The functional and structural neural basis of individual differences in loss aversion.

Science.gov (United States)

Canessa, Nicola; Crespi, Chiara; Motterlini, Matteo; Baud-Bovy, Gabriel; Chierchia, Gabriele; Pantaleo, Giuseppe; Tettamanti, Marco; Cappa, Stefano F

2013-09-04

Decision making under risk entails the anticipation of prospective outcomes, typically leading to the greater sensitivity to losses than gains known as loss aversion. Previous studies on the neural bases of choice-outcome anticipation and loss aversion provided inconsistent results, showing either bidirectional mesolimbic responses of activation for gains and deactivation for losses, or a specific amygdala involvement in processing losses. Here we focused on loss aversion with the aim to address interindividual differences in the neural bases of choice-outcome anticipation. Fifty-six healthy human participants accepted or rejected 104 mixed gambles offering equal (50%) chances of gaining or losing different amounts of money while their brain activity was measured with functional magnetic resonance imaging (fMRI). We report both bidirectional and gain/loss-specific responses while evaluating risky gambles, with amygdala and posterior insula specifically tracking the magnitude of potential losses. At the individual level, loss aversion was reflected both in limbic fMRI responses and in gray matter volume in a structural amygdala-thalamus-striatum network, in which the volume of the "output" centromedial amygdala nuclei mediating avoidance behavior was negatively correlated with monetary performance. We conclude that outcome anticipation and ensuing loss aversion involve multiple neural systems, showing functional and structural individual variability directly related to the actual financial outcomes of choices. By supporting the simultaneous involvement of both appetitive and aversive processing in economic decision making, these results contribute to the interpretation of existing inconsistencies on the neural bases of anticipating choice outcomes.

Photoelectron Energy Loss in Al(002) Revisited: Retrieval of the Single Plasmon Loss Energy Distribution by a Fourier Transform Method

Science.gov (United States)

Santana, Victor Mancir da Silva; David, Denis; de Almeida, Jailton Souza; Godet, Christian

2018-06-01

A Fourier transform (FT) algorithm is proposed to retrieve the energy loss function (ELF) of solid surfaces from experimental X-ray photoelectron spectra. The intensity measured over a broad energy range towards lower kinetic energies results from convolution of four spectral distributions: photoemission line shape, multiple plasmon loss probability, X-ray source line structure and Gaussian broadening of the photoelectron analyzer. The FT of the measured XPS spectrum, including the zero-loss peak and all inelastic scattering mechanisms, being a mathematical function of the respective FT of X-ray source, photoemission line shape, multiple plasmon loss function, and Gaussian broadening of the photoelectron analyzer, the proposed algorithm gives straightforward access to the bulk ELF and effective dielectric function of the solid, assuming identical ELF for intrinsic and extrinsic plasmon excitations. This method is applied to aluminum single crystal Al(002) where the photoemission line shape has been computed accurately beyond the Doniach-Sunjic approximation using the Mahan-Wertheim-Citrin approach which takes into account the density of states near the Fermi level; the only adjustable parameters are the singularity index and the broadening energy D (inverse hole lifetime). After correction for surface plasmon excitations, the q-averaged bulk loss function, q , of Al(002) differs from the optical value Im[- 1 / ɛ( E, q = 0)] and is well described by the Lindhard-Mermin dispersion relation. A quality criterion of the inversion algorithm is given by the capability of observing weak interband transitions close to the zero-loss peak, namely at 0.65 and 1.65 eV in ɛ( E, q) as found in optical spectra and ab initio calculations of aluminum.

Photoelectron Energy Loss in Al(002) Revisited: Retrieval of the Single Plasmon Loss Energy Distribution by a Fourier Transform Method

Science.gov (United States)

Santana, Victor Mancir da Silva; David, Denis; de Almeida, Jailton Souza; Godet, Christian

2018-04-01

A Fourier transform (FT) algorithm is proposed to retrieve the energy loss function (ELF) of solid surfaces from experimental X-ray photoelectron spectra. The intensity measured over a broad energy range towards lower kinetic energies results from convolution of four spectral distributions: photoemission line shape, multiple plasmon loss probability, X-ray source line structure and Gaussian broadening of the photoelectron analyzer. The FT of the measured XPS spectrum, including the zero-loss peak and all inelastic scattering mechanisms, being a mathematical function of the respective FT of X-ray source, photoemission line shape, multiple plasmon loss function, and Gaussian broadening of the photoelectron analyzer, the proposed algorithm gives straightforward access to the bulk ELF and effective dielectric function of the solid, assuming identical ELF for intrinsic and extrinsic plasmon excitations. This method is applied to aluminum single crystal Al(002) where the photoemission line shape has been computed accurately beyond the Doniach-Sunjic approximation using the Mahan-Wertheim-Citrin approach which takes into account the density of states near the Fermi level; the only adjustable parameters are the singularity index and the broadening energy D (inverse hole lifetime). After correction for surface plasmon excitations, the q-averaged bulk loss function, q , of Al(002) differs from the optical value Im[- 1 / ɛ(E, q = 0)] and is well described by the Lindhard-Mermin dispersion relation. A quality criterion of the inversion algorithm is given by the capability of observing weak interband transitions close to the zero-loss peak, namely at 0.65 and 1.65 eV in ɛ(E, q) as found in optical spectra and ab initio calculations of aluminum.

Mechanical losses in thin fused silica fibres

International Nuclear Information System (INIS)

Bilenko, I A; Braginsky, V B; Lourie, S L

2004-01-01

Intracavity topology of the readout system for LIGO III project and table-top QND mechanical measurements under development require the use of small probe masses and suspensions with a very low level of internal losses. A good choice is to use thin fused silica fibres similar to LIGO II mirrors suspensions. Mechanical losses of silica fibres are investigated in this work through the study of quality factor dependence on diameter for pendulum and violin modes of oscillations with diameters ranging from 1.5 to 40 μm. The estimated values of effective mechanical loss angle show noticeably greater growth with lower diameters than might be expected while extrapolating known results of research done for thicker fibres

Mechanical losses in thin fused silica fibres

Energy Technology Data Exchange (ETDEWEB)

Bilenko, I A; Braginsky, V B; Lourie, S L [Department of Oscillatory Physics, Physics Faculty, Moscow State University (Russian Federation)

2004-03-07

Intracavity topology of the readout system for LIGO III project and table-top QND mechanical measurements under development require the use of small probe masses and suspensions with a very low level of internal losses. A good choice is to use thin fused silica fibres similar to LIGO II mirrors suspensions. Mechanical losses of silica fibres are investigated in this work through the study of quality factor dependence on diameter for pendulum and violin modes of oscillations with diameters ranging from 1.5 to 40 {mu}m. The estimated values of effective mechanical loss angle show noticeably greater growth with lower diameters than might be expected while extrapolating known results of research done for thicker fibres.

Computational Fluid Dynamic Investigation of Loss Mechanisms in a Pulse-Tube Refrigerator

International Nuclear Information System (INIS)

Martin, K; Esguerra, J; Dodson, C; Razani, A

2015-01-01

In predicting Pulse-Tube Cryocooler (PTC) performance, One-Dimensional (1-D) PTR design and analysis tools such as Gedeon Associates SAGE® typically include models for performance degradation due to thermodynamically irreversible processes. SAGE®, in particular, accounts for convective loss, turbulent conductive loss and numerical diffusion “loss” via correlation functions based on analysis and empirical testing.In this study, we compare CFD and SAGE® estimates of PTR refrigeration performance for four distinct pulse-tube lengths. Performance predictions from PTR CFD models are compared to SAGE® predictions for all four cases. Then, to further demonstrate the benefits of higher-fidelity and multidimensional CFD simulation, the PTR loss mechanisms are characterized in terms of their spatial and temporal locations. (paper)

Integrasi Taguchi Loss Function dengan Fuzzy Analytical Hierarchy Process dalam Pemilih Pemasok

Directory of Open Access Journals (Sweden)

Ahmad S. Indrapriyatna

2011-01-01

Full Text Available One important issue in the line production is the selection of the company's best supplier. Various criteria should be considered for determining the best supplier. Answering to that challenge, we apply Taguchi loss function- Analytical Hierarchy Process Fuzzy-Linear Programming (Taguchi loss function-Fuzzy AHP to find out the best supplier. Moreover, we also consider multiple criteria, i.e., goods’ completeness, quality, delivery, and quality loss in that analysis. By maximizing the suppliers’ performances based on each criterion and aggregated the suppliers’ performances based on the overall criteria, we selected the best one. Applying this method for selecting the best pressure gauge’s supplier in PT. Coca Cola Bottling Indonesia Central Sumatera (PT. CCBICS, we found out that among three suppliers, the second supplier is the best one.

ANGDelMut – a web-based tool for predicting and analyzing functional loss mechanisms of amyotrophic lateral sclerosis-associated angiogenin mutations [v2; ref status: indexed, http://f1000r.es/2mc

Directory of Open Access Journals (Sweden)

Aditya K Padhi

2013-12-01

Full Text Available ANGDelMut is a web-based tool for predicting the functional consequences of missense mutations in the angiogenin (ANG protein, which is associated with amyotrophic lateral sclerosis (ALS. Missense mutations in ANG result in loss of either ribonucleolytic activity or nuclear translocation activity or both of these functions, and in turn cause ALS. However, no web-based tools are available to predict whether a newly identified ANG mutation will possibly lead to ALS. More importantly, no web-implemented method is currently available to predict the mechanisms of loss-of-function(s of ANG mutants. In light of this observation, we developed the ANGDelMut web-based tool, which predicts whether an ANG mutation is deleterious or benign. The user selects certain attributes from the input panel, which serves as a query to infer whether a mutant will exhibit loss of ribonucleolytic activity or nuclear translocation activity or whether the overall stability will be affected. The output states whether the mutation is deleterious or benign, and if it is deleterious, gives the possible mechanism(s of loss-of-function. This web-based tool, freely available at http://bioschool.iitd.ernet.in/DelMut/, is the first of its kind to provide a platform for researchers and clinicians, to infer the functional consequences of ANG mutations and correlate their possible association with ALS ahead of experimental findings.

ANGDelMut – a web-based tool for predicting and analyzing functional loss mechanisms of amyotrophic lateral sclerosis-associated angiogenin mutations [v3; ref status: indexed, http://f1000r.es/2yt

Directory of Open Access Journals (Sweden)

Aditya K Padhi

2014-02-01

Full Text Available ANGDelMut is a web-based tool for predicting the functional consequences of missense mutations in the angiogenin (ANG protein, which is associated with amyotrophic lateral sclerosis (ALS. Missense mutations in ANG result in loss of either ribonucleolytic activity or nuclear translocation activity or both of these functions, and in turn cause ALS. However, no web-based tools are available to predict whether a newly identified ANG mutation will possibly lead to ALS. More importantly, no web-implemented method is currently available to predict the mechanisms of loss-of-function(s of ANG mutants. In light of this observation, we developed the ANGDelMut web-based tool, which predicts whether an ANG mutation is deleterious or benign. The user selects certain attributes from the input panel, which serves as a query to infer whether a mutant will exhibit loss of ribonucleolytic activity or nuclear translocation activity or whether the overall stability will be affected. The output states whether the mutation is deleterious or benign, and if it is deleterious, gives the possible mechanism(s of loss-of-function. This web-based tool, freely available at http://bioschool.iitd.ernet.in/DelMut/, is the first of its kind to provide a platform for researchers and clinicians, to infer the functional consequences of ANG mutations and correlate their possible association with ALS ahead of experimental findings.

The role of MAC1 in diesel exhaust particle-induced microglial activation and loss of dopaminergic neuron function.

Science.gov (United States)

Levesque, Shannon; Taetzsch, Thomas; Lull, Melinda E; Johnson, Jo Anne; McGraw, Constance; Block, Michelle L

2013-06-01

Increasing reports support that air pollution causes neuroinflammation and is linked to central nervous system (CNS) disease/damage. Diesel exhaust particles (DEP) are a major component of urban air pollution, which has been linked to microglial activation and Parkinson's disease-like pathology. To begin to address how DEP may exert CNS effects, microglia and neuron-glia cultures were treated with either nanometer-sized DEP (neuron function was assessed. All three treatments showed enhanced ameboid microglia morphology, increased H2 O2 production, and decreased DA uptake. Mechanistic inquiry revealed that the scavenger receptor inhibitor fucoidan blocked DEP internalization in microglia, but failed to alter DEP-induced H2 O2 production in microglia. However, pre-treatment with the MAC1/CD11b inhibitor antibody blocked microglial H2 O2 production in response to DEP. MAC1(-/-) mesencephalic neuron-glia cultures were protected from DEP-induced loss of DA neuron function, as measured by DA uptake. These findings support that DEP may activate microglia through multiple mechanisms, where scavenger receptors regulate internalization of DEP and the MAC1 receptor is mandatory for both DEP-induced microglial H2 O2 production and loss of DA neuron function. © 2013 International Society for Neurochemistry.

Mechanisms of Weight Regain following Weight Loss.

Science.gov (United States)

Blomain, Erik Scott; Dirhan, Dara Anne; Valentino, Michael Anthony; Kim, Gilbert Won; Waldman, Scott Arthur

2013-01-01

Obesity is a world-wide pandemic and its incidence is on the rise along with associated comorbidities. Currently, there are few effective therapies to combat obesity. The use of lifestyle modification therapy, namely, improvements in diet and exercise, is preferable over bariatric surgery or pharmacotherapy due to surgical risks and issues with drug efficacy and safety. Although they are initially successful in producing weight loss, such lifestyle intervention strategies are generally unsuccessful in achieving long-term weight maintenance, with the vast majority of obese patients regaining their lost weight during followup. Recently, various compensatory mechanisms have been elucidated by which the body may oppose new weight loss, and this compensation may result in weight regain back to the obese baseline. The present review summarizes the available evidence on these compensatory mechanisms, with a focus on weight loss-induced changes in energy expenditure, neuroendocrine pathways, nutrient metabolism, and gut physiology. These findings have added a major focus to the field of antiobesity research. In addition to investigating pathways that induce weight loss, the present work also focuses on pathways that may instead prevent weight regain. Such strategies will be necessary for improving long-term weight loss maintenance and outcomes for patients who struggle with obesity.

Stochastic Loss of an Occasionally-Essential Function

Science.gov (United States)

Jerison, Elizabeth; Desai, Michael

2013-03-01

Many biological functions are useful only in specific circumstances. For example, hundreds of single-gene deletions in yeast increase growth rate in some laboratory conditions. During periods of disuse, these genes are vulnerable to disruption or loss via random mutation and genetic drift. Yet they are maintained in natural populations, suggesting that they must be useful at least occasionally. Here we quantify the risk of loss of such occasionally-important functions. We focus on predicting how the statistics of environmental change determine the mean time to loss of the function. Our results suggest a refinement to the Savageau 'use-it-or-lose-it' principle of regulation, and put theoretical lower bounds on how often these functions must be necessary to the organism, in order to be maintained.

Data Acquisition for Quality Loss Function Modelling

DEFF Research Database (Denmark)

Pedersen, Søren Nygaard; Howard, Thomas J.

2016-01-01

Quality loss functions can be a valuable tool when assessing the impact of variation on product quality. Typically, the input for the quality loss function would be a measure of the varying product performance and the output would be a measure of quality. While the unit of the input is given by t...... by the product function in focus, the quality output can be measured and quantified in a number of ways. In this article a structured approach for acquiring stakeholder satisfaction data for use in quality loss function modelling is introduced.......Quality loss functions can be a valuable tool when assessing the impact of variation on product quality. Typically, the input for the quality loss function would be a measure of the varying product performance and the output would be a measure of quality. While the unit of the input is given...

Decentralized Model Predictive Control for Cooperative Multiple Vehicles Subject to Communication Loss

Directory of Open Access Journals (Sweden)

Hojjat A. Izadi

2011-01-01

Full Text Available The decentralized model predictive control (DMPC of multiple cooperative vehicles with the possibility of communication loss/delay is investigated. The neighboring vehicles exchange their predicted trajectories at every sample time to maintain the cooperation objectives. In the event of a communication loss (packet dropout, the most recent available information, which is potentially delayed, is used. Then the communication loss problem changes to a cooperative problem when random large communication delays are present. Such large communication delays can lead to poor cooperation performance and unsafe behaviors such as collisions. A new DMPC approach is developed to improve the cooperation performance and achieve safety in the presence of the large communication delays. The proposed DMPC architecture estimates the tail of neighbor's trajectory which is not available due to the large communication delays for improving the performance. The concept of the tube MPC is also employed to provide the safety of the fleet against collisions, in the presence of large intervehicle communication delays. In this approach, a tube shaped trajectory set is assumed around the trajectory of the neighboring vehicles whose trajectory is delayed/lost. The radius of tube is a function of the communication delay and vehicle's maneuverability (in the absence of model uncertainty. The simulation of formation problem of multiple vehicles is employed to illustrate the effectiveness of the proposed approach.

A new soft dielectric silicone elastomer matrix with high mechanical integrity and low losses

DEFF Research Database (Denmark)

Madsen, Frederikke Bahrt; Yu, Liyun; Daugaard, Anders Egede

2015-01-01

Though dielectric elastomers (DEs) have many favourable properties, the issue of high driving voltages limits the commercial viability of the technology. Driving voltage can be lowered by decreasing the Young's modulus and increasing the dielectric permittivity of silicone elastomers. A decrease...... in Young's modulus, however, is often accompanied by the loss of mechanical stability and thereby the lifetime of the DE. A new soft elastomer matrix, with no loss of mechanical stability and high dielectric permittivity, was prepared through the use of alkyl chloride-functional siloxane copolymers...

Modulation of working memory function by motivation through loss-aversion.

Science.gov (United States)

Krawczyk, Daniel C; D'Esposito, Mark

2013-04-01

Cognitive performance is affected by motivation. Few studies, however, have investigated the neural mechanisms of the influence of motivation through potential monetary punishment on working memory. We employed functional MRI during a delayed recognition task that manipulated top-down control demands with added monetary incentives to some trials in the form of potential losses of bonus money. Behavioral performance on the task was influenced by loss-threatening incentives in the form of faster and more accurate performance. As shown previously, we found enhancement of activity for relevant stimuli occurs throughout all task periods (e.g., stimulus encoding, maintenance, and response) in both prefrontal and visual association cortex. Further, these activation patterns were enhanced for trials with possible monetary loss relative to nonincentive trials. During the incentive cue, the amygdala and striatum showed significantly greater activation when money was at a possible loss on the trial. We also evaluated patterns of functional connectivity between regions responsive to monetary consequences and prefrontal areas responsive to the task. This analysis revealed greater delay period connectivity between and the left insula and prefrontal cortex with possible monetary loss relative to nonincentive trials. Overall, these results reveal that incentive motivation can modulate performance on working memory tasks through top-down signals via amplification of activity within prefrontal and visual association regions selective to processing the perceptual inputs of the stimuli to be remembered. Copyright © 2011 Wiley Periodicals, Inc.

Mechanism of Selenium Loss in Copper Slag

Science.gov (United States)

Desai, Bhavin; Tathavadkar, Vilas; Basu, Somnath

2018-03-01

During smelting of copper sulfide concentrate, selenium is distributed between silica-saturated iron-silicate slag and copper-iron sulfide matte. The recovery coefficients of selenium between slag and matte were determined as a function of the initial concentration of selenium at 1523 K (1250 °C) under an inert atmosphere in a vertical tubular furnace. The initial concentration of selenium was varied by the addition of metallic selenium as well as selenium dioxide to the mixture of slag and matte. Analysis of the results indicated high affinity of selenium for matte. The apparent loss of selenium with the slag was attributed to the presence of selenium-enriched matte particles entrapped in the slag, rather than dissolved SeO2. The mechanisms proposed by previous investigators were discussed and also compared with the results of the present investigation.

Mechanism of Selenium Loss in Copper Slag

Science.gov (United States)

Desai, Bhavin; Tathavadkar, Vilas; Basu, Somnath

2018-06-01

During smelting of copper sulfide concentrate, selenium is distributed between silica-saturated iron-silicate slag and copper-iron sulfide matte. The recovery coefficients of selenium between slag and matte were determined as a function of the initial concentration of selenium at 1523 K (1250 °C) under an inert atmosphere in a vertical tubular furnace. The initial concentration of selenium was varied by the addition of metallic selenium as well as selenium dioxide to the mixture of slag and matte. Analysis of the results indicated high affinity of selenium for matte. The apparent loss of selenium with the slag was attributed to the presence of selenium-enriched matte particles entrapped in the slag, rather than dissolved SeO2. The mechanisms proposed by previous investigators were discussed and also compared with the results of the present investigation.

Chapter 6 Quantum Mechanical Methods for Loss-Excitation and Loss-Ionization in Fast Ion-Atom Collisions

Science.gov (United States)

Belkic, Dzevad

quantum mechanical perturbation theories applied to electron loss collisions involving two hydrogen-like atoms. Both the one- and two-electron transitions (target unaffected by collision, as well as loss-ionization) are thoroughly examined in various intervals of impact energies varying from the threshold via the Massey peak to the Bethe asymptotic region. Systematics are established for the fast, simple, and accurate computations of cross sections for loss-excitation and loss-ionization accounting for the entire spectra of all four particles, including two free electrons and two free protons. The expounded algorithmic strategy of quantum mechanical methodologies is of great importance for wide applications to particle transport physics, especially in fusion research and hadron radiotherapy. This should advantageously replace the current overwhelming tendency in these fields for using phenomenological modeling with artificial functions extracted from fitting the existing experimental/theoretical data bases for cross sections.

Time functions function best as functions of multiple times

NARCIS (Netherlands)

Desain, P.; Honing, H.

1992-01-01

This article presents an elegant way of representing control functions at an abstractlevel. It introduces time functions that have multiple times as arguments. In this waythe generalized concept of a time function can support absolute and relative kinds of time behavior. Furthermore the

Modified distal shoe appliance for premature loss of multiple deciduous molars: a case report.

Science.gov (United States)

Bhat, Prasanna Kumar; K, Navin H; Idris, Mohammed; Christopher, Pradeep; Rai, Niharika

2014-08-01

Preservation of the primary dentition until the normal time of exfoliation is one of the most important factor involved in preventive and interceptive dentistry. The premature loss of second primary molar before the eruption of permanent first molar can create a significant arch space/tooth size discrepancy. Distal shoe space maintainer is a valuable part of the Paediatric Dentist's armamentarium in those cases where the second primary molar is prematurely lost and it helps to guide the first permanent molar into place. Conventional design poses various limitations in cases of premature loss of multiple deciduous molars. Thus, it is required to modify the conventional designs according to the needs of the patient. This case report describes an innovative modification of distal shoe appliance in cases of premature loss of multiple deciduous molars. In the present case, modification of distal shoe space maintainer was advocated because of inadequate abutments caused due to multiple loss of deciduous molars. Bilateral design of distal shoe was planned for unilateral loss of deciduous molars.

A Multivariate Quality Loss Function Approach for Optimization of Spinning Processes

Science.gov (United States)

Chakraborty, Shankar; Mitra, Ankan

2018-05-01

Recent advancements in textile industry have given rise to several spinning techniques, such as ring spinning, rotor spinning etc., which can be used to produce a wide variety of textile apparels so as to fulfil the end requirements of the customers. To achieve the best out of these processes, they should be utilized at their optimal parametric settings. However, in presence of multiple yarn characteristics which are often conflicting in nature, it becomes a challenging task for the spinning industry personnel to identify the best parametric mix which would simultaneously optimize all the responses. Hence, in this paper, the applicability of a new systematic approach in the form of multivariate quality loss function technique is explored for optimizing multiple quality characteristics of yarns while identifying the ideal settings of two spinning processes. It is observed that this approach performs well against the other multi-objective optimization techniques, such as desirability function, distance function and mean squared error methods. With slight modifications in the upper and lower specification limits of the considered quality characteristics, and constraints of the non-linear optimization problem, it can be successfully applied to other processes in textile industry to determine their optimal parametric settings.

Executive functions predict weight loss in a medically supervised weight loss programme

OpenAIRE

Galioto, R.; Bond, D.; Gunstad, J.; Pera, V.; Rathier, L.; Tremont, G.

2016-01-01

Summary Background Deficits in executive functions are related to poorer weight loss after bariatric surgery; however, less is known about the role that these deficits may play during participation in nonsurgical weight loss programmes. This study examined associations between objectively measured executive functions and weight loss during participation in a medically supervised weight loss programme. Methods Twenty?three adult patients (age 50.4???15.1, BMI 44.2???8.8, 68% female, 92% White)...

Tackling Energy Loss for High-Efficiency Organic Solar Cells with Integrated Multiple Strategies.

Science.gov (United States)

Zuo, Lijian; Shi, Xueliang; Jo, Sae Byeok; Liu, Yun; Lin, Fracis; Jen, Alex K-Y

2018-04-01

Limited by the various inherent energy losses from multiple channels, organic solar cells show inferior device performance compared to traditional inorganic photovoltaic techniques, such as silicon and CuInGaSe. To alleviate these fundamental limitations, an integrated multiple strategy is implemented including molecular design, interfacial engineering, optical manipulation, and tandem device construction into one cell. Considering the close correlation among these loss channels, a sophisticated quantification of energy-loss reduction is tracked along with each strategy in a perspective to reach rational overall optimum. A novel nonfullerene acceptor, 6TBA, is synthesized to resolve the thermalization and V OC loss, and another small bandgap nonfullerene acceptor, 4TIC, is used in the back sub-cell to alleviate transmission loss. Tandem architecture design significantly reduces the light absorption loss, and compensates carrier dynamics and thermalization loss. Interfacial engineering further reduces energy loss from carrier dynamics in the tandem architecture. As a result of this concerted effort, a very high power conversion efficiency (13.20%) is obtained. A detailed quantitative analysis on the energy losses confirms that the improved device performance stems from these multiple strategies. The results provide a rational way to explore the ultimate device performance through molecular design and device engineering. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Loss-of-function mutations in co-chaperone BAG3 destabilize small HSPs and cause cardiomyopathy.

Science.gov (United States)

Fang, Xi; Bogomolovas, Julius; Wu, Tongbin; Zhang, Wei; Liu, Canzhao; Veevers, Jennifer; Stroud, Matthew J; Zhang, Zhiyuan; Ma, Xiaolong; Mu, Yongxin; Lao, Dieu-Hung; Dalton, Nancy D; Gu, Yusu; Wang, Celine; Wang, Michael; Liang, Yan; Lange, Stephan; Ouyang, Kunfu; Peterson, Kirk L; Evans, Sylvia M; Chen, Ju

2017-08-01

Defective protein quality control (PQC) systems are implicated in multiple diseases. Molecular chaperones and co-chaperones play a central role in functioning PQC. Constant mechanical and metabolic stress in cardiomyocytes places great demand on the PQC system. Mutation and downregulation of the co-chaperone protein BCL-2-associated athanogene 3 (BAG3) are associated with cardiac myopathy and heart failure, and a BAG3 E455K mutation leads to dilated cardiomyopathy (DCM). However, the role of BAG3 in the heart and the mechanisms by which the E455K mutation leads to DCM remain obscure. Here, we found that cardiac-specific Bag3-KO and E455K-knockin mice developed DCM. Comparable phenotypes in the 2 mutants demonstrated that the E455K mutation resulted in loss of function. Further experiments revealed that the E455K mutation disrupted the interaction between BAG3 and HSP70. In both mutants, decreased levels of small heat shock proteins (sHSPs) were observed, and a subset of proteins required for cardiomyocyte function was enriched in the insoluble fraction. Together, these observations suggest that interaction between BAG3 and HSP70 is essential for BAG3 to stabilize sHSPs and maintain cardiomyocyte protein homeostasis. Our results provide insight into heart failure caused by defects in BAG3 pathways and suggest that increasing BAG3 protein levels may be of therapeutic benefit in heart failure.

Social stigma and compounded losses: quality-of-life issues for multiple-birth families.

Science.gov (United States)

Ellison, Marcia A; Hall, Janet E

2003-08-01

To determine the quality-of-life domains most impacted by multiple births. Focus groups, qualitative research. Human volunteers in a medical research environment.Forty-three mothers, 29 raising multiple-birth children, 13 raising singletons, identified from random and convenience samples. None. Maternal self-reports of the psychosocial sequelae of multiple or singleton births, based on qualitative data analysis of transcribed group discussions. The quality-of-life domains that were most impacted by raising multiple birth children were social stigma, pregnancy loss, marital satisfaction, children's health, unmet family needs, parenting stress, maternal depression, and the infertility experience. Qualitative methods identified two novel quality-of-life domains in iatrogenic multiple birth families: social stigma and compounded losses. An unexpected finding was the potential for increased marital solidification as parents coped with the inordinate stresses of multiple births. As anticipated, children's health, unmet family needs, maternal depression, and parental stress were key areas of concern. In addition, the infertility experience had a lasting impact. These findings are significant, given that at least 38% of all assisted conceptions result in a multiple birth. This study lays the groundwork for further research on the impact of iatrogenic multiple births.

Contact force and mechanical loss of multistage cable under tension and bending

Science.gov (United States)

Ru, Yanyun; Yong, Huadong; Zhou, Youhe

2016-10-01

A theoretical model for calculating the stress and strain states of cabling structures with different loadings has been developed in this paper. We solve the problem for the first- and second-stage cable with tensile or bending strain. The contact and friction forces between the strands are presented by two-dimensional contact model. Several theoretical models have been proposed to verify the results when the triplet subjected to the tensile strain, including contact force, contact stresses, and mechanical loss. It is found that loadings will affect the friction force and the mechanical loss of the triplet. The results show that the contact force and mechanical loss are dependent on the twist pitch. A shorter twist pitch can lead to higher contact force, while the trend of mechanical loss with twist pitch is complicated. The mechanical loss may be reduced by adjusting the twist pitch reasonably. The present model provides a simple analysis method to investigate the mechanical behaviors in multistage-structures under different loads.

Endangered species: mitochondrial DNA loss as a mechanism of human disease.

Science.gov (United States)

Herrera, Alan; Garcia, Iraselia; Gaytan, Norma; Jones, Edith; Maldonado, Alicia; Gilkerson, Robert

2015-06-01

Human mitochondrial DNA (mtDNA) is a small maternally inherited DNA, typically present in hundreds of copies in a single human cell. Thus, despite its small size, the mitochondrial genome plays a crucial role in the metabolic homeostasis of the cell. Our understanding of mtDNA genotype-phenotype relationships is derived largely from studies of the classical mitochondrial neuromuscular diseases, in which mutations of mtDNA lead to compromised mitochondrial bioenergetic function, with devastating pathological consequences. Emerging research suggests that loss, rather than mutation, of mtDNA plays a major role across a range of prevalent human diseases, including diabetes mellitus, cardiovascular disease, and aging. Here, we examine the 'rules' of mitochondrial genetics and function, the clinical settings in which loss of mtDNA is an emerging pathogenic mechanism, and explore mtDNA damage and its consequences for the organellar network and cell at large. As extranuclear genetic material arrayed throughout the cell to support metabolism, mtDNA is increasingly implicated in a host of disease conditions, opening a range of exciting questions regarding mtDNA and its role in cellular homeostasis.

Functional Multiple-Set Canonical Correlation Analysis

Science.gov (United States)

Hwang, Heungsun; Jung, Kwanghee; Takane, Yoshio; Woodward, Todd S.

2012-01-01

We propose functional multiple-set canonical correlation analysis for exploring associations among multiple sets of functions. The proposed method includes functional canonical correlation analysis as a special case when only two sets of functions are considered. As in classical multiple-set canonical correlation analysis, computationally, the…

Tuning Cell and Tissue Development by Combining Multiple Mechanical Signals.

Science.gov (United States)

Sinha, Ravi; Verdonschot, Nico; Koopman, Bart; Rouwkema, Jeroen

2017-10-01

Mechanical signals offer a promising way to control cell and tissue development. It has been established that cells constantly probe their mechanical microenvironment and employ force feedback mechanisms to modify themselves and when possible, their environment, to reach a homeostatic state. Thus, a correct mechanical microenvironment (external forces and mechanical properties and shapes of cellular surroundings) is necessary for the proper functioning of cells. In vitro or in the case of nonbiological implants in vivo, where cells are in an artificial environment, addition of the adequate mechanical signals can, therefore, enable the cells to function normally as in vivo. Hence, a wide variety of approaches have been developed to apply mechanical stimuli (such as substrate stretch, flow-induced shear stress, substrate stiffness, topography, and modulation of attachment area) to cells in vitro. These approaches have not just revealed the effects of the mechanical signals on cells but also provided ways for probing cellular molecules and structures that can provide a mechanistic understanding of the effects. However, they remain lower in complexity compared with the in vivo conditions, where the cellular mechanical microenvironment is the result of a combination of multiple mechanical signals. Therefore, combinations of mechanical stimuli have also been applied to cells in vitro. These studies have had varying focus-developing novel platforms to apply complex combinations of mechanical stimuli, observing the co-operation/competition between stimuli, combining benefits of multiple stimuli toward an application, or uncovering the underlying mechanisms of their action. In general, they provided new insights that could not have been predicted from previous knowledge. We present here a review of several such studies and the insights gained from them, thereby making a case for such studies to be continued and further developed.

Work, social support and leisure protect the elderly from functional loss: EPIDOSO study.

Science.gov (United States)

d'Orsi, Eleonora; Xavier, André Junqueira; Ramos, Luiz Roberto

2011-08-01

To identify risk factors for functional capacity loss in elderly people. Epidoso (Epidemiology of the Elderly) cohort study with elderly people living in São Paulo (Southeastern Brazil). A total of 326 participants in the first interview (1991-1992) who were independent or had mild dependence (one or two activities of daily living) were selected. Those who presented functional loss in the second (1994-1995) or third interviews (1998-1999) were compared to those who did not present it. The incidence of functional loss was calculated according to sociodemographic variables, life habits, cognitive status, morbidity, hospitalization, self-rated health, tooth loss, social support and leisure activities. Crude and adjusted relative risks with 95% confidence intervals were estimated through bivariate and multiple analyses with Poisson regression. The criterion for the inclusion of the variables in the model was p 0.10. The incidence of functional loss was 17.8% (13.6; 21.9). The risk factors in the final model were: age group 70-74 years RR=1.9 (0.9;3.9); age group 75-79 years RR=2.8 (1.4;5.5); age group 80 years or older RR=5.4 (3.0;9.6); score in the mini-mental state examination work RR=0.3 (0.1;1.0); monthly relationship with friends RR=0.5 (0.3;0.8); watching TV RR=0.5 (0.3;0.9); and handcrafting RR=0.7 (0.4;1.0). The prevention of functional loss should include adequate control of chronic diseases, like hypertension, asthma and diabetes, as well as cognitive stimulation. Work, leisure and relationships with friends should be valued due to their protective effect.

The effect of loss functions on empirical Bayes reliability analysis

Directory of Open Access Journals (Sweden)

Camara Vincent A. R.

1998-01-01

Full Text Available The aim of the present study is to investigate the sensitivity of empirical Bayes estimates of the reliability function with respect to changing of the loss function. In addition to applying some of the basic analytical results on empirical Bayes reliability obtained with the use of the “popular” squared error loss function, we shall derive some expressions corresponding to empirical Bayes reliability estimates obtained with the Higgins–Tsokos, the Harris and our proposed logarithmic loss functions. The concept of efficiency, along with the notion of integrated mean square error, will be used as a criterion to numerically compare our results. It is shown that empirical Bayes reliability functions are in general sensitive to the choice of the loss function, and that the squared error loss does not always yield the best empirical Bayes reliability estimate.

Mechanisms of multiple production processes

International Nuclear Information System (INIS)

Dremin, I.M.

1977-01-01

Theoretical approaches to multiple production processes are discussed. A large number of models proceeds from the notion about common excited system produced by colliding hadrons. This class of models includes the hydrodynamical, statistical, thermodynamical and statistical bootstrap models. Sometimes the production process is due to excitation and decay of two colliding particles. The fragmentation bremsstrahlung and inelastic diffraction models belong to this group. The largest group of models describes the multiple production process as a result of formation of many excited centers. The typical example is the multiperipheral model. An interesting direction is given by the attempts to interrelate the mechanism of multiple production with internal structure of particles that is with their constituents (C-group)'-quarks, gluons, etc. Besides the models there are phenomenological (p group) attempts to connect different features of multiple production. Experimental data indicate the existence of leading and pionization particles thus giving an evidence for applications of different models. The data about increase of total and inclusive cross sections, the behaviour of the mean multiplicity and correlations at high energies provide a clue for further development of multiple production theory

On the mechanical friction losses occurring in automotive differential gearboxes.

Science.gov (United States)

Antoni, Grégory

2014-01-01

In the automobile industry, the mechanical losses resulting from friction are largely responsible for various kinds of surface damage, such as the scuffing occurring in some mechanical assemblies. These scuffing processes seem to be due to a local loss of lubrication between certain mechanical elements of the same assembly, leading to a sharp increase in the friction, which can lead to a surface and volume damage in some of them, and even can cause, in the worst case, the whole destruction of the mechanical system if it has continued to operate. Predicting and checking the occurrence of this kind of undesirable phenomena, especially in some principal systems of the vehicle, represents nowadays, a crucial challenge in terms of automobile reliability and safety. This study focuses on the mechanical friction losses liable to occur in differential automobile gearboxes, which can lead in the long term to the scuffing of these mechanical systems. The friction losses involved were modeled, using a simple analytical approach, which is presented and discussed.

Functional equation for the Mordell-Tornheim multiple zeta-function

OpenAIRE

Okamoto, Takuya; Onozuka, Tomokazu

2016-01-01

We show a relation between the Mordell-Tornheim multiple zeta-function and the confluent hypergeometric function, and using it, we give the functional equation for the Mordell-Tornheim multiple zeta-function. In the double case, the functional equation includes the known functional equation for the Euler-Zagier double zeta-function.

