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.

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.

Gaze stabilization in chronic vestibular-loss and in cerebellar ataxia: interactions of feedforward and sensory feedback mechanisms.

Science.gov (United States)

Sağlam, M; Lehnen, N

2014-01-01

During gaze shifts, humans can use visual, vestibular, and proprioceptive feedback, as well as feedforward mechanisms, for stabilization against active and passive head movements. The contributions of feedforward and sensory feedback control, and the role of the cerebellum, are still under debate. To quantify these contributions, we increased the head moment of inertia in three groups (ten healthy, five chronic vestibular-loss and nine cerebellar-ataxia patients) while they performed large gaze shifts to flashed targets in darkness. This induces undesired head oscillations. Consequently, both active (desired) and passive (undesired) head movements had to be compensated for to stabilize gaze. All groups compensated for active and passive head movements, vestibular-loss patients less than the other groups (P feedforward mechanisms substantially contribute to gaze stabilization. Proprioception alone is not sufficient (gain 0.2). Stabilization against active and passive head movements was not impaired in our cerebellar ataxia patients.

Calf Strength Loss During Mechanical Unloading: Does It Matter?

Science.gov (United States)

English, K. L.; Mulavara, A.; Bloomberg, J.; Ploutz-Snyder, LL

2016-01-01

During the mechanical unloading of spaceflight and its ground-based analogs, muscle mass and muscle strength of the calf are difficult to preserve despite exercise countermeasures that effectively protect these parameters in the thigh. It is unclear what effects these local losses have on balance and whole body function which will be essential for successful performance of demanding tasks during future exploration missions.

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.

The contribution of family history to hearing loss in an older population.

Science.gov (United States)

McMahon, Catherine M; Kifley, Annette; Rochtchina, Elena; Newall, Philip; Mitchell, Paul

2008-08-01

Although it has been well established that the prevalence of and severity of hearing loss increase with age, the contribution of familial factors to age-related hearing loss cannot be quantified. This is largely because hearing loss in older people has both genetic and environmental contributions. As environmental factors play an increasing role with age, it is difficult to delineate the separate contribution of genetic factors to age-related hearing loss. In a population-based survey of hearing loss in a representative older Australian community, we attempted to overcome this using logistic regression analysis, accounting for known factors associated with hearing loss including age, sex, noise exposure at work, diabetes, and current smoking. We tested hearing thresholds using pure tone audiometry and used a forced choice questionnaire to determine the nature of family history in a population of individuals aged 50 yrs or older in a defined region, west of Sydney, Australia (N = 2669). We compared the characteristics of participants with and without family history of hearing loss. Of those reporting a positive family history, we compared subgroups for age, gender and severity of hearing loss, and trends by the severity of hearing loss. Logistic regression was used to obtain odds ratios (ORs) with 95% confidence intervals (CIs) that compared the chances of having hearing loss in participants with and without family history, after adjusting for other factors known associated with hearing loss. Our findings indicate that family history was most strongly associated with moderate to severe age-related hearing loss. We found a strong association between maternal family history of hearing loss and moderate to severe hearing loss in women (adjusted OR 3.0; 95% CI 1.6-5.6 in women with without a maternal history). Paternal family history of hearing loss was also significantly, though less strongly, associated with moderate-severe hearing loss in men (adjusted OR 2.0; CI 1

Functional vision loss: a diagnosis of exclusion.

Science.gov (United States)

Villegas, Rex B; Ilsen, Pauline F

2007-10-01

Most cases of visual acuity or visual field loss can be attributed to ocular pathology or ocular manifestations of systemic pathology. They can also occasionally be attributed to nonpathologic processes or malingering. Functional vision loss is any decrease in vision the origin of which cannot be attributed to a pathologic or structural abnormality. Two cases of functional vision loss are described. In the first, a 58-year-old man presented for a baseline eye examination for enrollment in a vision rehabilitation program. He reported bilateral blindness since a motor vehicle accident with head trauma 4 years prior. Entering visual acuity was "no light perception" in each eye. Ocular health examination was normal and the patient made frequent eye contact with the examiners. He was referred for neuroimaging and electrophysiologic testing. The second case was a 49-year-old man who presented with a long history of intermittent monocular diplopia. His medical history was significant for psycho-medical evaluations and a diagnosis of factitious disorder. Entering uncorrected visual acuities were 20/20 in each eye, but visual field testing found constriction. No abnormalities were found that could account for the monocular diplopia or visual field deficit. A diagnosis of functional vision loss secondary to factitious disorder was made. Functional vision loss is a diagnosis of exclusion. In the event of reduced vision in the context of a normal ocular health examination, all other pathology must be ruled out before making the diagnosis of functional vision loss. Evaluation must include auxiliary ophthalmologic testing, neuroimaging of the visual pathway, review of the medical history and lifestyle, and psychiatric evaluation. Comanagement with a psychiatrist is essential for patients with functional vision loss.

Diagnosis of functional loss using with PET or SPECT

International Nuclear Information System (INIS)

Maeda, Tetsuya; Nagata, Ken

2009-01-01

Described are outlines of positron emission tomography (PET) and single photon emission computed tomography (SPECT) imaging, and their application to diagnosis of brain diseases accompanying functional loss. PET imaging by annihilation photons is useful to see the brain metabolic activity with use of compounds labeled by positron emitters like 11 C, 15 O, 13 N and 18 F. Cerebral blood flow (CBF), CB volume and oxygen extraction fraction correlate well with the cerebral activity and can be measured by PET with C 15 O 2 , H 2 15 O or 15 O 2 . 18 F-glucose is usable to measure the cerebral metabolic rate of glucose. SPECT imaging by γ-rays of 133 Xe, 123 I-iofetamine (IMP), 99m Tc-hexamethyl propylene amine oxime (HMPAO) and 99m Tc-ethyl cysteinate dimer (ECD) is useful also to measure CBF in different mechanisms from agent to agent, which often reflect the pathophysiology of the lesion in problem. These imaging techniques are applied to the diagnosis of regional functional loss in ischemic brain diseases like infarction, dementia (Alzheimer and multiple vascular) and Parkinsonism, of which characters and details of actual images are presented herein. Authors say that although the imaging diagnosis for brain functional loss has progressed, the integration of neurological finding, clinical process and simple morphological brain image as well is still important in the routine examination. (K.T.)

Electron loss mechanisms in collisions of He+ ions with various targets

International Nuclear Information System (INIS)

Sant'Anna, M.M.; Melo, W.S.; Santos, A.C.F.; Sigaud, G.M.; Montenegro, E.C.

1995-01-01

The electron loss of high-velocity ions by neutral atoms is due to two different and competing mechanisms. In the screening mode, the electron loss is basically due to the nucleus-electron interaction, with the target electrons assuming the passive role of decreasing the Coulomb field of the target nucleus in the vicinity of the projectile active electron. For a fixed projectile velocity, this contribution is expected to give a non-linear dependence with the target atomic number Z 2 due to the incomplete screening at the impact parameter region where the projectile ionization is more likely to occur. Within first-order theories, if the screening is completely absent, the expected dependence would be Z 2 2 ; with screening, it should scale between Z 2 and Z 2 2 . On the other hand, in the antiscreening mode, where the loss is due to the action of the target electrons and the target nucleus plays no active role, the expected dependence would be approximately linear with Z 2 . Thus, for first-order theories, the expected overall dependence with Z 2 would be dominated by the screening mode as Z 2 increases. We have measured total electron-loss cross sections of He + ions impinging upon He, Ne, Ar, Kr and Xe targets in the energy range from 1.0 to 4.0 MeV to complement previous measurements and the results point towards a much smaller contribution from the screening mode than expected from first-order theories, possibly due to a saturation effect manifested only in the screening channel. (orig.)

Contribution of Cultural Eutrophication to Marsh Loss in Jamaica Bay (NY)

Science.gov (United States)

Loss of salt marsh area in the Jamaica Bay Estuary (NY) has accelerated in recent years, with loss rates as high as 45 acres per year. A contributing factor to this acceleration is likely cultural eutrophication due to over 6 decades of sewage effluent inputs. We examined marsh...

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)

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.

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.

Contribution of elastic tissues to the mechanics and energetics of muscle function during movement.

Science.gov (United States)

Roberts, Thomas J

2016-01-01

Muscle force production occurs within an environment of tissues that exhibit spring-like behavior, and this elasticity is a critical determinant of muscle performance during locomotion. Muscle force and power output both depend on the speed of contraction, as described by the isotonic force-velocity curve. By influencing the speed of contractile elements, elastic structures can have a profound effect on muscle force, power and work. In very rapid movements, elastic mechanisms can amplify muscle power by storing the work of muscle contraction slowly and releasing it rapidly. When energy must be dissipated rapidly, such as in landing from a jump, energy stored rapidly in elastic elements can be released more slowly to stretch muscle contractile elements, reducing the power input to muscle and possibly protecting it from damage. Elastic mechanisms identified so far rely primarily on in-series tendons, but many structures within muscles exhibit spring-like properties. Actomyosin cross-bridges, actin and myosin filaments, titin, and the connective tissue scaffolding of the extracellular matrix all have the potential to store and recover elastic energy during muscle contraction. The potential contribution of these elements can be assessed from their stiffness and estimates of the strain they undergo during muscle function. Such calculations provide boundaries for the possible roles these springs might play in locomotion, and may help to direct future studies of the uses of elastic elements in muscle. © 2016. Published by The Company of Biologists Ltd.

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.

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.

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...

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.

Mechanical loss in tantala/silica dielectric mirror coatings

International Nuclear Information System (INIS)

Penn, Steven D; Sneddon, Peter H; Armandula, Helena; Betzwieser, Joseph C; Cagnoli, Gianpietro; Camp, Jordan; Crooks, D R M; Fejer, Martin M; Gretarsson, Andri M; Harry, Gregory M; Hough, Jim; Kittelberger, Scott E; Mortonson, Michael J; Route, Roger; Rowan, Sheila; Vassiliou, Christophoros C

2003-01-01

Current interferometric gravitational wave detectors use test masses with mirror coatings formed from multiple layers of dielectric materials, most commonly alternating layers of SiO 2 (silica) and Ta 2 O 5 (tantala). However, mechanical loss in the Ta 2 O 5 /SiO 2 coatings may limit the design sensitivity for advanced detectors. We have investigated sources of mechanical loss in the Ta 2 O 5 /SiO 2 coatings, including loss associated with the coating-substrate interface, with the coating-layer interfaces and with the coating materials. Our results indicate that the loss is associated with the coating materials and that the loss of Ta 2 O 5 is substantially larger than that of SiO 2

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.

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.

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.

Magnetic loss analysis in Mn-Zn ferrite cores

International Nuclear Information System (INIS)

Beatrice, C.; Bottauscio, O.; Chiampi, M.; Fiorillo, F.; Manzin, A.

2006-01-01

Magnetic losses have been measured and analyzed upon a wide range of frequencies in Mn-Zn ferrite ring cores. Exploiting the concept of loss separation and modeling the conductivity process in the heterogeneous material as a function of frequency, the role of the different energy dissipation mechanisms has been elucidated. It is shown, in particular, that eddy current effects can be appreciated, in standard materials and cores, only on approaching and overcoming the MHz range. The basic mechanism for hysteresis and low-frequency losses is therefore identified with the domain wall relaxation engendered by spin damping processes. Resonant absorption of energy associated with magnetization rotation is in turn deemed to chiefly contribute to the loss upon the practical range of frequencies going from a few 10 4 Hz to a few MHz

Cooperation and Noise in Public Goods Experiments: Applying the Contribution Function Approach

NARCIS (Netherlands)

Brandts, J.; Schram, A.

2001-01-01

We introduce a new design for experiments with the voluntary contributions mechanism for public goods. Subjects report a complete con-tri-bution function in each period, i.e., a contribution level for various marginal rates of transformation between a public and a private good. The results show that

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)...

Single or in Combination Antimicrobial Resistance Mechanisms of Klebsiella pneumoniae Contribute to Varied Susceptibility to Different Carbapenems

Science.gov (United States)

Tsai, Yu-Kuo; Liou, Ci-Hong; Fung, Chang-Phone; Lin, Jung-Chung; Siu, L. Kristopher

2013-01-01

Resistance to carbapenems has been documented by the production of carbapenemase or the loss of porins combined with extended-spectrum β-lactamases or AmpC β-lactamases. However, no complete comparisons have been made regarding the contributions of each resistance mechanism towards carbapenem resistance. In this study, we genetically engineered mutants of Klebsiella pneumoniae with individual and combined resistance mechanisms, and then compared each resistance mechanism in response to ertapenem, imipenem, meropenem, doripenem and other antibiotics. Among the four studied carbapenems, ertapenem was the least active against the loss of porins, cephalosporinases and carbapenemases. In addition to the production of KPC-2 or NDM-1 alone, resistance to all four carbapenems could also be conferred by the loss of two major porins, OmpK35 and OmpK36, combined with CTX-M-15 or DHA-1 with its regulator AmpR. Because the loss of OmpK35/36 alone or the loss of a single porin combined with bla CTX-M-15 or bla DHA-1-ampR expression was only sufficient for ertapenem resistance, our results suggest that carbapenems other than ertapenem should still be effective against these strains and laboratory testing for non-susceptibility to other carbapenems should improve the accurate identification of these isolates. PMID:24265784

26 CFR 1.721-1 - Nonrecognition of gain or loss on contribution.

Science.gov (United States)

2010-04-01

... partnership in the process of formation or to a partnership which is already formed and operating. Section 721...) whether made at the formation of the partnership or subsequent thereto. To the extent that any of the... Nonrecognition of gain or loss on contribution. (a) No gain or loss shall be recognized either to the partnership...

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.

The cascade probabilistic functions with taking into account energy losses for ions. Chapter 3

International Nuclear Information System (INIS)

2003-01-01

In the Chapter 3 the cascade probabilistic functions mathematical simulation with taking into account energy losses for ions are considered. The calculation of the CPF on the computer is carried out. The influence of both the interaction number and the penetration depth on the CPF determination field for ions are revealed. The estimation of energy losses contribution in the simplest CPF is made. Calculation algorithm for radiation defects concentration at ion irradiation with use of the CPF with taking into account of energy losses is given

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.

Investigation of local losses as a function of material removal in a large-grain superconducting niobium cavity

International Nuclear Information System (INIS)

Gianluigi Ciovati; Peter Kneisel

2006-01-01

The performance of a superconducting radio-frequency (RF) cavity made of residual resistivity ratio (RRR) > 200 large-grain niobium has been investigated as a function of material removal, between 70 and 240 ?m, by buffered chemical polishing (BCP). Temperature maps of the cavity surface at 1.7 and 2.0 K were taken for each step of chemical etching and revealed localized losses (''hot-spots''), which contribute to the degradation of the cavity quality factor as a function of the RF surface field. It was found that the number of ''hot-spots'' decreased for larger material removal. Interestingly, the losses at the ''hot-spots'' at different locations evolved differently for successive material removal. The cavity achieved peak surface magnetic fields of about of 130 mT and was limited mostly by thermal quench. By measuring the temperature dependence of the surface resistance (Rs) at low field between 4.2 K and 1.7 K, the variation of material parameters such as the energy gap at 0 K, the residual resistance and the mean free path as a function of material removal could also be investigated. This contribution presents the results of the RF tests along with the temperature maps and the analysis of the losses caused by the ''hot-spots''

Interactive effects of climate change and biodiversity loss on ecosystem functioning.

Science.gov (United States)

Pires, Aliny P F; Srivastava, Diane S; Marino, Nicholas A C; MacDonald, A Andrew M; Figueiredo-Barros, Marcos Paulo; Farjalla, Vinicius F

2018-05-01

Climate change and biodiversity loss are expected to simultaneously affect ecosystems, however research on how each driver mediates the effect of the other has been limited in scope. The multiple stressor framework emphasizes non-additive effects, but biodiversity may also buffer the effects of climate change, and climate change may alter which mechanisms underlie biodiversity-function relationships. Here, we performed an experiment using tank bromeliad ecosystems to test the various ways that rainfall changes and litter diversity may jointly determine ecological processes. Litter diversity and rainfall changes interactively affected multiple functions, but how depends on the process measured. High litter diversity buffered the effects of altered rainfall on detritivore communities, evidence of insurance against impacts of climate change. Altered rainfall affected the mechanisms by which litter diversity influenced decomposition, reducing the importance of complementary attributes of species (complementarity effects), and resulting in an increasing dependence on the maintenance of specific species (dominance effects). Finally, altered rainfall conditions prevented litter diversity from fueling methanogenesis, because such changes in rainfall reduced microbial activity by 58%. Together, these results demonstrate that the effects of climate change and biodiversity loss on ecosystems cannot be understood in isolation and interactions between these stressors can be multifaceted. © 2018 by the Ecological Society of America.

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.

Surface mass balance contributions to acceleration of Antarctic ice mass loss during 2003-2013

OpenAIRE

Seo, Ki-Weon; Wilson, Clark R.; Scambos, Ted; Kim, Baek-Min; Waliser, Duane E.; Tian, Baijun; Kim, Byeong-Hoon; Eom, Jooyoung

2015-01-01

Abstract Recent observations from satellite gravimetry (the Gravity Recovery and Climate Experiment (GRACE) mission) suggest an acceleration of ice mass loss from the Antarctic Ice Sheet (AIS). The contribution of surface mass balance changes (due to variable precipitation) is compared with GRACE?derived mass loss acceleration by assessing the estimated contribution of snow mass from meteorological reanalysis data. We find that over much of the continent, the acceleration can be explained by ...

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.

Applications of tensor functions in creep mechanics

International Nuclear Information System (INIS)

Betten, J.

1991-01-01

Within this contribution a short survey is given of some recent advances in the mathematical modelling of materials behaviour under creep conditions. The mechanical behaviour of anisotropic solids requires a suitable mathematical modelling. The properties of tensor functions with several argument tensors constitute a rational basis for a consistent mathematical modelling of complex material behaviour. This paper presents certain principles, methods, and recent successfull applications of tensor functions in solid mechanics. The rules for specifying irreducible sets of tensor invariants and tensor generators for material tensors of rank two and four are also discussed. Furthermore, it is very important that the scalar coefficients in constitutive and evolutional equations are determined as functions of the integrity basis and experimental data. It is explained in detail that these coefficients can be determined by using tensorial interpolation methods. Some examples for practical use are discussed. (orig./RHM)

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.

