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Sample records for impaired drug-binding capacity

  1. Inflammatory remodeling of the HDL proteome impairs cholesterol efflux capacity.

    PubMed

    Vaisar, Tomáš; Tang, Chongren; Babenko, Ilona; Hutchins, Patrick; Wimberger, Jake; Suffredini, Anthony F; Heinecke, Jay W

    2015-08-01

    Recent studies demonstrate that HDL's ability to promote cholesterol efflux from macrophages associates strongly with cardioprotection in humans independently of HDL-cholesterol (HDL-C) and apoA-I, HDL's major protein. However, the mechanisms that impair cholesterol efflux capacity during vascular disease are unclear. Inflammation, a well-established risk factor for cardiovascular disease, has been shown to impair HDL's cholesterol efflux capacity. We therefore tested the hypothesis that HDL's impaired efflux capacity is mediated by specific changes of its protein cargo. Humans with acute inflammation induced by low-level endotoxin had unchanged HDL-C levels, but their HDL-C efflux capacity was significantly impaired. Proteomic analyses demonstrated that HDL's cholesterol efflux capacity correlated inversely with HDL content of serum amyloid A (SAA)1 and SAA2. In mice, acute inflammation caused a marked impairment of HDL-C efflux capacity that correlated with a large increase in HDL SAA. In striking contrast, the efflux capacity of mouse inflammatory HDL was preserved with genetic ablation of SAA1 and SAA2. Our observations indicate that the inflammatory impairment of HDL-C efflux capacity is due in part to SAA-mediated remodeling of HDL's protein cargo. PMID:25995210

  2. Hypercholesterolemia Impairs Exercise Capacity in Mice

    PubMed Central

    Maxwell, Andrew J.; Niebauer, Josef; Lin, Patrick S.; Tsao, Philip S.; Bernstein, Daniel; Cooke, John P.

    2011-01-01

    Objective We previously reported an attenuation of both exercise hyperemia and measures of aerobic capacity in hypercholesterolemic mice. In this study we expanded upon the previous findings by examining the temporal and quantitative relationship of hypercholesterolemia to aerobic and anaerobic capacity and by exploring several potential mechanisms of dysfunction. Methods Eight-week old wild type (n=123) and apoE knockout (n=79) C57BL/6J mice were divided into groups with distinct cholesterol levels by feeding regular or high fat diets. At various ages the mice underwent treadmill ergospirometry. To explore mechanisms, aortic ring vasodilator function and nitrate (NOx) activity, urinary excretion of NOx, running muscle microvascular density and citrate synthase activity, as well as myocardial mass and histologic evidence of ischemia were measured. Results At 8 weeks of age, all mice had similar measures of exercise capacity. All indices of aerobic exercise capacity progressively declined at 12 and 20 weeks of age in the hypercholesterolemic mice as cholesterol levels increased while indices of anaerobic capacity remained unaffected. Across the 4 cholesterol groups, the degree of aerobic dysfunction was related to serum cholesterol levels; a relationship that was maintained after correcting for confounding factors. Associated with the deterioration in exercise capacity was a decline in measures of nitric oxide-mediated vascular function while there was no evidence of aberrations in functional or oxidative capacities or in other components of transport capacity. Conclusion Aerobic exercise dysfunction is observed in murine models of genetic and diet-induced hypercholesterolemia and is associated with a reduction in vascular nitric oxide production. PMID:19651675

  3. Clinical relevance of drug binding to plasma proteins

    NASA Astrophysics Data System (ADS)

    Ascenzi, Paolo; Fanali, Gabriella; Fasano, Mauro; Pallottini, Valentina; Trezza, Viviana

    2014-12-01

    Binding to plasma proteins highly influences drug efficacy, distribution, and disposition. Serum albumin, the most abundant protein in plasma, is a monomeric multi-domain macromolecule that displays an extraordinary ligand binding capacity, providing a depot and carrier for many endogenous and exogenous compounds, such as fatty acids and most acidic drugs. α-1-Acid glycoprotein, the second main plasma protein, is a glycoprotein physiologically involved in the acute phase reaction and is the main carrier for basic and neutral drugs. High- and low-density lipoproteins play a limited role in drug binding and are natural drug delivery system only for few lipophilic drugs or lipid-based formulations. Several factors influence drug binding to plasma proteins, such as pathological conditions, concurrent administration of drugs, sex, and age. Any of these factors, in turn, influences drug efficacy and toxicity. Here, biochemical, biomedical, and biotechnological aspects of drug binding to plasma proteins are reviewed.

  4. Measuring Decision-Making Capacity in Cognitively Impaired Individuals

    PubMed Central

    Karlawish, Jason

    2009-01-01

    Cognitive and functional losses are only part of the spectrum of disability experienced by persons with Alzheimer’s disease and related dementias. They also experience losses in the ability to make decisions, known as decision-making capacity. Researchers have made substantial progress in developing a model of capacity assessment that rests upon the concept of the 4 decision-making abilities: understanding, appreciation, choice and reasoning. Empirical research has increased our understanding of the effects of late-life cognitive impairment on a person’s ability to make decisions. This review examines studies of the capacity to consent to treatment, research and the management of everyday functional abilities. The results illustrate the clinical phenotype of the patient who retains the capacity to consent. They also suggest that measures of capacity can improve how researchers measure the benefits of cognitive enhancements and stage dementia. PMID:18097164

  5. Human mitochondrial oxidative capacity is acutely impaired following burn trauma

    PubMed Central

    Cree, Melanie G.; Fram, Ricki Y.; Herndon, David N.; Qian, Ting; Angel, Carlos; Green, Justin M.; Mlcak, Ronald; Aarsland, Asle; Wolfe, Robert R.

    2008-01-01

    Background Mitochondrial proteins and genes are damaged after burn injury in animals but have not previously been assessed in human burn patients. Methods The rates of maximal muscle mitochondrial oxidative capacity(ATP production) and uncoupled oxidation(heat production) for both palmitate and pyruvate were measured in muscle biopsies from 40 children sustaining burns >40% body surface area and from 13 healthy children controls. Results Maximal mitochondrial oxidation of pyruvate and palmitate were reduced in burn patients compared to controls (4.0±0.2:1.9±0.1 µmolO2/citrate synthase activity/mg protein/min pyruvate; Control:Burn;P<0.001 and 3.0±0.1:0.9±0.03 µmolO2/citrate synthase activity/mg protein/min palmatyl CoA; Control:Burn;P=0.003). Uncoupled oxidation was the same between groups. Conclusions The maximal coupled mitochondrial oxidative capacity is severely impaired after burn injury, although there are no alterations in the rate of uncoupled oxidative capacity. It may be that the ratio of these indicates that a larger portion of energy production in trauma patients is wasted through uncoupling, rather than used for healing. PMID:18639661

  6. Higher Self-Control Capacity Predicts Lower Anxiety-Impaired Cognition during Math Examinations

    PubMed Central

    Bertrams, Alex; Baumeister, Roy F.; Englert, Chris

    2016-01-01

    We assumed that self-control capacity, self-efficacy, and self-esteem would enable students to keep attentional control during tests. Therefore, we hypothesized that the three personality traits would be negatively related to anxiety-impaired cognition during math examinations. Secondary school students (N = 158) completed measures of self-control capacity, self-efficacy, and self-esteem at the beginning of the school year. Five months later, anxiety-impaired cognition during math examinations was assessed. Higher self-control capacity, but neither self-efficacy nor self-esteem, predicted lower anxiety-impaired cognition 5 months later, over and above baseline anxiety-impaired cognition. Moreover, self-control capacity was indirectly related to math grades via anxiety-impaired cognition. The findings suggest that improving self-control capacity may enable students to deal with anxiety-related problems during school tests. PMID:27065013

  7. Higher Self-Control Capacity Predicts Lower Anxiety-Impaired Cognition during Math Examinations.

    PubMed

    Bertrams, Alex; Baumeister, Roy F; Englert, Chris

    2016-01-01

    We assumed that self-control capacity, self-efficacy, and self-esteem would enable students to keep attentional control during tests. Therefore, we hypothesized that the three personality traits would be negatively related to anxiety-impaired cognition during math examinations. Secondary school students (N = 158) completed measures of self-control capacity, self-efficacy, and self-esteem at the beginning of the school year. Five months later, anxiety-impaired cognition during math examinations was assessed. Higher self-control capacity, but neither self-efficacy nor self-esteem, predicted lower anxiety-impaired cognition 5 months later, over and above baseline anxiety-impaired cognition. Moreover, self-control capacity was indirectly related to math grades via anxiety-impaired cognition. The findings suggest that improving self-control capacity may enable students to deal with anxiety-related problems during school tests. PMID:27065013

  8. Impairment of endothelial progenitor cell function and vascularization capacity by aldosterone in mice and humans

    PubMed Central

    Thum, Thomas; Schmitter, Kerstin; Fleissner, Felix; Wiebking, Volker; Dietrich, Bernd; Widder, Julian D.; Jazbutyte, Virginija; Hahner, Stefanie; Ertl, Georg; Bauersachs, Johann

    2011-01-01

    Aims Hyperaldosteronism is associated with vascular injury and increased cardiovascular events. Bone marrow-derived endothelial progenitor cells (EPCs) play an important role in endothelial repair and vascular homeostasis. We hypothesized that hyperaldosteronism impairs EPC function and vascularization capacity in mice and humans. Methods and results We characterized the effects of aldosterone and mineralocorticoid receptor (MR) blockade on EPC number and function as well as vascularization capacity and endothelial function. Treatment of human EPC with aldosterone induced translocation of the MR and impaired multiple cellular functions of EPC, such as differentiation, migration, and proliferation in vitro. Impaired EPC function was rescued by pharmacological blockade or genetic ablation of the MR. Aldosterone protein kinase A (PKA) dependently increased reactive oxygen species formation in EPC. Aldosterone infusion in mice impaired EPC function, EPC homing to vascular structures and vascularization capacity in a MR-dependent but blood pressure-independent manner. Endothelial progenitor cells from patients with primary hyperaldosteronism compared with controls of similar age displayed reduced migratory potential. Impaired EPC function was associated with endothelial dysfunction. MR blockade in patients with hyperaldosteronism improved EPC function and arterial stiffness. Conclusion Endothelial progenitor cells express a MR that mediates functional impairment by PKA-dependent increase of reactive oxygen species. Normalization of EPC function may represent a novel mechanism contributing to the beneficial effects of MR blockade in cardiovascular disease prevention and treatment. PMID:20926363

  9. Impaired Semantic Knowledge Underlies the Reduced Verbal Short-Term Storage Capacity in Alzheimer's Disease

    ERIC Educational Resources Information Center

    Peters, Frederic; Majerus, Steve; De Baerdemaeker, Julie; Salmon, Eric; Collette, Fabienne

    2009-01-01

    A decrease in verbal short-term memory (STM) capacity is consistently observed in patients with Alzheimer's disease (AD). Although this impairment has been mainly attributed to attentional deficits during encoding and maintenance, the progressive deterioration of semantic knowledge in early stages of AD may also be an important determinant of poor…

  10. Impaired Contingent Attentional Capture Predicts Reduced Working Memory Capacity in Schizophrenia

    PubMed Central

    Mayer, Jutta S.; Fukuda, Keisuke; Vogel, Edward K.; Park, Sohee

    2012-01-01

    Although impairments in working memory (WM) are well documented in schizophrenia, the specific factors that cause these deficits are poorly understood. In this study, we hypothesized that a heightened susceptibility to attentional capture at an early stage of visual processing would result in working memory encoding problems. 30 patients with schizophrenia and 28 demographically matched healthy participants were presented with a search array and asked to report the orientation of the target stimulus. In some of the trials, a flanker stimulus preceded the search array that either matched the color of the target (relevant-flanker capture) or appeared in a different color (irrelevant-flanker capture). Working memory capacity was determined in each individual using the visual change detection paradigm. Patients needed considerably more time to find the target in the no-flanker condition. After adjusting the individual exposure time, both groups showed equivalent capture costs in the irrelevant-flanker condition. However, in the relevant-flanker condition, capture costs were increased in patients compared to controls when the stimulus onset asynchrony between the flanker and the search array was high. Moreover, the increase in relevant capture costs correlated negatively with working memory capacity. This study demonstrates preserved stimulus-driven attentional capture but impaired contingent attentional capture associated with low working memory capacity in schizophrenia. These findings suggest a selective impairment of top-down attentional control in schizophrenia, which may impair working memory encoding. PMID:23152783