Skin and scales of teleost fish: Simple structure but high performance and multiple functions

Science.gov (United States)

Vernerey, Franck J.; Barthelat, Francois

2014-08-01

Natural and man-made structural materials perform similar functions such as structural support or protection. Therefore they rely on the same types of properties: strength, robustness, lightweight. Nature can therefore provide a significant source of inspiration for new and alternative engineering designs. We report here some results regarding a very common, yet largely unknown, type of biological material: fish skin. Within a thin, flexible and lightweight layer, fish skins display a variety of strain stiffening and stabilizing mechanisms which promote multiple functions such as protection, robustness and swimming efficiency. We particularly discuss four important features pertaining to scaled skins: (a) a strongly elastic tensile behavior that is independent from the presence of rigid scales, (b) a compressive response that prevents buckling and wrinkling instabilities, which are usually predominant for thin membranes, (c) a bending response that displays nonlinear stiffening mechanisms arising from geometric constraints between neighboring scales and (d) a robust structure that preserves the above characteristics upon the loss or damage of structural elements. These important properties make fish skin an attractive model for the development of very thin and flexible armors and protective layers, especially when combined with the high penetration resistance of individual scales. Scaled structures inspired by fish skin could find applications in ultra-light and flexible armor systems, flexible electronics or the design of smart and adaptive morphing structures for aerospace vehicles.

TDP-43 Loss-of-Function Causes Neuronal Loss Due to Defective Steroid Receptor-Mediated Gene Program Switching in Drosophila

Directory of Open Access Journals (Sweden)

Lies Vanden Broeck

2013-01-01

Full Text Available TDP-43 proteinopathy is strongly implicated in the pathogenesis of amyotrophic lateral sclerosis and related neurodegenerative disorders. Whether TDP-43 neurotoxicity is caused by a novel toxic gain-of-function mechanism of the aggregates or by a loss of its normal function is unknown. We increased and decreased expression of TDP-43 (dTDP-43 in Drosophila. Although upregulation of dTDP-43 induced neuronal ubiquitin and dTDP-43-positive inclusions, both up- and downregulated dTDP-43 resulted in selective apoptosis of bursicon neurons and highly similar transcriptome alterations at the pupal-adult transition. Gene network analysis and genetic validation showed that both up- and downregulated dTDP-43 directly and dramatically increased the expression of the neuronal microtubule-associated protein Map205, resulting in cytoplasmic accumulations of the ecdysteroid receptor (EcR and a failure to switch EcR-dependent gene programs from a pupal to adult pattern. We propose that dTDP-43 neurotoxicity is caused by a loss of its normal function.

Bisphenol A affects androgen receptor function via multiple mechanisms.

Science.gov (United States)

Teng, Christina; Goodwin, Bonnie; Shockley, Keith; Xia, Menghang; Huang, Ruili; Norris, John; Merrick, B Alex; Jetten, Anton M; Austin, Christopher P; Tice, Raymond R

2013-05-25

Bisphenol A (BPA), is a well-known endocrine disruptor compound (EDC) that affects the normal development and function of the female and male reproductive system, however the mechanisms of action remain unclear. To investigate the molecular mechanisms of how BPA may affect ten different nuclear receptors, stable cell lines containing individual nuclear receptor ligand binding domain (LBD)-linked to the β-Gal reporter were examined by a quantitative high throughput screening (qHTS) format in the Tox21 Screening Program of the NIH. The results showed that two receptors, estrogen receptor alpha (ERα) and androgen receptor (AR), are affected by BPA in opposite direction. To confirm the observed effects of BPA on ERα and AR, we performed transient transfection experiments with full-length receptors and their corresponding response elements linked to luciferase reporters. We also included in this study two BPA analogs, bisphenol AF (BPAF) and bisphenol S (BPS). As seen in African green monkey kidney CV1 cells, the present study confirmed that BPA and BPAF act as ERα agonists (half maximal effective concentration EC50 of 10-100 nM) and as AR antagonists (half maximal inhibitory concentration IC50 of 1-2 μM). Both BPA and BPAF antagonized AR function via competitive inhibition of the action of synthetic androgen R1881. BPS with lower estrogenic activity (EC50 of 2.2 μM), did not compete with R1881 for AR binding, when tested at 30 μM. Finally, the effects of BPA were also evaluated in a nuclear translocation assays using EGPF-tagged receptors. Similar to 17β-estradiol (E2) which was used as control, BPA was able to enhance ERα nuclear foci formation but at a 100-fold higher concentration. Although BPA was able to bind AR, the nuclear translocation was reduced. Furthermore, BPA was unable to induce functional foci in the nuclei and is consistent with the transient transfection study that BPA is unable to activate AR. Published by Elsevier Ireland Ltd.

Representations of Multiple-Valued Logic Functions

CERN Document Server

Stankovic, Radomir S

2012-01-01

Compared to binary switching functions, multiple-valued functions offer more compact representations of the information content of signals modeled by logic functions and, therefore, their use fits very well in the general settings of data compression attempts and approaches. The first task in dealing with such signals is to provide mathematical methods for their representation in a way that will make their application in practice feasible.Representation of Multiple-Valued Logic Functions is aimed at providing an accessible introduction to these mathematical techniques that are necessary for ap

Effect of reduction of mechanical losses in AC superconducting coils having various FRP bobbins

International Nuclear Information System (INIS)

Sekine, N.; Tada, S.; Higuchi, T.; Takao, T.; Yamanaka, A.; Fukui, S.

2004-01-01

We have demonstrated in our previous works that a use of the particular structural material for superconducting coils was effective to mechanical-loss reduction under AC operation. In this study, we measured losses to investigate influence of the mechanical losses in the coils having various fiber reinforced plastics (FRPs) with different thermal expansion coefficients. The losses were small in the coils whose winding tension at coil-operating temperature were strong, on the contrary, the losses of the coil having the weak winding tension were large. The coil having the strongest winding tension at liquid helium temperature showed the smallest loss in all coils, and the loss agreed with a value from the Norris's analysis. We think that the mechanical loss becomes almost zero in this coil since the strong tension can prevent the periodic vibration of the superconducting wire. The dependence of the loss on the difference in surface conditions of the materials of the superconducting coil's bobbins was not observed, however, the mechanical losses in AC coils strongly depended on the winding tensions at cryogenic temperature

Investigations of the mechanical loss of tantala films between 5 and 300 K

Energy Technology Data Exchange (ETDEWEB)

Hudl, Matthias; Nawrodt, Ronny; Zimmer, Anja; Nietzsche, Sandor; Vodel, Wolfgang; Seidel, Paul [Friedrich Schiller University (Germany); Tuennermann, Andreas [Institute of Solid-State Physics, Helmholtzweg 5, D-07743 Jena (Germany),; Friedrich Schiller University-Institute of Applied Physics, Jena (Germany)

2007-07-01

Mechanical losses in dielectric mirror coatings of interferometric gravitational wave detectors are a main issue for the proposed advanced generation of gravitational wave detectors. Recent investigations have shown that the mechanical loss of the dielectric mirror coatings (tantala/silica stacks) is probably the main contribution to the detector noise. There are indications that among both coating materials tantala gives the major contribute to mechanical loss. Experimental details of a measuring setup and investigations of the temperature dependency of the mechanical dissipation in thin tantala films on different substrates are presented.

Loss of function JAK1 mutations occur at high frequency in cancers with microsatellite instability and are suggestive of immune evasion.

Science.gov (United States)

Albacker, Lee A; Wu, Jeremy; Smith, Peter; Warmuth, Markus; Stephens, Philip J; Zhu, Ping; Yu, Lihua; Chmielecki, Juliann

2017-01-01

Immune evasion is a well-recognized hallmark of cancer and recent studies with immunotherapy agents have suggested that tumors with increased numbers of neoantigens elicit greater immune responses. We hypothesized that the immune system presents a common selective pressure on high mutation burden tumors and therefore immune evasion mutations would be enriched in high mutation burden tumors. The JAK family of kinases is required for the signaling of a host of immune modulators in tumor, stromal, and immune cells. Therefore, we analyzed alterations in this family for the hypothesized signature of an immune evasion mutation. Here, we searched a database of 61,704 unique solid tumors for alterations in the JAK family kinases (JAK1/2/3, TYK2). We used The Cancer Genome Atlas and Cancer Cell Line Encyclopedia data to confirm and extend our findings by analyzing gene expression patterns. Recurrent frameshift mutations in JAK1 were associated with high mutation burden and microsatellite instability. These mutations occurred in multiple tumor types including endometrial, colorectal, stomach, and prostate carcinomas. Analyzing gene expression signatures in endometrial and stomach adenocarcinomas revealed that tumors with a JAK1 frameshift exhibited reduced expression of interferon response signatures and multiple anti-tumor immune signatures. Importantly, endometrial cancer cell lines exhibited similar gene expression changes that were expected to be tumor cell intrinsic (e.g. interferon response) but not those expected to be tumor cell extrinsic (e.g. NK cells). From these data, we derive two primary conclusions: 1) JAK1 frameshifts are loss of function alterations that represent a potential pan-cancer adaptation to immune responses against tumors with microsatellite instability; 2) The mechanism by which JAK1 loss of function contributes to tumor immune evasion is likely associated with loss of the JAK1-mediated interferon response.

Land use intensification alters ecosystem multifunctionality via loss of biodiversity and changes to functional composition

OpenAIRE

Allan, Eric; Manning, Pete; et al

2015-01-01

Global change, especially land-use intensification, affects human well-being by impacting the deliv-ery of multiple ecosystem services (multifunctionality). However, whether biodiversity loss is amajor component of global change effects on multifunctionality in real-world ecosystems, as inexperimental ones, remains unclear. Therefore, we assessed biodiversity, functional compositionand 14 ecosystem services on 150 agricultural grasslands differing in land-use intensity. We alsointroduce five mu...

Land use intensification alters ecosystem multifunctionality via loss of biodiversity and changes to functional composition.

OpenAIRE

Allan Eric; Manning Pete; Alt Fabian; Binkenstein Julia; Blaser Stefan; Blüthgen Nico; Böhm Stefan; Grassein Fabrice; Hölzel Norbert; Klaus Valentin H.; Kleinebecker Till; Morrys Elisabeth Kathryn; Oelmann Yvonne; Prati Daniel; Renner Sven C.

2015-01-01

Abstract Global change, especially land?use intensification, affects human well?being by impacting the delivery of multiple ecosystem services (multifunctionality). However, whether biodiversity loss is a major component of global change effects on multifunctionality in real?world ecosystems, as in experimental ones, remains unclear. Therefore, we assessed biodiversity, functional composition and 14 ecosystem services on 150 agricultural grasslands differing in land?use intensity. We also int...

De novo loss- or gain-of-function mutations in KCNA2 cause epileptic encephalopathy

DEFF Research Database (Denmark)

Syrbe, Steffen; Hedrich, Ulrike B S; Riesch, Erik

2015-01-01

disability, delayed speech development and sometimes ataxia. Functional studies of the two mutations associated with this phenotype showed almost complete loss of function with a dominant-negative effect. Two further individuals presented with a different and more severe epileptic encephalopathy phenotype....... They carried mutations inducing a drastic gain-of-function effect leading to permanently open channels. These results establish KCNA2 as a new gene involved in human neurodevelopmental disorders through two different mechanisms, predicting either hyperexcitability or electrical silencing of KV1.2-expressing...

Protein mislocalization: mechanisms, functions and clinical applications in cancer

Science.gov (United States)

Wang, Xiaohong; Li, Shulin

2014-01-01

The changes from normal cells to cancer cells are primarily regulated by genome instability, which foster hallmark functions of cancer through multiple mechanisms including protein mislocalization. Mislocalization of these proteins, including oncoproteins, tumor suppressors, and other cancer-related proteins, can interfere with normal cellular function and cooperatively drive tumor development and metastasis. This review describes the cancer-related effects of protein subcellular mislocalization, the related mislocalization mechanisms, and the potential application of this knowledge to cancer diagnosis, prognosis, and therapy. PMID:24709009

Knowing When to Stop: The Brain Mechanisms of Chasing Losses

DEFF Research Database (Denmark)

Campbell-Meiklejohn, Daniel; Woolrich, Mark; Passingham, Dick

2008-01-01

adult participants decided to chase losses or decided to quit gambling to prevent further losses.ResultsChasing losses was associated with increased activity in cortical areas linked to incentive-motivation and an expectation of reward. By contrast, quitting was associated with decreased activity...... in pathological gambling might involve a failure to appropriately balance activity within neural systems coding conflicting motivational states. Similar mechanisms might underlie the loss-of-control over appetitive behaviors in other impulse control disorders....

Loss of Peripheral Sensory Function Explains Much of the Increase in Postural Sway in Healthy Older Adults

Directory of Open Access Journals (Sweden)

Eric Anson

2017-06-01

Full Text Available Postural sway increases with age and peripheral sensory disease. Whether, peripheral sensory function is related to postural sway independent of age in healthy adults is unclear. Here, we investigated the relationship between tests of visual function (VISFIELD, vestibular function (CANAL or OTOLITH, proprioceptive function (PROP, and age, with center of mass sway area (COM measured with eyes open then closed on firm and then a foam surface. A cross-sectional sample of 366 community dwelling healthy adults from the Baltimore Longitudinal Study of Aging was tested. Multiple linear regressions examined the association between COM and VISFIELD, PROP, CANAL, and OTOLITH separately and in multi-sensory models controlling for age and gender. PROP dominated sensory prediction of sway across most balance conditions (β's = 0.09–0.19, p's < 0.001, except on foam eyes closed where CANAL function loss was the only significant sensory predictor of sway (β = 2.12, p < 0.016. Age was not a consistent predictor of sway. This suggests loss of peripheral sensory function explains much of the age-associated increase in sway.

Monte Carlo Simulations of Electron Energy-Loss Spectra with the Addition of Fine Structure from Density Functional Theory Calculations.

Science.gov (United States)

Attarian Shandiz, Mohammad; Guinel, Maxime J-F; Ahmadi, Majid; Gauvin, Raynald

2016-02-01

A new approach is presented to introduce the fine structure of core-loss excitations into the electron energy-loss spectra of ionization edges by Monte Carlo simulations based on an optical oscillator model. The optical oscillator strength is refined using the calculated electron energy-loss near-edge structure by density functional theory calculations. This approach can predict the effects of multiple scattering and thickness on the fine structure of ionization edges. In addition, effects of the fitting range for background removal and the integration range under the ionization edge on signal-to-noise ratio are investigated.

Kramers-Kronig transform for the surface energy loss function

International Nuclear Information System (INIS)

Tan, G.L.; DeNoyer, L.K.; French, R.H.; Guittet, M.J.; Gautier-Soyer, M.

2005-01-01

A new pair of Kramers-Kronig (KK) dispersion relationships for the transformation of surface energy loss function Im[-1/(ε + 1)] has been proposed. The validity of the new surface KK transform is confirmed, using both a Lorentz oscillator model and the surface energy loss functions determined from the experimental complex dielectric function of SrTiO 3 and tungsten metal. The interband transition strength spectra (J cv ) have been derived either directly from the original complex dielectric function or from the derived dielectric function obtained from the KK transform of the surface energy loss function. The original J cv trace and post-J cv trace overlapped together for the three modes, indicating that the new surface Kramers-Kronig dispersion relationship is valid for the surface energy loss function

Multiplicative formulation of quantum mechanics

International Nuclear Information System (INIS)

Voros, A.; Leboeuf, P.

1991-01-01

A general semi-classical description for the eigenfunctions of the multidimensional Schroedinger operator cannot be based on the WKB method which is incompatible with classically ergodic behavior. An alternative, more general multiplicative parametrization of quantum wave functions is suggested, whereby the semi-classical behavior of eigenfunctions can be traced in the presence of classical ergodicity, in the form of diffusive patterns of phase-space zeros in the quantum wave functions. (author) 24 refs.; 4 figs

Axonal loss in the multiple sclerosis spinal cord revisited.

Science.gov (United States)

Petrova, Natalia; Carassiti, Daniele; Altmann, Daniel R; Baker, David; Schmierer, Klaus

2018-05-01

Preventing chronic disease deterioration is an unmet need in people with multiple sclerosis, where axonal loss is considered a key substrate of disability. Clinically, chronic multiple sclerosis often presents as progressive myelopathy. Spinal cord cross-sectional area (CSA) assessed using MRI predicts increasing disability and has, by inference, been proposed as an indirect index of axonal degeneration. However, the association between CSA and axonal loss, and their correlation with demyelination, have never been systematically investigated using human post mortem tissue. We extensively sampled spinal cords of seven women and six men with multiple sclerosis (mean disease duration= 29 years) and five healthy controls to quantify axonal density and its association with demyelination and CSA. 396 tissue blocks were embedded in paraffin and immuno-stained for myelin basic protein and phosphorylated neurofilaments. Measurements included total CSA, areas of (i) lateral cortico-spinal tracts, (ii) gray matter, (iii) white matter, (iv) demyelination, and the number of axons within the lateral cortico-spinal tracts. Linear mixed models were used to analyze relationships. In multiple sclerosis CSA reduction at cervical, thoracic and lumbar levels ranged between 19 and 24% with white (19-24%) and gray (17-21%) matter atrophy contributing equally across levels. Axonal density in multiple sclerosis was lower by 57-62% across all levels and affected all fibers regardless of diameter. Demyelination affected 24-48% of the gray matter, most extensively at the thoracic level, and 11-13% of the white matter, with no significant differences across levels. Disease duration was associated with reduced axonal density, however not with any area index. Significant association was detected between focal demyelination and decreased axonal density. In conclusion, over nearly 30 years multiple sclerosis reduces axonal density by 60% throughout the spinal cord. Spinal cord cross sectional area

Determining the mechanism and parameters of hydrate formation and loss in glucose.

Science.gov (United States)

Scholl, Sarah K; Schmidt, Shelly J

2014-11-01

Water-solid interactions are known to play a major role in the chemical and physical stability of food materials. Despite its extensive use throughout the food industry, the mechanism and parameters of hydrate formation and loss in glucose are not well characterized. Hydrate formation in alpha-anhydrous glucose (α-AG) and hydrate loss in glucose monohydrate (GM) were studied under equilibrium conditions at various relative humidity (RH) values using saturated salt slurries for 1 y. The mechanism of hydrate formation and hydrate loss were determined through mathematical modeling of Dynamic Vapor Sorption data and Raman spectroscopy was used to confirm the mechanisms. The critical temperature for hydrate loss in GM was determined using thermogravimetric analysis (TGA). The moisture sorption profiles of α-AG and GM were also studied under dynamic conditions using an AquaSorp Isotherm Generator. Hydrate formation was observed at and above 68% RH at 25 °C and the conversion of α-AG to GM can best be described as following a nucleation mechanism, however, diffusion and/or geometric contraction mechanisms were also observed by Raman spectroscopy subsequent to the coalescence of initial nucleation sites. Hydrate loss was observed to occur at and below 11% RH at 25 °C during RH storage and at 70 °C during TGA. The conversion of GM to α-AG follows nucleation and diffusion mechanisms. Hydrate formation was evident under dynamic conditions in α-AG and GM prior to deliquescence. This research is the first to report hydrate formation and loss parameters for crystalline α-AG and GM during extended storage at 25 ˚C. © 2014 Institute of Food Technologists®

The effect of loss functions on empirical Bayes reliability analysis

Directory of Open Access Journals (Sweden)

Vincent A. R. Camara

1999-01-01

Full Text Available The aim of the present study is to investigate the sensitivity of empirical Bayes estimates of the reliability function with respect to changing of the loss function. In addition to applying some of the basic analytical results on empirical Bayes reliability obtained with the use of the “popular” squared error loss function, we shall derive some expressions corresponding to empirical Bayes reliability estimates obtained with the Higgins–Tsokos, the Harris and our proposed logarithmic loss functions. The concept of efficiency, along with the notion of integrated mean square error, will be used as a criterion to numerically compare our results.

ESTIMATION OF PARAMETERS AND RELIABILITY FUNCTION OF EXPONENTIATED EXPONENTIAL DISTRIBUTION: BAYESIAN APPROACH UNDER GENERAL ENTROPY LOSS FUNCTION

Directory of Open Access Journals (Sweden)

Sanjay Kumar Singh

2011-06-01

Full Text Available In this Paper we propose Bayes estimators of the parameters of Exponentiated Exponential distribution and Reliability functions under General Entropy loss function for Type II censored sample. The proposed estimators have been compared with the corresponding Bayes estimators obtained under Squared Error loss function and maximum likelihood estimators for their simulated risks (average loss over sample space.

Power balance and loss mechanism analysis in RF transmit coil arrays.

Science.gov (United States)

Kuehne, Andre; Goluch, Sigrun; Waxmann, Patrick; Seifert, Frank; Ittermann, Bernd; Moser, Ewald; Laistler, Elmar

2015-10-01

To establish a framework for transmit array power balance calculations based on power correlation matrices to accurately quantify the loss contributions from different mechanisms such as coupling, lumped components, and radiation. Starting from Poynting's theorem, power correlation matrices are derived for all terms in the power balance, which is formulated as a matrix equation. Finite-difference time-domain simulations of two 7 T eight-channel head array coils at 297.2 MHz are used to verify the theoretical considerations and demonstrate their application. Care is taken to accurately incorporate all loss mechanisms. The power balance for static B1 phase shims as well as two-dimensional spatially selective transmit SENSE pulses is shown. The simulated power balance shows an excellent agreement with theory, with a maximum power imbalance of less than 0.11%. Power loss contributions from the different loss mechanisms vary significantly between the investigated setups, and depending on the excitation mode imposed on the coil. The presented approach enables a straightforward loss evaluation for an arbitrary excitation of transmit coil arrays. Worst-case power imbalance and losses are calculated in a straightforward manner. This allows for deeper insight into transmit array loss mechanisms, incorporation of radiated power components in specific absorption rate calculations and verification of electromagnetic simulations. © 2014 Wiley Periodicals, Inc.

Computation of Hydration Free Energies Using the Multiple Environment Single System Quantum Mechanical/Molecular Mechanical Method.

Science.gov (United States)

König, Gerhard; Mei, Ye; Pickard, Frank C; Simmonett, Andrew C; Miller, Benjamin T; Herbert, John M; Woodcock, H Lee; Brooks, Bernard R; Shao, Yihan

2016-01-12

A recently developed MESS-E-QM/MM method (multiple-environment single-system quantum mechanical molecular/mechanical calculations with a Roothaan-step extrapolation) is applied to the computation of hydration free energies for the blind SAMPL4 test set and for 12 small molecules. First, free energy simulations are performed with a classical molecular mechanics force field using fixed-geometry solute molecules and explicit TIP3P solvent, and then the non-Boltzmann-Bennett method is employed to compute the QM/MM correction (QM/MM-NBB) to the molecular mechanical hydration free energies. For the SAMPL4 set, MESS-E-QM/MM-NBB corrections to the hydration free energy can be obtained 2 or 3 orders of magnitude faster than fully converged QM/MM-NBB corrections, and, on average, the hydration free energies predicted with MESS-E-QM/MM-NBB fall within 0.10-0.20 kcal/mol of full-converged QM/MM-NBB results. Out of five density functionals (BLYP, B3LYP, PBE0, M06-2X, and ωB97X-D), the BLYP functional is found to be most compatible with the TIP3P solvent model and yields the most accurate hydration free energies against experimental values for solute molecules included in this study.

[Disease concept, etiology and mechanisms of multiple sclerosis].

Science.gov (United States)

Kira, Jun-Ichi

2014-11-01

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system(CNS). MS is assumed to be caused by a complex interplay between genes and environments. Autoimmune mechanisms targeting CNS myelin has long been proposed, yet it has not been proved. Th17 cells producing interleukin-17 and Th1 cells producing interferon-gamma are postulated to play major roles in initiating inflammation while regulatory T cell functions are dampened. The forth nationwide survey of MS in Japan revealed that MS prevalence showed four-folds increase over 30 years and the increase was especially prominent in female. Thus, westernized life style and improved sanitation are suspected to increase MS susceptibility. Genome-wide association studies in Western MS patients disclosed more than 100 disease-susceptibility genes, most of which are immune-related genes. It therefore supports immune-mediated mechanisms to be operative. Detailed magnetic resonance imaging studies revealed an early atrophy of the cerebral gray matter where T cell infiltration is pathologically scarce. Therefore, neurodegenerative process also takes place in the early course beside neuroinflammation.

Loss-of-function and gain-of-function phenotypes of stomatocytosis mutant RhAG F65S

Science.gov (United States)

Stewart, Andrew K.; Shmukler, Boris E.; Vandorpe, David H.; Rivera, Alicia; Heneghan, John F.; Li, Xiaojin; Hsu, Ann; Karpatkin, Margaret; O'Neill, Allison F.; Bauer, Daniel E.; Heeney, Matthew M.; John, Kathryn; Kuypers, Frans A.; Gallagher, Patrick G.; Lux, Samuel E.; Brugnara, Carlo; Westhoff, Connie M.

2011-01-01

Four patients with overhydrated cation leak stomatocytosis (OHSt) exhibited the heterozygous RhAG missense mutation F65S. OHSt erythrocytes were osmotically fragile, with elevated Na and decreased K contents and increased cation channel-like activity. Xenopus oocytes expressing wild-type RhAG and RhAG F65S exhibited increased ouabain and bumetanide-resistant uptake of Li+ and 86Rb+, with secondarily increased 86Rb+ influx sensitive to ouabain and to bumetanide. Increased RhAG-associated 14C-methylammonium (MA) influx was severely reduced in RhAG F65S-expressing oocytes. RhAG-associated influxes of Li+, 86Rb+, and 14C-MA were pharmacologically distinct, and Li+ uptakes associated with RhAG and RhAG F65S were differentially inhibited by NH4+ and Gd3+. RhAG-expressing oocytes were acidified and depolarized by 5 mM bath NH3/NH4+, but alkalinized and depolarized by subsequent bath exposure to 5 mM methylammonium chloride (MA/MA+). RhAG F65S-expressing oocytes exhibited near-wild-type responses to NH4Cl, but MA/MA+ elicited attenuated alkalinization and strong hyperpolarization. Expression of RhAG or RhAG F65S increased steady-state cation currents unaltered by bath Li+ substitution or bath addition of 5 mM NH4Cl or MA/MA+. These oocyte studies suggest that 1) RhAG expression increases oocyte transport of NH3/NH4+ and MA/MA+; 2) RhAG F65S exhibits gain-of-function phenotypes of increased cation conductance/permeability, and loss-of-function phenotypes of decreased and modified MA/MA+ transport, and decreased NH3/NH4+-associated depolarization; and 3) RhAG transports NH3/NH4+ and MA/MA+ by distinct mechanisms, and/or the substrates elicit distinct cellular responses. Thus, RhAG F65S is a loss-of-function mutation for amine transport. The altered oocyte intracellular pH, membrane potential, and currents associated with RhAG or RhAG F65S expression may reflect distinct transport mechanisms. PMID:21849667

Dysfunction in endoplasmic reticulum-mitochondria crosstalk underlies SIGMAR1 loss of function mediated motor neuron degeneration.

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Bernard-Marissal, Nathalie; Médard, Jean-Jacques; Azzedine, Hamid; Chrast, Roman

2015-04-01

Mutations in Sigma 1 receptor (SIGMAR1) have been previously identified in patients with amyotrophic lateral sclerosis and disruption of Sigmar1 in mouse leads to locomotor deficits. However, cellular mechanisms underlying motor phenotypes in human and mouse with disturbed SIGMAR1 function have not been described so far. Here we used a combination of in vivo and in vitro approaches to investigate the role of SIGMAR1 in motor neuron biology. Characterization of Sigmar1(-/-) mice revealed that affected animals display locomotor deficits associated with muscle weakness, axonal degeneration and motor neuron loss. Using primary motor neuron cultures, we observed that pharmacological or genetic inactivation of SIGMAR1 led to motor neuron axonal degeneration followed by cell death. Disruption of SIGMAR1 function in motor neurons disturbed endoplasmic reticulum-mitochondria contacts, affected intracellular calcium signalling and was accompanied by activation of endoplasmic reticulum stress and defects in mitochondrial dynamics and transport. These defects were not observed in cultured sensory neurons, highlighting the exacerbated sensitivity of motor neurons to SIGMAR1 function. Interestingly, the inhibition of mitochondrial fission was sufficient to induce mitochondria axonal transport defects as well as axonal degeneration similar to the changes observed after SIGMAR1 inactivation or loss. Intracellular calcium scavenging and endoplasmic reticulum stress inhibition were able to restore mitochondrial function and consequently prevent motor neuron degeneration. These results uncover the cellular mechanisms underlying motor neuron degeneration mediated by loss of SIGMAR1 function and provide therapeutically relevant insight into motor neuronal diseases. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Executive function in weight loss and weight loss maintenance: a conceptual review and novel neuropsychological model of weight control.

Science.gov (United States)

Gettens, Katelyn M; Gorin, Amy A

2017-10-01

Weight loss maintenance is a complex, multifaceted process that presents a significant challenge for most individuals who lose weight. A growing body of literature indicates a strong relationship between cognitive dysfunction and excessive body weight, and suggests that a subset of high-order cognitive processes known as executive functions (EF) likely play an important role in weight management. Recent reviews cover neuropsychological correlates of weight status yet fail to address the role of executive function in the central dilemma of successful weight loss maintenance. In this paper, we provide an overview of the existing literature examining executive functions as they relate to weight status and initial weight loss. Further, we propose a novel conceptual model of the relationships between EF, initial weight loss, and weight loss maintenance, mapping specific executive functions onto strategies known to be associated with both phases of the weight control process. Implications for the development of more efficacious weight loss maintenance interventions are discussed.

Progressive multiple sclerosis: from pathogenic mechanisms to treatment.

Science.gov (United States)

Correale, Jorge; Gaitán, María I; Ysrraelit, María C; Fiol, Marcela P

2017-03-01

During the past decades, better understanding of relapsing-remitting multiple sclerosis disease mechanisms have led to the development of several disease-modifying therapies, reducing relapse rates and severity, through immune system modulation or suppression. In contrast, current therapeutic options for progressive multiple sclerosis remain comparatively disappointing and challenging. One possible explanation is a lack of understanding of pathogenic mechanisms driving progressive multiple sclerosis. Furthermore, diagnosis is usually retrospective, based on history of gradual neurological worsening with or without occasional relapses, minor remissions or plateaus. In addition, imaging methods as well as biomarkers are not well established. Magnetic resonance imaging studies in progressive multiple sclerosis show decreased blood-brain barrier permeability, probably reflecting compartmentalization of inflammation behind a relatively intact blood-brain barrier. Interestingly, a spectrum of inflammatory cell types infiltrates the leptomeninges during subpial cortical demyelination. Indeed, recent magnetic resonance imaging studies show leptomeningeal contrast enhancement in subjects with progressive multiple sclerosis, possibly representing an in vivo marker of inflammation associated to subpial demyelination. Treatments for progressive disease depend on underlying mechanisms causing central nervous system damage. Immunity sheltered behind an intact blood-brain barrier, energy failure, and membrane channel dysfunction may be key processes in progressive disease. Interfering with these mechanisms may provide neuroprotection and prevent disability progression, while potentially restoring activity and conduction along damaged axons by repairing myelin. Although most previous clinical trials in progressive multiple sclerosis have yielded disappointing results, important lessons have been learnt, improving the design of novel ones. This review discusses mechanisms involved

Evaluation of heatup and recovery in a loss of feedwater accident with multiple failure

International Nuclear Information System (INIS)

Bang, Young Seok; Seul, Kwang Won; Kim, Hho Jung

1991-01-01

A loss of feedwater accident with multiple failure has been studied in order to identify the potential severity of the accident when compared with the design basis accident in PWR. The PCS heatup and recovery mode in a LOFA with multiple failure was evaluated using the LOFT L9-1/L3-3 experiment. From experimental result, 4 separable subphase were identified and the associated phenomena were also addressed

Plant litter functional diversity effects on litter mass loss depend on the macro-detritivore community.

Science.gov (United States)

Patoine, Guillaume; Thakur, Madhav P; Friese, Julia; Nock, Charles; Hönig, Lydia; Haase, Josephine; Scherer-Lorenzen, Michael; Eisenhauer, Nico

2017-11-01

A better understanding of the mechanisms driving litter diversity effects on decomposition is needed to predict how biodiversity losses affect this crucial ecosystem process. In a microcosm study, we investigated the effects of litter functional diversity and two major groups of soil macro-detritivores on the mass loss of tree leaf litter mixtures. Furthermore, we tested the effects of litter trait community means and dissimilarity on litter mass loss for seven traits relevant to decomposition. We expected macro-detritivore effects on litter mass loss to be most pronounced in litter mixtures of high functional diversity. We used 24 leaf mixtures differing in functional diversity, which were composed of litter from four species from a pool of 16 common European tree species. Earthworms, isopods, or a combination of both were added to each litter combination for two months. Litter mass loss was significantly higher in the presence of earthworms than in that of isopods, whereas no synergistic effects of macro-detritivore mixtures were found. The effect of functional diversity of the litter material was highest in the presence of both macro-detritivore groups, supporting the notion that litter diversity effects are most pronounced in the presence of different detritivore species. Species-specific litter mass loss was explained by nutrient content, secondary compound concentration, and structural components. Moreover, dissimilarity in N concentrations increased litter mass loss, probably because detritivores having access to nutritionally diverse food sources. Furthermore, strong competition between the two macro-detritivores for soil surface litter resulted in a decrease of survival of both macro-detritivores. These results show that the effects of litter functional diversity on decomposition are contingent upon the macro-detritivore community and composition. We conclude that the temporal dynamics of litter trait diversity effects and their interaction with

Oceans and continents: Similarities and differences in the mechanisms of heat loss

International Nuclear Information System (INIS)

Sclater, J.G.; Parsons, B.; Jaupart, C.

1981-01-01

The principal objective of this paper is to present a simple and self-consistent review of the basic physical processes controlling heat loss from the earth. To accomplish this objective, we give a short summary of the oceanic and continental data and compare and contrast the respective mechanisms of heat loss . In the oceans we concentrate on the effect of hydrothermal circulation, and on the continents we consider in some detail a model relating surface heat flow to varying depth scales for the distribution of potassium, thorium, and uranium. From this comparison we conclude that the range in possible geotherms at depths below 100 to 150 km under continents and oceans overlaps and the thermal structure beneath an old stable continent is indistinguishable from that beneath an ocean were it at equilibrium. Oceans and continents are part of the same thermal system. Both have an upper rigid mechanical layer where heat loss is by conduction and a lower thermal boundary layer where convection is dominant. The simple conductive definition of the plate thickness is an oversimplification. The observed distribution of area versus age in the ocean allows us to investigate the dominant mechanism of heat loss which is plate creation. This distribution and an understanding of the heat flow through oceans and continents can be used to calculate the heat loss of the earth. This heat loss is 10 13 cal/s (4.2 x 10 13 W) of which more than 60% results from the creation of oceanic plate. The relation between area and age of the oceans is coupled to the ridge and subducting slab forces that contribute to the driving mechanism for plate motions. These forces are self-regulating and maintain the rate of plate generation required to achieve a balance between heat loss and heat generation

Predicting hearing thresholds and occupational hearing loss with multiple-frequency auditory steady-state responses.

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Hsu, Ruey-Fen; Ho, Chi-Kung; Lu, Sheng-Nan; Chen, Shun-Sheng

2010-10-01

An objective investigation is needed to verify the existence and severity of hearing impairments resulting from work-related, noise-induced hearing loss in arbitration of medicolegal aspects. We investigated the accuracy of multiple-frequency auditory steady-state responses (Mf-ASSRs) between subjects with sensorineural hearing loss (SNHL) with and without occupational noise exposure. Cross-sectional study. Tertiary referral medical centre. Pure-tone audiometry and Mf-ASSRs were recorded in 88 subjects (34 patients had occupational noise-induced hearing loss [NIHL], 36 patients had SNHL without noise exposure, and 18 volunteers were normal controls). Inter- and intragroup comparisons were made. A predicting equation was derived using multiple linear regression analysis. ASSRs and pure-tone thresholds (PTTs) showed a strong correlation for all subjects (r = .77 ≈ .94). The relationship is demonstrated by the equationThe differences between the ASSR and PTT were significantly higher for the NIHL group than for the subjects with non-noise-induced SNHL (p tool for objectively evaluating hearing thresholds. Predictive value may be lower in subjects with occupational hearing loss. Regardless of carrier frequencies, the severity of hearing loss affects the steady-state response. Moreover, the ASSR may assist in detecting noise-induced injury of the auditory pathway. A multiple linear regression equation to accurately predict thresholds was shown that takes into consideration all effect factors.

Dimensions of biodiversity loss: Spatial mismatch in land-use impacts on species, functional and phylogenetic diversity of European bees.

Science.gov (United States)

De Palma, Adriana; Kuhlmann, Michael; Bugter, Rob; Ferrier, Simon; Hoskins, Andrew J; Potts, Simon G; Roberts, Stuart P M; Schweiger, Oliver; Purvis, Andy

2017-12-01

Agricultural intensification and urbanization are important drivers of biodiversity change in Europe. Different aspects of bee community diversity vary in their sensitivity to these pressures, as well as independently influencing ecosystem service provision (pollination). To obtain a more comprehensive understanding of human impacts on bee diversity across Europe, we assess multiple, complementary indices of diversity. One Thousand four hundred and forty six sites across Europe. We collated data on bee occurrence and abundance from the published literature and supplemented them with the PREDICTS database. Using Rao's Quadratic Entropy, we assessed how species, functional and phylogenetic diversity of 1,446 bee communities respond to land-use characteristics including land-use class, cropland intensity, human population density and distance to roads. We combined these models with statistically downscaled estimates of land use in 2005 to estimate and map-at a scale of approximately 1 km 2 -the losses in diversity relative to semi-natural/natural baseline (the predicted diversity of an uninhabited grid square, consisting only of semi-natural/natural vegetation). We show that-relative to the predicted local diversity in uninhabited semi-natural/natural habitat-half of all EU27 countries have lost over 10% of their average local species diversity and two-thirds of countries have lost over 5% of their average local functional and phylogenetic diversity. All diversity measures were generally lower in pasture and higher-intensity cropland than in semi-natural/natural vegetation, but facets of diversity showed less consistent responses to human population density. These differences have led to marked spatial mismatches in losses: losses in phylogenetic diversity were in some areas almost 20 percentage points (pp.) more severe than losses in species diversity, but in other areas losses were almost 40 pp. less severe. These results highlight the importance of exploring

[Multiple time scales analysis of spatial differentiation characteristics of non-point source nitrogen loss within watershed].