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

Size modulated transition in the fluid–structure interaction losses in nano mechanical beam resonators

Energy Technology Data Exchange (ETDEWEB)

Vishwakarma, S. D.; Pratap, R., E-mail: pratap@mecheng.iisc.ernet.in [Center for Nano Science and Engineering, Indian Institute of Science, Bengaluru 560012 (India); Pandey, A. K., E-mail: ashok@iith.ac.in [Department of Mechanical and Aerospace Engineering, Indian Institute of Technology, Hyderabad, Kandi, Sangareddy - 502285 (India); Parpia, J. M.; Craighead, H. G. [Center for Materials Research, Cornell University, Ithaca, New York 14853 (United States); Verbridge, S. S. [Biomedical Engineering and Mechanics, Virginia Tech, Blacksburg, Virginia 24061 (United States)

2016-05-21

An understanding of the dominant dissipative mechanisms is crucial for the design of a high-Q doubly clamped nanobeam resonator to be operated in air. We focus on quantifying analytically the viscous losses—the squeeze film damping and drag force damping—that limit the net quality factor of a beam resonator, vibrating in its flexural fundamental mode with the surrounding fluid as air at atmospheric pressure. Specifically, drag force damping dominates at smaller beam widths and squeeze film losses dominate at larger beam widths, with no significant contribution from structural losses and acoustic radiation losses. The combined viscous losses agree well with the experimentally measured Q of the resonator over a large range of beam widths, within the limits of thin beam theory. We propose an empirical relation between the maximum quality factor and the ratio of maximum beam width to the squeeze film air gap thickness.

The contribution of mangrove expansion to salt marsh loss on the Texas Gulf Coast.

Science.gov (United States)

Armitage, Anna R; Highfield, Wesley E; Brody, Samuel D; Louchouarn, Patrick

2015-01-01

Landscape-level shifts in plant species distribution and abundance can fundamentally change the ecology of an ecosystem. Such shifts are occurring within mangrove-marsh ecotones, where over the last few decades, relatively mild winters have led to mangrove expansion into areas previously occupied by salt marsh plants. On the Texas (USA) coast of the western Gulf of Mexico, most cases of mangrove expansion have been documented within specific bays or watersheds. Based on this body of relatively small-scale work and broader global patterns of mangrove expansion, we hypothesized that there has been a recent regional-level displacement of salt marshes by mangroves. We classified Landsat-5 Thematic Mapper images using artificial neural networks to quantify black mangrove (Avicennia germinans) expansion and salt marsh (Spartina alterniflora and other grass and forb species) loss over 20 years across the entire Texas coast. Between 1990 and 2010, mangrove area grew by 16.1 km(2), a 74% increase. Concurrently, salt marsh area decreased by 77.8 km(2), a 24% net loss. Only 6% of that loss was attributable to mangrove expansion; most salt marsh was lost due to conversion to tidal flats or water, likely a result of relative sea level rise. Our research confirmed that mangroves are expanding and, in some instances, displacing salt marshes at certain locations. However, this shift is not widespread when analyzed at a larger, regional level. Rather, local, relative sea level rise was indirectly implicated as another important driver causing regional-level salt marsh loss. Climate change is expected to accelerate both sea level rise and mangrove expansion; these mechanisms are likely to interact synergistically and contribute to salt marsh loss.

AC loss performance of cable-in-conduit conductor. Influence of cable mechanical property on coupling loss reduction

International Nuclear Information System (INIS)

Matsui, Kunihiro; Koizumi, Norikiyo; Isono, Takaaki; Hamada, Kazuya; Nunoya, Yoshihiko

2003-01-01

The ITER Central Solenoid (CS) model coil, CS Insert and Nb 3 Al Insert were developed and tested from 2000 to 2002. The AC loss performances of these coils were investigated in various experiments. In addition, the AC losses of the CS and Nb 3 Al Insert conductors were measured using short CS and Nb 3 Al Insert conductors before the coil tests. The coupling time constants of these conductors were estimated to be 30 and 120 ms, respectively. On the other hand, the test results of the CS and Nb 3 Al Inserts show that the coupling currents induced in these conductors had multiple decay time constants. In fact, the existence of the coupling currents with long decay time constants, the order of which was in the thousands of seconds, was directly observed with hall sensors and voltage taps. Moreover, the AC loss test results show that electromagnetic force decreases coupling losses with exponential decay constants. This is because the weak sinter among the strands, which originated during heat treatment, was broken due to the electromagnetic force, and then the contact resistance among strands increased. It was found that this exponential decay constant was the function of a gap (i.e., a mechanical property of the cable) created between the cable and conduit due to electromagnetic force. The gap can be estimated by pressure drop, measured under the electromagnetic force. The pressure drop can easily be measured at an initial trial charge, and then it is possible to estimate the exponential decay constant before normal coil operation. Accordingly, it is possible to predict promptly how many times the trial operations are necessary to decrease the coupling losses to the designed value by measuring the coupling losses and the pressure drop during the initial coil operation trial. (author)

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...

Preserved microvascular endothelial function in young, obese adults with functional loss of nitric oxide signaling

Directory of Open Access Journals (Sweden)

John eHarrell

2015-12-01

Full Text Available Data indicate endothelium-dependent dilation (EDD may be preserved in the skeletal muscle microcirculation of young, obese adults. Preserved EDD might be mediated by compensatory mechanisms, impeding insight into preclinical vascular dysfunction. We aimed to determine the functional roles of nitric oxide synthase (NOS and cyclooxygenase (COX toward EDD in younger obese adults. We first hypothesized EDD would be preserved in young, obese adults. Further, we hypothesized a reduced contribution of NOS in young, obese adults would be replaced by increased COX signaling. Microvascular EDD was assessed with Doppler ultrasound and brachial artery infusion of acetylcholine (ACh in younger (27±1 yr obese (n=29 and lean (n=46 humans. Individual and combined contributions of NOS and COX were examined with intra-arterial infusions of L-NMMA and ketorolac, respectively. Vasodilation was quantified as an increase in forearm vascular conductance (ΔFVC. Arterial endothelial cell biopsies were analyzed for protein expression of endothelial nitric oxide synthase (eNOS. ΔFVC to ACh was similar between groups. After L-NMMA, ΔFVC to ACh was greater in obese adults (p<0.05. There were no group differences in ΔFVC to ACh with ketorolac. With combined NOS-COX inhibition, ΔFVC was greater in obese adults at the intermediate dose of ACh. Surprisingly, arterial endothelial cell eNOS and phosphorylated eNOS were similar between groups. Younger obese adults exhibit preserved EDD and eNOS expression despite functional dissociation of NOS-mediated vasodilation and similar COX signaling. Compensatory NOS- and COX-independent vasodilatory mechanisms conceal reduced NOS contributions in otherwise healthy obese adults early in life, which may contribute to vascular dysfunction.

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....

Identification of factors contributing to successful self-directed weight loss: a qualitative study.

Science.gov (United States)

Rafiei, N; Gill, T

2017-11-21

Despite the number of weight management programmes and their wide promotion, most overweight and obese individuals tend to lose weight on their own. The present study aimed to understand the characteristics and strategies of those who successfully engage in self-directed weight loss, which could empower other overweight and obese individuals with information and strategies to manage their weight on their own. Men and women who had lost at least 5% of their body weight without direct interaction with professionals or weight management programmes were recruited. Demographic data were collected by questionnaire and participants' weight-loss experiences were explored using semi- structured interviews to elicit in-depth individual experiences and perspectives. Iterative thematic method data analysis was used to generate themes describing contributing factors to the success of self-directed weight loss identified by participants. Most characteristics of those who successfully self-managed their weight loss were in line with those reported by successful weight losers participating in professional-led projects. However, strategies such as early embedding of new lifestyle behaviours into daily routine, the ability to learn from previous weight-loss experiences, and not requiring social support were identified as distinctive factors that contributed to the success of self-directed weight loss by participants of the present study. Overweight or obese individuals with strong internal motivation, problem-solving skills and self-reliance are more likely to be successful at achieving self-directed weight loss. The patients identified with these characteristics could be encouraged to self-manage their weight-loss process, leaving the places available in more resource-intensive professional-led programmes to those individuals unlikely to succeed on their own. © 2017 The British Dietetic Association Ltd.

Cognitive function predicts 24-month weight loss success after bariatric surgery.

Science.gov (United States)

Spitznagel, Mary Beth; Alosco, Michael; Strain, Gladys; Devlin, Michael; Cohen, Ronald; Paul, Robert; Crosby, Ross D; Mitchell, James E; Gunstad, John

2013-01-01

Clinically significant cognitive impairment, particularly in attention/executive and memory function, is found in many patients undergoing bariatric surgery. These difficulties have previously been linked to decreased weight loss 12 months after surgery, but more protracted examination of this relationship has not yet been conducted. The present study prospectively examined the independent contribution of cognitive function to weight loss 24 months after bariatric surgery. Given the rapid rate of cognitive improvement observed after surgery, postoperative cognitive function (i.e., cognition 12 weeks after surgery, controlling for baseline cognition) was expected to predict lower body mass index (BMI) and higher percent total weight loss (%WL) at 24-month follow-up. Data were collected by 3 sites of the Longitudinal Assessment of Bariatric Surgery (LABS) parent project. Fifty-seven individuals enrolled in the LABS project who were undergoing bariatric surgery completed cognitive evaluation at baseline, 12 weeks, and 24 months. BMI and %WL were calculated for 24-month postoperative follow-up. Better cognitive function 12 weeks after surgery predicted higher %WL and lower BMI at 24 months, and specific domains of attention/executive and memory function were robustly related to decreased BMI and greater %WL at 24 months. Results show that cognitive performance shortly after bariatric surgery predicts greater long-term %WL and lower BMI 24 months after bariatric surgery. Further work is needed to clarify the degree to which this relationship is mediated by adherence to postoperative guidelines. Copyright © 2013 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

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

Genetic reduction of mitochondrial complex I function does not lead to loss of dopamine neurons in vivo.

Science.gov (United States)

Kim, Hyung-Wook; Choi, Won-Seok; Sorscher, Noah; Park, Hyung Joon; Tronche, François; Palmiter, Richard D; Xia, Zhengui

2015-09-01

Inhibition of mitochondrial complex I activity is hypothesized to be one of the major mechanisms responsible for dopaminergic neuron death in Parkinson's disease. However, loss of complex I activity by systemic deletion of the Ndufs4 gene, one of the subunits comprising complex I, does not cause dopaminergic neuron death in culture. Here, we generated mice with conditional Ndufs4 knockout in dopaminergic neurons (Ndufs4 conditional knockout mice [cKO]) to examine the effect of complex I inhibition on dopaminergic neuron function and survival during aging and on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment in vivo. Ndufs4 cKO mice did not show enhanced dopaminergic neuron loss in the substantia nigra pars compacta or dopamine-dependent motor deficits over the 24-month life span. These mice were just as susceptible to MPTP as control mice. However, compared with control mice, Ndufs4 cKO mice exhibited an age-dependent reduction of dopamine in the striatum and increased α-synuclein phosphorylation in dopaminergic neurons of the substantia nigra pars compacta. We also used an inducible Ndufs4 knockout mouse strain (Ndufs4 inducible knockout) in which Ndufs4 is conditionally deleted in all cells in adult to examine the effect of adult onset, complex I inhibition on MPTP sensitivity of dopaminergic neurons. The Ndufs4 inducible knockout mice exhibited similar sensitivity to MPTP as control littermates. These data suggest that mitochondrial complex I inhibition in dopaminergic neurons does contribute to dopamine loss and the development of α-synuclein pathology. However, it is not sufficient to cause cell-autonomous dopaminergic neuron death during the normal life span of mice. Furthermore, mitochondrial complex I inhibition does not underlie MPTP toxicity in vivo in either cell autonomous or nonautonomous manner. These results provide strong evidence that inhibition of mitochondrial complex I activity is not sufficient to cause dopaminergic neuron

Generation of mice harbouring a conditional loss-of-function allele of Gata6

Directory of Open Access Journals (Sweden)

Duncan Stephen A

2006-04-01

Full Text Available Abstract The zinc finger transcription factor GATA6 is believed to have important roles in the development of several organs including the liver, gastrointestinal tract and heart. However, analyses of the contribution of GATA6 toward organogenesis have been hampered because Gata6-/- mice fail to develop beyond gastrulation due to defects in extraembryonic endoderm function. We have therefore generated a mouse line harbouring a conditional loss-of-function allele of Gata6 using Cre/loxP technology. LoxP elements were introduced into introns flanking exon 2 of the Gata6 gene by homologous recombination in ES cells. Mice containing this altered allele were bred to homozygosity and were found to be viable and fertile. To assess the functional integrity of the loxP sites and to confirm that we had generated a Gata6 loss-of-function allele, we bred Gata6 'floxed' mice to EIIa-Cre mice in which Cre is ubiquitously expressed, and to Villin-Cre mice that express Cre in the epithelial cells of the intestine. We conclude that we have generated a line of mice in which GATA6 activity can be ablated in a cell type specific manner by expression of Cre recombinase. This line of mice can be used to establish the role of GATA6 in regulating embryonic development and various aspects of mammalian physiology.

Commissioning and operational scenarios of the LHC beam loss monitor system

International Nuclear Information System (INIS)

Holzer, E.B.

2007-01-01

One of the most critical elements for the protection of CERN's Large Hadron Collider (LHC) is its beam loss monitoring (BLM) system. It must prevent quenches in the super conducting magnets and damage of machine components due to beam losses. The contribution will discuss the commissioning procedures of the BLM system and envisaged operational scenarios. About 4000 monitors will be installed around the ring. When the loss rate exceeds a predefined threshold value, a beam abort is requested. Magnet quench and damage levels vary as a function of beam energy and loss duration. Consequently, the beam abort threshold values vary accordingly. By measuring the loss pattern, the BLM system helps to identify the loss mechanism. Furthermore, it will be an important tool for commissioning, machine setup and studies. Special monitors will be used for the setup and control of the collimators. (author)

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®

Gain and loss learning differentially contribute to life financial outcomes.

Directory of Open Access Journals (Sweden)

Brian Knutson

Full Text Available Emerging findings imply that distinct neurobehavioral systems process gains and losses. This study investigated whether individual differences in gain learning and loss learning might contribute to different life financial outcomes (i.e., assets versus debt. In a community sample of healthy adults (n = 75, rapid learners had smaller debt-to-asset ratios overall. More specific analyses, however, revealed that those who learned rapidly about gains had more assets, while those who learned rapidly about losses had less debt. These distinct associations remained strong even after controlling for potential cognitive (e.g., intelligence, memory, and risk preferences and socioeconomic (e.g., age, sex, ethnicity, income, education confounds. Self-reported measures of assets and debt were additionally validated with credit report data in a subset of subjects. These findings support the notion that different gain and loss learning systems may exert a cumulative influence on distinct life financial outcomes.

The effect of loss functions on empirical Bayes reliability analysis

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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.

Hearing loss and contributing factors among airport workers in Malaysia.

Science.gov (United States)

Nasir, H M; Rampal, K G

2012-02-01

Sensorineural hearing loss is a common and important source of disability among the workers and often caused by occupational noise exposure. Aims of the study were to determine the prevalence and contributing factors of hearing loss among airport workers. A cross-sectional study was carried out at an airport in Malaysia. This study used stratified sampling method that involved 358 workers who were working in 3 different units between November 2008 and March 2009. Data for this study were collected by using questionnaires eliciting sociodemographic, occupational exposure history (previous and present), life-style including smoking habits and health-related data. Otoscopic and pure-tone audiometric tests were conducted for hearing assessment. Noise exposure status was categorize by using a noise logging dosimeter to obtain 8-hour Time-Weighted Average (TWA). Data was analyzed by using SPSS version 12.0.1 and EpiInfo 6.04. The prevalence of hearing loss was 33.5%. Age >40 years old (aOR 4.3, 95%CI 2.2-8.3) is the main risk factors for hearing loss followed by duration of noise exposure >5 years (aOR 2.5, 95%CI 1.4-4.7), smoking (aOR 2.1, 95%CI 1.2-3.4), duration of service >5 years (aOR 2.1, 95%CI 1.1-3.9), exposure to explosion (aOR 6.1, 95%CI 1.3-29.8), exposure to vibration (aOR 2.2, 95%CI 1.1-4.3) and working in engineering unit (aOR 5.9, 95%CI 1.1-30.9). The prevalence rate ratio of hearing loss for nonsmokers aged 40 years old and younger, smokers aged 40 years old and younger, non-smokers older than 40 years old and smokers older than 40 years old was 1.0, 1.7, 2.8 and 4.6 respectively. This result contributes towards better understanding of risk factors for hearing loss, which is relatively common among Malaysian workers.

Whole-protein alanine-scanning mutagenesis of allostery: A large percentage of a protein can contribute to mechanism.

Science.gov (United States)

Tang, Qingling; Fenton, Aron W

2017-09-01

Many studies of allosteric mechanisms use limited numbers of mutations to test whether residues play "key" roles. However, if a large percentage of the protein contributes to allosteric function, mutating any residue would have a high probability of modifying allostery. Thus, a predicted mechanism that is dependent on only a few residues could erroneously appear to be supported. We used whole-protein alanine-scanning mutagenesis to determine which amino acid sidechains of human liver pyruvate kinase (hL-PYK; approved symbol PKLR) contribute to regulation by fructose-1,6-bisphosphate (Fru-1,6-BP; activator) and alanine (inhibitor). Each nonalanine/nonglycine residue of hL-PYK was mutated to alanine to generate 431 mutant proteins. Allosteric functions in active proteins were quantified by following substrate affinity over a concentration range of effectors. Results show that different residues contribute to the two allosteric functions. Only a small fraction of mutated residues perturbed inhibition by alanine. In contrast, a large percentage of mutated residues influenced activation by Fru-1,6-BP; inhibition by alanine is not simply the reverse of activation by Fru-1,6-BP. Moreover, the results show that Fru-1,6-BP activation would be extremely difficult to elucidate using a limited number of mutations. Additionally, this large mutational data set will be useful to train and test computational algorithms aiming to predict allosteric mechanisms. © 2017 Wiley Periodicals, Inc.

Does Impaired Gallbladder Function Contribute to the Development of Barrett's Esophagus and Esophageal Adenocarcinoma?

LENUS (Irish Health Repository)

Nassr, Ayman O

2011-06-01

Esophageal adenocarcinoma is aetiologically associated with gastro-esophageal reflux, but the mechanisms responsible for the metaplasia-dysplasia sequence are unknown. Bile components are implicated. Impaired gallbladder function may contribute to duodenogastric reflux (DGR) and harmful GERD.

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

contribute to understand the mechanisms of ecosystem process and sustainable manage the susceptible alpine meadow ecosystem. Keywords: Biodiversity-ecosystem function; Land-use intensification; Plant productivity; Alpine meadow; Functional diversity

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

Contributing to Functionality

DEFF Research Database (Denmark)

Törpel, Bettina

2006-01-01

The objective of this paper is the design of computer supported joint action spaces. It is argued against a view of functionality as residing in computer applications. In such a view the creation of functionality is equivalent to the creation of computer applications. Functionality, in the view...... advocated in this paper, emerges in the specific dynamic interplay of actors, objectives, structures, practices and means. In this view, functionality is the result of creating, harnessing and inhabiting computer supported joint action spaces. The successful creation and further development of a computer...... supported joint action space comprises a whole range of appropriate design contributions. The approach is illustrated by the example of the creation of the computer supported joint action space "exchange network of voluntary union educators". As part of the effort a group of participants created...

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

Science.gov (United States)

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.

