternative reinforcement procedure in humans

PubMed Central

Sweeney, Mary M.; Shahan, Timothy A.

2016-01-01

Resurgence following removal of alternative reinforcement has been studied in non-human animals, children with developmental disabilities, and typically functioning adults. Adult human laboratory studies have included responses without a controlled history of reinforcement, included only two response options, or involved extensive training. Arbitrary responses allow for control over history of reinforcement. Including an inactive response never associated with reinforcement allows the conclusion that resurgence exceeds extinction-induced variability. Although procedures with extensive training produce reliable resurgence, a brief procedure with the same experimental control would allow more efficient examination of resurgence in adult humans. We tested the acceptability of a brief, single-session, three-alternative forced-choice procedure as a model of resurgence in undergraduates. Selecting a shape was the target response (reinforced in Phase I), selecting another shape was the alternative response (reinforced in Phase II), and selecting a third shape was never reinforced. Despite manipulating number of trials and probability of reinforcement, resurgence of the target response did not consistently exceed increases in the inactive response. Our findings reiterate the importance of an inactive control response and call for reexamination of resurgence studies using only two response options. We discuss potential approaches to generate an acceptable, brief human laboratory resurgence procedure. PMID:26724752

49 CFR 172.704 - Training requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... PROVISIONS, HAZARDOUS MATERIALS COMMUNICATIONS, EMERGENCY RESPONSE INFORMATION, TRAINING REQUIREMENTS, AND... communication standards of this subchapter. (2) Function-specific training. (i) Each hazmat employee must be... must include company security objectives, organizational security structure, specific security...

Organization and Function of a School Health Council.

ERIC Educational Resources Information Center

Valente, Carmine M.; Lumb, Karen J.

1981-01-01

The purpose, activities, organization, and responsibility of the Prince George's County School Health Council are described. The purposes of the Council include advisement, representation, screening, and the development of new programs. (JN)

RNA-Seq and Gene Network Analysis Uncover Activation of an ABA-Dependent Signalosome During the Cork Oak Root Response to Drought

PubMed Central

Magalhães, Alexandre P.; Verde, Nuno; Reis, Francisca; Martins, Inês; Costa, Daniela; Lino-Neto, Teresa; Castro, Pedro H.; Tavares, Rui M.; Azevedo, Herlânder

2016-01-01

Quercus suber (cork oak) is a West Mediterranean species of key economic interest, being extensively explored for its ability to generate cork. Like other Mediterranean plants, Q. suber is significantly threatened by climatic changes, imposing the need to quickly understand its physiological and molecular adaptability to drought stress imposition. In the present report, we uncovered the differential transcriptome of Q. suber roots exposed to long-term drought, using an RNA-Seq approach. 454-sequencing reads were used to de novo assemble a reference transcriptome, and mapping of reads allowed the identification of 546 differentially expressed unigenes. These were enriched in both effector genes (e.g., LEA, chaperones, transporters) as well as regulatory genes, including transcription factors (TFs) belonging to various different classes, and genes associated with protein turnover. To further extend functional characterization, we identified the orthologs of differentially expressed unigenes in the model species Arabidopsis thaliana, which then allowed us to perform in silico functional inference, including gene network analysis for protein function, protein subcellular localization and gene co-expression, and in silico enrichment analysis for TFs and cis-elements. Results indicated the existence of extensive transcriptional regulatory events, including activation of ABA-responsive genes and ABF-dependent signaling. We were then able to establish that a core ABA-signaling pathway involving PP2C-SnRK2-ABF components was induced in stressed Q. suber roots, identifying a key mechanism in this species’ response to drought. PMID:26793200

Engineered control of enzyme structural dynamics and function.

PubMed

Boehr, David D; D'Amico, Rebecca N; O'Rourke, Kathleen F

2018-04-01

Enzymes undergo a range of internal motions from local, active site fluctuations to large-scale, global conformational changes. These motions are often important for enzyme function, including in ligand binding and dissociation and even preparing the active site for chemical catalysis. Protein engineering efforts have been directed towards manipulating enzyme structural dynamics and conformational changes, including targeting specific amino acid interactions and creation of chimeric enzymes with new regulatory functions. Post-translational covalent modification can provide an additional level of enzyme control. These studies have not only provided insights into the functional role of protein motions, but they offer opportunities to create stimulus-responsive enzymes. These enzymes can be engineered to respond to a number of external stimuli, including light, pH, and the presence of novel allosteric modulators. Altogether, the ability to engineer and control enzyme structural dynamics can provide new tools for biotechnology and medicine. © 2018 The Protein Society.

Predictive information processing is a fundamental learning mechanism present in early development: evidence from infants.

PubMed

Trainor, Laurel J

2012-02-01

Evidence is presented that predictive coding is fundamental to brain function and present in early infancy. Indeed, mismatch responses to unexpected auditory stimuli are among the earliest robust cortical event-related potential responses, and have been measured in young infants in response to many types of deviation, including in pitch, timing, and melodic pattern. Furthermore, mismatch responses change quickly with specific experience, suggesting that predictive coding reflects a powerful, early-developing learning mechanism. Copyright © 2011 Elsevier B.V. All rights reserved.

Physiological responses to environmental factors related to space flight

NASA Technical Reports Server (NTRS)

Pace, N.; Grunbaum, B. W.; Kodama, A. M.; Mains, R. C.; Rahlmann, D. F.

1975-01-01

Physiological procedures and instrumentation developed for the measurement of hemodynamic and metabolic parameters during prolonged periods of weightlessness are described along with the physiological response of monkeys to weightlessness. Specific areas examined include: cardiovascular studies; thyroid function; blood oxygen transport; growth and reproduction; excreta analysis for metabolic balance studies; and electrophoretic separation of creatine phosphokinase isoenzymes in human blood.

Congenital Cytomegalovirus Infection: Molecular Mechanisms Mediating Viral Pathogenesis

PubMed Central

Schleiss, Mark R.

2013-01-01

Human cytomegalovirus (CMV) is responsible for approximately 40,000 congenital infections in the United States each year. Congenital CMV disease frequently produces serious neurodevelopmental disability, as well as vision impairment and sensorineural hearing loss. Development of a CMV vaccine is therefore considered to be a major public health priority. The mechanisms by which CMV injures the fetus are complex and likely include a combination of direct fetal injury induced by pathologic virally-encoded gene products, an inability of the maternal immune response to control infection, and the direct impact of infection on placental function. CMV encodes gene products that function, both at the RNA and the protein level, to interfere with many cellular processes. These include gene products that modify the cell cycle; interfere with apoptosis; induce an inflammatory response; mediate vascular injury; induce site-specific breakage of chromosomes; promote oncogenesis; dysregulate cellular proliferation; and facilitate evasion of host immune responses. This minireview summarizes current concepts regarding these aspects of the molecular virology of CMV and the potential pathogenic impact of viral gene expression on the developing fetus. Areas for potential development of novel therapeutic intervention are suggested for improving the outcome of this disabling congenital infection. PMID:21827434

Genome-Wide Analyses of the Soybean F-Box Gene Family in Response to Salt Stress

PubMed Central

Jia, Qi; Xiao, Zhi-Xia; Wong, Fuk-Ling; Sun, Song; Liang, Kang-Jing; Lam, Hon-Ming

2017-01-01

The F-box family is one of the largest gene families in plants that regulate diverse life processes, including salt responses. However, the knowledge of the soybean F-box genes and their roles in salt tolerance remains limited. Here, we conducted a genome-wide survey of the soybean F-box family, and their expression analysis in response to salinity via in silico analysis of online RNA-sequencing (RNA-seq) data and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) to predict their potential functions. A total of 725 potential F-box proteins encoded by 509 genes were identified and classified into 9 subfamilies. The gene structures, conserved domains and chromosomal distributions were characterized. There are 76 pairs of duplicate genes identified, including genome-wide segmental and tandem duplication events, which lead to the expansion of the number of F-box genes. The in silico expression analysis showed that these genes would be involved in diverse developmental functions and play an important role in salt response. Our qRT-PCR analysis confirmed 12 salt-responding F-box genes. Overall, our results provide useful information on soybean F-box genes, especially their potential roles in salt tolerance. PMID:28417911

Genome-Wide Analyses of the Soybean F-Box Gene Family in Response to Salt Stress.

PubMed

Jia, Qi; Xiao, Zhi-Xia; Wong, Fuk-Ling; Sun, Song; Liang, Kang-Jing; Lam, Hon-Ming

2017-04-12

The F-box family is one of the largest gene families in plants that regulate diverse life processes, including salt responses. However, the knowledge of the soybean F-box genes and their roles in salt tolerance remains limited. Here, we conducted a genome-wide survey of the soybean F-box family, and their expression analysis in response to salinity via in silico analysis of online RNA-sequencing (RNA-seq) data and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) to predict their potential functions. A total of 725 potential F-box proteins encoded by 509 genes were identified and classified into 9 subfamilies. The gene structures, conserved domains and chromosomal distributions were characterized. There are 76 pairs of duplicate genes identified, including genome-wide segmental and tandem duplication events, which lead to the expansion of the number of F-box genes. The in silico expression analysis showed that these genes would be involved in diverse developmental functions and play an important role in salt response. Our qRT-PCR analysis confirmed 12 salt-responding F-box genes. Overall, our results provide useful information on soybean F-box genes, especially their potential roles in salt tolerance.

Functional specificity for high-level linguistic processing in the human brain.

PubMed

Fedorenko, Evelina; Behr, Michael K; Kanwisher, Nancy

2011-09-27

Neuroscientists have debated for centuries whether some regions of the human brain are selectively engaged in specific high-level mental functions or whether, instead, cognition is implemented in multifunctional brain regions. For the critical case of language, conflicting answers arise from the neuropsychological literature, which features striking dissociations between deficits in linguistic and nonlinguistic abilities, vs. the neuroimaging literature, which has argued for overlap between activations for linguistic and nonlinguistic processes, including arithmetic, domain general abilities like cognitive control, and music. Here, we use functional MRI to define classic language regions functionally in each subject individually and then examine the response of these regions to the nonlinguistic functions most commonly argued to engage these regions: arithmetic, working memory, cognitive control, and music. We find little or no response in language regions to these nonlinguistic functions. These data support a clear distinction between language and other cognitive processes, resolving the prior conflict between the neuropsychological and neuroimaging literatures.

Evaluation of a toxicogenomic approach to the local lymph node assay (LLNA).

PubMed

Boverhof, Darrell R; Gollapudi, B Bhaskar; Hotchkiss, Jon A; Osterloh-Quiroz, Mandy; Woolhiser, Michael R

2009-02-01

Genomic technologies have the potential to enhance and complement existing toxicology endpoints; however, assessment of these approaches requires a systematic evaluation including a robust experimental design with genomic endpoints anchored to traditional toxicology endpoints. The present study was conducted to assess the sensitivity of genomic responses when compared with the traditional local lymph node assay (LLNA) endpoint of lymph node cell proliferation and to evaluate the responses for their ability to provide insights into mode of action. Female BALB/c mice were treated with the sensitizer trimellitic anhydride (TMA), following the standard LLNA dosing regimen, at doses of 0.1, 1, or 10% and traditional tritiated thymidine ((3)HTdR) incorporation and gene expression responses were monitored in the auricular lymph nodes. Additional mice dosed with either vehicle or 10% TMA and sacrificed on day 4 or 10, were also included to examine temporal effects on gene expression. Analysis of (3)HTdR incorporation revealed TMA-induced stimulation indices of 2.8, 22.9, and 61.0 relative to vehicle with an EC(3) of 0.11%. Examination of the dose-response gene expression responses identified 9, 833, and 2122 differentially expressed genes relative to vehicle for the 0.1, 1, and 10% TMA dose groups, respectively. Calculation of EC(3) values for differentially expressed genes did not identify a response that was more sensitive than the (3)HTdR value, although a number of genes displayed comparable sensitivity. Examination of temporal responses revealed 1760, 1870, and 953 differentially expressed genes at the 4-, 6-, and 10-day time points respectively. Functional analysis revealed many responses displayed dose- and time-specific induction patterns within the functional categories of cellular proliferation and immune response, including numerous immunoglobin genes which were highly induced at the day 10 time point. Overall, these experiments have systematically illustrated the potential utility of genomic endpoints to enhance the LLNA and support further exploration of this approach through examination of a more diverse array of chemicals.

Climate extremes drive changes in functional community structure.

PubMed

Boucek, Ross E; Rehage, Jennifer S

2014-06-01

The response of communities to climate extremes can be quite variable. Much of this variation has been attributed to differences in community-specific functional trait diversity, as well as community composition. Yet, few if any studies have explicitly tested the response of the functional trait structure of communities following climate extremes (CEs). Recently in South Florida, two independent, but sequential potential CEs took place, a 2010 cold front, followed by a 2011 drought, both of which had profound impacts on a subtropical estuarine fish community. These CEs provided an opportunity to test whether the structure of South Florida fish communities following each extreme was a result of species-specific differences in functional traits. From historical temperature (1927-2012) and freshwater inflows records into the estuary (1955-2012), we determined that the cold front was a statistically extreme disturbance, while the drought was not, but rather a decadal rare disturbance. The two disturbances predictably affected different parts of functional community structure and thus different component species. The cold front virtually eliminated tropical species, including large-bodied snook, mojarra species, nonnative cichlids, and striped mullet, while having little affect on temperate fishes. Likewise, the drought severely impacted freshwater fishes including Florida gar, bowfin, and two centrarchids, with little effect on euryhaline species. Our findings illustrate the ability of this approach to predict and detect both the filtering effects of different types of disturbances and the implications of the resulting changes in community structure. Further, we highlight the value of this approach to developing predictive frameworks for better understanding community responses to global change. © 2014 John Wiley & Sons Ltd.

Brain local and regional neuroglial alterations in Alzheimer's Disease: cell types, responses and implications.

PubMed

Toledano, Adolfo; Álvarez, María-Isabel; Toledano-Díaz, Adolfo; Merino, José-Joaquín; Rodríguez, José Julio

2016-01-01

From birth to death, neurons are dynamically accompanied by neuroglial cells in a very close morphological and functional relationship. Three families have been classically considered within the CNS: astroglia, oligodendroglia and microglia. Many types/subtypes (including NGR2+ cells), with a wide variety of physiological and pathological effects on neurons, have been described using morphological and immunocytochemical criteria. Glio-glial, glio-neuronal and neuro-glial cell signaling and gliotransmission are phenomena that are essential to support brain functions. Morphofunctional changes resulting from the plasticity of all the glial cell types parallel the plastic neuronal changes that optimize the functionality of neuronal circuits. Moreover, neuroglia possesses the ability to adopt a reactive status (gliosis) in which, generally, new functions arise to improve and restore if needed the neural functionality. All these features make neuroglial cells elements of paramount importance when attempting to explain any physiological or pathological processes in the CNS, because they are involved in both, neuroprotection/neurorepair and neurodegeneration. There exist diverse and profound, regional and local, neuroglial changes in all involutive processes (physiological and pathological aging; neurodegenerative disorders, including Alzheimer ´s disease -AD-), but today, the exact meaning of such modifications (the modifications of the different neuroglial types, in time and place), is not well understood. In this review we consider the different neuroglial cells and their responses in order to understand the possible role they fulfill in pathogenesis, diagnosis and treatment (preventive or palliative) of AD. The existence of differentiated and/or concurrent pathogenic and neuro-protective/neuro-restorative astroglial and microglial responses is highlighted.

Stress and strain in the contractile and cytoskeletal filaments of airway smooth muscle.

PubMed

Deng, Linhong; Bosse, Ynuk; Brown, Nathan; Chin, Leslie Y M; Connolly, Sarah C; Fairbank, Nigel J; King, Greg G; Maksym, Geoffrey N; Paré, Peter D; Seow, Chun Y; Stephen, Newman L

2009-10-01

Stress and strain are omnipresent in the lung due to constant lung volume fluctuation associated with respiration, and they modulate the phenotype and function of all cells residing in the airways including the airway smooth muscle (ASM) cell. There is ample evidence that the ASM cell is very sensitive to its physical environment, and can alter its structure and/or function accordingly, resulting in either desired or undesired consequences. The forces that are either conferred to the ASM cell due to external stretching or generated inside the cell must be borne and transmitted inside the cytoskeleton (CSK). Thus, maintaining appropriate levels of stress and strain within the CSK is essential for maintaining normal function. Despite the importance, the mechanisms regulating/dysregulating ASM cytoskeletal filaments in response to stress and strain remained poorly understood until only recently. For example, it is now understood that ASM length and force are dynamically regulated, and both can adapt over a wide range of length, rendering ASM one of the most malleable living tissues. The malleability reflects the CSK's dynamic mechanical properties and plasticity, both of which strongly interact with the loading on the CSK, and all together ultimately determines airway narrowing in pathology. Here we review the latest advances in our understanding of stress and strain in ASM cells, including the organization of contractile and cytoskeletal filaments, range and adaptation of functional length, structural and functional changes of the cell in response to mechanical perturbation, ASM tone as a mediator of strain-induced responses, and the novel glassy dynamic behaviors of the CSK in relation to asthma pathophysiology.

Inhibitor of lysyl oxidase improves cardiac function and the collagen/MMP profile in response to volume overload.

PubMed

El Hajj, Elia C; El Hajj, Milad C; Ninh, Van K; Gardner, Jason D

2018-05-18

The cardiac extracellular matrix is a complex architectural network that serves many functions including providing structural and biochemical support to surrounding cells, and regulating intercellular signaling pathways. Cardiac function is directly affected by extracellular matrix (ECM) composition, and alterations of the ECM contribute to progression of heart failure. Initially, collagen deposition is an adaptive response that aims to preserve tissue integrity and maintain normal ventricular function. However, the synergistic effects of the pro-inflammatory and pro-fibrotic responses induce a vicious cycle which causes excess activation of myofibroblasts, significantly increasing collagen deposition and accumulation in the matrix. Further, excess synthesis and activation of the enzyme lysyl oxidase (LOX) during disease increases collagen cross-linking, which significantly increases collagen resistance to degradation by matrix metalloproteinases (MMPs). In this study, the aortocaval fistula model of volume overload (VO) was used to determine whether LOX inhibition could prevent adverse changes in the ECM and subsequent cardiac dysfunction. The major findings from this study are that LOX inhibition: (a) prevented VO-induced increases in LV wall stress, (b) partially attenuated VO-induced ventricular hypertrophy, (c) completely blocked the increases in fibrotic proteins, including collagens, MMPs, and their tissue inhibitors (TIMPs), and (d) prevented the VO-induced decline in cardiac function. It remains unclear whether a direct interaction between LOX and MMPs exists; however our studies suggest a potential link between the two since LOX inhibition completely attenuated the VO-induced increases in MMPs. Overall, our studies demonstrate key cardioprotective effects of LOX inhibition against adverse cardiac remodeling due to chronic VO.