  11. Correlation Between Working Capacity and APDL in Middle-Aged and Elderly People with Intellectual Impairment

    PubMed Central

    Nakajima, Kazuo

    1999-01-01

    In this study we investigated the correlation between working capacity and APDL of middle-aged and elderly residents of welfare homes for the intellectually retarded. The subjects were 313 intellectually retarded people over 35 years old. The subjects were chosen from residents of four welfare institutions and job-placement centers for intellectually retarded people in Otaru, Hokkaido. Personal attributes, working capacity, and APDL were investigated in each subject. The items of personal attributes were: gender, chronological age, severity of intellectual impairment, and presence/absence of Down's syndrome. Working capacity was evaluated according to the 6 items. APDL was evaluated according to the 51 items. For statistical analysis of the working capacity of the subjects, the variables were summarized using principal component analysis and scored. Next, a search was made for the common factors in the 51 items of APDL using the principal component method. Finally, the correlation between working capacity and APDL was investigated by multiple regression analysis, with the obtained composite scores as dependent variables and the scores of APDL factors extracted by principal component analysis as independent variables. The following three factors were selected for the subjects: health management, outdoor movement and social activity. The multiple correlation coefficient using these three factors was R=0.63 (F=55.20, p<0.01). This indicates the necessity, from the viewpoints of prevention of senility, to focus not only on the decrease in working capacity of aging residents with intellectual impairment in welfare institutions but to establish various countermeasures based on the interrelationship between working capacity and APDL. PMID:25792909

  12. Impaired seminal antioxidant capacity in human semen with hyperviscosity or oligoasthenozoospermia.

    PubMed

    Siciliano, L; Tarantino, P; Longobardi, F; Rago, V; De Stefano, C; Carpino, A

    2001-01-01

    Antioxidant capacity of seminal plasma was evaluated in 120 semen samples subdivided into asthenozoospermic and oligoasthenozoospermic specimens with normal consistency and into asthenozoospermic and oligoasthenozoospermic specimens with hyperviscosity. Semen samples (n = 25) from normozoospermic donors were used as a control group. Scavenger antioxidant capacity of reactive oxygen species was evaluated by superoxide dismutase and catalase activity measurements, whereas the chain-breaking antioxidant efficiency was detected by total antioxidant status assessment. In semen with normal viscosity, unaltered enzymatic and nonenzymatic antioxidant capacity was revealed in the asthenozoospermic specimens, whereas low superoxide dismutase activity was detected in oligoasthenozoospermic samples. On the contrary, impairment of both the scavenger and chain-breaking antioxidative systems was revealed in asthenozoospermic and oligoasthenozoospermic hyperviscous ejaculates, regardless of sperm count. Catalase activity and total antioxidant status values were also reduced in the 2 subgroups of hyperviscous ejaculates compared with their respective matched controls, whereas similar superoxide dismutase activities were detected in oligoasthenozoospermic samples with normal and high consistencies. These results suggest that asthenozoospermia could be related to an antioxidant deficiency only in combined ejaculate pathologies, and that a severe impairment of the low and high molecular weight seminal antioxidative capacities could be associated with semen hyperviscosity. PMID:11545292

  13. Augmentation of Normal and Glutamate-Impaired Neuronal Respiratory Capacity by Exogenous Alternative Biofuels

    PubMed Central

    Laird, Melissa D.; Clerc, Pascaline; Polster, Brian M.; Fiskum, Gary

    2013-01-01

    Mitochondrial respiratory capacity is critical for responding to changes in neuronal energy demand. One approach toward neuroprotection is administration of alternative energy substrates (“biofuels”) to overcome brain injury-induced inhibition of glucose-based aerobic energy metabolism. This study tested the hypothesis that exogenous pyruvate, lactate, β-hydroxybutyrate, and acetyl-L-carnitine each increase neuronal respiratory capacity in vitro either in the absence of, or following transient excitotoxic glutamate receptor stimulation. Compared to the presence of 5 mM glucose alone, the addition of pyruvate, lactate, or β-hydroxybutyrate (1.0 – 10.0 mM) to either day in vitro (DIV) 14 or 7 rat cortical neurons resulted in significant, dose-dependent stimulation of respiratory capacity, measured by cell respirometry as the maximal O2 consumption rate in the presence of the respiratory uncoupler FCCP. A thirty minute exposure to 100 μM glutamate impaired respiratory capacity for DIV 14 but not DIV 7 neurons. Glutamate reduced the respiratory capacity for DIV 14 neurons with glucose alone by 25% and also reduced respiratory capacity with glucose plus pyruvate, lactate or β-hydroxybutyrate. However, respiratory capacity in glutamate-exposed neurons following pyruvate or β-hydroxybutyrate addition was still at least as high as that obtained with glucose alone in the absence of glutamate exposure. These results support the interpretation that previously observed neuroprotection by exogenous pyruvate, lactate, or β-hydroxybutyrate is at least partially mediated by their preservation of neuronal respiratory capacity. PMID:24323418

  14. Does lung diffusion impairment affect exercise capacity in patients with heart failure?

    PubMed Central

    Agostoni, P G; Bussotti, M; Palermo, P; Guazzi, M

    2002-01-01

    Objective: To determine whether there is a relation between impairment of lung diffusion and reduced exercise capacity in chronic heart failure. Design: 40 patients with heart failure in stable clinical condition and 40 controls participated in the study. All subjects underwent standard pulmonary function tests plus measurements of resting lung diffusion (carbon monoxide transfer, Tlco), pulmonary capillary volume (Vc), and membrane resistance (Dm), and maximal cardiopulmonary exercise testing. In 20 patients and controls, the following investigations were also done: (1) resting and constant work rate Tlco; (2) maximal cardiopulmonary exercise testing with inspiratory O2 fractions of 0.21 and 0.16; and (3) rest and peak exercise blood gases. The other subjects underwent Tlco, Dm, and Vc measurements during constant work rate exercise. Results: In normoxia, exercise induced reductions of haemoglobin O2 saturation never occurred. With hypoxia, peak exercise uptake (peak V̇o2) decreased from (mean (SD)) 1285 (395) to 1081 (396) ml/min (p < 0.01) in patients, and from 1861 (563) to 1771 (457) ml/min (p < 0.05) in controls. Resting Tlco correlated with peak V̇o2 in heart failure (normoxia < hypoxia). In heart failure patients and normal subjects, Tlco and peak V̇o2 correlated with O2 arterial content at rest and during peak exercise in both normoxia and hypoxia. Tlco, Vc, and Dm increased during exercise. The increase in Tlco was greater in patients who had a smaller reduction of exercise capacity with hypoxia. Alveolar–arterial O2 gradient at peak correlated with exercise capacity in heart failure during normoxia and, to a greater extent, during hypoxia. Conclusions: Lung diffusion impairment is related to exercise capacity in heart failure. PMID:12381630

  15. [Capacity impairments and participation restrictions : Assessment and qualifying in the sociomedical evaluation of mental disorders].

    PubMed

    Linden, Michael

    2016-09-01

    Participation is defined, according to the International Classification of Functioning, Disability and Health (ICF), as inclusion in life. Participation restrictions are the result of a mismatch between capacities and context requirements. Mental disorders are more impairing than many somatic disorders.There are instruments to assess and operationalize capacity and participation restrictions like the ADL-scales, the GAF, the ICF-AT-50, the ICFPsych A&P, the IMET, the ICF-Coresets, the WHODAS, or the Mini-ICF-APP, which differ in respect to indications, differentiation between function, capacity or context and context-adjusted qualifying.In addition to the type of participation restrictions, their chronicity must also be assessed. This is done in reference to the present mental disorder, the course, and the earlier treatment in respect to functions, capacities, and context.The assessment and qualifying of participation restrictions needs an adjustment to the environment or context. This is not only a problem for the individual but also for societal developments. PMID:27474691

  16. Modeling and Estimating Recall Processing Capacity: Sensitivity and Diagnostic Utility in Application to Mild Cognitive Impairment.

    PubMed

    Wenger, Michael K; Negash, Selamawit; Petersen, Ronald C; Petersen, Lyndsay

    2010-02-01

    We investigate the potential for using latency-based measures of retrieval processing capacity to assess changes in perfomance specific to individuals with mild cognitive impairment (MCI), a reliable precursor state to Alzheimer's Disease. Use of these capacity measures is motivated in part by exploration of the effects of atrophy on a computational model of a basic hippocampal circuit. We use this model to suggest that capacity may be a more sensitive indicator of undelying atrophy than speed of processing, and test this hypothesis by adapting a standard behavioral measure of memory (the free and cued selective reminding test, FCSRT) to allow for the collection of cued recall latencies. Participants were drawn from five groups: college-aged, middle-aged, healthy elderly, those with a diagnosis of MCI, and a sample of MCI control participants. The measure of capacity is shown to offer increased classificatory sensitivity relative to the standard behavioral measures, and is also shown to be the behavioral measure that correlated most strongly with hippocampal volume. PMID:20436932

  17. Modeling and Estimating Recall Processing Capacity: Sensitivity and Diagnostic Utility in Application to Mild Cognitive Impairment

    PubMed Central

    Wenger, Michael K.; Negash, Selamawit; Petersen, Ronald C.; Petersen, Lyndsay

    2009-01-01

    We investigate the potential for using latency-based measures of retrieval processing capacity to assess changes in perfomance specific to individuals with mild cognitive impairment (MCI), a reliable precursor state to Alzheimer's Disease. Use of these capacity measures is motivated in part by exploration of the effects of atrophy on a computational model of a basic hippocampal circuit. We use this model to suggest that capacity may be a more sensitive indicator of undelying atrophy than speed of processing, and test this hypothesis by adapting a standard behavioral measure of memory (the free and cued selective reminding test, FCSRT) to allow for the collection of cued recall latencies. Participants were drawn from five groups: college-aged, middle-aged, healthy elderly, those with a diagnosis of MCI, and a sample of MCI control participants. The measure of capacity is shown to offer increased classificatory sensitivity relative to the standard behavioral measures, and is also shown to be the behavioral measure that correlated most strongly with hippocampal volume. PMID:20436932

  18. Inducible depletion of satellite cells in adult, sedentary mice impairs muscle regenerative capacity without affecting sarcopenia.

    PubMed

    Fry, Christopher S; Lee, Jonah D; Mula, Jyothi; Kirby, Tyler J; Jackson, Janna R; Liu, Fujun; Yang, Lin; Mendias, Christopher L; Dupont-Versteegden, Esther E; McCarthy, John J; Peterson, Charlotte A

    2015-01-01

    A key determinant of geriatric frailty is sarcopenia, the age-associated loss of skeletal muscle mass and strength. Although the etiology of sarcopenia is unknown, the correlation during aging between the loss of activity of satellite cells, which are endogenous muscle stem cells, and impaired muscle regenerative capacity has led to the hypothesis that the loss of satellite cell activity is also a cause of sarcopenia. We tested this hypothesis in male sedentary mice by experimentally depleting satellite cells in young adult animals to a degree sufficient to impair regeneration throughout the rest of their lives. A detailed analysis of multiple muscles harvested at various time points during aging in different cohorts of these mice showed that the muscles were of normal size, despite low regenerative capacity, but did have increased fibrosis. These results suggest that lifelong reduction of satellite cells neither accelerated nor exacerbated sarcopenia and that satellite cells did not contribute to the maintenance of muscle size or fiber type composition during aging, but that their loss may contribute to age-related muscle fibrosis. PMID:25501907

  19. Osteoblasts with impaired spreading capacity benefit from the positive charges of plasma polymerised allylamine.

    PubMed

    Kunz, F; Rebl, H; Quade, A; Matschegewski, C; Finke, B; Nebe, J B

    2015-01-01

    Bone diseases such as osteoporosis, osteoarthritis and rheumatoid arthritis, impinge on the performance of orthopaedic implants by impairing bone regeneration. For this reason, the development of effective surface modifications supporting the ingrowth of implants in morbid bone tissue is essential. Our study is designed to elucidate if cells with restricted cell-function limiting adhesion processes benefit from plasma polymer deposition on titanium. We used the actin filament disrupting agent cytochalasin D (CD) as an experimental model for cells with impaired actin cytoskeleton. Indeed, the cell's capacity to adhere and spread was drastically reduced due to shortened actin filaments and vinculin contacts that were smaller. The coating of titanium with a positively charged nanolayer of plasma polymerised allylamine (PPAAm) abrogated these disadvantages in cell adhesion and the CD-treated osteoblasts were able to spread significantly. Interestingly, PPAAm increased spreading by causing enhanced vinculin number and contact length, but without significantly reorganising actin filaments. PPAAm with the monomer allylamine was deposited in a microwave-excited low-pressure plasma-processing reactor. Cell physiology was monitored by flow cytometry and confocal laser scanning microscopy, and the length and number of actin filaments was quantified by mathematical image processing. We showed that biomaterial surface modification with PPAAm could be beneficial even for osteoblasts with impaired cytoskeleton components. These insights into in vitro conditions may be used for the evaluation of future strategies to design implants for morbid bone tissue. PMID:25738585

  20. Physiological responses to heat of resting man with impaired sweating capacity

    NASA Technical Reports Server (NTRS)

    Totel, G. L.