Cancer and Chemotherapy Contribute to Muscle Loss by Activating Common Signaling Pathways

Science.gov (United States)

Barreto, Rafael; Mandili, Giorgia; Witzmann, Frank A.; Novelli, Francesco; Zimmers, Teresa A.; Bonetto, Andrea

2016-01-01

Cachexia represents one of the primary complications of colorectal cancer due to its effects on depletion of muscle and fat. Evidence suggests that chemotherapeutic regimens, such as Folfiri, contribute to cachexia-related symptoms. The purpose of the present study was to investigate the cachexia signature in different conditions associated with severe muscle wasting, namely Colon-26 (C26) and Folfiri-associated cachexia. Using a quantitative LC-MS/MS approach, we identified significant changes in 386 proteins in the quadriceps muscle of Folfiri-treated mice, and 269 proteins differentially expressed in the C26 hosts (p < 0.05; −1.5 ≥ fold change ≥ +1.5). Comparative analysis isolated 240 proteins that were modulated in common, with a large majority (218) that were down-regulated in both experimental settings. Interestingly, metabolic (47.08%) and structural (21.25%) proteins were the most represented. Pathway analysis revealed mitochondrial dysfunctions in both experimental conditions, also consistent with reduced expression of mediators of mitochondrial fusion (OPA-1, mitofusin-2), fission (DRP-1) and biogenesis (Cytochrome C, PGC-1α). Alterations of oxidative phosphorylation within the TCA cycle, fatty acid metabolism, and Ca2+ signaling were also detected. Overall, the proteomic signature in the presence of both chemotherapy and cancer suggests the activation of mechanisms associated with movement disorders, necrosis, muscle cell death, muscle weakness and muscle damage. Conversely, this is consistent with the inhibition of pathways that regulate nucleotide and fatty acid metabolism, synthesis of ATP, muscle and heart function, as well as ROS scavenging. Interestingly, strong up-regulation of pro-inflammatory acute-phase proteins and a more coordinated modulation of mitochondrial and lipidic metabolisms were observed in the muscle of the C26 hosts that were different from the Folfiri-treated animals. In conclusion, our results suggest that both cancer

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

Study of the dislocation contribution to the internal friction background of gold

Science.gov (United States)

Baur, J.; Benoit, W.

1987-04-01

The dislocation contribution to the internal friction (IF) background is studied in annealed gold samples containing various dilute concentrations of platinum impurities. The measurements are performed in the kHz frequency range in order to determine the loss mechanism responsible for the high IF background observed at these low frequencies. To this end, the IF background was systematically measured as a function of frequency, vibration amplitude, temperature, and impurity concentration. The experimental results show that the high dislocation contribution observed in annealed samples is strain-amplitude independent for amplitudes in the range 10-7 to 2×10-6, but rapidly decreases for amplitudes smaller than 10-7. In particular, the dislocation contribution tends to zero when the strain amplitude tends to zero. Furthermore, this contribution is frequency independent. These observations demonstrate that the dislocation contribution cannot be explained by relaxations. In particular, this contribution cannot be attributed to a viscous damping of the dislocation motion. On the contrary, the experiments show that the IF background due to dislocations must be explained by hysteretic and athermal motions of dislocations interacting with point defects. However, these hysteretic motions are not due to breakaway of dislocations from pinning points distributed along their length. The experimental results can be explained by the presence of point defects close to the dislocations, but not on them. The mechanical energy loss is attributed to hysteretic motions of dislocations between potential minima created by point defects.

Loss of melanocortin-4 receptor function attenuates HPA responses to psychological stress

DEFF Research Database (Denmark)

Ryan, Karen K; Mul, Joram D; Clemmensen, Christoffer

2014-01-01

function. These results support the hypothesis that endogenous MC4R signaling contributes to the HPA axis response to stress. Because MC4R plays a critical role in the regulation of energy balance, the present work suggests that it may also serve as an important communication link between brain metabolic...... in hypothalamic-pituitary-adrenocortical axis (HPA) regulation. The present work investigated the role of chronic Mc4r function to modulate basal HPA axis tone and to facilitate acute HPA responses to psychological stress, using a novel rat model with Mc4r loss-of-function. In this study, adult male rats were......The melanocortin 4 receptor (MC4R), well-known for its role in the regulation of energy balance, is widely expressed in stress-regulatory brain regions, including the paraventricular nucleus of the hypothalamus (PVH) and the medial amygdala (MeA). In agreement with this, MC4R has been implicated...

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

Mechanism Design for Incentivizing Social Media Contributions

Science.gov (United States)

Singh, Vivek K.; Jain, Ramesh; Kankanhalli, Mohan

Despite recent advancements in user-driven social media platforms, tools for studying user behavior patterns and motivations remain primitive. We highlight the voluntary nature of user contributions and that users can choose when (and when not) to contribute to the common media pool. A Game theoretic framework is proposed to study the dynamics of social media networks where contribution costs are individual but gains are common. We model users as rational selfish agents, and consider domain attributes like voluntary participation, virtual reward structure, network effect, and public-sharing to model the dynamics of this interaction. The created model describes the most appropriate contribution strategy from each user's perspective and also highlights issues like 'free-rider' problem and individual rationality leading to irrational (i.e. sub-optimal) group behavior. We also consider the perspective of the system designer who is interested in finding the best incentive mechanisms to influence the selfish end-users so that the overall system utility is maximized. We propose and compare multiple mechanisms (based on optimal bonus payment, social incentive leveraging, and second price auction) to study how a system designer can exploit the selfishness of its users, to design incentive mechanisms which improve the overall task-completion probability and system performance, while possibly still benefiting the individual users.

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.

Aroma Effects on Physiologic and Cognitive Function Following Acute Stress: A Mechanism Investigation

OpenAIRE

Chamine, Irina; Oken, Barry S.

2016-01-01

Objective: Aromas may improve physiologic and cognitive function after stress, but associated mechanisms remain unknown. This study evaluated the effects of lavender aroma, which is commonly used for stress reduction, on physiologic and cognitive functions. The contribution of pharmacologic, hedonic, and expectancy-related mechanisms of the aromatherapy effects was evaluated.

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...

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...

Genetic and Epigenetic Mechanisms That Maintain Hematopoietic Stem Cell Function

Science.gov (United States)

Kosan, Christian; Godmann, Maren

2016-01-01

All hematopoiesis cells develop from multipotent progenitor cells. Hematopoietic stem cells (HSC) have the ability to develop into all blood lineages but also maintain their stemness. Different molecular mechanisms have been identified that are crucial for regulating quiescence and self-renewal to maintain the stem cell pool and for inducing proliferation and lineage differentiation. The stem cell niche provides the microenvironment to keep HSC in a quiescent state. Furthermore, several transcription factors and epigenetic modifiers are involved in this process. These create modifications that regulate the cell fate in a more or less reversible and dynamic way and contribute to HSC homeostasis. In addition, HSC respond in a unique way to DNA damage. These mechanisms also contribute to the regulation of HSC function and are essential to ensure viability after DNA damage. How HSC maintain their quiescent stage during the entire life is still matter of ongoing research. Here we will focus on the molecular mechanisms that regulate HSC function. PMID:26798358

Genetic and Epigenetic Mechanisms That Maintain Hematopoietic Stem Cell Function

Directory of Open Access Journals (Sweden)

Christian Kosan

2016-01-01

Full Text Available All hematopoiesis cells develop from multipotent progenitor cells. Hematopoietic stem cells (HSC have the ability to develop into all blood lineages but also maintain their stemness. Different molecular mechanisms have been identified that are crucial for regulating quiescence and self-renewal to maintain the stem cell pool and for inducing proliferation and lineage differentiation. The stem cell niche provides the microenvironment to keep HSC in a quiescent state. Furthermore, several transcription factors and epigenetic modifiers are involved in this process. These create modifications that regulate the cell fate in a more or less reversible and dynamic way and contribute to HSC homeostasis. In addition, HSC respond in a unique way to DNA damage. These mechanisms also contribute to the regulation of HSC function and are essential to ensure viability after DNA damage. How HSC maintain their quiescent stage during the entire life is still matter of ongoing research. Here we will focus on the molecular mechanisms that regulate HSC function.

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.

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

Physiological Factors Contributing to Postflight Changes in Functional Performance

Science.gov (United States)

Bloomberg, J. J.; Feedback, D. L.; Feiverson, A. H.; Lee, S. M. C.; Mulavara, A. P.; Peters, B. T.; Platts, S. H.; Reschke, M. F.; Ryder, J.; Spiering, B. A.;

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

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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.

CONTRIBUTIONS TO THE FUNCTIONAL MORPHOLOGY OF ...

African Journals Online (AJOL)

CONTRIBUTIONS TO THE FUNCTIONAL MORPHOLOGY OF FISHES ... The exact phylogeny of the chimaeroids is obscure due to difficulties encountered in ...... species was obtained from the University of Cape Town Ecological Records;.

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.

[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.

Impaired neural structure and function contributing to autonomic symptoms in congenital central hypoventilation syndrome.

Science.gov (United States)

Harper, Ronald M; Kumar, Rajesh; Macey, Paul M; Harper, Rebecca K; Ogren, Jennifer A

2015-01-01

Congenital central hypoventilation syndrome (CCHS) patients show major autonomic alterations in addition to their better-known breathing deficiencies. The processes underlying CCHS, mutations in the PHOX2B gene, target autonomic neuronal development, with frame shift extent contributing to symptom severity. Many autonomic characteristics, such as impaired pupillary constriction and poor temperature regulation, reflect parasympathetic alterations, and can include disturbed alimentary processes, with malabsorption and intestinal motility dyscontrol. The sympathetic nervous system changes can exert life-threatening outcomes, with dysregulation of sympathetic outflow leading to high blood pressure, time-altered and dampened heart rate and breathing responses to challenges, cardiac arrhythmia, profuse sweating, and poor fluid regulation. The central mechanisms contributing to failed autonomic processes are readily apparent from structural and functional magnetic resonance imaging studies, which reveal substantial cortical thinning, tissue injury, and disrupted functional responses in hypothalamic, hippocampal, posterior thalamic, and basal ganglia sites and their descending projections, as well as insular, cingulate, and medial frontal cortices, which influence subcortical autonomic structures. Midbrain structures are also compromised, including the raphe system and its projections to cerebellar and medullary sites, the locus coeruleus, and medullary reflex integrating sites, including the dorsal and ventrolateral medullary nuclei. The damage to rostral autonomic sites overlaps metabolic, affective and cognitive regulatory regions, leading to hormonal disruption, anxiety, depression, behavioral control, and sudden death concerns. The injuries suggest that interventions for mitigating hypoxic exposure and nutrient loss may provide cellular protection, in the same fashion as interventions in other conditions with similar malabsorption, fluid turnover, or hypoxic exposure.

Impaired Neural Structure and Function Contributing to Autonomic Symptoms in Congenital Central Hypoventilation Syndrome

Directory of Open Access Journals (Sweden)

Ronald M Harper

2015-10-01

Full Text Available Congenital central hypoventilation syndrome (CCHS patients show major autonomic alterations in addition to their better-known breathing deficiencies. The processes underlying CCHS, mutations in the PHOX2B gene, target autonomic neuronal development, with frame shift extent contributing to symptom severity. Many autonomic characteristics, such as impaired pupillary constriction and poor temperature regulation, reflect parasympathetic alterations, and can include disturbed alimentary processes, with malabsorption and intestinal motility dyscontrol. The sympathetic nervous system changes can exert life-threatening outcomes, with dysregulation of sympathetic outflow leading to high blood pressure, time-altered and dampened heart rate and breathing responses to challenges, cardiac arrhythmia, profuse sweating, and poor fluid regulation. The central mechanisms contributing to failed autonomic processes are readily apparent from structural and functional magnetic resonance imaging studies, which reveal substantial cortical thinning, tissue injury, and disrupted functional responses in hypothalamic, hippocampal, posterior thalamic, and basal ganglia sites and their descending projections, as well as insular, cingulate, and medial frontal cortices, which influence subcortical autonomic structures. Midbrain structures are also compromised, including the raphe system and its projections to cerebellar and medullary sites, the locus coeruleus, and medullary reflex integrating sites, including the dorsal and ventrolateral medullary nuclei. The damage to rostral autonomic sites overlaps metabolic, affective and cognitive regulatory regions, leading to hormonal disruption, anxiety, depression, behavioral control, and sudden death concerns. The injuries suggest that interventions for mitigating hypoxic exposure and nutrient loss may provide cellular protection, in the same fashion as interventions in other conditions with similar malabsorption, fluid turnover

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.

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.

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.

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...

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.

Contributions to mechanics Markus Reiner eightieth anniversary volume

CERN Document Server

Abir, David

1969-01-01

Contributions to Mechanics presents a biographical survey of Professor Markus Reiner's life. This book is a manifestation of affection and esteem to Professor Reiner, expressed by various authors who eagerly contributed original works in the field of mechanics. Organized into five parts encompassing 26 chapters, this book begins with a biographical article of Professor Markus Reiner that includes a detailed account of his works. This text then explores the approach for the interpretation of certain features commonly accepted in quantum theory on the basis of its mathematical formalism. Other c

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.

Thalamo-Cortical Disruption Contributes to Short-Term Memory Deficits in Patients with Medial Temporal Lobe Damage.

Science.gov (United States)

Voets, Natalie L; Menke, Ricarda A L; Jbabdi, Saad; Husain, Masud; Stacey, Richard; Carpenter, Katherine; Adcock, Jane E

2015-11-01

Short-term (STM) and long-term memory (LTM) have largely been considered as separate brain systems reflecting fronto-parietal and medial temporal lobe (MTL) functions, respectively. This functional dichotomy has been called into question by evidence of deficits on aspects of working memory in patients with MTL damage, suggesting a potentially direct hippocampal contribution to STM. As the hippocampus has direct anatomical connections with the thalamus, we tested the hypothesis that damage to thalamic nuclei regulating cortico-cortical interactions may contribute to STM deficits in patients with hippocampal dysfunction. We used diffusion-weighted magnetic resonance imaging-based tractography to identify anatomical subdivisions in patients with MTL epilepsy. From these, we measured resting-state functional connectivity with detailed cortical divisions of the frontal, temporal, and parietal lobes. Whereas thalamo-temporal functional connectivity reflected LTM performance, thalamo-prefrontal functional connectivity specifically predicted STM performance. Notably, patients with hippocampal volume loss showed thalamic volume loss, most prominent in the pulvinar region, not detected in patients with normal hippocampal volumes. Aberrant thalamo-cortical connectivity in the epileptic hemisphere was mirrored in a loss of behavioral association with STM performance specifically in patients with hippocampal atrophy. These findings identify thalamo-cortical disruption as a potential mechanism contributing to STM deficits in the context of MTL damage. © The Author 2015. Published by Oxford University Press.

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)

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....

Factors contributing to tooth loss among the elderly: A cross sectional study.

Science.gov (United States)

Natto, Zuhair S; Aladmawy, Majdi; Alasqah, Mohammed; Papas, Athena

2014-12-01

The present study evaluates the influence of several demographic, health, personal, and clinical factors on the number of missing teeth in old age sample. The number of patients included was 259; they received a full mouth examination and answered a questionnaire provided by one examiner. All the variables related to teeth loss based on the literature were included. These variables focused on age, gender, race, marital status, clinical attachment level, pocket depth, year of smoking, number of cigarettes smoked per day, number of medications, root decay, coronal decay, health status, and year of education. Statistical analysis involved stepwise multivariate linear regression. Teeth loss was statistically associated with clinical attachment level (CAL)(p value 0.0001), pocket depth (PD) (0.0007) and education level (0.0048). When smoking was included in the model, age was significantly associated with teeth loss (0.0037). At least one of these four factors was also related to teeth loss in several specific groups such as diabetes mellitus, male, and White. The multiple linear regressions for all the proposed variables showed that they contributed to teeth loss by about 23%. It can be concluded that less education or increased clinical attachment level loss may increase number of missing teeth. Additionally, age may cause teeth loss in the presence of smoking. Copyright © 2014. Published by Elsevier B.V.

Loss of Sphingosine Kinase Alters Life History Traits and Locomotor Function in Caenorhabditis elegans

Directory of Open Access Journals (Sweden)

Jason P. Chan

2017-09-01

Full Text Available Sphingolipid metabolism is important to balance the abundance of bioactive lipid molecules involved in cell signaling, neuronal function, and survival. Specifically, the sphingolipid sphingosine mediates cell death signaling, whereas its phosphorylated form, sphingosine-1-phosphate (S1P, mediates cell survival signaling. The enzyme sphingosine kinase produces S1P, and the activity of sphingosine kinase impacts the ability of cells to survive under stress and challenges. To examine the influence of sphingolipid metabolism, particularly enzymes regulating sphingosine and S1P, in mediating aging, neuronal function and stress response, we examined life history traits, locomotor capacities and heat stress responses of young and old animals using the model organism Caenorhabditis elegans. We found that C. elegans sphk-1 mutants, which lack sphingosine kinase, had shorter lifespans, reduced brood sizes, and smaller body sizes compared to wild type animals. By analyzing a panel of young and old animals with genetic mutations in the sphingolipid signaling pathway, we showed that aged sphk-1 mutants exhibited a greater decline in neuromuscular function and locomotor behavior. In addition, aged animals lacking sphk-1 were more susceptible to death induced by acute and prolonged heat exposure. On the other hand, older animals with loss of function mutations in ceramide synthase (hyl-1, which converts sphingosine to ceramide, showed improved neuromuscular function and stress response with age. This phenotype was dependent on sphk-1. Together, our data show that loss of sphingosine kinase contributes to poor animal health span, suggesting that sphingolipid signaling may be important for healthy neuronal function and animal stress response during aging.

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.

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.

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.

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.

The contribution of radio-frequency rectification to field-aligned losses of high-harmonic fast wave power to the divertor in the National Spherical Torus eXperiment

Energy Technology Data Exchange (ETDEWEB)

Perkins, R. J., E-mail: rperkins@pppl.gov; Hosea, J. C.; Jaworski, M. A.; Diallo, A.; Bell, R. E.; Bertelli, N.; Gerhardt, S.; Kramer, G. J.; LeBlanc, B. P.; Phillips, C. K.; Podestà, M.; Roquemore, L.; Taylor, G.; Wilson, J. R. [Princeton Plasma Physics Laboratory, Princeton, New Jersey 08543 (United States); Ahn, J.-W.; Gray, T. K. [Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831 (United States); McLean, A. [Lawrence Livermore National Laboratory, Livermore, California 94550 (United States); Sabbagh, S. [Department of Applied Physics and Applied Mathematics, Columbia University, New York, New York 10027 (United States)

2015-04-15

The National Spherical Torus eXperiment (NSTX) can exhibit a major loss of high-harmonic fast wave (HHFW) power along scrape-off layer (SOL) field lines passing in front of the antenna, resulting in bright and hot spirals on both the upper and lower divertor regions. One possible mechanism for this loss is RF sheaths forming at the divertors. Here, we demonstrate that swept-voltage Langmuir probe characteristics for probes under the spiral are shifted relative to those not under the spiral in a manner consistent with RF rectification. We estimate both the magnitude of the RF voltage across the sheath and the sheath heat flux transmission coefficient in the presence of the RF field. Although precise comparison between the computed heat flux and infrared (IR) thermography cannot yet be made, the computed heat deposition compares favorably with the projections from IR camera measurements. The RF sheath losses are significant and contribute substantially to the total SOL losses of HHFW power to the divertor for the cases studied. This work will guide future experimentation on NSTX-U, where a wide-angle IR camera and a dedicated set of coaxial Langmuir probes for measuring the RF sheath voltage directly will quantify the contribution of RF sheath rectification to the heat deposition from the SOL to the divertor.