Filtered molasses concentrate from sugar cane: natural functional ingredient effective in lowering the glycaemic index and insulin response of high carbohydrate foods.

PubMed

Wright, Alison G; Ellis, Timothy P; Ilag, Leodevico L

2014-12-01

An aqueous filtered molasses concentrate (FMC) sourced from sugar cane was used as a functional ingredient in a range of carbohydrate-containing foods to reduce glycaemic response. When compared to untreated controls, postprandial glucose responses in the test products were reduced 5-20%, assessed by accredited glycaemic index (GI) testing. The reduction in glucose response in the test foods was dose-dependent and directly proportional to the ratio of FMC added to the amount of available carbohydrate in the test products. The insulin response to the foods was also reduced with FMC addition as compared to untreated controls. Inclusion of FMC in test foods did not replace any formulation ingredients; it was incorporated as an additional ingredient to existing formulations. Filtered molasses concentrate, made by a proprietary and patented process, contains many naturally occurring compounds. Some of the identified compounds are known to influence carbohydrate metabolism, and include phenolic compounds, minerals and organic acids. FMC, sourced from a by-product of sugar cane processing, shows potential as a natural functional ingredient capable of modifying carbohydrate metabolism and contributing to GI reduction of processed foods and beverages.

Evaluating and interpreting the chemical relevance of the linear response kernel for atoms II: open shell.

PubMed

Boisdenghien, Zino; Fias, Stijn; Van Alsenoy, Christian; De Proft, Frank; Geerlings, Paul

2014-07-28

Most of the work done on the linear response kernel χ(r,r') has focussed on its atom-atom condensed form χAB. Our previous work [Boisdenghien et al., J. Chem. Theory Comput., 2013, 9, 1007] was the first effort to truly focus on the non-condensed form of this function for closed (sub)shell atoms in a systematic fashion. In this work, we extend our method to the open shell case. To simplify the plotting of our results, we average our results to a symmetrical quantity χ(r,r'). This allows us to plot the linear response kernel for all elements up to and including argon and to investigate the periodicity throughout the first three rows in the periodic table and in the different representations of χ(r,r'). Within the context of Spin Polarized Conceptual Density Functional Theory, the first two-dimensional plots of spin polarized linear response functions are presented and commented on for some selected cases on the basis of the atomic ground state electronic configurations. Using the relation between the linear response kernel and the polarizability we compare the values of the polarizability tensor calculated using our method to high-level values.

Physiological genomics of response to soil drying in diverse Arabidopsis accessions.

PubMed

Des Marais, David L; McKay, John K; Richards, James H; Sen, Saunak; Wayne, Tierney; Juenger, Thomas E

2012-03-01

Arabidopsis thaliana, like many species, is characterized by abundant genetic variation. This variation is rapidly being cataloged at the sequence level, but careful dissection of genetic variation in whole-organism responses to stresses encountered in the natural environment are lacking; this functional variation can be exploited as a natural mutant screen to determine gene function. Here, we document physiological and transcriptomic response to soil drying in 17 natural accessions of Arabidopsis. By imposing ecologically realistic stress conditions, we found that acclimation in Arabidopsis involved a strong signature of increased investment in photosynthesis, carbohydrate turnover, and root growth. Our results extend previous work in the Columbia accession suggesting that abscisic acid signaling pathways play an important role in drought stress response. We also identified several mechanisms, including an increase in leaf nitrogen concentration and upregulation of two-component signaling relays, that were common to most natural accessions but had not been identified in studies using only the Columbia accession. Principal component analysis reveals strong correlations between suites of genes and specific physiological responses to stress. The functional variants we identified may represent adaptive mutations in natural habitats and useful variants for agronomic improvement of crop species.

Matricellular homologs in the foreign body response: hevin suppresses inflammation, but hevin and SPARC together diminish angiogenesis.

PubMed

Barker, Thomas H; Framson, Paul; Puolakkainen, Pauli A; Reed, May; Funk, Sarah E; Sage, E Helene

2005-03-01

Implanted foreign materials, used to restore or assist tissue function, elicit an initial acute inflammatory response followed by chronic fibrosis that leads to the entrapment of the biomaterial in a thick, poorly vascularized collagenous capsule. Matricellular proteins, secreted macromolecules that interact with extracellular matrix proteins but do not in themselves serve structural roles, have been identified as important mediators of the foreign body response that includes inflammation, angiogenesis, and collagen synthesis and assembly. In this report we delineate functions of hevin and SPARC, two homologs of the SPARC family of matricellular proteins, in the foreign body response. Despite their sequence similarity, hevin and SPARC mediate different aspects of this fibrotic response. Using mice with targeted gene deletions, we show that hevin is central to the progression of biomaterial-induced inflammation whereas SPARC regulates the formation of the collagenous capsule. Although vascular density within the capsule is unaltered in the absence of either protein, SPARC-hevin double-null capsules show substantially increased numbers of vessels, indicating compensatory functions for these two proteins in the inhibition of angiogenesis. These results provide important information for further development of implant technology.

Physiological Genomics of Response to Soil Drying in Diverse Arabidopsis Accessions[W][OA

PubMed Central

Des Marais, David L.; McKay, John K.; Richards, James H.; Sen, Saunak; Wayne, Tierney; Juenger, Thomas E.

2012-01-01

Arabidopsis thaliana, like many species, is characterized by abundant genetic variation. This variation is rapidly being cataloged at the sequence level, but careful dissection of genetic variation in whole-organism responses to stresses encountered in the natural environment are lacking; this functional variation can be exploited as a natural mutant screen to determine gene function. Here, we document physiological and transcriptomic response to soil drying in 17 natural accessions of Arabidopsis. By imposing ecologically realistic stress conditions, we found that acclimation in Arabidopsis involved a strong signature of increased investment in photosynthesis, carbohydrate turnover, and root growth. Our results extend previous work in the Columbia accession suggesting that abscisic acid signaling pathways play an important role in drought stress response. We also identified several mechanisms, including an increase in leaf nitrogen concentration and upregulation of two-component signaling relays, that were common to most natural accessions but had not been identified in studies using only the Columbia accession. Principal component analysis reveals strong correlations between suites of genes and specific physiological responses to stress. The functional variants we identified may represent adaptive mutations in natural habitats and useful variants for agronomic improvement of crop species. PMID:22408074

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.

Quantum Dot and Polymer Composite Cross-Reactive Array for Chemical Vapor Detection.

PubMed

Bright, Collin J; Nallon, Eric C; Polcha, Michael P; Schnee, Vincent P

2015-12-15

A cross-reactive chemical sensing array was made from CdSe Quantum Dots (QDs) and five different organic polymers by inkjet printing to create segmented fluorescent composite regions on quartz substrates. The sensor array was challenged with exposures from two sets of analytes, including one set of 14 different functionalized benzenes and one set of 14 compounds related to security concerns, including the explosives trinitrotoluene (TNT) and ammonium nitrate. The array was broadly responsive to analytes with different chemical functionalities due to the multiple sensing mechanisms that altered the QDs' fluorescence. The sensor array displayed excellent discrimination between members within both sets. Classification accuracy of more than 93% was achieved, including the complete discrimination of very similar dinitrobenzene isomers and three halogenated, substituted benzene compounds. The simple fabrication, broad responsivity, and high discrimination capacity of this type of cross-reactive array are ideal qualities for the development of sensors with excellent sensitivity to chemical and explosive threats while maintaining low false alarm rates.

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.

Eosinophils in mucosal immune responses

PubMed Central

Travers, J; Rothenberg, M E

2015-01-01

Eosinophils, multifunctional cells that contribute to both innate and adaptive immunity, are involved in the initiation, propagation and resolution of immune responses, including tissue repair. They achieve this multifunctionality by expression of a diverse set of activation receptors, including those that directly recognize pathogens and opsonized targets, and by their ability to store and release preformed cytotoxic mediators that participate in host defense, to produce a variety of de novo pleotropic mediators and cytokines and to interact directly and indirectly with diverse cell types, including adaptive and innate immunocytes and structural cells. Herein, we review the basic biology of eosinophils and then focus on new emerging concepts about their role in mucosal immune homeostasis, particularly maintenance of intestinal IgA. We review emerging data about their development and regulation and describe new concepts concerning mucosal eosinophilic diseases. We describe recently developed therapeutic strategies to modify eosinophil levels and function and provide collective insight about the beneficial and detrimental functions of these enigmatic cells. PMID:25807184

Why is impaired sexual function distressing to women? The primacy of pleasure in female sexual dysfunction.

PubMed

Stephenson, Kyle R; Meston, Cindy M

2015-03-01

Recent research has highlighted a complex association between female sexual function and subjective distress regarding sexual activity. These findings are difficult to explain given limited knowledge as to the mechanisms through which impaired sexual function causes distress. The current study assessed whether a number of specific consequences of impaired sexual function, including decreased physical pleasure, disruption of sexual activity, and negative partner responses, mediated the association between sexual function and distress. Eighty-seven women in sexually active relationships reporting impairments in sexual function completed validated self-report measures and daily online assessments of sexual experiences. Participants completed the Sexual Satisfaction Scale for Women, the Female Sexual Function Index, and the Measure of Sexual Consequences. Results suggested that decreased physical pleasure and disruption of sexual activity, but not partner responses, statistically mediated the association between sexual function and distress. Sexual consequences represent potential maintaining factors of sexual dysfunction that are highly distressing to women. Results are discussed in the context of theoretical models of sexual dysfunction and related treatments. © 2014 International Society for Sexual Medicine.

Why is impaired sexual function distressing to women? The primacy of pleasure in female sexual dysfunction

PubMed Central

Stephenson, Kyle R.; Meston, Cindy M.

2015-01-01

Introduction Recent research has highlighted a complex association between female sexual function and subjective distress regarding sexual activity. These findings are difficult to explain given limited knowledge as to the mechanisms through which impaired sexual function causes distress. Aim The current study assessed whether a number of specific consequences of impaired sexual function, including decreased physical pleasure, disruption of sexual activity, and negative partner responses, mediated the association between sexual function and distress. Methods Eighty seven women in sexually active relationships reporting impairments in sexual function completed validated self-report measures and daily online assessments of sexual experiences. Main Outcome Measures Participants completed the Sexual Satisfaction Scale for Women (SSS-W), the Female Sexual Function Index (FSFI), and the Measure of Sexual Consequences (MSC). Results Results suggested that decreased physical pleasure and disruption of sexual activity, but not partner responses, statistically mediated the association between sexual function and distress. Conclusion Sexual consequences represent potential maintaining factors of sexual dysfunction that are highly distressing to women. Results are discussed in the context of theoretical models of sexual dysfunction and related treatments. PMID:25556719

Family involvement in the psychological treatment of obsessive-compulsive disorder: A meta-analysis

PubMed Central

Thompson-Hollands, Johanna; Edson, Aubrey; Tompson, Martha C.; Comer, Jonathan S.

2014-01-01

Psychological treatments for OCD are increasingly aimed at improving outcomes by directly incorporating family members to address family disruption, dysfunction, or symptom accommodation. Much remains to be learned about the pooled effects of “family-inclusive treatment” (FIT) for OCD and factors that may explain variation in response. Random-effects meta-analytic procedures were conducted to empirically evaluate the overall effect of FITs on OCD, and treatment moderators. Study search criteria yielded 29 studies examining FIT response in 1,366 OCD patients. Outcome variables included OCD symptoms and global functioning. Examined moderators included age group, gender, minority status, treatment length and format, and inclusion of specific family-focused treatment elements. FITs for OCD demonstrated a large overall effect on OCD symptoms (pooled d = 1.68, SE = 0.14) and global functioning (pooled d = 0.98, SE = 0.14). Moderator analyses found that individual family treatments (versus group) and FITs targeting family accommodation of symptoms (versus those that did not target accommodation) were associated with greater improvements in patient functioning. Results indicate a robust overall response to FITs for OCD and clarify key moderators that inform optimal circumstances for effective treatment. Findings underscore the need for continued momentum in the development, evaluation, and dissemination of FITs for OCD. PMID:24798816

Processing communications events in parallel active messaging interface by awakening thread from wait state

DOEpatents

Archer, Charles J; Blocksome, Michael A; Ratterman, Joseph D; Smith, Brian E

2013-10-22

Processing data communications events in a parallel active messaging interface (`PAMI`) of a parallel computer that includes compute nodes that execute a parallel application, with the PAMI including data communications endpoints, and the endpoints are coupled for data communications through the PAMI and through other data communications resources, including determining by an advance function that there are no actionable data communications events pending for its context, placing by the advance function its thread of execution into a wait state, waiting for a subsequent data communications event for the context; responsive to occurrence of a subsequent data communications event for the context, awakening by the thread from the wait state; and processing by the advance function the subsequent data communications event now pending for the context.

Disordered follicle development

PubMed Central

Chang, R. Jeffrey; Cook-Andersen, Heidi

2013-01-01

Alterations of ovarian follicle morphology and function have been well documented in women with PCOS. These include increased numbers of growing preantral follicles, failure of follicle growth beyond the mid-antral stage, evidence of granulosa call degeneration, and theca cell hyperplasia. Functional abnormalities include paradoxical granulosa cell hyperresponsiveness to FSH which is clinically linked to ovarian hyperstimulation during ovulation induction. In addition, there is likely a primary theca cell defect that accounts for the majority of excess androgen production in this disorder. The precise mechanisms responsible for altered follicle function are not completely clear. However, several factors appear to influence normal advancement of follicle development as well as impair ovarian steroidogenesis. These include intra- as well as extraovarian influences that distort normal ovarian growth and disrupt steroid production by follicle cells. PMID:22874072

Biochemical factors modulating female genital sexual arousal physiology.

PubMed

Traish, Abdulmaged M; Botchevar, Ella; Kim, Noel N

2010-09-01

Female genital sexual arousal responses are complex neurophysiological processes consisting of central and peripheral components that occur following sexual stimulation. The peripheral responses in sexual arousal include genital vasocongestion, engorgement and lubrication resulting from a surge of vaginal and clitoral blood flow. These hemodynamic events are mediated by a host of neurotransmitters and vasoactive agents. To discuss the role of various biochemical factors modulating female genital sexual arousal responses. A comprehensive literature review was conducted using the PubMed database and citations were selected, based on topical relevance, and examined for study methodology and major findings. Data from peer-reviewed publications. Adrenergic as well as non-adrenergic non-cholinergic neurotransmitters play an important role in regulating genital physiological responses by mediating vascular and non-vascular smooth muscle contractility. Vasoactive peptides and neuropeptides also modulate genital sexual responses by regulating vascular and non-vascular smooth muscle cells and epithelial function. The endocrine milieu, particularly sex steroid hormones, is critical in the maintenance of tissue structure and function. Reduced levels of estrogens and androgen are associated with dramatic alterations in genital tissue structure, including the nerve network, as well as the response to physiological modulators. Furthermore, estrogen and androgen deficiency is associated with reduced expression of sex steroid receptors and most importantly with attenuated genital blood flow and lubrication in response to pelvic nerve stimulation. This article provides an integrated framework describing the physiological and molecular basis of various pathophysiological conditions associated with female genital sexual arousal dysfunction. © 2010 International Society for Sexual Medicine.

Different Signal Enhancement Pathways of Attention and Consciousness Underlie Perception in Humans.

PubMed

van Boxtel, Jeroen J A

2017-06-14

It is not yet known whether attention and consciousness operate through similar or largely different mechanisms. Visual processing mechanisms are routinely characterized by measuring contrast response functions (CRFs). In this report, behavioral CRFs were obtained in humans (both males and females) by measuring afterimage durations over the entire range of inducer stimulus contrasts to reveal visual mechanisms behind attention and consciousness. Deviations relative to the standard CRF, i.e., gain functions, describe the strength of signal enhancement, which were assessed for both changes due to attentional task and conscious perception. It was found that attention displayed a response-gain function, whereas consciousness displayed a contrast-gain function. Through model comparisons, which only included contrast-gain modulations, both contrast-gain and response-gain effects can be explained with a two-level normalization model, in which consciousness affects only the first level and attention affects only the second level. These results demonstrate that attention and consciousness can effectively show different gain functions because they operate through different signal enhancement mechanisms. SIGNIFICANCE STATEMENT The relationship between attention and consciousness is still debated. Mapping contrast response functions (CRFs) has allowed (neuro)scientists to gain important insights into the mechanistic underpinnings of visual processing. Here, the influence of both attention and consciousness on these functions were measured and they displayed a strong dissociation. First, attention lowered CRFs, whereas consciousness raised them. Second, attention manifests itself as a response-gain function, whereas consciousness manifests itself as a contrast-gain function. Extensive model comparisons show that these results are best explained in a two-level normalization model in which consciousness affects only the first level, whereas attention affects only the second level. These findings show dissociations between both the computational mechanisms behind attention and consciousness and the perceptual consequences that they induce. Copyright © 2017 the authors 0270-6474/17/375912-11$15.00/0.

Impact of Sofosbuvir-Based Regimens for the Treatment of Hepatitis C After Liver Transplant on Renal Function: Results of a Canadian National Retrospective Study.

PubMed

Faisal, Nabiha; Bilodeau, Marc; Aljudaibi, Bandar; Hirch, Geri; Yoshida, Eric M; Hussaini, Trana; Ghali, Maged P; Congly, Stephen E; Ma, Mang M; Lilly, Leslie B

2018-04-04

We assessed the impact of sofosbuvir-based regimens on renal function in liver transplant recipients with recurrent hepatitis C virus and the role of renal function on the efficacy and safety of these regimens. In an expanded pan-Canadian cohort, 180 liver transplant recipients were treated with sofosbuvir-based regimens for hepatitis C virus recurrence from January 2014 to May 2015. Mean age was 58 ± 6.85 years, and 50% had F3/4 fibrosis. Patients were stratified into 4 groups based on baseline estimated glomerular filtration rate (calculated by the Modification of Diet in Renal Disease formula): < 30, 30 to 45, 46 to 60, and > 60 mL/min/173 m2. The primary outcome was posttreatment changes in renal function from baseline. Secondary outcomes included sustained virologic response at 12 weeks posttreatment and anemia-related and serious adverse events. Posttreatment renal function was improved in most patients (58%). Renal function declined in 22% of patients, which was more marked in those with estimated glomerular filtration rate < 30 mL/min/173 m2, advanced cirrhosis (P = .05), and aggressive hepatitis C virus/fibrosing cholestatic hepatitis (P < .05). High rates (80%-88%) of sustained virologic response at 12 weeks posttreatment were seen across all renal function strata. Cirrhotic patients with glomerular filtration rates < 30 mL/min/173 m2 had sustained virologic response rates at 12 weeks posttreatment comparable to the overall patient group. Rates of anemia-related adverse events and transfusion requirements increased across decreasing estimated glomerular filtration rate groups, with notably more occurrences with ribavirin-based regimens. Sofosbuvir-based regimens improved overall renal function in liver transplant recipients, with sustained virologic response, suggesting an association of subclinical hepatitis C virus-related renal disease. Sustained virologic response rates at 12 weeks posttreatment (80%-88%) were comparable regardless of baseline renal function but lower in cirrhosis.