    1974-01-01

    The effects of total-body heat exposure were studied in three groups of subjects with varied degrees of impaired sweating capacity. The responses of two ectodermal dysplasic men, six quadriplegic men, and a man with widespread burned scar tissue were compared with the responses of three able-bodied men resting in the heat. It was found that the able-bodied and burned subjects competed successfully with a controlled environment of 38 C and 20% relative humidity for up to 150 min, whereas the quadriplegic and ectodermal dysplasic men developed hyperthermia, hyperventilation, and distress after only 120 and 75 min of heat exposure, respectively. The intolerance to heat is thus ascribed directly to the inability to produce and evaporate sweat.

  1. Impaired spare respiratory capacity in cortical synaptosomes from Sod2 null mice

    PubMed Central

    Flynn, James M.; Choi, Sung W.; Day, Nicholas U.; Gerencser, Akos A.; Hubbard, Alan; Melov, Simon

    2011-01-01

    Pre-synaptic nerve terminals require high levels of ATP for the maintenance of synaptic function. Failure of synaptic mitochondria to generate adequate ATP has been implicated as a causative event preceding loss of synaptic networks in neurodegenerative disease. Endogenous oxidative stress has often been postulated as an etiological basis for this pathology, but has been difficult to test in vivo. Inactivation of the superoxide dismutase gene (Sod2) encoding the chief defense enzyme against mitochondrial superoxide radicals results in neonatal lethality. However, intervention with an SOD mimetic extends the lifespan of this model, and uncovers a neurodegenerative phenotype providing a unique model for the examination of in vivo oxidative stress. We present here studies on synaptic termini isolated from the frontal cortex of Sod2 null mice demonstrating impaired bioenergetic function as a result of mitochondrial oxidative stress. Cortical synaptosomes from Sod2 null mice demonstrate a severe decline in mitochondrial spare respiratory capacity to physiological demand induced by mitochondrial respiratory chain uncoupling with FCCP or plasma membrane depolarization induced by 4-aminopyridine treatment. However, Sod2 null animals compensate for impaired oxidative metabolism in part by Pasteur effect allowing for normal neurotransmitter release at the synapse, setting up a potentially detrimental energetic paradigm. The results of this study demonstrate that high throughput respirometry is a facile method for analyzing specific regions of the brain in transgenic models, and can uncover bioenergetic deficits in subcellular regions due to endogenous oxidative stress. PMID:21215798

  2. Impaired Adipose Tissue Expandability and Lipogenic Capacities as Ones of the Main Causes of Metabolic Disorders

    PubMed Central

    Tinahones, Francisco José

    2015-01-01

    Obesity is considered a major health problem. However, mechanisms involved and its comorbidities are not elucidated. Recent theories concerning the causes of obesity have focused on a limit to the functional capacity of adipose tissue, comparing it with other vital organs. This assumption has been the central point of interest in our laboratory. We proposed that the failure of adipose tissue is initiated by the difficulty of this tissue to increase its cellularity due to excess in fat contribution, owing to genetic or environmental factors. Nevertheless, why the adipose tissue reduces its capacity to make new adipocytes via mesenchymal cells of the stroma has not yet been elucidated. Thus, we suggest that this tissue ceases fulfilling its main function, the storage of excess fat, thereby affecting some of the key factors involved in lipogenesis, some of which are reviewed in this paper (PPARγ, ROR1, FASN, SCD1, Rab18, BrCa1, ZAG, and FABP4). On the other hand, mechanisms involved in adipose tissue expandability are also impaired, predominating hypertrophy via an increase in apoptosis and a decrease in adipogenesis and angiogenesis. However, adipose tissue failure is only part of this great orchestra, only a chapter of this nightmare. PMID:25922847

  3. Abnormal spirometry after the Fontan procedure is common and associated with impaired aerobic capacity.

    PubMed

    Opotowsky, Alexander R; Landzberg, Michael J; Earing, Michael G; Wu, Fred M; Triedman, John K; Casey, Alicia; Ericson, Dawn A; Systrom, David; Paridon, Stephen M; Rhodes, Jonathan

    2014-07-01

    Impaired exercise capacity is common after the Fontan procedure and is attributed to cardiovascular limits. The Fontan circulation, however, is also distinctively vulnerable to unfavorable lung mechanics. This study aimed to define the prevalence and physiological relevance of pulmonary dysfunction in patients with Fontan physiology. We analyzed data from the Pediatric Heart Network Fontan Cross-Sectional Study to assess the prevalence and pattern of abnormal spirometry in Fontan patients (6-18 yr old) and investigated the relationship between low forced vital capacity (FVC) and maximum exercise variables, including peak O2 consumption (Vo2peak), among those who demonstrated adequate effort (n = 260). Average ages at the time of exercise testing and Fontan completion were 13.2 ± 3.0 and 3.5 ± 2.2 yr old, respectively. Aerobic capacity was reduced (Vo2peak: 67.3 ± 15.6% predicted). FVC averaged 79.0 ± 14.8% predicted, with 45.8% having a FVC less then the lower limit of normal. Only 7.8% demonstrated obstructive spirometry. Patients with low FVC had lower Vo2peak (64.4 ± 15.9% vs. 69.7 ± 14.9% predicted, P < 0.01); low FVC independently predicted lower Vo2peak after adjusting for relevant covariates. Among those with Vo2peak < 80% predicted (n = 204/260), 22.5% demonstrated a pulmonary mechanical contribution to exercise limitation (breathing reserve < 20%). Those with both low FVC and ventilatory inefficiency (minute ventilation/CO2 production > 40) had markedly reduced Vo2peak (61.5 ± 15.3% vs. 72.0 ± 14.9% predicted, P < 0.01) and a higher prevalence of pulmonary mechanical limit compared with patients with normal FVC and efficient ventilation (36.1% vs. 4.8%). In conclusion, abnormal FVC is common in young patients after the Fontan procedure and is independently associated with reduced exercise capacity. A large subset has a pathologically low breathing reserve, consistent with a pulmonary mechanical contribution to exercise limitation. PMID:24791784

  4. Subclinical zinc deficiency impairs pancreatic digestive enzyme activity and digestive capacity of weaned piglets.

    PubMed

    Brugger, Daniel; Windisch, Wilhelm M

    2016-08-01

    This study investigated the effects of short-term subclinical Zn deficiency on exocrine pancreatic activity and changes in digestive capacity. A total of forty-eight weaned piglets were fed ad libitum a basal diet (maize and soyabean meal) with adequate Zn supply (88 mg Zn/kg diet) during a 2-week acclimatisation phase. Animals were then assigned to eight dietary treatment groups (n 6) according to a complete randomised block design considering litter, live weight and sex. All pigs were fed restrictively (450 g diet/d) the basal diet but with varying ZnSO4.7H2O additions, resulting in 28·1, 33·6, 38·8, 42·7, 47·5, 58·2, 67·8 and 88·0 mg Zn/kg diet for a total experimental period of 8 d. Pancreatic Zn concentrations and pancreatic activities of trypsin, chymotrypsin, carboxypeptidase A and B, elastase and α-amylase exhibited a broken-line response to stepwise reduction in dietary Zn by declining beneath thresholds of 39·0, 58·0, 58·0, 41·2, 47·5, 57·7 and 58·0 mg Zn/kg diet, respectively. Furthermore, carboxypeptidase B and α-amylase activities were significantly lower in samples with reduced pancreatic Zn contents. Coefficients of faecal digestibility of DM, crude protein, total lipids and crude ash responded similarly to pancreatic enzyme activities by declining below dietary thresholds of 54·7, 45·0, 46·9 and 58·2 mg Zn/kg diet, respectively. In conclusion, (1) subclinical Zn deficiency impaired pancreatic exocrine enzymes, (2) this response was connected to pancreatic Zn metabolism and (3) the decline in catalytic activity impaired faecal digestibility already after 1 week of insufficient alimentary Zn supply and very early before clinical deficiency symptoms arise. PMID:27230230

  5. Sentence Comprehension in Specific Language Impairment: A Task Designed to Distinguish between Cognitive Capacity and Syntactic Complexity

    ERIC Educational Resources Information Center

    Leonard, Laurence B.; Deevy, Patricia; Fey, Marc E.; Bredin-Oja, Shelley L.

    2013-01-01

    Purpose: This study examined sentence comprehension in children with specific language impairment (SLI) in a manner designed to separate the contribution of cognitive capacity from the effects of syntactic structure. Method: Nineteen children with SLI, 19 typically developing children matched for age (TD-A), and 19 younger typically developing…

  6. Working Memory Capacity and Its Relation to Stroop Interference and Facilitation Effects in Individuals with Mild Cognitive Impairment

    ERIC Educational Resources Information Center

    Sung, Jee Eun; Kim, Jin Hee; Jeong, Jee Hyang; Kang, Heejin

    2012-01-01

    Purpose: The purposes of the study were to investigate (a) the task-specific differences in short-term memory (STM) and working memory capacity (WMC) in individuals with mild cognitive impairment (MCI) and normal elderly adults (NEAs), (b) the Stroop interference and facilitation effects, and (c) the relationship of STM and WMC to the Stroop…

  7. Executive function impairment and recidivism in adult protective services clients referred for a decision making capacity assessment.