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 ...

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

Mechanical contribution of lamellar and interlamellar elastin along the mouse aorta.

Science.gov (United States)

Clark, T E; Lillie, M A; Vogl, A W; Gosline, J M; Shadwick, R E

2015-10-15

The mechanical properties of aortic elastin vary regionally, but the microstructural basis for this variation is unknown. This study was designed to identify the relative contributions of lamellar and interlamellar elastin to circumferential load bearing in the mouse thoracic and abdominal aortas. Forces developed in uniaxial tests of samples of fresh and autoclaved aorta were correlated with elastin content and morphology obtained from histology and multiphoton laser scanning microscopy. Autoclaving should render much of the interlamellar elastin mechanically incompetent. In autoclaved tissue force per unit sample width correlated with lamellar elastin content (P≪0.001) but not total elastin content. In fresh tissue at low strain where elastin dominates the mechanical response, forces were higher than in the autoclaved tissue, but force did not correlate with total elastin content. Therefore although interlamellar elastin likely contributed to the stiffness in the fresh aorta, its contribution appeared not in proportion to its quantity. In both fresh and autoclaved tissue, elastin stiffness consistently decreased along the abdominal aorta, a key area for aneurysm development, and this difference could not be fully accounted for on the basis of either lamellar or total elastin content. These findings are relevant to the development of mathematical models of arterial mechanics, particularly for mouse models of arterial diseases involving elastic tissue. In microstructural based models the quantity of each mural constituent determines its contribution to the total response. This study shows elastin's mechanical response cannot necessarily be accounted for on the basis of fibre quantity, orientation, and modulus. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

Directory of Open Access Journals (Sweden)

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.

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

Directory of Open Access Journals (Sweden)

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

Resonance contribution to electromagnetic structure functions

International Nuclear Information System (INIS)

Bowling, A.L. Jr.

1974-01-01

The part of the pion and proton electromagnetic structure functions due to direct channel resonances in the virtual Compton amplitude is discussed. After a phenomenological discussion, based on the work of Bloom and Gilman, of resonance production in inelastic electroproduction, the single resonance contribution to the pion and proton structure functions is expressed in terms of transition form factors. Froissart-Gribov representations of the Compton amplitude partial waves are presented and are used to specify the spin dependence of the transition form factors. The dependence of the form factors on momentum transfer and resonance mass is assumed on the basis of the behavior of exclusive resonance electroproduction. The single resonance contributions are summed in the Bjorken limit, and the result exhibits Bjorken scaling. Transverse photons are found to dominate in the Bjorken limit, and the threshold behavior of the resonant part of the structure functions is related to the asymptotic behavior of exclusive form factors at large momentum transfer. The resonant parts of the annihilation structure functions are not in general given by simple analytic continuation in the scaling vari []ble ω' of the electroproduction structure functions. (Diss. Abstr. Int., B)

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.

Directory of Open Access Journals (Sweden)

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...

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.

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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.

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

Cholesterol contributes to dopamine-neuronal loss in MPTP mouse model of Parkinson's disease: Involvement of mitochondrial dysfunctions and oxidative stress.

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Rajib Paul

Full Text Available Hypercholesterolemia is a known contributor to the pathogenesis of Alzheimer's disease while its role in the occurrence of Parkinson's disease (PD is only conjecture and far from conclusive. Altered antioxidant homeostasis and mitochondrial functions are the key mechanisms in loss of dopaminergic neurons in the substantia nigra (SN region of the midbrain in PD. Hypercholesterolemia is reported to cause oxidative stress and mitochondrial dysfunctions in the cortex and hippocampus regions of the brain in rodents. However, the impact of hypercholesterolemia on the midbrain dopaminergic neurons in animal models of PD remains elusive. We tested the hypothesis that hypercholesterolemia in MPTP model of PD would potentiate dopaminergic neuron loss in SN by disrupting mitochondrial functions and antioxidant homeostasis. It is evident from the present study that hypercholesterolemia in naïve animals caused dopamine neuronal loss in SN with subsequent reduction in striatal dopamine levels producing motor impairment. Moreover, in the MPTP model of PD, hypercholesterolemia exacerbated MPTP-induced reduction of striatal dopamine as well as dopaminergic neurons in SN with motor behavioral depreciation. Activity of mitochondrial complexes, mainly complex-I and III, was impaired severely in the nigrostriatal pathway of hypercholesterolemic animals treated with MPTP. Hypercholesterolemia caused oxidative stress in the nigrostriatal pathway with increased generation of hydroxyl radicals and enhanced activity of antioxidant enzymes, which were further aggravated in the hypercholesterolemic mice with Parkinsonism. In conclusion, our findings provide evidence of increased vulnerability of the midbrain dopaminergic neurons in PD with hypercholesterolemia.

Cholesterol contributes to dopamine-neuronal loss in MPTP mouse model of Parkinson's disease: Involvement of mitochondrial dysfunctions and oxidative stress.

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Paul, Rajib; Choudhury, Amarendranath; Kumar, Sanjeev; Giri, Anirudha; Sandhir, Rajat; Borah, Anupom

2017-01-01

Hypercholesterolemia is a known contributor to the pathogenesis of Alzheimer's disease while its role in the occurrence of Parkinson's disease (PD) is only conjecture and far from conclusive. Altered antioxidant homeostasis and mitochondrial functions are the key mechanisms in loss of dopaminergic neurons in the substantia nigra (SN) region of the midbrain in PD. Hypercholesterolemia is reported to cause oxidative stress and mitochondrial dysfunctions in the cortex and hippocampus regions of the brain in rodents. However, the impact of hypercholesterolemia on the midbrain dopaminergic neurons in animal models of PD remains elusive. We tested the hypothesis that hypercholesterolemia in MPTP model of PD would potentiate dopaminergic neuron loss in SN by disrupting mitochondrial functions and antioxidant homeostasis. It is evident from the present study that hypercholesterolemia in naïve animals caused dopamine neuronal loss in SN with subsequent reduction in striatal dopamine levels producing motor impairment. Moreover, in the MPTP model of PD, hypercholesterolemia exacerbated MPTP-induced reduction of striatal dopamine as well as dopaminergic neurons in SN with motor behavioral depreciation. Activity of mitochondrial complexes, mainly complex-I and III, was impaired severely in the nigrostriatal pathway of hypercholesterolemic animals treated with MPTP. Hypercholesterolemia caused oxidative stress in the nigrostriatal pathway with increased generation of hydroxyl radicals and enhanced activity of antioxidant enzymes, which were further aggravated in the hypercholesterolemic mice with Parkinsonism. In conclusion, our findings provide evidence of increased vulnerability of the midbrain dopaminergic neurons in PD with hypercholesterolemia.

Antibiotic losses from unprotected manure stockpiles.

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Dolliver, Holly A S; Gupta, Satish C

2008-01-01

Manure management is a major concern in livestock production systems. Although historically the primary concerns have been nutrients and pathogens, manure is also a source of emerging contaminants, such as antibiotics, to the environment. There is a growing concern that antibiotics in manure are reaching surface and ground waters and contributing to the development and spread of antibiotic resistance in the environment. One such pathway is through leaching and runoff from manure stockpiles. In this study, we quantified chlortetracycline, monensin, and tylosin losses in runoff from beef manure stockpiles during two separate but consecutive experiments representing different weather conditions (i.e., temperature and precipitation amount and form). Concentrations of chlortetracycline, monensin, and tylosin in runoff were positively correlated with initial concentrations of antibiotics in manure. The highest concentrations of chlortetracycline, monensin, and tylosin in runoff were 210, 3175, and 2544 microg L(-1), respectively. Relative antibiotic losses were primarily a function of water losses. In the experiment that had higher runoff water losses, antibiotic losses ranged from 1.2 to 1.8% of total extractable antibiotics in manure. In the experiment with lower runoff water losses, antibiotic losses varied from 0.2 to 0.6% of the total extractable antibiotics in manure. Manure analysis over time suggests that in situ degradation is an important mechanism for antibiotic losses. Degradation losses during manure stockpiling may exceed cumulative losses from runoff events. Storing manure in protected (i.e., covered) facilities could reduce the risk of aquatic contamination associated with manure stockpiling and other outdoor manure management practices.

Shaping vulnerability to addiction - the contribution of behavior, neural circuits and molecular mechanisms.

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Egervari, Gabor; Ciccocioppo, Roberto; Jentsch, J David; Hurd, Yasmin L

2018-02-01

Substance use disorders continue to impose increasing medical, financial and emotional burdens on society in the form of morbidity and overdose, family disintegration, loss of employment and crime, while advances in prevention and treatment options remain limited. Importantly, not all individuals exposed to abused substances effectively develop the disease. Genetic factors play a significant role in determining addiction vulnerability and interactions between innate predisposition, environmental factors and personal experiences are also critical. Thus, understanding individual differences that contribute to the initiation of substance use as well as on long-term maladaptations driving compulsive drug use and relapse propensity is of critical importance to reduce this devastating disorder. In this paper, we discuss current topics in the field of addiction regarding individual vulnerability related to behavioral endophenotypes, neural circuits, as well as genetics and epigenetic mechanisms. Expanded knowledge of these factors is of importance to improve and personalize prevention and treatment interventions in the future. Copyright © 2017 Elsevier Ltd. All rights reserved.

Defining the Physiological Factors that Contribute to Postflight Changes in Functional Performance

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Bloomberg, J. J.; Arzeno, N.; Buxton, R.; Feiveson, A. H.; Kofman, I.; Lawrence, E.; Lee, S. M. C.; Mulavara, A. P.; Peters, B. T.; Platts, S. H.;

Assessing the functional mechanical properties of bioengineered organs with emphasis on the lung.

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Suki, Béla

2014-09-01

Recently, an exciting new approach has emerged in regenerative medicine pushing the forefront of tissue engineering to create bioartificial organs. The basic idea is to create biological scaffolds made of extracellular matrix (ECM) that preserves the three-dimensional architecture of an entire organ. These scaffolds are then used as templates for functional tissue and organ reconstruction after re-seeding the structure with stem cells or appropriately differentiated cells. In order to make sure that these bioartificial organs will be able to function in the mechanical environment of the native tissue, it is imperative to fully characterize their mechanical properties and match them with those of the normal native organs. This mini-review briefly summarizes modern measurement techniques of mechanical function characterized mostly by the material or volumetric stiffness. Micro-scale and macro-scale techniques such as atomic force microscopy and the tissue strip stress-strain approach are discussed with emphasis on those that combine mechanical measurements with structural visualization. Proper micro-scale stiffness helps attachment and differentiation of cells in the bioartificial organ whereas macro-scale functionality is provided by the overall mechanical properties of the construct. Several approaches including failure mechanics are also described, which specifically probe the contributions of the main ECM components including collagen, elastin, and proteoglycans to organ level ECM function. Advantages, drawbacks, and possible pitfalls as well as interpretation of the data are given throughout. Finally, specific techniques to assess the functionality of the ECM of bioartificial lungs are separately discussed. © 2014 Wiley Periodicals, Inc.

A contribution to the study of mechanical behaviour of concrete structures taking into account the effects of desiccation

International Nuclear Information System (INIS)

Hubert, F.X.

2004-12-01

In this work, is given a model of the drying influence on the mechanical behaviour of concrete and a reliable anticipating tool is proposed for engineers. The drying of hardened concrete has several consequences on the mechanical properties of concrete. The desiccation shrinkage is the first sign, generating crack visible at the surface level under the form of crackling and core cracking particularly on the account of the presence of aggregates which prevent the shrinkage of the cement paste to make easily. Then, the elastic parameters are strongly affected (decrease of stiffness, of the Poisson coefficient). A simplified model of the stiffness loss during the drying is proposed under the form of an isotropic hydric damage. The model is validated in the unidimensional case with tests results carried out in the LML. With this model, it is possible to estimate with more accuracy the state of the hydric constraints in concrete. Numerical simulations on 3D structures are then proposed. An application to the case of a wall being manufactured is given. The contributions of the model are tested too in the case where the global mechanical response of cylindrical mortar specimens submitted to drying and to compression tests is simulated. The effect of the capillary suction as well as the increase of the elastic limit during drying are then discussed. At last, the contributions of the model for creep calculations and desiccation are presented. (O.M.)

Cellular mechanisms of cyclophosphamide-induced taste loss in mice.

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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.

Cerebral mGluR5 availability contributes to elevated sleep need and behavioral adjustment after sleep deprivation.

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Holst, Sebastian C; Sousek, Alexandra; Hefti, Katharina; Saberi-Moghadam, Sohrab; Buck, Alfred; Ametamey, Simon M; Scheidegger, Milan; Franken, Paul; Henning, Anke; Seifritz, Erich; Tafti, Mehdi; Landolt, Hans-Peter

2017-10-05

Increased sleep time and intensity quantified as low-frequency brain electrical activity after sleep loss demonstrate that sleep need is homeostatically regulated, yet the underlying molecular mechanisms remain elusive. We here demonstrate that metabotropic glutamate receptors of subtype 5 (mGluR5) contribute to the molecular machinery governing sleep-wake homeostasis. Using positron emission tomography, magnetic resonance spectroscopy, and electroencephalography in humans, we find that increased mGluR5 availability after sleep loss tightly correlates with behavioral and electroencephalographic biomarkers of elevated sleep need. These changes are associated with altered cortical myo-inositol and glycine levels, suggesting sleep loss-induced modifications downstream of mGluR5 signaling. Knock-out mice without functional mGluR5 exhibit severe dysregulation of sleep-wake homeostasis, including lack of recovery sleep and impaired behavioral adjustment to a novel task after sleep deprivation. The data suggest that mGluR5 contribute to the brain's coping mechanisms with sleep deprivation and point to a novel target to improve disturbed wakefulness and sleep.

Cerebral mGluR5 availability contributes to elevated sleep need and behavioral adjustment after sleep deprivation

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Hefti, Katharina; Saberi-Moghadam, Sohrab; Buck, Alfred; Ametamey, Simon M; Scheidegger, Milan; Franken, Paul; Henning, Anke; Seifritz, Erich

2017-01-01

Increased sleep time and intensity quantified as low-frequency brain electrical activity after sleep loss demonstrate that sleep need is homeostatically regulated, yet the underlying molecular mechanisms remain elusive. We here demonstrate that metabotropic glutamate receptors of subtype 5 (mGluR5) contribute to the molecular machinery governing sleep-wake homeostasis. Using positron emission tomography, magnetic resonance spectroscopy, and electroencephalography in humans, we find that increased mGluR5 availability after sleep loss tightly correlates with behavioral and electroencephalographic biomarkers of elevated sleep need. These changes are associated with altered cortical myo-inositol and glycine levels, suggesting sleep loss-induced modifications downstream of mGluR5 signaling. Knock-out mice without functional mGluR5 exhibit severe dysregulation of sleep-wake homeostasis, including lack of recovery sleep and impaired behavioral adjustment to a novel task after sleep deprivation. The data suggest that mGluR5 contribute to the brain's coping mechanisms with sleep deprivation and point to a novel target to improve disturbed wakefulness and sleep. PMID:28980941

Surface Mass Balance Contributions to Acceleration of Antarctic Ice Mass Loss during 2003- 2013

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Seo, K. W.; Wilson, C. R.; Scambos, T. A.; Kim, B. M.; Waliser, D. E.; Tian, B.; Kim, B.; Eom, J.

2015-12-01

Recent observations from satellite gravimetry (the GRACE mission) suggest an acceleration of ice mass loss from the Antarctic Ice Sheet (AIS). The contribution of surface mass balance changes (due to variable precipitation) is compared with GRACE-derived mass loss acceleration by assessing the estimated contribution of snow mass from meteorological reanalysis data. We find that over much of the continent, the acceleration can be explained by precipitation anomalies. However, on the Antarctic Peninsula and other parts of West Antarctica mass changes are not explained by precipitation and are likely associated with ice discharge rate increases. The total apparent GRACE acceleration over all of the AIS between 2003 and 2013 is -13.6±7.2 GTon/yr2. Of this total, we find that the surface mass balance component is -8.2±2.0 GTon/yr2. However, the GRACE estimate appears to contain errors arising from the atmospheric pressure fields used to remove air mass effects. The estimated acceleration error from this effect is about 9.8±5.8 GTon/yr2. Correcting for this yields an ice discharge acceleration of -15.1±6.5 GTon/yr2.

Mechanisms of change of a novel weight loss programme provided by a third sector organisation: a qualitative interview study.

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McMahon, Naoimh E; Visram, Shelina; Connell, Louise A

2016-05-10

There is a need for theory-driven studies that explore the underlying mechanisms of change of complex weight loss programmes. Such studies will contribute to the existing evidence-base on how these programmes work and thus inform the future development and evaluation of tailored, effective interventions to tackle overweight and obesity. This study explored the mechanisms by which a novel weight loss programme triggered change amongst participants. The programme, delivered by a third sector organisation, addressed both diet and physical activity. Over a 26 week period participants engaged in three weekly sessions (education and exercise in a large group, exercise in a small group and a one-to-one education and exercise session). Novel aspects included the intensity and duration of the programme, a competitive selection process, milestone physical challenges (e.g. working up to a 5 K and 10 K walk/run during the programme), alumni support (face-to-face and online) and family attendance at exercise sessions. Data were collected through interviews with programme providers (n = 2) and focus groups with participants (n = 12). Discussions were audio-recorded, transcribed and analysed using NVivo10. Published behaviour change frameworks and behaviour change technique taxonomies were used to guide the coding process. Clients' interactions with components of the weight loss programme brought about a change in their commitment, knowledge, beliefs about capabilities and social and environmental contexts. Intervention components that generated these changes included the competitive selection process, group and online support, family involvement and overcoming milestone challenges over the 26 week programme. The mechanisms by which these components triggered change differed between participants. There is an urgent need to establish robust interventions that can support people who are overweight and obese to achieve a healthy weight and maintain this change. Third

Mechanisms of change of a novel weight loss programme provided by a third sector organisation: a qualitative interview study

Directory of Open Access Journals (Sweden)

Naoimh E. McMahon

2016-05-01

Full Text Available Abstract Background There is a need for theory-driven studies that explore the underlying mechanisms of change of complex weight loss programmes. Such studies will contribute to the existing evidence-base on how these programmes work and thus inform the future development and evaluation of tailored, effective interventions to tackle overweight and obesity. This study explored the mechanisms by which a novel weight loss programme triggered change amongst participants. The programme, delivered by a third sector organisation, addressed both diet and physical activity. Over a 26 week period participants engaged in three weekly sessions (education and exercise in a large group, exercise in a small group and a one-to-one education and exercise session. Novel aspects included the intensity and duration of the programme, a competitive selection process, milestone physical challenges (e.g. working up to a 5 K and 10 K walk/run during the programme, alumni support (face-to-face and online and family attendance at exercise sessions. Methods Data were collected through interviews with programme providers (n = 2 and focus groups with participants (n = 12. Discussions were audio-recorded, transcribed and analysed using NVivo10. Published behaviour change frameworks and behaviour change technique taxonomies were used to guide the coding process. Results Clients’ interactions with components of the weight loss programme brought about a change in their commitment, knowledge, beliefs about capabilities and social and environmental contexts. Intervention components that generated these changes included the competitive selection process, group and online support, family involvement and overcoming milestone challenges over the 26 week programme. The mechanisms by which these components triggered change differed between participants. Conclusions There is an urgent need to establish robust interventions that can support people who are overweight and

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

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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.