Science.gov (United States)

Liu, Mei-bing; Chen, Xing-wei; Chen, Ying

2015-07-01

Identification of the critical source areas of non-point source pollution is an important means to control the non-point source pollution within the watershed. In order to further reveal the impact of multiple time scales on the spatial differentiation characteristics of non-point source nitrogen loss, a SWAT model of Shanmei Reservoir watershed was developed. Based on the simulation of total nitrogen (TN) loss intensity of all 38 subbasins, spatial distribution characteristics of nitrogen loss and critical source areas were analyzed at three time scales of yearly average, monthly average and rainstorms flood process, respectively. Furthermore, multiple linear correlation analysis was conducted to analyze the contribution of natural environment and anthropogenic disturbance on nitrogen loss. The results showed that there were significant spatial differences of TN loss in Shanmei Reservoir watershed at different time scales, and the spatial differentiation degree of nitrogen loss was in the order of monthly average > yearly average > rainstorms flood process. TN loss load mainly came from upland Taoxi subbasin, which was identified as the critical source area. At different time scales, land use types (such as farmland and forest) were always the dominant factor affecting the spatial distribution of nitrogen loss, while the effect of precipitation and runoff on the nitrogen loss was only taken in no fertilization month and several processes of storm flood at no fertilization date. This was mainly due to the significant spatial variation of land use and fertilization, as well as the low spatial variability of precipitation and runoff.

Aortic stiffness and hypotension episodes are associated with impaired cognitive function in older subjects with subjective complaints of memory loss.

Science.gov (United States)

Scuteri, Angelo; Tesauro, Manfredi; Guglini, Letizia; Lauro, Davide; Fini, Massimo; Di Daniele, Nicola

2013-11-20

Though CV risk factors and markers of arterial aging are recognized risky for cognition, no study has simultaneously investigated the impact of multiple cardiac, arterial (large and small vessels), and hemodynamic parameters on cognitive function in older subjects. Two hundred eighty older subjects with subjective complaints of memory loss and no previous stroke (mean age 78.3 ± 6.3 years) were studied. Global cognitive function was evaluated with the Mini-Mental State Examination (MMSE). Cognitive impairment was defined as a MMSE cognitive function-controlling for age, sex, education, depression, traditional CV risk factors, and medications. LV mass was no longer associated with cognition in multiple regression. Older subjects with stiffer arteries or episodes of hypotension presented a 4-fold and an 11-fold, respectively, greater odds for progression from normal cognitive function to cognitive impairment. A synergistic effect between PWV, WML, and hypotension was observed: the occurrence of any two of PWV, WML, or hypotension was accompanied by lower MMSE; in the presence of all three factors, a further significant decline in cognitive function was observed. Systemic hemodynamic parameters (higher PWV and hypotension) together with cerebral microvascular damage (WML) are significantly associated with poorer cognitive function and may identify older subjects with subjective complaints of memory loss at higher risk of cognitive decline. © 2013.

Mechanisms of hearing loss in neurofibromatosis type 2.

Directory of Open Access Journals (Sweden)

Ashok R Asthagiri

Full Text Available Patients with neurofibromatosis type 2 (NF2 develop bilateral cochleovestibular schwannomas (CVSs that cause binaural deafness in most individuals. Hearing loss occurs in an unpredictable manner and the underlying mechanisms are not known. To gain insight into the pathophysiologic basis for hearing loss in NF2, we performed a prospective cross-sectional study of untreated ears in NF2 patients.One hundred consecutive NF2 patients in a prospective natural history study were included. Clinical and audiometric data were analyzed for treatment naïve ears. In addition to standard MR-imaging sequences, alterations in intralabyrinthine protein content were determined utilizing high resolution FLAIR, the presence of cochlear aperture obstruction was determined by examining 3D T2 sequences, and endolymphatic hydrops was identified on delayed post-contrast FLAIR sequences.Eighty-nine ears harboring 84 untreated CVSs in 56 consecutive NF2 patients (age 30 ± 16 years were analyzed. Thirty-four (38% ears had varying degrees of hearing loss. Elevated intralabyrinthine protein was identified in 70 (75% ears by FLAIR MR-imaging and was strongly associated with the presence of hearing loss (32/34 hearing loss ears; 94%(Fisher's exact test; P= .005. Elevated intralabyrinthine protein was associated with the presence of CVS-associated cochlear aperture obstruction (64 of 67 ears with elevated protein; 96%(Fisher's exact test; P<0.0001 in both normal and hearing loss ears. Elevated intralabyrinthine protein was not identified in ears without CVS (5 ears. While larger tumor size was associated with hearing loss (P=0.006, 16 hearing loss ears (47% harbored CVSs less than 0.5 cm(3, including 14 ears (88% with block of the cochlear aperture and elevated protein.These findings are consistent with a model in which hearing loss develops as a result of cochlear aperture obstruction and accumulation of intralabyrinthine protein. MRI based identification of elevated

Towards trans-diagnostic mechanisms in psychiatry: neurobehavioral profile of rats with a loss-of-function point mutation in the dopamine transporter gene

Directory of Open Access Journals (Sweden)

Valentina Vengeliene

2017-04-01

Full Text Available The research domain criteria (RDoC matrix has been developed to reorient psychiatric research towards measurable behavioral dimensions and underlying mechanisms. Here, we used a new genetic rat model with a loss-of-function point mutation in the dopamine transporter (DAT gene (Slc6a3_N157K to systematically study the RDoC matrix. First, we examined the impact of the Slc6a3_N157K mutation on monoaminergic signaling. We then performed behavioral tests representing each of the five RDoC domains: negative and positive valence systems, cognitive, social and arousal/regulatory systems. The use of RDoC may be particularly helpful for drug development. We studied the effects of a novel pharmacological approach metabotropic glutamate receptor mGluR2/3 antagonism, in DAT mutants in a comparative way with standard medications. Loss of DAT functionality in mutant rats not only elevated subcortical extracellular dopamine concentration but also altered the balance of monoaminergic transmission. DAT mutant rats showed deficits in all five RDoC domains. Thus, mutant rats failed to show conditioned fear responses, were anhedonic, were unable to learn stimulus-reward associations, showed impaired cognition and social behavior, and were hyperactive. Hyperactivity in mutant rats was reduced by amphetamine and atomoxetine, which are well-established medications to reduce hyperactivity in humans. The mGluR2/3 antagonist LY341495 also normalized hyperactivity in DAT mutant rats without affecting extracellular dopamine levels. We systematically characterized an altered dopamine system within the context of the RDoC matrix and studied mGluR2/3 antagonism as a new pharmacological strategy to treat mental disorders with underlying subcortical dopaminergic hyperactivity.

Preoperative thyroid function and weight loss after bariatric surgery.

Science.gov (United States)

Neves, João Sérgio; Souteiro, Pedro; Oliveira, Sofia Castro; Pedro, Jorge; Magalhães, Daniela; Guerreiro, Vanessa; Costa, Maria Manuel; Bettencourt-Silva, Rita; Santos, Ana Cristina; Queirós, Joana; Varela, Ana; Freitas, Paula; Carvalho, Davide

2018-05-16

Thyroid function has an important role on body weight regulation. However, the impact of thyroid function on weight loss after bariatric surgery is still largely unknown. We evaluated the association between preoperative thyroid function and the excess weight loss 1 year after surgery, in 641 patients with morbid obesity who underwent bariatric surgery. Patients with a history of thyroid disease, treatment with thyroid hormone or antithyroid drugs and those with preoperative evaluation consistent with overt hypothyroidism or hyperthyroidism were excluded. The preoperative levels of TSH and FT4 were not associated with weight loss after bariatric surgery. The variation of FT3 within the reference range was also not associated with weight loss. In contrast, the subgroup with FT3 above the reference range (12.3% of patients) had a significantly higher excess weight loss than patients with normal FT3. This difference remained significant after adjustment for age, sex, BMI, type of surgery, TSH and FT4. In conclusion, we observed an association between high FT3 and a greater weight loss after bariatric surgery, highlighting a group of patients with an increased benefit from this intervention. Our results also suggest a novel hypothesis: the pharmacological modulation of thyroid function may be a potential therapeutic target in patients undergoing bariatric surgery.

Optimization of multiple performance characteristics in turning using Taguchi’s quality loss function: An experimental investigation

Directory of Open Access Journals (Sweden)

Tanmaya Mohanty

2013-06-01

Full Text Available Cutting force and chip reduction coefficient is the important index of machinability as it determines the power consumption and amount of energy invested in machining actions. It is primarily influenced by process parameters like cutting speed, feed and depth of cut. This paper presents the application of Taguchi’s parameter design to optimize the parameters for individual responses. For multi-response optimization, Taguchi’s quality loss function approach is proposed. In the present investigation, optimal values of cutting speed, feed and depth of cut are determined to minimize cutting force and chip reduction coefficient during orthogonal turning. The effectiveness of the proposed methodology is illustrated through an experimental investigation in turning mild steel workpiece using high speed steel tool.

Mechanics of advanced functional materials

CERN Document Server

Wang, Biao

2013-01-01

Mechanics of Advanced Functional Materials emphasizes the coupling effect between the electric and mechanical field in the piezoelectric, ferroelectric and other functional materials. It also discusses the size effect on the ferroelectric domain instability and phase transition behaviors using the continuum micro-structural evolution models. Functional materials usually have a very wide application in engineering due to their unique thermal, electric, magnetic, optoelectronic, etc., functions. Almost all the applications demand that the material should have reasonable stiffness, strength, fracture toughness and the other mechanical properties. Furthermore, usually the stress and strain fields on the functional materials and devices have some important coupling effect on the functionality of the materials. Much progress has been made concerning the coupling electric and mechanical behaviors such as the coupled electric and stress field distribution in piezoelectric solids, ferroelectric domain patterns in ferr...

Human dental pulp-derived stem cells promote locomotor recovery after complete transection of the rat spinal cord by multiple neuro-regenerative mechanisms.

Science.gov (United States)

Sakai, Kiyoshi; Yamamoto, Akihito; Matsubara, Kohki; Nakamura, Shoko; Naruse, Mami; Yamagata, Mari; Sakamoto, Kazuma; Tauchi, Ryoji; Wakao, Norimitsu; Imagama, Shiro; Hibi, Hideharu; Kadomatsu, Kenji; Ishiguro, Naoki; Ueda, Minoru

2012-01-01

Spinal cord injury (SCI) often leads to persistent functional deficits due to loss of neurons and glia and to limited axonal regeneration after injury. Here we report that transplantation of human dental pulp stem cells into the completely transected adult rat spinal cord resulted in marked recovery of hind limb locomotor functions. Transplantation of human bone marrow stromal cells or skin-derived fibroblasts led to substantially less recovery of locomotor function. The human dental pulp stem cells exhibited three major neuroregenerative activities. First, they inhibited the SCI-induced apoptosis of neurons, astrocytes, and oligodendrocytes, which improved the preservation of neuronal filaments and myelin sheaths. Second, they promoted the regeneration of transected axons by directly inhibiting multiple axon growth inhibitors, including chondroitin sulfate proteoglycan and myelin-associated glycoprotein, via paracrine mechanisms. Last, they replaced lost cells by differentiating into mature oligodendrocytes under the extreme conditions of SCI. Our data demonstrate that tooth-derived stem cells may provide therapeutic benefits for treating SCI through both cell-autonomous and paracrine neuroregenerative activities.

Oracle Inequalities for Convex Loss Functions with Non-Linear Targets

DEFF Research Database (Denmark)

Caner, Mehmet; Kock, Anders Bredahl

This paper consider penalized empirical loss minimization of convex loss functions with unknown non-linear target functions. Using the elastic net penalty we establish a finite sample oracle inequality which bounds the loss of our estimator from above with high probability. If the unknown target...... of the same order as that of the oracle. If the target is linear we give sufficient conditions for consistency of the estimated parameter vector. Next, we briefly discuss how a thresholded version of our estimator can be used to perform consistent variable selection. We give two examples of loss functions...

Distinct mutational signatures characterize concurrent loss of polymerase proofreading and mismatch repair.

Science.gov (United States)

Haradhvala, N J; Kim, J; Maruvka, Y E; Polak, P; Rosebrock, D; Livitz, D; Hess, J M; Leshchiner, I; Kamburov, A; Mouw, K W; Lawrence, M S; Getz, G

2018-05-01

Fidelity of DNA replication is maintained using polymerase proofreading and the mismatch repair pathway. Tumors with loss of function of either mechanism have elevated mutation rates with characteristic mutational signatures. Here we report that tumors with concurrent loss of both polymerase proofreading and mismatch repair function have mutational patterns that are not a simple sum of the signatures of the individual alterations, but correspond to distinct, previously unexplained signatures: COSMIC database signatures 14 and 20. We then demonstrate that in all five cases in which the chronological order of events could be determined, polymerase epsilon proofreading alterations precede the defect in mismatch repair. Overall, we illustrate that multiple distinct mutational signatures can result from different combinations of a smaller number of mutational processes (of either damage or repair), which can influence the interpretation and discovery of mutational signatures.

Regulator Loss Functions and Hierarchical Modeling for Safety Decision Making.

Science.gov (United States)

Hatfield, Laura A; Baugh, Christine M; Azzone, Vanessa; Normand, Sharon-Lise T

2017-07-01

Regulators must act to protect the public when evidence indicates safety problems with medical devices. This requires complex tradeoffs among risks and benefits, which conventional safety surveillance methods do not incorporate. To combine explicit regulator loss functions with statistical evidence on medical device safety signals to improve decision making. In the Hospital Cost and Utilization Project National Inpatient Sample, we select pediatric inpatient admissions and identify adverse medical device events (AMDEs). We fit hierarchical Bayesian models to the annual hospital-level AMDE rates, accounting for patient and hospital characteristics. These models produce expected AMDE rates (a safety target), against which we compare the observed rates in a test year to compute a safety signal. We specify a set of loss functions that quantify the costs and benefits of each action as a function of the safety signal. We integrate the loss functions over the posterior distribution of the safety signal to obtain the posterior (Bayes) risk; the preferred action has the smallest Bayes risk. Using simulation and an analysis of AMDE data, we compare our minimum-risk decisions to a conventional Z score approach for classifying safety signals. The 2 rules produced different actions for nearly half of hospitals (45%). In the simulation, decisions that minimize Bayes risk outperform Z score-based decisions, even when the loss functions or hierarchical models are misspecified. Our method is sensitive to the choice of loss functions; eliciting quantitative inputs to the loss functions from regulators is challenging. A decision-theoretic approach to acting on safety signals is potentially promising but requires careful specification of loss functions in consultation with subject matter experts.

Behavioral training promotes multiple adaptive processes following acute hearing loss.

Science.gov (United States)

Keating, Peter; Rosenior-Patten, Onayomi; Dahmen, Johannes C; Bell, Olivia; King, Andrew J

2016-03-23

The brain possesses a remarkable capacity to compensate for changes in inputs resulting from a range of sensory impairments. Developmental studies of sound localization have shown that adaptation to asymmetric hearing loss can be achieved either by reinterpreting altered spatial cues or by relying more on those cues that remain intact. Adaptation to monaural deprivation in adulthood is also possible, but appears to lack such flexibility. Here we show, however, that appropriate behavioral training enables monaurally-deprived adult humans to exploit both of these adaptive processes. Moreover, cortical recordings in ferrets reared with asymmetric hearing loss suggest that these forms of plasticity have distinct neural substrates. An ability to adapt to asymmetric hearing loss using multiple adaptive processes is therefore shared by different species and may persist throughout the lifespan. This highlights the fundamental flexibility of neural systems, and may also point toward novel therapeutic strategies for treating sensory disorders.

Multiple Scattering in Random Mechanical Systems and Diffusion Approximation

Science.gov (United States)

Feres, Renato; Ng, Jasmine; Zhang, Hong-Kun

2013-10-01

This paper is concerned with stochastic processes that model multiple (or iterated) scattering in classical mechanical systems of billiard type, defined below. From a given (deterministic) system of billiard type, a random process with transition probabilities operator P is introduced by assuming that some of the dynamical variables are random with prescribed probability distributions. Of particular interest are systems with weak scattering, which are associated to parametric families of operators P h , depending on a geometric or mechanical parameter h, that approaches the identity as h goes to 0. It is shown that ( P h - I)/ h converges for small h to a second order elliptic differential operator on compactly supported functions and that the Markov chain process associated to P h converges to a diffusion with infinitesimal generator . Both P h and are self-adjoint (densely) defined on the space of square-integrable functions over the (lower) half-space in , where η is a stationary measure. This measure's density is either (post-collision) Maxwell-Boltzmann distribution or Knudsen cosine law, and the random processes with infinitesimal generator respectively correspond to what we call MB diffusion and (generalized) Legendre diffusion. Concrete examples of simple mechanical systems are given and illustrated by numerically simulating the random processes.

Multiple joint muscle function with ageing: the force-velocity and power-velocity relationships in young and older men.

Science.gov (United States)

Allison, Sarah J; Brooke-Wavell, Katherine; Folland, Jonathan P

2013-05-01

Whilst extensive research has detailed the loss of muscle strength with ageing for isolated single joint actions, there has been little attention to power production during more functionally relevant multiple joint movements. The extent to which force or velocity are responsible for the loss in power with ageing is also equivocal. The aim of this study was to evaluate the contribution of force and velocity to the differences in power with age by comparing the force-velocity and power-velocity relationships in young and older men during a multiple joint leg press movement. Twenty-one older men (66 ± 3 years) and twenty-three young men (24 ± 2 years) completed a series of isometric (maximum and explosive) and dynamic contractions on a leg press dynamometer instrumented to record force and displacement. The force-velocity relationship was lower for the older men as reflected by their 19 % lower maximum isometric strength (p decrement in force was greater and therefore the major explanation for the attenuation of power during a functionally relevant multiple joint movement.

Childhood Parental Loss and Adult Hypothalamic-Pituitary-Adrenal Function

Science.gov (United States)

Tyrka, Audrey R.; Wier, Lauren; Price, Lawrence H.; Ross, Nicole; Anderson, George M.; Wilkinson, Charles W.; Carpenter, Linda L.

2009-01-01

Background Several decades of research link childhood parental loss with risk for major depression and other forms of psychopathology. A large body of preclinical work on maternal separation and some recent studies of humans with childhood parental loss have demonstrated alterations of hypothalamic-pituitary-adrenal (HPA) axis function which could predispose to the development of psychiatric disorders. Methods Eighty-eight healthy adults with no current Axis I psychiatric disorder participated in this study. Forty-four participants experienced parental loss during childhood, including 19 with a history of parental death and 25 with a history of prolonged parental separation. The loss group was compared to a matched group of individuals who reported no history of childhood parental separation or childhood maltreatment. Participants completed diagnostic interviews and questionnaires and the dexamethasone/corticotropin-releasing hormone (Dex/CRH) test. Repeated measures general linear models were used to test the effects of parental loss, a measure of parental care, sex, and age on the hormone responses to the Dex/CRH test. Results Parental loss was associated with increased cortisol responses to the test, particularly in males. The effect of loss was moderated by levels of parental care; participants with parental desertion and very low levels of care had attenuated cortisol responses. ACTH responses to the Dex/CRH test did not differ significantly as a function of parental loss. Conclusions These findings are consistent with the hypothesis that early parental loss induces enduring changes in neuroendocrine function. PMID:18339361

Claudin Loss-of-Function Disrupts Tight Junctions and Impairs Amelogenesis.

Science.gov (United States)

Bardet, Claire; Ribes, Sandy; Wu, Yong; Diallo, Mamadou Tidiane; Salmon, Benjamin; Breiderhoff, Tilman; Houillier, Pascal; Müller, Dominik; Chaussain, Catherine

2017-01-01

Claudins are a family of proteins that forms paracellular barriers and pores determining tight junctions (TJ) permeability. Claudin-16 and -19 are pore forming TJ proteins allowing calcium and magnesium reabsorption in the thick ascending limb of Henle's loop (TAL). Loss-of-function mutations in the encoding genes, initially identified to cause Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis (FHHNC), were recently shown to be also involved in Amelogenesis Imperfecta (AI). In addition, both claudins were expressed in the murine tooth germ and Claudin-16 knockout (KO) mice displayed abnormal enamel formation. Claudin-3, an ubiquitous claudin expressed in epithelia including kidney, acts as a barrier-forming tight junction protein. We determined that, similarly to claudin-16 and claudin-19, claudin-3 was expressed in the tooth germ, more precisely in the TJ located at the apical end of secretory ameloblasts. The observation of Claudin-3 KO teeth revealed enamel defects associated to impaired TJ structure at the secretory ends of ameloblasts and accumulation of matrix proteins in the forming enamel. Thus, claudin-3 protein loss-of-function disturbs amelogenesis similarly to claudin-16 loss-of-function, highlighting the importance of claudin proteins for the TJ structure. These findings unravel that loss-of-function of either pore or barrier-forming TJ proteins leads to enamel defects. Hence, the major structural function of claudin proteins appears essential for amelogenesis.

Claudin Loss-of-Function Disrupts Tight Junctions and Impairs Amelogenesis

Directory of Open Access Journals (Sweden)

Claire Bardet

2017-05-01

Full Text Available Claudins are a family of proteins that forms paracellular barriers and pores determining tight junctions (TJ permeability. Claudin-16 and -19 are pore forming TJ proteins allowing calcium and magnesium reabsorption in the thick ascending limb of Henle's loop (TAL. Loss-of-function mutations in the encoding genes, initially identified to cause Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis (FHHNC, were recently shown to be also involved in Amelogenesis Imperfecta (AI. In addition, both claudins were expressed in the murine tooth germ and Claudin-16 knockout (KO mice displayed abnormal enamel formation. Claudin-3, an ubiquitous claudin expressed in epithelia including kidney, acts as a barrier-forming tight junction protein. We determined that, similarly to claudin-16 and claudin-19, claudin-3 was expressed in the tooth germ, more precisely in the TJ located at the apical end of secretory ameloblasts. The observation of Claudin-3 KO teeth revealed enamel defects associated to impaired TJ structure at the secretory ends of ameloblasts and accumulation of matrix proteins in the forming enamel. Thus, claudin-3 protein loss-of-function disturbs amelogenesis similarly to claudin-16 loss-of-function, highlighting the importance of claudin proteins for the TJ structure. These findings unravel that loss-of-function of either pore or barrier-forming TJ proteins leads to enamel defects. Hence, the major structural function of claudin proteins appears essential for amelogenesis.

Construction of energy loss function for low-energy electrons in helium

Energy Technology Data Exchange (ETDEWEB)

Dayashankar, [Bhabha Atomic Research Centre, Bombay (India). Div. of Radiation Protection

1976-02-01

The energy loss function for electrons in the energy range from 50 eV to 1 keV in helium gas has been constructed by considering separately the energy loss in overcoming the ionization threshold, the loss manifested as kinetic energy of secondary electrons and the loss in the discrete state excitations. This has been done by utilizing recent measurements of Opal et al. on the energy spectrum of secondary electrons and incorporating the experimental data on cross sections for twenty-four excited states. The present results of the energy loss function are in good agreement with the Bethe formula for energies above 500 eV. For lower energies, where the Bethe formula is not applicable, the present results should be particularly useful.

Functional and structural balances of homologous sensorimotor regions in multiple sclerosis fatigue

DEFF Research Database (Denmark)

Cogliati Dezza, I; Zito, G; Tomasevic, L

2015-01-01

regions-known to be crucial for sensorimotor networks effectiveness-decrease with MS fatigue increase. Functional connectivity measures at rest and during a simple motor task (weak handgrip of either the right or left hand) were derived from primary sensorimotor areas electroencephalographic recordings......Fatigue in multiple sclerosis (MS) is a highly disabling symptom. Among the central mechanisms behind it, an involvement of sensorimotor networks is clearly evident from structural and functional studies. We aimed at assessing whether functional/structural balances of homologous sensorimotor...... in 27 mildly disabled MS patients. Structural MRI-derived inter-hemispheric asymmetries included the cortical thickness of Rolandic regions and the volume of thalami. Fatigue symptoms increased together with the functional inter-hemispheric imbalance of sensorimotor homologous areas activities at rest...

[Aberrant topological properties of whole-brain functional network in chronic right-sided sensorineural hearing loss: a resting-state functional MRI study].

Science.gov (United States)

Zhang, Lingling; Liu, Bin; Xu, Yangwen; Yang, Ming; Feng, Yuan; Huang, Yaqing; Huan, Zhichun; Hou, Zhaorui

2015-02-03

To investigate the topological properties of the functional brain network in unilateral sensorineural hearing loss patients. In this study, we acquired resting-state BOLD- fMRI data from 19 right-sided SNHL patients and 31 healthy controls with normal hearing and constructed their whole brain functional networks. Two-sample two-tailed t-tests were performed to investigate group differences in topological parameters between the USNHL patients and the controls. Partial correlation analysis was conducted to determine the relationships between the network metrics and USNHL-related variables. Both USNHL patients and controls exhibited small-word architecture in their brain functional networks within the range 0. 1 - 0. 2 of sparsity. Compared to the controls, USNHL patients showed significant increase in characteristic path length and normalized characteristic path length, but significant decrease in global efficiency. Clustering coefficient, local efficiency and normalized clustering coefficient demonstrated no significant difference. Furthermore, USNHL patients exhibited no significant association between the altered network metrics and the duration of USNHL or the severity of hearing loss. Our results indicated the altered topological properties of whole brain functional networks in USNHL patients, which may help us to understand pathophysiologic mechanism of USNHL patients.

Towards trans-diagnostic mechanisms in psychiatry: neurobehavioral profile of rats with a loss-of-function point mutation in the dopamine transporter gene.

Science.gov (United States)

Vengeliene, Valentina; Bespalov, Anton; Roßmanith, Martin; Horschitz, Sandra; Berger, Stefan; Relo, Ana L; Noori, Hamid R; Schneider, Peggy; Enkel, Thomas; Bartsch, Dusan; Schneider, Miriam; Behl, Berthold; Hansson, Anita C; Schloss, Patrick; Spanagel, Rainer

2017-04-01

The research domain criteria (RDoC) matrix has been developed to reorient psychiatric research towards measurable behavioral dimensions and underlying mechanisms. Here, we used a new genetic rat model with a loss-of-function point mutation in the dopamine transporter (DAT) gene ( Slc6a3 _N157K) to systematically study the RDoC matrix. First, we examined the impact of the Slc6a3 _N157K mutation on monoaminergic signaling. We then performed behavioral tests representing each of the five RDoC domains: negative and positive valence systems, cognitive, social and arousal/regulatory systems. The use of RDoC may be particularly helpful for drug development. We studied the effects of a novel pharmacological approach metabotropic glutamate receptor mGluR2/3 antagonism, in DAT mutants in a comparative way with standard medications. Loss of DAT functionality in mutant rats not only elevated subcortical extracellular dopamine concentration but also altered the balance of monoaminergic transmission. DAT mutant rats showed deficits in all five RDoC domains. Thus, mutant rats failed to show conditioned fear responses, were anhedonic, were unable to learn stimulus-reward associations, showed impaired cognition and social behavior, and were hyperactive. Hyperactivity in mutant rats was reduced by amphetamine and atomoxetine, which are well-established medications to reduce hyperactivity in humans. The mGluR2/3 antagonist LY341495 also normalized hyperactivity in DAT mutant rats without affecting extracellular dopamine levels. We systematically characterized an altered dopamine system within the context of the RDoC matrix and studied mGluR2/3 antagonism as a new pharmacological strategy to treat mental disorders with underlying subcortical dopaminergic hyperactivity. © 2017. Published by The Company of Biologists Ltd.

Pancreatic cancerrelated cachexia: influence on metabolism and correlation to weight loss and pulmonary function

Energy Technology Data Exchange (ETDEWEB)

Bachmann, Jeannine; Ketterer, Knut [Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Munich (Germany); Marsch, Christiane [Department of General Surgery, University of Heidelberg, Heidelberg (Germany); Fechtner, Kerstin [Department of Radiology, University of Heidelberg, Heidelberg (Germany); Krakowski-Roosen, Holger [German Cancer Research Center, Heidelberg (Germany); Büchler, Markus W [Department of General Surgery, University of Heidelberg, Heidelberg (Germany); Friess, Helmut; Martignoni, Marc E [Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Munich (Germany)

2009-07-28

Dramatic weight loss is an often underestimated symptom in pancreatic cancer patients. Cachexia- defined as an unintended loss of stable weight exceeding 10% – is present in up to 80% of patients with cancer of the upper gastrointestinal tract, and has a significant influence on survival. The aim of the study was to show the multiple systemic effects of cachexia in pancreatic cancer patients, in terms of resection rate, effects on pulmonary function, amount of fat and muscle tissue, as well as changes in laboratory parameters. In patients with pancreatic cancer, clinical appearance was documented, including the amount of weight loss. Laboratory parameters and lung-function tests were evaluated, and the thickness of muscle and fat tissue was measured with computed tomography scans. Statistical analysis, including multivariate analysis, was performed using SPSS software. Survival curves were calculated using Kaplan-Meier analysis and the log-rank test. To test for significant differences between the examined groups we used Student's t-test and the Mann-Whitney U test. Significance was defined as p < 0.05. Of 198 patients with a ductal adenocarcinoma of the pancreas, 70% were suffering from weight loss when they presented for operation, and in 40% weight loss exceeded 10% of the stable weight. In patients with cachexia, metastases were diagnosed significantly more often (47% vs. 24%, P < 0.001), leading to a significantly reduced resection rate in these patients. Patients with cachexia had significantly reduced fat tissue amounts. Hence, dramatic weight loss in a patient with pancreatic cancer may be a hint of a more progressed or more aggressive tumour. Pancreatic cancer patients with cachexia had a higher rate of more progressed tumour stages and a worse nutritional status. Furthermore, patients with cachexia had an impaired lung function and a reduction in fat tissue. Patients with pancreatic cancer and cachexia had significantly reduced survival. If weight loss

Pancreatic cancerrelated cachexia: influence on metabolism and correlation to weight loss and pulmonary function

International Nuclear Information System (INIS)

Bachmann, Jeannine; Ketterer, Knut; Marsch, Christiane; Fechtner, Kerstin; Krakowski-Roosen, Holger; Büchler, Markus W; Friess, Helmut; Martignoni, Marc E

2009-01-01

Dramatic weight loss is an often underestimated symptom in pancreatic cancer patients. Cachexia- defined as an unintended loss of stable weight exceeding 10% – is present in up to 80% of patients with cancer of the upper gastrointestinal tract, and has a significant influence on survival. The aim of the study was to show the multiple systemic effects of cachexia in pancreatic cancer patients, in terms of resection rate, effects on pulmonary function, amount of fat and muscle tissue, as well as changes in laboratory parameters. In patients with pancreatic cancer, clinical appearance was documented, including the amount of weight loss. Laboratory parameters and lung-function tests were evaluated, and the thickness of muscle and fat tissue was measured with computed tomography scans. Statistical analysis, including multivariate analysis, was performed using SPSS software. Survival curves were calculated using Kaplan-Meier analysis and the log-rank test. To test for significant differences between the examined groups we used Student's t-test and the Mann-Whitney U test. Significance was defined as p < 0.05. Of 198 patients with a ductal adenocarcinoma of the pancreas, 70% were suffering from weight loss when they presented for operation, and in 40% weight loss exceeded 10% of the stable weight. In patients with cachexia, metastases were diagnosed significantly more often (47% vs. 24%, P < 0.001), leading to a significantly reduced resection rate in these patients. Patients with cachexia had significantly reduced fat tissue amounts. Hence, dramatic weight loss in a patient with pancreatic cancer may be a hint of a more progressed or more aggressive tumour. Pancreatic cancer patients with cachexia had a higher rate of more progressed tumour stages and a worse nutritional status. Furthermore, patients with cachexia had an impaired lung function and a reduction in fat tissue. Patients with pancreatic cancer and cachexia had significantly reduced survival. If weight

Acupuncture Mechanisms: Anesthesia, Analgesia and Protection on Organ Functions

Directory of Open Access Journals (Sweden)

Jing Wang

2015-01-01

Full Text Available Acupuncture, as a healing art in traditional Chinese medicine, has been widely used to treat various diseases. In the history of acupuncture anesthesia, in the past decades, mechanisms of acupuncture analgesia has been widely investigated, and in recent years, acupuncture protection on organ functions has attracted great interest. This review summarized the research progress on mechanisms of acupuncture for analgesia and its protection against organ function injury in anesthesia, and its perspective of analgesia, immunomodulation, neuroendocrine regulation and multiple organ protection. The current evidence supports that acupuncture analgesia and its organ protection in anesthesia is associated with the integration of neuroendocrine-immune networks in the level of neurotransmitters, cytokines, hormones, neuronal ensembles, lymphocytes, and endocrine cells. Although the mechanisms of acupuncture analgesia and its organ protection are still not completely understood, basic as well as clinic researches on the mechanisms and applications of acupuncture and related techniques are being carried out.

BAYESIAN ESTIMATION OF THE SHAPE PARAMETER OF THE GENERALISED EXPONENTIAL DISTRIBUTION UNDER DIFFERENT LOSS FUNCTIONS

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SANKU DEY

2010-11-01

Full Text Available The generalized exponential (GE distribution proposed by Gupta and Kundu (1999 is an important lifetime distribution in survival analysis. In this article, we propose to obtain Bayes estimators and its associated risk based on a class of  non-informative prior under the assumption of three loss functions, namely, quadratic loss function (QLF, squared log-error loss function (SLELF and general entropy loss function (GELF. The motivation is to explore the most appropriate loss function among these three loss functions. The performances of the estimators are, therefore, compared on the basis of their risks obtained under QLF, SLELF and GELF separately. The relative efficiency of the estimators is also obtained. Finally, Monte Carlo simulations are performed to compare the performances of the Bayes estimates under different situations.

Reward loss and the basolateral amygdala: A function in reward comparisons.

Science.gov (United States)

Kawasaki, Katsuyoshi; Annicchiarico, Iván; Glueck, Amanda C; Morón, Ignacio; Papini, Mauricio R

2017-07-28

The neural circuitry underlying behavior in reward loss situations is poorly understood. We considered two such situations: reward devaluation (from large to small rewards) and reward omission (from large rewards to no rewards). There is evidence that the central nucleus of the amygdala (CeA) plays a role in the negative emotion accompanying reward loss. However, little is known about the function of the basolateral nucleus (BLA) in reward loss. Two hypotheses of BLA function in reward loss, negative emotion and reward comparisons, were tested in an experiment involving pretraining excitotoxic BLA lesions followed by training in four tasks: consummatory successive negative contrast (cSNC), autoshaping (AS) acquisition and extinction, anticipatory negative contrast (ANC), and open field testing (OF). Cell counts in the BLA (but not in the CeA) were significantly lower in animals with lesions vs. shams. BLA lesions eliminated cSNC and ANC, and accelerated extinction of lever pressing in AS. BLA lesions had no effect on OF testing: higher activity in the periphery than in the central area. This pattern of results provides support for the hypothesis that BLA neurons are important for reward comparison. The three affected tasks (cSNC, ANC, and AS extinction) involve reward comparisons. However, ANC does not seem to involve negative emotions and it was affected, whereas OF activity is known to involve negative emotion, but it was not affected. It is hypothesized that a circuit involving the thalamus, insular cortex, and BLA is critically involved in the mechanism comparing current and expected rewards. Copyright © 2017 Elsevier B.V. All rights reserved.

Analysis of Behavioral Economics in Crowdsensing: A Loss Aversion Cooperation Model

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Deng Li

2018-01-01

Full Text Available The existing incentive mechanisms of crowdsourcing construct the expected utility function based on the assumption of rational people in traditional economics. A large number of studies in behavioral economics have demonstrated the defects of the traditional utility function and introduced a new parameter called loss aversion coefficient to calculate individual utility when it suffers a loss. In this paper, combination of behavioral economics and a payment algorithm based on the loss aversion is proposed. Compared with usual incentive mechanisms, the node utility function is redefined by the loss aversion characteristic of the node. Experimental results show that the proposed algorithm can get a higher rate of cooperation with a lower payment price and has good scalability compared with the traditional incentive mechanism.

Multiple complexes of nitrogen assimilatory enzymes in spinach chloroplasts: possible mechanisms for the regulation of enzyme function.

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Yoko Kimata-Ariga

Full Text Available Assimilation of nitrogen is an essential biological process for plant growth and productivity. Here we show that three chloroplast enzymes involved in nitrogen assimilation, glutamate synthase (GOGAT, nitrite reductase (NiR and glutamine synthetase (GS, separately assemble into distinct protein complexes in spinach chloroplasts, as analyzed by western blots under blue native electrophoresis (BN-PAGE. GOGAT and NiR were present not only as monomers, but also as novel complexes with a discrete size (730 kDa and multiple sizes (>120 kDa, respectively, in the stromal fraction of chloroplasts. These complexes showed the same mobility as each monomer on two-dimensional (2D SDS-PAGE after BN-PAGE. The 730 kDa complex containing GOGAT dissociated into monomers, and multiple complexes of NiR reversibly converted into monomers, in response to the changes in the pH of the stromal solvent. On the other hand, the bands detected by anti-GS antibody were present not only in stroma as a conventional decameric holoenzyme complex of 420 kDa, but also in thylakoids as a novel complex of 560 kDa. The polypeptide in the 560 kDa complex showed slower mobility than that of the 420 kDa complex on the 2D SDS-PAGE, implying the assembly of distinct GS isoforms or a post-translational modification of the same GS protein. The function of these multiple complexes was evaluated by in-gel GS activity under native conditions and by the binding ability of NiR and GOGAT with their physiological electron donor, ferredoxin. The results indicate that these multiplicities in size and localization of the three nitrogen assimilatory enzymes may be involved in the physiological regulation of their enzyme function, in a similar way as recently described cases of carbon assimilatory enzymes.