The International Index of Erectile Function: development of an adapted tool for use in HIV-positive men who have sex with men.

PubMed

Coyne, Katherine; Mandalia, Sundhiya; McCullough, Sonya; Catalan, Jose; Noestlinger, Christiana; Colebunders, Robert; Asboe, David

2010-02-01

Erectile dysfunction is common in HIV-positive men who have sex with men (MSM). A standardized scale is needed to assess erectile function in clinical practice and research studies. The International Index of Erectile Function (IIEF) is a widely accepted tool for assessing erectile function designed for heterosexual men. We modified the tool for MSM. We present an analysis of internal consistency of the questionnaire in an HIV-positive cohort. The adapted questionnaire included modified questions within each of the five domains of the IIEF: (i) erectile function, (ii) intercourse satisfaction, (iii) orgasmic function, (iv) sexual desire, and (v) overall satisfaction with sex. MSM at seven European HIV treatment centers completed the questionnaire. Responses were analyzed for internal consistency using standardized Cronbach's alpha values within each of the five domains. A factor analysis was performed to confirm the domain structure of the questionnaire. Data from 486 MSM were analyzed. The factor analysis supported the domain structure described. Questions about erectile function, orgasmic function, and sexual desire performed well, with Cronbach's alpha values of 0.82, 0.83, and 0.89, respectively. Questions concerning intercourse satisfaction were less consistent (Cronbach's alpha 0.55) because frequency of attempts at sexual intercourse did not correlate with other responses. Responses about satisfaction with sex with a regular partner diverged from satisfaction with overall sex life. Frequency of morning erections diverged from other aspects of erectile function, whereas erections with masturbation correlated better. Internal consistency was high overall. This tool is suitable for HIV-positive MSM and can be used in screening, research, and monitoring treatment response.

Phenotype and function of nasal dendritic cells

PubMed Central

Lee, Haekyung; Ruane, Darren; Law, Kenneth; Ho, Yan; Garg, Aakash; Rahman, Adeeb; Esterházy, Daria; Cheong, Cheolho; Goljo, Erden; Sikora, Andrew G.; Mucida, Daniel; Chen, Benjamin; Govindraj, Satish; Breton, Gaëlle; Mehandru, Saurabh

2015-01-01

Intranasal vaccination generates immunity across local, regional and distant sites. However, nasal dendritic cells (DC), pivotal for the induction of intranasal vaccine- induced immune responses, have not been studied in detail. Here, using a variety of parameters, we define nasal DCs in mice and humans. Distinct subsets of “classical” DCs, dependent on the transcription factor zbtb46 were identified in the murine nose. The murine nasal DCs were FLT3 ligand-responsive and displayed unique phenotypic and functional characteristics including the ability to present antigen, induce an allogeneic T cell response and migrate in response to LPS or live bacterial pathogens. Importantly, in a cohort of human volunteers, BDCA-1+ DCs were observed to be the dominant nasal DC population at steady state. During chronic inflammation, the frequency of both BDCA-1+ and BDCA-3hi DCs was reduced in the nasal tissue, associating the loss of these immune sentinels with chronic nasal inflammation. The present study is the first detailed description of the phenotypic, ontogenetic and functional properties of nasal DCs and will inform the design of preventative immunization strategies as well as therapeutic modalities against chronic rhinosinusitis. PMID:25669151

Leptin regulates dopamine responses to sustained stress in humans.

PubMed

Burghardt, Paul R; Love, Tiffany M; Stohler, Christian S; Hodgkinson, Colin; Shen, Pei-Hong; Enoch, Mary-Anne; Goldman, David; Zubieta, Jon-Kar

2012-10-31

Neural systems that identify and respond to salient stimuli are critical for survival in a complex and changing environment. In addition, interindividual differences, including genetic variation and hormonal and metabolic status likely influence the behavioral strategies and neuronal responses to environmental challenges. Here, we examined the relationship between leptin allelic variation and plasma leptin levels with DAD2/3R availability in vivo as measured with [(11)C]raclopride PET at baseline and during a standardized pain stress challenge. Allelic variation in the leptin gene was associated with varying levels of dopamine release in response to the pain stressor, but not with baseline D2/3 receptor availability. Circulating leptin was also positively associated with stress-induced dopamine release. These results show that leptin serves as a regulator of neuronal function in humans and provides an etiological mechanism for differences in dopamine neurotransmission in response to salient stimuli as related to metabolic function. The capacity for leptin to influence stress-induced dopaminergic function is of importance for pathological states where dopamine is thought to play an integral role, such as mood, substance-use disorders, eating disorders, and obesity.

Improvement in Renal Function and Symptoms of Patients Treated with Laparoscopic Pyeloplasty for Ureteropelvic Junction Obstruction with Less Than 20% Split Renal Function.

PubMed

Nishi, Morihiro; Matsumoto, Kazumasa; Fujita, Tetsuo; Iwamura, Masatsugu

2016-11-01

To evaluate the efficacy of laparoscopic pyeloplasty (LPP) for lower functioning kidney, we investigated the outcome of this procedure for patients with ureteropelvic junction obstruction with decreased renal function, defined as less than 20% split renal function. Between October 1998 and June 2015, we performed transperitoneal dismembered LPP in 224 patients. Among them, 15 patients with less than 20% split renal function were included in this study. Patient characteristics, perioperative split renal functions, complications, and surgical outcomes were retrospectively investigated. Fourteen of 15 patients had preoperative symptoms, including flank pain in 13 patients and gross hematuria in 1 patient. Preoperative 99mTc-mercaptoacetyltriglycine (MAG3) renogram revealed no response to diuretic injection and median split renal function was 16.5%. Median operative time and blood loss were 170 minutes and 20 mL, respectively. There were no complications during the perioperative period. Postoperative MAG3 renogram at 6 and 12 months after the operation revealed significantly increased split renal function (median: 23.8% and 23.7%, p = 0.001 and 0.008, respectively) and response to diuretic injection in all patients. Preoperative symptoms disappeared and no recurrence was seen during the follow-up period for all patients except for one who experienced flank pain again 4 months after the surgery. He subsequently underwent open pyeloplasty, and flank pain disappeared soon after. LPP for patients with low split renal function and flank pain significantly improved symptoms and split renal functions. Although the long-term clinical effects of LPP are unknown, we recommend performing LPP before considering nephrectomy for patients with lower functioning kidney.

LC-MS/MS based proteomic analysis and functional inference of hypothetical proteins in Desulfovibrio vulgaris

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

Zhang, Weiwen; Culley, David E.; Gritsenko, Marina A.

2006-11-03

ABSTRACT In the previous study, the whole-genome gene expression profiles of D. vulgaris in response to oxidative stress and heat shock were determined. The results showed 24-28% of the responsive genes were hypothetical proteins that have not been experimentally characterized or whose function can not be deduced by simple sequence comparison. To further explore the protecting mechanisms employed in D. vulgaris against the oxidative stress and heat shock, attempt was made in this study to infer functions of these hypothetical proteins by phylogenomic profiling along with detailed sequence comparison against various publicly available databases. By this approach we were abletomore » assign possible functions to 25 responsive hypothetical proteins. The findings included that DVU0725, induced by oxidative stress, may be involved in lipopolysaccharide biosynthesis, implying that the alternation of lipopolysaccharide on cell surface might service as a mechanism against oxidative stress in D. vulgaris. In addition, two responsive proteins, DVU0024 encoding a putative transcriptional regulator and DVU1670 encoding predicted redox protein, were sharing co-evolution atterns with rubrerythrin in Archaeoglobus fulgidus and Clostridium perfringens, respectively, implying that they might be part of the stress response and protective systems in D. vulgaris. The study demonstrated that phylogenomic profiling is a useful tool in interpretation of experimental genomics data, and also provided further insight on cellular response to oxidative stress and heat shock in D. vulgaris.« less

Evidence for vestibular regulation of autonomic functions in a mouse genetic model

NASA Technical Reports Server (NTRS)

Murakami, Dean M.; Erkman, Linda; Hermanson, Ola; Rosenfeld, Michael G.; Fuller, Charles A.

2002-01-01

Physiological responses to changes in the gravitational field and body position, as well as symptoms of patients with anxiety-related disorders, have indicated an interrelationship between vestibular function and stress responses. However, the relative significance of cochlear and vestibular information in autonomic regulation remains unresolved because of the difficulties in distinguishing the relative contributions of other proprioceptive and interoceptive inputs, including vagal and somatic information. To investigate the role of cochlear and vestibular function in central and physiological responses, we have examined the effects of increased gravity in wild-type mice and mice lacking the POU homeodomain transcription factor Brn-3.1 (Brn-3bPou4f3). The only known phenotype of the Brn-3.1(-/-) mouse is related to hearing and balance functions, owing to the failure of cochlear and vestibular hair cells to differentiate properly. Here, we show that normal physiological responses to increased gravity (2G exposure), such as a dramatic drop in body temperature and concomitant circadian adjustment, were completely absent in Brn-3.1(-/-) mice. In line with the lack of autonomic responses, the massive increase in neuronal activity after 2G exposure normally detected in wild-type mice was virtually abolished in Brn-3.1(-/-) mice. Our results suggest that cochlear and vestibular hair cells are the primary regulators of autonomic responses to altered gravity and provide genetic evidence that these cells are sufficient to alter neural activity in regions involved in autonomic and neuroendocrine control.

Comparing the responsiveness of functional outcome assessment measures for trauma registries.

PubMed

Williamson, Owen D; Gabbe, Belinda J; Sutherland, Ann M; Wolfe, Rory; Forbes, Andrew B; Cameron, Peter A

2011-07-01

Measuring long-term disability and functional outcomes after major trauma is not standardized across trauma registries. An ideal measure would be responsive to change but not have significant ceiling effects. The aim of this study was to compare the responsiveness of the Glasgow Outcome Scale (GOS), GOS-Extended (GOSE), Functional Independence Measure (FIM), and modified FIM in major trauma patients, with and without significant head injuries. Patients admitted to two adult Level I trauma centers in Victoria, Australia, who survived to discharge from hospital, were aged 15 years to 80 years with a blunt mechanism of injury, and had an estimated Injury Severity Score >15 on admission, were recruited for this prospective study. The instruments were administered at baseline (hospital discharge) and by telephone interview 6 months after injury. Measures of responsiveness, including effect sizes, were calculated. Bootstrapping techniques, and floor and ceiling effects, were used to compare the measures. Two hundred forty-three patients participated, of which 234 patients (96%) completed the study. The GOSE and GOS were the most responsive instruments in this major trauma population with effect sizes of 5.3 and 4.4, respectively. The GOSE had the lowest ceiling effect (17%). The GOSE was the instrument with greatest responsiveness and the lowest ceiling effect in a major trauma population with and without significant head injuries and is recommended for use by trauma registries for monitoring functional outcomes and benchmarking care. The results of this study do not support the use of the modified FIM for this purpose.

The Sensitivity to Change and Responsiveness of the Adult Responses to Children’s Symptoms in Children and Adolescents With Chronic Pain

PubMed Central

Alberts, Nicole; Langer, Shelby L.; Levy, Rona L.; Walker, Lynn S.; Palermo, Tonya M.

2016-01-01

Abstract Objective  To examine the sensitivity to change and responsiveness of the Adult Responses to Children’s Symptoms (ARCS) among parents of youth with chronic pain.  Methods  Participants included 330 youth (89 children aged 7–11 years, 241 children aged 12–17 years) and their parents who participated in randomized controlled trials of family-based cognitive-behavioral therapy for chronic pain. Child pain and disability, parental emotional functioning, and parental responses to child pain were assessed at baseline and posttreatment.  Results  The Protect and Monitor scales of the ARCS were sensitive to change following intervention for both developmental groups, with clinically meaningful reductions in these behaviors, thereby demonstrating responsiveness. Among the adolescent sample, greater change on some ARCS scales was associated with better parental emotional functioning and lower child pain at posttreatment.  Conclusions  Findings support the sensitivity to change and responsiveness of the Protect and Monitor scales among parents of youth with chronic pain. PMID:26493601

Proceedings of the First Joint NASA Cardiopulmonary Workshop

NASA Technical Reports Server (NTRS)

Fortney, Suzanne M. (Editor); Hargens, Alan R. (Editor)

1991-01-01

The topics covered include the following: flight echocardiography, pulmonary function, central hemodynamics, glycerol hyperhydration, spectral analysis, lower body negative pressure countermeasures, orthostatic tolerance, autonomic function, cardiac deconditioning, fluid and renal responses to head-down tilt, local fluid regulation, endocrine regulation during bed rest, autogenic feedback, and chronic cardiovascular measurements. The program ended with a general discussion of weightlessness models and countermeasures.

Big-conductance Ca2+-activated K+ channels in physiological and pathophysiological urinary bladder smooth muscle cells

PubMed Central

Parajuli, Shankar P.; Zheng, Yun-Min; Levin, Robert; Wang, Yong-Xiao

2016-01-01

ABSTRACT Contraction and relaxation of urinary bladder smooth muscle cells (UBSMCs) represent the important physiological functions of the bladder. Contractile responses in UBSMCs are regulated by a number of ion channels including big-conductance Ca2+- activated K+ (BK) channels. Great progress has been made in studies of BK channels in UBSMCs. The intent of this review is to summarize recent exciting findings with respect to the functional interactions of BK channels with muscarinic receptors, ryanodine receptors (RyRs) and inositol triphosphate receptors (IP3Rs) as well as their functional importance under normal and pathophysiological conditions. BK channels are highly expressed in UBSMCs. Activation of muscarinic M3 receptors inhibits the BK channel activity, facilitates opening of voltage-dependent Ca2+ (CaV) channels, and thereby enhances excitability and contractility of UBSMCs. Signaling molecules and regulatory mechanisms involving RyRs and IP3Rs have a significant effect on functions of BK channels and thereby regulate cellular responses in UBSMCs under normal and pathophysiological conditions including overactive bladders. Moreover, BK channels may represent a novel target for the treatment of bladder dysfunctions. PMID:27101440

Role of Pore-Forming Toxins in Bacterial Infectious Diseases

PubMed Central

Los, Ferdinand C. O.; Randis, Tara M.

2013-01-01

SUMMARY Pore-forming toxins (PFTs) are the most common bacterial cytotoxic proteins and are required for virulence in a large number of important pathogens, including Streptococcus pneumoniae, group A and B streptococci, Staphylococcus aureus, Escherichia coli, and Mycobacterium tuberculosis. PFTs generally disrupt host cell membranes, but they can have additional effects independent of pore formation. Substantial effort has been devoted to understanding the molecular mechanisms underlying the functions of certain model PFTs. Likewise, specific host pathways mediating survival and immune responses in the face of toxin-mediated cellular damage have been delineated. However, less is known about the overall functions of PFTs during infection in vivo. This review focuses on common themes in the area of PFT biology, with an emphasis on studies addressing the roles of PFTs in in vivo and ex vivo models of colonization or infection. Common functions of PFTs include disruption of epithelial barrier function and evasion of host immune responses, which contribute to bacterial growth and spreading. The widespread nature of PFTs make this group of toxins an attractive target for the development of new virulence-targeted therapies that may have broad activity against human pathogens. PMID:23699254

The Fifth Generation. An annotated bibliography

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

Bramer, M.; Bramer, D.

The Japanese Fifth Generation Computer System project constitutes a radical reappraisal of the functions which an advanced computer system should be able to perform, the programming languages needed to implement such functions, and the machine architectures suitable for supporting the chosen languages. The book guides the reader through the ever-growing literature on the project, and the international responses, including the United Kingdom Government's Alvey Program and the MCC Program in the United States. Evaluative abstracts are given, including books, journal articles, unpublished reports and material at both overview and technical levels.

Statistics of some atmospheric turbulence records relevant to aircraft response calculations

NASA Technical Reports Server (NTRS)

Mark, W. D.; Fischer, R. W.

1981-01-01

Methods for characterizing atmospheric turbulence are described. The methods illustrated include maximum likelihood estimation of the integral scale and intensity of records obeying the von Karman transverse power spectral form, constrained least-squares estimation of the parameters of a parametric representation of autocorrelation functions, estimation of the power spectra density of the instantaneous variance of a record with temporally fluctuating variance, and estimation of the probability density functions of various turbulence components. Descriptions of the computer programs used in the computations are given, and a full listing of these programs is included.

Recent advances in understanding hematopoiesis in Fanconi Anemia

PubMed Central

Bagby, Grover

2018-01-01

Fanconi anemia is an inherited disease characterized by genomic instability, hypersensitivity to DNA cross-linking agents, bone marrow failure, short stature, skeletal abnormalities, and a high relative risk of myeloid leukemia and epithelial malignancies. The 21 Fanconi anemia genes encode proteins involved in multiple nuclear biochemical pathways that effect DNA interstrand crosslink repair. In the past, bone marrow failure was attributed solely to the failure of stem cells to repair DNA. Recently, non-canonical functions of many of the Fanconi anemia proteins have been described, including modulating responses to oxidative stress, viral infection, and inflammation as well as facilitating mitophagic responses and enhancing signals that promote stem cell function and survival. Some of these functions take place in non-nuclear sites and do not depend on the DNA damage response functions of the proteins. Dysfunctions of the canonical and non-canonical pathways that drive stem cell exhaustion and neoplastic clonal selection are reviewed, and the potential therapeutic importance of fully investigating the scope and interdependences of the canonical and non-canonical pathways is emphasized. PMID:29399332

Functional, structural and phylogenetic analysis of domains underlying the Al sensitivity of the aluminum-activated malate/anion transporter, TaALMT1.