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

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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

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

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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

Loss of function of ATXN1 increases amyloid beta-protein levels by potentiating beta-secretase processing of beta-amyloid precursor protein.

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Zhang, Can; Browne, Andrew; Child, Daniel; Divito, Jason R; Stevenson, Jesse A; Tanzi, Rudolph E

2010-03-19

Alzheimer disease (AD) is a devastating neurodegenerative disease with complex and strong genetic inheritance. Four genes have been established to either cause familial early onset AD (APP, PSEN1, and PSEN2) or to increase susceptibility for late onset AD (APOE). To date approximately 80% of the late onset AD genetic variance remains elusive. Recently our genome-wide association screen identified four novel late onset AD candidate genes. Ataxin 1 (ATXN1) is one of these four AD candidate genes and has been indicated to be the disease gene for spinocerebellar ataxia type 1, which is also a neurodegenerative disease. Mounting evidence suggests that the excessive accumulation of Abeta, the proteolytic product of beta-amyloid precursor protein (APP), is the primary AD pathological event. In this study, we ask whether ATXN1 may lead to AD pathogenesis by affecting Abeta and APP processing utilizing RNA interference in a human neuronal cell model and mouse primary cortical neurons. We show that knock-down of ATXN1 significantly increases the levels of both Abeta40 and Abeta42. This effect could be rescued with concurrent overexpression of ATXN1. Moreover, overexpression of ATXN1 decreased Abeta levels. Regarding the underlying molecular mechanism, we show that the effect of ATXN1 expression on Abeta levels is modulated via beta-secretase cleavage of APP. Taken together, ATXN1 functions as a genetic risk modifier that contributes to AD pathogenesis through a loss-of-function mechanism by regulating beta-secretase cleavage of APP and Abeta levels.

Loss of Function of ATXN1 Increases Amyloid β-Protein Levels by Potentiating β-Secretase Processing of β-Amyloid Precursor Protein*

Science.gov (United States)

Zhang, Can; Browne, Andrew; Child, Daniel; DiVito, Jason R.; Stevenson, Jesse A.; Tanzi, Rudolph E.

2010-01-01

Alzheimer disease (AD) is a devastating neurodegenerative disease with complex and strong genetic inheritance. Four genes have been established to either cause familial early onset AD (APP, PSEN1, and PSEN2) or to increase susceptibility for late onset AD (APOE). To date ∼80% of the late onset AD genetic variance remains elusive. Recently our genome-wide association screen identified four novel late onset AD candidate genes. Ataxin 1 (ATXN1) is one of these four AD candidate genes and has been indicated to be the disease gene for spinocerebellar ataxia type 1, which is also a neurodegenerative disease. Mounting evidence suggests that the excessive accumulation of Aβ, the proteolytic product of β-amyloid precursor protein (APP), is the primary AD pathological event. In this study, we ask whether ATXN1 may lead to AD pathogenesis by affecting Aβ and APP processing utilizing RNA interference in a human neuronal cell model and mouse primary cortical neurons. We show that knock-down of ATXN1 significantly increases the levels of both Aβ40 and Aβ42. This effect could be rescued with concurrent overexpression of ATXN1. Moreover, overexpression of ATXN1 decreased Aβ levels. Regarding the underlying molecular mechanism, we show that the effect of ATXN1 expression on Aβ levels is modulated via β-secretase cleavage of APP. Taken together, ATXN1 functions as a genetic risk modifier that contributes to AD pathogenesis through a loss-of-function mechanism by regulating β-secretase cleavage of APP and Aβ levels. PMID:20097758

Loss of hfe function reverses impaired recognition memory caused by olfactory manganese exposure in mice.

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Ye, Qi; Kim, Jonghan

2015-03-01

Excessive manganese (Mn) in the brain promotes a variety of abnormal behaviors, including memory deficits, decreased motor skills and psychotic behavior resembling Parkinson's disease. Hereditary hemochromatosis (HH) is a prevalent genetic iron overload disorder worldwide. Dysfunction in HFE gene is the major cause of HH. Our previous study has demonstrated that olfactory Mn uptake is altered by HFE deficiency, suggesting that loss of HFE function could alter manganese-associated neurotoxicity. To test this hypothesis, Hfe-knockout (Hfe (-/-)) and wild-type (Hfe (+/+)) mice mice were intranasally-instilled with manganese chloride (MnCl2 5 mg/kg) or water daily for 3 weeks and examined for memory function. Olfactory Mn diminished both short-term recognition and spatial memory in Hfe (+/+) mice, as examined by novel object recognition task and Barnes maze test, respectively. Interestingly, Hfe (-/-) mice did not show impaired recognition memory caused by Mn exposure, suggesting a potential protective effect of Hfe deficiency against Mn-induced memory deficits. Since many of the neurotoxic effects of manganese are thought to result from increased oxidative stress, we quantified activities of anti-oxidant enzymes in the prefrontal cortex (PFC). Mn instillation decreased superoxide dismutase 1 (SOD1) activity in Hfe (+/+) mice, but not in Hfe (-/-) mice. In addition, Hfe deficiency up-regulated SOD1 and glutathione peroxidase activities. These results suggest a beneficial role of Hfe deficiency in attenuating Mn-induced oxidative stress in the PFC. Furthermore, Mn exposure reduced nicotinic acetylcholine receptor levels in the PFC, indicating that blunted acetylcholine signaling could contribute to impaired memory associated with intranasal manganese. Together, our model suggests that disrupted cholinergic system in the brain is involved in airborne Mn-induced memory deficits and loss of HFE function could in part prevent memory loss via a potential up-regulation of

The gluon contribution to polarised nucleon structure functions

International Nuclear Information System (INIS)

Ross, G.G.; Roberts, R.G.

1990-08-01

As with all parton distributions in quantum chromodynamics (QCD) the separation of polarised nucleon structure functions into gluon and quark contributions must be specified. We consider a definition of the gluon contribution to polarised nucleon structure functions based on exclusive processes which is explicitly gauge invariant, has no regularisation ambiguities, is insensitive to infrared singularities and can be related to other polarised scattering processes. We discuss the relationship of this gluon definition to others that have recently been used and to the estimates that have been made of the gluon contribution using current algebra and other methods. A quantitative analysis of the structure function g 1 (x,Q 2 ) for polarised deep inelastic scattering is carried out, with the aim of examining the importance of the gluon contribution. Using the positivity of parton distributions the magnitude of Δg(x,Q 2 ) is constrained by a realistic estimate of the unpolarised glue. With the appropriate choice of the hard scattering cross-section, Δσ γg , we find that even with a maximally polarised glue (for x > 0.1), some polarised strange quark contribution is still needed by the data of the EMC. (author)

Multiple parton scattering in nuclei: heavy quark energy loss and modified fragmentation functions

International Nuclear Information System (INIS)

Zhang Benwei; Wang, Enke; Wang Xinnian

2005-01-01

Multiple scattering, induced radiative energy loss and modified fragmentation functions of a heavy quark in nuclear matter are studied within the framework of generalized factorization in perturbative QCD. Modified heavy quark fragmentation functions and energy loss are derived in detail with illustration of the mass dependencies of the Landau-Pomeranchuk-Migdal interference effects and heavy quark energy loss. Due to the quark mass dependence of the gluon formation time, the nuclear size dependencies of nuclear modification of the heavy quark fragmentation function and heavy quark energy loss are 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 of the heavy quark is also significantly suppressed due to limited cone of gluon radiation imposed by the mass. Medium modification of the heavy quark fragmentation functions is found to be limited to the large z region due to the form of heavy quark fragmentation functions in vacuum

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.

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

Science.gov (United States)

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

2007-10-01

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

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)

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.

[Contribution of soil fauna to the mass loss of Betula albosinensis leaf litter at early decomposition stage of subalpine forest litter in western Sichuan].

Science.gov (United States)

Xia, Lei; Wu, Fu-Zhong; Yang, Wan-Qin; Tan, Bo

2012-02-01

In order to quantify the contribution of soil fauna to the decomposition of birch (Betula albosinensis) leaf litter in subalpine forests in western Sichuan of Southwest China during freeze-thaw season, a field experiment with different mesh sizes (0.02, 0.125, 1 and 3 mm) of litterbags was conducted in a representative birch-fir (Abies faxoniana) forest to investigate the mass loss rate of the birch leaf litter from 26 October, 2010 to 18 April, 2011, and the contributions of micro-, meso- and macro-fauna to the decomposition of the leaf litter. Over the freeze-thaw season, 11.8%, 13.2%, 15.4% and 19.5% of the mass loss were detected in the litterbags with 0.02, 0. 125, 1 and 3 mm mesh sizes, respectively. The total contribution of soil fauna to the litter decomposition accounted for 39.5% of the mass loss, and the taxa and individual relative density of the soil fauna in the litterbags had the similar variation trend with that of the mass loss rate. The contribution rate of soil fauna to the leaf litter mass loss showed the order of micro- soil fauna played an important role in the litter decomposition in subalpine forests of western Sichuan during freeze-thaw season.

Contributing Determinants to Hearing Loss in Elderly Men and Women: Results from the Population-Based Rotterdam Study

NARCIS (Netherlands)

S.C. Rigters (Stephanie); R.M. Metselaar (Mick); Wieringa, M.H. (Marjan H.); De Jong, R.J.B. (Robert J. Baatenburg); A. Hofman (Albert); A. Goedegebure (Andre)

2016-01-01

textabstractTo contribute to a better understanding of the etiology in age-related hearing loss, we carried out a cross-sectional study of 3,315 participants (aged 52-99 years) in the Rotterdam Study, to analyze both low- and high-frequency hearing loss in men and women. Hearing thresholds with

Correlation between videogame mechanics and executive functions through EEG analysis.

Science.gov (United States)

Mondéjar, Tania; Hervás, Ramón; Johnson, Esperanza; Gutierrez, Carlos; Latorre, José Miguel

2016-10-01

This paper addresses a different point of view of videogames, specifically serious games for health. This paper contributes to that area with a multidisciplinary perspective focus on neurosciences and computation. The experiment population has been pre-adolescents between the ages of 8 and 12 without any cognitive issues. The experiment consisted in users playing videogames as well as performing traditional psychological assessments; during these tasks the frontal brain activity was evaluated. The main goal was to analyse how the frontal lobe of the brain (executive function) works in terms of prominent cognitive skills during five types of game mechanics widely used in commercial videogames. The analysis was made by collecting brain signals during the two phases of the experiment, where the signals were analysed with an electroencephalogram neuroheadset. The validated hypotheses were whether videogames can develop executive functioning and if it was possible to identify which kind of cognitive skills are developed during each kind of typical videogame mechanic. The results contribute to the design of serious games for health purposes on a conceptual level, particularly in support of the diagnosis and treatment of cognitive-related pathologies. Copyright © 2016 Elsevier Inc. All rights reserved.

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

Antifatigue Functions and Mechanisms of Edible and Medicinal Mushrooms

Directory of Open Access Journals (Sweden)

Ping Geng

2017-01-01

Full Text Available Fatigue is the symptom of tiredness caused by physical and/or psychological stresses. As fatigue is becoming a serious problem in the modern society affecting human health, work efficiency, and quality of life, effective antifatigue remedies other than pharmacological drugs or therapies are highly needed. Mushrooms have been widely used as health foods, because of their various bioactive constituents such as polysaccharides, proteins, vitamins, minerals, and dietary fiber. This paper reviews the major findings from previous studies on the antifatigue effects, the active components of mushrooms, and the possible mechanisms. Many studies have demonstrated the antifatigue effects of edible and medicinal mushrooms. These mushrooms probably mitigate human fatigue through effects on the functional systems, including the muscular, cardiovascular, hormone, and immune system. The bioactive constituents that contribute to the antifatigue effects of mushrooms may include polysaccharides, peptides, nucleosides, phenolic compounds, and triterpenoids. Further research is still needed to identify the active ingredients and to investigate their mechanism of action on the antifatigue effects. Since most previous studies have been carried out in animal models, more human trials should be performed to verify the antifatigue function of edible and medicinal mushrooms.

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.

Coupling Langevin Dynamics With Continuum Mechanics: Exposing the Role of Sarcomere Stretch Activation Mechanisms to Cardiac Function

Directory of Open Access Journals (Sweden)

Takumi Washio

2018-04-01

Full Text Available High-performance computing approaches that combine molecular-scale and macroscale continuum mechanics have long been anticipated in various fields. Such approaches may enrich our understanding of the links between microscale molecular mechanisms and macroscopic properties in the continuum. However, there have been few successful examples to date owing to various difficulties associated with overcoming the large spatial (from 1 nm to 10 cm and temporal (from 1 ns to 1 ms gaps between the two scales. In this paper, we propose an efficient parallel scheme to couple a microscopic model using Langevin dynamics for a protein motor with a finite element continuum model of a beating heart. The proposed scheme allows us to use a macroscale time step that is an order of magnitude longer than the microscale time step of the Langevin model, without loss of stability or accuracy. This reduces the overhead required by the imbalanced loads of the microscale computations and the communication required when switching between scales. An example of the Langevin dynamics model that demonstrates the usefulness of the coupling approach is the molecular mechanism of the actomyosin system, in which the stretch-activation phenomenon can be successfully reproduced. This microscopic Langevin model is coupled with a macroscopic finite element ventricle model. In the numerical simulations, the Langevin dynamics model reveals that a single sarcomere can undergo spontaneous oscillation (15 Hz accompanied by quick lengthening due to cooperative movements of the myosin molecules pulling on the common Z-line. Also, the coupled simulations using the ventricle model show that the stretch-activation mechanism contributes to the synchronization of the quick lengthening of the sarcomeres at the end of the systolic phase. By comparing the simulation results given by the molecular model with and without the stretch-activation mechanism, we see that this synchronization contributes to

The relative contributions of function, perceived psychological burden and partner support to cognitive distress in bladder cancer.

Science.gov (United States)

Heyes, Susan M; Bond, Malcolm J; Harrington, Ann; Belan, Ingrid

2016-09-01

Bladder cancer is a genitourinary disease of increasing incidence. Despite improvements in treatment, outcomes remain equivocal with high recurrence rates. It is associated with poor psychosocial outcomes due to reduced functioning of the genitourinary system. The objective of these analyses was to query whether reported loss of function or the perception of psychological burden caused by this functional impedance was the key to understanding psychosocial outcomes. The sample comprised 119 participants with a confirmed diagnosis of bladder cancer. They completed a self-report questionnaire comprising the Bladder Cancer Index, Mini-mental Adjustment to Cancer Scale, Psychosocial Adjustment to Illness Scale and standard sociodemographic details. Simple mediation and serial mediation were used to explore the potential for psychological burden to mediate associations between loss of function and cognitive distress, and the potential additional contribution of positive partner support on these relationships. Age and duration of cancer were considered as covariates. Simple mediation demonstrated that the association between function and cognitive distress was fully mediated by perceived psychological burden. Serial mediation, which allowed for the addition of partner support, again demonstrated full mediation, with partner support being the key predictive variable. These analyses emphasise the importance of an appreciation of individuals' interpretation of the burden occasioned by bladder cancer and the role of a supportive partner. The implications for management discussions and support services in alleviating negative psychological outcomes in bladder cancer are highlighted. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Impairments in Motor Neurons, Interneurons and Astrocytes Contribute to Hyperexcitability in ALS: Underlying Mechanisms and Paths to Therapy.

Science.gov (United States)

Do-Ha, Dzung; Buskila, Yossi; Ooi, Lezanne

2018-02-01

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterised by the loss of motor neurons leading to progressive paralysis and death. Using transcranial magnetic stimulation (TMS) and nerve excitability tests, several clinical studies have identified that cortical and peripheral hyperexcitability are among the earliest pathologies observed in ALS patients. The changes in the electrophysiological properties of motor neurons have been identified in both sporadic and familial ALS patients, despite the diverse etiology of the disease. The mechanisms behind the change in neuronal signalling are not well understood, though current findings implicate intrinsic changes in motor neurons and dysfunction of cells critical in regulating motor neuronal excitability, such as astrocytes and interneurons. Alterations in ion channel expression and/or function in motor neurons has been associated with changes in cortical and peripheral nerve excitability. In addition to these intrinsic changes in motor neurons, inhibitory signalling through GABAergic interneurons is also impaired in ALS, likely contributing to increased neuronal excitability. Astrocytes have also recently been implicated in increasing neuronal excitability in ALS by failing to adequately regulate glutamate levels and extracellular K + concentration at the synaptic cleft. As hyperexcitability is a common and early feature of ALS, it offers a therapeutic and diagnostic target. Thus, understanding the underlying pathways and mechanisms leading to hyperexcitability in ALS offers crucial insight for future development of ALS treatments.

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.

Functional traits drive the contribution of solar radiation to leaf litter decomposition among multiple arid-zone species.

Science.gov (United States)

Pan, Xu; Song, Yao-Bin; Liu, Guo-Fang; Hu, Yu-Kun; Ye, Xue-Hua; Cornwell, William K; Prinzing, Andreas; Dong, Ming; Cornelissen, Johannes H C

2015-08-18

In arid zones, strong solar radiation has important consequences for ecosystem processes. To better understand carbon and nutrient dynamics, it is important to know the contribution of solar radiation to leaf litter decomposition of different arid-zone species. Here we investigated: (1) whether such contribution varies among plant species at given irradiance regime, (2) whether interspecific variation in such contribution correlates with interspecific variation in the decomposition rate under shade; and (3) whether this correlation can be explained by leaf traits. We conducted a factorial experiment to determine the effects of solar radiation and environmental moisture for the mass loss and the decomposition constant k-values of 13 species litters collected in Northern China. The contribution of solar radiation to leaf litter decomposition varied significantly among species. Solar radiation accelerated decomposition in particular in the species that already decompose quickly under shade. Functional traits, notably specific leaf area, might predict the interspecific variation in that contribution. Our results provide the first empirical evidence for how the effect of solar radiation on decomposition varies among multiple species. Thus, the effect of solar radiation on the carbon flux between biosphere and atmosphere may depend on the species composition of the vegetation.