Mechanisms of stable lipid loss in a social insect

Science.gov (United States)

Ament, Seth A.; Chan, Queenie W.; Wheeler, Marsha M.; Nixon, Scott E.; Johnson, S. Peir; Rodriguez-Zas, Sandra L.; Foster, Leonard J.; Robinson, Gene E.

2011-01-01

SUMMARY Worker honey bees undergo a socially regulated, highly stable lipid loss as part of their behavioral maturation. We used large-scale transcriptomic and proteomic experiments, physiological experiments and RNA interference to explore the mechanistic basis for this lipid loss. Lipid loss was associated with thousands of gene expression changes in abdominal fat bodies. Many of these genes were also regulated in young bees by nutrition during an initial period of lipid gain. Surprisingly, in older bees, which is when maximum lipid loss occurs, diet played less of a role in regulating fat body gene expression for components of evolutionarily conserved nutrition-related endocrine systems involving insulin and juvenile hormone signaling. By contrast, fat body gene expression in older bees was regulated more strongly by evolutionarily novel regulatory factors, queen mandibular pheromone (a honey bee-specific social signal) and vitellogenin (a conserved yolk protein that has evolved novel, maturation-related functions in the bee), independent of nutrition. These results demonstrate that conserved molecular pathways can be manipulated to achieve stable lipid loss through evolutionarily novel regulatory processes. PMID:22031746

Mechanisms of stable lipid loss in a social insect.

Science.gov (United States)

Ament, Seth A; Chan, Queenie W; Wheeler, Marsha M; Nixon, Scott E; Johnson, S Peir; Rodriguez-Zas, Sandra L; Foster, Leonard J; Robinson, Gene E

2011-11-15

Worker honey bees undergo a socially regulated, highly stable lipid loss as part of their behavioral maturation. We used large-scale transcriptomic and proteomic experiments, physiological experiments and RNA interference to explore the mechanistic basis for this lipid loss. Lipid loss was associated with thousands of gene expression changes in abdominal fat bodies. Many of these genes were also regulated in young bees by nutrition during an initial period of lipid gain. Surprisingly, in older bees, which is when maximum lipid loss occurs, diet played less of a role in regulating fat body gene expression for components of evolutionarily conserved nutrition-related endocrine systems involving insulin and juvenile hormone signaling. By contrast, fat body gene expression in older bees was regulated more strongly by evolutionarily novel regulatory factors, queen mandibular pheromone (a honey bee-specific social signal) and vitellogenin (a conserved yolk protein that has evolved novel, maturation-related functions in the bee), independent of nutrition. These results demonstrate that conserved molecular pathways can be manipulated to achieve stable lipid loss through evolutionarily novel regulatory processes.

Interaural multiple frequency tympanometry measures: clinical utility for unilateral conductive hearing loss.

Science.gov (United States)

Norrix, Linda W; Burgan, Briana; Ramirez, Nicholas; Velenovsky, David S

2013-03-01

Tympanometry is a routine clinical measurement of the acoustic immittance of the ear as a function of ear canal air pressure. The 226 Hz tympanogram can provide clinical evidence for conditions such as a tympanic membrane perforation, Eustachian tube dysfunction, middle ear fluid, and ossicular discontinuity. Multiple frequency tympanometry using a range of probe tone frequencies from low to high has been shown to be more sensitive than a single probe tone tympanogram in distinguishing between mass- and stiffness-related middle ear pathologies (Colletti, 1975; Funasaka et al, 1984; Van Camp et al, 1986). In this study we obtained normative measures of middle ear resonance by using multiple probe tone frequency tympanometry. Ninety percent ranges for middle ear resonance and for interaural differences were calculated. In a mixed design, normative data were collected from both ears of male and female adults. Twelve male and 12 female adults with normal hearing and normal middle ear function participated in the study. Multiple frequency tympanograms were recorded with a commercially available immittance instrument (GSI Tympstar) to obtain estimates of middle ear resonant frequency (RF) using ΔB, positive tail, and negative tail methods. Data were analyzed using three-way mixed analyses of variance with gender as a between-subject variable and ear and method as within-subject variables. T-tests were performed, using the Bonferroni adjustment, to determine significant differences between means. Using the positive and negative tail methods, a wide range of approximately 500 Hz was found for middle ear resonance in adults with normal hearing and normal middle ear function. The difference in RF between an individual's ears is small with 90% ranges of approximately ±200 Hz, indicating that the right ear RF should be either 200 Hz higher or lower in frequency compared to the left ear. This was true for both negative and positive tail methods. Ninety percent ranges were

Performance potential of mechanical ventilation systems with minimized pressure loss

DEFF Research Database (Denmark)

Terkildsen, Søren; Svendsen, Svend

2013-01-01

simulations that quantify fan power consumption, heating demand and indoor environmental conditions. The system was designed with minimal pressure loss in the duct system and heat exchanger. Also, it uses state-of-the-art components such as electrostatic precipitators, diffuse ceiling inlets and demand......In many locations mechanical ventilation has been the most widely used principle of ventilation over the last 50 years but the conventional system design must be revised to comply with future energy requirements. This paper examines the options and describes a concept for the design of mechanical...... ventilation systems with minimal pressure loss and minimal energy use. This can provide comfort ventilation and avoid overheating through increased ventilation and night cooling. Based on this concept, a test system was designed for a fictive office building and its performance was documented using building...

Resource partitioning along multiple niche axes drives functional diversity in parrotfishes on Caribbean coral reefs.

Science.gov (United States)

Adam, Thomas C; Kelley, Megan; Ruttenberg, Benjamin I; Burkepile, Deron E

2015-12-01

The recent loss of key consumers to exploitation and habitat degradation has significantly altered community dynamics and ecosystem function across many ecosystems worldwide. Predicting the impacts of consumer losses requires knowing the level of functional diversity that exists within a consumer assemblage. In this study, we document functional diversity among nine species of parrotfishes on Caribbean coral reefs. Parrotfishes are key herbivores that facilitate the maintenance and recovery of coral-dominated reefs by controlling algae and provisioning space for the recruitment of corals. We observed large functional differences among two genera of parrotfishes that were driven by differences in diet. Fishes in the genus Scarus targeted filamentous algal turf assemblages, crustose coralline algae, and endolithic algae and avoided macroalgae, while fishes in the genus Sparisoma preferentially targeted macroalgae. However, species with similar diets were dissimilar in other attributes, including the habitats they frequented, the types of substrate they fed from, and the spatial scale at which they foraged. These differences indicate that species that appear to be functionally redundant when looking at diet alone exhibit high levels of complementarity when we consider multiple functional traits. By identifying key functional differences among parrotfishes, we provide critical information needed to manage parrotfishes to enhance the resilience of coral-dominated reefs and reverse phase shifts on algal-dominated reefs throughout the wider Caribbean. Further, our study provides a framework for predicting the impacts of consumer losses in other species rich ecosystems.

Effect of elevated substrate temperature deposition on the mechanical losses in tantala thin film coatings

Science.gov (United States)

Vajente, G.; Birney, R.; Ananyeva, A.; Angelova, S.; Asselin, R.; Baloukas, B.; Bassiri, R.; Billingsley, G.; Fejer, M. M.; Gibson, D.; Godbout, L. J.; Gustafson, E.; Heptonstall, A.; Hough, J.; MacFoy, S.; Markosyan, A.; Martin, I. W.; Martinu, L.; Murray, P. G.; Penn, S.; Roorda, S.; Rowan, S.; Schiettekatte, F.; Shink, R.; Torrie, C.; Vine, D.; Reid, S.; Adhikari, R. X.

2018-04-01

Brownian thermal noise in dielectric multilayer coatings limits the sensitivity of current and future interferometric gravitational wave detectors. In this work we explore the possibility of improving the mechanical losses of tantala, often used as the high refractive index material, by depositing it on a substrate held at elevated temperature. Promising results have been previously obtained with this technique when applied to amorphous silicon. We show that depositing tantala on a hot substrate reduced the mechanical losses of the as-deposited coating, but subsequent thermal treatments had a larger impact, as they reduced the losses to levels previously reported in the literature. We also show that the reduction in mechanical loss correlates with increased medium range order in the atomic structure of the coatings using x-ray diffraction and Raman spectroscopy. Finally, a discussion is included on our results, which shows that the elevated temperature deposition of pure tantala coatings does not appear to reduce mechanical loss in a similar way to that reported in the literature for amorphous silicon; and we suggest possible future research directions.

Akinetic Crisis in Parkinson's Disease Is Associated with a Severe Loss of Striatal Dopamine Transporter Function: A Report of Two Cases

Directory of Open Access Journals (Sweden)

Valtteri Kaasinen

2014-11-01

Full Text Available Akinetic crisis or acute akinesia is a life-threatening complication of Parkinson's disease (PD with unknown pathophysiological mechanisms. Clinically, it resembles the neuroleptic malignant syndrome, and dopaminergic drugs are transiently ineffective in the acute phase of the condition. There are no published dopaminergic functional imaging studies on PD patients with akinetic crisis. Here we report 2 advanced PD patients with akinetic crisis who were scanned with SPECT using brain dopamine transporter ligand [123I]FP-CIT. The first patient was additionally scanned before the condition developed, and the second patient was scanned after recovery. Striatal dopamine transporter binding was lower during than before the crisis, and both patients showed a nearly complete loss of dopamine transporter binding during the crisis. Serial imaging showed that the uptake remained negligible despite an improvement in motor function after recovery. Akinetic crisis in PD appears to be associated with a particularly severe loss of presynaptic striatal dopamine function that does not improve after recovery. Apart from presynaptic dopaminergic function, other dopaminergic or nondopaminergic mechanisms are involved in the clinical improvement of motor functions after akinetic crisis in PD.

Metal uptake and acute toxicity in zebrafish: Common mechanisms across multiple metals

Energy Technology Data Exchange (ETDEWEB)

Alsop, Derek, E-mail: alsopde@mcmaster.ca [Department of Biology, McMaster University, 1280 Main St. W., Hamilton, ON L8S 4K1 (Canada); Wood, Chris M. [Department of Biology, McMaster University, 1280 Main St. W., Hamilton, ON L8S 4K1 (Canada)

2011-10-15

All metals tested reduced calcium uptake in zebrafish larvae. However, it was whole body sodium loss that was functionally related to toxicity. The zebrafish larvae acute toxicity assay save time, space and resources. - Abstract: Zebrafish larvae (Danio rerio) were used to examine the mechanisms of action and acute toxicities of metals. Larvae had similar physiological responses and sensitivities to waterborne metals as adults. While cadmium and zinc have previously been shown to reduce Ca{sup 2+} uptake, copper and nickel also decreased Ca{sup 2+} uptake, suggesting that the epithelial transport of all these metals is through Ca{sup 2+} pathways. However, exposure to cadmium, copper or nickel for up to 48 h had little or no effect on total whole body Ca{sup 2+} levels, indicating that the reduction of Ca{sup 2+} uptake is not the acute toxic mechanism of these metals. Instead, mortalities were effectively related to whole body Na{sup +}, which decreased up to 39% after 48 h exposures to different metals around their respective 96 h LC50s. Decreases in whole body K{sup +} were also observed, although they were not as pronounced or frequent as Na{sup +} losses. None of the metals tested inhibited Na{sup +} uptake in zebrafish (Na{sup +} uptake was in fact increased with exposure) and the observed losses of Na{sup +}, K{sup +}, Ca{sup 2+} and Mg{sup 2+} were proportional to the ionic gradients between the plasma and water, indicating diffusive ion loss with metal exposure. This study has shown that there is a common pathway for metal uptake and a common mechanism of acute toxicity across groups of metals in zebrafish. The disruption of ion uptake accompanying metal exposure does not appear to be responsible for the acute toxicity of metals, as has been previously suggested, but rather the toxicity is instead due to total ion loss (predominantly Na{sup +}).

QUALITY LOSS FUNCTION FOR MACHINING PROCESS ACCURACY

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Adrian Stere PARIS

2017-05-01

Full Text Available The main goal of the paper is to propose new quality loss models for machining process accuracy in the classical case “zero the best”, MMF and Harris type. In addition a numerical example illustrates that the choose regression functions are directly linked with the quality loss of manufacturing process. The proposed models can be adapted for the “maximal the best” and “nominal the best” cases.

On some properties of bone functional adaptation phenomenon useful in mechanical design.

Science.gov (United States)

Nowak, Michał

2010-01-01

The paper discusses some unique properties of trabecular bone functional adaptation phenomenon, useful in mechanical design. On the basis of the biological process observations and the principle of constant strain energy density on the surface of the structure, the generic structural optimisation system has been developed. Such approach allows fulfilling mechanical theorem for the stiffest design, comprising the optimisations of size, shape and topology, using the concepts known from biomechanical studies. Also the biomimetic solution of multiple load problems is presented.

Asymptotic functions and multiplication of distributions

International Nuclear Information System (INIS)

Todorov, T.D.

1979-01-01

Considered is a new type of generalized asymptotic functions, which are not functionals on some space of test functions as the Schwartz distributions. The definition of the generalized asymptotic functions is given. It is pointed out that in future the particular asymptotic functions will be used for solving some topics of quantum mechanics and quantum theory

MULTIPLE LINEAR REGRESSION ANALYSIS FOR PREDICTION OF BOILER LOSSES AND BOILER EFFICIENCY

OpenAIRE

Chayalakshmi C.L

2018-01-01

MULTIPLE LINEAR REGRESSION ANALYSIS FOR PREDICTION OF BOILER LOSSES AND BOILER EFFICIENCY ABSTRACT Calculation of boiler efficiency is essential if its parameters need to be controlled for either maintaining or enhancing its efficiency. But determination of boiler efficiency using conventional method is time consuming and very expensive. Hence, it is not recommended to find boiler efficiency frequently. The work presented in this paper deals with establishing the statistical mo...

Heat loss mechanisms in a measurement of specific heat capacity of graphite

International Nuclear Information System (INIS)

Shipley, D.R.; Duane, S.

1996-01-01

Absorbed dose to graphite in electron beams with nominal energies in the range 3-20 MeV is determined by measuring the temperature rise in the core of a primary standard graphite calorimeter. This temperature rise is related to absorbed dose by a separate measurement of the specific heat capacity of the graphite core. There is, however, a small but significant amount of heat loss from the sample in the determination of specific heat capacity and corrections for these losses are required. This report discusses the sources of heat loss in the measurements and, where possible, provides estimates for the magnitude of these losses. For those mechanisms which are significant, a more realistic model of the measurement system is analysed and corrections for the losses are provided. (UK)

Relative Contributions of Various Cellular Mechanisms to Loss of Algae during Cnidarian Bleaching.

Science.gov (United States)

Bieri, Tamaki; Onishi, Masayuki; Xiang, Tingting; Grossman, Arthur R; Pringle, John R

2016-01-01

When exposed to stress such as high seawater temperature, corals and other cnidarians can bleach due to loss of symbiotic algae from the host tissue and/or loss of pigments from the algae. Although the environmental conditions that trigger bleaching are reasonably well known, its cellular and molecular mechanisms are not well understood. Previous studies have reported the occurrence of at least four different cellular mechanisms for the loss of symbiotic algae from the host tissue: in situ degradation of algae, exocytic release of algae from the host, detachment of host cells containing algae, and death of host cells containing algae. The relative contributions of these several mechanisms to bleaching remain unclear, and it is also not known whether these relative contributions change in animals subjected to different types and/or durations of stresses. In this study, we used a clonal population of the small sea anemone Aiptasia, exposed individuals to various precisely controlled stress conditions, and quantitatively assessed the several possible bleaching mechanisms in parallel. Under all stress conditions tested, except for acute cold shock at 4°C, expulsion of intact algae from the host cells appeared to be by far the predominant mechanism of bleaching. During acute cold shock, in situ degradation of algae and host-cell detachment also became quantitatively significant, and the algae released under these conditions appeared to be severely damaged.

Relative Contributions of Various Cellular Mechanisms to Loss of Algae during Cnidarian Bleaching

Science.gov (United States)

Bieri, Tamaki; Onishi, Masayuki; Xiang, Tingting; Grossman, Arthur R.; Pringle, John R

2016-01-01

When exposed to stress such as high seawater temperature, corals and other cnidarians can bleach due to loss of symbiotic algae from the host tissue and/or loss of pigments from the algae. Although the environmental conditions that trigger bleaching are reasonably well known, its cellular and molecular mechanisms are not well understood. Previous studies have reported the occurrence of at least four different cellular mechanisms for the loss of symbiotic algae from the host tissue: in situ degradation of algae, exocytic release of algae from the host, detachment of host cells containing algae, and death of host cells containing algae. The relative contributions of these several mechanisms to bleaching remain unclear, and it is also not known whether these relative contributions change in animals subjected to different types and/or durations of stresses. In this study, we used a clonal population of the small sea anemone Aiptasia, exposed individuals to various precisely controlled stress conditions, and quantitatively assessed the several possible bleaching mechanisms in parallel. Under all stress conditions tested, except for acute cold shock at 4°C, expulsion of intact algae from the host cells appeared to be by far the predominant mechanism of bleaching. During acute cold shock, in situ degradation of algae and host-cell detachment also became quantitatively significant, and the algae released under these conditions appeared to be severely damaged. PMID:27119147

TDP-43 loss of function increases TFEB activity and blocks autophagosome-lysosome fusion.

Science.gov (United States)

Xia, Qin; Wang, Hongfeng; Hao, Zongbing; Fu, Cheng; Hu, Qingsong; Gao, Feng; Ren, Haigang; Chen, Dong; Han, Junhai; Ying, Zheng; Wang, Guanghui

2016-01-18

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that is characterized by selective loss of motor neurons in brain and spinal cord. TAR DNA-binding protein 43 (TDP-43) was identified as a major component of disease pathogenesis in ALS, frontotemporal lobar degeneration (FTLD), and other neurodegenerative disease. Despite the fact that TDP-43 is a multi-functional protein involved in RNA processing and a large number of TDP-43 RNA targets have been discovered, the initial toxic effect and the pathogenic mechanism underlying TDP-43-linked neurodegeneration remain elusive. In this study, we found that loss of TDP-43 strongly induced a nuclear translocation of TFEB, the master regulator of lysosomal biogenesis and autophagy, through targeting the mTORC1 key component raptor. This regulation in turn enhanced global gene expressions in the autophagy-lysosome pathway (ALP) and increased autophagosomal and lysosomal biogenesis. However, loss of TDP-43 also impaired the fusion of autophagosomes with lysosomes through dynactin 1 downregulation, leading to accumulation of immature autophagic vesicles and overwhelmed ALP function. Importantly, inhibition of mTORC1 signaling by rapamycin treatment aggravated the neurodegenerative phenotype in a TDP-43-depleted Drosophila model, whereas activation of mTORC1 signaling by PA treatment ameliorated the neurodegenerative phenotype. Taken together, our data indicate that impaired mTORC1 signaling and influenced ALP may contribute to TDP-43-mediated neurodegeneration. © 2015 The Authors.

On the loss function of the Bank of Canada: A note

DEFF Research Database (Denmark)

Stadtmann, Georg; Pierdzioch; Ruelke

2012-01-01

Based on the approach advanced by Elliott et al. [Elliott, G., Komunjer, I., Timmermann, A., 2005. Estimation and testing of forecast rationality under flexible loss. Review of Economic Studies 72, 1107–1125], we studied whether the inflation and output growth projections published by the Bank...... of Canada are consistent with an asymmetric loss function. Current-year projections provide no signs of asymmetry, but next-year projections do. The hypothesis of rationality of the projections can be rejected under symmetric loss, but not under asymmetric loss....

Unified Sequence-Based Association Tests Allowing for Multiple Functional Annotations and Meta-analysis of Noncoding Variation in Metabochip Data.

Science.gov (United States)

He, Zihuai; Xu, Bin; Lee, Seunggeun; Ionita-Laza, Iuliana

2017-09-07

Substantial progress has been made in the functional annotation of genetic variation in the human genome. Integrative analysis that incorporates such functional annotations into sequencing studies can aid the discovery of disease-associated genetic variants, especially those with unknown function and located outside protein-coding regions. Direct incorporation of one functional annotation as weight in existing dispersion and burden tests can suffer substantial loss of power when the functional annotation is not predictive of the risk status of a variant. Here, we have developed unified tests that can utilize multiple functional annotations simultaneously for integrative association analysis with efficient computational techniques. We show that the proposed tests significantly improve power when variant risk status can be predicted by functional annotations. Importantly, when functional annotations are not predictive of risk status, the proposed tests incur only minimal loss of power in relation to existing dispersion and burden tests, and under certain circumstances they can even have improved power by learning a weight that better approximates the underlying disease model in a data-adaptive manner. The tests can be constructed with summary statistics of existing dispersion and burden tests for sequencing data, therefore allowing meta-analysis of multiple studies without sharing individual-level data. We applied the proposed tests to a meta-analysis of noncoding rare variants in Metabochip data on 12,281 individuals from eight studies for lipid traits. By incorporating the Eigen functional score, we detected significant associations between noncoding rare variants in SLC22A3 and low-density lipoprotein and total cholesterol, associations that are missed by standard dispersion and burden tests. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Towards identifying the mechanisms underlying field-aligned edge-loss of HHFW power on NSTX

International Nuclear Information System (INIS)

Perkins, R. J.; Bell, R. E.; Bertelli, N.; Diallo, A.; Gerhardt, S.; Hosea, J. C.; Jaworski, M. A.; LeBlanc, B. P.; Kramer, G. J.; Maingi, R.; Phillips, C. K.; Podestà, M.; Roquemore, L.; Scotti, F.; Taylor, G.; Wilson, J. R.; Ahn, J-W.; Gray, T. K.; Green, D. L.; McLean, A.

2014-01-01

Fast-wave heating will be a major heating scheme on ITER, as it can heat ions directly and is relatively unaffected by the large machine size unlike neutral beams. However, fast-wave interactions with the plasma edge can lead to deleterious effects such as, in the case of the high-harmonic fast-wave (HHFW) system on NSTX, large losses of fast-wave power in the scrape off layer (SOL) under certain conditions. In such scenarios, a large fraction of the lost HHFW power is deposited on the upper and lower divertors in bright spiral shapes. The responsible mechanism(s) has not yet been identified but may include fast-wave propagation in the scrape off layer, parametric decay instability, and RF currents driven by the antenna reactive fields. Understanding and mitigating these losses is important not only for improving the heating and current-drive on NSTX-Upgrade but also for understanding fast-wave propagation across the SOL in any fast-wave system. This talk summarizes experimental results demonstrating that the flow of lost HHFW power to the divertor regions largely follows the open SOL magnetic field lines. This lost power flux is relatively large close to both the antenna and the last closed flux surface with a reduced level in between, so the loss mechanism cannot be localized to the antenna. At the same time, significant losses also occur along field lines connected to the inboard edge of the bottom antenna plate. The power lost within the spirals is roughly estimated, showing that these field-aligned losses to the divertor are significant but may not account for the total HHFW loss. To elucidate the role of the onset layer for perpendicular fast-wave propagation with regards to fast-wave propagation in the SOL, a cylindrical cold-plasma model is being developed. This model, in addition to advanced RF codes such as TORIC and AORSA, is aimed at identifying the underlying mechanism(s) behind these SOL losses, to minimize their effects in NSTX-U, and to predict

Towards identifying the mechanisms underlying field-aligned edge-loss of HHFW power on NSTX

Energy Technology Data Exchange (ETDEWEB)

Perkins, R. J.; Bell, R. E.; Bertelli, N.; Diallo, A.; Gerhardt, S.; Hosea, J. C.; Jaworski, M. A.; LeBlanc, B. P.; Kramer, G. J.; Maingi, R.; Phillips, C. K.; Podestà, M.; Roquemore, L.; Scotti, F.; Taylor, G.; Wilson, J. R. [Princeton Plasma Physics Laboratory, Princeton, NJ (United States); Ahn, J-W.; Gray, T. K.; Green, D. L.; McLean, A. [Oak Ridge National Laboratory, Oak Ridge, TN (United States); and others

2014-02-12

Fast-wave heating will be a major heating scheme on ITER, as it can heat ions directly and is relatively unaffected by the large machine size unlike neutral beams. However, fast-wave interactions with the plasma edge can lead to deleterious effects such as, in the case of the high-harmonic fast-wave (HHFW) system on NSTX, large losses of fast-wave power in the scrape off layer (SOL) under certain conditions. In such scenarios, a large fraction of the lost HHFW power is deposited on the upper and lower divertors in bright spiral shapes. The responsible mechanism(s) has not yet been identified but may include fast-wave propagation in the scrape off layer, parametric decay instability, and RF currents driven by the antenna reactive fields. Understanding and mitigating these losses is important not only for improving the heating and current-drive on NSTX-Upgrade but also for understanding fast-wave propagation across the SOL in any fast-wave system. This talk summarizes experimental results demonstrating that the flow of lost HHFW power to the divertor regions largely follows the open SOL magnetic field lines. This lost power flux is relatively large close to both the antenna and the last closed flux surface with a reduced level in between, so the loss mechanism cannot be localized to the antenna. At the same time, significant losses also occur along field lines connected to the inboard edge of the bottom antenna plate. The power lost within the spirals is roughly estimated, showing that these field-aligned losses to the divertor are significant but may not account for the total HHFW loss. To elucidate the role of the onset layer for perpendicular fast-wave propagation with regards to fast-wave propagation in the SOL, a cylindrical cold-plasma model is being developed. This model, in addition to advanced RF codes such as TORIC and AORSA, is aimed at identifying the underlying mechanism(s) behind these SOL losses, to minimize their effects in NSTX-U, and to predict

Weight-loss changes PPAR expression, reduces atherosclerosis and improves cardiovascular function in obese insulin-resistant mice

Energy Technology Data Exchange (ETDEWEB)

Verreth, Wim; Verhamme, Peter; Pelat, Michael; Ganame, Javier; Bielicki, John K.; Mertens, Ann; Quarck, Rozenn; Benhabiles, Nora; Marguerie, Gerard; Mackness, Bharti; Mackness, Mike; Ninio, Ewa; Herregods, Marie-Christine; Balligand, Jean-Luc; Holvoet, Paul

2003-09-01

Weight-loss in obese insulin-resistant, but not in insulin-sensitive, persons reduces CHD risk. It is not known to what extent changes in the adipose gene expression profile are important for reducing CHD risk. We studied the effect of diet restriction-induced weight-loss on gene expression in adipose tissue, atherosclerosis and cardiovascular function in mice with combined leptin and LDL-receptor deficiency. Obesity, hypertriglyceridemia and insulin-resistance are associated with hypertension, impaired left ventricle function and accelerated atherosclerosis in those mice. Diet restriction during 12 weeks caused a 45% weight-loss and changes in the gene expression in adipose tissue of PPARa and PPAR? and of key genes regulating glucose transport and insulin sensitivity, lipid metabolism, oxidative stress and inflammation, most of which are under the transcriptional control of PPARs. These changes were associated with increased insulin-sensitivity, decreased hypertriglyceridemia, reduced mean 24-hour blood pressure and heart rate, restored circadian variations of blood pressure and heart rate, increased ejection fraction, and reduced atherosclerosis. Thus, induction of PPARa and PPAR? in adipose tissue is a key mechanism for reducing atherosclerosis and improving cardiovascular function resulting from weight-loss. Our observations point to the critical role of PPARs in the pathogenesis of cardiovascular features of the metabolic syndrome.

Snails and their trails: the multiple functions of trail-following in gastropods.

Science.gov (United States)

Ng, Terence P T; Saltin, Sara H; Davies, Mark S; Johannesson, Kerstin; Stafford, Richard; Williams, Gray A

2013-08-01

Snails are highly unusual among multicellular animals in that they move on a layer of costly mucus, leaving behind a trail that can be followed and utilized for various purposes by themselves or by other animals. Here we review more than 40 years of experimental and theoretical research to try to understand the ecological and evolutionary rationales for trail-following in gastropods. Data from over 30 genera are currently available, representing a broad taxonomic range living in both aquatic and terrestrial environments. The emerging picture is that the production of mucus trails, which initially was an adaptation to facilitate locomotion and/or habitat extension, has evolved to facilitate a multitude of additional functions. Trail-following supports homing behaviours, and provides simple mechanisms for self-organisation in groups of snails, promoting aggregation and thus relieving desiccation and predation pressures. In gastropods that copulate, trail-following is an important component in mate-searching, either as an alternative, or in addition to the release of water- or air-borne pheromones. In some species, this includes a capacity of males not only to identify trails of conspecifics but also to discriminate between trails laid by females and males. Notably, trail discrimination seems important as a pre-zygotic barrier to mating in some snail species. As production of a mucus trail is the most costly component of snail locomotion, it is also tempting to speculate that evolution has given rise to various ways to compensate for energy losses. Some snails, for example, increase energy intake by eating particles attached to the mucus of trails that they follow, whereas others save energy through reducing the production of their own mucus by moving over previously laid mucus trails. Trail-following to locate a prey item or a mate is also a way to save energy. While the rationale for trail-following in many cases appears clear, the basic mechanisms of trail

Comparing population exposure to multiple Washington earthquake scenarios for prioritizing loss estimation studies

Science.gov (United States)

Wood, Nathan J.; Ratliff, Jamie L.; Schelling, John; Weaver, Craig S.

2014-01-01

Scenario-based, loss-estimation studies are useful for gauging potential societal impacts from earthquakes but can be challenging to undertake in areas with multiple scenarios and jurisdictions. We present a geospatial approach using various population data for comparing earthquake scenarios and jurisdictions to help emergency managers prioritize where to focus limited resources on data development and loss-estimation studies. Using 20 earthquake scenarios developed for the State of Washington (USA), we demonstrate how a population-exposure analysis across multiple jurisdictions based on Modified Mercalli Intensity (MMI) classes helps emergency managers understand and communicate where potential loss of life may be concentrated and where impacts may be more related to quality of life. Results indicate that certain well-known scenarios may directly impact the greatest number of people, whereas other, potentially lesser-known, scenarios impact fewer people but consequences could be more severe. The use of economic data to profile each jurisdiction’s workforce in earthquake hazard zones also provides additional insight on at-risk populations. This approach can serve as a first step in understanding societal impacts of earthquakes and helping practitioners to efficiently use their limited risk-reduction resources.

Diffuse nitrogen loss simulation and impact assessment of stereoscopic agriculture pattern by integrated water system model and consideration of multiple existence forms

Science.gov (United States)

Zhang, Yongyong; Gao, Yang; Yu, Qiang

2017-09-01

Agricultural nitrogen loss becomes an increasingly important source of water quality deterioration and eutrophication, even threatens water safety for humanity. Nitrogen dynamic mechanism is still too complicated to be well captured at watershed scale due to its multiple existence forms and instability, disturbance of agricultural management practices. Stereoscopic agriculture is a novel agricultural planting pattern to efficiently use local natural resources (e.g., water, land, sunshine, heat and fertilizer). It is widely promoted as a high yield system and can obtain considerable economic benefits, particularly in China. However, its environmental quality implication is not clear. In our study, Qianyanzhou station is famous for its stereoscopic agriculture pattern of Southern China, and an experimental watershed was selected as our study area. Regional characteristics of runoff and nitrogen losses were simulated by an integrated water system model (HEQM) with multi-objective calibration, and multiple agriculture practices were assessed to find the effective approach for the reduction of diffuse nitrogen losses. Results showed that daily variations of runoff and nitrogen forms were well reproduced throughout watershed, i.e., satisfactory performances for ammonium and nitrate nitrogen (NH4-N and NO3-N) loads, good performances for runoff and organic nitrogen (ON) load, and very good performance for total nitrogen (TN) load. The average loss coefficient was 62.74 kg/ha for NH4-N, 0.98 kg/ha for NO3-N, 0.0004 kg/ha for ON and 63.80 kg/ha for TN. The dominating form of nitrogen losses was NH4-N due to the applied fertilizers, and the most dramatic zones aggregated in the middle and downstream regions covered by paddy and orange orchard. In order to control diffuse nitrogen losses, the most effective practices for Qianyanzhou stereoscopic agriculture pattern were to reduce farmland planting scale in the valley by afforestation, particularly for orchard in the

The relationships between cognitive function and hearing loss among the elderly.

Science.gov (United States)

Huh, MyungJin

2018-01-01

[Purpose] Research related to dementia has gained momentum in South Korea and studies have found that the auditory sense affects dementia. This study aims to examine the relationship between the decline in hearing function and the overall cognitive function among the elderly. [Subjects and Methods] Eighty-two older adults aged 65-90 years (mean age: 79.3, SD: 5.2) participated. The Korean Mini-Mental State Examination was used to assess cognitive function. Further, to assess the hearing function, pure-tone audiometry was performed prior to the cognitive function test. We used a paired t-test and Pearson's correlation test for the analysis. [Results] Generally, the higher the frequency band, the more hearing loss was identified among the elderly. In addition, the difference in hearing between both ears was significant; particularly, hearing loss in the right ear was significantly higher than that in the left. Cognitive function was not related to age, however, the correlation between cognitive function and hearing loss in the right ear was statistically significant. [Conclusion] Hearing loss influences cognitive function among the elderly.

Energy loss mechanism for suspended micro- and nanoresonators due to the Casimir force

OpenAIRE

Gusso, André

2011-01-01

A so far not considered energy loss mechanism in suspended micro- and nanoresonators due to noncontact acoustical energy loss is investigated theoretically. The mechanism consists on the conversion of the mechanical energy from the vibratory motion of the resonator into acoustic waves on large nearby structures, such as the substrate, due to the coupling between the resonator and those structures resulting from the Casimir force acting over the separation gaps. Analytical expressions for the ...

SEARCHING FOR ELECTRICAL PROPERTIES, PHENOMENA AND MECHANISMS IN THE CONSTRUCTION AND FUNCTION OF CHROMOSOMES

Directory of Open Access Journals (Sweden)

Ivan Kanev

2013-03-01

Full Text Available Our studies reveal previously unidentified electrical properties of chromosomes: (1 chromosomes are amazingly similar in construction and function to electrical transformers; (2 chromosomes possess in their construction and function, components similar to those of electric generators, conductors, condensers, switches, and other components of electrical circuits; (3 chromosomes demonstrate in nano-scale level electromagnetic interactions, resonance, fusion and other phenomena similar to those described by equations in classical physics. These electrical properties and phenomena provide a possible explanation for unclear and poorly understood mechanisms in clinical genetics including: (a electrically based mechanisms responsible for breaks, translocations, fusions, and other chromosomal abnormalities associated with cancer, intellectual disability, infertility, pregnancy loss, Down syndrome, and other genetic disorders; (b electrically based mechanisms involved in crossing over, non-disjunction and other events during meiosis and mitosis; (c mechanisms demonstrating heterochromatin to be electrically active and genetically important.

Loss of mass and performance in skeletal muscle tissue: a continuum model

Directory of Open Access Journals (Sweden)

Giantesio Giulia

2018-02-01

Full Text Available We present a continuum hyperelastic model which describes the mechanical response of a skeletal muscle tissue when its strength and mass are reduced by aging. Such a reduction is typical of a geriatric syndrome called sarcopenia. The passive behavior of the material is described by a hyperelastic, polyconvex, transversely isotropic strain energy function, and the activation of the muscle is modeled by the so called active strain approach. The loss of ability of activating of an elder muscle is then obtained by lowering of some percentage the active part of the stress, while the loss of mass is modeled through a multiplicative decomposition of the deformation gradient. The obtained stress-strain relations are graphically represented and discussed in order to study some of the effects of sarcopenia.

Loss-of-function analyses of the fragile X-related and dopamine receptor genes by RNA interference in the cricket Gryllus bimaculatus.

Science.gov (United States)

Hamada, Aska; Miyawaki, Katsuyuki; Honda-sumi, Eri; Tomioka, Kenji; Mito, Taro; Ohuchi, Hideyo; Noji, Sumihare

2009-08-01

In order to explore a possibility that the cricket Gryllus bimaculatus would be a useful model to unveil molecular mechanisms of human diseases, we performed loss-of-function analyses of Gryllus genes homologous to human genes that are responsible for human disorders, fragile X mental retardation 1 (fmr1) and Dopamine receptor (DopR). We cloned cDNAs of their Gryllus homologues, Gb'fmr1, Gb'DopRI, and Gb'DopRII, and analyzed their functions with use of nymphal RNA interference (RNAi). For Gb'fmr1, three major phenotypes were observed: (1) abnormal wing postures, (2) abnormal calling song, and (3) loss of the circadian locomotor rhythm, while for Gb'DopRI, defects of wing posture and morphology were found. These results indicate that the cricket has the potential to become a novel model system to explore human neuronal pathogenic mechanisms and to screen therapeutic drugs by RNAi. Copyright (c) 2009 Wiley-Liss, Inc.

Weight loss improves biomarkers endothelial function and systemic ...

African Journals Online (AJOL)

Background: Although postmenopausal associated disorders are important public health problems worldwide, to date limited studies evaluated the endothelial function and systemic inflammation response to weight loss in obese postmenopausal women. Objective: This study was done to evaluate the endothelial function ...

Loss of laminin alpha 1 results in multiple structural defects and divergent effects on adhesion during vertebrate optic cup morphogenesis

Science.gov (United States)

Bryan, Chase D.; Chien, Chi-Bin; Kwan, Kristen M.