PubMed

Ligaba, Ayalew; Dreyer, Ingo; Margaryan, Armine; Schneider, David J; Kochian, Leon; Piñeros, Miguel

2013-12-01

Triticum aestivum aluminum-activated malate transporter (TaALMT1) is the founding member of a unique gene family of anion transporters (ALMTs) that mediate the efflux of organic acids. A small sub-group of root-localized ALMTs, including TaALMT1, is physiologically associated with in planta aluminum (Al) resistance. TaALMT1 exhibits significant enhancement of transport activity in response to extracellular Al. In this study, we integrated structure-function analyses of structurally altered TaALMT1 proteins expressed in Xenopus oocytes with phylogenic analyses of the ALMT family. Our aim is to re-examine the role of protein domains in terms of their potential involvement in the Al-dependent enhancement (i.e. Al-responsiveness) of TaALMT1 transport activity, as well as the roles of all its 43 negatively charged amino acid residues. Our results indicate that the N-domain, which is predicted to form the conductive pathway, mediates ion transport even in the absence of the C-domain. However, segments in both domains are involved in Al(3+) sensing. We identified two regions, one at the N-terminus and a hydrophobic region at the C-terminus, that jointly contribute to the Al-response phenotype. Interestingly, the characteristic motif at the N-terminus appears to be specific for Al-responsive ALMTs. Our study highlights the need to include a comprehensive phylogenetic analysis when drawing inferences from structure-function analyses, as a significant proportion of the functional changes observed for TaALMT1 are most likely the result of alterations in the overall structural integrity of ALMT family proteins rather than modifications of specific sites involved in Al(3+) sensing. © 2013 The Authors The Plant Journal © 2013 John Wiley & Sons Ltd.

Sexual Function Across Aging.

PubMed

Clayton, Anita H; Harsh, Veronica

2016-03-01

Women experience multiple changes in social and reproductive statuses across the life span which can affect sexual functioning. Various phases of the sexual response cycle may be impacted and can lead to sexual dysfunction. Screening for sexual problems and consideration of contributing factors such as neurobiology, reproductive life events, medical problems, medication use, and depression can help guide appropriate treatment and thereby improve the sexual functioning and quality of life of affected women. Treatment options include psychotropic medications, hormone therapy, and psychotherapy.

Intraspecies variation in a widely distributed tree species regulates the responses of soil microbiome to different temperature regimes.

PubMed

Zhang, Cui-Jing; Delgado-Baquerizo, Manuel; Drake, John E; Reich, Peter B; Tjoelker, Mark G; Tissue, David T; Wang, Jun-Tao; He, Ji-Zheng; Singh, Brajesh K

2018-04-01

Plant characteristics in different provenances within a single species may vary in response to climate change, which might alter soil microbial communities and ecosystem functions. We conducted a glasshouse experiment and grew seedlings of three provenances (temperate, subtropical and tropical origins) of a tree species (i.e., Eucalyptus tereticornis) at different growth temperatures (18, 21.5, 25, 28.5, 32 and 35.5°C) for 54 days. At the end of the experiment, bacterial and fungal community composition, diversity and abundance were characterized. Measured soil functions included surrogates of microbial respiration, enzyme activities and nutrient cycling. Using Permutation multivariate analysis of variance (PerMANOVA) and network analysis, we found that the identity of tree provenances regulated both structure and function of soil microbiomes. In some cases, tree provenances substantially affected the response of microbial communities to the temperature treatments. For example, we found significant interactions of temperature and tree provenance on bacterial community and relative abundances of Chloroflexi and Zygomycota, and inorganic nitrogen. Microbial abundance was altered in response to increasing temperature, but was not affected by tree provenances. Our study provides novel evidence that even a small variation in biotic components (i.e., intraspecies tree variation) can significantly influence the response of soil microbial community composition and specific soil functions to global warming. © 2018 Society for Applied Microbiology and John Wiley & Sons Ltd.

Testing the dose-response specification in epidemiology: public health and policy consequences for lead.

PubMed

Rothenberg, Stephen J; Rothenberg, Jesse C

2005-09-01

Statistical evaluation of the dose-response function in lead epidemiology is rarely attempted. Economic evaluation of health benefits of lead reduction usually assumes a linear dose-response function, regardless of the outcome measure used. We reanalyzed a previously published study, an international pooled data set combining data from seven prospective lead studies examining contemporaneous blood lead effect on IQ (intelligence quotient) of 7-year-old children (n = 1,333). We constructed alternative linear multiple regression models with linear blood lead terms (linear-linear dose response) and natural-log-transformed blood lead terms (log-linear dose response). We tested the two lead specifications for nonlinearity in the models, compared the two lead specifications for significantly better fit to the data, and examined the effects of possible residual confounding on the functional form of the dose-response relationship. We found that a log-linear lead-IQ relationship was a significantly better fit than was a linear-linear relationship for IQ (p = 0.009), with little evidence of residual confounding of included model variables. We substituted the log-linear lead-IQ effect in a previously published health benefits model and found that the economic savings due to U.S. population lead decrease between 1976 and 1999 (from 17.1 microg/dL to 2.0 microg/dL) was 2.2 times (319 billion dollars) that calculated using a linear-linear dose-response function (149 billion dollars). The Centers for Disease Control and Prevention action limit of 10 microg/dL for children fails to protect against most damage and economic cost attributable to lead exposure.

Test-Anchored Vibration Response Predictions for an Acoustically Energized Curved Orthogrid Panel with Mounted Components

NASA Technical Reports Server (NTRS)

Frady, Gregory P.; Duvall, Lowery D.; Fulcher, Clay W. G.; Laverde, Bruce T.; Hunt, Ronald A.

2011-01-01

A rich body of vibroacoustic test data was recently generated at Marshall Space Flight Center for a curved orthogrid panel typical of launch vehicle skin structures. Several test article configurations were produced by adding component equipment of differing weights to the flight-like vehicle panel. The test data were used to anchor computational predictions of a variety of spatially distributed responses including acceleration, strain and component interface force. Transfer functions relating the responses to the input pressure field were generated from finite element based modal solutions and test-derived damping estimates. A diffuse acoustic field model was employed to describe the assumed correlation of phased input sound pressures across the energized panel. This application demonstrates the ability to quickly and accurately predict a variety of responses to acoustically energized skin panels with mounted components. Favorable comparisons between the measured and predicted responses were established. The validated models were used to examine vibration response sensitivities to relevant modeling parameters such as pressure patch density, mesh density, weight of the mounted component and model form. Convergence metrics include spectral densities and cumulative root-mean squared (RMS) functions for acceleration, velocity, displacement, strain and interface force. Minimum frequencies for response convergence were established as well as recommendations for modeling techniques, particularly in the early stages of a component design when accurate structural vibration requirements are needed relatively quickly. The results were compared with long-established guidelines for modeling accuracy of component-loaded panels. A theoretical basis for the Response/Pressure Transfer Function (RPTF) approach provides insight into trends observed in the response predictions and confirmed in the test data. The software modules developed for the RPTF method can be easily adapted for quick replacement of the diffuse acoustic field with other pressure field models; for example a turbulent boundary layer (TBL) model suitable for vehicle ascent. Wind tunnel tests have been proposed to anchor the predictions and provide new insight into modeling approaches for this type of environment. Finally, component vibration environments for design were developed from the measured and predicted responses and compared with those derived from traditional techniques such as Barrett scaling methods for unloaded and component-loaded panels.

The Role of Left Hemispheric Structures for Emotional Processing as a Monitor of Bodily Reaction and Felt Chill - a Case-Control Functional Imaging Study.

PubMed

Grunkina, Viktoria; Holtz, Katharina; Klepzig, Kai; Neubert, Jörg; Horn, Ulrike; Domin, Martin; Hamm, Alfons O; Lotze, Martin

2016-01-01

Background: The particular function of the left anterior human insula on emotional arousal has been illustrated with several case studies. Only after left hemispheric insula lesions, patients lose their pleasure in habits such as listening to joyful music. In functional magnetic resonance imaging studies (fMRI) activation in the left anterior insula has been associated with both processing of emotional valence and arousal. Tight interactions with different areas of the prefrontal cortex are involved in bodily response monitoring and cognitive appraisal of a given stimulus. Therefore, a large left hemispheric lesion including the left insula should impair the bodily response of chill experience (objective chill response) but leave the cognitive aspects of chill processing (subjective chill response) unaffected. Methods: We investigated a patient (MC) with a complete left hemispheric media cerebral artery stroke, testing fMRI representation of pleasant (music) and unpleasant (harsh sounds) chill response. Results: Although chill response to both pleasant and unpleasant rated sounds was confirmed verbally at passages also rated as chilling by healthy participants, skin conductance response was almost absent in MC. For a healthy control (HC) objective and subjective chill response was positively associated. Bilateral prefrontal fMRI-response to chill stimuli was sustained in MC whereas insula activation restricted to the right hemisphere. Diffusion imaging together with lesion maps revealed that left lateral tracts were completely damaged but medial prefrontal structures were intact. Conclusion: With this case study we demonstrate how bodily response and cognitive appraisal are differentially participating in the internal monitor of chill response.

DRD2 Schizophrenia-Risk Allele Is Associated With Impaired Striatal Functioning in Unaffected Siblings of Schizophrenia Patients

PubMed Central

Vink, Matthijs; de Leeuw, Max; Luykx, Jurjen J.; van Eijk, Kristel R.; van den Munkhof, Hanna E.; van Buuren, Mariët; Kahn, René S.

2016-01-01

A recent Genome-Wide Association Study showed that the rs2514218 single nucleotide polymorphism (SNP) in close proximity to dopamine receptor D2 is strongly associated with schizophrenia. Further, an in silico experiment showed that rs2514218 has a cis expression quantitative trait locus effect in the basal ganglia. To date, however, the functional consequence of this SNP is unknown. Here, we used functional Magnetic resonance imaging to investigate the impact of this risk allele on striatal activation during proactive and reactive response inhibition in 45 unaffected siblings of schizophrenia patients. We included siblings to circumvent the illness specific confounds affecting striatal functioning independent from gene effects. Behavioral analyses revealed no differences between the carriers (n = 21) and noncarriers (n = 24). Risk allele carriers showed a diminished striatal response to increasing proactive inhibitory control demands, whereas overall level of striatal activation in carriers was elevated compared to noncarriers. Finally, risk allele carriers showed a blunted striatal response during successful reactive inhibition compared to the noncarriers. These data are consistent with earlier reports showing similar deficits in schizophrenia patients, and point to a failure to flexibly engage the striatum in response to contextual cues. This is the first study to demonstrate an association between impaired striatal functioning and the rs2514218 polymorphism. We take our findings to indicate that striatal functioning is impaired in carriers of the DRD2 risk allele, likely due to dopamine dysregulation at the DRD2 location. PMID:26598739

SeaWiFS technical report series. Volume 15: The simulated SesWiFS data set, version 2

NASA Technical Reports Server (NTRS)

Hooker, Stanford B. (Editor); Firestone, Elaine R. (Editor); Gregg, Watson W.; Patt, Frederick S.; Woodward, Robert H.

1994-01-01

This document describes the second version of the simulated SeaWiFS data set. A realistic simulated data set is essential for mission readiness preparations and can potentially assist in all phases of ground support for a future mission. The second version improves on the first version primarily through additional realism and complexity. This version incorporates a representation of virtually every aspect of the flight mission. Thus, it provides a high-fidelity data set for testing several aspects of the ground system, including data acquisition, data processing, data transfers, calibration and validation, quality control, and mission operations. The data set is constructed for a seven-day period, 25-31 March 1994. Specific features of the data set include Global Area coverage (GAC), recorded Local Area Coverage (LAC), and realtime High Resolution Picture Transmission (HRPT) data for the seven-day period. A realistic orbit, which is propagated using a Brouwer-Lyddane model with drag, is used to simulate orbit positions. The simulated data corresponds to the command schedule based on the orbit for this seven-day period. It includes total (at-satellite) radiances not only for ocean, but for land, clouds, and ice. The simulation also utilizes a high-resolution land-sea mask. It includes the April 1993 SeaWiFS spectral responses and sensor saturation responses. The simulation is formatted according to July 1993 onboard data structures, which include corresponding telemetry (instrument and spacecraft) data. The methods are described and some examples of the output are given. The instrument response functions made available in April 1993 have been used to produce the Version 2 simulated data. These response functions will change as part of the sensor improvements initiated in July-August 1993.

Technical advance: live-imaging analysis of human dendritic cell migrating behavior under the influence of immune-stimulating reagents in an organotypic model of lung.

PubMed

Nguyen Hoang, Anh Thu; Chen, Puran; Björnfot, Sofia; Högstrand, Kari; Lock, John G; Grandien, Alf; Coles, Mark; Svensson, Mattias

2014-09-01

This manuscript describes technical advances allowing manipulation and quantitative analyses of human DC migratory behavior in lung epithelial tissue. DCs are hematopoietic cells essential for the maintenance of tissue homeostasis and the induction of tissue-specific immune responses. Important functions include cytokine production and migration in response to infection for the induction of proper immune responses. To design appropriate strategies to exploit human DC functional properties in lung tissue for the purpose of clinical evaluation, e.g., candidate vaccination and immunotherapy strategies, we have developed a live-imaging assay based on our previously described organotypic model of the human lung. This assay allows provocations and subsequent quantitative investigations of DC functional properties under conditions mimicking morphological and functional features of the in vivo parental tissue. We present protocols to set up and prepare tissue models for 4D (x, y, z, time) fluorescence-imaging analysis that allow spatial and temporal studies of human DCs in live epithelial tissue, followed by flow cytometry analysis of DCs retrieved from digested tissue models. This model system can be useful for elucidating incompletely defined pathways controlling DC functional responses to infection and inflammation in lung epithelial tissue, as well as the efficacy of locally administered candidate interventions. © 2014 Society for Leukocyte Biology.

Key ecological responses to nitrogen are altered by climate change

EPA Science Inventory

Here we review the effects of nitrogen and climate (e.g. temperature and precipitation) on four aspects of ecosystem structure and function including hydrologic-coupled nitrogen cycling, carbon cycling, acidification and biodiversity.

Space shuttle pogo studies. [systems stability

NASA Technical Reports Server (NTRS)

Coppolino, R. N.; Lock, M. H.; Rubin, S.

1977-01-01

Topics covered include: (1) pogo suppression for main propulsion subsystem operation; (2) application of quarter-scale low pressure oxidizer turbopump transfer functions; (3) pogo stability during orbital maneuvering subsystem operation; and (4) errors in frequency response measurements.

42 CFR 476.104 - Coordination of activities.

Code of Federal Regulations, 2012 CFR

2012-10-01

... (CONTINUED) QUALITY IMPROVEMENT ORGANIZATIONS UTILIZATION AND QUALITY CONTROL REVIEW Review Responsibilities of Utilization and Quality Control Quality Improvement Organizations (QIOs) Qio Review Functions... coordinate its activities (including information exchanges) with the activities of— (a) Medicare fiscal...

42 CFR 476.104 - Coordination of activities.

Code of Federal Regulations, 2013 CFR

2013-10-01

... (CONTINUED) QUALITY IMPROVEMENT ORGANIZATIONS UTILIZATION AND QUALITY CONTROL REVIEW Review Responsibilities of Utilization and Quality Control Quality Improvement Organizations (QIOs) Qio Review Functions... coordinate its activities (including information exchanges) with the activities of— (a) Medicare...

42 CFR 476.104 - Coordination of activities.

Code of Federal Regulations, 2011 CFR

2011-10-01

... (CONTINUED) QUALITY IMPROVEMENT ORGANIZATIONS UTILIZATION AND QUALITY CONTROL REVIEW Review Responsibilities of Utilization and Quality Control Quality Improvement Organizations (QIOs) Qio Review Functions... coordinate its activities (including information exchanges) with the activities of— (a) Medicare fiscal...

Post-Translational Modification Control of Innate Immunity.

PubMed

Liu, Juan; Qian, Cheng; Cao, Xuetao

2016-07-19

A coordinated balance between the positive and negative regulation of pattern-recognition receptor (PRR)-initiated innate inflammatory responses is required to ensure the most favorable outcome for the host. Post-translational modifications (PTMs) of innate sensors and downstream signaling molecules influence their activity and function by inducing their covalent linkage to new functional groups. PTMs including phosphorylation and polyubiquitination have been shown to potently regulate innate inflammatory responses through the activation, cellular translocation, and interaction of innate receptors, adaptors, and downstream signaling molecules in response to infectious and dangerous signals. Other PTMs such as methylation, acetylation, SUMOylation, and succinylation are increasingly implicated in the regulation of innate immunity and inflammation. In this review, we focus on the roles of PTMs in controlling PRR-triggered innate immunity and inflammatory responses. The emerging roles of PTMs in the pathogenesis and potential treatment of infectious and inflammatory immune diseases are also discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

A cascade reaction network mimicking the basic functional steps of adaptive immune response

NASA Astrophysics Data System (ADS)

Han, Da; Wu, Cuichen; You, Mingxu; Zhang, Tao; Wan, Shuo; Chen, Tao; Qiu, Liping; Zheng, Zheng; Liang, Hao; Tan, Weihong

2015-10-01

Biological systems use complex ‘information-processing cores’ composed of molecular networks to coordinate their external environment and internal states. An example of this is the acquired, or adaptive, immune system (AIS), which is composed of both humoral and cell-mediated components. Here we report the step-by-step construction of a prototype mimic of the AIS that we call an adaptive immune response simulator (AIRS). DNA and enzymes are used as simple artificial analogues of the components of the AIS to create a system that responds to specific molecular stimuli in vitro. We show that this network of reactions can function in a manner that is superficially similar to the most basic responses of the vertebrate AIS, including reaction sequences that mimic both humoral and cellular responses. As such, AIRS provides guidelines for the design and engineering of artificial reaction networks and molecular devices.

A meta-analysis to determine the effect of pharmacological and non-pharmacological treatments on fibromyalgia symptoms comprising OMERACT-10 response criteria.