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 ...

Mechanism of growth retardation of the adenocarcinoma EO 771

International Nuclear Information System (INIS)

Bassukas, I.D.; Maurer-Schultze, B.

1987-01-01

Growth retardation of tumors has been predominantly described by an increase of the ''cell loss factor'' Φ. However, this cell loss factor alone merely reflects the growth deceleration without giving information on the mechanism that causes growth retardation. In the present study a quantitative analysis of the mechanism causing growth retardation of the adenocarcinoma EO 771 has been carried out by determining separately the components of the cell loss factor Φ, namely the cell production rate and the cell loss rate of the tumor cell population. For this purpose the alteration of the histology of the tumor (proportion of necrotic tumor tissue, tumor cell density) and the proliferative capacity of the tumor cell population as a function of the tumor size was studied by applying morphometric and cell kinetic methods. The results show that growth deceleration is due to a decrease of the cell production rate k p and a simultaneous increase of the cell rate k l . Both processes contribute to about the same extent to the growth deceleration of the tumor cell population. In early tumor growth deceleration is mainly due to a prolongation of the cycle time of the tumor cells, in later phases of tumor growth to an increasing probability of the tumor cells to decycle leading to a decrease of the growth fraction GF and an increase of the cell loss rate k l . (orig.)

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

Age-related synaptic loss of the medial olivocochlear efferent innervation

Directory of Open Access Journals (Sweden)

Schrader Angela

2010-11-01

Full Text Available Abstract Age-related functional decline of the nervous system is consistently observed, though cellular and molecular events responsible for this decline remain largely unknown. One of the most prevalent age-related functional declines is age-related hearing loss (presbycusis, a major cause of which is the loss of outer hair cells (OHCs and spiral ganglion neurons. Previous studies have also identified an age-related functional decline in the medial olivocochlear (MOC efferent system prior to age-related loss of OHCs. The present study evaluated the hypothesis that this functional decline of the MOC efferent system is due to age-related synaptic loss of the efferent innervation of the OHCs. To this end, we used a recently-identified transgenic mouse line in which the expression of yellow fluorescent protein (YFP, under the control of neuron-specific elements from the thy1 gene, permits the visualization of the synaptic connections between MOC efferent fibers and OHCs. In this model, there was a dramatic synaptic loss between the MOC efferent fibers and the OHCs in older mice. However, age-related loss of efferent synapses was independent of OHC status. These data demonstrate for the first time that age-related loss of efferent synapses may contribute to the functional decline of the MOC efferent system and that this synaptic loss is not necessary for age-related loss of OHCs.

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...

Molecular mechanisms of renal aging.

Science.gov (United States)

Schmitt, Roland; Melk, Anette

2017-09-01

Epidemiologic, clinical, and molecular evidence suggest that aging is a major contributor to the increasing incidence of acute kidney injury and chronic kidney disease. The aging kidney undergoes complex changes that predispose to renal pathology. The underlying molecular mechanisms could be the target of therapeutic strategies in the future. Here, we summarize recent insight into cellular and molecular processes that have been shown to contribute to the renal aging phenotype.The main clinical finding of renal aging is the decrease in glomerular filtration rate, and its structural correlate is the loss of functioning nephrons. Mechanistically, this has been linked to different processes, such as podocyte hypertrophy, glomerulosclerosis, tubular atrophy, and gradual microvascular rarefaction. Renal functional recovery after an episode of acute kidney injury is significantly worse in elderly patients. This decreased regenerative potential, which is a hallmark of the aging process, may be caused by cellular senescence. Accumulation of senescent cells could explain insufficient repair and functional loss, a view that has been strengthened by recent studies showing that removal of senescent cells results in attenuation of renal aging. Other potential mechanisms are alterations in autophagy as an important component of a disturbed renal stress response and functional differences in the inflammatory system. Promising therapeutic measures to counteract these age-related problems include mimetics of caloric restriction, pharmacologic renin-angiotensin-aldosterone system inhibition, and novel strategies of senotherapy with the goal of reducing the number of senescent cells to decrease aging-related disease in the kidney. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

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.

Losses in Ferroelectric Materials

Science.gov (United States)

Liu, Gang; Zhang, Shujun; Jiang, Wenhua; Cao, Wenwu

2015-01-01

loss mechanisms are discussed in terms of compositions, crystal structures, temperature, domain configurations, domain sizes and grain boundaries. The intrinsic and extrinsic contributions to the total energy dissipation are quantified. In domain engineered ferroelectric single crystals and ceramics, polarization rotations, domain wall motions and mechanical wave scatterings at grain boundaries are believed to control the mechanical quality factors of piezoelectric resonators. We show that a thorough understanding on the kinetic processes is critical in analyzing energy loss behavior and other time-dependent properties in ferroelectric materials. At the end of the review, existing challenges in the study and control of losses in ferroelectric materials are analyzed, and future perspective in resolving these issues is discussed. PMID:25814784

Losses in Ferroelectric Materials.

Science.gov (United States)

Liu, Gang; Zhang, Shujun; Jiang, Wenhua; Cao, Wenwu

2015-03-01

loss mechanisms are discussed in terms of compositions, crystal structures, temperature, domain configurations, domain sizes and grain boundaries. The intrinsic and extrinsic contributions to the total energy dissipation are quantified. In domain engineered ferroelectric single crystals and ceramics, polarization rotations, domain wall motions and mechanical wave scatterings at grain boundaries are believed to control the mechanical quality factors of piezoelectric resonators. We show that a thorough understanding on the kinetic processes is critical in analyzing energy loss behavior and other time-dependent properties in ferroelectric materials. At the end of the review, existing challenges in the study and control of losses in ferroelectric materials are analyzed, and future perspective in resolving these issues is discussed.

Elucidating Jet Energy Loss Using Jets: Prospects from ATLAS

International Nuclear Information System (INIS)

Grau, N.

2009-01-01

Jets at the LHC are expected to provide the testing ground for studying QCD energy loss. In this contribution, we briefly outline the strategy that will be used to measure jets in ATLAS and how we will go about studying energy loss. We describe the utility of measuring the jet R AA , the fragmentation function, and heavy flavor jets. Utilizing the collision energy provided by the LHC and the nearly hermetic and highly segmented calorimeter, ATLAS is expected to make important contributions to the understanding of parton energy loss using fully reconstructed jets.

Elucidating Jet Energy Loss Using Jets Prospects from ATLAS

CERN Document Server

Grau, N

2009-01-01

Jets at the LHC are expected to provide the testing ground for studying QCD energy loss. In this contribution, we briefly outline the strategy that will be used to measure jets in ATLAS and how we will go about studying energy loss. We describe the utility of measuring the jet $R_{AA}$, the fragmentation function, and heavy flavor jets. Utilizing the collision energy provided by the LHC and the nearly hermetic and highly segmented calorimeter, ATLAS is expected to make important contributions to the understanding of parton energy loss using fully reconstructed jets.

A qualitative evaluation of a group phone-based weight loss intervention for rural breast cancer survivors: Themes and mechanisms of success.

Science.gov (United States)

Fazzino, Tera L; Sporn, Nora J; Befort, Christie A

2016-07-01

Obesity is prevalent in breast cancer survivors and is a significant risk factor for recurrence and mortality. Weight management interventions for survivors have been diverse in design (in-person vs. phone-based, group vs. individual) and yielded varying weight loss results. Given these issues, participants themselves may provide insight into treatment-based factors that contributed to their weight loss outcomes. Here, we report qualitative results from interviews with survivors in a group phone-based weight loss intervention, with the objective of identifying mechanisms that facilitated or hindered adherence and weight loss. We explored interest in paying for continued treatment as an indicator of dissemination potential. Individual interviews were conducted with 186 rural, obese breast cancer survivors upon completion of a 6-month weight loss intervention that produced clinically meaningful weight loss (>5 %) in 91 % of participants. A thematic analysis of the interview data was performed. Five themes were identified as impacting adherence and success: (1) accountability; (2) importance of the group, with varying levels of connectedness; (3) dietary convenience; (4) difficulty maintaining intervention components that required more effort; and (5) importance of internal motivation to attributions of physical activity success or failure. Most were interested in paying to continue the program if it were extended beyond the study. Key intervention components that participants attributed to their success included supportive group processes and convenience. Results highlight the group phone-based approach as a potential venue for disseminating an effective weight loss program for breast cancer survivors. NCT01441011.

Chamber identity programs drive early functional partitioning of the heart.

Science.gov (United States)

Mosimann, Christian; Panáková, Daniela; Werdich, Andreas A; Musso, Gabriel; Burger, Alexa; Lawson, Katy L; Carr, Logan A; Nevis, Kathleen R; Sabeh, M Khaled; Zhou, Yi; Davidson, Alan J; DiBiase, Anthony; Burns, Caroline E; Burns, C Geoffrey; MacRae, Calum A; Zon, Leonard I

2015-08-26

The vertebrate heart muscle (myocardium) develops from the first heart field (FHF) and expands by adding second heart field (SHF) cells. While both lineages exist already in teleosts, the primordial contributions of FHF and SHF to heart structure and function remain incompletely understood. Here we delineate the functional contribution of the FHF and SHF to the zebrafish heart using the cis-regulatory elements of the draculin (drl) gene. The drl reporters initially delineate the lateral plate mesoderm, including heart progenitors. Subsequent myocardial drl reporter expression restricts to FHF descendants. We harnessed this unique feature to uncover that loss of tbx5a and pitx2 affect relative FHF versus SHF contributions to the heart. High-resolution physiology reveals distinctive electrical properties of each heart field territory that define a functional boundary within the single zebrafish ventricle. Our data establish that the transcriptional program driving cardiac septation regulates physiologic ventricle partitioning, which successively provides mechanical advantages of sequential contraction.

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

The role of proximal versus distal stomach resection in the weight loss seen after vertical sleeve gastrectomy

Science.gov (United States)

Kulkarni, Bhushan V.; LaSance, Kathleen; Sorrell, Joyce E.; Lemen, Lisa; Woods, Stephen C.; Seeley, Randy J.

2016-01-01

The mechanisms involved in the weight loss seen after vertical sleeve gastrectomy (VSG) are not clear. The rat stomach has two morphologically and functionally distinct proximal and distal parts. The rat model for VSG involves complete removal of the proximal part and 80% removal of the distal part along the greater curvature. The purpose of this study was to understand the potential independent contributions of removal of these distinct gastric sections to VSG outcomes. We prepared four surgical groups of male Long-Evans rats: VSG, sham surgery (control), selective proximal section removal (PR), and selective distal section removal (DR). Gastric emptying rate (GER) was highest after VSG compared with all other groups. However, PR, in turn, had significantly greater GER compared with both DR and sham groups. The surgery-induced weight loss followed the same pattern with VSG causing the greatest weight loss and PR having greater weight loss compared with DR and sham groups. The results were robust for rats fed regular chow or a high-fat diet. Body mass analysis revealed that the weight loss was due to the loss of fat mass, and there was no change in lean mass after the surgeries. In conclusion, removal of the proximal stomach contributes to most, but not all, of the physiological impact of VSG. PMID:27581811

Functional Analysis of In-frame Indel ARID1A Mutations Reveals New Regulatory Mechanisms of Its Tumor Suppressor Functions

Directory of Open Access Journals (Sweden)

Bin Guan

2012-10-01

Full Text Available AT-rich interactive domain 1A (ARID1A has emerged as a new tumor suppressor in which frequent somatic mutations have been identified in several types of human cancers. Although most ARID1A somatic mutations are frame-shift or nonsense mutations that contribute to mRNA decay and loss of protein expression, 5% of ARID1A mutations are in-frame insertions or deletions (indels that involve only a small stretch of peptides. Naturally occurring in-frame indel mutations provide unique and useful models to explore the biology and regulatory role of ARID1A. In this study, we analyzed indel mutations identified in gynecological cancers to determine how these mutations affect the tumor suppressor function of ARID1A. Our results demonstrate that all in-frame mutants analyzed lost their ability to inhibit cellular proliferation or activate transcription of CDKN1A, which encodes p21, a downstream effector of ARID1A. We also showed that ARID1A is a nucleocytoplasmic protein whose stability depends on its subcellular localization. Nuclear ARID1A is less stable than cytoplasmic ARID1A because ARID1A is rapidly degraded by the ubiquitin-proteasome system in the nucleus. In-frame deletions affecting the consensus nuclear export signal reduce steady-state protein levels of ARID1A. This defect in nuclear exportation leads to nuclear retention and subsequent degradation. Our findings delineate a mechanism underlying the regulation of ARID1A subcellular distribution and protein stability and suggest that targeting the nuclear ubiquitin-proteasome system can increase the amount of the ARID1A protein in the nucleus and restore its tumor suppressor functions.

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

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.

Cochlear Synaptopathy and Noise-Induced Hidden Hearing Loss

Directory of Open Access Journals (Sweden)

Lijuan Shi

2016-01-01

Full Text Available Recent studies on animal models have shown that noise exposure that does not lead to permanent threshold shift (PTS can cause considerable damage around the synapses between inner hair cells (IHCs and type-I afferent auditory nerve fibers (ANFs. Disruption of these synapses not only disables the innervated ANFs but also results in the slow degeneration of spiral ganglion neurons if the synapses are not reestablished. Such a loss of ANFs should result in signal coding deficits, which are exacerbated by the bias of the damage toward synapses connecting low-spontaneous-rate (SR ANFs, which are known to be vital for signal coding in noisy background. As there is no PTS, these functional deficits cannot be detected using routine audiological evaluations and may be unknown to subjects who have them. Such functional deficits in hearing without changes in sensitivity are generally called “noise-induced hidden hearing loss (NIHHL.” Here, we provide a brief review to address several critical issues related to NIHHL: (1 the mechanism of noise induced synaptic damage, (2 reversibility of the synaptic damage, (3 the functional deficits as the nature of NIHHL in animal studies, (4 evidence of NIHHL in human subjects, and (5 peripheral and central contribution of NIHHL.

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...

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...

Loss mechanisms in organic solar cells based on perylene diimide acceptors studied by time-resolved photoluminescence

KAUST Repository

Gerhard, Marina

2016-04-27

In organic photovoltaics (OPV), perylene diimide (PDI) acceptor materials are promising candidates to replace the commonly used, but more expensive fullerene derivatives. The use of alternative acceptor materials however implies new design guidelines for OPV devices. It is therefore important to understand the underlying photophysical processes, which either lead to charge generation or geminate recombination. In this contribution, we investigate radiative losses in a series of OPV materials based on two polymers, P3HT and PTB7, respectively, which were blended with different PDI derivatives. Our time-resolved photoluminescence measurements (TRPL) allow us to identify different loss mechanisms by the decay characteristics of several excitonic species. In particular, we find evidence for unfavorable morphologies in terms of large-scale pure domains, inhibited exciton transport and incomplete charge transfer. Furthermore, in one of the P3HT-blends, an interfacial emissive charge transfer (CT) state with strong trapping character is identified. © (2016) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.

Loss mechanisms in organic solar cells based on perylene diimide acceptors studied by time-resolved photoluminescence

KAUST Repository

Gerhard, Marina; Gehrig, Dominik; Howard, Ian A.; Arndt, Andreas P.; Bilal, Mü henad; Rahimi-Iman, Arash; Lemmer, Uli; Laquai, Fré dé ric; Koch, Martin

2016-01-01

In organic photovoltaics (OPV), perylene diimide (PDI) acceptor materials are promising candidates to replace the commonly used, but more expensive fullerene derivatives. The use of alternative acceptor materials however implies new design guidelines for OPV devices. It is therefore important to understand the underlying photophysical processes, which either lead to charge generation or geminate recombination. In this contribution, we investigate radiative losses in a series of OPV materials based on two polymers, P3HT and PTB7, respectively, which were blended with different PDI derivatives. Our time-resolved photoluminescence measurements (TRPL) allow us to identify different loss mechanisms by the decay characteristics of several excitonic species. In particular, we find evidence for unfavorable morphologies in terms of large-scale pure domains, inhibited exciton transport and incomplete charge transfer. Furthermore, in one of the P3HT-blends, an interfacial emissive charge transfer (CT) state with strong trapping character is identified. © (2016) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.

Functional consequences of sarcopenia and dynapenia in the elderly.

Science.gov (United States)

Clark, Brian C; Manini, Todd M

2010-05-01

The economic burden due to the sequela of sarcopenia (muscle wasting in the elderly) are staggering and rank similarly to the costs associated with osteoporotic fractures. In this article, we discuss the societal burden and determinants of the loss of physical function with advancing age, the physiologic mechanisms underlying dynapenia (muscle weakness in the elderly), and provide perspectives on related critical issues to be addressed. Recent epidemiological findings from longitudinal aging studies suggest that dynapenia is highly associated with both mortality and physical disability even when adjusting for sarcopenia indicating that sarcopenia may be secondary to the effects of dynapenia. These findings are consistent with the physiologic underpinnings of muscle strength, as recent evidence demonstrates that alterations in muscle quantity, contractile quality and neural activation all collectively contribute to dynapenia. Although muscle mass is essential for regulation of whole body metabolic balance, overall neuromuscular function seems to be a critical factor for maintaining muscle strength and physical independence in the elderly. The relative contribution of physiologic factors contributing to muscle weakness are not fully understood and further research is needed to better elucidate these mechanisms between muscle groups and across populations.

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.

Re-Emergent Inhibition of Cochlear Inner Hair Cells in a Mouse Model of Hearing Loss.

Science.gov (United States)

Zachary, Stephen Paul; Fuchs, Paul Albert

2015-07-01

Hearing loss among the elderly correlates with diminished social, mental, and physical health. Age-related cochlear cell death does occur, but growing anatomical evidence suggests that synaptic rearrangements on sensory hair cells also contribute to auditory functional decline. Here we present voltage-clamp recordings from inner hair cells of the C57BL/6J mouse model of age-related hearing loss, which reveal that cholinergic synaptic inputs re-emerge during aging. These efferents are functionally inhibitory, using the same ionic mechanisms as do efferent contacts present transiently before the developmental onset of hearing. The strength of efferent inhibition of inner hair cells increases with hearing threshold elevation. These data indicate that the aged cochlea regains features of the developing cochlea and that efferent inhibition of the primary receptors of the auditory system re-emerges with hearing impairment. Synaptic changes in the auditory periphery are increasingly recognized as important factors in hearing loss. To date, anatomical work has described the loss of afferent contacts from cochlear hair cells. However, relatively little is known about the efferent innervation of the cochlea during hearing loss. We performed intracellular recordings from mouse inner hair cells across the lifespan and show that efferent innervation of inner hair cells arises in parallel with the loss of afferent contacts and elevated hearing threshold during aging. These efferent neurons inhibit inner hair cells, raising the possibility that they play a role in the progression of age-related hearing loss. Copyright © 2015 the authors 0270-6474/15/359701-06$15.00/0.

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.

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...