    PubMed

    Terracina, Katherine A; Aamodt, Whitley W; Schillerstrom, Jason E

    2015-01-01

    The objective of this study was to determine if recidivistic Adult Protective Services (APS) cases referred for a decision-making capacity assessment were more cognitively impaired than nonrecidivistic cases. A retrospective medical record review of neuropsychological and demographic data was gathered during decisional capacity assessments. Recidivistic clients were those referred to APS more than once; those with a single open case were nonrecidivistic. Mean neuropsychological test scores were compared between recidivistic (n = 138) and nonrecidivistic (n = 95) subjects. No significant differences were found for age, gender, ethnicity, education, or dwelling status. Both recidivistic and nonrecidivistic cases performed poorly in all cognitive domains. Recidivistic clients performed significantly worse on measures of executive function (CLOX1, EXIT25). Executive function impairments seem to be one risk factor for recidivism in APS referrals. With 60% of cases referred for decision capacity assessments being recidivistic, identifying risk factors may help identify when targeted interventions are indicated to preclude recurrence of abuse. PMID:25495662

  8. Physicochemical features of the HERG channel drug binding site.

    PubMed

    Fernandez, David; Ghanta, Azad; Kauffman, Gregory W; Sanguinetti, Michael C

    2004-03-12

    Blockade of hERG K(+) channels in the heart is an unintentional side effect of many drugs and can induce cardiac arrhythmia and sudden death. It has become common practice in the past few years to screen compounds for hERG channel activity early during the drug discovery process. Understanding the molecular basis of drug binding to hERG is crucial for the rational design of medications devoid of this activity. We previously identified 2 aromatic residues, Tyr-652 and Phe-656, located in the S6 domain of hERG, as critical sites of interaction with structurally diverse drugs. Here, Tyr-652 and Phe-656 were systematically mutated to different residues to determine how the physicochemical properties of the amino acid side group affected channel block by cisapride, terfenadine, and MK-499. The potency for block by all three drugs was well correlated with measures of hydrophobicity, especially the two-dimensional approximation of the van der Waals hydrophobic surface area of the side chain of residue 656. For residue 652, an aromatic side group was essential for high affinity block, suggesting the importance of a cation-pi interaction between Tyr-652 and the basic tertiary nitrogen of these drugs. hERG also lacks a Pro-Val-Pro motif common to the S6 domain of most other voltage-gated K(+) channels. Introduction of Pro-Val-Pro into hERG reduced sensitivity to drugs but also altered channel gating. Together, these findings assign specific residues to receptor fields predicted by pharmacophore models of hERG channel blockers and provide a refined molecular understanding of the drug binding site. PMID:14699101

  9. Impaired glucose metabolism and exercise capacity with muscle-specific glycogen synthase 1 (gys1) deletion in adult mice

    PubMed Central

    Xirouchaki, Chrysovalantou E.; Mangiafico, Salvatore P.; Bate, Katherine; Ruan, Zheng; Huang, Amy M.; Tedjosiswoyo, Bing Wilari; Lamont, Benjamin; Pong, Wynne; Favaloro, Jenny; Blair, Amy R.; Zajac, Jeffrey D.; Proietto, Joseph; Andrikopoulos, Sofianos

    2016-01-01

    Objective Muscle glucose storage and muscle glycogen synthase (gys1) defects have been associated with insulin resistance. As there are multiple mechanisms for insulin resistance, the specific role of glucose storage defects is not clear. The aim of this study was to examine the effects of muscle-specific gys1 deletion on glucose metabolism and exercise capacity. Methods Tamoxifen inducible and muscle specific gys-1 KO mice were generated using the Cre/loxP system. Mice were subjected to glucose tolerance tests, euglycemic/hyperinsulinemic clamps and exercise tests. Results gys1-KO mice showed ≥85% reduction in muscle gys1 mRNA and protein concentrations, 70% reduction in muscle glycogen levels, postprandial hyperglycaemia and hyperinsulinaemia and impaired glucose tolerance. Under insulin-stimulated conditions, gys1-KO mice displayed reduced glucose turnover and muscle glucose uptake, indicative of peripheral insulin resistance, as well as increased plasma and muscle lactate levels and reductions in muscle hexokinase II levels. gys1-KO mice also exhibited markedly reduced exercise and endurance capacity. Conclusions Thus, muscle-specific gys1 deletion in adult mice results in glucose intolerance due to insulin resistance and reduced muscle glucose uptake as well as impaired exercise and endurance capacity. In brief This study demonstrates why the body prioritises muscle glycogen storage over liver glycogen storage despite the critical role of the liver in supplying glucose to the brain in the fasting state and shows that glycogen deficiency results in impaired glucose metabolism and reduced exercise capacity. PMID:26977394

  10. Impaired Capacity of Fibroblasts to Support Airway Epithelial Progenitors in Bronchiolitis Obliterans Syndrome

    PubMed Central

    Zhang, Su-Bei; Sun, Xin; Wu, Qi; Wu, Jun-Ping; Chen, Huai-Yong

    2016-01-01

    Background: Bronchiolitis obliterans syndrome (BOS) often develops in transplant patients and results in injury to the respiratory and terminal airway epithelium. Owing to its rising incidence, the pathogenesis of BOS is currently an area of intensive research. Studies have shown that injury to the respiratory epithelium results in dysregulation of epithelial repair. Airway epithelial regeneration is supported by stromal cells, including fibroblasts. This study aimed to investigate whether the supportive role of lung fibroblasts is altered in BOS. Methods: Suspensions of lung cells were prepared by enzyme digestion. Lung progenitor cells (LPCs) were separated by fluorescence-activated cell sorting. Lung fibroblasts from patients with BOS or healthy controls were mixed with sorted mouse LPCs to compare the colony-forming efficiency of LPCs by counting the number of colonies with a diameter of ≥50 μm in each culture. Statistical analyses were performed using the SPSS 17.0 software (SPSS Inc., USA). The paired Student's t-test was used to test for statistical significance. Results: LPCs were isolated with the surface phenotype of CD31- CD34- CD45- EpCAM+ Sca-1+. The colony-forming efficiency of LPCs was significantly reduced when co-cultured with fibroblasts isolated from patients with BOS. The addition of SB431542 increased the colony-forming efficiency of LPCs to 1.8%; however, it was still significantly less than that in co-culture with healthy control fibroblasts (P < 0.05). Conclusion: The epithelial-supportive capacity of fibroblasts is impaired in the development of BOS and suggest that inefficient repair of airway epithelium could contribute to persistent airway inflammation in BOS. PMID:27569228

  11. Investigating medical decision-making capacity in patients with cognitive impairment using a protocol based on linguistic features.

    PubMed

    Tallberg, Ing-Mari; Stormoen, Sara; Almkvist, Ove; Eriksdotter, Maria; Sundström, Erik

    2013-10-01

    A critical question is whether cognitively impaired patients have the competence for autonomous decisions regarding participation in clinical trials. The present study aimed to investigate medical decision-making capacity by use of a Swedish linguistic instrument for medical decision-making (LIMD) in hypothetical clinical trials in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI). Three comparable groups (age, education) participated in the study: AD (n = 20; MMSE: 24.1 ± 3.3) and MCI (n = 22; MMSE: 26.7 ± 2.4) patients and healthy controls (n = 37; MMSE: 29.1 ± 1.0). Medical decision-making capacity was operationalized as answers to questions regarding participation in three hypothetical clinical trials. Answers were scored regarding comprehension, evaluation and intelligibility of decisions, and a total LIMD score was used as the measure of medical decision-making ability. Groups differed significantly in LIMD with AD patients performing worst and MCI poorer than the control group. A strong association was found between all LIMD scores and diagnosis which supported the assertion that LIMD as it is designed is a one-dimensional instrument of medical decision-making capacity (MDMC). The results indicate that a fundamental communicative ability has an impact on the competence for autonomous decisions in cognitive impairment. PMID:23841467

  12. Increased Muscle Sympathetic Nerve Activity and Impaired Executive Performance Capacity in Obstructive Sleep Apnea

    PubMed Central

    Goya, Thiago T.; Silva, Rosyvaldo F.; Guerra, Renan S.; Lima, Marta F.; Barbosa, Eline R.F.; Cunha, Paulo Jannuzzi; Lobo, Denise M.L.; Buchpiguel, Carlos A.; Busatto-Filho, Geraldo; Negrão, Carlos E.; Lorenzi-Filho, Geraldo; Ueno-Pardi, Linda M.

    2016-01-01

    impaired executive performance capacity in obstructive sleep apnea. SLEEP 2016;39(1):25–33. PMID:26237773

  13. Aging-Induced Dysregulation of Dicer1-Dependent MicroRNA Expression Impairs Angiogenic Capacity of Rat Cerebromicrovascular Endothelial Cells

    PubMed Central

    2013-01-01

    Age-related impairment of angiogenesis is likely to play a central role in cerebromicrovascular rarefaction and development of vascular cognitive impairment, but the underlying mechanisms remain elusive. To test the hypothesis that dysregulation of Dicer1 (ribonuclease III, a key enzyme of the microRNA [miRNA] machinery) impairs endothelial angiogenic capacity in aging, primary cerebromicrovascular endothelial cells (CMVECs) were isolated from young (3 months old) and aged (24 months old) Fischer 344 × Brown Norway rats. We found an age-related downregulation of Dicer1 expression both in CMVECs and in small cerebral vessels isolated from aged rats. In aged CMVECs, Dicer1 expression was increased by treatment with polyethylene glycol–catalase. Compared with young cells, aged CMVECs exhibited altered miRNA expression profile, which was associated with impaired proliferation, adhesion to vitronectin, collagen and fibronectin, cellular migration (measured by a wound-healing assay using electric cell–substrate impedance sensing technology), and impaired ability to form capillary-like structures. Overexpression of Dicer1 in aged CMVECs partially restored miRNA expression profile and significantly improved angiogenic processes. In young CMVECs, downregulation of Dicer1 (siRNA) resulted in altered miRNA expression profile associated with impaired proliferation, adhesion, migration, and tube formation, mimicking the aging phenotype. Collectively, we found that Dicer1 is essential for normal endothelial angiogenic processes, suggesting that age-related dysregulation of Dicer1-dependent miRNA expression may be a potential mechanism underlying impaired angiogenesis and cerebromicrovascular rarefaction in aging. PMID:23239824

  14. Impaired mechanical stability, migration and contractile capacity in vimentin-deficient fibroblasts

    NASA Technical Reports Server (NTRS)

    Eckes, B.; Dogic, D.; Colucci-Guyon, E.; Wang, N.; Maniotis, A.; Ingber, D.; Merckling, A.; Langa, F.; Aumailley, M.; Delouvee, A.; Koteliansky, V.; Babinet, C.; Krieg, T.

    1998-01-01

    Loss of a vimentin network due to gene disruption created viable mice that did not differ overtly from wild-type littermates. Here, primary fibroblasts derived from vimentin-deficient (-/-) and wild-type (+/+) mouse embryos were cultured, and biological functions were studied in in vitro systems resembling stress situations. Stiffness of -/- fibroblasts was reduced by 40% in comparison to wild-type cells. Vimentin-deficient cells also displayed reduced mechanical stability, motility and directional migration towards different chemo-attractive stimuli. Reorganization of collagen fibrils and contraction of collagen lattices were severely impaired. The spatial organization of focal contact proteins, as well as actin microfilament organization was disturbed. Thus, absence of a vimentin filament network does not impair basic cellular functions needed for growth in culture, but cells are mechanically less stable, and we propose that therefore they are impaired in all functions depending upon mechanical stability.

  15. Enhanced Glucose Transport, but not Phosphorylation Capacity, Ameliorates Lipopolysaccharide-Induced Impairments in Insulin-Stimulated Muscle Glucose Uptake.

    PubMed

    Otero, Yolanda F; Mulligan, Kimberly X; Barnes, Tammy M; Ford, Eric A; Malabanan, Carlo M; Zong, Haihong; Pessin, Jeffrey E; Wasserman, David H; McGuinness, Owen P

    2016-06-01

    Lipopolysaccharide (LPS) is known to impair insulin-stimulated muscle glucose uptake (MGU). We determined if increased glucose transport (GLUT4) or phosphorylation capacity (hexokinase II; HKII) could overcome the impairment in MGU. We used mice that overexpressed GLUT4 (GLUT4) or HKII (HK) in skeletal muscle. Studies were performed in conscious, chronically catheterized (carotid artery and jugular vein) mice. Mice received an intravenous bolus of either LPS (10 μg/g body weight) or vehicle (VEH). After 5 h, a hyperinsulinemic-euglycemic clamp was performed. As MGU is also dependent on cardiovascular function that is negatively affected by LPS, cardiac function was assessed using echocardiography. LPS decreased whole body glucose disposal and MGU in wild-type (WT) and HK mice. In contrast, the decrease was attenuated in GLUT4 mice. Although membrane-associated GLUT4 was increased in VEH-treated GLUT4 mice, LPS impaired membrane-associated GLUT4 in GLUT4 mice to the same level as LPS-treated WT mice. This suggested that overexpression of GLUT4 had further benefits beyond preserving transport activity. In fact, GLUT4 overexpression attenuated the LPS-induced decrease in cardiac function. The maintenance of MGU in GLUT4 mice following LPS was accompanied by sustained anaerobic glycolytic flux as suggested by increased muscle Pdk4 expression, and elevated lactate availability. Thus, enhanced glucose transport, but not phosphorylation capacity, ameliorates LPS-induced impairments in MGU. This benefit is mediated by long-term adaptations to the overexpression of GLUT4 that sustain muscle anaerobic glycolytic flux and cardiac function in response to LPS. PMID:26682946

  16. Sustained Selective Attention Skills of Preschool Children with Specific Language Impairment: Evidence for Separate Attentional Capacities

    ERIC Educational Resources Information Center

    Spaulding, Tammie J.; Plante, Elena; Vance, Rebecca

    2008-01-01

    Purpose: The present study was designed to investigate the performance of preschool children with specific language impairment (SLI) and their typically developing (TD) peers on sustained selective attention tasks. Method: This study included 23 children diagnosed with SLI and 23 TD children matched for age, gender, and maternal education level.…

  17. Visual Impairment does not Limit Training Effects in Development of Aerobic and Anaerobic Capacity in Tandem Cyclists.