PubMed

Papadopoulou, Despoina; Fassoulaki, Argyro; Tsoulas, Christos; Siafaka, Ioanna; Vadalouca, Athina

2016-03-01

Fibromyalgia is characterized by widespread pain, sleep problems, fatigue, functional impairment, psychological distress, and cognitive dysfunction. The objective of this meta-analysis is to synthesize the available data on the effectiveness of pharmacological and non-pharmacological interventions across all domains included in the Outcome Measures in Rheumatology Clinical Trials (OMERACT-10) fibromyalgia response definitions, and to examine response based on these definitions. We searched Cochrane, PubMed, Scopus, and the reference lists of articles for randomized controlled trials of any drug formulation or non-pharmacological intervention used for fibromyalgia treatment. We extracted efficacy data regarding pain, sleep, physical function, fatigue, anxiety, depression, and cognition. The available data were insufficient to draw definite conclusions regarding response. Indirect evidence indicates that it may be expected with the use of serotonin noradrenaline reuptake inhibitors (SNRIs), noradrenaline reuptake inhibitors (NRIs), and multidisciplinary treatment.

AESOP: An interactive computer program for the design of linear quadratic regulators and Kalman filters

NASA Technical Reports Server (NTRS)

Lehtinen, B.; Geyser, L. C.

1984-01-01

AESOP is a computer program for use in designing feedback controls and state estimators for linear multivariable systems. AESOP is meant to be used in an interactive manner. Each design task that the program performs is assigned a "function" number. The user accesses these functions either (1) by inputting a list of desired function numbers or (2) by inputting a single function number. In the latter case the choice of the function will in general depend on the results obtained by the previously executed function. The most important of the AESOP functions are those that design,linear quadratic regulators and Kalman filters. The user interacts with the program when using these design functions by inputting design weighting parameters and by viewing graphic displays of designed system responses. Supporting functions are provided that obtain system transient and frequency responses, transfer functions, and covariance matrices. The program can also compute open-loop system information such as stability (eigenvalues), eigenvectors, controllability, and observability. The program is written in ANSI-66 FORTRAN for use on an IBM 3033 using TSS 370. Descriptions of all subroutines and results of two test cases are included in the appendixes.

Common and Distinct Neural Mechanisms of Attentional Switching and Response Conflict

PubMed Central

Kim, Chobok; Johnson, Nathan F.; Gold, Brian T.

2012-01-01

The human capacities for overcoming prepotent actions and flexibly switching between tasks represent cornerstones of cognitive control. Functional neuroimaging has implicated a diverse set of brain regions contributing to each of these cognitive control processes. However, the extent to which attentional switching and response conflict draw on shared or distinct neural mechanisms remains unclear. The current study examined the neural correlates of response conflict and attentional switching using event-related functional magnetic resonance imaging (fMRI) and a fully randomized 2×2 design. We manipulated an arrow-word version of the Stroop task to measure conflict and switching in the context of a single task decision, in response to a common set of stimuli. Under these common conditions, both behavioral and imaging data showed significant main effects of conflict and switching but no interaction. However, conjunction analyses identified frontal regions involved in both switching and response conflict, including the dorsal anterior cingulate cortex (dACC) and left inferior frontal junction. In addition, connectivity analyses demonstrated task-dependent functional connectivity patterns between dACC and inferior temporal cortex for attentional switching and between dACC and posterior parietal cortex for response conflict. These results suggest that the brain makes use of shared frontal regions, but can dynamically modulate the connectivity patterns of some of those regions, to deal with attentional switching and response conflict. PMID:22750124

Common and distinct neural mechanisms of attentional switching and response conflict.

PubMed

Kim, Chobok; Johnson, Nathan F; Gold, Brian T

2012-08-21

The human capacities for overcoming prepotent actions and flexibly switching between tasks represent cornerstones of cognitive control. Functional neuroimaging has implicated a diverse set of brain regions contributing to each of these cognitive control processes. However, the extent to which attentional switching and response conflict draw on shared or distinct neural mechanisms remains unclear. The current study examined the neural correlates of response conflict and attentional switching using event-related functional magnetic resonance imaging (fMRI) and a fully randomized 2×2 design. We manipulated an arrow-word version of the Stroop task to measure conflict and switching in the context of a single task decision, in response to a common set of stimuli. Under these common conditions, both behavioral and imaging data showed significant main effects of conflict and switching but no interaction. However, conjunction analyses identified frontal regions involved in both switching and response conflict, including the dorsal anterior cingulate cortex (dACC) and left inferior frontal junction. In addition, connectivity analyses demonstrated task-dependent functional connectivity patterns between dACC and inferior temporal cortex for attentional switching and between dACC and posterior parietal cortex for response conflict. These results suggest that the brain makes use of shared frontal regions, but can dynamically modulate the connectivity patterns of some of those regions, to deal with attentional switching and response conflict. Copyright © 2012 Elsevier B.V. All rights reserved.

The CRF Family of Neuropeptides and their Receptors - Mediators of the Central Stress Response

PubMed Central

Dedic, Nina; Chen, Alon; Deussing, Jan M.

2018-01-01

Background: Dysregulated stress neurocircuits, caused by genetic and/or environmental changes, underlie the development of many neuropsychiatric disorders. Corticotropin-releasing factor (CRF) is the major physiological activator of the hypothalamic-pituitary-adrenal (HPA) axis and conse-quently a primary regulator of the mammalian stress response. Together with its three family members, urocortins (UCNs) 1, 2, and 3, CRF integrates the neuroendocrine, autonomic, metabolic and behavioral responses to stress by activating its cognate receptors CRFR1 and CRFR2. Objective: Here we review the past and current state of the CRF/CRFR field, ranging from pharmacologi-cal studies to genetic mouse models and virus-mediated manipulations. Results: Although it is well established that CRF/CRFR1 signaling mediates aversive responses, includ-ing anxiety and depression-like behaviors, a number of recent studies have challenged this viewpoint by revealing anxiolytic and appetitive properties of specific CRF/CRFR1 circuits. In contrast, the UCN/CRFR2 system is less well understood and may possibly also exert divergent functions on physiol-ogy and behavior depending on the brain region, underlying circuit, and/or experienced stress conditions. Conclusion: A plethora of available genetic tools, including conventional and conditional mouse mutants targeting CRF system components, has greatly advanced our understanding about the endogenous mecha-nisms underlying HPA system regulation and CRF/UCN-related neuronal circuits involved in stress-related behaviors. Yet, the detailed pathways and molecular mechanisms by which the CRF/UCN-system translates negative or positive stimuli into the final, integrated biological response are not completely un-derstood. The utilization of future complementary methodologies, such as cell-type specific Cre-driver lines, viral and optogenetic tools will help to further dissect the function of genetically defined CRF/UCN neurocircuits in the context of adaptive and maladaptive stress responses. PMID:28260504

The occurrence of hormetic dose responses in the toxicological literature, the hormesis database: an overview

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

Calabrese, Edward J.; Blain, Robyn

A relational retrieval database has been developed compiling toxicological studies assessing the occurrence of hormetic dose responses and their quantitative characteristics. This database permits an evaluation of these studies over numerous parameters, including study design and dose-response features and physical/chemical properties of the agents. The database contains approximately 5600 dose-response relationships satisfying evaluative criteria for hormesis across over approximately 900 agents from a broadly diversified spectrum of chemical classes and physical agents. The assessment reveals that hormetic dose-response relationships occur in males and females of numerous animal models in all principal age groups as well as across species displaying amore » broad range of differential susceptibilities to toxic agents. The biological models are extensive, including plants, viruses, bacteria, fungi, insects, fish, birds, rodents, and primates, including humans. The spectrum of endpoints displaying hormetic dose responses is also broad being inclusive of growth, longevity, numerous metabolic parameters, disease incidences (including cancer), various performance endpoints such as cognitive functions, immune responses among others. Quantitative features of the hormetic dose response reveal that the vast majority of cases display a maximum stimulatory response less than two-fold greater than the control while the width of the stimulatory response is typically less than 100-fold in dose range immediately contiguous with the toxicological NO(A)EL. The database also contains a quantitative evaluation component that differentiates among the various dose responses concerning the strength of the evidence supporting a hormetic conclusion based on study design features, magnitude of the stimulatory response, statistical significance, and reproducibility of findings.« less

The occurrence of hormetic dose responses in the toxicological literature, the hormesis database: an overview.

PubMed

Calabrese, Edward J; Blain, Robyn

2005-02-01

A relational retrieval database has been developed compiling toxicological studies assessing the occurrence of hormetic dose responses and their quantitative characteristics. This database permits an evaluation of these studies over numerous parameters, including study design and dose-response features and physical/chemical properties of the agents. The database contains approximately 5600 dose-response relationships satisfying evaluative criteria for hormesis across over approximately 900 agents from a broadly diversified spectrum of chemical classes and physical agents. The assessment reveals that hormetic dose-response relationships occur in males and females of numerous animal models in all principal age groups as well as across species displaying a broad range of differential susceptibilities to toxic agents. The biological models are extensive, including plants, viruses, bacteria, fungi, insects, fish, birds, rodents, and primates, including humans. The spectrum of endpoints displaying hormetic dose responses is also broad being inclusive of growth, longevity, numerous metabolic parameters, disease incidences (including cancer), various performance endpoints such as cognitive functions, immune responses among others. Quantitative features of the hormetic dose response reveal that the vast majority of cases display a maximum stimulatory response less than two-fold greater than the control while the width of the stimulatory response is typically less than 100-fold in dose range immediately contiguous with the toxicological NO(A)EL. The database also contains a quantitative evaluation component that differentiates among the various dose responses concerning the strength of the evidence supporting a hormetic conclusion based on study design features, magnitude of the stimulatory response, statistical significance, and reproducibility of findings.

Complementary Roles of Estrogen-Related Receptors in Brown Adipocyte Thermogenic Function

PubMed Central

Gantner, Marin L.; Hazen, Bethany C.; Eury, Elodie; Brown, Erin L.

2016-01-01

Brown adipose tissue (BAT) thermogenesis relies on a high abundance of mitochondria and the unique expression of the mitochondrial Uncoupling Protein 1 (UCP1), which uncouples substrate oxidation from ATP synthesis. Adrenergic stimulation of brown adipocytes activates UCP1-mediated thermogenesis; it also induces the expression of Ucp1 and other genes important for thermogenesis, thereby endowing adipocytes with higher oxidative and uncoupling capacities. Adipocyte mitochondrial biogenesis and oxidative capacity are controlled by multiple transcription factors, including the estrogen-related receptor (ERR)α. Whole-body ERRα knockout mice show decreased BAT mitochondrial content and oxidative function but normal induction of Ucp1 in response to cold. In addition to ERRα, brown adipocytes express ERRβ and ERRγ, 2 nuclear receptors that are highly similar to ERRα and whose function in adipocytes is largely unknown. To gain insights into the roles of all 3 ERRs, we assessed mitochondrial function and adrenergic responses in primary brown adipocytes lacking combinations of ERRs. We show that adipocytes lacking just ERRα, the most abundant ERR, show only mild mitochondrial defects. Adipocytes lacking ERRβ and ERRγ also show just mild defects. In contrast, adipocytes lacking all 3 ERRs have severe reductions in mitochondrial content and oxidative capacity. Moreover, adipocytes lacking all 3 ERRs have defects in the transcriptional and metabolic response to adrenergic stimulation, suggesting a wider role of ERRs in BAT function than previously appreciated. Our study shows that ERRs have a great capacity to compensate for each other in protecting mitochondrial function and the metabolic response to adrenergic signaling, processes vital to BAT function. PMID:27763777

Investigation of endothelial function by pulse contour analysis: a protocol for drug administration and timing of pulse contour assessment

PubMed Central

Gordon, Sarah E; Cartwright, Neil; Griffiths, Mark J D

2009-01-01

AIMS Pulse contour analysis (PCA) obtained by finger photoplethysmography produces a digital volume pulse (DVP) including an inflection point in its down-slope. The reflection index (RI: ratio of the inflection point height over the maximal DVP) is responsive to vasodilatation. We aimed to optimize the drug dose and time interval for assessing endothelial function using PCA in healthy volunteers and patients with severe coronary artery disease. METHODS Time and dose to RI response relationships were constructed in 16 volunteers and nine patients to inhaled salbutamol (100–400 µg) or sublingual nitroglycerin (NTG; 25–400 µg). RESULTS For the volunteers, the time to maximum RI response to inhaled salbutamol and sublingual NTG was 10.73 ± 0.41 and 3.66 ± 0.21 min, respectively. A plateau in the RI response to salbutamol occurred between 5 and 15 min after inhalation and results were averaged over this period. A dose-dependent response was observed to inhaled salbutamol and sublingual NTG (P= 0.05 and P < 0.001 by repeated-measures anova, respectively) in healthy volunteers. By contrast, in patients with severe coronary artery disease inhaled salbutamol (100–400 µg) did not cause a significant change in RI. CONCLUSIONS In healthy volunteers the RI response to inhaled salbutamol (100–200 µg) averaged over 5–15 min after administration may be used to investigate endothelial function by PCA. The response to sublingual NTG (50 µg) should be determined at 4 min. This technique may not be suitable for the assessment of endothelial function in subjects with extensive coronary artery disease owing to the small responses observed and potential confounding effect of vasoactive medication. PMID:19843066

Isotype Diversification of IgG Antibodies to HIV Gag Proteins as a Therapeutic Vaccination Strategy for HIV Infection

PubMed Central

French, Martyn A.; Abudulai, Laila N.; Fernandez, Sonia

2013-01-01

The development of vaccines to treat and prevent human immunodeficiency virus (HIV) infection has been hampered by an incomplete understanding of “protective” immune responses against HIV. Natural control of HIV-1 infection is associated with T-cell responses against HIV-1 Gag proteins, particularly CD8+ T-cell responses restricted by “protective” HLA-B alleles, but other immune responses also contribute to immune control. These immune responses appear to include IgG antibodies to HIV-1 Gag proteins, interferon-α-dependant natural killer (NK) cell responses and plasmacytoid dendritic cell (pDC) responses. Here, it is proposed that isotype diversification of IgG antibodies against HIV-1 Gag proteins, to include IgG2, as well as IgG3 and IgG1 antibodies, will broaden the function of the antibody response and facilitate accessory cell responses against HIV-1 by NK cells and pDCs. We suggest that this should be investigated as a vaccination strategy for HIV-1 infection. PMID:26344116

Repeated Exposure to Media Violence Is Associated with Diminished Response in an Inhibitory Frontolimbic Network

PubMed Central

Hirsch, Joy

2007-01-01

Background Media depictions of violence, although often claimed to induce viewer aggression, have not been shown to affect the cortical networks that regulate behavior. Methodology/Principal Findings Using functional magnetic resonance imaging (fMRI), we found that repeated exposure to violent media, but not to other equally arousing media, led to both diminished response in right lateral orbitofrontal cortex (right ltOFC) and a decrease in right ltOFC-amygdala interaction. Reduced function in this network has been previously associated with decreased control over a variety of behaviors, including reactive aggression. Indeed, we found reduced right ltOFC responses to be characteristic of those subjects that reported greater tendencies toward reactive aggression. Furthermore, the violence-induced reduction in right ltOFC response coincided with increased throughput to behavior planning regions. Conclusions These novel findings establish that even short-term exposure to violent media can result in diminished responsiveness of a network associated with behaviors such as reactive aggression. PMID:18060062

Organizational Perspectives on Rapid Response Team Structure, Function, and Cost: A Qualitative Study.

PubMed

Smith, Patricia L; McSweeney, Jean

Understanding how an organization determines structure and function of a rapid response team (RRT), as well as cost evaluation and implications, can provide foundational knowledge to guide decisions about RRTs. The objectives were to (1) identify influencing factors in organizational development of RRT structure and function and (2) describe evaluation of RRT costs. Using a qualitative, ethnographic design, nurse executives and experts in 15 moderate-size hospitals were interviewed to explore their decision-making processes in determining RRT structure and function. Face-to-face interviews were audio recorded and transcribed verbatim and verified for accurateness. Using content analysis and constant comparison, interview data were analyzed. Demographic data were analyzed using descriptive statistics. The sample included 27 participants from 15 hospitals in 5 south-central states. They described a variety of RRT responders and functions, with the majority of hospitals having a critical care charge nurse attending all RRT calls for assistance. Others described a designated RRT nurse with primary RRT duties as responder to all RRT calls. Themes of RRT development from the data included influencers, decision processes, and thoughts about cost. It is important to understand how hospitals determine optimal structure and function to enhance support of quality nursing care. Determining the impact of an RRT on costs and benefits is vital in balancing patient safety and limited resources. Future research should focus on clarifying differences between team structure and function in outcomes as well as the most effective means to estimate costs and benefits.

Angular response calibration of the burst and transient source experiment

NASA Technical Reports Server (NTRS)

Lestrade, John Patrick

1988-01-01

The Gamma Ray Observatory includes four experiments designed to observe the gamma-ray universe. Laboratory measurements to test the response the Burst and Transient Source Experiment (BATSE) modules to gamma-ray sources that are non-axial were recently completed. The results of these observations are necessary for the correct interpretation of BATSE data obtained after it is put in Earth orbit. The launch is planned for March, 1900. Preliminary analyses of these test data show the presence of a radial dependence to the detector's light collection efficiency. It is proposed to evaluate the importance of this radial response, analyze future experimental data to derive the actual functional dependence on radius, and calculate the net effect on the output spectrum as a function of the angle of incidence.

Arabidopsis nph1 and npl1: Blue light receptors that mediate both phototropism and chloroplast relocation

PubMed Central

Sakai, Tatsuya; Kagawa, Takatoshi; Kasahara, Masahiro; Swartz, Trevor E.; Christie, John M.; Briggs, Winslow R.; Wada, Masamitsu; Okada, Kiyotaka

2001-01-01

UV-A/blue light acts to regulate a number of physiological processes in higher plants. These include light-driven chloroplast movement and phototropism. The NPH1 gene of Arabidopsis encodes an autophosphorylating protein kinase that functions as a photoreceptor for phototropism in response to low-intensity blue light. However, nph1 mutants have been reported to exhibit normal phototropic curvature under high-intensity blue light, indicating the presence of an additional phototropic receptor. A likely candidate is the nph1 homologue, npl1, which has recently been shown to mediate the avoidance response of chloroplasts to high-intensity blue light in Arabidopsis. Here we demonstrate that npl1, like nph1, noncovalently binds the chromophore flavin mononucleotide (FMN) within two specialized PAS domains, termed LOV domains. Furthermore, when expressed in insect cells, npl1, like nph1, undergoes light-dependent autophosphorylation, indicating that npl1 also functions as a light receptor kinase. Consistent with this conclusion, we show that a nph1npl1 double mutant exhibits an impaired phototropic response under both low- and high-intensity blue light. Hence, npl1 functions as a second phototropic receptor under high fluence rate conditions and is, in part, functionally redundant to nph1. We also demonstrate that both chloroplast accumulation in response to low-intensity light and chloroplast avoidance movement in response to high-intensity light are lacking in the nph1npl1 double mutant. Our findings therefore indicate that nph1 and npl1 show partially overlapping functions in two different responses, phototropism and chloroplast relocation, in a fluence rate-dependent manner. PMID:11371609

Functional significance of the electrocorticographic auditory responses in the premotor cortex.