2016-01-01

The vertebrate eye forms via a complex set of morphogenetic events. The optic vesicle evaginates and undergoes transformative shape changes to form the optic cup, in which neural retina and retinal pigmented epithelium enwrap the lens. It has long been known that a complex, glycoprotein-rich extracellular matrix layer surrounds the developing optic cup throughout the process, yet the functions of the matrix and its specific molecular components have remained unclear. Previous work established a role for laminin extracellular matrix in particular steps of eye development, including optic vesicle evagination, lens differentiation, and retinal ganglion cell polarization, yet it is unknown what role laminin might play in the early process of optic cup formation subsequent to the initial step of optic vesicle evagination. Here, we use the zebrafish lama1 mutant (lama1UW1) to determine the function of laminin during optic cup morphogenesis. Using live imaging, we find, surprisingly, that loss of laminin leads to divergent effects on focal adhesion assembly in a spatiotemporally-specific manner, and that laminin is required for multiple steps of optic cup morphogenesis, including optic stalk constriction, invagination, and formation of a spherical lens. Laminin is not required for single cell behaviors and changes in cell shape. Rather, in lama1UW1 mutants, loss of epithelial polarity and altered adhesion lead to defective tissue architecture and formation of a disorganized retina. These results demonstrate that the laminin extracellular matrix plays multiple critical roles regulating adhesion and polarity to establish and maintain tissue structure during optic cup morphogenesis. PMID:27339294

Rapid genome reshaping by multiple-gene loss after whole-genome duplication in teleost fish suggested by mathematical modeling

Science.gov (United States)

Sato, Yukuto; Tsukamoto, Katsumi; Nishida, Mutsumi

2015-01-01

Whole-genome duplication (WGD) is believed to be a significant source of major evolutionary innovation. Redundant genes resulting from WGD are thought to be lost or acquire new functions. However, the rates of gene loss and thus temporal process of genome reshaping after WGD remain unclear. The WGD shared by all teleost fish, one-half of all jawed vertebrates, was more recent than the two ancient WGDs that occurred before the origin of jawed vertebrates, and thus lends itself to analysis of gene loss and genome reshaping. Using a newly developed orthology identification pipeline, we inferred the post–teleost-specific WGD evolutionary histories of 6,892 protein-coding genes from nine phylogenetically representative teleost genomes on a time-calibrated tree. We found that rapid gene loss did occur in the first 60 My, with a loss of more than 70–80% of duplicated genes, and produced similar genomic gene arrangements within teleosts in that relatively short time. Mathematical modeling suggests that rapid gene loss occurred mainly by events involving simultaneous loss of multiple genes. We found that the subsequent 250 My were characterized by slow and steady loss of individual genes. Our pipeline also identified about 1,100 shared single-copy genes that are inferred to have become singletons before the divergence of clupeocephalan teleosts. Therefore, our comparative genome analysis suggests that rapid gene loss just after the WGD reshaped teleost genomes before the major divergence, and provides a useful set of marker genes for future phylogenetic analysis. PMID:26578810

Gain and loss of function of ALS-related mutations of TARDBP (TDP-43) cause motor deficits in vivo.

Science.gov (United States)

Kabashi, Edor; Lin, Li; Tradewell, Miranda L; Dion, Patrick A; Bercier, Valérie; Bourgouin, Patrick; Rochefort, Daniel; Bel Hadj, Samar; Durham, Heather D; Vande Velde, Christine; Rouleau, Guy A; Drapeau, Pierre

2010-02-15

TDP-43 has been found in inclusion bodies of multiple neurological disorders, including amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson's disease and Alzheimer's disease. Mutations in the TDP-43 encoding gene, TARDBP, have been subsequently reported in sporadic and familial ALS patients. In order to investigate the pathogenic nature of these mutants, the effects of three consistently reported TARDBP mutations (A315T, G348C and A382T) were tested in cell lines, primary cultured motor neurons and living zebrafish embryos. Each of the three mutants and wild-type (WT) human TDP-43 localized to nuclei when expressed in COS1 and Neuro2A cells by transient transfection. However, when expressed in motor neurons from dissociated spinal cord cultures these mutant TARDBP alleles, but less so for WT TARDBP, were neurotoxic, concomitant with perinuclear localization and aggregation of TDP-43. Finally, overexpression of mutant, but less so of WT, human TARDBP caused a motor phenotype in zebrafish (Danio rerio) embryos consisting of shorter motor neuronal axons, premature and excessive branching as well as swimming deficits. Interestingly, knock-down of zebrafisfh tardbp led to a similar phenotype, which was rescued by co-expressing WT but not mutant human TARDBP. Together these approaches showed that TARDBP mutations cause motor neuron defects and toxicity, suggesting that both a toxic gain of function as well as a novel loss of function may be involved in the molecular mechanism by which mutant TDP-43 contributes to disease pathogenesis.

Mediators of Physical Activity on Neurocognitive Function: A Review at Multiple Levels of Analysis.

Science.gov (United States)

Stillman, Chelsea M; Cohen, Jamie; Lehman, Morgan E; Erickson, Kirk I

2016-01-01

Physical activity (PA) is known to maintain and improve neurocognitive health. However, there is still a poor understanding of the mechanisms by which PA exerts its effects on the brain and cognition in humans. Many of the most widely discussed mechanisms of PA are molecular and cellular and arise from animal models. While information about basic cellular and molecular mechanisms is an important foundation from which to build our understanding of how PA promotes cognitive health in humans, there are other pathways that could play a role in this relationship. For example, PA-induced changes to cellular and molecular pathways likely initiate changes to macroscopic properties of the brain and/or to behavior that in turn influence cognition. The present review uses a more macroscopic lens to identify potential brain and behavioral/socioemotional mediators of the association between PA and cognitive function. We first summarize what is known regarding cellular and molecular mechanisms, and then devote the remainder of the review to discussing evidence for brain systems and behavioral/socioemotional pathways by which PA influences cognition. It is our hope that discussing mechanisms at multiple levels of analysis will stimulate the field to examine both brain and behavioral mediators. Doing so is important, as it could lead to a more complete characterization of the processes by which PA influences neurocognitive function, as well as a greater variety of targets for modifying neurocognitive function in clinical contexts.

Mediators of Physical Activity on Neurocognitive Function: A Review at Multiple Levels of Analysis

Directory of Open Access Journals (Sweden)

Chelsea M. Stillman

2016-12-01

Full Text Available Physical activity (PA is known to maintain and improve neurocognitive health. However, there is still a poor understanding of the mechanisms by which PA exerts its effects on the brain and cognition in humans. Many of the most widely discussed mechanisms of PA are molecular and cellular and arise from animal models. While information about basic cellular and molecular mechanisms is an important foundation from which to build our understanding of how PA promotes cognitive health in humans, there are other pathways that could play a role in this relationship. For example, PA-induced changes to cellular and molecular pathways likely initiate changes to macroscopic properties of the brain and/or to behavior that in turn influence cognition. The present review uses a more macroscopic lens to identify potential brain and behavioral/socioemotional mediators of the association between PA and cognitive function. We first summarize what is known regarding cellular and molecular mechanisms, and then devote the remainder of the review to discussing evidence for brain systems and behavioral/socioemotional pathways by which PA influences cognition. It is our hope that discussing mechanisms at multiple levels of analysis will stimulate the field to examine both brain and behavioral mediators. Doing so is important, as it could lead to a more complete characterization of the processes by which PA influences neurocognitive function, as well as a greater variety of targets for modifying neurocognitive function in clinical contexts.

Loss of renal function causes premature aging of the immune system.

Science.gov (United States)

Betjes, Michiel G H; Meijers, Ruud W J; Litjens, Nicolle H R

2013-01-01

Uremia-associated immune deficiency is a well-known complication of loss of renal function and contributes significantly to the overall mortality and morbidity of patients with end-stage renal disease. Chronic inflammation and increased oxidative stress are underlying the uremia-associated immune deficiency. In this review, the differential impact of uremia on the cellular immune system is summarized. Virtually all immune cells studied show a combination of an activated status and loss of function. However, uremia preferentially decreases the number and function of lymphoid cells while myeloid cells show normal and/or elevated cell numbers with increased production of inflammatory cytokines and reactive oxygen species. These particular changes are compatible with immunological aging, which is characterized by loss of thymic function, attrition of telomeres and an expanded memory T cell population. Similar to aging in healthy individuals, the proinflammatory and potential cardiotoxic subsets of CD28(null) T cells and CD16(+) monocytes are increased. Epigenetically changed hematopoietic stem cells may be involved in immunological aging as specific DNA regions become hypermethylated. Proinflammatory T cells and monocytes persist after kidney transplantation, which constitutes a persistent cardiovascular risk factor. Possible therapeutic options to reverse or halt uremia-associated immunological aging are discussed. Premature aging of the immune system is a dominant feature in patients with end-stage renal failure, which corresponds to immunological aging in elderly healthy individuals, which is characterized by preferential loss of cells belonging to the lymphoid cell lineage, inflammation and expansion of proinflammatory immune cells. © 2013 S. Karger AG, Basel.

Contribution of mechanical unloading to trabecular bone loss following non-invasive knee injury in mice.

Science.gov (United States)

Anderson, Matthew J; Diko, Sindi; Baehr, Leslie M; Baar, Keith; Bodine, Sue C; Christiansen, Blaine A

2016-10-01

Development of osteoarthritis commonly involves degeneration of epiphyseal trabecular bone. In previous studies, we observed 30-44% loss of epiphyseal trabecular bone (BV/TV) from the distal femur within 1 week following non-invasive knee injury in mice. Mechanical unloading (disuse) may contribute to this bone loss; however, it is unclear to what extent the injured limb is unloaded following injury, and whether disuse can fully account for the observed magnitude of bone loss. In this study, we investigated the contribution of mechanical unloading to trabecular bone changes observed following non-invasive knee injury in mice (female C57BL/6N). We investigated changes in gait during treadmill walking, and changes in voluntary activity level using Open Field analysis at 4, 14, 28, and 42 days post-injury. We also quantified epiphyseal trabecular bone using μCT and weighed lower-limb muscles to quantify atrophy following knee injury in both ground control and hindlimb unloaded (HLU) mice. Gait analysis revealed a slightly altered stride pattern in the injured limb, with a decreased stance phase and increased swing phase. However, Open Field analysis revealed no differences in voluntary movement between injured and sham mice at any time point. Both knee injury and HLU resulted in comparable magnitudes of trabecular bone loss; however, HLU resulted in considerably more muscle loss than knee injury, suggesting another mechanism contributing to bone loss following injury. Altogether, these data suggest that mechanical unloading likely contributes to trabecular bone loss following non-invasive knee injury, but the magnitude of this bone loss cannot be fully explained by disuse. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1680-1687, 2016. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Linkage mechanisms in the vertebrate skull: Structure and function of three-dimensional, parallel transmission systems.

Science.gov (United States)

Olsen, Aaron M; Westneat, Mark W

2016-12-01

Many musculoskeletal systems, including the skulls of birds, fishes, and some lizards consist of interconnected chains of mobile skeletal elements, analogous to linkage mechanisms used in engineering. Biomechanical studies have applied linkage models to a diversity of musculoskeletal systems, with previous applications primarily focusing on two-dimensional linkage geometries, bilaterally symmetrical pairs of planar linkages, or single four-bar linkages. Here, we present new, three-dimensional (3D), parallel linkage models of the skulls of birds and fishes and use these models (available as free kinematic simulation software), to investigate structure-function relationships in these systems. This new computational framework provides an accessible and integrated workflow for exploring the evolution of structure and function in complex musculoskeletal systems. Linkage simulations show that kinematic transmission, although a suitable functional metric for linkages with single rotating input and output links, can give misleading results when applied to linkages with substantial translational components or multiple output links. To take into account both linear and rotational displacement we define force mechanical advantage for a linkage (analogous to lever mechanical advantage) and apply this metric to measure transmission efficiency in the bird cranial mechanism. For linkages with multiple, expanding output points we propose a new functional metric, expansion advantage, to measure expansion amplification and apply this metric to the buccal expansion mechanism in fishes. Using the bird cranial linkage model, we quantify the inaccuracies that result from simplifying a 3D geometry into two dimensions. We also show that by combining single-chain linkages into parallel linkages, more links can be simulated while decreasing or maintaining the same number of input parameters. This generalized framework for linkage simulation and analysis can accommodate linkages of differing

Mouse Models for Pendrin-Associated Loss of Cochlear and Vestibular Function

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Philine Wangemann

2013-12-01

Full Text Available The human gene SLC26A4 and the mouse ortholog Slc26a4 code for the protein pendrin, which is an anion exchanger expressed in apical membranes of selected epithelia. In the inner ear, pendrin is expressed in the cochlea, the vestibular labyrinth and the endolymphatic sac. Loss-of-function and hypo-functional mutations cause an enlargement of the vestibular aqueduct (EVA and sensorineural hearing loss. The relatively high prevalence of SLC26A4 mutations provides a strong imperative to develop rational interventions that delay, ameliorate or prevent pendrin-associated loss of cochlear and vestibular function. This review summarizes recent studies in mouse models that have been developed to delineate the role of pendrin in the physiology of hearing and balance and that have brought forward the concept that a temporally and spatially limited therapy may be sufficient to secure a life-time of normal hearing in children bearing mutations of SLC26A4.

Modal loss mechanism of micro-structured VCSELs studied using full vector FDTD method.

Science.gov (United States)

Jo, Du-Ho; Vu, Ngoc Hai; Kim, Jin-Tae; Hwang, In-Kag

2011-09-12

Modal properties of vertical cavity surface-emitting lasers (VCSELs) with holey structures are studied using a finite difference time domain (FDTD) method. We investigate loss behavior with respect to the variation of structural parameters, and explain the loss mechanism of VCSELs. We also propose an effective method to estimate the modal loss based on mode profiles obtained using FDTD simulation. Our results could provide an important guideline for optimization of the microstructures of high-power single-mode VCSELs.

Electrolyte loss mechanism of molten carbonate fuel cells. 1; Yoyu tansan`engata nenryo denchi ni okeru denkaishitsu loss kiko ni tsuite. 1

Energy Technology Data Exchange (ETDEWEB)

Sonai, A; Murata, K [Toshiba Research and Development Center, Kawasaki (Japan)

1993-11-01

During a single-cell disassembly test of molten carbonate fuel cells having been operated for 90 hours to 5500 hours, correlativity was discovered between decrease in the retained amount of electrolyte due to decrease in pore capacity of electrodes and electrolyte plates and the electrolyte loss. The electrolyte loss amount cannot be explained with the conventional mechanisms, thereby a new model was proposed. The cathode has shown very little change in the capacity change in pores with diameters smaller than 2 {mu}m per unit area. The anode has remained almost constant after 1000 hours, but the electrolyte plates have shown remarkable decrease. Therefore, it is possible to estimate that the electrolyte plates should have been the major cause for the electrolyte loss. The result of measuring the electrolyte loss amount agreed well with that estimated using pore capacity curves. This fact suggests that the electrolyte loss can be explained by a new mechanism that hypothesizes the existence of a largest size of retaining pores that can support carbonates and defines that the electrolyte loss is generated from decrease in the pore capacity. 7 refs., 8 figs., 1 tab.

Mechanisms of telomere loss and their consequences for chromosome instability

International Nuclear Information System (INIS)

Muraki, Keiko; Nyhan, Kristine; Han, Limei; Murnane, John P.

2012-01-01

The ends of chromosomes in mammals, called telomeres, are composed of a 6-bp repeat sequence, TTAGGG, which is added on by the enzyme telomerase. In combination with a protein complex called shelterin, these telomeric repeat sequences form a cap that protects the ends of chromosomes. Due to insufficient telomerase expression, telomeres shorten gradually with each cell division in human somatic cells, which limits the number of times they can divide. The extensive cell division involved in cancer cell progression therefore requires that cancer cells must acquire the ability to maintain telomeres, either through expression of telomerase, or through an alternative mechanism involving recombination. It is commonly thought that the source of many chromosome rearrangements in cancer cells is a result of the extensive telomere shortening that occurs prior to the expression of telomerase. However, despite the expression of telomerase, tumor cells can continue to show chromosome instability due to telomere loss. Dysfunctional telomeres in cancer cells can result from oncogene-induced replication stress, which results in double-strand breaks (DSBs) at fragile sites, including telomeres. DSBs near telomeres are especially prone to chromosome rearrangements, because telomeric regions are deficient in DSB repair. The deficiency in DSB repair near telomeres is also an important mechanism for ionizing radiation-induced replicative senescence in normal human cells. In addition, DSBs near telomeres can result in chromosome instability in mouse embryonic stem cells, suggesting that telomere loss can contribute to heritable chromosome rearrangements. Consistent with this possibility, telomeric regions in humans are highly heterogeneous, and chromosome rearrangements near telomeres are commonly involved in human genetic disease. Understanding the mechanisms of telomere loss will therefore provide important insights into both human cancer and genetic disease.

Mechanisms of telomere loss and their consequences for chromosome instability

Directory of Open Access Journals (Sweden)

Keiko eMuraki

2012-10-01

Full Text Available The ends of chromosomes in mammals, called telomeres, are composed of a 6 base pair repeat sequence, TTAGGG, which is added on by the enzyme telomerase. In combination with a protein complex called shelterin, these telomeric repeat sequences form a cap that protects the ends of chromosomes. Due to insufficient telomerase expression, telomeres shorten gradually with each cell division in human somatic cells, which limits the number of times they can divide. The extensive cell division involved in cancer cell progression therefore requires that cancer cells must acquire the ability to maintain telomeres, either through expression of telomerase, or through an alternative mechanism involving recombination. It is commonly thought that the source of many chromosome rearrangements in cancer cells is a result of the extensive telomere shortening that occurs prior to the expression of telomerase. However, despite the expression of telomerase, tumor cells can continue to show chromosome instability due to telomere loss. Dysfunctional telomeres in cancer cells can result from oncogene-induced replication stress, which results in double-strand breaks (DSBs at fragile sites, including telomeres. DSBs near telomeres are especially prone to chromosome rearrangements, because telomeric regions are deficient in DSB repair. The deficiency in DSB repair near telomeres is also an important mechanism for ionizing radiation-induced replicative senescence in normal human cells. In addition, DSBs near telomeres can result in chromosome instability in mouse embryonic stem cells, suggesting that telomere loss can contribute to heritable chromosome rearrangements. Consistent with this possibility, telomeric regions in humans are highly heterogeneous, and chromosome rearrangements near telomeres are commonly involved in human genetic disease. Understanding the mechanisms of telomere loss will therefore provide important insights into both human cancer and genetic disease.

Mechanisms of telomere loss and their consequences for chromosome instability

Energy Technology Data Exchange (ETDEWEB)

Muraki, Keiko; Nyhan, Kristine; Han, Limei; Murnane, John P., E-mail: jmurnane@radonc.ucsf.edu [Department of Radiation Oncology, University of California at San Francisco, San Francisco, CA (United States)

2012-10-04

The ends of chromosomes in mammals, called telomeres, are composed of a 6-bp repeat sequence, TTAGGG, which is added on by the enzyme telomerase. In combination with a protein complex called shelterin, these telomeric repeat sequences form a cap that protects the ends of chromosomes. Due to insufficient telomerase expression, telomeres shorten gradually with each cell division in human somatic cells, which limits the number of times they can divide. The extensive cell division involved in cancer cell progression therefore requires that cancer cells must acquire the ability to maintain telomeres, either through expression of telomerase, or through an alternative mechanism involving recombination. It is commonly thought that the source of many chromosome rearrangements in cancer cells is a result of the extensive telomere shortening that occurs prior to the expression of telomerase. However, despite the expression of telomerase, tumor cells can continue to show chromosome instability due to telomere loss. Dysfunctional telomeres in cancer cells can result from oncogene-induced replication stress, which results in double-strand breaks (DSBs) at fragile sites, including telomeres. DSBs near telomeres are especially prone to chromosome rearrangements, because telomeric regions are deficient in DSB repair. The deficiency in DSB repair near telomeres is also an important mechanism for ionizing radiation-induced replicative senescence in normal human cells. In addition, DSBs near telomeres can result in chromosome instability in mouse embryonic stem cells, suggesting that telomere loss can contribute to heritable chromosome rearrangements. Consistent with this possibility, telomeric regions in humans are highly heterogeneous, and chromosome rearrangements near telomeres are commonly involved in human genetic disease. Understanding the mechanisms of telomere loss will therefore provide important insights into both human cancer and genetic disease.

Flood loss modelling with FLF-IT: a new flood loss function for Italian residential structures

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R. Hasanzadeh Nafari

2017-07-01

Full Text Available The damage triggered by different flood events costs the Italian economy millions of euros each year. This cost is likely to increase in the future due to climate variability and economic development. In order to avoid or reduce such significant financial losses, risk management requires tools which can provide a reliable estimate of potential flood impacts across the country. Flood loss functions are an internationally accepted method for estimating physical flood damage in urban areas. In this study, we derived a new flood loss function for Italian residential structures (FLF-IT, on the basis of empirical damage data collected from a recent flood event in the region of Emilia-Romagna. The function was developed based on a new Australian approach (FLFA, which represents the confidence limits that exist around the parameterized functional depth–damage relationship. After model calibration, the performance of the model was validated for the prediction of loss ratios and absolute damage values. It was also contrasted with an uncalibrated relative model with frequent usage in Europe. In this regard, a three-fold cross-validation procedure was carried out over the empirical sample to measure the range of uncertainty from the actual damage data. The predictive capability has also been studied for some sub-classes of water depth. The validation procedure shows that the newly derived function performs well (no bias and only 10 % mean absolute error, especially when the water depth is high. Results of these validation tests illustrate the importance of model calibration. The advantages of the FLF-IT model over other Italian models include calibration with empirical data, consideration of the epistemic uncertainty of data, and the ability to change parameters based on building practices across Italy.

Flood loss modelling with FLF-IT: a new flood loss function for Italian residential structures

Science.gov (United States)

Hasanzadeh Nafari, Roozbeh; Amadio, Mattia; Ngo, Tuan; Mysiak, Jaroslav

2017-07-01

The damage triggered by different flood events costs the Italian economy millions of euros each year. This cost is likely to increase in the future due to climate variability and economic development. In order to avoid or reduce such significant financial losses, risk management requires tools which can provide a reliable estimate of potential flood impacts across the country. Flood loss functions are an internationally accepted method for estimating physical flood damage in urban areas. In this study, we derived a new flood loss function for Italian residential structures (FLF-IT), on the basis of empirical damage data collected from a recent flood event in the region of Emilia-Romagna. The function was developed based on a new Australian approach (FLFA), which represents the confidence limits that exist around the parameterized functional depth-damage relationship. After model calibration, the performance of the model was validated for the prediction of loss ratios and absolute damage values. It was also contrasted with an uncalibrated relative model with frequent usage in Europe. In this regard, a three-fold cross-validation procedure was carried out over the empirical sample to measure the range of uncertainty from the actual damage data. The predictive capability has also been studied for some sub-classes of water depth. The validation procedure shows that the newly derived function performs well (no bias and only 10 % mean absolute error), especially when the water depth is high. Results of these validation tests illustrate the importance of model calibration. The advantages of the FLF-IT model over other Italian models include calibration with empirical data, consideration of the epistemic uncertainty of data, and the ability to change parameters based on building practices across Italy.

Mechanisms and mechanics of shape loss during supersolidus liquid-phase sintering

Science.gov (United States)

Lal, Anand

Rapid sinter densification of relatively coarse prealloyed powders is possible by exceeding the solidus temperature in an approach termed supersolidus liquid phase sintering (SLPS). However, narrow processing windows for densification without distortion often limit this process. The liquid films at the grain boundaries that are responsible for densification also reduce the structural rigidity of components. Hence, components tend to slump under their own weight. Thus, the present study investigates shape loss during SLPS and rationalizes the processing and material factors with regard to separating densification from distortion. Experiments are performed on various prealloyed powders, including bronze, 316L stainless steel, and T15 tool steel. Differential thermal analysis, dilatometry, and in situ video imaging of sintering compacts are used to follow melting, densification, and distortion, respectively. Further, density and dimensional measurements are performed on sintered compacts. Results indicate a dependence of distortion on the sintering temperature and time, compact size, and melting behavior of the alloy. It is shown that the sintering temperature window, where high-density, precise components are obtained, can be widened for 316L stainless steel by boron addition. For the first time, a beam bending technique is used to measure the macroscopic apparent viscosity of semisolid bronze. The viscosity drops with temperature above the solidus and lies in the range of 108 to 106 Pa-s. Additionally, the in situ transverse rupture strength of bronze is measured to demonstrate the softening above the solidus temperature. Further, microstructural measurements are performed to enable correlation with the slumping behavior and viscosity. A model combining the deformation mechanisms, driving forces, and microstructural characteristics is developed to predict the conditions for densification and distortion onset. The microstructure is also correlated with the magnitude

Allocation and management issues in multiple-transaction open access transmission networks

Science.gov (United States)

Tao, Shu

This thesis focuses on some key issues related to allocation and management by the independent grid operator (IGO) of unbundled services in multiple-transaction open access transmission networks. The three unbundled services addressed in the thesis are transmission real power losses, reactive power support requirements from generation sources, and transmission congestion management. We develop the general framework that explicitly represents multiple transactions undertaken simultaneously in the transmission grid. This framework serves as the basis for formulating various problems treated in the thesis. We use this comprehensive framework to develop a physical-flow-based mechanism to allocate the total transmission losses to each transaction using the system. An important property of the allocation scheme is its capability to effectively deal with counter flows that result in the presence of specific transactions. Using the loss allocation results as the basis, we construct the equivalent loss compensation concept and apply it to develop flexible and effective procedures for compensating losses in multiple-transaction networks. We present a new physical-flow-based mechanism for allocating the reactive power support requirements provided by generators in multiple-transaction networks. The allocatable reactive support requirements are formulated as the sum of two specific components---the voltage magnitude variation component and the voltage angle variation component. The formulation utilizes the multiple-transaction framework and makes use of certain simplifying approximations. The formulation leads to a natural allocation as a function of the amount of each transaction. The physical interpretation of each allocation as a sensitivity of the reactive output of a generator is discussed. We propose a congestion management allocation scheme for multiple-transaction networks. The proposed scheme determines the allocation of congestion among the transactions on a physical

Brain mechanisms for loss of awareness of thought and movement

Science.gov (United States)

Oakley, David A.; Halligan, Peter W.; Mehta, Mitul A.; Deeley, Quinton

2017-01-01

Abstract Loss or reduction of awareness is common in neuropsychiatric disorders and culturally influenced dissociative phenomena but the underlying brain mechanisms are poorly understood. fMRI was combined with suggestions for automatic writing in 18 healthy highly hypnotically suggestible individuals in a within-subjects design to determine whether clinical alterations in awareness of thought and movement can be experimentally modelled and studied independently of illness. Subjective ratings of control, ownership, and awareness of thought and movement, and fMRI data were collected following suggestions for thought insertion and alien control of writing movement, with and without loss of awareness. Subjective ratings confirmed that suggestions were effective. At the neural level, our main findings indicated that loss of awareness for both thought and movement during automatic writing was associated with reduced activation in a predominantly left-sided posterior cortical network including BA 7 (superior parietal lobule and precuneus), and posterior cingulate cortex, involved in self-related processing and awareness of the body in space. Reduced activity in posterior parietal cortices may underlie specific clinical and cultural alterations in awareness of thought and movement. Clinically, these findings may assist development of imaging assessments for loss of awareness of psychological origin, and interventions such as neurofeedback. PMID:28338742

Titanium Dioxide Nanoparticles Trigger Loss of Function and Perturbation of Mitochondrial Dynamics in Primary Hepatocytes.

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Vaishaali Natarajan

Full Text Available Titanium dioxide (TiO2 nanoparticles are one of the most highly manufactured and employed nanomaterials in the world with applications in copious industrial and consumer products. The liver is a major accumulation site for many nanoparticles, including TiO2, directly through intentional exposure or indirectly through unintentional ingestion via water, food or animals and increased environmental contamination. Growing concerns over the current usage of TiO2 coupled with the lack of mechanistic understanding of its potential health risk is the motivation for this study. Here we determined the toxic effect of three different TiO2 nanoparticles (commercially available rutile, anatase and P25 on primary rat hepatocytes. Specifically, we evaluated events related to hepatocyte functions and mitochondrial dynamics: (1 urea and albumin synthesis using colorimetric and ELISA assays, respectively; (2 redox signaling mechanisms by measuring reactive oxygen species (ROS production, manganese superoxide dismutase (MnSOD activity and mitochondrial membrane potential (MMP; (3 OPA1 and Mfn-1 expression that mediates the mitochondrial dynamics by PCR; and (4 mitochondrial morphology by MitoTracker Green FM staining. All three TiO2 nanoparticles induced a significant loss (p < 0.05 in hepatocyte functions even at concentrations as low as 50 ppm with commercially used P25 causing maximum damage. TiO2 nanoparticles induced a strong oxidative stress in primary hepatocytes. TiO2 nanoparticles exposure also resulted in morphological changes in mitochondria and substantial loss in the fusion process, thus impairing the mitochondrial dynamics. Although this study demonstrated that TiO2 nanoparticles exposure resulted in substantial damage to primary hepatocytes, more in vitro and in vivo studies are required to determine the complete toxicological mechanism in primary hepatocytes and subsequently liver function.

Carrier loss mechanisms in textured crystalline Si-based solar cells

OpenAIRE

Nakane, Akihiro; Fujimoto, Shohei; Fujiwara, Hiroyuki

2017-01-01

A quite general device analysis method that allows the direct evaluation of optical and recombination losses in crystalline silicon (c-Si)-based solar cells has been developed. By applying this technique, the optical and physical limiting factors of the state-of-the-art solar cells with ~20% efficiencies have been revealed. In the established method, the carrier loss mechanisms are characterized from the external quantum efficiency (EQE) analysis with very low computational cost. In particula...

Microstructural response and grain refinement mechanism of commercially pure titanium subjected to multiple laser shock peening impacts

International Nuclear Information System (INIS)

Lu, J.Z.; Wu, L.J.; Sun, G.F.; Luo, K.Y.; Zhang, Y.K.; Cai, J.; Cui, C.Y.; Luo, X.M.

2017-01-01

The microstructural response and grain subdivision process in commercially pure (CP) titanium subjected to multiple laser shock peening (LSP) impacts were investigated by means of optical microscopy (OM), scanning electron microscopy (SEM) and transmission electron microscopy (TEM) observations. The micro-hardness curves as a function of the impact time were also determined. The deformation-induced grain refinement mechanism of the close-packed hexagonal (hcp) material by laser shock wave was subsequently analyzed. Experimental results showed that uniform equiaxed grains with an average size of less than 50 nm were generated due to the ultra-high plastic strain induced by multiple LSP impacts. Special attention was paid to four types of novel deformation-induced microstructural features, including a layered slip band in the tension deformation zone, and inverse-transformation martensite, micro-twin grating and micro-twin collision in the compression deformation zone. Furthermore, the grain refinement mechanism in the near-surface layer of CP titanium subjected to multiple LSP impacts contains two types of simultaneous subdivision modes: multi-directional mechanical twin (MT)-MT intersections at (sub)micrometer scale, and the intersection between longitudinal secondary MTs and transverse dislocation walls at nanometer scale. In addition, both grain refinement (nanocrystallization) and the existence of a small amount of inverse-transformation martensite induced by multiple LSP impacts contribute to an increase in the micro-hardness of the near-surface layer.

P2X7 receptor regulates osteoclast function and bone loss in a mouse model of osteoporosis.

Science.gov (United States)

Wang, Ning; Agrawal, Ankita; Jørgensen, Niklas Rye; Gartland, Alison

2018-02-22

Post-menopausal osteoporosis is a condition that affects millions worldwide and places a huge socio-economic burden on society. Previous research has shown an association of loss of function SNPs in the gene for the purinergic receptor P2X7R with low bone mineral density, increased rates of bone loss and vertebral fractures in post-menopausal women. In this study we use a mouse model of oestrogen deficiency-induced bone loss and the BALB/cJ P2X7R -/- to show that absence of the P2X7R resulted in increased bone loss. Osteoclast precursors were isolated from both BALB/cJ P2X7R -/- and BALB/cJ P2X7R +/+ mice and then cultured in vitro to form mature resorbing osteoclasts. The BALB/cJ P2X7R -/- derived precursors generated slightly more osteoclasts but with a significant reduction in the amount of resorption per osteoclast. Furthermore, when using modified culture conditions osteoclast activity was additionally increased in the absence of the P2X7R suggest that P2X7R may regulate the lifespan and activity of osteoclasts. Finally using mechanical loading as an anabolic stimulus for bone formation, we demonstrated that the increased oestrogen-deficient bone loss could be rescued, even in the absence of P2X7R. This study paves the way for clinical intervention for women with post-menopausal osteoporosis and P2XR7 loss of function polymorphisms.

The Role of Mechanical Stimulation in Recovery of Bone Loss-High versus Low Magnitude and Frequency of Force.

Science.gov (United States)

Nagaraja, Mamta Patel; Jo, Hanjoong

2014-04-02

Musculoskeletal pathologies associated with decreased bone mass, including osteoporosis and disuse-induced bone loss, affect millions of Americans annually. Microgravity-induced bone loss presents a similar concern for astronauts during space missions. Many pharmaceutical treatments have slowed osteoporosis, and recent data shows promise for countermeasures for bone loss observed in astronauts. Additionally, high magnitude and low frequency impact such as running has been recognized to increase bone and muscle mass under normal but not microgravity conditions. However, a low magnitude and high frequency (LMHF) mechanical load experienced in activities such as postural control, has also been shown to be anabolic to bone. While several clinical trials have demonstrated that LMHF mechanical loading normalizes bone loss in vivo, the target tissues and cells of the mechanical load and underlying mechanisms mediating the responses are unknown. In this review, we provide an overview of bone adaptation under a variety of loading profiles and the potential for a low magnitude loading as a way to counteract bone loss as experienced by astronauts.

Loss of positional information when tracking multiple moving dots: the role of visual memory.

Science.gov (United States)

Narasimhan, Sathyasri; Tripathy, Srimant P; Barrett, Brendan T

2009-01-01

Pylyshyn, Z.W. and Storm, R.W. (1988) (Tracking multiple independent targets: Evidence for a parallel tracking mechanism. Spatial Vision, 3(3), 179-197) proposed that human observers could simultaneously track up to five dots when presented with an array of dots moving in a random manner. In contrast, Tripathy, S.P., and Barrett, B.T. (2004) (Severe loss of positional information when detecting deviations in multiple trajectories. Journal of Vision, 4(12):4, 1020-1043, http://journalofvision.org/4/14/4/, doi: 10.1167/4.12.4) showed that when a threshold paradigm was employed, observers' ability to track deviations in straight-line trajectories is severely compromised when attending to two or more dots. In this study we present a series of four experiments that investigates the role of attention and visual memory while tracking deviations in multiple trajectories using a threshold paradigm. Our stimuli consisted of several linear, non-parallel, left-to-right trajectories, each moving at the same speed. At the trajectory mid-point (reached simultaneously by all dots), one of the dots (target) deviated clockwise or counter-clockwise. The observers' task was to identify the direction of deviation. The target trajectory was cued in the second half of the trial either by disappearance of distractors at the monitor's mid-line (Experiment 1) or by means of a change in colour of the target (Experiment 2); in both cases deviation thresholds rose steeply when the number of distractor trajectories was increased from 0 (typical threshold approximately 2 degrees) to 3 (typical threshold>20 degrees). When all the trajectories were presented statically in a single frame (Experiment 3), thresholds for identifying the orientation change of the target trajectory remained relatively unchanged as the number of distractor trajectories was increased. When a temporal delay of a few hundred milliseconds was introduced between the first and second halves of trajectories (Experiment 4

Target genes of myostatin loss-of-function in muscles of late bovine fetuses

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Hocquette Jean-François

2007-03-01

Full Text Available Abstract Background Myostatin, a muscle-specific member of the Transforming Growth Factor beta family, negatively regulates muscle development. Double-muscled (DM cattle have a loss-of-function mutation in their myostatin gene responsible for the hypermuscular phenotype. Thus, these animals are a good model for understanding the mechanisms underpinning muscular hypertrophy. In order to identify individual genes or networks that may be myostatin targets, we looked for genes that were differentially expressed between DM and normal (NM animals (n = 3 per group in the semitendinosus muscle (hypertrophied in DM animals at 260 days of fetal development (when the biochemical differentiation of muscle is intensive. A heterologous microarray (human and murine oligonucleotide sequences of around 6,000 genes expressed in muscle was used. Results Many genes were found to be differentially expressed according to genetic type (some with a more than 5-fold change, and according to the presence of one or two functional myostatin allele(s. They belonged to various functional categories. The genes down-regulated in DM fetuses were mainly those encoding extracellular matrix proteins, slow contractile proteins and ribosomal proteins. The genes up-regulated in DM fetuses were mainly involved in the regulation of transcription, cell cycle/apoptosis, translation or DNA metabolism. These data highlight features indicating that DM muscle is shifted towards a more glycolytic metabolism, and has an altered extracellular matrix composition (e.g. down-regulation of COL1A1 and COL1A2, and up-regulation of COL4A2 and decreased adipocyte differentiation (down-regulation of C1QTNF3. The altered gene expression in the three major muscle compartments (fibers, connective tissue and intramuscular adipose tissue is consistent with the well-known characteristics of DM cattle. In addition, novel potential targets of the myostatin gene were identified (MB, PLN, troponins, ZFHX1B

Multiple environment single system quantum mechanical/molecular mechanical (MESS-QM/MM) calculations. 1. Estimation of polarization energies.

Science.gov (United States)

Sodt, Alexander J; Mei, Ye; König, Gerhard; Tao, Peng; Steele, Ryan P; Brooks, Bernard R; Shao, Yihan

2015-03-05

In combined quantum mechanical/molecular mechanical (QM/MM) free energy calculations, it is often advantageous to have a frozen geometry for the quantum mechanical (QM) region. For such multiple-environment single-system (MESS) cases, two schemes are proposed here for estimating the polarization energy: the first scheme, termed MESS-E, involves a Roothaan step extrapolation of the self-consistent field (SCF) energy; whereas the other scheme, termed MESS-H, employs a Newton-Raphson correction using an approximate inverse electronic Hessian of the QM region (which is constructed only once). Both schemes are extremely efficient, because the expensive Fock updates and SCF iterations in standard QM/MM calculations are completely avoided at each configuration. They produce reasonably accurate QM/MM polarization energies: MESS-E can predict the polarization energy within 0.25 kcal/mol in terms of the mean signed error for two of our test cases, solvated methanol and solvated β-alanine, using the M06-2X or ωB97X-D functionals; MESS-H can reproduce the polarization energy within 0.2 kcal/mol for these two cases and for the oxyluciferin-luciferase complex, if the approximate inverse electronic Hessians are constructed with sufficient accuracy.