Diverse Functional Properties of Wilson Disease ATP7B Variants

Science.gov (United States)

Huster, Dominik; Kühne, Angelika; Bhattacharjee, Ashima; Raines, Lily; Jantsch, Vanessa; Noe, Johannes; Schirrmeister, Wiebke; Sommerer, Ines; Sabri, Osama; Berr, Frieder; Mössner, Joachim; Stieger, Bruno; Caca, Karel; Lutsenko, Svetlana

2012-01-01

BACKGROUND & AIMS Wilson disease is a severe disorder of copper metabolism caused by mutations in ATP7B, which encodes a copper-transporting adenosine triphosphatase. The disease presents with a variable phenotype that complicates the diagnostic process and treatment. Little is known about the mechanisms that contribute to the different phenotypes of the disease. METHODS We analyzed 28 variants of ATP7B from patients with Wilson disease that affected different functional domains; the gene products were expressed using the baculovirus expression system in Sf9 cells. Protein function was analyzed by measuring catalytic activity and copper (64Cu) transport into vesicles. We studied intracellular localization of variants of ATP7B that had measurable transport activities and were tagged with green fluorescent protein in mammalian cells using confocal laser scanning microscopy. RESULTS Properties of ATP7B variants with pathogenic amino-acid substitution varied greatly even if substitutions were in the same functional domain. Some variants had complete loss of catalytic and transport activity, whereas others lost transport activity but retained phosphor-intermediate formation or had partial losses of activity. In mammalian cells, transport-competent variants differed in stability and subcellular localization. CONCLUSIONS Variants in ATP7B associated with Wilson disease disrupt the protein’s transport activity, result in its mislocalization, and reduce its stability. Single assays are insufficient to accurately predict the effects of ATP7B variants the function of its product and development of Wilson disease. These findings will contribute to our understanding of genotype–phenotype correlation and mechanisms of disease pathogenesis. PMID:22240481

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.

[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.

Contributions of chemical and mechanical surface properties and temperature effect on the adhesion at the nanoscale

International Nuclear Information System (INIS)

Awada, Houssein; Noel, Olivier; Hamieh, Tayssir; Kazzi, Yolla; Brogly, Maurice

2011-01-01

The atomic force microscope (AFM) is a powerful tool to investigate surface properties of model systems at the nanoscale. However, to get semi-quantitative and reproducible data with the AFM, it is necessary to establish a rigorous experimental procedure. In particular, a systematic calibration procedure of AFM measurements is necessary before producing reliable semi-quantitative data. In this paper, we study the contributions of the chemical and mechanical surface properties or the temperature influence on the adhesion energy at a local scale. To reach this objective, two types of model systems were considered. The first one is composed of rigid substrates (silicon wafers or AFM tips covered with gold) which were chemically modified by molecular self-assembling monolayers to display different surface properties (methyl and hydroxyl functional groups). The second one consists of model polymer networks (cross-linked polydimethylsiloxane) of variable mechanical properties. The comparison of the force curves obtained from the two model systems shows that the viscoelastic contributions dominate for the adhesion with polymer substrates, whereas, chemical contributions dominate for the rigid substrates. The temperature effect on the adhesion energy is also reported. Finally, we propose a relation for the adhesion energy at the nanoscale. This relation relates the energy measured during the separation of the contact to the three parameters: the surface properties of the polymer, the energy dissipated within the contact zone and the temperature.

The Contribution of Executive Functions to Narrative Writing in Fourth Grade Children

Science.gov (United States)

Drijbooms, Elise; Groen, Margriet A.; Verhoeven, Ludo

2015-01-01

The present study investigated the contribution of executive functions to narrative writing in fourth grade children, and evaluated to what extent executive functions contribute differentially to different levels of narrative composition. The written skills of 102 Dutch children in fourth grade were assessed using a narrative picture-elicitation…

Tinnitus Neural Mechanisms and Structural Changes in the Brain: The Contribution of Neuroimaging Research

Directory of Open Access Journals (Sweden)

Simonetti, Patricia

2015-03-01

Full Text Available Introduction Tinnitus is an abnormal perception of sound in the absence of an external stimulus. Chronic tinnitus usually has a high impact in many aspects of patients' lives, such as emotional stress, sleep disturbance, concentration difficulties, and so on. These strong reactions are usually attributed to central nervous system involvement. Neuroimaging has revealed the implication of brain structures in the auditory system. Objective This systematic review points out neuroimaging studies that contribute to identifying the structures involved in the pathophysiological mechanism of generation and persistence of various forms of tinnitus. Data Synthesis Functional imaging research reveals that tinnitus perception is associated with the involvement of the nonauditory brain areas, including the front parietal area; the limbic system, which consists of the anterior cingulate cortex, anterior insula, and amygdala; and the hippocampal and parahippocampal area. Conclusion The neuroimaging research confirms the involvement of the mechanisms of memory and cognition in the persistence of perception, anxiety, distress, and suffering associated with tinnitus.

Contributions of natural and anthropogenic radiative forcing to mass loss of Northern Hemisphere mountain glaciers and quantifying their uncertainties.

Science.gov (United States)

Hirabayashi, Yukiko; Nakano, Kazunari; Zhang, Yong; Watanabe, Satoshi; Tanoue, Masahiro; Kanae, Shinjiro

2016-07-20

Observational evidence indicates that a number of glaciers have lost mass in the past. Given that glaciers are highly impacted by the surrounding climate, human-influenced global warming may be partly responsible for mass loss. However, previous research studies have been limited to analyzing the past several decades, and it remains unclear whether past glacier mass losses are within the range of natural internal climate variability. Here, we apply an optimal fingerprinting technique to observed and reconstructed mass losses as well as multi-model general circulation model (GCM) simulations of mountain glacier mass to detect and attribute past glacier mass changes. An 8,800-year control simulation of glaciers enabled us to evaluate detectability. The results indicate that human-induced increases in greenhouse gases have contributed to the decreased area-weighted average masses of 85 analyzed glaciers. The effect was larger than the mass increase caused by natural forcing, although the contributions of natural and anthropogenic forcing to decreases in mass varied at the local scale. We also showed that the detection of anthropogenic or natural influences could not be fully attributed when natural internal climate variability was taken into account.

Contributions of natural and anthropogenic radiative forcing to mass loss of Northern Hemisphere mountain glaciers and quantifying their uncertainties

Science.gov (United States)

Hirabayashi, Yukiko; Nakano, Kazunari; Zhang, Yong; Watanabe, Satoshi; Tanoue, Masahiro; Kanae, Shinjiro

2016-07-01

Observational evidence indicates that a number of glaciers have lost mass in the past. Given that glaciers are highly impacted by the surrounding climate, human-influenced global warming may be partly responsible for mass loss. However, previous research studies have been limited to analyzing the past several decades, and it remains unclear whether past glacier mass losses are within the range of natural internal climate variability. Here, we apply an optimal fingerprinting technique to observed and reconstructed mass losses as well as multi-model general circulation model (GCM) simulations of mountain glacier mass to detect and attribute past glacier mass changes. An 8,800-year control simulation of glaciers enabled us to evaluate detectability. The results indicate that human-induced increases in greenhouse gases have contributed to the decreased area-weighted average masses of 85 analyzed glaciers. The effect was larger than the mass increase caused by natural forcing, although the contributions of natural and anthropogenic forcing to decreases in mass varied at the local scale. We also showed that the detection of anthropogenic or natural influences could not be fully attributed when natural internal climate variability was taken into account.

Operating point resolved loss computation in electrical machines

Directory of Open Access Journals (Sweden)

Pfingsten Georg Von

2016-03-01

Full Text Available Magnetic circuits of electromagnetic energy converters, such as electrical machines, are nowadays highly utilized. This proposition is intrinsic for the magnetic as well as the electric circuit and depicts that significant enhancements of electrical machines are difficult to achieve in the absence of a detailed understanding of underlying effects. In order to improve the properties of electrical machines the accurate determination of the locally distributed iron losses based on idealized model assumptions solely is not sufficient. Other loss generating effects have to be considered and the possibility being able to distinguish between the causes of particular loss components is indispensable. Parasitic loss mechanisms additionally contributing to the total losses originating from field harmonics, non-linear material behaviour, rotational magnetizations, and detrimental effects caused by the manufacturing process or temperature, are not explicitly considered in the common iron-loss models, probably even not specifically contained in commonly used calibration factors. This paper presents a methodology being able to distinguish between different loss mechanisms and enables to individually consider particular loss mechanisms in the model of the electric machine. A sensitivity analysis of the model parameters can be performed to obtain information about which decisive loss origin for which working point has to be manipulated by the electromagnetic design or the control of the machine.

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.)

Mechanisms of Sensorineural Cell Damage, Death and Survival in the Cochlea

Directory of Open Access Journals (Sweden)

Allen Frederic Ryan

2015-04-01

Full Text Available The majority of acquired hearing loss, including presbycusis, is caused by irreversible damage to the sensorineural tissues of the cochlea. This article reviews the intracellular mechanisms that contribute to sensorineural damage in the cochlea, as well as the survival signaling pathways that can provide endogenous protection and tissue rescue. These data have primarily been generated in hearing loss not directly related to age. However, there is evidence that similar mechanisms operate in presbycusis. Moreover, accumulation of damage from other causes can contribute to age-related hearing loss. Potential therapeutic interventions to balance opposing but interconnected cell damage and survival pathways, such as antioxidants, anti-apoptotics, and pro-inflammatory cytokine inhibitors, are also discussed.

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

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)

Higher twist contributions to deep-inelastic structure functions

International Nuclear Information System (INIS)

Bluemlein, J.; Boettcher, H.

2008-07-01

We report on a recent extraction of the higher twist contributions to the deep inelastic structure functions F ep,ed 2 (x,Q 2 ) in the large x region. It is shown that the size of the extracted higher twist contributions is strongly correlated with the higher order corrections applied to the leading twist part. A gradual lowering of the higher twist contributions going from NLO to N 4 LO is observed, where in the latter case only the leading large x terms were considered. (orig.)

Using zebrafish as a model to study the role of epigenetics in hearing loss.

Science.gov (United States)

He, Yingzi; Bao, Beier; Li, Huawei

2017-09-01

The rapid progress of bioinformatics and high-throughput screening techniques in recent years has led to the identification of many candidate genes and small-molecule drugs that have the potential to make significant contributions to our understanding of the developmental and pathological processes of hearing, but it remains unclear how these genes and regulatory factors are coordinated. Increasing evidence suggests that epigenetic mechanisms are essential for establishing gene expression profiles and likely play an important role in the development of inner ear and in the pathology of hearing-associated diseases. Zebrafish are a valuable and tractable in vivo model organism for monitoring changes in the epigenome and for identifying new epigenetic processes and drug molecules that can influence vertebrate development. Areas covered: In this review, the authors focus on zebrafish as a model to summarize recent findings concerning the roles of epigenetics in the development, regeneration, and protection of hair cells. Expert opinion: Using the zebrafish model in combination with high-throughput screening and genome-editing technologies to investigate the function of epigenetics in hearing is crucial to help us better understand the molecular and genetic mechanisms of auditory development and function. It will also contribute to the development of new strategies to restore hearing loss.

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...

ALS-associated mutant FUS induces selective motor neuron degeneration through toxic gain of function.

Science.gov (United States)

Sharma, Aarti; Lyashchenko, Alexander K; Lu, Lei; Nasrabady, Sara Ebrahimi; Elmaleh, Margot; Mendelsohn, Monica; Nemes, Adriana; Tapia, Juan Carlos; Mentis, George Z; Shneider, Neil A

2016-02-04

Mutations in FUS cause amyotrophic lateral sclerosis (ALS), including some of the most aggressive, juvenile-onset forms of the disease. FUS loss-of-function and toxic gain-of-function mechanisms have been proposed to explain how mutant FUS leads to motor neuron degeneration, but neither has been firmly established in the pathogenesis of ALS. Here we characterize a series of transgenic FUS mouse lines that manifest progressive, mutant-dependent motor neuron degeneration preceded by early, structural and functional abnormalities at the neuromuscular junction. A novel, conditional FUS knockout mutant reveals that postnatal elimination of FUS has no effect on motor neuron survival or function. Moreover, endogenous FUS does not contribute to the onset of the ALS phenotype induced by mutant FUS. These findings demonstrate that FUS-dependent motor degeneration is not due to loss of FUS function, but to the gain of toxic properties conferred by ALS mutations.

Distinct mechanisms of loss of IFN-gamma mediated HLA class I inducibility in two melanoma cell lines

International Nuclear Information System (INIS)

Rodríguez, Teresa; Méndez, Rosa; Del Campo, Ana; Jiménez, Pilar; Aptsiauri, Natalia; Garrido, Federico; Ruiz-Cabello, Francisco

2007-01-01

The inability of cancer cells to present antigen on the cell surface via MHC class I molecules is one of the mechanisms by which tumor cells evade anti-tumor immunity. Alterations of Jak-STAT components of interferon (IFN)-mediated signaling can contribute to the mechanism of cell resistance to IFN, leading to lack of MHC class I inducibility. Hence, the identification of IFN-γ-resistant tumors may have prognostic and/or therapeutic relevance. In the present study, we investigated a mechanism of MHC class I inducibility in response to IFN-γ treatment in human melanoma cell lines. Basal and IFN-induced expression of HLA class I antigens was analyzed by means of indirect immunofluorescence flow cytometry, Western Blot, RT-PCR, and quantitative real-time RT-PCR (TaqMan ® Gene Expression Assays). In demethylation studies cells were cultured with 5-aza-2'-deoxycytidine. Electrophoretic Mobility Shift Assay (EMSA) was used to assay whether IRF-1 promoter binding activity is induced in IFN-γ-treated cells. Altered IFN-γ mediated HLA-class I induction was observed in two melanoma cells lines (ESTDAB-004 and ESTDAB-159) out of 57 studied, while treatment of these two cell lines with IFN-α led to normal induction of HLA class I antigen expression. Examination of STAT-1 in ESTDAB-004 after IFN-γ treatment demonstrated that the STAT-1 protein was expressed but not phosphorylated. Interestingly, IFN-α treatment induced normal STAT-1 phosphorylation and HLA class I expression. In contrast, the absence of response to IFN-γ in ESTDAB-159 was found to be associated with alterations in downstream components of the IFN-γ signaling pathway. We observed two distinct mechanisms of loss of IFN-γ inducibility of HLA class I antigens in two melanoma cell lines. Our findings suggest that loss of HLA class I induction in ESTDAB-004 cells results from a defect in the earliest steps of the IFN-γ signaling pathway due to absence of STAT-1 tyrosine-phosphorylation, while absence

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.

Analysis of Msx1 and Msx2 transactivation function in the context of the heat shock 70 (Hspa1b) gene promoter.

Science.gov (United States)

Zhuang, Fengfeng; Nguyen, Manuel P; Shuler, Charles; Liu, Yi-Hsin

2009-04-03

Previous studies have shown that Msx proteins control gene transcription predominantly through repression mechanisms. However, gene expression studies using either the gain-of-function or the loss-of-function mutants revealed many gene targets whose expression require functional Msx proteins. To date, investigations into the mechanisms of Msx-dependent transactivation have been hindered by the lack of a responsive promoter. Here, we demonstrated the usefulness of the mouse Hspa1b promoter in probing Msx-dependent mechanisms of gene activation. We showed that Msx protein activates Hspa1b promoter via its C-terminal domain. The activation absolutely depends on the HSEs and physical interactions between Msx proteins and heat shock factors may play a contributing role.

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.

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

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.

Science.gov (United States)

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.

The Physiological Bases of Hidden Noise-Induced Hearing Loss: Protocol for a Functional Neuroimaging Study.

Science.gov (United States)

Dewey, Rebecca Susan; Hall, Deborah A; Guest, Hannah; Prendergast, Garreth; Plack, Christopher J; Francis, Susan T

2018-03-09

Rodent studies indicate that noise exposure can cause permanent damage to synapses between inner hair cells and high-threshold auditory nerve fibers, without permanently altering threshold sensitivity. These demonstrations of what is commonly known as hidden hearing loss have been confirmed in several rodent species, but the implications for human hearing are unclear. Our Medical Research Council-funded program aims to address this unanswered question, by investigating functional consequences of the damage to the human peripheral and central auditory nervous system that results from cumulative lifetime noise exposure. Behavioral and neuroimaging techniques are being used in a series of parallel studies aimed at detecting hidden hearing loss in humans. The planned neuroimaging study aims to (1) identify central auditory biomarkers associated with hidden hearing loss; (2) investigate whether there are any additive contributions from tinnitus or diminished sound tolerance, which are often comorbid with hearing problems; and (3) explore the relation between subcortical functional magnetic resonance imaging (fMRI) measures and the auditory brainstem response (ABR). Individuals aged 25 to 40 years with pure tone hearing thresholds ≤20 dB hearing level over the range 500 Hz to 8 kHz and no contraindications for MRI or signs of ear disease will be recruited into the study. Lifetime noise exposure will be estimated using an in-depth structured interview. Auditory responses throughout the central auditory system will be recorded using ABR and fMRI. Analyses will focus predominantly on correlations between lifetime noise exposure and auditory response characteristics. This paper reports the study protocol. The funding was awarded in July 2013. Enrollment for the study described in this protocol commenced in February 2017 and was completed in December 2017. Results are expected in 2018. This challenging and comprehensive study will have the potential to impact diagnostic

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

Science.gov (United States)

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.

Annexin A6 contributes to the invasiveness of breast carcinoma cells by influencing the organization and localization of functional focal adhesions

Energy Technology Data Exchange (ETDEWEB)

Sakwe, Amos M., E-mail: asakwe@mmc.edu [Department of Biochemistry and Cancer Biology, Meharry Medical College, Nashville, TN 37208 (United States); Koumangoye, Rainelli; Guillory, Bobby [Department of Biochemistry and Cancer Biology, Meharry Medical College, Nashville, TN 37208 (United States); Ochieng, Josiah [Department of Biochemistry and Cancer Biology, Meharry Medical College, Nashville, TN 37208 (United States); Center for Aids Health Disparity Research, Meharry Medical College, Nashville, TN 37208 (United States); Department of Cancer Biology, Vanderbilt University, Nashville, TN (United States)

2011-04-01

The interaction of annexin A6 (AnxA6) with membrane phospholipids and either specific extracellular matrix (ECM) components or F-actin suggests that it may influence cellular processes associated with rapid plasma membrane reorganization such as cell adhesion and motility. Here, we examined the putative roles of AnxA6 in adhesion-related cellular processes that contribute to breast cancer progression. We show that breast cancer cells secrete annexins via the exosomal pathway and that the secreted annexins are predominantly cell surface-associated. Depletion of AnxA6 in the invasive BT-549 breast cancer cells is accompanied by enhanced anchorage-independent cell growth but cell-cell cohesion, cell adhesion/spreading onto collagen type IV or fetuin-A, cell motility and invasiveness were strongly inhibited. To explain the loss in adhesion/motility, we show that vinculin-based focal adhesions in the AnxA6-depleted BT-549 cells are elongated and randomly distributed. These focal contacts are also functionally defective because the activation of focal adhesion kinase and the phosphoinositide-3 kinase/Akt pathway were strongly inhibited while the MAP kinase pathway remained constitutively active. Compared with normal human breast tissues, reduced AnxA6 expression in breast carcinoma tissues correlates with enhanced cell proliferation. Together this suggests that reduced AnxA6 expression contributes to breast cancer progression by promoting the loss of functional cell-cell and/or cell-ECM contacts and anchorage-independent cell proliferation.