PubMed

Tanji, Kazuyo; Sakurada, Kaori; Funiu, Hayato; Matsuda, Kenichiro; Kayama, Takamasa; Ito, Sayuri; Suzuki, Kyoko

2015-01-01

Other than well-known motor activities in the precentral gyrus, functional magnetic resonance imaging (fMRI) studies have found that the ventral part of the precentral gyrus is activated in response to linguistic auditory stimuli. It has been proposed that the premotor cortex in the precentral gyrus is responsible for the comprehension of speech, but the precise function of this area is still debated because patients with frontal lesions that include the precentral gyrus do not exhibit disturbances in speech comprehension. We report on a patient who underwent resection of the tumor in the precentral gyrus with electrocorticographic recordings while she performed the verb generation task during awake brain craniotomy. Consistent with previous fMRI studies, high-gamma band auditory activity was observed in the precentral gyrus. Due to the location of the tumor, the patient underwent resection of the auditory responsive precentral area which resulted in the post-operative expression of a characteristic articulatory disturbance known as apraxia of speech (AOS). The language function of the patient was otherwise preserved and she exhibited intact comprehension of both spoken and written language. The present findings demonstrated that a lesion restricted to the ventral precentral gyrus is sufficient for the expression of AOS and suggest that the auditory-responsive area plays an important role in the execution of fluent speech rather than the comprehension of speech. These findings also confirm that the function of the premotor area is predominantly motor in nature and its sensory responses is more consistent with the "sensory theory of speech production," in which it was proposed that sensory representations are used to guide motor-articulatory processes.

Validity and Responsiveness of the Two-Minute Walk Test for Measuring Functional Recovery After Total Knee Arthroplasty.

PubMed

Unnanuntana, Aasis; Ruangsomboon, Pakpoom; Keesukpunt, Worawut

2018-06-01

The 2-minute walk test (2mwt) is a performance-based test that evaluates functional recovery after total knee arthroplasty (TKA). This study evaluated its validity compared with the modified Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Oxford Knee Score (OKS), modified Knee Score, Numerical Pain Rating Scale, and Timed Up and Go test, and its responsiveness in assessing functional recovery in TKA patients. This prospective cohort study included 162 patients undergoing primary TKA between 2013 and 2015. We used patient-reported outcome measures (modified WOMAC, OKS, modified Knee Score, Numerical Pain Rating Scale) and performance-based tests (2mwt and Timed Up and Go test) at baseline and 3, 6, and 12 months postoperatively. The construct validity of 2mwt was determined between the 2mwt distances walked and other outcome measurements. To assess responsiveness, effect size and standardized response mean were analyzed. Minimal clinically important difference of 2mwt at 12 months after TKA was also calculated. All outcome measurements improved significantly from baseline to 3, 6, and 12 months postoperatively. Bivariate analysis revealed mild to moderate associations between the 2mwt and modified WOMAC function subscales, and moderate to strong associations with OKS. Mild to moderate correlations were found for pain and stiffness between 2mwt and other outcome measurements. The effect size and standardized response mean at 12 months were large, with a minimal clinically important difference of 12.7 m. 2mwt is a validated performance-based test with responsiveness properties. Being simple and easy to perform, it can be used routinely in clinical practice to evaluate functional recovery after TKA. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Lipid transfer proteins and protease inhibitors as key factors in the priming of barley responses to Fusarium head blight disease by a biocontrol strain of Pseudomonas fluorescens.

PubMed

Petti, Carloalberto; Khan, Mojibur; Doohan, Fiona

2010-11-01

Strains of non-pathogenic pseudomonad bacteria, can elicit host defence responses against pathogenic microorganisms. Pseudomonas fluorescens strain MKB158 can protect cereals from pathogenesis by Fusarium fungi, including Fusarium head blight which is an economically important disease due to its association with both yield loss and mycotoxin contamination of grain. Using the 22 K barley Affymetrix chip, trancriptome studies were undertaken to determine the local effect of P. fluorescens strain MKB158 on the transcriptome of barley head tissue, and to discriminate transcripts primed by the bacterium to respond to challenge by Fusarium culmorum, a causal agent of the economically important Fusarium head blight disease of cereals. The bacterium significantly affected the accumulation of 1203 transcripts and primed 74 to positively, and 14 to negatively, respond to the pathogen (P = 0.05). This is the first study to give insights into bacterium priming in the Triticeae tribe of grasses and associated transcripts were classified into 13 functional classes, associated with diverse functions, including detoxification, cell wall biosynthesis and the amplification of host defence responses. In silico analysis of Arabidopsis homologs of bacterium-primed barley genes indicated that, as is the case in dicots, jasmonic acid plays a role in pseudomonad priming of host responses. Additionally, the transcriptome studies described herein also reveal new insights into bacterium-mediated priming of host defences against necrotrophs, including the positive effects on grain filling, lignin deposition, oxidative stress responses, and the inhibition of protease inhibitors and proteins that play a key role in programmed cell death.

A sestrin-dependent Erk/Jnk/p38 MAPK activation complex inhibits immunity during ageing

PubMed Central

Lanna, Alessio; Gomes, Daniel C O; Muller-Durovic, Bojana; McDonnell, Thomas; Escors, David; Gilroy, Derek W; Lee, Jun Hee; Karin, Michael; Akbar, Arne N

2016-01-01

Mitogen activated protein kinases (MAPKs) including Erk, Jnk and p38 regulate diverse cellular functions, and are thought to be controlled by independent upstream activation cascades. Here we show that the sestrins bind to and co-ordinate simultaneous Erk, Jnk and p38 MAPK activation in T lymphocytes within a new immune-inhibitory complex (sestrin-MAPK Activation Complex; sMAC). Whereas sestrin ablation resulted in broad reconstitution of immune function in stressed T cells, inhibition of individual MAPKs only allowed partial functional recovery. T cells from old humans and mice were more likely to form the sMAC, and disruption of this complex restored antigen-specific functional responses in these cells. Correspondingly, sestrin deficiency or simultaneous inhibition of all three MAPKs enhanced vaccine responsiveness in old mice. Thus, disruption of sMAC provides a foundation for rejuvenating immunity during ageing. PMID:28114291

Intermediates of Metabolism: From Bystanders to Signalling Molecules.

PubMed

Haas, Robert; Cucchi, Danilo; Smith, Joanne; Pucino, Valentina; Macdougall, Claire Elizabeth; Mauro, Claudio

2016-05-01

The integration of biochemistry into immune cell biology has contributed immensely to our understanding of immune cell function and the associated pathologies. So far, most studies have focused on the regulation of metabolic pathways during an immune response and their contribution to its success. More recently, novel signalling functions of metabolic intermediates are being discovered that might play important roles in the regulation of immunity. Here we describe the three long-known small metabolites lactate, acetyl-CoA, and succinate in the context of immunometabolic signalling. Functions of these ubiquitous molecules are largely dependent on their intra- and extracellular concentrations as well as their subcompartmental localisation. Importantly, the signalling functions of these metabolic intermediates extend beyond self-regulatory roles and include cell-to-cell communication and sensing of microenvironmental conditions to elicit stress responses and cellular adaptation. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

Directional Unfolded Source Term (DUST) for Compton Cameras.

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

Mitchell, Dean J.; Horne, Steven M.; O'Brien, Sean

2018-03-01

A Directional Unfolded Source Term (DUST) algorithm was developed to enable improved spectral analysis capabilities using data collected by Compton cameras. Achieving this objective required modification of the detector response function in the Gamma Detector Response and Analysis Software (GADRAS). Experimental data that were collected in support of this work include measurements of calibration sources at a range of separation distances and cylindrical depleted uranium castings.

p53 -Dependent and -Independent Nucleolar Stress Responses

PubMed Central

Olausson, Karl Holmberg; Nistér, Monica; Lindström, Mikael S.

2012-01-01

The nucleolus has emerged as a cellular stress sensor and key regulator of p53-dependent and -independent stress responses. A variety of abnormal metabolic conditions, cytotoxic compounds, and physical insults induce alterations in nucleolar structure and function, a situation known as nucleolar or ribosomal stress. Ribosomal proteins, including RPL11 and RPL5, become increasingly bound to the p53 regulatory protein MDM2 following nucleolar stress. Ribosomal protein binding to MDM2 blocks its E3 ligase function leading to stabilization and activation of p53. In this review we focus on a number of novel regulators of the RPL5/RPL11-MDM2-p53 complex including PICT1 (GLTSCR2), MYBBP1A, PML and NEDD8. p53-independent pathways mediating the nucleolar stress response are also emerging and in particular the negative control that RPL11 exerts on Myc oncoprotein is of importance, given the role of Myc as a master regulator of ribosome biogenesis. We also briefly discuss the potential of chemotherapeutic drugs that specifically target RNA polymerase I to induce nucleolar stress. PMID:24710530

Amygdala response to faces parallels social behavior in Williams syndrome

PubMed Central

Snyder, Abraham Z.; Haist, Frank; Raichle, Marcus E.; Bellugi, Ursula; Stiles, Joan

2009-01-01

Individuals with Williams syndrome (WS), a genetically determined disorder, show relatively strong face-processing abilities despite poor visuospatial skills and depressed intellectual function. Interestingly, beginning early in childhood they also show an unusually high level of interest in face-to-face social interaction. We employed functional magnetic resonance imaging (fMRI) to investigate physiological responses in face-sensitive brain regions, including ventral occipito-temporal cortex and the amygdala, in this unique genetic disorder. Participants included 17 individuals with WS, 17 age- and gender-matched healthy adults (chronological age-matched controls, CA) and 17 typically developing 8- to 9-year-old children (developmental age controls, DA). While engaged in a face discrimination task, WS participants failed to recruit the amygdala, unlike both CA and DA controls. WS fMRI responses in ventral occipito-temporal cortex, however, were comparable to those of DA controls. Given the integral role of the amygdala in social behavior, the failure of WS participants to recruit this region during face processing may be a neural correlate of the abnormally high sociability that characterizes this disorder. PMID:19633063

Stability and bifurcation analysis of three-species predator-prey model with non-monotonic delayed predator response

NASA Astrophysics Data System (ADS)

Balilo, Aldrin T.; Collera, Juancho A.

2018-03-01

In this paper, we consider delayed three-species predator-prey model with non-monotonic functional response where two predator populations feed on a single prey population. Response function in both predator populations includes a time delay which represents the gestation period of the predator populations. We call a positive equlibrium solution of the form E*S=(x*,y*,y*) as a symmetric equilibrium. The goal of this paper is to determine the effect of the difference in gestation periods of predator populations to the local dynamics of symmetric equilibria. Our results include conditions on the existence of equilibrium solutions, and stability and bifurcations of symmetric equilibria as the gestation periods of predator populations are varied. A numerical bifurcation analysis tool is also used to illustrate our results. Stability switch occurs at a Hopf bifurcation. Moreover, a branch of stable periodic solutions, obtained using numerical continuation, emerges from the Hopf bifurcation. This shows that the predator population with longer gestation period oscillates higher than the predator population with shorter gestation period.

Vagal-immune interactions involved in cholinergic anti-inflammatory pathway.

PubMed

Zila, I; Mokra, D; Kopincova, J; Kolomaznik, M; Javorka, M; Calkovska, A

2017-09-22

Inflammation and other immune responses are involved in the variety of diseases and disorders. The acute response to endotoxemia includes activation of innate immune mechanisms as well as changes in autonomic nervous activity. The autonomic nervous system and the inflammatory response are intimately linked and sympathetic and vagal nerves are thought to have anti-inflammation functions. The basic functional circuit between vagus nerve and inflammatory response was identified and the neuroimmunomodulation loop was called cholinergic anti-inflammatory pathway. Unique function of vagus nerve in the anti-inflammatory reflex arc was found in many experimental and pre-clinical studies. They brought evidence on the cholinergic signaling interacting with systemic and local inflammation, particularly suppressing immune cells function. Pharmacological/electrical modulation of vagal activity suppressed TNF-alpha and other proinflammatory cytokines production and had beneficial therapeutic effects. Many questions related to mapping, linking and targeting of vagal-immune interactions have been elucidated and brought understanding of its basic physiology and provided the initial support for development of Tracey´s inflammatory reflex. This review summarizes and critically assesses the current knowledge defining cholinergic anti-inflammatory pathway with main focus on studies employing an experimental approach and emphasizes the potential of modulation of vagally-mediated anti-inflammatory pathway in the treatment strategies.

The Melanopic Sensitivity Function Accounts for Melanopsin-Driven Responses in Mice under Diverse Lighting Conditions

PubMed Central

Brown, Timothy M.; Allen, Annette E.; al-Enezi, Jazi; Wynne, Jonathan; Schlangen, Luc; Hommes, Vanja; Lucas, Robert J.

2013-01-01

In addition to rods and cones, photoreception in mammals extends to a third retinal cell type expressing the photopigment melanopsin. The influences of this novel opsin are widespread, ranging from pupillary and circadian responses to brightness perception, yet established approaches to quantifying the biological effects of light do not adequately account for melanopsin sensitivity. We have recently proposed a novel metric, the melanopic sensitivity function (VZλ), to address this deficiency. Here, we further validate this new measure with a variety of tests based on potential barriers to its applicability identified in the literature or relating to obvious practical benefits. Using electrophysiogical approaches and pupillometry, initially in rodless+coneless mice, our data demonstrate that under a very wide range of different conditions (including switching between stimuli with highly divergent spectral content) the VZλ function provides an accurate prediction of the sensitivity of melanopsin-dependent responses. We further show that VZλ provides the best available description of the spectral sensitivity of at least one aspect of the visual response in mice with functional rods and cones: tonic firing activity in the lateral geniculate nuclei. Together, these data establish VZλ as an important new approach for light measurement with widespread practical utility. PMID:23301090

Cardiac autonomic function in children with type 1 diabetes.

PubMed

Metwalley, Kotb Abbass; Hamed, Sherifa Ahmed; Farghaly, Hekma Saad

2018-06-01

Cardiovascular autonomic neuropathy (CAN) is a major complication of type 1 diabetes (T1D). This study aimed to evaluate cardiac autonomic nervous system (ANS) function in children with T1D and its relation to different demographic, clinical and laboratory variable. This cross-sectional study included 60 children with T1D (mean age = 15.1 ± 3.3 years; duration of diabetes = 7.95 ± 3.83 years). The following 8 non-invasive autonomic testing were used for evaluation: heart rate at rest and in response to active standing (30:15 ratio), deep breathing and Valsalva maneuver (indicating parasympathetic function); blood pressure response to standing (orthostatic hypotension or OH), sustained handgrip and cold; and heart rate response to standing or positional orthostatic tachycardia syndrome or POTs (indicating sympathetic function). None had clinically manifest CAN. Compared to healthy children (5%), 36.67% of children with T1D had ≥ 2 abnormal tests (i.e., CAN) (P = 0.0001) which included significantly abnormal heart rate response to standing (POTs) (P = 0.052), active standing (30:15 ratio) (P = 0.0001) and Valsalva maneuver (P = 0.0001), indicating parasympathetic autonomic dysfunction, and blood pressure response to cold (P = 0.01), indicating sympathetic autonomic dysfunction. 54.55, 27.27 and 18.18% had early, definite and severe dysfunction of ANS. All patients had sensorimotor peripheral neuropathy. The longer duration of diabetes (> 5 years), presence of diabetic complications and worse glycemic control were significantly associated with CAN. The study concluded that both parasympathetic and sympathetic autonomic dysfunctions are common in children with T1D particularly with longer duration of diabetes and presence of microvascular complications. What is Known: • Cardiovascular autonomic neuropathy (CAN) is a major complication of type 1 diabetes (T1D). • Limited studies evaluated CAN in children with T1D. What is New: • CAN is common in children with T1D. • Cardiac autonomic functions should be assessed in children with T1D particularly in presence of microvascular complications.

A general framework for numerical simulation of improvised explosive device (IED)-detection scenarios using density functional theory (DFT) and terahertz (THz) spectra.

PubMed

Shabaev, Andrew; Lambrakos, Samuel G; Bernstein, Noam; Jacobs, Verne L; Finkenstadt, Daniel

2011-04-01

We have developed a general framework for numerical simulation of various types of scenarios that can occur for the detection of improvised explosive devices (IEDs) through the use of excitation using incident electromagnetic waves. A central component model of this framework is an S-matrix representation of a multilayered composite material system. Each layer of the system is characterized by an average thickness and an effective electric permittivity function. The outputs of this component are the reflectivity and the transmissivity as functions of frequency and angle of the incident electromagnetic wave. The input of the component is a parameterized analytic-function representation of the electric permittivity as a function of frequency, which is provided by another component model of the framework. The permittivity function is constructed by fitting response spectra calculated using density functional theory (DFT) and parameter adjustment according to any additional information that may be available, e.g., experimentally measured spectra or theory-based assumptions concerning spectral features. A prototype simulation is described that considers response characteristics for THz excitation of the high explosive β-HMX. This prototype simulation includes a description of a procedure for calculating response spectra using DFT as input to the Smatrix model. For this purpose, the DFT software NRLMOL was adopted. © 2011 Society for Applied Spectroscopy

Interaction of CSFV E2 protein with swine host factors as detected by yeast two-hybrid system

USDA-ARS?s Scientific Manuscript database

E2 is one of the envelope glycoproteins of pestiviruses, including classical swine fever virus (CSFV) and bovine viral diarrhea virus (BVDV). E2 is involved in several critical functions, including virus entry into target cells, induction of a protective immune response and virulence in swine. Howev...

Satellite Cell Functional Alterations Following Cutaneous Burn in rats Include an Increase in Their Osteogenic Potential

DTIC Science & Technology

2013-10-07

response to local injury [3]. They have also been recognized as having a role in diseases, including cachexia and sarcopenia, where muscle mass may be...1961;9:493. [4] Dasarathy S. Consilience in sarcopenia of cirrhosis. J Cachexia Sarcopenia Muscle 2012;3:225. [5] Glass DJ. Signaling pathways that mediate

Immunotherapy Response Assessment in Neuro-Oncology (iRANO): A Report of the RANO Working Group

PubMed Central

Okada, Hideho; Weller, Michael; Huang, Raymond; Finocchiaro, Gaetano; Gilbert, Mark R.; Wick, Wolfgang; Ellingson, Benjamin M.; Hashimoto, Naoya; Pollack, Ian F.; Brandes, Alba A.; Franceschi, Enrico; Herold-Mende, Christel; Nayak, Lakshmi; Panigrahy, Ashok; Pope, Whitney B.; Prins, Robert; Sampson, John H.; Wen, Patrick Y.; Reardon, David A.