    PubMed

    Malwina, Kamelska Anna; Krzysztof, Mazurek; Piotr, Zmijewski

    2015-11-22

    The study aimed to investigate the differences in the effects of 7-month training on aerobic and anaerobic capacity in tandem cycling athletes with and without visual impairment. In this study, Polish elite (n=13) and sub-elite (n=13) visually impaired (VI) (n=13; 40.8 ±12.8 years) and properly sighted (PS) (n=13; 36.7 ±12.2 years) tandem-cycling athletes participated voluntarily in 7-month routine training. The following pre-/post-training measurements were conducted on separate days: maximal oxygen uptake (VO2max) was estimated with age correction using the Physical Working Capacity test on a bicycle ergometer according to the Astrand-Ryhming method. Maximal power output (Pmax) was evaluated using the Quebec test on a bicycle ergometer. At baseline, VO2max (47.8 ±14.1 vs 42.0 ±8.3 ml/kg/min, respectively) and Pmax (11.5 ±1.5 vs 11.5 ±1.0 W/kg) did not differ significantly between PS and VI cyclists. However, differences in aerobic capacity were considered as clinically significant. Two-way ANOVA revealed that after 7 month training, there were statistically significant increases in VO2max (p=0.003) and Pmax (p=0.009) among VI (VO2max, +9.1%; Pmax, +6.3%) and PS (VO2max, +9.1%; Pmax, +11.7%) cyclists, however, no time × visual impairment interaction effect was found (VO2max, p=0.467; Pmax, p=0.364). After training, VO2max (p=0.03), but not Pmax (p=0.13), was significantly greater in elite compared to sub-elite tandem cyclists. VI and PS tandem cyclists showed similar rates of improvement in VO2max and Pmax after 7-month training. VO2max was a significant determinant of success in tandem cycling. This is one of the first studies providing reference values for aerobic and anaerobic capacity in visually impaired cyclists. PMID:26834877

  18. Visual Impairment does not Limit Training Effects in Development of Aerobic and Anaerobic Capacity in Tandem Cyclists

    PubMed Central

    Malwina, Kamelska Anna; Krzysztof, Mazurek; Piotr, Zmijewski

    2015-01-01

    The study aimed to investigate the differences in the effects of 7-month training on aerobic and anaerobic capacity in tandem cycling athletes with and without visual impairment. In this study, Polish elite (n=13) and sub-elite (n=13) visually impaired (VI) (n=13; 40.8 ±12.8 years) and properly sighted (PS) (n=13; 36.7 ±12.2 years) tandem-cycling athletes participated voluntarily in 7-month routine training. The following pre-/post-training measurements were conducted on separate days: maximal oxygen uptake (VO2max) was estimated with age correction using the Physical Working Capacity test on a bicycle ergometer according to the Astrand-Ryhming method. Maximal power output (Pmax) was evaluated using the Quebec test on a bicycle ergometer. At baseline, VO2max (47.8 ±14.1 vs 42.0 ±8.3 ml/kg/min, respectively) and Pmax (11.5 ±1.5 vs 11.5 ±1.0 W/kg) did not differ significantly between PS and VI cyclists. However, differences in aerobic capacity were considered as clinically significant. Two-way ANOVA revealed that after 7 month training, there were statistically significant increases in VO2max (p=0.003) and Pmax (p=0.009) among VI (VO2max, +9.1%; Pmax, +6.3%) and PS (VO2max, +9.1%; Pmax, +11.7%) cyclists, however, no time × visual impairment interaction effect was found (VO2max, p=0.467; Pmax, p=0.364). After training, VO2max (p=0.03), but not Pmax (p=0.13), was significantly greater in elite compared to sub-elite tandem cyclists. VI and PS tandem cyclists showed similar rates of improvement in VO2max and Pmax after 7-month training. VO2max was a significant determinant of success in tandem cycling. This is one of the first studies providing reference values for aerobic and anaerobic capacity in visually impaired cyclists. PMID:26834877

  19. Extending MIL-STD-1553 bandwidth: a study of impairments, EMI, and channel capacity

    NASA Astrophysics Data System (ADS)

    Hegarty, Michael G.

    2004-09-01

    This paper explores the possibility of increasing the data rates on existing MIL-STD-1553 networks beyond its current one megabit per second rate. A combination of empirical and theoretical methods is used in predicting the capacity of a MIL-STD-1553 network. The analysis begins with an assessment of the usable bandwidth in a 1553 network followed by the development of models to predict signal-to-noise ratios based on a transmit signal level that meets the emissions limits of MIL-STD-461 and a noise level that is representative of a real 1553 system. This paper presents the theoretical capacity limits for several 1553 network configurations. The results of the analysis predict that the theoretical capacity within a legacy MIL-STD-1553 system is expected to be several hundred megabits per second. The achievable rate depends on network configuration and usable bandwidth. Methods of approaching these theoretical capacity limits is not discussed in this paper, rather, this paper provides a framework and a baseline for the analysis of higher data rates over legacy MIL-STD-1553 networks.

  20. Pioglitazone ameliorates the lowered exercise capacity and impaired mitochondrial function of the skeletal muscle in type 2 diabetic mice.

    PubMed

    Takada, Shingo; Hirabayashi, Kagami; Kinugawa, Shintaro; Yokota, Takashi; Matsushima, Shouji; Suga, Tadashi; Kadoguchi, Tomoyasu; Fukushima, Arata; Homma, Tsuneaki; Mizushima, Wataru; Masaki, Yoshihiro; Furihata, Takaaki; Katsuyama, Ryoichi; Okita, Koichi; Tsutsui, Hiroyuki

    2014-10-01

    We have reported that exercise capacity is reduced in high fat diet (HFD)-induced diabetic mice, and that this reduction is associated with impaired mitochondrial function in skeletal muscle (SKM). However, it remains to be clarified whether the treatment of diabetes ameliorates the reduced exercise capacity. Therefore, we examined whether an insulin-sensitizing drug, pioglitazone, could improve exercise capacity in HFD mice. C57BL/6J mice were fed a normal diet (ND) or HFD, then treated with or without pioglitazone (3 mg/kg/day) to yield the following 4 groups: ND+vehicle, ND+pioglitazone, HFD+vehicle, and HFD+pioglitazone (n=10 each). After 8 weeks, body weight, plasma glucose, and insulin in the HFD+vehicle were significantly increased compared to the ND+vehicle group. Pioglitazone normalized the insulin levels in HFD-fed mice, but did not affect the body weight or plasma glucose. Exercise capacity determined by treadmill tests was significantly reduced in the HFD+vehicle, and this reduction was almost completely ameliorated in HFD+pioglitazone mice. ADP-dependent mitochondrial respiration, complex I and III activities, and citrate synthase activity were significantly decreased in the SKM of the HFD+vehicle animals, and these decreases were also attenuated by pioglitazone. NAD(P)H oxidase activity was significantly increased in the HFD+vehicle compared with the ND+vehicle, and this increase was ameliorated in HFD+pioglitazone mice. Pioglitazone improved the exercise capacity in diabetic mice, which was due to the improvement in mitochondrial function and attenuation of oxidative stress in the SKM. Our data suggest that pioglitazone may be useful as an agent for the treatment of diabetes mellitus. PMID:24964389

  1. Gait analysis in chronic heart failure: The calf as a locus of impaired walking capacity.

    PubMed

    Panizzolo, Fausto A; Maiorana, Andrew J; Naylor, Louise H; Dembo, Lawrence; Lloyd, David G; Green, Daniel J; Rubenson, Jonas

    2014-11-28

    Reduced walking capacity, a hallmark of chronic heart failure (CHF), is strongly correlated with hospitalization and morbidity. The aim of this work was to perform a detailed biomechanical gait analysis to better identify mechanisms underlying reduced walking capacity in CHF. Inverse dynamic analyses were conducted in CHF patients and age- and exercise level-matched control subjects on an instrumented treadmill at self-selected treadmill walking speeds and at speeds representing +20% and -20% of the subjects' preferred speed. Surprisingly, no difference in preferred speed was observed between groups, possibly explained by an optimization of the mechanical cost of transport in both groups (the mechanical cost to travel a given distance; J/kg/m). The majority of limb kinematics and kinetics were also similar between groups, with the exception of greater ankle dorsiflexion angles during stance in CHF. Nevertheless, over two times greater ankle plantarflexion work during stance and per distance traveled is required for a given triceps surae muscle volume in CHF patients. This, together with a greater reliance on the ankle compared to the hip to power walking in CHF patients, especially at faster speeds, may contribute to the earlier onset of fatigue in CHF patients. This observation also helps explain the high correlation between triceps surae muscle volume and exercise capacity that has previously been reported in CHF. Considering the key role played by the plantarflexors in powering walking and their association with exercise capacity, our findings strongly suggest that exercise-based rehabilitation in CHF should not omit the ankle muscle group. PMID:25307437

  2. Increased fibrin formation and impaired fibrinolytic capacity in severe chronic kidney disease.

    PubMed

    Mörtberg, Josefin; Blombäck, Margareta; Wallén, Åkan; He, Shu; Jacobson, Stefan H; Spaak, Jonas

    2016-06-01

    Chronic kidney disease (CKD) is associated with a concurrent increased risk of thrombosis and bleeding. We aimed to investigate whether CKD is associated with increased fibrin formation, impaired fibrin degradation, or both. Twenty-one patients with CKD stage 4 (CKD 4), 15 haemodialysis patients, and 13 controls (C) without kidney disease were studied. We used a global assay to determine fibrin formation and degradation in plasma. Fibrin turbidity was measured over time to obtain a value of the coagulation activation profile (Cp) and the fibrinolysis activation profile (Fp), and the amount of fibrin formed, termed fibrin optical density sum (fibrin OD-sum). We used scanning electron microscopy (SEM) to visualize the fibrin network. Plasminogen activator inhibitor type-1 antigen, thrombin-activatable fibrinolysis inhibitor activity, fibrinogen, von Willebrand factor, antithrombin, albumin, and C-reactive protein were measured in plasma. Fibrin OD-sum was significantly elevated in haemodialysis patients [312 a.u.; 278-435 (median; interquartile range); P < 0.0013] and in CKD 4 (293 a.u.; 169-434; P = 0.0119) compared with controls (115 a.u.; 82-234). SEM showed a tight fibrin network in haemodialysis and CKD 4 patients. Fp was lower in the haemodialysis group than in controls (P = 0.030). Plasminogen activator inhibitor type-1 was lower in haemodialysis patients (P = 0.034). Thrombin-activatable fibrinolysis inhibitor activity, Cp, antithrombin, and C-reactive protein did not differ between groups. Fibrinogen was significantly elevated and albumin decreased in both haemodialysis and CKD 4 patients compared with controls. Von Willebrand factor was elevated in haemodialysis patients compared with controls (P = 0.010). The prothrombotic state in severe CKD is characterized by impaired fibrinolysis in association with increased fibrin formation despite normal levels of endogenous fibrinolysis inhibitors. PMID:26650459