Annexin A6 contributes to the invasiveness of breast carcinoma cells by influencing the organization and localization of functional focal adhesions

International Nuclear Information System (INIS)

Sakwe, Amos M.; Koumangoye, Rainelli; Guillory, Bobby; Ochieng, Josiah

2011-01-01

The interaction of annexin A6 (AnxA6) with membrane phospholipids and either specific extracellular matrix (ECM) components or F-actin suggests that it may influence cellular processes associated with rapid plasma membrane reorganization such as cell adhesion and motility. Here, we examined the putative roles of AnxA6 in adhesion-related cellular processes that contribute to breast cancer progression. We show that breast cancer cells secrete annexins via the exosomal pathway and that the secreted annexins are predominantly cell surface-associated. Depletion of AnxA6 in the invasive BT-549 breast cancer cells is accompanied by enhanced anchorage-independent cell growth but cell-cell cohesion, cell adhesion/spreading onto collagen type IV or fetuin-A, cell motility and invasiveness were strongly inhibited. To explain the loss in adhesion/motility, we show that vinculin-based focal adhesions in the AnxA6-depleted BT-549 cells are elongated and randomly distributed. These focal contacts are also functionally defective because the activation of focal adhesion kinase and the phosphoinositide-3 kinase/Akt pathway were strongly inhibited while the MAP kinase pathway remained constitutively active. Compared with normal human breast tissues, reduced AnxA6 expression in breast carcinoma tissues correlates with enhanced cell proliferation. Together this suggests that reduced AnxA6 expression contributes to breast cancer progression by promoting the loss of functional cell-cell and/or cell-ECM contacts and anchorage-independent cell proliferation.

Mapping causal functional contributions derived from the clinical assessment of brain damage after stroke

Directory of Open Access Journals (Sweden)

Melissa Zavaglia

2015-01-01

Full Text Available Lesion analysis reveals causal contributions of brain regions to mental functions, aiding the understanding of normal brain function as well as rehabilitation of brain-damaged patients. We applied a novel lesion inference technique based on game theory, Multi-perturbation Shapley value Analysis (MSA, to a large clinical lesion dataset. We used MSA to analyze the lesion patterns of 148 acute stroke patients together with their neurological deficits, as assessed by the National Institutes of Health Stroke Scale (NIHSS. The results revealed regional functional contributions to essential behavioral and cognitive functions as reflected in the NIHSS, particularly by subcortical structures. There were also side specific differences of functional contributions between the right and left hemispheric brain regions which may reflect the dominance of the left hemispheric syndrome aphasia in the NIHSS. Comparison of MSA to established lesion inference methods demonstrated the feasibility of the approach for analyzing clinical data and indicated its capability for objectively inferring functional contributions from multiple injured, potentially interacting sites, at the cost of having to predict the outcome of unknown lesion configurations. The analysis of regional functional contributions to neurological symptoms measured by the NIHSS contributes to the interpretation of this widely used standardized stroke scale in clinical practice as well as clinical trials and provides a first approximation of a ‘map of stroke’.

Mapping causal functional contributions derived from the clinical assessment of brain damage after stroke.

Science.gov (United States)

Zavaglia, Melissa; Forkert, Nils D; Cheng, Bastian; Gerloff, Christian; Thomalla, Götz; Hilgetag, Claus C

2015-01-01

Lesion analysis reveals causal contributions of brain regions to mental functions, aiding the understanding of normal brain function as well as rehabilitation of brain-damaged patients. We applied a novel lesion inference technique based on game theory, Multi-perturbation Shapley value Analysis (MSA), to a large clinical lesion dataset. We used MSA to analyze the lesion patterns of 148 acute stroke patients together with their neurological deficits, as assessed by the National Institutes of Health Stroke Scale (NIHSS). The results revealed regional functional contributions to essential behavioral and cognitive functions as reflected in the NIHSS, particularly by subcortical structures. There were also side specific differences of functional contributions between the right and left hemispheric brain regions which may reflect the dominance of the left hemispheric syndrome aphasia in the NIHSS. Comparison of MSA to established lesion inference methods demonstrated the feasibility of the approach for analyzing clinical data and indicated its capability for objectively inferring functional contributions from multiple injured, potentially interacting sites, at the cost of having to predict the outcome of unknown lesion configurations. The analysis of regional functional contributions to neurological symptoms measured by the NIHSS contributes to the interpretation of this widely used standardized stroke scale in clinical practice as well as clinical trials and provides a first approximation of a 'map of stroke'.

Mapping causal functional contributions derived from the clinical assessment of brain damage after stroke

Science.gov (United States)

Zavaglia, Melissa; Forkert, Nils D.; Cheng, Bastian; Gerloff, Christian; Thomalla, Götz; Hilgetag, Claus C.

2015-01-01

Lesion analysis reveals causal contributions of brain regions to mental functions, aiding the understanding of normal brain function as well as rehabilitation of brain-damaged patients. We applied a novel lesion inference technique based on game theory, Multi-perturbation Shapley value Analysis (MSA), to a large clinical lesion dataset. We used MSA to analyze the lesion patterns of 148 acute stroke patients together with their neurological deficits, as assessed by the National Institutes of Health Stroke Scale (NIHSS). The results revealed regional functional contributions to essential behavioral and cognitive functions as reflected in the NIHSS, particularly by subcortical structures. There were also side specific differences of functional contributions between the right and left hemispheric brain regions which may reflect the dominance of the left hemispheric syndrome aphasia in the NIHSS. Comparison of MSA to established lesion inference methods demonstrated the feasibility of the approach for analyzing clinical data and indicated its capability for objectively inferring functional contributions from multiple injured, potentially interacting sites, at the cost of having to predict the outcome of unknown lesion configurations. The analysis of regional functional contributions to neurological symptoms measured by the NIHSS contributes to the interpretation of this widely used standardized stroke scale in clinical practice as well as clinical trials and provides a first approximation of a ‘map of stroke’. PMID:26448908

Free electrons and ionic liquids: study of excited states by means of electron-energy loss spectroscopy and the density functional theory multireference configuration interaction method.

Science.gov (United States)

Regeta, Khrystyna; Bannwarth, Christoph; Grimme, Stefan; Allan, Michael

2015-06-28

The technique of low energy (0-30 eV) electron impact spectroscopy, originally developed for gas phase molecules, is applied to room temperature ionic liquids (IL). Electron energy loss (EEL) spectra recorded near threshold, by collecting 0-2 eV electrons, are largely continuous, assigned to excitation of a quasi-continuum of high overtones and combination vibrations of low-frequency modes. EEL spectra recorded by collecting 10 eV electrons show predominantly discrete vibrational and electronic bands. The vibrational energy-loss spectra correspond well to IR spectra except for a broadening (∼0.04 eV) caused by the liquid surroundings, and enhanced overtone activity indicating a contribution from resonant excitation mechanism. The spectra of four representative ILs were recorded in the energy range of electronic excitations and compared to density functional theory multireference configuration interaction (DFT/MRCI) calculations, with good agreement. The spectra up to about 8 eV are dominated by π-π* transitions of the aromatic cations. The lowest bands were identified as triplet states. The spectral region 2-8 eV was empty in the case of a cation without π orbitals. The EEL spectrum of a saturated solution of methylene green in an IL band showed the methylene green EEL band at 2 eV, indicating that ILs may be used as a host to study nonvolatile compounds by this technique in the future.

[Volume Homeostasis and Renal Function in Rats Exposed to Simulated and Actual Microgravity

Science.gov (United States)

Tucker, Bryan J.

1993-01-01

This project has investigated mechanisms that influence alterations in compartmental fluid and electrolyte balance in microgravity and evaluates countermeasures to control renal fluid and electrolyte losses. Determining the alterations due to space flight in fluid compartments and renal function is an important component in understanding long term adaptation to spaceflight and the contribution to post-flight orthostatic intolerance. Four definition phase studies and two studies examining neuro-humoral and vascular mechanisms have been completed.

Premature loss of muscle mass and function in type 2 diabetes.

Science.gov (United States)

Guerrero, N; Bunout, D; Hirsch, S; Barrera, G; Leiva, L; Henríquez, S; De la Maza, M P

2016-07-01

Muscle mass and function are among the most relevant factors that contribute to an optimal quality of life, and are strong predictors of mortality in the elderly. Loss of lean tissues and deterioration of muscle function have been described as one of the many complications of type 2 diabetes mellitus (DM2), but most studies do not isolate age as an intervening factor. To study whether adult DM2 patients up to 60years of age have decreased muscle mass and function compared with healthy non-diabetic (ND) subjects of similar age. Appendicular fat-free mass (ApFFM) by dual X-ray absorptiometry (DEXA), handgrip strength (HS), quadriceps strength (QS), 12 min walking capacity (12MW) and the Timed Up and Go test (TUG) were measured in 100 DM2 patients and 39 ND controls. Muscle quality, or the ratio between lean mass and muscle strength of upper and lower limbs, and the functional limitations associated with pain and stiffness assessed according to the Western Ontario and McMaster Universities Arthrosis Index (WOMAC) were also recorded. Specific tests were performed to rule out microvascular diabetic complications (retinal and peripheral nerves), metabolic control, kidney function and vitamin D status and examine their association with ApFFM and function. ApFFM was significantly higher among DM2 female patients and lower among diabetic men. However opposite results were obtained when individual values were corrected for body mass index (BMI), specifically among women, who were more likely to be obese. As for muscle strength and global functionality tests, significantly better performances in TUG, 12MW, QS and HS were observed among ND subjects of both sexes. These differences prevailed even after excluding diabetic patients with microvascular complications as well as those with more than 10years of diabetes. Muscle quality was also significantly better among ND women. Higher scores of pain and stiffness in the WOMAC scale correlated with 12MW and TUG in both groups but

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

Voltage-probe-position dependence and magnetic-flux contribution to the measured voltage in ac transport measurements: which measuring circuit determines the real losses?

International Nuclear Information System (INIS)

Pe, T.; McDonald, J.; Clem, J.R.

1995-01-01

The voltage V ab measured between two voltage taps a and b during magnetic flux transport in a type-II superconductor carrying current I is the sum of two contributions, the line integral from a to b of the electric field along an arbitrary path C s through the superconductor and a term proportional to the time rate of change of magnetic flux through the area bounded by the path C s and the measuring circuit leads. When the current I(t) is oscillating with time t, the apparent ac loss (the time average of the product IV ab ) depends upon the measuring circuit used. Only when the measuring-circuit leads are brought out far from the surface does the apparent power dissipation approach the real (or true) ac loss associated with the length of sample probed. Calculations showing comparisons between the apparent and real ac losses in a flat strip of rectangular cross section will be presented, showing the behavior as a function of the measuring-circuit dimensions. Corresponding calculations also are presented for a sample of elliptical cross section

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

Science.gov (United States)

Wakabayashi, Hidetaka; Takahashi, Rimiko; Watanabe, Naoko; Oritsu, Hideyuki; Shimizu, Yoshitaka

2017-06-01

The aim of this study was to assess the prevalence of skeletal muscle mass loss and its association with swallowing function in patients with dysphagia after cardiovascular surgery. A retrospective cohort study was performed in 65 consecutive patients with dysphagia after cardiovascular surgery who were prescribed speech therapy. Skeletal muscle index (SMI) was calculated as total psoas muscle area assessed via abdominal computed tomography divided by height squared. Cutoff values were 6.36 cm 2 /m 2 for men and 3.92 cm 2 /m 2 for women. The Food Intake Level Scale (FILS) was used to assess the swallowing function. Univariate and ordered logistic regression analyses were applied to examine the associations between skeletal muscle mass loss and dysphagia. The study included 50 men and 15 women (mean age 73 ± 8 y). The mean SMI was 4.72 ± 1.37 cm 2 /m 2 in men and 3.33 ± 1.42 cm 2 /m 2 in women. Skeletal muscle mass loss was found in 53 (82%) patients. Twelve had tracheostomy cannula. Thirteen were non-oral feeding (FILS levels 1-3), 5 were oral food intake and alternative nutrition (levels 4-6), and 47 were oral food intake alone (levels 7-9) at discharge. The FILS at discharge was significantly lower in patients with skeletal muscle mass loss. Ordered logistic regression analysis of swallowing function showed that skeletal muscle mass loss and tracheostomy cannula were associated independently with the FILS at discharge. The prevalence of skeletal muscle mass loss is very high, and skeletal muscle mass loss is associated with swallowing function. Copyright © 2017 Elsevier Inc. All rights reserved.

Integral transforms of the quantum mechanical path integral: Hit function and path-averaged potential

Science.gov (United States)

Edwards, James P.; Gerber, Urs; Schubert, Christian; Trejo, Maria Anabel; Weber, Axel

2018-04-01

We introduce two integral transforms of the quantum mechanical transition kernel that represent physical information about the path integral. These transforms can be interpreted as probability distributions on particle trajectories measuring respectively the relative contribution to the path integral from paths crossing a given spatial point (the hit function) and the likelihood of values of the line integral of the potential along a path in the ensemble (the path-averaged potential).

High Q diamond hemispherical resonators: fabrication and energy loss mechanisms

International Nuclear Information System (INIS)

Bernstein, Jonathan J; Bancu, Mirela G; Bauer, Joseph M; Cook, Eugene H; Kumar, Parshant; Nyinjee, Tenzin; Perlin, Gayatri E; Ricker, Joseph A; Teynor, William A; Weinberg, Marc S; Newton, Eric

2015-01-01

We have fabricated polycrystalline diamond hemispheres by hot-filament CVD (HFCVD) in spherical cavities wet-etched into a high temperature glass substrate CTE matched to silicon. Hemispherical resonators 1.4 mm in diameter have a Q of up to 143 000 in the fundamental wineglass mode, for a ringdown time of 2.4 s. Without trimming, resonators have the two degenerate wineglass modes frequency matched as close as 2 Hz, or 0.013% of the resonant frequency (∼16 kHz). Laser trimming was used to match resonant modes on hemispheres to 0.3 Hz. Experimental and FEA energy loss studies on cantilevers and hemispheres examine various energy loss mechanisms, showing that surface related losses are dominant. Diamond cantilevers with a Q of 400 000 and a ringdown time of 15.4 s were measured, showing the potential of polycrystalline diamond films for high Q resonators. These resonators show great promise for use as hemispherical resonant gyroscopes (HRGs) on a chip. (paper)

[The contributing risk factors, prevention and treatment of functional dependence among the oldest-old and elderly subjects].

Science.gov (United States)

Liu, Dianrong; Tan, Jiping; Guo, Yuhe; Ye, Guanghua; Zhu, Linqi; Zhang, Jun; Li, Yinghao; Deng, Yucheng; Wang, Guichen; Wang, Luning

2014-10-01

To compare the risk factors on the functional dependence between the oldest-old and elderly veterans. A cross-sectional survey was conducted among veterans ( ≥ 60 years of age) lived in 44 veterans' communities in Beijing. The socio-demographic information and history of non-communicable chronic diseases were collected via face-to-face interviews, and the functional status was assessed by the 20-item version of the Activities of Daily Living Scale. The risk factors associated with increased hazard of the functional dependence in the oldest-old ( ≥ 80 years old) were cognitive impairment, extrapyramidal diseases, cerebral infarction, transient ischemic attack, sleep disorders, hypnotics, osteoarthrosis, hypertension and fall with the odds ratio (OR) of 1.241-2.962 (all P fall, cardiovascular diseases, osteoarthrosis and hearing loss were the risk factors for that in the elderly subjects (aged 60-79 years). The OR was 1.232-5.790 (all P risk of functional dependence in both the oldest-old and elderly people. Neuropsychiatric disorders are the leading causes contributed to the functional dependence among oldest-old and elderly population. Neurodegenerative diseases in the oldest-old, stroke and depression in elderly people should be the priorities in ameliorating disability. Healthy lifestyle and avocational activities could improve the functional status of the oldest-old and elderly population.

Critical Quality Source Diagnosis for Dam Concrete Construction Based on Quality Gain-loss Function

Directory of Open Access Journals (Sweden)

Bo Wang

2014-06-01

Full Text Available In dam concrete construction process, it not only has quality loss arising from quality fluctuation, but also gains quality compensation effect due to the mutual cooperation and adaptation coupling between working procedures (WPs. The calculation and transmission complexity of the quality loss and quality compensation affect the quality management of dam concrete construction. As the quality compensation effect existing in the production practice cannot be described by Taguchi quality loss function, the concept of quality gain-loss function was presented in this paper, which was based on endowing the constant term in the expansion of Taylor series with physical meaning—quality compensation. Based on quality gain-loss function theory, a new quality gain-loss transmission model of dam concrete construction based on GERT network was constructed and its effective algorithm was designed. WP quality gain-loss and its impact on the final product were reasonably measured, and the critical quality routes and critical quality WPs were detected and diagnosed in dam concrete construction network. Summer temperature-controlled concrete construction in the third phase of Three Gorges Project (TGP was taken as an example to carry out the study, and the calculation results showed the validity and practicability of the presented model and algorithm.

Causal functional contributions and interactions in the attention network of the brain: an objective multi-perturbation analysis.

Science.gov (United States)

Zavaglia, Melissa; Hilgetag, Claus C

2016-06-01

Spatial attention is a prime example for the distributed network functions of the brain. Lesion studies in animal models have been used to investigate intact attentional mechanisms as well as perspectives for rehabilitation in the injured brain. Here, we systematically analyzed behavioral data from cooling deactivation and permanent lesion experiments in the cat, where unilateral deactivation of the posterior parietal cortex (in the vicinity of the posterior middle suprasylvian cortex, pMS) or the superior colliculus (SC) cause a severe neglect in the contralateral hemifield. Counterintuitively, additional deactivation of structures in the opposite hemisphere reverses the deficit. Using such lesion data, we employed a game-theoretical approach, multi-perturbation Shapley value analysis (MSA), for inferring functional contributions and network interactions of bilateral pMS and SC from behavioral performance in visual attention studies. The approach provides an objective theoretical strategy for lesion inferences and allows a unique quantitative characterization of regional functional contributions and interactions on the basis of multi-perturbations. The quantitative analysis demonstrated that right posterior parietal cortex and superior colliculus made the strongest positive contributions to left-field orienting, while left brain regions had negative contributions, implying that their perturbation may reverse the effects of contralateral lesions or improve normal function. An analysis of functional modulations and interactions among the regions revealed redundant interactions (implying functional overlap) between regions within each hemisphere, and synergistic interactions between bilateral regions. To assess the reliability of the MSA method in the face of variable and incomplete input data, we performed a sensitivity analysis, investigating how much the contribution values of the four regions depended on the performance of specific configurations and on the