A mutation in the heparin-binding site of noggin as a novel mechanism of proximal symphalangism and conductive hearing loss.

Science.gov (United States)

Masuda, Sawako; Namba, Kazunori; Mutai, Hideki; Usui, Satoko; Miyanaga, Yuko; Kaneko, Hiroki; Matsunaga, Tatsuo

2014-05-09

The access of bone morphogenetic protein (BMP) to the BMP receptors on the cell surface is regulated by its antagonist noggin, which binds to heparan-sulfate proteoglycans on the cell surface. Noggin is encoded by NOG and mutations in the gene are associated with aberrant skeletal formation, such as in the autosomal dominant disorders proximal symphalangism (SYM1), multiple synostoses syndrome, Teunissen-Cremers syndrome, and tarsal-carpal coalition syndrome. NOG mutations affecting a specific function may produce a distinct phenotype. In this study, we investigated a Japanese pedigree with SYM1 and conductive hearing loss and found that it carried a novel heterozygous missense mutation of NOG (c.406C>T; p.R136C) affecting the heparin-binding site of noggin. As no mutations of the heparin-binding site of noggin have previously been reported, we investigated the crystal structure of wild-type noggin to investigate molecular mechanism of the p.R136C mutation. We found that the positively charged arginine at position 136 was predicted to be important for binding to the negatively charged heparan-sulfate proteoglycan (HSPG). An in silico docking analysis showed that one of the salt bridges between noggin and heparin disappeared following the replacement of the arginine with a non-charged cysteine. We propose that the decreased binding affinity of NOG with the p.R136C mutation to HSPG leads to an excess of BMP signaling and underlies the SYM1 and conductive hearing loss phenotype of carriers. Copyright © 2014 Elsevier Inc. All rights reserved.

Loss of CIB2 Causes Profound Hearing Loss and Abolishes Mechanoelectrical Transduction in Mice

Directory of Open Access Journals (Sweden)

Yanfei Wang

2017-12-01

Full Text Available Calcium and integrin-binding protein 2 (CIB2 belongs to a protein family with four known members, CIB1 through CIB4, which are characterized by multiple calcium-binding EF-hand domains. Among the family members, the Cib1 and Cib2 genes are expressed in mouse cochlear hair cells, and mutations in the human CIB2 gene have been associated with nonsyndromic deafness DFNB48 and syndromic deafness USH1J. To further explore the function of CIB1 and CIB2 in hearing, we established Cib1 and Cib2 knockout mice using the clustered regularly interspaced short palindromic repeat (CRISPR-associated Cas9 nuclease (CRISPR/Cas9 genome editing technique. We found that loss of CIB1 protein does not affect auditory function, whereas loss of CIB2 protein causes profound hearing loss in mice. Further investigation revealed that hair cell stereocilia development is affected in Cib2 knockout mice. Noticeably, loss of CIB2 abolishes mechanoelectrical transduction (MET currents in auditory hair cells. In conclusion, we show here that although both CIB1 and CIB2 are readily detected in the cochlea, only loss of CIB2 results in profound hearing loss, and that CIB2 is essential for auditory hair cell MET.

Cellular mechanisms of cyclophosphamide-induced taste loss in mice.

Science.gov (United States)

Mukherjee, Nabanita; Pal Choudhuri, Shreoshi; Delay, Rona J; Delay, Eugene R

2017-01-01

Many commonly prescribed chemotherapy drugs such as cyclophosphamide (CYP) have adverse side effects including disruptions in taste which can result in loss of appetite, malnutrition, poorer recovery and reduced quality of life. Previous studies in mice found evidence that CYP has a two-phase disturbance in taste behavior: a disturbance immediately following drug administration and a second which emerges several days later. In this study, we examined the processes by which CYP disturbs the taste system by examining the effects of the drug on taste buds and cells responsible for taste cell renewal using immunohistochemical assays. Data reported here suggest CYP has direct cytotoxic effects on lingual epithelium immediately following administration, causing an early loss of taste sensory cells. Types II and III cells in fungiform taste buds appear to be more susceptible to this effect than circumvallate cells. In addition, CYP disrupts the population of rapidly dividing cells in the basal layer of taste epithelium responsible for taste cell renewal, manifesting a disturbance days later. The loss of these cells temporarily retards the system's capacity to replace Type II and Type III taste sensory cells that survived the cytotoxic effects of CYP and died at the end of their natural lifespan. The timing of an immediate, direct loss of taste cells and a delayed, indirect loss without replacement of taste sensory cells are broadly congruent with previously published behavioral data reporting two periods of elevated detection thresholds for umami and sucrose stimuli. These findings suggest that chemotherapeutic disturbances in the peripheral mechanisms of the taste system may cause dietary challenges at a time when the cancer patient has significant need for well balanced, high energy nutritional intake.

Motivation by potential gains and losses affects control processes via different mechanisms in the attentional network.

Science.gov (United States)

Paschke, Lena M; Walter, Henrik; Steimke, Rosa; Ludwig, Vera U; Gaschler, Robert; Schubert, Torsten; Stelzel, Christine

2015-05-01

Attentional control in demanding cognitive tasks can be improved by manipulating the motivational state. Motivation to obtain gains and motivation to avoid losses both usually result in faster reaction times and stronger activation in relevant brain areas such as the prefrontal cortex, but little is known about differences in the underlying neurocognitive mechanisms of these types of motivation in an attentional control context. In the present functional magnetic resonance imaging (fMRI) study, we tested whether potential gain and loss as motivating incentives lead to overlapping or distinct neural effects in the attentional network, and whether one of these conditions is more effective than the other. A Flanker task with word stimuli as targets and distracters was performed by 115 healthy participants. Using a mixed blocked and event-related design allowed us to investigate transient and sustained motivation-related effects. Participants could either gain money (potential gain) or avoid losing money (potential loss) in different task blocks. Participants showed a congruency effect with increased reaction times for incongruent compared to congruent trials. Potential gain led to generally faster responses compared to the neutral condition and to stronger improvements than potential loss. Potential loss also led to shorter response times compared to the neutral condition, but participants improved mainly during incongruent and not during congruent trials. The event-related fMRI data revealed a main effect of congruency with increased activity in the left inferior frontal gyrus (IFG) and inferior frontal junction area (IFJ), the pre-supplementary motor area (pre-SMA), bilateral insula, intraparietal sulcus (IPS) and visual word form area (VWFA). While potential gain led to increased activity in a cluster of the IFJ and the VWFA only during incongruent trials, potential loss was linked to activity increases in these regions during incongruent and congruent trials. The

Testing for Nonuniform Differential Item Functioning with Multiple Indicator Multiple Cause Models

Science.gov (United States)

Woods, Carol M.; Grimm, Kevin J.

2011-01-01

In extant literature, multiple indicator multiple cause (MIMIC) models have been presented for identifying items that display uniform differential item functioning (DIF) only, not nonuniform DIF. This article addresses, for apparently the first time, the use of MIMIC models for testing both uniform and nonuniform DIF with categorical indicators. A…

The cost of misremembering: Inferring the loss function in visual working memory.

Science.gov (United States)

Sims, Chris R

2015-03-04

Visual working memory (VWM) is a highly limited storage system. A basic consequence of this fact is that visual memories cannot perfectly encode or represent the veridical structure of the world. However, in natural tasks, some memory errors might be more costly than others. This raises the intriguing possibility that the nature of memory error reflects the costs of committing different kinds of errors. Many existing theories assume that visual memories are noise-corrupted versions of afferent perceptual signals. However, this additive noise assumption oversimplifies the problem. Implicit in the behavioral phenomena of visual working memory is the concept of a loss function: a mathematical entity that describes the relative cost to the organism of making different types of memory errors. An optimally efficient memory system is one that minimizes the expected loss according to a particular loss function, while subject to a constraint on memory capacity. This paper describes a novel theoretical framework for characterizing visual working memory in terms of its implicit loss function. Using inverse decision theory, the empirical loss function is estimated from the results of a standard delayed recall visual memory experiment. These results are compared to the predicted behavior of a visual working memory system that is optimally efficient for a previously identified natural task, gaze correction following saccadic error. Finally, the approach is compared to alternative models of visual working memory, and shown to offer a superior account of the empirical data across a range of experimental datasets. © 2015 ARVO.

Ethylbenzene-induced hearing loss, neurobehavioral function, and neurotransmitter alterations in petrochemical workers.

Science.gov (United States)

Zhang, Ming; Wang, Yanrang; Wang, Qian; Yang, Deyi; Zhang, Jingshu; Wang, Fengshan; Gu, Qing

2013-09-01

To estimate hearing loss, neurobehavioral function, and neurotransmitter alteration induced by ethylbenzene in petrochemical workers. From two petrochemical plants, 246 and 307 workers exposed to both ethylbenzene and noise were recruited-290 workers exposed to noise only from a power station plant and 327 office personnel as control group, respectively. Hearing and neurobehavioral functions were evaluated. Serum neurotransmitters were also determined. The prevalence of hearing loss was much higher in petrochemical groups than that in power station and control groups (P workers (P hearing loss, neurobehavioral function impairment, and imbalance of neurotransmitters.

Identification of LHC beam loss mechanism: a deterministic treatment of loss patterns

International Nuclear Information System (INIS)

Marsili, A.

2012-01-01

The goal of this work was to identify patterns in the beam loss profiles, both in their spatial distribution and time evolution. CERN's Large Hadron Collider (LHC) is the largest device ever built, with a total circumference of 26.7 km; and it is the most powerful accelerator ever, both in beam energy and beam intensity. The main magnets are superconducting, and contain the particles into two counter circulating beams which collide in four interaction points. CERN and the LHC will be described in chapter 1. The superconducting magnets of the LHC have to be protected against particle losses. Depending on the number of lost particles, the coils of the magnets could become normal conducting and/or will be damaged. To avoid these events a beam loss monitoring (BLM) system was installed to measure the particle loss rates. If the predefined safe thresholds of loss rates are exceeded, the beams are directed out of the accelerator ring towards the beam dump. The detectors of the BLM system are mainly ionization chambers located outside of the cryostats. In total, about 3600 ionisation chambers are installed. Further challenges include the high dynamical range of losses (chamber currents ranging between 2 pA and 1 mA). The BLM system will be further described in chapter 2. The subject of this thesis is to study the loss patterns and nd the origin of the losses in a deterministic way, by comparing measured losses to well understood loss scenarios. This is done through a case study: different techniques were used on a restrained set of loss scenarios, as a proof of concept of the possibility to extract information from a loss profile. Finding the origin of the losses should allow acting in response. A justification of the doctoral work will be given at the end of chapter 2. This thesis will then focus on the theoretical understanding and the implementation of the decomposition of a measured loss profile as a linear combination of the reference scenarios; and the evaluation of

Simulation of electron energy loss spectra of nanomaterials with linear-scaling density functional theory

International Nuclear Information System (INIS)

Tait, E W; Payne, M C; Ratcliff, L E; Haynes, P D; Hine, N D M

2016-01-01

Experimental techniques for electron energy loss spectroscopy (EELS) combine high energy resolution with high spatial resolution. They are therefore powerful tools for investigating the local electronic structure of complex systems such as nanostructures, interfaces and even individual defects. Interpretation of experimental electron energy loss spectra is often challenging and can require theoretical modelling of candidate structures, which themselves may be large and complex, beyond the capabilities of traditional cubic-scaling density functional theory. In this work, we present functionality to compute electron energy loss spectra within the onetep linear-scaling density functional theory code. We first demonstrate that simulated spectra agree with those computed using conventional plane wave pseudopotential methods to a high degree of precision. The ability of onetep to tackle large problems is then exploited to investigate convergence of spectra with respect to supercell size. Finally, we apply the novel functionality to a study of the electron energy loss spectra of defects on the (1 0 1) surface of an anatase slab and determine concentrations of defects which might be experimentally detectable. (paper)

Ganglion cell loss in relation to visual disability in multiple sclerosis.

Science.gov (United States)

Walter, Scott D; Ishikawa, Hiroshi; Galetta, Kristin M; Sakai, Reiko E; Feller, Daniel J; Henderson, Sam B; Wilson, James A; Maguire, Maureen G; Galetta, Steven L; Frohman, Elliot; Calabresi, Peter A; Schuman, Joel S; Balcer, Laura J

2012-06-01

We used high-resolution spectral-domain optical coherence tomography (SD-OCT) with retinal segmentation to determine how ganglion cell loss relates to history of acute optic neuritis (ON), retinal nerve fiber layer (RNFL) thinning, visual function, and vision-related quality of life (QOL) in multiple sclerosis (MS). Cross-sectional study. A convenience sample of patients with MS (n = 122; 239 eyes) and disease-free controls (n = 31; 61 eyes). Among MS eyes, 87 had a history of ON before enrollment. The SD-OCT images were captured using Macular Cube (200×200 or 512×128) and ONH Cube 200×200 protocols. Retinal layer segmentation was performed using algorithms established for glaucoma studies. Thicknesses of the ganglion cell layer/inner plexiform layer (GCL+IPL), RNFL, outer plexiform/inner nuclear layers (OPL+INL), and outer nuclear/photoreceptor layers (ONL+PRL) were measured and compared in MS versus control eyes and MS ON versus non-ON eyes. The relation between changes in macular thickness and visual disability was also examined. The OCT measurements of GCL+IPL and RNFL thickness; high contrast visual acuity (VA); low-contrast letter acuity (LCLA) at 2.5% and 1.25% contrast; on the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) and 10-Item Neuro-Ophthalmic Supplement composite score. Macular RNFL and GCL+IPL were significantly decreased in MS versus control eyes (Pvisual function and vision-specific QOL in MS, and may serve as a useful structural marker of disease. Our findings parallel those of magnetic resonance imaging studies that show gray matter disease is a marker of neurologic disability in MS. Proprietary or commercial disclosure may be found after the references. Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Multiple sclerosis : Mechanisms of myelin phagocytosis and lesion expansion

NARCIS (Netherlands)

Hendrickx, D.A.E.

2018-01-01

Multiple sclerosis (MS) is characterized by immune activation and focal demyelination in the central nervous system. The aim of this thesis was to gain more insight into the mechanisms of myelin phagocytosis by resident microglia and infiltrating macrophages. We first evaluated the expression of the

Cellular mechanisms of cyclophosphamide-induced taste loss in mice

Science.gov (United States)

Mukherjee, Nabanita; Pal Choudhuri, Shreoshi; Delay, Rona J.

2017-01-01

Many commonly prescribed chemotherapy drugs such as cyclophosphamide (CYP) have adverse side effects including disruptions in taste which can result in loss of appetite, malnutrition, poorer recovery and reduced quality of life. Previous studies in mice found evidence that CYP has a two-phase disturbance in taste behavior: a disturbance immediately following drug administration and a second which emerges several days later. In this study, we examined the processes by which CYP disturbs the taste system by examining the effects of the drug on taste buds and cells responsible for taste cell renewal using immunohistochemical assays. Data reported here suggest CYP has direct cytotoxic effects on lingual epithelium immediately following administration, causing an early loss of taste sensory cells. Types II and III cells in fungiform taste buds appear to be more susceptible to this effect than circumvallate cells. In addition, CYP disrupts the population of rapidly dividing cells in the basal layer of taste epithelium responsible for taste cell renewal, manifesting a disturbance days later. The loss of these cells temporarily retards the system’s capacity to replace Type II and Type III taste sensory cells that survived the cytotoxic effects of CYP and died at the end of their natural lifespan. The timing of an immediate, direct loss of taste cells and a delayed, indirect loss without replacement of taste sensory cells are broadly congruent with previously published behavioral data reporting two periods of elevated detection thresholds for umami and sucrose stimuli. These findings suggest that chemotherapeutic disturbances in the peripheral mechanisms of the taste system may cause dietary challenges at a time when the cancer patient has significant need for well balanced, high energy nutritional intake. PMID:28950008

Cellular mechanisms of cyclophosphamide-induced taste loss in mice.

Directory of Open Access Journals (Sweden)

Nabanita Mukherjee

Full Text Available Many commonly prescribed chemotherapy drugs such as cyclophosphamide (CYP have adverse side effects including disruptions in taste which can result in loss of appetite, malnutrition, poorer recovery and reduced quality of life. Previous studies in mice found evidence that CYP has a two-phase disturbance in taste behavior: a disturbance immediately following drug administration and a second which emerges several days later. In this study, we examined the processes by which CYP disturbs the taste system by examining the effects of the drug on taste buds and cells responsible for taste cell renewal using immunohistochemical assays. Data reported here suggest CYP has direct cytotoxic effects on lingual epithelium immediately following administration, causing an early loss of taste sensory cells. Types II and III cells in fungiform taste buds appear to be more susceptible to this effect than circumvallate cells. In addition, CYP disrupts the population of rapidly dividing cells in the basal layer of taste epithelium responsible for taste cell renewal, manifesting a disturbance days later. The loss of these cells temporarily retards the system's capacity to replace Type II and Type III taste sensory cells that survived the cytotoxic effects of CYP and died at the end of their natural lifespan. The timing of an immediate, direct loss of taste cells and a delayed, indirect loss without replacement of taste sensory cells are broadly congruent with previously published behavioral data reporting two periods of elevated detection thresholds for umami and sucrose stimuli. These findings suggest that chemotherapeutic disturbances in the peripheral mechanisms of the taste system may cause dietary challenges at a time when the cancer patient has significant need for well balanced, high energy nutritional intake.

Evaporation Loss of Light Elements as a Function of Cooling Rate: Logarithmic Law

Science.gov (United States)

Xiong, Yong-Liang; Hewins, Roger H.

2003-01-01

Knowledge about the evaporation loss of light elements is important to our understanding of chondrule formation processes. The evaporative loss of light elements (such as B and Li) as a function of cooling rate is of special interest because recent investigations of the distribution of Li, Be and B in meteoritic chondrules have revealed that Li varies by 25 times, and B and Be varies by about 10 times. Therefore, if we can extrapolate and interpolate with confidence the evaporation loss of B and Li (and other light elements such as K, Na) at a wide range of cooling rates of interest based upon limited experimental data, we would be able to assess the full range of scenarios relating to chondrule formation processes. Here, we propose that evaporation loss of light elements as a function of cooling rate should obey the logarithmic law.

Functional visual fields: relationship of visual field areas to self-reported function.

Science.gov (United States)

Subhi, Hikmat; Latham, Keziah; Myint, Joy; Crossland, Michael D

2017-07-01

The aim of this study is to relate areas of the visual field to functional difficulties to inform the development of a binocular visual field assessment that can reflect the functional consequences of visual field loss. Fifty-two participants with peripheral visual field loss undertook binocular assessment of visual fields using the 30-2 and 60-4 SITA Fast programs on the Humphrey Field Analyser, and mean thresholds were derived. Binocular visual acuity, contrast sensitivity and near reading performance were also determined. Self-reported overall and mobility function were assessed using the Dutch ICF Activity Inventory. Greater visual field loss (0-60°) was associated with worse self-reported function both overall (R 2 = 0.50; p function (R 2 = 0.61, p function in multiple regression analyses. Superior and inferior visual field areas related similarly to mobility function (R 2 = 0.56, p function in multiple regression analysis. Mean threshold of the binocular visual field to 60° eccentricity is a good predictor of self-reported function overall, and particularly of mobility function. Both the central (0-30°) and peripheral (30-60°) mean threshold are good predictors of self-reported function, but the peripheral (30-0°) field is a slightly better predictor of mobility function, and should not be ignored when considering functional consequences of field loss. The inferior visual field is a slightly stronger predictor of perceived overall and mobility function than the superior field. © 2017 The Authors Ophthalmic & Physiological Optics © 2017 The College of Optometrists.

On Multiple Interpolation Functions of the -Genocchi Polynomials

Directory of Open Access Journals (Sweden)

Jin Jeong-Hee

2010-01-01

Full Text Available Abstract Recently, many mathematicians have studied various kinds of the -analogue of Genocchi numbers and polynomials. In the work (New approach to q-Euler, Genocchi numbers and their interpolation functions, "Advanced Studies in Contemporary Mathematics, vol. 18, no. 2, pp. 105–112, 2009.", Kim defined new generating functions of -Genocchi, -Euler polynomials, and their interpolation functions. In this paper, we give another definition of the multiple Hurwitz type -zeta function. This function interpolates -Genocchi polynomials at negative integers. Finally, we also give some identities related to these polynomials.

The application of multiple biophysical cues to engineer functional neocartilage for treatment of osteoarthritis. Part II: signal transduction.

Science.gov (United States)

Brady, Mariea A; Waldman, Stephen D; Ethier, C Ross

2015-02-01

The unique mechanoelectrochemical environment of cartilage has motivated researchers to investigate the effect of multiple biophysical cues, including mechanical, magnetic, and electrical stimulation, on chondrocyte biology. It is well established that biophysical stimuli promote chondrocyte proliferation, differentiation, and maturation within "biological windows" of defined dose parameters, including mode, frequency, magnitude, and duration of stimuli (see companion review Part I: Cellular Response). However, the underlying molecular mechanisms and signal transduction pathways activated in response to multiple biophysical stimuli remain to be elucidated. Understanding the mechanisms of biophysical signal transduction will deepen knowledge of tissue organogenesis, remodeling, and regeneration and aiding in the treatment of pathologies such as osteoarthritis. Further, this knowledge will provide the tissue engineer with a potent toolset to manipulate and control cell fate and subsequently develop functional replacement cartilage. The aim of this article is to review chondrocyte signal transduction pathways in response to mechanical, magnetic, and electrical cues. Signal transduction does not occur along a single pathway; rather a number of parallel pathways appear to be activated, with calcium signaling apparently common to all three types of stimuli, though there are different modes of activation. Current tissue engineering strategies, such as the development of "smart" functionalized biomaterials that enable the delivery of growth factors or integration of conjugated nanoparticles, may further benefit from targeting known signal transduction pathways in combination with external biophysical cues.

Multiple Export Mechanisms for mRNAs

Science.gov (United States)

Delaleau, Mildred; Borden, Katherine L. B.

2015-01-01

Nuclear mRNA export plays an important role in gene expression. We describe the mechanisms of mRNA export including the importance of mRNP assembly, docking with the nuclear basket of the nuclear pore complex (NPC), transit through the central channel of the NPC and cytoplasmic release. We describe multiple mechanisms of mRNA export including NXF1 and CRM1 mediated pathways. Selective groups of mRNAs can be preferentially transported in order to respond to cellular stimuli. RNAs can be selected based on the presence of specific cis-acting RNA elements and binding of specific adaptor proteins. The role that dysregulation of this process plays in human disease is also discussed. PMID:26343730

Massive weight loss-induced mechanical plasticity in obese gait

NARCIS (Netherlands)

Hortobagyi, Tibor; Herring, Cortney; Pories, Walter J.; Rider, Patrick; DeVita, Paul

2011-01-01

Hortobagyi T, Herring C, Pories WJ, Rider P, DeVita P. Massive weight loss-induced mechanical plasticity in obese gait. J Appl Physiol 111: 1391-1399, 2011. First published August 18, 2011; doi:10.1152/japplphysiol.00291.2011.-We examined the hypothesis that metabolic surgery-induced massive weight

Pathogenesis of age-related bone loss in humans.

Science.gov (United States)

Khosla, Sundeep

2013-10-01

Although data from rodent systems are extremely useful in providing insights into possible mechanisms of age-related bone loss, concepts evolving from animal models need to ultimately be tested in humans. This review provides an update on mechanisms of age-related bone loss in humans based on the author's knowledge of the field and focused literature reviews. Novel imaging, experimental models, biomarkers, and analytic techniques applied directly to human studies are providing new insights into the patterns of bone mass acquisition and loss as well as the role of sex steroids, in particular estrogen, on bone metabolism and bone loss with aging in women and men. These studies have identified the onset of trabecular bone loss at multiple sites that begins in young adulthood and remains unexplained, at least based on current paradigms of the mechanisms of bone loss. In addition, estrogen appears to be a major regulator of bone metabolism not only in women but also in men. Studies assessing mechanisms of estrogen action on bone in humans have identified effects of estrogen on RANKL expression by several different cell types in the bone microenvironment, a role for TNF-α and IL-1β in mediating effects of estrogen deficiency on bone, and possible regulation of the Wnt inhibitor, sclerostin, by estrogen. There have been considerable advances in our understanding of age-related bone loss in humans. However, there are also significant gaps in knowledge, particularly in defining cell autonomous changes in bone in human studies to test or validate concepts emerging from studies in rodents. Decision Editor: Luigi Ferrucci, MD, PhD.

Beam size blow-up and current loss in the Fermilab Main Ring during storage

International Nuclear Information System (INIS)

Guignard, C.; Month, M.

1977-01-01

Observations at Fermilab during storage mode operation show characteristic forms of transverse beam size growth and current loss with time. There are three obvious mechanisms which can produce such blowup. The gas pressure is a source for immediate beam loss by direct nuclear scattering. Protons can also multiple scatter off the orbiting electrons of the gas atoms causing the trasnverse beam size to increase with time. A third mechanism not related to gas pressure is beam growth due to multiple crossing of betatron resonances arising from the synchrotron oscillations of the stored bunches. This simulates a random walk and causes the transverse beam size to grow. This is an attempt to describe the observations with direct nuclear scattering, multiple coulomb scattering, and multiple resonance crossing

Loss of function of C9orf72 causes motor deficits in a zebrafish model of amyotrophic lateral sclerosis.

Science.gov (United States)

Ciura, Sorana; Lattante, Serena; Le Ber, Isabelle; Latouche, Morwena; Tostivint, Hervé; Brice, Alexis; Kabashi, Edor

2013-08-01

To define the role that repeat expansions of a GGGGCC hexanucleotide sequence of the C9orf72 gene play in the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). A genetic model for ALS was developed to determine whether loss of function of the zebrafish orthologue of C9orf72 (zC9orf72) leads to abnormalities in neuronal development. C9orf72 mRNA levels were quantified in brain and lymphoblasts derived from FTLD and ALS/FTLD patients and in zebrafish. Knockdown of the zC9orf72 was performed using 2 specific antisense morpholino oligonucleotides to block transcription. Quantifications of spontaneous swimming and tactile escape response, as well as measurements of axonal projections from the spinal cord, were performed. Significantly decreased expression of C9orf72 transcripts in brain and lymphoblasts was found in sporadic FTLD and ALS/FTLD patients with normal-size or expanded hexanucleotide repeats. The zC9orf72 is selectively expressed in the developing nervous system at developmental stages. Loss of function of the zC9orf72 transcripts causes both behavioral and cellular deficits related to locomotion without major morphological abnormalities. These deficits were rescued upon overexpression of human C9orf72 mRNA transcripts. Our results indicate C9orf72 haploinsufficiency could be a contributing factor in the spectrum of ALS/FTLD neurodegenerative disorders. Loss of function of the zebrafish orthologue of zC9orf72 expression in zebrafish is associated with axonal degeneration of motor neurons that can be rescued by expressing human C9orf72 mRNA, highlighting the specificity of the induced phenotype. These results reveal a pathogenic consequence of decreased C9orf72 levels, supporting a loss of function mechanism of disease. © 2013 American Neurological Association.

Declining resilience of ecosystem functions under biodiversity loss.

Science.gov (United States)

Oliver, Tom H; Isaac, Nick J B; August, Tom A; Woodcock, Ben A; Roy, David B; Bullock, James M

2015-12-08

The composition of species communities is changing rapidly through drivers such as habitat loss and climate change, with potentially serious consequences for the resilience of ecosystem functions on which humans depend. To assess such changes in resilience, we analyse trends in the frequency of species in Great Britain that provide key ecosystem functions--specifically decomposition, carbon sequestration, pollination, pest control and cultural values. For 4,424 species over four decades, there have been significant net declines among animal species that provide pollination, pest control and cultural values. Groups providing decomposition and carbon sequestration remain relatively stable, as fewer species are in decline and these are offset by large numbers of new arrivals into Great Britain. While there is general concern about degradation of a wide range of ecosystem functions, our results suggest actions should focus on particular functions for which there is evidence of substantial erosion of their resilience.

Using machine-learning methods to analyze economic loss function of quality management processes

Science.gov (United States)

Dzedik, V. A.; Lontsikh, P. A.

2018-05-01

During analysis of quality management systems, their economic component is often analyzed insufficiently. To overcome this issue, it is necessary to withdraw the concept of economic loss functions from tolerance thinking and address it. Input data about economic losses in processes have a complex form, thus, using standard tools to solve this problem is complicated. Use of machine learning techniques allows one to obtain precise models of the economic loss function based on even the most complex input data. Results of such analysis contain data about the true efficiency of a process and can be used to make investment decisions.

Molecular evolution and functional characterization of Drosophila insulin-like peptides.

Directory of Open Access Journals (Sweden)

Sebastian Grönke

2010-02-01

Full Text Available Multicellular animals match costly activities, such as growth and reproduction, to the environment through nutrient-sensing pathways. The insulin/IGF signaling (IIS pathway plays key roles in growth, metabolism, stress resistance, reproduction, and longevity in diverse organisms including mammals. Invertebrate genomes often contain multiple genes encoding insulin-like ligands, including seven Drosophila insulin-like peptides (DILPs. We investigated the evolution, diversification, redundancy, and functions of the DILPs, combining evolutionary analysis, based on the completed genome sequences of 12 Drosophila species, and functional analysis, based on newly-generated knock-out mutations for all 7 dilp genes in D. melanogaster. Diversification of the 7 DILPs preceded diversification of Drosophila species, with stable gene diversification and family membership, suggesting stabilising selection for gene function. Gene knock-outs demonstrated both synergy and compensation of expression between different DILPs, notably with DILP3 required for normal expression of DILPs 2 and 5 in brain neurosecretory cells and expression of DILP6 in the fat body compensating for loss of brain DILPs. Loss of DILP2 increased lifespan and loss of DILP6 reduced growth, while loss of DILP7 did not affect fertility, contrary to its proposed role as a Drosophila relaxin. Importantly, loss of DILPs produced in the brain greatly extended lifespan but only in the presence of the endosymbiontic bacterium Wolbachia, demonstrating a specific interaction between IIS and Wolbachia in lifespan regulation. Furthermore, loss of brain DILPs blocked the responses of lifespan and fecundity to dietary restriction (DR and the DR response of these mutants suggests that IIS extends lifespan through mechanisms that both overlap with those of DR and through additional mechanisms that are independent of those at work in DR. Evolutionary conservation has thus been accompanied by synergy

A Switching Anti-windup Design Using Multiple Lyapunov Functions

NARCIS (Netherlands)

Lu, L.; Lin, Z.; Chen, J.

2009-01-01

This paper proposes a switching anti-windup design, which aims to enlarge the domain of attraction of the closed-loop system. Multiple anti-windup gains along with an index function that orchestrates the switching among these anti-windup gains are designed based on the min function of multiple

Predicting Protein Function via Semantic Integration of Multiple Networks.

Science.gov (United States)

Yu, Guoxian; Fu, Guangyuan; Wang, Jun; Zhu, Hailong

2016-01-01

Determining the biological functions of proteins is one of the key challenges in the post-genomic era. The rapidly accumulated large volumes of proteomic and genomic data drives to develop computational models for automatically predicting protein function in large scale. Recent approaches focus on integrating multiple heterogeneous data sources and they often get better results than methods that use single data source alone. In this paper, we investigate how to integrate multiple biological data sources with the biological knowledge, i.e., Gene Ontology (GO), for protein function prediction. We propose a method, called SimNet, to Semantically integrate multiple functional association Networks derived from heterogenous data sources. SimNet firstly utilizes GO annotations of proteins to capture the semantic similarity between proteins and introduces a semantic kernel based on the similarity. Next, SimNet constructs a composite network, obtained as a weighted summation of individual networks, and aligns the network with the kernel to get the weights assigned to individual networks. Then, it applies a network-based classifier on the composite network to predict protein function. Experiment results on heterogenous proteomic data sources of Yeast, Human, Mouse, and Fly show that, SimNet not only achieves better (or comparable) results than other related competitive approaches, but also takes much less time. The Matlab codes of SimNet are available at https://sites.google.com/site/guoxian85/simnet.

Alzheimer's disease due to loss of function

DEFF Research Database (Denmark)

Kepp, Kasper Planeta

2016-01-01

Alzheimer's Disease (AD) is a highly complex disease involving a broad range of clinical, cellular, and biochemical manifestations that are currently not understood in combination. This has led to many views of AD, e.g. the amyloid, tau, presenilin, oxidative stress, and metal hypotheses....... The amyloid hypothesis has dominated the field with its assumption that buildup of pathogenic β-amyloid (Aβ) peptide causes disease. This paradigm has been criticized, yet most data suggest that Aβ plays a key role in the disease. Here, a new loss-of-function hypothesis is synthesized that accounts...

Piecewise linearisation of the first order loss function for families of arbitrarily distributed random variables

NARCIS (Netherlands)

Rossi, R.; Hendrix, E.M.T.

2014-01-01

We discuss the problem of computing optimal linearisation parameters for the first order loss function of a family of arbitrarily distributed random variable. We demonstrate that, in contrast to the problem in which parameters must be determined for the loss function of a single random variable,

Sleep loss and structural plasticity.

Science.gov (United States)

Areal, Cassandra C; Warby, Simon C; Mongrain, Valérie

2017-06-01

Wakefulness and sleep are dynamic states during which brain functioning is modified and shaped. Sleep loss is detrimental to many brain functions and results in structural changes localized at synapses in the nervous system. In this review, we present and discuss some of the latest observations of structural changes following sleep loss in some vertebrates and insects. We also emphasize that these changes are region-specific and cell type-specific and that, most importantly, these structural modifications have functional roles in sleep regulation and brain functions. Selected mechanisms driving structural modifications occurring with sleep loss are also discussed. Overall, recent research highlights that extending wakefulness impacts synapse number and shape, which in turn regulate sleep need and sleep-dependent learning/memory. Copyright © 2017 Elsevier Ltd. All rights reserved.

Multiple mechanisms involved in diabetes protection by lipopolysaccharide in non-obese diabetic mice

Energy Technology Data Exchange (ETDEWEB)

Wang, Jun [Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Department of Pharmacology, College of Medicine, Wuhan University of Science and Technology, Wuhan (China); Cao, Hui [Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Wang, Hongjie [Section of Neurobiology, Torrey Pines Institute for Molecular Studies, Port Saint Lucie, FL (United States); Yin, Guoxiao; Du, Jiao; Xia, Fei; Lu, Jingli [Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Xiang, Ming, E-mail: xiangming@mails.tjmu.edu.cn [Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China)

2015-06-15

Toll-like receptor 4 (TLR4) activation has been proposed to be important for islet cell inflammation and eventually β cell loss in the course of type 1 diabetes (T1D) development. However, according to the “hygiene hypothesis”, bacterial endotoxin lipopolysaccharide (LPS), an agonist on TLR4, inhibits T1D progression. Here we investigated possible mechanisms for the protective effect of LPS on T1D development in non-obese diabetic (NOD) mice. We found that LPS administration to NOD mice during the prediabetic state neither prevented nor reversed insulitis, but delayed the onset and decreased the incidence of diabetes, and that a multiple-injection protocol is more effective than a single LPS intervention. Further, LPS administration suppressed spleen T lymphocyte proliferation, increased the generation of CD4{sup +}CD25{sup +}Foxp3{sup +} regulatory T cells (Tregs), reduced the synthesis of strong Th1 proinflammatory cytokines, and downregulated TLR4 and its downstream MyD88-dependent signaling pathway. Most importantly, multiple injections of LPS induced a potential tolerogenic dendritic cell (DC) subset with low TLR4 expression without influencing the DC phenotype. Explanting DCs from repeated LPS-treated NOD mice into NOD/SCID diabetic mice conferred sustained protective effects against the progression of diabetes in the recipients. Overall, these results suggest that multiple mechanisms are involved in the protective effects of LPS against the development of diabetes in NOD diabetic mice. These include Treg induction, down-regulation of TLR4 and its downstream MyD88-dependent signaling pathway, and the emergence of a potential tolerogenic DC subset. - Highlights: • Administration of lipopolysaccharide (LPS) prevented type 1 diabetes in NOD mice. • Downregulating TLR4 level and MyD88-dependent pathway contributed to protection of LPS. • LPS administration also hampered DC maturation and promoted Treg differentiation.

Multiple mechanisms involved in diabetes protection by lipopolysaccharide in non-obese diabetic mice

International Nuclear Information System (INIS)

Wang, Jun; Cao, Hui; Wang, Hongjie; Yin, Guoxiao; Du, Jiao; Xia, Fei; Lu, Jingli; Xiang, Ming

2015-01-01

Toll-like receptor 4 (TLR4) activation has been proposed to be important for islet cell inflammation and eventually β cell loss in the course of type 1 diabetes (T1D) development. However, according to the “hygiene hypothesis”, bacterial endotoxin lipopolysaccharide (LPS), an agonist on TLR4, inhibits T1D progression. Here we investigated possible mechanisms for the protective effect of LPS on T1D development in non-obese diabetic (NOD) mice. We found that LPS administration to NOD mice during the prediabetic state neither prevented nor reversed insulitis, but delayed the onset and decreased the incidence of diabetes, and that a multiple-injection protocol is more effective than a single LPS intervention. Further, LPS administration suppressed spleen T lymphocyte proliferation, increased the generation of CD4 + CD25 + Foxp3 + regulatory T cells (Tregs), reduced the synthesis of strong Th1 proinflammatory cytokines, and downregulated TLR4 and its downstream MyD88-dependent signaling pathway. Most importantly, multiple injections of LPS induced a potential tolerogenic dendritic cell (DC) subset with low TLR4 expression without influencing the DC phenotype. Explanting DCs from repeated LPS-treated NOD mice into NOD/SCID diabetic mice conferred sustained protective effects against the progression of diabetes in the recipients. Overall, these results suggest that multiple mechanisms are involved in the protective effects of LPS against the development of diabetes in NOD diabetic mice. These include Treg induction, down-regulation of TLR4 and its downstream MyD88-dependent signaling pathway, and the emergence of a potential tolerogenic DC subset. - Highlights: • Administration of lipopolysaccharide (LPS) prevented type 1 diabetes in NOD mice. • Downregulating TLR4 level and MyD88-dependent pathway contributed to protection of LPS. • LPS administration also hampered DC maturation and promoted Treg differentiation

Individual species affect plant traits structure in their surroundings: evidence of functional mechanisms of assembly.