2015-01-01

Immunotherapy represents a promising area of therapy among neuro-oncology patients. However, early phase studies reveal unique challenges associated with assessment of radiological changes reflecting delayed responses or therapy-induced inflammation. Clinical benefit, including long-term survival and tumor regression, can still occur following initial apparent progression or appearance of new lesions. Refinement of response assessment criteria for neuro-oncology patients undergoing immunotherapy is therefore warranted. A multinational and multidisciplinary panel of neuro-oncology immunotherapy experts describes immunotherapy response assessment for neuro-oncology (iRANO) criteria that are based on guidance for determination of tumor progression outlined by the immune-related response criteria (irRC) and the response assessment in neuro-oncology (RANO) working group. Among patients who demonstrate imaging findings meeting RANO criteria for progressive disease (PD) within six months of initiating immunotherapy including the development of new lesions, confirmation of radiographic progression on follow-up imaging is recommended provided that the patient is not significantly worse clinically. The proposed criteria also include guidelines for use of corticosteroids. The role of advanced imaging techniques and measurement of clinical benefit endpoints including neurologic and immunologic functions are reviewed. The iRANO guidelines put forth herein will evolve successively to improve their utility as further experience from immunotherapy trials in neuro-oncology accumulate. PMID:26545842

Gene, Immune and Cellular Responses to Single and Combined Space Flight Conditions-B (TripleLux-B):

NASA Image and Video Library

2015-03-31

ISS043E070945 (03/31/2015) --- ESA (European Space Agency) astronaut Samantha Cristoforetti, Expedition 43 flight engineer aboard the International Space Station, is seen working on a science experiment that includes photographic documentation of Cellular Responses to Single and Combined Space Flight Conditions. Some effects of the space environment level appear to act at the cellular level and it is important to understand the underlying mechanisms of these effects. This science project uses invertebrate hemocytes to focus on two aspects of cellular function which may have medical importance. The synergy between the effects of the space radiation environment and microgravity on cellular function is the goal of this experiment along with studying the impairment of immune functions under spaceflight conditions.

A FORTRAN program for the analysis of linear continuous and sample-data systems

NASA Technical Reports Server (NTRS)

Edwards, J. W.

1976-01-01

A FORTRAN digital computer program which performs the general analysis of linearized control systems is described. State variable techniques are used to analyze continuous, discrete, and sampled data systems. Analysis options include the calculation of system eigenvalues, transfer functions, root loci, root contours, frequency responses, power spectra, and transient responses for open- and closed-loop systems. A flexible data input format allows the user to define systems in a variety of representations. Data may be entered by inputing explicit data matrices or matrices constructed in user written subroutines, by specifying transfer function block diagrams, or by using a combination of these methods.

GSE, data management system programmers/User' manual

NASA Technical Reports Server (NTRS)

Schlagheck, R. A.; Dolerhie, B. D., Jr.; Ghiglieri, F. J.

1974-01-01

The GSE data management system is a computerized program which provides for a central storage source for key data associated with the mechanical ground support equipment (MGSE). Eight major sort modes can be requested by the user. Attributes that are printed automatically with each sort include the GSE end item number, description, class code, functional code, fluid media, use location, design responsibility, weight, cost, quantity, dimensions, and applicable documents. Multiple subsorts are available for the class code, functional code, fluid media, use location, design responsibility, and applicable document categories. These sorts and how to use them are described. The program and GSE data bank may be easily updated and expanded.

HIF-2α is essential for carotid body development and function

PubMed Central

Cowburn, Andrew S; Torres-Torrelo, Hortensia; Ortega-Sáenz, Patricia; López-Barneo, José

2018-01-01

Mammalian adaptation to oxygen flux occurs at many levels, from shifts in cellular metabolism to physiological adaptations facilitated by the sympathetic nervous system and carotid body (CB). Interactions between differing forms of adaptive response to hypoxia, including transcriptional responses orchestrated by the Hypoxia Inducible transcription Factors (HIFs), are complex and clearly synergistic. We show here that there is an absolute developmental requirement for HIF-2α, one of the HIF isoforms, for growth and survival of oxygen sensitive glomus cells of the carotid body. The loss of these cells renders mice incapable of ventilatory responses to hypoxia, and this has striking effects on processes as diverse as arterial pressure regulation, exercise performance, and glucose homeostasis. We show that the expansion of the glomus cells is correlated with mTORC1 activation, and is functionally inhibited by rapamycin treatment. These findings demonstrate the central role played by HIF-2α in carotid body development, growth and function. PMID:29671738

Coding and Plasticity in the Mammalian Thermosensory System.

PubMed

Yarmolinsky, David A; Peng, Yueqing; Pogorzala, Leah A; Rutlin, Michael; Hoon, Mark A; Zuker, Charles S

2016-12-07

Perception of the thermal environment begins with the activation of peripheral thermosensory neurons innervating the body surface. To understand how temperature is represented in vivo, we used genetically encoded calcium indicators to measure temperature-evoked responses in hundreds of neurons across the trigeminal ganglion. Our results show how warm, hot, and cold stimuli are represented by distinct population responses, uncover unique functional classes of thermosensory neurons mediating heat and cold sensing, and reveal the molecular logic for peripheral warmth sensing. Next, we examined how the peripheral somatosensory system is functionally reorganized to produce altered perception of the thermal environment after injury. We identify fundamental transformations in sensory coding, including the silencing and recruitment of large ensembles of neurons, providing a cellular basis for perceptual changes in temperature sensing, including heat hypersensitivity, persistence of heat perception, cold hyperalgesia, and cold analgesia. Copyright © 2016 Elsevier Inc. All rights reserved.

XIMPOL: a new x-ray polarimetry observation-simulation and analysis framework

NASA Astrophysics Data System (ADS)

Omodei, Nicola; Baldini, Luca; Pesce-Rollins, Melissa; di Lalla, Niccolò

2017-08-01

We present a new simulation framework, XIMPOL, based on the python programming language and the Scipy stack, specifically developed for X-ray polarimetric applications. XIMPOL is not tied to any specific mission or instrument design and is meant to produce fast and yet realistic observation-simulations, given as basic inputs: (i) an arbitrary source model including morphological, temporal, spectral and polarimetric information, and (ii) the response functions of the detector under study, i.e., the effective area, the energy dispersion, the point-spread function and the modulation factor. The format of the response files is OGIP compliant, and the framework has the capability of producing output files that can be directly fed into the standard visualization and analysis tools used by the X-ray community, including XSPEC which make it a useful tool not only for simulating physical systems, but also to develop and test end-to-end analysis chains.

Capacitive sensing of droplets for microfluidic devices based on thermocapillary actuation.

PubMed

Chen, Jian Z; Darhuber, Anton A; Troian, Sandra M; Wagner, Sigurd

2004-10-01

The design and performance of a miniaturized coplanar capacitive sensor is presented whose electrode arrays can also function as resistive microheaters for thermocapillary actuation of liquid films and droplets. Optimal compromise between large capacitive signal and high spatial resolution is obtained for electrode widths comparable to the liquid film thickness measured, in agreement with supporting numerical simulations which include mutual capacitance effects. An interdigitated, variable width design, allowing for wider central electrodes, increases the capacitive signal for liquid structures with non-uniform height profiles. The capacitive resolution and time response of the current design is approximately 0.03 pF and 10 ms, respectively, which makes possible a number of sensing functions for nanoliter droplets. These include detection of droplet position, size, composition or percentage water uptake for hygroscopic liquids. Its rapid response time allows measurements of the rate of mass loss in evaporating droplets.

[Neural and cognitive correlates of social cognition: findings on neuropsychological and neuroimaging studies].

PubMed

Kobayakawa, Mutsutaka; Kawamura, Mitsuru

2011-12-01

Social cognition includes various components of information processing related to communication with other individuals. In this review, we have discussed 3 components of social cognitive function: face recognition, empathy, and decision making. Our social behavior involves recognition based on facial features and also involves empathizing with others; while making decisions, it is important to consider the social consequences of the course of action followed. Face recognition is divided into 2 routes for information processing: a route responsible for overt recognition of the face's identity and a route for emotional and orienting responses based on the face's personal affective significance. Two systems are possibly involved in empathy: a basic emotional contagion "mirroring" system and a more advanced "theory of mind" system that considers the cognitive perspective. Decision making is mediated by a widespread system that includes several cortical and subcortical components. Numerous lesion and neuroimaging studies have contributed to clarifying the neural correlates of social cognitive function, and greater information can be obtained on social cognitive function by combining these 2 approaches.

R package PRIMsrc: Bump Hunting by Patient Rule Induction Method for Survival, Regression and Classification

PubMed Central

Dazard, Jean-Eudes; Choe, Michael; LeBlanc, Michael; Rao, J. Sunil

2015-01-01

PRIMsrc is a novel implementation of a non-parametric bump hunting procedure, based on the Patient Rule Induction Method (PRIM), offering a unified treatment of outcome variables, including censored time-to-event (Survival), continuous (Regression) and discrete (Classification) responses. To fit the model, it uses a recursive peeling procedure with specific peeling criteria and stopping rules depending on the response. To validate the model, it provides an objective function based on prediction-error or other specific statistic, as well as two alternative cross-validation techniques, adapted to the task of decision-rule making and estimation in the three types of settings. PRIMsrc comes as an open source R package, including at this point: (i) a main function for fitting a Survival Bump Hunting model with various options allowing cross-validated model selection to control model size (#covariates) and model complexity (#peeling steps) and generation of cross-validated end-point estimates; (ii) parallel computing; (iii) various S3-generic and specific plotting functions for data visualization, diagnostic, prediction, summary and display of results. It is available on CRAN and GitHub. PMID:26798326

The effects and potential mechanisms of folic acid on cognitive function: a comprehensive review.

PubMed

Enderami, Athena; Zarghami, Mehran; Darvishi-Khezri, Hadi

2018-06-23

Cognitive impairment and dementia are major neurocognitive disorders that cause a noticeable decline in cognitive abilities, including memory and thinking skills. The effectiveness of using folic acid as an adjuvant for management of neurocognitive disorders is not well-known. This paper explains the role of folic acid, including its usefulness, effectiveness, adverse side effects, and active mechanisms on cognitive functions of the elderly. In the current study, we reviewed clinical and experimental studies investigating the use of folic acid prior to November 2017, using PubMed, ISI Web of Knowledge, Science Direct, Scopus, Ovid, and Cochrane Library databases. A total of 142 articles were retrieved by electronic search. Based on the preset inclusion and exclusion criteria, a total of 36 articles were retrieved for full text analysis. According to data obtained from the review, it seems that folic acid supplementation may improve cognitive function by decreasing homocysteine (Hcy), vascular care, attenuating inflammatory status, modification of cerebral folic acid deficiency, and antioxidant responses. Specifically, people with high levels of Hcy have a better response to folic acid supplementation, which may arise from low serum folate concentration.

Functional Groups Based on Leaf Physiology: Are they Spatially and Temporally Robust?

NASA Technical Reports Server (NTRS)

Foster, Tammy E.; Brooks, J. Renee; Quincy, Charles (Technical Monitor)

2002-01-01

The functional grouping hypothesis, which suggests that complexity in function can be simplified by grouping species with similar responses, was tested in the Florida scrub habitat. Functional groups were identified based on how species in fire maintained FL scrub function in terms of carbon, water and nitrogen dynamics. The suite of physiologic parameters measured to determine function included both instantaneous gas exchange measurements obtained from photosynthetic light response curves and integrated measures of function. Using cluster analysis, five distinct physiologically-based functional groups were identified. Using non-parametric multivariate analyses, it was determined that these five groupings were not altered by plot differences or by the three different management regimes; prescribed burn, mechanically treated and burn, and fire-suppressed. The physiological groupings also remained robust between the two years 1999 and 2000. In order for these groupings to be of use for scaling ecosystem processes, there needs to be an easy-to-measure morphological indicator of function. Life form classifications were able to depict the physiological groupings more adequately than either specific leaf area or leaf thickness. THe ability of life forms to depict the groupings was improved by separating the parasitic Ximenia americana from the shrub category.

Light-Responsive and pH-Responsive DNA Microcapsules for Controlled Release of Loads.

PubMed

Huang, Fujian; Liao, Wei-Ching; Sohn, Yang Sung; Nechushtai, Rachel; Lu, Chun-Hua; Willner, Itamar

2016-07-20

A method to assemble light-responsive or pH-responsive microcapsules loaded with different loads (tetramethylrhodamine-modified dextran, TMR-D; microperoxidase-11, MP-11; CdSe/ZnS quantum dots; or doxorubicin-modified dextran, DOX-D) is described. The method is based on the layer-by-layer deposition of sequence-specific nucleic acids on poly(allylamine hydrochloride)-functionalized CaCO3 core microparticles, loaded with the different loads, that after the dissolution of the core particles with EDTA yields the stimuli-responsive microcapsules that include the respective loads. The light-responsive microcapsules are composed of photocleavable o-nitrobenzyl-phosphate-modified DNA shells, and the pH-responsive microcapsules are made of a cytosine-rich layer cross-linked by nucleic acid bridges. Irradiating the o-nitrobenzyl phosphate-functionalized microcapsules, λ = 365 nm, or subjecting the pH-responsive microcapsules to pH = 5.0, results in the cleavage of the microcapsule shells and the release of the loads. Preliminary studies address the cytotoxicity of the DOX-D-loaded microcapsules toward MDA-MB-231 breast cancer cells and normal MCF-10A breast epithelial cells. Selective cytotoxicity of the DOX-D-loaded microcapsules toward cancer cells is demonstrated.

Sequential Events Control System (SECS) Overview

NASA Technical Reports Server (NTRS)

Interbartolo, Michael

2009-01-01

This slide presentation will cover the Sequential Events Control System (SECS), which is the Apollo spacecraft subsystem that controls the automatically sequenced functions during the mission and during any a borts that could be performed. Included in this presentation are its general architecture, its integration into and use of the spacecraft' s other systems, and details on the functions it is responsible for c ontrolling during the mission. The objectives are to describe the system's architecture, the major components in the system, and the major system functions.

The Small Ethylene Response Factor ERF96 is Involved in the Regulation of the Abscisic Acid Response in Arabidopsis

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

Wang, Xiaoping; Liu, Shanda; Tian, Hainan

We report that ethylene regulates many aspects of plant growth and development including seed germination, leaf senescence, and fruit ripening, and of plant responses to environmental stimuli including both biotic and abiotic stresses. Ethylene response factors (ERFs) are plant-specific transcription factors and are a subfamily of the AP2 (APETALA2)/ERF transcription factor family. The function of many members in this large gene family remains largely unknown. ERF96, a member of the Group IX ERF family transcription factors, has recently been shown to be a transcriptional activator that is involved in plant defense response in Arabidopsis. Here we provide evidence that ERF96more » is a positive regulator of abscisic acid (ABA) responses. Bioinformatics analysis indicated that there are a total four small ERFs in Arabidopsis including ERF95, ERF96, ERF97, and ERF98, and that ERF96 forms a cluster with ERF95 and ERF97. By using quantitative RT-PCR, we found that ERF96 is expressed in all tissues and organs examined except roots, with relatively high expression in flowers and seeds. Results from the protoplast transfection assay indicated that the EDLL motif-containing C-terminal domain is responsible for ERF96’s transcriptional activity. Although loss-of-function mutant of ERF96 was morphologically similar to wild type plants, transgenic plants overexpressing ERF96 had smaller rosette size and were delayed in flowering time. In ABA sensitivity assays, we found that ERF96 overexpression plants were hypersensitive to ABA in terms of ABA inhibition of seed germination, early seedling development and root elongation. Consistent with these observations, elevated transcript levels of some ABA-responsive genes including RD29A, ABI5, ABF3, ABF4, P5CS, and COR15A were observed in the transgenic plants in the presence of ABA. However, in the absence of ABA treatment, the transcript levels of these ABA-responsive genes remained largely unchanged. Our experiments also showed that water loss in ERF96 overexpression plants was slower than that in Col wild type plants. Stomatal closure assays indicated that ERF96 overexpression plants had reduced stomatal aperture in the presence of ABA. In conclusion, taken together, our results suggest that ERF96 positively regulates ABA responses in Arabidopsis.« less

The Small Ethylene Response Factor ERF96 is Involved in the Regulation of the Abscisic Acid Response in Arabidopsis

DOE PAGES

Wang, Xiaoping; Liu, Shanda; Tian, Hainan; ...

2015-11-26

We report that ethylene regulates many aspects of plant growth and development including seed germination, leaf senescence, and fruit ripening, and of plant responses to environmental stimuli including both biotic and abiotic stresses. Ethylene response factors (ERFs) are plant-specific transcription factors and are a subfamily of the AP2 (APETALA2)/ERF transcription factor family. The function of many members in this large gene family remains largely unknown. ERF96, a member of the Group IX ERF family transcription factors, has recently been shown to be a transcriptional activator that is involved in plant defense response in Arabidopsis. Here we provide evidence that ERF96more » is a positive regulator of abscisic acid (ABA) responses. Bioinformatics analysis indicated that there are a total four small ERFs in Arabidopsis including ERF95, ERF96, ERF97, and ERF98, and that ERF96 forms a cluster with ERF95 and ERF97. By using quantitative RT-PCR, we found that ERF96 is expressed in all tissues and organs examined except roots, with relatively high expression in flowers and seeds. Results from the protoplast transfection assay indicated that the EDLL motif-containing C-terminal domain is responsible for ERF96’s transcriptional activity. Although loss-of-function mutant of ERF96 was morphologically similar to wild type plants, transgenic plants overexpressing ERF96 had smaller rosette size and were delayed in flowering time. In ABA sensitivity assays, we found that ERF96 overexpression plants were hypersensitive to ABA in terms of ABA inhibition of seed germination, early seedling development and root elongation. Consistent with these observations, elevated transcript levels of some ABA-responsive genes including RD29A, ABI5, ABF3, ABF4, P5CS, and COR15A were observed in the transgenic plants in the presence of ABA. However, in the absence of ABA treatment, the transcript levels of these ABA-responsive genes remained largely unchanged. Our experiments also showed that water loss in ERF96 overexpression plants was slower than that in Col wild type plants. Stomatal closure assays indicated that ERF96 overexpression plants had reduced stomatal aperture in the presence of ABA. In conclusion, taken together, our results suggest that ERF96 positively regulates ABA responses in Arabidopsis.« less

The work role functioning questionnaire 2.0 (Dutch version): examination of its reliability, validity and responsiveness in the general working population.