  3. Insulin-driven translational capacity is impaired in primary fibroblasts of Prader Willi

    PubMed Central

    Meneghello, Cristiana; Segat, Daniela; Fortunati, Elisabetta

    2016-01-01

    Summary Prader-Willi (PW) syndrome is a rare genetic disorder characterized by hypothalamic-pituitary abnormalities and severe hypotonia, hyperphagia, behavioural and psychiatric problems. Absence of satiety leads to severe obesity and frequently to diabetes. Furthermore, adult patients suffer from a severe loss of muscle mass, which severely impacts their quality of life. The mechanisms underlying alterations in muscle growth in PW remain to be clarified. In this study we explored the hypothesis that, in PW cells, alterations of protein synthesis are determined by dysfunctions in the promotion of cell growth. In order to study the molecular changes leading to dysfunction in protein translation, primary fibroblasts derived from four PW patients and five control subjects were used to study the insulin-mediated signaling pathway implicated in the control of protein synthesis by immunoblotting. Here we present, for the first time, evidences that the protein translation response to insulin is impaired in PW fibroblasts. Insulin alone has a major upregulatory effect on protein kinase B (AKT), glycogen synthase kinase (GSK3beta), while phosphorylation of p70S6K1 protein elongation factor controlled by mammalian target of rapamycin complex I (mTORC1) is reduced. In addition, we provide data that the response to insulin in PW cells can be restored by previous treatment with the amino acid L-Leucine (L-Leu). Our experiments in primary cell cultures demonstrate an impairment of insulin signaling that can be rescued by supplementation with the branched aminoacid L-Leu, indicating a possible therapeutic approach for alleviating muscle mass loss in PW patients. PMID:26989644

  4. Insulin-driven translational capacity is impaired in primary fibroblasts of Prader Willi.

    PubMed

    Meneghello, Cristiana; Segat, Daniela; Fortunati, Elisabetta

    2016-02-01

    Prader-Willi (PW) syndrome is a rare genetic disorder characterized by hypothalamic-pituitary abnormalities and severe hypotonia, hyperphagia, behavioural and psychiatric problems. Absence of satiety leads to severe obesity and frequently to diabetes. Furthermore, adult patients suffer from a severe loss of muscle mass, which severely impacts their quality of life. The mechanisms underlying alterations in muscle growth in PW remain to be clarified. In this study we explored the hypothesis that, in PW cells, alterations of protein synthesis are determined by dysfunctions in the promotion of cell growth. In order to study the molecular changes leading to dysfunction in protein translation, primary fibroblasts derived from four PW patients and five control subjects were used to study the insulin-mediated signaling pathway implicated in the control of protein synthesis by immunoblotting. Here we present, for the first time, evidences that the protein translation response to insulin is impaired in PW fibroblasts. Insulin alone has a major upregulatory effect on protein kinase B (AKT), glycogen synthase kinase (GSK3beta), while phosphorylation of p70S6K1 protein elongation factor controlled by mammalian target of rapamycin complex I (mTORC1) is reduced. In addition, we provide data that the response to insulin in PW cells can be restored by previous treatment with the amino acid L-Leucine (L-Leu). Our experiments in primary cell cultures demonstrate an impairment of insulin signaling that can be rescued by supplementation with the branched aminoacid L-Leu, indicating a possible therapeutic approach for alleviating muscle mass loss in PW patients. PMID:26989644

  5. Prion infection impairs lysosomal degradation capacity by interfering with rab7 membrane attachment in neuronal cells

    PubMed Central

    Shim, Su Yeon; Karri, Srinivasarao; Law, Sampson; Schatzl, Hermann M.; Gilch, Sabine

    2016-01-01

    Prions are proteinaceous infectious particles which cause fatal neurodegenerative disorders in humans and animals. They consist of a mostly β-sheeted aggregated isoform (PrPSc) of the cellular prion protein (PrPc). Prions replicate autocatalytically in neurons and other cell types by inducing conformational conversion of PrPc into PrPSc. Within neurons, PrPSc accumulates at the plasma membrane and in vesicles of the endocytic pathway. To better understand the mechanisms underlying neuronal dysfunction and death it is critical to know the impact of PrPSc accumulation on cellular pathways. We have investigated the effects of prion infection on endo-lysosomal transport. Our study demonstrates that prion infection interferes with rab7 membrane association. Consequently, lysosomal maturation and degradation are impaired. Our findings indicate a mechanism induced by prion infection that supports stable prion replication. We suggest modulation of endo-lysosomal vesicle trafficking and enhancement of lysosomal maturation as novel targets for the treatment of prion diseases. PMID:26865414

  6. Prion infection impairs lysosomal degradation capacity by interfering with rab7 membrane attachment in neuronal cells.

    PubMed

    Shim, Su Yeon; Karri, Srinivasarao; Law, Sampson; Schatzl, Hermann M; Gilch, Sabine

    2016-01-01

    Prions are proteinaceous infectious particles which cause fatal neurodegenerative disorders in humans and animals. They consist of a mostly β-sheeted aggregated isoform (PrP(Sc)) of the cellular prion protein (PrP(c)). Prions replicate autocatalytically in neurons and other cell types by inducing conformational conversion of PrP(c) into PrP(Sc). Within neurons, PrP(Sc) accumulates at the plasma membrane and in vesicles of the endocytic pathway. To better understand the mechanisms underlying neuronal dysfunction and death it is critical to know the impact of PrP(Sc) accumulation on cellular pathways. We have investigated the effects of prion infection on endo-lysosomal transport. Our study demonstrates that prion infection interferes with rab7 membrane association. Consequently, lysosomal maturation and degradation are impaired. Our findings indicate a mechanism induced by prion infection that supports stable prion replication. We suggest modulation of endo-lysosomal vesicle trafficking and enhancement of lysosomal maturation as novel targets for the treatment of prion diseases. PMID:26865414

  7. Diabetes mellitus Type II and cognitive capacity in healthy aging, mild cognitive impairment and Alzheimer's disease.

    PubMed

    Degen, Christina; Toro, Pablo; Schönknecht, Peter; Sattler, Christine; Schröder, Johannes

    2016-06-30

    While diabetes mellitus (DM) Type II has repeatedly been linked to Alzheimer´s disease (AD) and mild cognitive impairment (MCI), longitudinal research is scarce and disease duration has not always been taken into account. In a birth cohort born between 1930 and 1932 we investigated the influence of DM Type II and disease duration on neuropsychological functioning (memory/learning, attention, verbal fluency, visuospatial thinking and abstract thinking) across 14 years. Subjects who developed MCI or AD performed significantly poorer on all neuropsychological tests applied. While significant main effects DM Type II did not arise, its presence led to a significant deterioration of performance in the digit symbol test and visuospatial thinking over time. Additionally, in visuospatial thinking this change was more pronounced for individuals suffering from MCI/AD. We found that, as a concomitant disease DM Type II does not affect memory functioning, which is typically compromised in MCI and early AD. Rather, it may lead to deficits in cognitive flexibility and visuospatial thinking. DM Type II can be considered a frequent comorbid condition which can aggravate the course of MCI and AD. In this respect it may serve as a model for other comorbid conditions in AD. PMID:27082868

  8. Insulin Resistance in Adolescents with Type 2 Diabetes Is Associated with Impaired Exercise Capacity

    PubMed Central

    Nadeau, Kristen J.; Zeitler, Phillip S.; Bauer, Timothy A.; Brown, Mark S.; Dorosz, Jennifer L.; Draznin, Boris; Reusch, Jane E. B.; Regensteiner, Judith G.

    2009-01-01

    Context: The incidence of pediatric type 2 diabetes (T2D) is rising, with unclear effects on the cardiovascular system. Cardiopulmonary fitness, a marker of morbidity and mortality, is abnormal in adults with T2D, yet the mechanisms are incompletely understood. Objective: We hypothesized that cardiopulmonary fitness would be reduced in youth with T2D in association with insulin resistance (IR) and cardiovascular dysfunction. Design, Setting, and Participants: We conducted a cross-sectional study at an academic hospital that included 14 adolescents (age range, 12–19 yr) with T2D, 13 equally obese adolescents and 12 lean adolescents similar in age, pubertal stage, and activity level. Main Outcome Measures: Cardiopulmonary fitness was measured by peak oxygen consumption (VO2peak) and oxygen uptake kinetics (VO2kinetics), IR by hyperinsulinemic clamp, cardiac function by echocardiography, vascular function by venous occlusion plethysmography, body composition by dual-energy x-ray absorptiometry, intramyocellular lipid by magnetic resonance spectroscopy, and inflammation by serum markers. Results: Adolescents with T2D had significantly decreased VO2peak and insulin sensitivity, and increased soleus intramyocellular lipid, C-reactive protein, and IL-6 compared to obese or lean adolescents. Adolescents with T2D also had significantly prolonged VO2kinetics, decreased work rate, vascular reactivity, and adiponectin, and increased left ventricular mass and fatty acids compared to lean adolescents. In multivariate linear regression analysis, IR primarily, and fasting free fatty acids and forearm blood flow secondarily, were significant independent predictors of VO2peak. Conclusions: Given the strong relationship between decreased cardiopulmonary fitness and increased mortality, these findings in children are especially concerning and represent early signs of impaired cardiac function. PMID:19584191

  9. Integration of proprioceptive signals and attentional capacity during postural control are impaired but subject to improvement in dyslexic children.

    PubMed

    Quercia, Patrick; Demougeot, Laurent; Dos Santos, Mickaël; Bonnetblanc, François

    2011-04-01

    . Altogether, these results suggest that integration of proprioceptive signals in balance control and attentional capacity are impaired in dyslexic children. However, attention capacity during the control of stance could be improved significantly. PMID:21359661

  10. Isolation and chemical characterization of 2-hydroxybenzoylglycine as a drug binding inhibitor in uremia.

    PubMed Central

    Lichtenwalner, D M; Suh, B; Lichtenwalner, M R

    1983-01-01

    An organic compound that inhibits drug binding in uremia has been isolated from the sera of chronic renal failure patients, and its chemical structure has been determined. Addition of the compound to normal human sera in vitro resulted in drug binding defects similar to those seen in uremia. The purification of this substance was accomplished by n-butyl chloride extraction of acidified (pH 3.0) uremic sera followed by column chromatography, thin-layer chromatography, and paper electrophoresis. From analytical studies including ultraviolet and fluorescence spectroscopy, gas chromatography, chemical ionization and electron impact mass spectrometry, and proton nuclear magnetic resonance spectroscopy, the chemical structure of the uremic binding inhibitor was deduced to be 2-hydroxybenzoylglycine. This confirms the hypothesis that the drug binding defect in uremia is due to the accumulation of endogenous metabolic products rather than an intrinsic structural defect in albumin. Images PMID:6853715

  11. Crystal Structure of an Integron Gene Cassette-Associated Protein from Vibrio cholerae Identifies a Cationic Drug-Binding Module

    PubMed Central

    Deshpande, Chandrika N.; Harrop, Stephen J.; Boucher, Yan; Hassan, Karl A.; Leo, Rosa Di; Xu, Xiaohui; Cui, Hong; Savchenko, Alexei; Chang, Changsoo; Labbate, Maurizio; Paulsen, Ian T.; Stokes, H. W.; Curmi, Paul M. G.; Mabbutt, Bridget C.

    2011-01-01

    Background The direct isolation of integron gene cassettes from cultivated and environmental microbial sources allows an assessment of the impact of the integron/gene cassette system on the emergence of new phenotypes, such as drug resistance or virulence. A structural approach is being exploited to investigate the modularity and function of novel integron gene cassettes. Methodology/Principal Findings We report the 1.8 Å crystal structure of Cass2, an integron-associated protein derived from an environmental V. cholerae. The structure defines a monomeric beta-barrel protein with a fold related to the effector-binding portion of AraC/XylS transcription activators. The closest homologs of Cass2 are multi-drug binding proteins, such as BmrR. Consistent with this, a binding pocket made up of hydrophobic residues and a single glutamate side chain is evident in Cass2, occupied in the crystal form by polyethylene glycol. Fluorescence assays demonstrate that Cass2 is capable of binding cationic drug compounds with submicromolar affinity. The Cass2 module possesses a protein interaction surface proximal to its drug-binding cavity with features homologous to those seen in multi-domain transcriptional regulators. Conclusions/Significance Genetic analysis identifies Cass2 to be representative of a larger family of independent effector-binding proteins associated with lateral gene transfer within Vibrio and closely-related species. We propose that the Cass2 family not only has capacity to form functional transcription regulator complexes, but represents possible evolutionary precursors to multi-domain regulators associated with cationic drug compounds. PMID:21390267

  12. Crystal Structure of an Integron Gene Cassette-Associated Protein from Vibrio cholerae Identifies a Cationic Drug-Binding Module

    SciTech Connect

    Deshpande, Chandrika N.; Harrop, Stephen J.; Boucher, Yan; Hassan, Karl A.; Di Leo, Rosa; Xu, Xiaohui; Cui, Hong; Savchenko, Alexei; Chang, Changsoo; Labbate, Maurizio; Paulsen, Ian T.; Stokes, H.W.; Curmi, Paul M.G.; Mabbutt, Bridget C.