Science.gov (United States)

Chacón-Labella, Julia; de la Cruz, Marcelino; Pescador, David S; Escudero, Adrián

2016-04-01

Evaluating community assembly through the use of functional traits is a promising tool for testing predictions arising from Niche and Coexistence theories. Although interactions among neighboring species and their inter-specific differences are known drivers of coexistence with a strong spatial signal, assessing the role of individual species on the functional structure of the community at different spatial scales remains a challenge. Here, we ask whether individual species exert a measurable effect on the spatial organization of different functional traits in local assemblages. We first propose and compute two functions that describe different aspects of functional trait organization around individual species at multiple scales: individual weighted mean area relationship and individual functional diversity area relationship. Secondly, we develop a conceptual model on the relationship and simultaneous variation of these two metrics, providing five alternative scenarios in response to the ability of some target species to modify its neighbor environment and the possible assembly mechanisms involved. Our results show that some species influence the spatial structure of specific functional traits, but their effects were always restricted to the finest spatial scales. In the basis of our conceptual model, the observed patterns point to two main mechanisms driving the functional structure of the community at the fine scale, "biotic" filtering meditated by individual species and resource partitioning driven by indirect facilitation rather than by competitive mechanisms.

Collaboration Mechanism for Equipment Instruction of Multiple Energy Systems

Science.gov (United States)

Wang, Dong; Wang, Tuo; Wang, Qi; Zhang, Zhao; Zhao, Mingyu; Wang, Yinghui

2018-01-01

When multiple energy systems execute optimization instructions simultaneously, and the same equipment is Shared, the instruction conflict may occur. Aiming at the above problems, taking into account the control objectives of each system, the characteristics of different systems, such as comprehensive clean energy, energy efficiency, and peak filling, etc., designed the instruction coordination mechanism for the daemon. This mechanism mainly acts on the main station of the system, and form a final optimization instruction. For some specific scenarios, the collaboration mechanism of unlocking the terminal is supplemented. The mechanism determines the specific execution instructions based on the arrival time of the instruction. Finally, the experiment in Tianjin eco-city shows that this algorithm can meet the instruction and collaboration requirements of multi-energy systems, and ensure the safe operation of the equipment.

Parallel Low-Loss Measurement of Multiple Atomic Qubits.

Science.gov (United States)

Kwon, Minho; Ebert, Matthew F; Walker, Thad G; Saffman, M

2017-11-03

We demonstrate low-loss measurement of the hyperfine ground state of rubidium atoms by state dependent fluorescence detection in a dipole trap array of five sites. The presence of atoms and their internal states are minimally altered by utilizing circularly polarized probe light and a strictly controlled quantization axis. We achieve mean state detection fidelity of 97% without correcting for imperfect state preparation or background losses, and 98.7% when corrected. After state detection and correction for background losses, the probability of atom loss due to the state measurement is state is preserved with >98% probability.

Loss functions for structural flood mitigation measures

African Journals Online (AJOL)

drinie

2001-01-01

Jan 1, 2001 ... for spillways, levees, tramlines, public roads, drains and bridges. Introduction. The aim of this paper is to discuss the ... In the third section the steps that were followed to determine loss functions for ... Wilson's Cannal-, 31/2-, Low Level- and Monzi Bridge, are also maintained by the co-operative. A tramline ...

The primary mechanism of attenuation of bacillus Calmette–Guérin is a loss of secreted lytic function required for invasion of lung interstitial tissue

Science.gov (United States)

Hsu, Tsungda; Hingley-Wilson, Suzanne M.; Chen, Bing; Chen, Mei; Dai, Annie Z.; Morin, Paul M.; Marks, Carolyn B.; Padiyar, Jeevan; Goulding, Celia; Gingery, Mari; Eisenberg, David; Russell, Robert G.; Derrick, Steven C.; Collins, Frank M.; Morris, Sheldon L.; King, C. Harold; Jacobs, William R.

2003-01-01

Tuberculosis remains a leading cause of death worldwide, despite the availability of effective chemotherapy and a vaccine. Bacillus Calmette–Guérin (BCG), the tuberculosis vaccine, is an attenuated mutant of Mycobacterium bovis that was isolated after serial subcultures, yet the functional basis for this attenuation has never been elucidated. A single region (RD1), which is absent in all BCG substrains, was deleted from virulent M. bovis and Mycobacterium tuberculosis strains, and the resulting ΔRD1 mutants were significantly attenuated for virulence in both immunocompromised and immunocompetent mice. The M. tuberculosis ΔRD1 mutants were also shown to protect mice against aerosol challenge, in a similar manner to BCG. Interestingly, the ΔRD1 mutants failed to cause cytolysis of pneumocytes, a phenotype that had been previously used to distinguish virulent M. tuberculosis from BCG. A specific transposon mutation, which disrupts the Rv3874 Rv3875 (cfp-10 esat-6) operon of RD1, also caused loss of the cytolytic phenotype in both pneumocytes and macrophages. This mutation resulted in the attenuation of virulence in mice, as the result of reduced tissue invasiveness. Moreover, specific deletion of each transcriptional unit of RD1 revealed that three independent transcriptional units are required for virulence, two of which are involved in the secretion of ESAT-6 (6-kDa early secretory antigenic target). We conclude that the primary attenuating mechanism of bacillus Calmette–Guérin is the loss of cytolytic activity mediated by secreted ESAT-6, which results in reduced tissue invasiveness. PMID:14557547

Fast determination of the current loss mechanisms in textured crystalline Si-based solar cells

Science.gov (United States)

Nakane, Akihiro; Fujimoto, Shohei; Fujiwara, Hiroyuki

2017-11-01

A quite general device analysis method that allows the direct evaluation of optical and recombination losses in crystalline silicon (c-Si)-based solar cells has been developed. By applying this technique, the current loss mechanisms of the state-of-the-art solar cells with ˜20% efficiencies have been revealed. In the established method, the optical and electrical losses are characterized from the analysis of an experimental external quantum efficiency (EQE) spectrum with very low computational cost. In particular, we have performed the EQE analyses of textured c-Si solar cells by employing the experimental reflectance spectra obtained directly from the actual devices while using flat optical models without any fitting parameters. We find that the developed method provides almost perfect fitting to EQE spectra reported for various textured c-Si solar cells, including c-Si heterojunction solar cells, a dopant-free c-Si solar cell with a MoOx layer, and an n-type passivated emitter with rear locally diffused solar cell. The modeling of the recombination loss further allows the extraction of the minority carrier diffusion length and surface recombination velocity from the EQE analysis. Based on the EQE analysis results, the current loss mechanisms in different types of c-Si solar cells are discussed.

Somatic loss of function mutations in neurofibromin 1 and MYC associated factor X genes identified by exome-wide sequencing in a wild-type GIST case

International Nuclear Information System (INIS)

Belinsky, Martin G.; Rink, Lori; Cai, Kathy Q.; Capuzzi, Stephen J.; Hoang, Yen; Chien, Jeremy; Godwin, Andrew K.; Mehren, Margaret von

2015-01-01

Approximately 10–15 % of gastrointestinal stromal tumors (GISTs) lack gain of function mutations in the KIT and platelet-derived growth factor receptor alpha (PDGFRA) genes. An alternate mechanism of oncogenesis through loss of function of the succinate-dehydrogenase (SDH) enzyme complex has been identified for a subset of these “wild type” GISTs. Paired tumor and normal DNA from an SDH-intact wild-type GIST case was subjected to whole exome sequencing to identify the pathogenic mechanism(s) in this tumor. Selected findings were further investigated in panels of GIST tumors through Sanger DNA sequencing, quantitative real-time PCR, and immunohistochemical approaches. A hemizygous frameshift mutation (p.His2261Leufs*4), in the neurofibromin 1 (NF1) gene was identified in the patient’s GIST; however, no germline NF1 mutation was found. A somatic frameshift mutation (p.Lys54Argfs*31) in the MYC associated factor X (MAX) gene was also identified. Immunohistochemical analysis for MAX on a large panel of GISTs identified loss of MAX expression in the MAX-mutated GIST and in a subset of mainly KIT-mutated tumors. This study suggests that inactivating NF1 mutations outside the context of neurofibromatosis may be the oncogenic mechanism for a subset of sporadic GIST. In addition, loss of function mutation of the MAX gene was identified for the first time in GIST, and a broader role for MAX in GIST progression was suggested. The online version of this article (doi:10.1186/s12885-015-1872-y) contains supplementary material, which is available to authorized users

The aging lacrimal gland: changes in structure and function.

Science.gov (United States)

Rocha, Eduardo M; Alves, Monica; Rios, J David; Dartt, Darlene A

2008-10-01

The afferent nerves of the cornea and conjunctiva, efferent nerves of the lacrimal gland, and the lacrimal gland are a functional unit that works cooperatively to produce the aqueous component of tears. A decrease in the lacrimal gland secretory function can lead to dry eye disease. Because aging is a risk factor for dry eye disease, study of the changes in the function of the lacrimal gland functional unit with age is important for developing treatments to prevent dry eye disease. No one mechanism is known to induce the changes that occur with aging, although multiple different mechanisms have been associated with aging. These fall into two theoretical categories: programmed theories of aging (immunological, genetic, apoptotic, and neuroendocrine) and error theories of aging (protein alteration, somatic mutation, etc). Lacrimal glands undergo structural and functional alteration with increasing age. In mouse models of aging, it has been shown that neural stimulation of protein secretion is an early target of aging, accompanied by an increase in mast cells and lipofuscin accumulation. Hyperglycemia and increased lymphocytic infiltration can contribute to this loss of function at older ages. These findings suggest that an increase in oxidative stress may play a role in the loss of lacrimal gland function with age. For the afferent and efferent neural components of the lacrimal gland functional unit, immune or inflammatory mediated decrease in nerve function could contribute to loss of lacrimal gland secretion with age. More research in this area is critically needed.

A novel soil manganese mechanism drives plant species loss with increased nitrogen deposition in a temperate steppe.

Science.gov (United States)

Tian, Qiuying; Liu, Nana; Bai, Wenming; Li, Linghao; Chen, Jiquan; Reich, Peter B; Yu, Qiang; Guo, Dali; Smith, Melinda D; Knapp, Alan K; Cheng, Weixin; Lu, Peng; Gao, Yan; Yang, An; Wang, Tianzuo; Li, Xin; Wang, Zhengwen; Ma, Yibing; Han, Xingguo; Zhang, Wen-Hao

2016-01-01

Loss of plant diversity with increased anthropogenic nitrogen (N) deposition in grasslands has occurred globally. In most cases, competitive exclusion driven by preemption of light or space is invoked as a key mechanism. Here, we provide evidence from a 9-yr N-addition experiment for an alternative mechanism: differential sensitivity of forbs and grasses to increased soil manganese (Mn) levels. In Inner Mongolia steppes, increasing the N supply shifted plant community composition from grass-forb codominance (primarily Stipa krylovii and Artemisia frigida, respectively) to exclusive dominance by grass, with associated declines in overall species richness. Reduced abundance of forbs was linked to soil acidification that increased mobilization of soil Mn, with a 10-fold greater accumulation of Mn in forbs than in grasses. The enhanced accumulation of Mn in forbs was correlated with reduced photosynthetic rates and growth, and is consistent with the loss of forb species. Differential accumulation of Mn between forbs and grasses can be linked to fundamental differences between dicots and monocots in the biochemical pathways regulating metal transport. These findings provide a mechanistic explanation for N-induced species loss in temperate grasslands by linking metal mobilization in soil to differential metal acquisition and impacts on key functional groups in these ecosystems.

IKs Gain- and Loss-of-Function In Early-Onset Lone Atrial Fibrillation

DEFF Research Database (Denmark)

Steffensen, Annette Buur; Refsgaard, Lena; Andersen, Martin Nybo

2015-01-01

INTRODUCTION: Atrial fibrillation (AF) is the most frequent cardiac arrhythmia. The potassium current IKs is essential for cardiac repolarization. Gain-of-function mutation in KCNQ1, the gene encoding the pore-forming α-subunit of the IKs channel (KV 7.1), was the first ion channel dysfunction...... to be associated with familial AF. We hypothesized that early-onset lone AF is associated with a high prevalence of mutations in KCNQ1. METHODS AND RESULTS: We bidirectionally sequenced the entire coding sequence of KCNQ1 in 209 unrelated patients with early-onset lone AF (...-of-function phenotype. CONCLUSIONS: Mutations in the IKs channel leading to gain-of-function have previously been described in familial AF, yet this is the first time a loss-of-function mutation in KCNQ1 is associated with early-onset lone AF. These findings suggest that both gain-of function and loss...

Consequences of biodiversity loss diverge from expectation due to post-extinction compensatory responses

Science.gov (United States)

Thomsen, Matthias S.; Garcia, Clement; Bolam, Stefan G.; Parker, Ruth; Godbold, Jasmin A.; Solan, Martin

2017-03-01

Consensus has been reached that global biodiversity loss impairs ecosystem functioning and the sustainability of services beneficial to humanity. However, the ecosystem consequences of extinction in natural communities are moderated by compensatory species dynamics, yet these processes are rarely accounted for in impact assessments and seldom considered in conservation programmes. Here, we use marine invertebrate communities to parameterise numerical models of sediment bioturbation - a key mediator of biogeochemical cycling - to determine whether post-extinction compensatory mechanisms alter biodiversity-ecosystem function relations following non-random extinctions. We find that compensatory dynamics lead to trajectories of sediment mixing that diverge from those without compensation, and that the form, magnitude and variance of each probabilistic distribution is highly influenced by the type of compensation and the functional composition of surviving species. Our findings indicate that the generalized biodiversity-function relation curve, as derived from multiple empirical investigations of random species loss, is unlikely to yield representative predictions for ecosystem properties in natural systems because the influence of post-extinction community dynamics are under-represented. Recognition of this problem is fundamental to management and conservation efforts, and will be necessary to ensure future plans and adaptation strategies minimize the adverse impacts of the biodiversity crisis.

Freezing of enkephalinergic functions by multiple noxious foci: a source of pain sensitization?

Directory of Open Access Journals (Sweden)

François Cesselin

Full Text Available BACKGROUND: The functional significance of proenkephalin systems in processing pain remains an open question and indeed is puzzling. For example, a noxious mechanical stimulus does not alter the release of Met-enkephalin-like material (MELM from segments of the spinal cord related to the stimulated area of the body, but does increase its release from other segments. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that, in the rat, a noxious mechanical stimulus applied to either the right or the left hind paw elicits a marked increase of MELM release during perifusion of either the whole spinal cord or the cervico-trigeminal area. However, these stimulatory effects were not additive and indeed, disappeared completely when the right and left paws were stimulated simultaneously. CONCLUSION/SIGNIFICANCE: We have concluded that in addition to the concept of a diffuse control of the transmission of nociceptive signals through the dorsal horn, there is a diffuse control of the modulation of this transmission. The "freezing" of Met-enkephalinergic functions represents a potential source of central sensitization in the spinal cord, notably in clinical situations involving multiple painful foci, e.g. cancer with metastases, poly-traumatism or rheumatoid arthritis.

Alterations in the adenosine metabolism and CD39/CD73 adenosinergic machinery cause loss of Treg cell function and autoimmunity in ADA-deficient SCID.

Science.gov (United States)

Sauer, Aisha V; Brigida, Immacolata; Carriglio, Nicola; Hernandez, Raisa Jofra; Scaramuzza, Samantha; Clavenna, Daniela; Sanvito, Francesca; Poliani, Pietro L; Gagliani, Nicola; Carlucci, Filippo; Tabucchi, Antonella; Roncarolo, Maria Grazia; Traggiai, Elisabetta; Villa, Anna; Aiuti, Alessandro

2012-02-09

Adenosine acts as anti-inflammatory mediator on the immune system and has been described in regulatory T cell (Treg)-mediated suppression. In the absence of adenosine deaminase (ADA), adenosine and other purine metabolites accumulate, leading to severe immunodeficiency with recurrent infections (ADA-SCID). Particularly ADA-deficient patients with late-onset forms and after enzyme replacement therapy (PEG-ADA) are known to manifest immune dysregulation. Herein we provide evidence that alterations in the purine metabolism interfere with Treg function, thereby contributing to autoimmune manifestations in ADA deficiency. Tregs isolated from PEG-ADA-treated patients are reduced in number and show decreased suppressive activity, whereas they are corrected after gene therapy. Untreated murine ADA(-/-) Tregs show alterations in the plasma membrane CD39/CD73 ectonucleotidase machinery and limited suppressive activity via extracellular adenosine. PEG-ADA-treated mice developed multiple autoantibodies and hypothyroidism in contrast to mice treated with bone marrow transplantation or gene therapy. Tregs isolated from PEG-ADA-treated mice lacked suppressive activity, suggesting that this treatment interferes with Treg functionality. The alterations in the CD39/CD73 adenosinergic machinery and loss of function in ADA-deficient Tregs provide new insights into a predisposition to autoimmunity and the underlying mechanisms causing defective peripheral tolerance in ADA-SCID.

Disconnection as a Mechanism for Cognitive Dysfunction in Multiple Sclerosis

Science.gov (United States)

Dineen, R. A.; Vilisaar, J.; Hlinka, J.; Bradshaw, C. M.; Morgan, P. S.; Constantinescu, C. S.; Auer, D. P.

2009-01-01

Disconnection of cognitively important processing regions by injury to the interconnecting white matter provides a potential mechanism for cognitive dysfunction in multiple sclerosis. The contribution of tract-specific white matter injury to dysfunction in different cognitive domains in patients with multiple sclerosis has not previously been…

The opercular mouth-opening mechanism of largemouth bass functions as a 3D four-bar linkage with three degrees of freedom.

Science.gov (United States)

Olsen, Aaron M; Camp, Ariel L; Brainerd, Elizabeth L

2017-12-15

The planar, one degree of freedom (1-DoF) four-bar linkage is an important model for understanding the function, performance and evolution of numerous biomechanical systems. One such system is the opercular mechanism in fishes, which is thought to function like a four-bar linkage to depress the lower jaw. While anatomical and behavioral observations suggest some form of mechanical coupling, previous attempts to model the opercular mechanism as a planar four-bar have consistently produced poor model fits relative to observed kinematics. Using newly developed, open source mechanism fitting software, we fitted multiple three-dimensional (3D) four-bar models with varying DoF to in vivo kinematics in largemouth bass to test whether the opercular mechanism functions instead as a 3D four-bar with one or more DoF. We examined link position error, link rotation error and the ratio of output to input link rotation to identify a best-fit model at two different levels of variation: for each feeding strike and across all strikes from the same individual. A 3D, 3-DoF four-bar linkage was the best-fit model for the opercular mechanism, achieving link rotational errors of less than 5%. We also found that the opercular mechanism moves with multiple degrees of freedom at the level of each strike and across multiple strikes. These results suggest that active motor control may be needed to direct the force input to the mechanism by the axial muscles and achieve a particular mouth-opening trajectory. Our results also expand the versatility of four-bar models in simulating biomechanical systems and extend their utility beyond planar or single-DoF systems. © 2017. Published by The Company of Biologists Ltd.

Carriers of loss-of-function mutations in EXT display impaired pancreatic beta-cell reserve due to smaller pancreas volume.

Directory of Open Access Journals (Sweden)

Sophie J Bernelot Moens

Full Text Available Exotosin (EXT proteins are involved in the chain elongation step of heparan sulfate (HS biosynthesis, which is intricately involved in organ development. Loss of function mutations (LOF in EXT1 and EXT2 result in hereditary exostoses (HME. Interestingly, HS plays a role in pancreas development and beta-cell function, and genetic variations in EXT2 are associated with an increased risk for type 2 diabetes mellitus. We hypothesized that loss of function of EXT1 or EXT2 in subjects with hereditary multiple exostoses (HME affects pancreatic insulin secretion capacity and development. We performed an oral glucose tolerance test (OGTT followed by hyperglycemic clamps to investigate first-phase glucose-stimulated insulin secretion (GSIS in HME patients and age and gender matched non-affected relatives. Pancreas volume was assessed with magnetic resonance imaging (MRI. OGTT did not reveal significant differences in glucose disposal, but there was a markedly lower GSIS in HME subjects during hyperglycemic clamp (iAUC HME: 0.72 [0.46-1.16] vs. controls 1.53 [0.69-3.36] nmol·l-1·min-1, p<0.05. Maximal insulin response following arginine challenge was also significantly attenuated (iAUC HME: 7.14 [4.22-10.5] vs. controls 10.2 [7.91-12.70] nmol·l-1·min-1 p<0.05, indicative of an impaired beta-cell reserve. MRI revealed a significantly smaller pancreatic volume in HME subjects (HME: 72.0±15.8 vs. controls 96.5±26.0 cm3 p = 0.04. In conclusion, loss of function of EXT proteins may affect beta-cell mass and insulin secretion capacity in humans, and render subjects at a higher risk of developing type 2 diabetes when exposed to environmental risk factors.

Investigation of dominant loss mechanisms in low-temperature polymer electrolyte membrane fuel cells

OpenAIRE

Gerteisen, D.

2010-01-01

This thesis deals with the analysis of dominant loss mechanisms in direct methanol fuel cells (DMFC) and hydrogen fed polymer electrolyte membrane fuel cells (PEFC) by means of experimental characterization and modeling work.

Vibrations analysis and bifurcations in the self-sustained electromechanical system with multiple functions

International Nuclear Information System (INIS)

Yamapi, R.; Moukam Kakmeni, F.M.; Aziz-Alaoui, M.A.

2005-07-01

We consider in this paper the dynamics of the self-sustained electromechanical system with multiple functions, consisting of an electrical Rayleigh-Duffing oscillator, magnetically coupled with linear mechanical oscillators. The averaging and the balance harmonic method are used to and the amplitudes of the oscillatory states respectively in the autonomous and non-autonomous cases, and analyze the condition in which the quenching of self-sustained oscillations appears. The effects of the number of linear mechanical oscillators on the behavior of the model are discussed. Various bifurcation structures, the stability chart and the variation of the Lyapunov exponent are obtained, using numerical simulations of the equations of motion. (author)

Analysis of neutron multiplicity measurements with allowance for dead-time losses between time-correlated detections

International Nuclear Information System (INIS)

Vincent, C.H.

1992-01-01

An exact solution is found for dead-time losses between detections occurring within a gate interval, with constant dead time and with allowance for time correlation between detections from the same spontaneous initial event. This is used to obtain a close approximation to the losses with a multi-channel detection system, with allowance for dead times briding the gate opening. This is applied, inversely, to calculate the true detection multiplicity rates from the distribution of the recorded counts within that interval. A suggestion is made for a circuit change to give a major reduction in dead-time effects. The unavoidable statistical errors that would remain are calculated. Their minimization and the limits of such minimization are discussed. (orig.)

Review of inelastic losses of UCN and quantum mechanics of the de Broglie wave packet

International Nuclear Information System (INIS)

Ignatovich, V.K.; Utsuro, M.

1998-01-01

Different inelastic processes of ultracold neutrons (UCN) losses in traps are considered. A hypothesis of the de Broglie singular wave-packet description of the neutron wave-function to explain anomalous losses of UCN is proposed. An experiment to check the hypothesis and its results are discussed

Assessment of the consequences in premature loss of the temporary lower molars.

Science.gov (United States)

Petcu, Ana; Bălan, Adriana; Gavrilă, Laura Maria Vasilca; Savin, Carmen

2014-01-01

The consequences of premature loss of temporary teeth are complex, both of functional and morphological order and the clinical presentation depends on multiple factors: the temporary tooth loss rate as compared with permanent tooth eruption sequence and the number and topography of teeth extracted, so the clinical form of edentulous, which can be frontal or lateral, symmetric or asymmetric, isolated or continuous.

Plants-Derived Neuroprotective Agents: Cutting the Cycle of Cell Death through Multiple Mechanisms

Directory of Open Access Journals (Sweden)

Taiwo Olayemi Elufioye

2017-01-01

Full Text Available Neuroprotection is the preservation of the structure and function of neurons from insults arising from cellular injuries induced by a variety of agents or neurodegenerative diseases (NDs. The various NDs including Alzheimer’s, Parkinson’s, and Huntington’s diseases as well as amyotropic lateral sclerosis affect millions of people around the world with the main risk factor being advancing age. Each of these diseases affects specific neurons and/or regions in the brain and involves characteristic pathological and molecular features. Hence, several in vitro and in vivo study models specific to each disease have been employed to study NDs with the aim of understanding their underlying mechanisms and identifying new therapeutic strategies. Of the most prevalent drug development efforts employed in the past few decades, mechanisms implicated in the accumulation of protein-based deposits, oxidative stress, neuroinflammation, and certain neurotransmitter deficits such as acetylcholine and dopamine have been scrutinized in great detail. In this review, we presented classical examples of plant-derived neuroprotective agents by highlighting their structural class and specific mechanisms of action. Many of these natural products that have shown therapeutic efficacies appear to be working through the above-mentioned key multiple mechanisms of action.

Genotype-phenotype associations in filaggrin loss-of-function mutation carriers

NARCIS (Netherlands)

Landeck, Lilla; Visser, Maaike; Kezic, Sanja; John, Swen M.

2013-01-01

Loss-of-function mutations in the filaggrin gene (FLG) have been reported to be associated with specific phenotypic characteristics such as hyperlinearity and keratosis pilaris. To study phenotypic features in patients with occupational irritant contact eczema of the hands in relation to FLG

ADNP-CSMA Random Multiple Access protocol application with the function of monitoring in Ad Hoc network

Directory of Open Access Journals (Sweden)

Zhan Gang

2016-01-01

Full Text Available In Ad Hoc networks,the net work of mobile nodes exchange information with their wireless transceiver equipment,the network throughput is in increased,compared to other such multiple hops network.Moreover along with the rapid development of modern information,communication business also will be increase.However,the access and adaptive of previous CSMA protocol are insufficient.According to these properties,this paper presents a kind of adaptive dual clock with monitoring function P-CSMA random multiple access protocol(ADNP-CSMA,and discusses two kinds of P-CSMA.ACK with monitoring function is introduced to maintain the stability of the whole system,and the introduction of dual clock mechanism reduces the channel of idle period.It calculate the system throughput expression through the method of average period,and the simulation results show that the system is constant in the case of high load throughput.

Development and validation of a prediction model for loss of physical function in elderly hemodialysis patients.

Science.gov (United States)

Fukuma, Shingo; Shimizu, Sayaka; Shintani, Ayumi; Kamitani, Tsukasa; Akizawa, Tadao; Fukuhara, Shunichi

2017-09-05

Among aging hemodialysis patients, loss of physical function has become a major issue. We developed and validated a model of predicting loss of physical function among elderly hemodialysis patients. We conducted a cohort study involving maintenance hemodialysis patients  ≥65 years of age from the Dialysis Outcomes and Practice Pattern Study in Japan. The derivation cohort included 593 early phase (1996-2004) patients and the temporal validation cohort included 447 late-phase (2005-12) patients. The main outcome was the incidence of loss of physical function, defined as the 12-item Short Form Health Survey physical function score decreasing to 0 within a year. Using backward stepwise logistic regression by Akaike's Information Criteria, six predictors (age, gender, dementia, mental health, moderate activity and ascending stairs) were selected for the final model. Points were assigned based on the regression coefficients and the total score was calculated by summing the points for each predictor. In total, 65 (11.0%) and 53 (11.9%) hemodialysis patients lost their physical function within 1 year in the derivation and validation cohorts, respectively. This model has good predictive performance quantified by both discrimination and calibration. The proportion of the loss of physical function increased sequentially through low-, middle-, and high-score categories based on the model (2.5%, 11.7% and 22.3% in the validation cohort, respectively). The loss of physical function was strongly associated with 1-year mortality [adjusted odds ratio 2.48 (95% confidence interval 1.26-4.91)]. We developed and validated a risk prediction model with good predictive performance for loss of physical function in elderly hemodialysis patients. Our simple prediction model may help physicians and patients make more informed decisions for healthy longevity. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA.

Mechanisms and management of functional abdominal pain

OpenAIRE

Farmer, Adam D; Aziz, Qasim

2014-01-01

Functional abdominal pain syndrome is characterised by frequent or continuous abdominal pain associated with a degree of loss of daily activity. It has a reported population prevalence of between 0.5% and 1.7%, with a female preponderance. The pathophysiology of functional abdominal pain is incompletely understood although it has been postulated that peripheral sensitisation of visceral afferents, central sensitisation of the spinal dorsal horn and aberrancies within descending modulatory sys...

Land-use intensification can exaggerate the reduction of functionality with increasing soil biodiversity loss in an alpine meadow on eastern Tibetan Plateau

Science.gov (United States)

Liu, Manqiang; Chen, Xiaoyun; Chen, Chenying; Hu, Zhengkun; Guo, Hui; Li, Junyong; Du, Guozhen; Li, Huixin; Hu, Feng

2017-04-01

Soil biota plays a pivotal role in ecosystem functionality which is of central importance to sustainable services such as food and fiber production. Intensive land use is associated with species loss and subsequent the related functionality loss. Currently, the claim that negligible effects of soil biodiversity loss due to high functional redundancy has been questioned in the face of intense human activities. Recent studies corroborated that soil biodiversity guaranteed functionality following perturbation. Few studies have, however, attempted to explore the intensive land use on the relationship between soil biodiversity and function particularly for the region susceptible to human perturbation and climate change. With increasing demands for livestock on the Qinghai-Tibetan Plateau, extensive fertilization is a common way to fill the gap of grass productivity in the alpine meadow. However, excess chemical fertilizer can lead to the species loss and functionality degradation. Do the fertilizer-induced changes in soil biota lead to a higher risk of functionality? We predicted that fertilization would exacerbate effects of biodiversity-loss on the reduction of functionality. Herein, a dilution-to-extinction approach was used to set up soil biodiversity loss by inoculating serially diluted soil suspension (ranging from 100 to 10-8 levels) from two long-term fertilization treatments to the sterilized soil that has never been fertilized. The two fertilization treatments represented two distinct intensification land use including the unfertilized control (NP0) and a fertilized treatment (NP120) amended with (NH4)2HPO4 annually (120 kg ha-1 yr-1) since 2002 in an alpine meadow on the eastern Qinghai-Tibetan Plateau. Soil microcosms of 2 fertilization levels crossing 8 biodiversity levels were incubated for 8 months. Then, soil community and multi-functionality parameters including carbon (C)and nutrient mineralization, plant growth and functional stability were determined

Physical activity as intervention for age-related loss of muscle mass and function

DEFF Research Database (Denmark)

Eriksen, Christian Skou; Garde, Ellen; Reislev, Nina Linde

2016-01-01

insights into training-induced promotion of functional ability and independency after retirement and will help to formulate national recommendations regarding physical activity schemes for the growing population of older individuals in western societies. Results will be published in scientific peer......INTRODUCTION: Physical and cognitive function decline with age, accelerating during the 6th decade. Loss of muscle power (force×velocity product) is a dominant physical determinant for loss of functional ability, especially if the lower extremities are affected. Muscle strength training is known...... to maintain or even improve muscle power as well as physical function in older adults, but the optimal type of training for beneficial long-term training effects over several years is unknown. Moreover, the impact of muscle strength training on cognitive function and brain structure remains speculative...

Authority inside the firm: multiple mechanisms of coordination

OpenAIRE

Bernard Baudry; Bruno Tinel

2004-01-01

In the last twenty years, through a growing awareness of contractual incompleteness, the concept of authority has regained primacy in the analysis of the employment relationship. This article pursues two goals. First, we assess the famous controversy between Coase and Alchian and Demsetz via an analysis of the foundations of intra-firm authority. Second, we argue that intra-firm authority cannot hinge on a single variable and, to the contrary, rests on multiple mechanisms. The employer's auth...

Contribution of mechanical unloading to trabecular bone loss following non-invasive knee injury in mice

OpenAIRE

Anderson, Matthew J.; Diko, Sindi; Baehr, Leslie M.; Baar, Keith; Bodine, Sue C.; Christiansen, Blaine A.

2016-01-01

Development of osteoarthritis commonly involves degeneration of epiphyseal trabecular bone. In previous studies, we observed 30–44% loss of epiphyseal trabecular bone (BV/TV) from the distal femur within one week following non-invasive knee injury in mice. Mechanical unloading (disuse) may contribute to this bone loss, however it is unclear to what extent the injured limb is unloaded following injury, and whether disuse can fully account for the observed magnitude of bone loss. In this study,...

Alemtuzumab in Multiple Sclerosis: Mechanism of Action and Beyond

Directory of Open Access Journals (Sweden)

Tobias Ruck

2015-07-01

Full Text Available Alemtuzumab is a humanized monoclonal antibody against CD52 (cluster of differentiation 52 and is approved for the therapy of relapsing-remitting multiple sclerosis. The application of alemtuzumab leads to a rapid, but long-lasting depletion predominantly of CD52-bearing B and T cells with reprogramming effects on immune cell composition resulting in the restoration of tolerogenic networks. Alemtuzumab has proven high efficacy in clinical phase II and III trials, where interferon β-1a was used as active comparator. However, alemtuzumab is associated with frequent and considerable risks. Most importantly secondary autoimmune disease affects 30%–40% of patients, predominantly impairing thyroid function. Extensive monitoring and early intervention allow for an appropriate risk management. However, new and reliable biomarkers for individual risk stratification and treatment response to improve patient selection and therapy guidance are a significant unmet need. Only a deeper understanding of the underlying mechanisms of action (MOA will reveal such markers, maximizing the best potential risk-benefit ratio for the individual patient. This review provides and analyses the current knowledge on the MOA of alemtuzumab. Most recent data on efficacy and safety of alemtuzumab are presented and future research opportunities are discussed.

Child behavior check list and Korean personality inventory for children with functional visual loss.

Science.gov (United States)

Kyung, Sung Eun; Lee, Sang Mi; Lim, Myung Ho

2014-08-01

To investigate the clinical psychiatric characteristics of children with the main complaint of functional visual loss, their behavior and personality were evaluated by the means of the Korean child behavior check list (K-CBCL), and the Korean personality inventory for children (KPI-C). The evaluation was carried out by the K-CBCL and the KPI-C, the domestically standardized tools, with 20 child subjects suspected of functional visual loss, among the patients who visited our hospital, between August, 2005 and December, 2012. The control group included 160 children in general schools of the same region. The 20 patients whose main complaint was functional visual loss were diagnosed as having a functional visual disorder. The child patient group showed a higher score for the K-CBCL and KPI-C sub-scales of somatic complaints, social problems, aggressive behavior, internalizing problems, externalizing problems, total behavioral problems, somatization and hyperactivity, than that of the control group. The results of the K-CBCL and KPI-C tests among children with functional visual loss, were significantly different from those of the normal control group. This result suggested that psychological factors may influence children with a main complaint of functional visual loss.

Cascade-probabilistic function with taking unto account energy losses of ions. Chapter 3

International Nuclear Information System (INIS)

1998-01-01

Mathematical simulation of cascade-probabilistic functions (CPF) for ions with taking into account of energy losses is carried out. Recommendations for CPF calculation on computer are given. Influence of both the interaction number on CPF domain and the interaction depth on CPF domain are determined. Contribution of energy losses into simplest CPF is estimated. Algorithm of radiation defects concentration calculation under ion irradiation with taking into consideration energy losses is cited

Filaggrin loss-of-function mutations and incident cancer

DEFF Research Database (Denmark)

Skaaby, T; Husemoen, L L N; Thyssen, J P

2014-01-01

BACKGROUND: Loss-of-function mutations in the filaggrin gene (FLG) could have opposing effects on cancer risk, as mutations are associated with both 10% higher serum vitamin D levels, which may protect against cancer, and with impaired skin barrier function, which may lead to higher cancer...... (HR 1·09, 95% CI 0·61-1·94), urinary cancer (HR 1·30, 95% CI 0·51-3·29), malignant melanoma (HR 1·03, 95% CI 0·41-2·58) and NMSC (HR 0·70, 95% CI 0·47-1·05). Among participants aged over 60 years at baseline, we found statistically significant lower risks of all cancers and NMSC among FLG mutation...

Maternal Executive Functioning as a Mechanism in the Intergenerational Transmission of Parenting: Preliminary Evidence

OpenAIRE

Bridgett, David J.; Kanya, Meghan J.; Rutherford, Helena J. V.; Mayes, Linda C.

2016-01-01

Multiple lines of inquiry, including experimental animal models, have recently converged to suggest that executive functioning (EF) may be one mechanism by which parenting behavior is transmitted across generations. In the current investigation, we empirically test this notion by examining relations between maternal EF and parenting behaviors during mother-infant interactions, and by examining the role of maternal EF in the intergenerational transmission of parenting behavior. Mother-infant d...

Heavy quark energy loss in nuclear medium

International Nuclear Information System (INIS)

Zhang, Benr-Wei; Wang, Enke; Wang, Xin-Nian

2003-01-01

Multiple scattering, modified fragmentation functions and radiative energy loss of a heavy quark propagating in a nuclear medium are investigated in perturbative QCD. Because of the quark mass dependence of the gluon formation time, the medium size dependence of heavy quark energy loss is found to change from a linear to a quadratic form when the initial energy and momentum scale are increased relative to the quark mass. The radiative energy loss is also significantly suppressed relative to a light quark due to the suppression of collinear gluon emission by a heavy quark

[Weight loss in overweight or obese patients and family functioning].

Science.gov (United States)

Jaramillo-Sánchez, Rosalba; Espinosa-de Santillana, Irene; Espíndola-Jaramillo, Ilia Angélica

2012-01-01

to determine the association between weight loss and family functioning. a cohort of 168 persons with overweight or obesity from 20-49 years, either sex, with no comorbidity was studied at the nutrition department. A sociodemographic data was obtained and FACES III instrument to measure family functioning was applied. At the third month a new assessment of the body mass index was measured. Descriptive statistical analysis and relative risk were done. obesity presented in 50.6 %, 59.53 % of them did not lose weight. Family dysfunction was present in 56.6 % of which 50 % did not lose weight. From 43.4 % of functional families, 9.52 % did not lose weight (p = 0.001). The probability or risk of not losing weight was to belong to a dysfunctional family is 4.03 % (CI = 2.60-6.25). A significant association was found between the variables: weight loss and family functioning. Belonging to a dysfunctional family may be a risk factor for not losing weight.