PubMed

Abma, Femke I; van der Klink, Jac J L; Bültmann, Ute

2013-03-01

The promotion of a sustainable, healthy and productive working life attracts more and more attention. Recently the Work Role Functioning Questionnaire (WRFQ) has been cross-culturally translated and adapted to Dutch. This questionnaire aims to measure the health-related work functioning of workers with health problems. The aim of this study is to evaluate the reliability, validity (including five new items) and responsiveness of the WRFQ 2.0 in the working population. A longitudinal study was conducted among workers. The reliability (internal consistency, test-retest reliability, measurement error), validity (structural validity-factor analysis, construct validity by means of hypotheses testing) and responsiveness of the WRFQ 2.0 were evaluated. A total of N = 553 workers completed the survey. The final WRFQ 2.0 has four subscales and showed very good internal consistency, moderate test-retest reliability, good construct validity and moderate responsiveness in the working population. The WRFQ was able to distinguish between groups with different levels of mental health, physical health, fatigue and need for recovery. A moderate correlation was found between WRFQ and related constructs respectively work ability and work productivity. A weak relationship was found with general self-rated health, work engagement and work involvement. The WRFQ 2.0 is a reliable and valid instrument to measure health-related work functioning in the working population. Further validation in larger samples is recommended, especially for test-retest reliability, responsiveness and the questionnaire's ability to predict the future course of health-related work functioning.

The association between dry needling-induced twitch response and change in pain and muscle function in patients with low back pain: a quasi-experimental study.

PubMed

Koppenhaver, Shane L; Walker, Michael J; Rettig, Charles; Davis, Joel; Nelson, Chenae; Su, Jonathan; Fernández-de-Las-Peñas, Cesar; Hebert, Jeffrey J

2017-06-01

To investigate the relationship between dry needling-induced twitch response and change in pain, disability, nociceptive sensitivity, and lumbar multifidus muscle function, in patients with low back pain (LBP). Quasi-experimental study. Department of Defense Academic Institution. Sixty-six patients with mechanical LBP (38 men, 28 women, age: 41.3 [9.2] years). Dry needling treatment to the lumbar multifidus muscles between L3 and L5 bilaterally. Examination procedures included numeric pain rating, the Modified Oswestry Disability Index, pressure algometry, and real-time ultrasound imaging assessment of lumbar multifidus muscle function before and after dry needling treatment. Pain pressure threshold (PPT) was used to measure nocioceptive sensitivity. The percent change in muscle thickness from rest to contraction was calculated to represent muscle function. Participants were dichotomized and compared based on whether or not they experienced at least one twitch response on the most painful side and spinal level during dry needling. Participants experiencing local twitch response during dry needling exhibited greater immediate improvement in lumbar multifidus muscle function than participants who did not experience a twitch (thickness change with twitch: 12.4 [6]%, thickness change without twitch: 5.7 [11]%, mean difference adjusted for baseline value, 95%CI: 4.4 [1 to 8]%). However, this difference was not present after 1-week, and there were no between-groups differences in disability, pain intensity, or nociceptive sensitivity. The twitch response during dry needling might be clinically relevant, but should not be considered necessary for successful treatment. Published by Elsevier Ltd.

Characterization of CD4 and CD8 T Cell Responses in MuSK Myasthenia Gravis

PubMed Central

Yi, JS; Guidon, A; Sparks, S; Osborne, R; Juel, VC; Massey, JM; Sanders, DB; Weinhold, KJ; Guptill, JT

2014-01-01

Muscle specific tyrosine kinase myasthenia gravis (MuSK MG) is a form of autoimmune MG that predominantly affects women and has unique clinical features, including prominent bulbar weakness, muscle atrophy, and excellent response to therapeutic plasma exchange. Patients with MuSK MG have predominantly IgG4 autoantibodies directed against MuSK on the postsynaptic muscle membrane. Lymphocyte functionality has not been reported in this condition. The goal of this study was to characterize T-cell responses in patients with MuSK MG. Intracellular production of IFN-gamma, TNF-alpha, IL-2, IL-17, and IL-21 by CD4+ and CD8+ T-cells was measured by polychromatic flow cytometry in peripheral blood samples from 11 Musk MG patients and 10 healthy controls. Only one MuSK MG patient was not receiving immunosuppressive therapy. Regulatory T-cells (Treg) were also included in our analysis to determine if changes in T cell function were due to altered Treg frequencies. CD8+ T-cells from MuSK MG patients had higher frequencies of polyfunctional responses than controls, and CD4+ T-cells had higher IL-2, TNF-alpha, and IL-17. MuSK MG patients had a higher percentage of CD4+ T-cells producing combinations of IFN-gamma/IL-2/TNF-gamma, TNF-alpha/IL-2, and IFN-gamma/TNF-alpha. Interestingly, Treg numbers and CD39 expression were not different from control values. MuSK MG patients had increased frequencies of Th1 and Th17 cytokines and were primed for polyfunctional proinflammatory responses that cannot be explained by a defect in Treg function or number. PMID:24378287

Terrestrial Feedbacks Incorporated in Global Vegetation Models through Observed Trait-Environment Responses

NASA Astrophysics Data System (ADS)

Bodegom, P. V.

2015-12-01

Most global vegetation models used to evaluate climate change impacts rely on plant functional types to describe vegetation responses to environmental stresses. In a traditional set-up in which vegetation characteristics are considered constant within a vegetation type, the possibility to implement and infer feedback mechanisms are limited as feedback mechanisms will likely involve a changing expression of community trait values. Based on community assembly concepts, we implemented functional trait-environment relationships into a global dynamic vegetation model to quantitatively assess this feature. For the current climate, a different global vegetation distribution was calculated with and without the inclusion of trait variation, emphasizing the importance of feedbacks -in interaction with competitive processes- for the prevailing global patterns. These trait-environmental responses do, however, not necessarily imply adaptive responses of vegetation to changing conditions and may locally lead to a faster turnover in vegetation upon climate change. Indeed, when running climate projections, simulations with trait variation did not yield a more stable or resilient vegetation than those without. Through the different feedback expressions, global and regional carbon and water fluxes were -however- strongly altered. At a global scale, model projections suggest an increased productivity and hence an increased carbon sink in the next decades to come, when including trait variation. However, by the end of the century, a reduced carbon sink is projected. This effect is due to a downregulation of photosynthesis rates, particularly in the tropical regions, even when accounting for CO2-fertilization effects. Altogether, the various global model simulations suggest the critical importance of including vegetation functional responses to changing environmental conditions to grasp terrestrial feedback mechanisms at global scales in the light of climate change.

Multiple stressors, nonlinear effects and the implications of climate change impacts on marine coastal ecosystems.

PubMed

Hewitt, Judi E; Ellis, Joanne I; Thrush, Simon F

2016-08-01

Global climate change will undoubtedly be a pressure on coastal marine ecosystems, affecting not only species distributions and physiology but also ecosystem functioning. In the coastal zone, the environmental variables that may drive ecological responses to climate change include temperature, wave energy, upwelling events and freshwater inputs, and all act and interact at a variety of spatial and temporal scales. To date, we have a poor understanding of how climate-related environmental changes may affect coastal marine ecosystems or which environmental variables are likely to produce priority effects. Here we use time series data (17 years) of coastal benthic macrofauna to investigate responses to a range of climate-influenced variables including sea-surface temperature, southern oscillation indices (SOI, Z4), wind-wave exposure, freshwater inputs and rainfall. We investigate responses from the abundances of individual species to abundances of functional traits and test whether species that are near the edge of their tolerance to another stressor (in this case sedimentation) may exhibit stronger responses. The responses we observed were all nonlinear and some exhibited thresholds. While temperature was most frequently an important predictor, wave exposure and ENSO-related variables were also frequently important and most ecological variables responded to interactions between environmental variables. There were also indications that species sensitive to another stressor responded more strongly to weaker climate-related environmental change at the stressed site than the unstressed site. The observed interactions between climate variables, effects on key species or functional traits, and synergistic effects of additional anthropogenic stressors have important implications for understanding and predicting the ecological consequences of climate change to coastal ecosystems. © 2015 John Wiley & Sons Ltd.

Plant Abiotic Stress Proteomics: The Major Factors Determining Alterations in Cellular Proteome

PubMed Central

Kosová, Klára; Vítámvás, Pavel; Urban, Milan O.; Prášil, Ilja T.; Renaut, Jenny

2018-01-01

HIGHLIGHTS: Major environmental and genetic factors determining stress-related protein abundance are discussed.Major aspects of protein biological function including protein isoforms and PTMs, cellular localization and protein interactions are discussed.Functional diversity of protein isoforms and PTMs is discussed. Abiotic stresses reveal profound impacts on plant proteomes including alterations in protein relative abundance, cellular localization, post-transcriptional and post-translational modifications (PTMs), protein interactions with other protein partners, and, finally, protein biological functions. The main aim of the present review is to discuss the major factors determining stress-related protein accumulation and their final biological functions. A dynamics of stress response including stress acclimation to altered ambient conditions and recovery after the stress treatment is discussed. The results of proteomic studies aimed at a comparison of stress response in plant genotypes differing in stress adaptability reveal constitutively enhanced levels of several stress-related proteins (protective proteins, chaperones, ROS scavenging- and detoxification-related enzymes) in the tolerant genotypes with respect to the susceptible ones. Tolerant genotypes can efficiently adjust energy metabolism to enhanced needs during stress acclimation. Stress tolerance vs. stress susceptibility are relative terms which can reflect different stress-coping strategies depending on the given stress treatment. The role of differential protein isoforms and PTMs with respect to their biological functions in different physiological constraints (cellular compartments and interacting partners) is discussed. The importance of protein functional studies following high-throughput proteome analyses is presented in a broader context of plant biology. In summary, the manuscript tries to provide an overview of the major factors which have to be considered when interpreting data from proteomic studies on stress-treated plants. PMID:29472941

Auditory and visual health after ten years of exposure to metal-on-metal hip prostheses: a cross-sectional study follow up.

PubMed

Prentice, Jennifer R; Blackwell, Christopher S; Raoof, Naz; Bacon, Paul; Ray, Jaydip; Hickman, Simon J; Wilkinson, J Mark

2014-01-01

Case reports of patients with mal-functioning metal-on-metal hip replacement (MoMHR) prostheses suggest an association of elevated circulating metal levels with visual and auditory dysfunction. However, it is unknown if this is a cumulative exposure effect and the impact of prolonged low level exposure, relevant to the majority of patients with a well-functioning prosthesis, has not been studied. Twenty four male patients with a well-functioning MoMHR and an age and time since surgery matched group of 24 male patients with conventional total hip arthroplasty (THA) underwent clinical and electrophysiological assessment of their visual and auditory health at a mean of ten years after surgery. Median circulating cobalt and chromium concentrations were higher in patients after MoMHR versus those with THA (P<0.0001), but were within the Medicines and Healthcare Products Regulatory Agency (UK) investigation threshold. Subjective auditory tests including pure tone audiometric and speech discrimination findings were similar between groups (P>0.05). Objective assessments, including amplitude and signal-to-noise ratio of transient evoked and distortion product oto-acoustic emissions (TEOAE and DPOAE, respectively), were similar for all the frequencies tested (P>0.05). Auditory brainstem responses (ABR) and cortical evoked response audiometry (ACR) were also similar between groups (P>0.05). Ophthalmological evaluations, including self-reported visual function by visual functioning questionnaire, as well as binocular low contrast visual acuity and colour vision were similar between groups (P>0.05). Retinal nerve fibre layer thickness and macular volume measured by optical coherence tomography were also similar between groups (P>0.05). In the presence of moderately elevated metal levels associated with well-functioning implants, MoMHR exposure does not associate with clinically demonstrable visual or auditory dysfunction.

Turning on the alarm: the neural mechanisms of the transition from innocuous to painful sensation.

PubMed

Johnstone, Tom; Salomons, Tim V; Backonja, Miroslav Misha; Davidson, Richard J

2012-01-16

The experience of pain occurs when the level of a stimulus is sufficient to elicit a marked affective response, putatively to warn the organism of potential danger and motivate appropriate behavioral responses. Understanding the biological mechanisms of the transition from innocuous to painful levels of sensation is essential to understanding pain perception as well as clinical conditions characterized by abnormal relationships between stimulation and pain response. Thus, the primary objective of this study was to characterize the neural response associated with this transition and the correspondence between that response and subjective reports of pain. Towards this goal, this study examined BOLD response profiles across a range of temperatures spanning the pain threshold. 14 healthy adults underwent functional magnetic resonance imaging (fMRI) while a range of thermal stimuli (44-49°C) were applied. BOLD responses showed a sigmoidal profile along the range of temperatures in a network of brain regions including insula and mid-cingulate, as well as a number of regions associated with motor responses including ventral lateral nuclei of the thalamus, globus pallidus and premotor cortex. A sigmoid function fit to the BOLD responses in these regions explained up to 85% of the variance in individual pain ratings, and yielded an estimate of the temperature of steepest transition from non-painful to painful heat that was nearly identical to that generated by subjective ratings. These results demonstrate a precise characterization of the relationship between objective levels of stimulation, resulting neural activation, and subjective experience of pain and provide direct evidence for a neural mechanism supporting the nonlinear transition from innocuous to painful levels along the sensory continuum. Copyright © 2011 Elsevier Inc. All rights reserved.

Reduced aspirin responsiveness as assessed by impedance aggregometry is not associated with adverse outcome after cardiac surgery in a small low-risk cohort.

PubMed

Bolliger, Daniel; Filipovic, Miodrag; Matt, Peter; Tanaka, Kenichi A; Gregor, Michael; Zenklusen, Urs; Seeberger, Manfred D; Lurati Buse, Giovanna

2016-01-01

Reduced aspirin responsiveness (i.e. persistent high platelet reactivity in platelet function testing) might be associated with increased risk of myocardial ischemia and cardiac mortality in patients with coronary disease. However, the impact in patients undergoing coronary artery bypass grafting (CABG) is unclear. The aim of this prospective cohort study was to evaluate the predictive value of reduced aspirin responsiveness on cardiac and thromboembolic events in patients undergoing elective isolated CABG surgery with aspirin intake until at least two days before surgery. We included 304 patients in this prospective single-center cohort study. Impedance platelet aggregometry (Multiplate®) was performed directly before and on the first day after surgery. Reduced aspirin responsiveness was defined as area under the curve in ASPItest (AUCASPI) ≥300 U. The primary outcome was a composite of all-cause mortality and/or major adverse cardiac or thromboembolic events within 1 year. Reduced aspirin responsiveness was found in 13 and 24% of patients pre and postoperatively, respectively. There was no difference in the outcomes between patients with normal and reduced aspirin responsiveness in the preoperative measurement (log-rank test, p = 0.540). Multivariate analysis including logistic EuroSCORE I and postoperative troponin T levels did not show any association of reduced aspirin responsiveness with adverse outcome (hazard ratio, 0.576; (95% CI 0.128-2.585; p = 0.471). Similarly, postoperative reduced aspirin responsiveness was not associated with adverse events. To conclude, reduced aspirin responsiveness as evaluated by Multiplate® platelet function analyzer was not associated with increased incidence of major adverse cardiac and thromboembolic events and mortality after CABG surgery.

Cytokine effects on the basal ganglia and dopamine function: the subcortical source of inflammatory malaise.

PubMed

Felger, Jennifer C; Miller, Andrew H

2012-08-01

Data suggest that cytokines released during the inflammatory response target subcortical structures including the basal ganglia as well as dopamine function to acutely induce behavioral changes that support fighting infection and wound healing. However, chronic inflammation and exposure to inflammatory cytokines appears to lead to persisting alterations in the basal ganglia and dopamine function reflected by anhedonia, fatigue, and psychomotor slowing. Moreover, reduced neural responses to hedonic reward, decreased dopamine metabolites in the cerebrospinal fluid and increased presynaptic dopamine uptake and decreased turnover have been described. This multiplicity of changes in the basal ganglia and dopamine function suggest fundamental effects of inflammatory cytokines on dopamine synthesis, packaging, release and/or reuptake, which may sabotage and circumvent the efficacy of current treatment approaches. Thus, examination of the mechanisms by which cytokines alter the basal ganglia and dopamine function will yield novel insights into the treatment of cytokine-induced behavioral changes and inflammatory malaise. Copyright © 2012 Elsevier Inc. All rights reserved.

The diverse functions of Src family kinases in macrophages

PubMed Central

Abram, Clare L.; Lowell, Clifford A.

2015-01-01

Macrophages are key components of the innate immune response. These cells possess a diverse repertoire of receptors that allow them to respond to a host of external stimuli including cytokines, chemokines, and pathogen-associated molecules. Signals resulting from these stimuli activate a number of macrophage functional responses such as adhesion, migration, phagocytosis, proliferation, survival, cytokine release and production of reactive oxygen and nitrogen species. The cytoplasmic tyrosine kinase Src and its family members (SFKs) have been implicated in many intracellular signaling pathways in macrophages, initiated by a diverse set of receptors ranging from integrins to Toll-like receptors. However, it has been difficult to implicate any given member of the family in any specific pathway. SFKs appear to have overlapping and complementary functions in many pathways. Perhaps the function of these enzymes is to modulate the overall intracellular signaling network in macrophages, rather than operating as exclusive signaling switches for defined pathways. In general, SFKs may function more like rheostats, influencing the amplitude of many pathways. PMID:18508521

Nonparametric Conditional Estimation

DTIC Science & Technology

1987-02-01

the data because the statistician has complete control over the method. It is especially reasonable when there is a bone fide loss function to which...For example, the sample mean is m(Fn). Most calculations that statisticians perform on a set of data can be expressed as statistical functionals on...of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering

Prototype development and demonstration for response, emergency staging, communications, uniform management, and evacuation (R.E.S.C.U.M.E.) : R.E.S.C.U.M.E. final functional and performance requirements.

DOT National Transportation Integrated Search

2014-01-01

This document provides the high-level functional and performance requirements for the Prototype Development and Demonstration of a R.E.S.C.U.M.E. system. The requirements included in this document are based upon those that can be found in previous R....