    2012-02-15

    The direct isolation of integron gene cassettes from cultivated and environmental microbial sources allows an assessment of the impact of the integron/gene cassette system on the emergence of new phenotypes, such as drug resistance or virulence. A structural approach is being exploited to investigate the modularity and function of novel integron gene cassettes. We report the 1.8 {angstrom} crystal structure of Cass2, an integron-associated protein derived from an environmental V. cholerae. The structure defines a monomeric beta-barrel protein with a fold related to the effector-binding portion of AraC/XylS transcription activators. The closest homologs of Cass2 are multi-drug binding proteins, such as BmrR. Consistent with this, a binding pocket made up of hydrophobic residues and a single glutamate side chain is evident in Cass2, occupied in the crystal form by polyethylene glycol. Fluorescence assays demonstrate that Cass2 is capable of binding cationic drug compounds with submicromolar affinity. The Cass2 module possesses a protein interaction surface proximal to its drug-binding cavity with features homologous to those seen in multi-domain transcriptional regulators. Genetic analysis identifies Cass2 to be representative of a larger family of independent effector-binding proteins associated with lateral gene transfer within Vibrio and closely-related species. We propose that the Cass2 family not only has capacity to form functional transcription regulator complexes, but represents possible evolutionary precursors to multi-domain regulators associated with cationic drug compounds.

  13. Capacity of the Catalan and Spanish Versions of the Bilingual Aphasia Test to Distinguish between Healthy Aging, Mild Cognitive Impairment and Alzheimer's Disease

    ERIC Educational Resources Information Center

    Gomez-Ruiz, Isabel; Aguilar-Alonso, Angel

    2011-01-01

    This study analysed the capacity of the Catalan and Spanish versions of the Bilingual Aphasia Test (BAT) to distinguish between normal and pathological aging. Both versions of the test were administered to 45 bilingual subjects: 15 healthy aging subjects, 15 patients with mild cognitive impairment and 15 patients with Alzheimer's disease. To…

  14. Speech Perception and Phonological Short-Term Memory Capacity in Language Impairment: Preliminary Evidence from Adolescents with Specific Language Impairment (SLI) and Autism Spectrum Disorders (ASD)

    ERIC Educational Resources Information Center

    Loucas, Tom; Riches, Nick Greatorex; Charman, Tony; Pickles, Andrew; Simonoff, Emily; Chandler, Susie; Baird, Gillian

    2010-01-01

    Background: The cognitive bases of language impairment in specific language impairment (SLI) and autism spectrum disorders (ASD) were investigated in a novel non-word comparison task which manipulated phonological short-term memory (PSTM) and speech perception, both implicated in poor non-word repetition. Aims: This study aimed to investigate the…

  15. Combination of exercise training and diet restriction normalizes limited exercise capacity and impaired skeletal muscle function in diet-induced diabetic mice.

    PubMed

    Suga, Tadashi; Kinugawa, Shintaro; Takada, Shingo; Kadoguchi, Tomoyasu; Fukushima, Arata; Homma, Tsuneaki; Masaki, Yoshihiro; Furihata, Takaaki; Takahashi, Masashige; Sobirin, Mochamad A; Ono, Taisuke; Hirabayashi, Kagami; Yokota, Takashi; Tanaka, Shinya; Okita, Koichi; Tsutsui, Hiroyuki

    2014-01-01

    Exercise training (EX) and diet restriction (DR) are essential for effective management of obesity and insulin resistance in diabetes mellitus. However, whether these interventions ameliorate the limited exercise capacity and impaired skeletal muscle function in diabetes patients remains unexplored. Therefore, we investigated the effects of EX and/or DR on exercise capacity and skeletal muscle function in diet-induced diabetic mice. Male C57BL/6J mice that were fed a high-fat diet (HFD) for 8 weeks were randomly assigned for an additional 4 weeks to 4 groups: control, EX, DR, and EX+DR. A lean group fed with a normal diet was also studied. Obesity and insulin resistance induced by a HFD were significantly but partially improved by EX or DR and completely reversed by EX+DR. Although exercise capacity decreased significantly with HFD compared with normal diet, it partially improved with EX and DR and completely reversed with EX+DR. In parallel, the impaired mitochondrial function and enhanced oxidative stress in the skeletal muscle caused by the HFD were normalized only by EX+DR. Although obesity and insulin resistance were completely reversed by DR with an insulin-sensitizing drug or a long-term intervention, the exercise capacity and skeletal muscle function could not be normalized. Therefore, improvement in impaired skeletal muscle function, rather than obesity and insulin resistance, may be an important therapeutic target for normalization of the limited exercise capacity in diabetes. In conclusion, a comprehensive lifestyle therapy of exercise and diet normalizes the limited exercise capacity and impaired muscle function in diabetes mellitus. PMID:24189138

  16. Selective Life-Long Skeletal Myofiber-Targeted VEGF Gene Ablation Impairs Exercise Capacity in Adult Mice.

    PubMed

    Tang, Kechun; Gu, Yusu; Dalton, Nancy D; Wagner, Harrieth; Peterson, Kirk L; Wagner, Peter D; Breen, Ellen C

    2016-02-01

    Exercise is dependent on adequate oxygen supply for mitochondrial respiration in both cardiac and locomotor muscle. To determine whether skeletal myofiber VEGF is critical for regulating exercise capacity, independent of VEGF function in the heart, ablation of the VEGF gene was targeted to skeletal myofibers (skmVEGF-/-) during embryogenesis (∼ E9.5), leaving intact VEGF expression by all other cells in muscle. In adult mice, VEGF levels were decreased in the soleus (by 65%), plantaris (94%), gastrocnemius (74%), EDL (99%) and diaphragm (64%) (P < 0.0001, each muscle). VEGF levels were unchanged in the heart. Treadmill speed (WT 86 ± 4 cm/sec, skmVEGF-/- 70 ± 5 cm/sec, P = 0.006) and endurance (WT 78 ± 24 min, skmVEGF-/- 18 ± 4 min, P = 0.0004) were severely limited in skmVEGF-/- mice in contrast to minor effect of conditional skmVEGF gene deletion in the adult. Body weight was also reduced (WT 22.8 ± 1.6 g, skmVEGF-/-, 21.1 ± 1.5, P = 0.02), but the muscle mass/body weight ratio was unchanged. The capillary/fiber ratio was lower in skmVEGF-/- plantaris (WT 1.51 ± 0.12, skmVEGF-/- 1.16 ± 0.20, P = 0.01), gastrocnemius (WT 1.61 ± 0.08, skmVEGF-/- 1.39 ± 0.08, P = 0.01), EDL (WT 1.36 ± 0.07, skmVEGF-/- 1.14 ± 0.13, P = 0.03) and diaphragm (WT 1.39 ±  0.18, skmVEGF-/- 0.79 ± 0.16, P = 0.0001) but, not in soleus. Cardiac function (heart rate, maximal pressure, maximal dP/dt, minimal dP/dt,) in response to dobutamine was not impaired in anesthetized skmVEGF-/- mice. Isolated soleus and EDL fatigue times were 16% and 20% (P < 0.02) longer, respectively, in skmVEGF-/- mice than the WT group. These data suggest that skeletal myofiber VEGF expressed during development is necessary to establish capillary networks that allow maximal exercise capacity. PMID:26201683

  17. Impaired Cholesterol Efflux Capacity of High-Density Lipoprotein Isolated From Interstitial Fluid in Type 2 Diabetes Mellitus—Brief Report

    PubMed Central

    Tietge, Uwe J.F.; Dikkers, Arne; Parini, Paolo; Angelin, Bo; Rudling, Mats

    2016-01-01

    Objective— Patients with type 2 diabetes mellitus (T2D) have an increased risk of cardiovascular disease, the mechanism of which is incompletely understood. Their high-density lipoprotein (HDL) particles in plasma have been reported to have impaired cholesterol efflux capacity. However, the efflux capacity of HDL from interstitial fluid (IF), the starting point for reverse cholesterol transport, has not been studied. We here investigated the cholesterol efflux capacity of HDL from IF and plasma from T2D patients and healthy controls. Approach and Results— HDL was isolated from IF and peripheral plasma from 35 T2D patients and 35 age- and sex-matched healthy controls. Cholesterol efflux to HDL was determined in vitro, normalized for HDL cholesterol, using cholesterol-loaded macrophages. Efflux capacity of plasma HDL was 10% lower in T2D patients than in healthy controls, in line with previous observations. This difference was much more pronounced for HDL from IF, where efflux capacity was reduced by 28% in T2D. Somewhat surprisingly, the efflux capacity of HDL from IF was lower than that of plasma HDL, by 15% and 32% in controls and T2D patients, respectively. Conclusion— These data demonstrate that (1) HDL from IF has a lower cholesterol efflux capacity than plasma HDL and (2) the efflux capacity of HDL from IF is severely impaired in T2D when compared with controls. Because IF comprises the compartment where reverse cholesterol transport is initiated, the marked reduction in cholesterol efflux capacity of IF-HDL from T2D patients may play an important role for their increased risk to develop atherosclerosis. PMID:27034474

  18. Advanced Glycation End Products Modulate Structure and Drug Binding Properties of Albumin.

    PubMed

    Awasthi, Saurabh; Murugan, N Arul; Saraswathi, N T

    2015-09-01

    The extraordinary ligand binding properties of albumin makes it a key player in the pharmacokinetics and pharmacodynamics of many vital drugs. Albumin is highly susceptible for nonenzymatic glycation mediated structural modifications, and there is a need to determine structural and functional impact of specific AGEs modifications. The present study was aimed toward determining the AGE mediated structure and function changes, primarily looking into the effect on binding affinity of drugs in the two major drug binding sites of albumin. The impact of the two most predominant AGEs modifications, i.e., carboxyethyllysine (CEL) and argpyrimidine (Arg-P), was studied on the basis of the combination of in vitro and in silico experiments. In vitro studies were carried out by AGEs modification of bovine serum albumin (BSA) for the formation of Arg-P and CEL followed by drug interaction studies. In silico studies involved molecular dynamics (MD) simulations and docking studies for native and AGEs modified BSAs. In particular the side chain modification was specifically carried out for the residues in the drug binding sites, i.e., Arg-194, Arg-196, Arg-198, and Arg-217, and Lys-204 (site I) and Arg-409 and Lys-413 (site II). The equilibrated structures of native BSA (n-BSA) and glycated BSA (G-BSA) as obtained from MD were used for drug binding studies using molecular docking approach. It was evident from the results of both in vitro and in silico drug interaction studies that AGEs modification results in the reduced drug binding affinity for tolbutamide (TLB) and ibuprofen (IBP) in sites I and II. Moreover, the AGEs modification mediated conformational changes resulted in the shallow binding pockets with reduced accessibility for drugs. PMID:26281017

  19. Structure of P-Glycoprotein Reveals a Molecular Basis for Poly-Specific Drug Binding

    SciTech Connect

    Aller, Stephen G.; Yu, Jodie; Ward, Andrew; Weng, Yue; Chittaboina, Srinivas; Zhuo, Rupeng; Harrell, Patina M.; Trinh, Yenphuong T.; Zhang, Qinghai; Urbatsch, Ina L.; Chang, Geoffrey

    2009-04-22

    P-glycoprotein (P-gp) detoxifies cells by exporting hundreds of chemically unrelated toxins but has been implicated in multidrug resistance (MDR) in the treatment of cancers. Substrate promiscuity is a hallmark of P-gp activity, thus a structural description of poly-specific drug-binding is important for the rational design of anticancer drugs and MDR inhibitors. The x-ray structure of apo P-gp at 3.8 angstroms reveals an internal cavity of -6000 angstroms cubed with a 30 angstrom separation of the two nucleotide-binding domains. Two additional P-gp structures with cyclic peptide inhibitors demonstrate distinct drug-binding sites in the internal cavity capable of stereoselectivity that is based on hydrophobic and aromatic interactions. Apo and drug-bound P-gp structures have portals open to the cytoplasm and the inner leaflet of the lipid bilayer for drug entry. The inward-facing conformation represents an initial stage of the transport cycle that is competent for drug binding.