Loss of otolith function with age is associated with increased postural sway measures.

Science.gov (United States)

Serrador, Jorge M; Lipsitz, Lewis A; Gopalakrishnan, Gosala S; Black, F Owen; Wood, Scott J

2009-11-06

Loss of balance and increased fall risk is a common problem associated with aging. Changes in vestibular function occur with aging but the contribution of reduced vestibular otolith function to fall risk remains unknown. We examined a population of 151 healthy individuals (aged 21-93) for both balance (sway measures) and ocular counter-rolling (OCR) function. We assessed balance function with eyes open and closed on a firm surface, eyes open and closed on a foam surface and OCR during +/-20 degree roll tilt at 0.005 Hz. Subjects demonstrated a significant age-related reduction in OCR and increase in postural sway. The effect of age on OCR was greater in females than males. The reduction in OCR was strongly correlated with the mediolateral measures of sway with eyes closed. This correlation was also present in the elderly group alone, suggesting that aging alone does not account for this effect. OCR decreased linearly with age and at a greater rate in females than males. This loss of vestibular otolith-ocular function is associated with increased mediolateral measures of sway which have been shown to be related to increased risk of falls. These data suggest a role for loss of otolith function in contributing to fall risk in the elderly. Further prospective, longitudinal studies are necessary to confirm these findings.

Sleep Loss as a Factor to Induce Cellular and Molecular Inflammatory Variations

Directory of Open Access Journals (Sweden)

Gabriela Hurtado-Alvarado

2013-01-01

Full Text Available A reduction in the amount of time spent sleeping occurs chronically in modern society. Clinical and experimental studies in humans and animal models have shown that immune function is impaired when sleep loss is experienced. Sleep loss exerts a strong regulatory influence on peripheral levels of inflammatory mediators of the immune response. An increasing number of research projects support the existence of reciprocal regulation between sleep and low-intensity inflammatory response. Recent studies show that sleep deficient humans and rodents exhibit a proinflammatory component; therefore, sleep loss is considered as a risk factor for developing cardiovascular, metabolic, and neurodegenerative diseases (e.g., diabetes, Alzheimer's disease, and multiple sclerosis. Circulating levels of proinflammatory mediators depend on the intensity and duration of the method employed to induce sleep loss. Recognizing the fact that the concentration of proinflammatory mediators is different between acute and chronic sleep-loss may expand the understanding of the relationship between sleep and the immune response. The aim of this review is to integrate data from recent published reports (2002–2013 on the effects of sleep loss on the immune response. This review may allow readers to have an integrated view of the mechanisms involved in central and peripheral deficits induced by sleep loss.

Multiple mechanisms enable invasive species to suppress native species.

Science.gov (United States)

Bennett, Alison E; Thomsen, Meredith; Strauss, Sharon Y

2011-07-01

Invasive plants represent a significant threat to ecosystem biodiversity. To decrease the impacts of invasive species, a major scientific undertaking of the last few decades has been aimed at understanding the mechanisms that drive invasive plant success. Most studies and theories have focused on a single mechanism for predicting the success of invasive plants and therefore cannot provide insight as to the relative importance of multiple interactions in predicting invasive species' success. We examine four mechanisms that potentially contribute to the success of invasive velvetgrass Holcus lanatus: direct competition, indirect competition mediated by mammalian herbivores, interference competition via allelopathy, and indirect competition mediated by changes in the soil community. Using a combination of field and greenhouse approaches, we focus on the effects of H. lanatus on a common species in California coastal prairies, Erigeron glaucus, where the invasion is most intense. We found that H. lanatus had the strongest effects on E. glaucus via direct competition, but it also influenced the soil community in ways that feed back to negatively influence E. glaucus and other native species after H. lanatus removal. This approach provided evidence for multiple mechanisms contributing to negative effects of invasive species, and it identified when particular strategies were most likely to be important. These mechanisms can be applied to eradication of H. lanatus and conservation of California coastal prairie systems, and they illustrate the utility of an integrated set of experiments for determining the potential mechanisms of invasive species' success.

Mechanical property changes during neonatal development and healing using a multiple regression model.

Science.gov (United States)

Ansorge, Heather L; Adams, Sheila; Jawad, Abbas F; Birk, David E; Soslowsky, Louis J

2012-04-30

During neonatal development, tendons undergo a well orchestrated process whereby extensive structural and compositional changes occur in synchrony to produce a normal tissue. Conversely, during the repair response to injury, structural and compositional changes occur, but a mechanically inferior tendon is produced. As a result, developmental processes have been postulated as a potential paradigm for elucidation of mechanistic insight required to develop treatment modalities to improve adult tissue healing. The objective of this study was to compare and contrast normal development with injury during early and late developmental healing. Using backwards multiple linear regressions, quantitative and objective information was obtained into the structure-function relationships in tendon. Specifically, proteoglycans were shown to be significant predictors of modulus during early developmental healing but not during late developmental healing or normal development. Multiple independent parameters predicted percent relaxation during normal development, however, only biglycan and fibril diameter parameters predicted percent relaxation during early developmental healing. Lastly, multiple differential predictors were observed between early development and early developmental healing; however, no differential predictors were observed between late development and late developmental healing. This study presents a model through which objective analysis of how compositional and structural parameters that affect the development of mechanical parameters can be quantitatively measured. In addition, information from this study can be used to develop new treatment and therapies through which improved adult tendon healing can be obtained. Copyright © 2012 Elsevier Ltd. All rights reserved.

Heavy-flavour production as a function of multiplicity in pp collisions at ALICE

CERN Multimedia

CERN. Geneva

2015-01-01

The measurement of inclusive heavy-flavour production cross sections in proton-proton (pp) collisions at LHC energies constituted an important test of perturbative QCD calculations. The measured cross sections can be described within uncertainties by next-to-leading order (NLO) and fixed-order with next-to-leading-log re-summation (FONLL) calculations with collinear factorization, as well as by leading-order (LO) calculations in the kt-factorization approach. More differential measurements of charm and beauty production in pp collisions can provide further information about the particle production mechanisms. The production of prompt D mesons and non-prompt J/psi mesons in proton-proton collisions at a centre-of-mass energy of 7 TeV was measured by the ALICE Collaboration as a function of the multiplicity of charged particles produced in the collision. D0, D+ and D*+ mesons were reconstructed from their hadronic decay channels in the central rapidity region and their yields were measured in different multipl...

Control rod drive mechanism stator loss of coolant test

International Nuclear Information System (INIS)

Besel, L.; Ibatuan, R.

1977-04-01

This report documents the stator loss of coolant test conducted at HEDL on the lead unit Control Rod Drive Mechanism (CRDM) in February, 1977. The purpose of the test was to demonstrate scram capability of the CRDM with an uncooled stator and to obtain a time versus temperature curve of an uncooled stator under power. Brief descriptions of the test, hardware used, and results obtained are presented in the report. The test demonstrated that the CRDM could be successfully scrammed with no anomalies in both the two-phase and three-phase stator winding hold conditions after the respective equilibrium stator temperatures had been obtained with no stator coolant

Anderson phase-slip theory and loss mechanism of the motion of vortices in superconductors

International Nuclear Information System (INIS)

Xu, L.K.; Shan, L.; Tang, Y.L.; Wang, F.; Xu, X.N.; Jin, X.; Nanjing Univ.

2001-01-01

The loss mechanism of the super-current is discussed in the frame of Anderson phase-slip theory and G-L theory. In the discussion we also use vortex conservation equations instead of Maxwell equations. It is found that this method is more reasonable to apply the vortex motion induced energy loss in type II superconductors than the traditional deduction in terms of Maxwell equations. Moreover, we propose a new method to determine the effective pinning energy of vortex lines in type II superconductors. (orig.)

Margins Associated with Loss of Assured Safety for Systems with Multiple Time-Dependent Failure Modes.

Energy Technology Data Exchange (ETDEWEB)

Helton, Jon C. [Arizona State Univ., Tempe, AZ (United States); Brooks, Dusty Marie [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Sallaberry, Cedric Jean-Marie. [Engineering Mechanics Corp. of Columbus, OH (United States)

2018-02-01

Representations for margins associated with loss of assured safety (LOAS) for weak link (WL)/strong link (SL) systems involving multiple time-dependent failure modes are developed. The following topics are described: (i) defining properties for WLs and SLs, (ii) background on cumulative distribution functions (CDFs) for link failure time, link property value at link failure, and time at which LOAS occurs, (iii) CDFs for failure time margins defined by (time at which SL system fails) – (time at which WL system fails), (iv) CDFs for SL system property values at LOAS, (v) CDFs for WL/SL property value margins defined by (property value at which SL system fails) – (property value at which WL system fails), and (vi) CDFs for SL property value margins defined by (property value of failing SL at time of SL system failure) – (property value of this SL at time of WL system failure). Included in this presentation is a demonstration of a verification strategy based on defining and approximating the indicated margin results with (i) procedures based on formal integral representations and associated quadrature approximations and (ii) procedures based on algorithms for sampling-based approximations.

Redefining "Critical" Bone Loss in Shoulder Instability: Functional Outcomes Worsen With "Subcritical" Bone Loss.

Science.gov (United States)

Shaha, James S; Cook, Jay B; Song, Daniel J; Rowles, Douglas J; Bottoni, Craig R; Shaha, Steven H; Tokish, John M

2015-07-01

Glenoid bone loss is a common finding in association with anterior shoulder instability. This loss has been identified as a predictor of failure after operative stabilization procedures. Historically, 20% to 25% has been accepted as the "critical" cutoff where glenoid bone loss should be addressed in a primary procedure. Few data are available, however, on lesser, "subcritical" amounts of bone loss (below the 20%-25% range) on functional outcomes and failure rates after primary arthroscopic stabilization for shoulder instability. To evaluate the effect of glenoid bone loss, especially in subcritical bone loss (below the 20%-25% range), on outcomes assessments and redislocation rates after an isolated arthroscopic Bankart repair for anterior shoulder instability. Cohort study; Level of evidence, 3. Subjects were 72 consecutive anterior instability patients (73 shoulders) who underwent isolated anterior arthroscopic labral repair at a single military institution by 1 of 3 sports medicine fellowship-trained orthopaedic surgeons. Data were collected on demographics, the Western Ontario Shoulder Instability (WOSI) score, Single Assessment Numeric Evaluation (SANE) score, and failure rates. Failure was defined as recurrent dislocation. Glenoid bone loss was calculated via a standardized technique on preoperative imaging. The average bone loss across the group was calculated, and patients were divided into quartiles based on the percentage of glenoid bone loss. Outcomes were analyzed for the entire cohort, between the quartiles, and within each quartile. Outcomes were then further stratified between those sustaining a recurrence versus those who remained stable. The mean age at surgery was 26.3 years (range, 20-42 years), and the mean follow-up was 48.3 months (range, 23-58 months). The cohort was divided into quartiles based on bone loss. Quartile 1 (n = 18) had a mean bone loss of 2.8% (range, 0%-7.1%), quartile 2 (n = 19) had 10.4% (range, 7.3%-13.5%), quartile 3 (n

Antiviral Defense Mechanisms in Honey Bees

Science.gov (United States)

Brutscher, Laura M.; Daughenbaugh, Katie F.; Flenniken, Michelle L.

2015-01-01

Honey bees are significant pollinators of agricultural crops and other important plant species. High annual losses of honey bee colonies in North America and in some parts of Europe have profound ecological and economic implications. Colony losses have been attributed to multiple factors including RNA viruses, thus understanding bee antiviral defense mechanisms may result in the development of strategies that mitigate colony losses. Honey bee antiviral defense mechanisms include RNA-interference, pathogen-associated molecular pattern (PAMP) triggered signal transduction cascades, and reactive oxygen species generation. However, the relative importance of these and other pathways is largely uncharacterized. Herein we review the current understanding of honey bee antiviral defense mechanisms and suggest important avenues for future investigation. PMID:26273564

Sequential optimization of matrix chain multiplication relative to different cost functions

KAUST Repository

Chikalov, Igor; Hussain, Shahid; Moshkov, Mikhail

2011-01-01

In this paper, we present a methodology to optimize matrix chain multiplication sequentially relative to different cost functions such as total number of scalar multiplications, communication overhead in a multiprocessor environment, etc. For n matrices our optimization procedure requires O(n 3) arithmetic operations per one cost function. This work is done in the framework of a dynamic programming extension that allows sequential optimization relative to different criteria. © 2011 Springer-Verlag Berlin Heidelberg.

The Effects of Gain- versus Loss-Framed Messages Following Health Risk Information on Physical Activity in Individuals With Multiple Sclerosis.

Science.gov (United States)

Lithopoulos, Alexander; Bassett-Gunter, Rebecca L; Martin Ginis, Kathleen A; Latimer-Cheung, Amy E

2017-06-01

Few people with multiple sclerosis engage in physical activity. Messaging interventions may motivate more physical activity among these individuals. The purpose of this online study was to evaluate an intervention presenting participants with multiple sclerosis (N = 237) with risk information (i.e., information demonstrating people with multiple sclerosis are more likely to experience certain health issues) or no risk information followed by gain- or loss-framed physical activity messages. Participants completed questionnaires on Days 1, 6, and 28 and received information material on Days 2-5. The dependent variables were as follows: physical activity intentions and behavior, response and task efficacy, perceived threat (i.e., perception of threat to health issues relevant to people with multiple sclerosis), and avoidance (i.e., avoiding thinking about/doing something about the health issues presented in the messages). Analyses indicated physical activity and response efficacy increased over time. Also, participants receiving risk information had higher levels of physical activity and perceived threat. However, manipulation checks showed no differences between participants regarding perceptions of risk information or gain/loss-framed messages. Despite the lack of impact of the framing intervention, this study suggests that a brief informational intervention can positively influence physical activity and certain correlates of physical activity among people with multiple sclerosis.

Alterations in the adenosine metabolism and CD39/CD73 adenosinergic machinery cause loss of Treg cell function and autoimmunity in ADA-deficient SCID

Science.gov (United States)

Sauer, Aisha V.; Brigida, Immacolata; Carriglio, Nicola; Jofra Hernandez, Raisa; Scaramuzza, Samantha; Clavenna, Daniela; Sanvito, Francesca; Poliani, Pietro L.; Gagliani, Nicola; Carlucci, Filippo; Tabucchi, Antonella; Roncarolo, Maria Grazia; Traggiai, Elisabetta; Villa, Anna

2012-01-01

Adenosine acts as anti-inflammatory mediator on the immune system and has been described in regulatory T cell (Treg)–mediated suppression. In the absence of adenosine deaminase (ADA), adenosine and other purine metabolites accumulate, leading to severe immunodeficiency with recurrent infections (ADA-SCID). Particularly ADA-deficient patients with late-onset forms and after enzyme replacement therapy (PEG-ADA) are known to manifest immune dysregulation. Herein we provide evidence that alterations in the purine metabolism interfere with Treg function, thereby contributing to autoimmune manifestations in ADA deficiency. Tregs isolated from PEG-ADA–treated patients are reduced in number and show decreased suppressive activity, whereas they are corrected after gene therapy. Untreated murine ADA−/− Tregs show alterations in the plasma membrane CD39/CD73 ectonucleotidase machinery and limited suppressive activity via extracellular adenosine. PEG-ADA–treated mice developed multiple autoantibodies and hypothyroidism in contrast to mice treated with bone marrow transplantation or gene therapy. Tregs isolated from PEG-ADA–treated mice lacked suppressive activity, suggesting that this treatment interferes with Treg functionality. The alterations in the CD39/CD73 adenosinergic machinery and loss of function in ADA-deficient Tregs provide new insights into a predisposition to autoimmunity and the underlying mechanisms causing defective peripheral tolerance in ADA-SCID. Trials were registered at www.clinicaltrials.gov as NCT00598481/NCT00599781. PMID:22184407

Using Loss Functions for DIF Detection: An Empirical Bayes Approach.

Science.gov (United States)

Zwick, Rebecca; Thayer, Dorothy; Lewis, Charles

2000-01-01

Studied a method for flagging differential item functioning (DIF) based on loss functions. Builds on earlier research that led to the development of an empirical Bayes enhancement to the Mantel-Haenszel DIF analysis. Tested the method through simulation and found its performance better than some commonly used DIF classification systems. (SLD)

Functional analysis screening for multiple topographies of problem behavior.

Science.gov (United States)

Bell, Marlesha C; Fahmie, Tara A

2018-04-23

The current study evaluated a screening procedure for multiple topographies of problem behavior in the context of an ongoing functional analysis. Experimenters analyzed the function of a topography of primary concern while collecting data on topographies of secondary concern. We used visual analysis to predict the function of secondary topographies and a subsequent functional analysis to test those predictions. Results showed that a general function was accurately predicted for five of six (83%) secondary topographies. A specific function was predicted and supported for a subset of these topographies. The experimenters discuss the implication of these results for clinicians who have limited time for functional assessment. © 2018 Society for the Experimental Analysis of Behavior.

Functional Connectivity with Distinct Neural Networks Tracks Fluctuations in Gain/Loss Framing Susceptibility

Science.gov (United States)

Smith, David V.; Sip, Kamila E.; Delgado, Mauricio R.

2016-01-01

Multiple large-scale neural networks orchestrate a wide range of cognitive processes. For example, interoceptive processes related to self-referential thinking have been linked to the default-mode network (DMN); whereas exteroceptive processes related to cognitive control have been linked to the executive-control network (ECN). Although the DMN and ECN have been postulated to exert opposing effects on cognition, it remains unclear how connectivity with these spatially overlapping networks contribute to fluctuations in behavior. While previous work has suggested the medial prefrontal cortex (MPFC) is involved in behavioral change following feedback, these observations could be linked to interoceptive processes tied to DMN or exteroceptive processes tied to ECN because MPFC is positioned in both networks. To address this problem, we employed independent component analysis combined with dual-regression functional connectivity analysis. Participants made a series of financial decisions framed as monetary gains or losses. In some sessions, participants received feedback from a peer observing their choices; in other sessions, feedback was not provided. Following feedback, framing susceptibility—indexed as the increase in gambling behavior in loss frames compared to gain frames—was heightened in some participants and diminished in others. We examined whether these individual differences were linked to differences in connectivity by contrasting sessions containing feedback against those that did not contain feedback. We found two key results. As framing susceptibility increased, the MPFC increased connectivity with DMN; in contrast, temporal-parietal junction decreased connectivity with the ECN. Our results highlight how functional connectivity patterns with distinct neural networks contribute to idiosyncratic behavioral changes. PMID:25858445

Identification of LHC beam loss mechanism : a deterministic treatment of loss patterns

CERN Document Server

Marsili, Aurélien

CERN's Large Hadron Collider (LHC) is the largest machine ever built, with a total circumference of 26.7 km; and it is the most powerful accelerator ever, both in beam energy and beam intensity. The main magnets are superconducting, keeping the particles into two counter circulating beams, which collide in four interaction points. CERN and the LHC will be described in chap. 1. The superconducting magnets of the LHC have to be protected against particle losses. Depending on the number of lost particles, the coils of the magnets will become normal conducting and/or will be damaged. To avoid these events a beam loss monitoring (BLM) system was installed to measure the particle loss rates. If the predefined safe thresholds of loss rates are exceeded, the beams are directed out of the accelerator ring towards the beam dump. The detectors of the BLM system are mainly ionization chambers located outside of the cryostats. In total, about 3500 ionisation chambers are installed. Further challenges include the high dyna...

Honeybee immunity and colony losses

Directory of Open Access Journals (Sweden)

F. Nazzi

2014-10-01

Full Text Available The decline of honeybee colonies and their eventual collapse is a widespread phenomenon in the Northern hemisphere of the globe, which severely limits the beekeeping industry. This dramatic event is associated with an enhanced impact of parasites and pathogens on honeybees, which is indicative of reduced immunocompetence. The parasitic mite Varroa destructor and the vectored viral pathogens appear to play a key-role in the induction of this complex syndrome. In particular, the Deformed Wing Virus (DWV is widespread and is now considered, along with Varroa, one of the major causes of bee colony losses. Several lines of evidence indicate that this mite/DWV association severely affects the immune system of honeybees and makes them more sensitive to the action of other stress factors. The molecular mechanisms underpinning these complex interactions are currently being investigated and the emerging information has allowed the development of a new functional model, describing how different stress factors may synergistically concur in the induction of bee immune alteration and health decline. This provides a new logical framework in which to interpret the proposed multifactorial origin of bee colony losses and sets the stage for a more comprehensive and integrated analysis of the effect that multiple stress agents may have on honeybees.

Detection of reduced interhemispheric cortical communication during task execution in multiple sclerosis patients using functional near-infrared spectroscopy

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Jimenez, Jon J.; Yang, Runze; Nathoo, Nabeela; Varshney, Vishal P.; Golestani, Ali-Mohammad; Goodyear, Bradley G.; Metz, Luanne M.; Dunn, Jeff F.

2014-07-01

Multiple sclerosis (MS) impairs brain activity through demyelination and loss of axons. Increased brain activity is accompanied by increases in microvascular hemoglobin oxygen saturation (oxygenation) and total hemoglobin, which can be measured using functional near-infrared spectroscopy (fNIRS). Due to the potentially reduced size and integrity of the white matter tracts within the corpus callosum, it may be expected that MS patients have reduced functional communication between the left and right sides of the brain; this could potentially be an indicator of disease progression. To assess interhemispheric communication in MS, we used fNIRS during a unilateral motor task and the resting state. The magnitude of the change in hemoglobin parameters in the motor cortex was significantly reduced in MS patients during the motor task relative to healthy control subjects. There was also a significant decrease in interhemispheric communication between the motor cortices (expressed as coherence) in MS patients compared to controls during the motor task, but not during the resting state. fNIRS assessment of interhemispheric coherence during task execution may be a useful marker in disorders with white matter damage or axonal loss, including MS.

Local loss and spatial homogenization of plant diversity reduce ecosystem multifunctionality

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Experimental studies show that local plant species loss decreases ecosystem functioning and services, but it remains unclear how other changes in biodiversity, such as spatial homogenization, alter multiple processes (multifunctionality) in natural ecosystems. We present a global analysis of eight ...

Functional Neuroanatomy Involved in Automatic order Mental Arithmetic and Recitation of the Multiplication Table

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Wang, Li-Qun; Saito, Masao

We used 1.5T functional magnetic resonance imaging (fMRI) to explore that which brain areas contribute uniquely to numeric computation. The BOLD effect activation pattern of metal arithmetic task (successive subtraction: actual calculation task) was compared with multiplication tables repetition task (rote verbal arithmetic memory task) response. The activation found in right parietal lobule during metal arithmetic task suggested that quantitative cognition or numeric computation may need the assistance of sensuous convert, such as spatial imagination and spatial sensuous convert. In addition, this mechanism may be an ’analog algorithm’ in the simple mental arithmetic processing.

Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis

DEFF Research Database (Denmark)

Palmer, Colin N A; Irvine, Alan D; Terron-Kwiatkowski, Ana

2006-01-01

most genetic studies have focused on immunological mechanisms, a primary epithelial barrier defect has been anticipated. Filaggrin is a key protein that facilitates terminal differentiation of the epidermis and formation of the skin barrier. Here we show that two independent loss-of-function genetic...... variants (R510X and 2282del4) in the gene encoding filaggrin (FLG) are very strong predisposing factors for atopic dermatitis. These variants are carried by approximately 9% of people of European origin. These variants also show highly significant association with asthma occurring in the context of atopic...

Quantum mechanics of history: The decoherence functional in quantum mechanics

International Nuclear Information System (INIS)

Dowker, H.F.; Halliwell, J.J.

1992-01-01

We study a formulation of quantum mechanics in which the central notion is that of a quantum-mechanical history---a sequence of events at a succession of times. The primary aim is to identify sets of ''decoherent'' (or ''consistent'') histories for the system. These are quantum-mechanical histories suffering negligible interference with each other, and, therefore, to which probabilities may be assigned. These histories may be found for a given system using the so-called decoherence functional. When the decoherence functional is exactly diagonal, probabilities may be assigned to the histories, and all probability sum rules are satisfied exactly. We propose a condition for approximate decoherence, and argue that it implies that most probability sum rules will be satisfied to approximately the same degree. We also derive an inequality bounding the size of the off-diagonal terms of the decoherence functional. We calculate the decoherence functional for some simple one-dimensional systems, with a variety of initial states. For these systems, we explore the extent to which decoherence is produced using two different types of coarse graining. The first type of coarse graining involves imprecise specification of the particle's position. The second involves coupling the particle to a thermal bath of harmonic oscillators and ignoring the details of the bath (the Caldeira-Leggett model). We argue that both types of coarse graining are necessary in general. We explicitly exhibit the degree of decoherence as a function of the temperature of the bath, and of the width to within which the particle's position is specified. We study the diagonal elements of the decoherence functional, representing the probabilities for the possible histories of the system

Neurodegenerative disease mutations in TREM2 reveal a functional surface and distinct loss-of-function mechanisms

Energy Technology Data Exchange (ETDEWEB)

Kober, Daniel L.; Alexander-Brett, Jennifer M.; Karch, Celeste M.; Cruchaga, Carlos; Colonna, Marco; Holtzman, Michael J.; Brett, Thomas J. (WU-MED)

2016-12-20

Genetic variations in the myeloid immune receptor TREM2 are linked to several neurodegenerative diseases. To determine how TREM2 variants contribute to these diseases, we performed structural and functional studies of wild-type and variant proteins. Our 3.1 Å TREM2 crystal structure revealed that mutations found in Nasu-Hakola disease are buried whereas Alzheimer’s disease risk variants are found on the surface, suggesting that these mutations have distinct effects on TREM2 function. Biophysical and cellular methods indicate that Nasu-Hakola mutations impact protein stability and decrease folded TREM2 surface expression, whereas Alzheimer’s risk variants impact binding to a TREM2 ligand. Additionally, the Alzheimer’s risk variants appear to epitope map a functional surface on TREM2 that is unique within the larger TREM family. These findings provide a guide to structural and functional differences among genetic variants of TREM2, indicating that therapies targeting the TREM2 pathway should be tailored to these genetic and functional differences with patient-specific medicine approaches for neurodegenerative disorders.

A mechanical characterisation on multiple timescales of electroconductive magnetorheological elastomers

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Schümann, M.; Morich, J.; Kaufhold, T.; Böhm, V.; Zimmermann, K.; Odenbach, S.

2018-05-01

Magnetorheological elastomers are a type of smart hybrid material which combines elastic properties of a soft elastomer matrix with magnetic properties of magnetic micro particles. This leads to a material with magnetically controllable mechanical properties of which the magnetorheological effect is the best known. The addition of electroconductive particles to the polymer mix adds electrical properties to the material behaviour. The resulting electrical resistance of the sample can be manipulated by external magnetic fields and mechanical loads. This results in a distinct interplay of mechanical, electrical and magnetic effects with a highly complex time behaviour. In this paper a mechanical characterisation on multiple time scales was conducted to get an insight on the short and long-term electrical and mechanical behaviour of this novel material. The results show a complex resistivity behaviour on several timescales, sensitive to magnetic fields and strain velocity. The observed material exhibits fatigue and relaxation behaviour, whereas the magnetorheological effect appears not to interfere with the piezoresistive properties.

Exponential Decline of Deep-Sea Ecosystem Functioning Linked to Benthic Biodiversity Loss

OpenAIRE

Danovaro, Roberto; Gambi, Cristina; Dell'Anno, Antonio; Corinaldesi, Cinzia; Fraschetti, Simonetta; Vanreusel, Ann; Vincx, Magda; Gooday, Andrew J.

2008-01-01

BackgroundRecent investigations suggest that biodiversity loss might impair the functioning and sustainability of ecosystems. Although deep-sea ecosystems are the most extensive on Earth, represent the largest reservoir of biomass, and host a large proportion of undiscovered biodiversity, the data needed to evaluate the consequences of biodiversity loss on the ocean floor are completely lacking.ResultsHere, we present a global-scale study based on 116 deep-sea sites that relates benthic biodi...

Role of vision loss, functional limitations and the supporting network in depression in a general population.

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van Nispen, Ruth M A; Vreeken, Hilde L; Comijs, Hannie C; Deeg, Dorly J H; van Rens, Ger H M B

2016-02-01

Although the prevalence of depression in visually impaired older persons is high, the association between vision loss and depression seems to be influenced by factors other than visual impairment. In this study, the role of vision loss, functional limitations and social network characteristics in relation to depressive symptoms was investigated. Cross-sectional data (N = 1237) from the Longitudinal Aging Study Amsterdam were used to investigate the prevalence of depression (Center of Epidemiological Studies-Depression scale) within subgroups with increasing vision loss. In linear regression models, functional limitations and social network characteristics were examined as possible mediators in the association between vision loss and depression. Having a partner was considered to be a potential moderator. Although a significant linear trend was found in the presence of depressive symptoms with 14% in normally sighted, 23% in mild and 37% in severe vision loss (χ(2)(1) = 14.9; p depression. Mediators were functional limitations (p depression, a trend was found with increasing severity of vision loss, indicating the need for more attention in (mental) health care and low-vision rehabilitation. In the general older population, vision loss was not an independent determinant of depression but was mediated by functional limitations and social network size. Rather than receiving actual social support, the idea of having a social network to rely on when needed seemed to be associated with lower levels of depression. © 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Numerical study of impact erosion of multiple solid particle

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Zheng, Chao; Liu, Yonghong; Chen, Cheng; Qin, Jie; Ji, Renjie; Cai, Baoping

2017-11-01

Material erosion caused by continuous particle impingement during hydraulic fracturing results in significant economic loss and increased production risks. The erosion process is complex and has not been clearly explained through physical experiments. To address this problem, a multiple particle model in a 3D configuration was proposed to investigate the dynamic erosion process. This approach can significantly reduce experiment costs. The numerical model considered material damping and elastic-plastic material behavior of target material. The effects of impact parameters on erosion characteristics, such as plastic deformation, contact time, and energy loss rate, were investigated. Based on comprehensive studies, the dynamic erosion mechanism and geometry evolution of eroded crater was obtained. These findings can provide a detailed erosion process of target material and insights into the material erosion caused by multiple particle impingement.

Does psychological functioning mediate the relationship between bullying involvement and weight loss preoccupation in adolescents? A two-stage cross-sectional study.

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Lee, Kirsty; Guy, Alexa; Dale, Jeremy; Wolke, Dieter

2017-03-24

Adolescent bullying is associated with a range of adversities for those who are bullied i.e., victims and bully-victims (e.g., those who bully others and get victimised), including reduced psychological functioning and eating disorder symptoms. Bullies are generally well-adjusted psychologically, but previous research suggests that bullies may also engage in problematic diet behaviours. This study investigates a) whether adolescents involved in bullying (bullies, victims, bully-victims) are at increased risk of weight loss preoccupation, b) whether psychological functioning mediates this relationship and c) whether sex is a key moderator. A two-stage design was used. In stage 1, adolescents (n = 2782) from five UK secondary schools were screened for bullying involvement using self and peer reports. In stage 2, a sample of bullies, victims, bully-victims and uninvolved adolescents (n = 767) completed a battery of assessments. The measures included the eating behaviours component of the Child and Adolescent Psychiatric Assessment, which was reduced to one factor (weight loss preoccupation) and used as the outcome variable. Measures of self-esteem, body-esteem and emotional problems were reduced to a latent (mediator) variable of psychological functioning. Multi-group analysis examined the effects of sex and all models were adjusted for covariates (BMI, pubertal stage, age, parental education and ethnicity). Bullies, victims and bully-victims were at increased risk of weight loss preoccupation compared to adolescents uninvolved in bullying. The mechanism by which bullying involvement related to increased weight loss preoccupation varied by bullying role: in bullies the effect was direct, in victims the effect was indirect (via reduced psychological functioning) and in bully-victims the effect was both direct and indirect. Sex significantly moderated the relationship in bullies: weight loss preoccupation was only statistically significant in bullies who were

Changes in biodiversity and functioning of reef fish assemblages following coral bleaching and coral loss

KAUST Repository

Pratchett, M.S.; Hoey, A.S.; Wilson, S.K.; Messmer, V.; Graham, N.A.J.

2011-01-01

Coral reef ecosystems are increasingly subject to severe, large-scale disturbances caused by climate change (e.g., coral bleaching) and other more direct anthropogenic impacts. Many of these disturbances cause coral loss and corresponding changes in habitat structure, which has further important effects on abundance and diversity of coral reef fishes. Declines in the abundance and diversity of coral reef fishes are of considerable concern, given the potential loss of ecosystem function. This study explored the effects of coral loss, recorded in studies conducted throughout the world, on the diversity of fishes and also on individual responses of fishes within different functional groups. Extensive (>60%) coral loss almost invariably led to declines in fish diversity. Moreover, most fishes declined in abundance following acute disturbances that caused >10% declines in local coral cover. Response diversity, which is considered critical in maintaining ecosystem function and promoting resilience, was very low for corallivores, but was much higher for herbivores, omnivores and carnivores. Sustained and ongoing climate change thus poses a significant threat to coral reef ecosystems and diversity hotspots are no less susceptible to projected changes in diversity and function.

Changes in biodiversity and functioning of reef fish assemblages following coral bleaching and coral loss

KAUST Repository

Pratchett, M.S.

2011-08-12

Coral reef ecosystems are increasingly subject to severe, large-scale disturbances caused by climate change (e.g., coral bleaching) and other more direct anthropogenic impacts. Many of these disturbances cause coral loss and corresponding changes in habitat structure, which has further important effects on abundance and diversity of coral reef fishes. Declines in the abundance and diversity of coral reef fishes are of considerable concern, given the potential loss of ecosystem function. This study explored the effects of coral loss, recorded in studies conducted throughout the world, on the diversity of fishes and also on individual responses of fishes within different functional groups. Extensive (>60%) coral loss almost invariably led to declines in fish diversity. Moreover, most fishes declined in abundance following acute disturbances that caused >10% declines in local coral cover. Response diversity, which is considered critical in maintaining ecosystem function and promoting resilience, was very low for corallivores, but was much higher for herbivores, omnivores and carnivores. Sustained and ongoing climate change thus poses a significant threat to coral reef ecosystems and diversity hotspots are no less susceptible to projected changes in diversity and function.

Optimal Reinsurance Design for Pareto Optimum: From the Perspective of Multiple Reinsurers

Directory of Open Access Journals (Sweden)

Xing Rong

2016-01-01

Full Text Available This paper investigates optimal reinsurance strategies for an insurer which cedes the insured risk to multiple reinsurers. Assume that the insurer and every reinsurer apply the coherent risk measures. Then, we find out the necessary and sufficient conditions for the reinsurance market to achieve Pareto optimum; that is, every ceded-loss function and the retention function are in the form of “multiple layers reinsurance.”

Heterogeneity of reward mechanisms.

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Lajtha, A; Sershen, H

2010-06-01

The finding that many drugs that have abuse potential and other natural stimuli such as food or sexual activity cause similar chemical changes in the brain, an increase in extracellular dopamine (DA) in the shell of the nucleus accumbens (NAccS), indicated some time ago that the reward mechanism is at least very similar for all stimuli and that the mechanism is relatively simple. The presently available information shows that the mechanisms involved are more complex and have multiple elements. Multiple brain regions, multiple receptors, multiple distinct neurons, multiple transmitters, multiple transporters, circuits, peptides, proteins, metabolism of transmitters, and phosphorylation, all participate in reward mechanisms. The system is variable, is changed during development, is sex-dependent, and is influenced by genetic differences. Not all of the elements participate in the reward of all stimuli. Different set of mechanisms are involved in the reward of different drugs of abuse, yet different mechanisms in the reward of natural stimuli such as food or sexual activity; thus there are different systems that distinguish different stimuli. Separate functions of the reward system such as anticipation, evaluation, consummation and identification; all contain function-specific elements. The level of the stimulus also influences the participation of the elements of the reward system, there are possible reactions to even below threshold stimuli, and excessive stimuli can change reward to aversion involving parts of the system. Learning and memory of past reward is an important integral element of reward and addictive behavior. Many of the reward elements are altered by repeated or chronic stimuli, and chronic exposure to one drug is likely to alter the response to another stimulus. To evaluate and identify the reward stimulus thus requires heterogeneity of the reward components in the brain.

Loss-of-Function Sodium Channel Mutations in Infancy A Pattern Unfolds

NARCIS (Netherlands)

Chockalingam, Priya; Wilde, Arthur A. M.

2012-01-01

The role of channelopathies in the pathogenesis of sudden cardiac death (SCD) in patients with structurally normal hearts is a rapidly evolving story.(1) Many ion channels are involved, including loss-of-function sodium channelopathies of which the phenotypic spectrum ranges from lethal arrhythmias

Recent advances in the study of age-related hearing loss - A Mini-Review

Science.gov (United States)

Kidd, Ambrose R; Bao, Jianxin

2013-01-01

Hearing loss is a common age-associated affliction that can result from the loss of hair cells and spiral ganglion neurons (SGNs) in the cochlea. Although hair cells and SGNs are typically lost in the same cochlea, recent analysis suggests that they can occur independently, via unique mechanisms. Research has identified both environmental and genetic factors that contribute to degeneration of cochlear cells. Additionally, molecular analysis has identified multiple cell signaling mechanisms that likely contribute to pathological changes that result in hearing deficiencies. These analyses should serve as useful primers for future work, including genomic and proteomic analysis, to elucidate the mechanisms driving cell loss in the aging cochlea. Significant progress in this field has occurred in the past decade. As our understanding of aging-induced cochlear changes continues to improve, our ability to offer medical intervention will surely benefit the growing elderly population. PMID:22710288

Prevalence of skeletal muscle mass loss and its association with swallowing function after cardiovascular surgery.