  20. Calorimetric investigation of diclofenac drug binding to a panel of moderately glycated serum albumins.

    PubMed

    Indurthi, Venkata S K; Leclerc, Estelle; Vetter, Stefan W

    2014-08-01

    Glycation alters the drug binding properties of serum proteins and could affect free drug concentrations in diabetic patients with elevated glycation levels. We investigated the effect of bovine serum albumin glycation by eight physiologically relevant glycation reagents (glucose, ribose, carboxymethyllysine, acetoin, methylglyoxal, glyceraldehyde, diacetyl and glycolaldehyde) on diclofenac drug binding. We used this non-steroidal anti-inflammatory drug diclofenac as a paradigm for acidic drugs with high serum binding and because of its potential cardiovascular risks in diabetic patients. Isothermal titration calorimetry showed that glycation reduced the binding affinity Ka of serum albumin and diclofenac 2 to 6-fold by reducing structural rigidity of albumin. Glycation affected the number of drug binding sites in a glycation reagent dependent manner and lead to a 25% decrease for most reagent, expect for ribose, with decreased by 60% and for the CML-modification, increased the number of binding sites by 60%. Using isothermal titration calorimetry and differential scanning calorimetry we derived the complete thermodynamic characterization of diclofenac binding to all glycated BSA samples. Our results suggest that glycation in diabetic patients could significantly alter the pharmacokinetics of the widely used over-the-counter NSDAI drug diclofenac and with possibly negative implications for patients. PMID:24751671

  1. Exposure to runoff from coal-tar-sealed pavement induces genotoxicity and impairment of DNA repair capacity in the RTL-W1 fish liver cell line.

    PubMed

    Kienzler, Aude; Mahler, Barbara J; Van Metre, Peter C; Schweigert, Nathalie; Devaux, Alain; Bony, Sylvie

    2015-07-01

    Coal-tar-based (CTB) sealcoat, frequently applied to parking lots and driveways in North America, contains elevated concentrations of polycyclic aromatic hydrocarbons (PAHs) and related compounds. The RTL-W1 fish liver cell line was used to investigate two endpoints (genotoxicity and DNA-repair-capacity impairment) associated with exposure to runoff from asphalt pavement with CTB sealcoat or with an asphalt-based sealcoat hypothesized to contain about 7% CTB sealcoat (AS-blend). Genotoxic potential was assessed by the Formamido pyrimidine glycosylase (Fpg)-modified comet assay for 1:10 and 1:100 dilutions of runoff samples collected from 5 h to 36 d following sealcoat application. DNA-repair capacity was assessed by the base excision repair comet assay for 1:10 dilution of samples collected 26 h and 36 d following application. Both assays were run with and without co-exposure to ultraviolet-A radiation (UVA). With co-exposure to UVA, genotoxic effects were significant for both dilutions of CTB runoff for three of four sample times, and for some samples of AS-blend runoff. Base excision repair was significantly impaired for CTB runoff both with and without UVA exposure, and for AS-blend runoff only in the absence of UVA. This study is the first to investigate the effects of exposure to the complex mixture of chemicals in coal tar on DNA repair capacity. The results indicate that co-exposure to runoff from CT-sealcoated pavement and UVA as much as a month after sealcoat application has the potential to cause genotoxicity and impair DNA repair capacity. PMID:25795989

  2. Exposure to runoff from coal-tar-sealed pavement induces genotoxicity and impairment of DNA repair capacity in the RTL-W1 fish liver cell line

    USGS Publications Warehouse

    Kienzler, Aude; Mahler, Barbara J.; Van Metre, Peter C.; Schweigert, Nathalie; Devaux, Alain; Bony, Sylvie

    2015-01-01

    Coal-tar-based (CTB) sealcoat, frequently applied to parking lots and driveways in North America, contains elevated concentrations of polycyclic aromatic hydrocarbons (PAHs) and related compounds. The RTL-W1 fish liver cell line was used to investigate two endpoints (genotoxicity and DNA-repair-capacity impairment) associated with exposure to runoff from asphalt pavement with CTB sealcoat or with an asphalt-based sealcoat hypothesized to contain about 7% CTB sealcoat (AS-blend). Genotoxic potential was assessed by the Formamido pyrimidine glycosylase (Fpg)-modified comet assay for 1:10 and 1:100 dilutions of runoff samples collected from 5 h to 36 d following sealcoat application. DNA-repair capacity was assessed by the base excision repair comet assay for 1:10 dilution of samples collected 26 h and 36 d following application. Both assays were run with and without co-exposure to ultraviolet-A radiation (UVA). With co-exposure to UVA, genotoxic effects were significant for both dilutions of CTB runoff for three of four sample times, and for some samples of AS-blend runoff. Base excision repair was significantly impaired for CTB runoff both with and without UVA exposure, and for AS-blend runoff only in the absence of UVA. This study is the first to investigate the effects of exposure to the complex mixture of chemicals in coal tar on DNA repair capacity. The results indicate that co-exposure to runoff from CT-sealcoated pavement and UVA as much as a month after sealcoat application has the potential to cause genotoxicity and impair DNA repair capacity.

  3. Do drugs have access to the P-glycoprotein drug-binding pocket through gates?

    PubMed

    Ferreira, Ricardo J; Ferreira, Maria-José U; Dos Santos, Daniel J V A

    2015-10-13

    The P-glycoprotein efflux mechanism is being studied since its identification as a leading protagonist in multidrug resistance. Recently, it was suggested that drugs enter the drug-binding pocket (DBP) through gates located between the transmembrane domains. For both a substrate and a modulator, the potential of mean force curves along the reaction coordinate obtained with the WHAM approach were similar, with no activation energy required for crossing the gate. Moreover, drug transit from bulk water into the DBP was characterized as an overall free-energy downhill process. PMID:26574244

  4. Age-related decline in verbal learning is moderated by demographic factors, working memory capacity, and presence of amnestic mild cognitive impairment.

    PubMed

    Constantinidou, Fofi; Zaganas, Ioannis; Papastefanakis, Emmanouil; Kasselimis, Dimitrios; Nidos, Andreas; Simos, Panagiotis G

    2014-09-01

    Age-related memory changes are highly varied and heterogeneous. The study examined the rate of decline in verbal episodic memory as a function of education level, auditory attention span and verbal working memory capacity, and diagnosis of amnestic mild cognitive impairment (a-MCI). Data were available on a community sample of 653 adults aged 17-86 years and 70 patients with a-MCI recruited from eight broad geographic areas in Greece and Cyprus. Measures of auditory attention span and working memory capacity (digits forward and backward) and verbal episodic memory (Auditory Verbal Learning Test [AVLT]) were used. Moderated mediation regressions on data from the community sample did not reveal significant effects of education level on the rate of age-related decline in AVLT indices. The presence of a-MCI was a significant moderator of the direct effect of Age on both immediate and delayed episodic memory indices. The rate of age-related decline in verbal episodic memory is normally mediated by working memory capacity. Moreover, in persons who display poor episodic memory capacity (a-MCI group), age-related memory decline is expected to advance more rapidly for those who also display relatively poor verbal working memory capacity. PMID:25156204

  5. Oligomycin frames a common drug-binding site in the ATP synthase

    SciTech Connect

    Symersky, Jindrich; Osowski, Daniel; Walters, D. Eric; Mueller, David M.

    2015-12-01

    We report the high-resolution (1.9 {angstrom}) crystal structure of oligomycin bound to the subunit c10 ring of the yeast mitochondrial ATP synthase. Oligomycin binds to the surface of the c10 ring making contact with two neighboring molecules at a position that explains the inhibitory effect on ATP synthesis. The carboxyl side chain of Glu59, which is essential for proton translocation, forms an H-bond with oligomycin via a bridging water molecule but is otherwise shielded from the aqueous environment. The remaining contacts between oligomycin and subunit c are primarily hydrophobic. The amino acid residues that form the oligomycin-binding site are 100% conserved between human and yeast but are widely different from those in bacterial homologs, thus explaining the differential sensitivity to oligomycin. Prior genetics studies suggest that the oligomycin-binding site overlaps with the binding site of other antibiotics, including those effective against Mycobacterium tuberculosis, and thereby frames a common 'drug-binding site.' We anticipate that this drug-binding site will serve as an effective target for new antibiotics developed by rational design.

  6. Crystal structure of equine serum albumin in complex with cetirizine reveals a novel drug binding site.

    PubMed

    Handing, Katarzyna B; Shabalin, Ivan G; Szlachta, Karol; Majorek, Karolina A; Minor, Wladek

    2016-03-01

    Serum albumin (SA) is the main transporter of drugs in mammalian blood plasma. Here, we report the first crystal structure of equine serum albumin (ESA) in complex with antihistamine drug cetirizine at a resolution of 2.1Å. Cetirizine is bound in two sites--a novel drug binding site (CBS1) and the fatty acid binding site 6 (CBS2). Both sites differ from those that have been proposed in multiple reports based on equilibrium dialysis and fluorescence studies for mammalian albumins as cetirizine binding sites. We show that the residues forming the binding pockets in ESA are highly conserved in human serum albumin (HSA), and suggest that binding of cetirizine to HSA will be similar. In support of that hypothesis, we show that the dissociation constants for cetirizine binding to CBS2 in ESA and HSA are identical using tryptophan fluorescence quenching. Presence of lysine and arginine residues that have been previously reported to undergo nonenzymatic glycosylation in CBS1 and CBS2 suggests that cetirizine transport in patients with diabetes could be altered. A review of all available SA structures from the PDB shows that in addition to the novel drug binding site we present here (CBS1), there are two pockets on SA capable of binding drugs that do not overlap with fatty acid binding sites and have not been discussed in published reviews. PMID:26896718

  7. Microstructural Integrity of the Superior Cerebellar Peduncle Is Associated with an Impaired Proprioceptive Weighting Capacity in Individuals with Non-Specific Low Back Pain

    PubMed Central

    Pijnenburg, Madelon; Caeyenberghs, Karen; Janssens, Lotte; Goossens, Nina; Swinnen, Stephan P.; Sunaert, Stefan; Brumagne, Simon

    2014-01-01

    Introduction Postural control is a complex sensorimotor task that requires an intact network of white matter connections. The ability to weight proprioceptive signals is crucial for postural control. However, research into central processing of proprioceptive signals for postural control is lacking. This is specifically of interest in individuals with non-specific low back pain (NSLBP), because impairments in postural control have been observed as possible underlying mechanisms of NSLBP. Therefore, the objective was to investigate potential differences in sensorimotor white matter microstructure between individuals with NSLBP and healthy controls, and to determine whether the alterations in individuals with NSLBP are associated with the capacity to weight proprioceptive signals for postural control. Methods The contribution of proprioceptive signals from the ankle and back muscles to postural control was evaluated by local muscle vibration in 18 individuals with NSLBP and 18 healthy controls. Center of pressure displacement in response to muscle vibration was determined during upright standing on a stable and unstable support surface. Diffusion magnetic resonance imaging was applied to examine whether this proprioceptive contribution was associated with sensorimotor white matter microstructure. Results Individuals with NSLBP showed a trend towards a reduced fractional anisotropy along the left superior cerebellar peduncle compared to healthy controls (p = 0.039). The impaired microstructural integrity of the superior cerebellar peduncle in individuals with NSLBP was significantly correlated with the response to ankle muscle vibration (p<0.003). Conclusions In individuals with NSLBP, a decreased integrity of the superior cerebellar peduncle was associated with an increased reliance on ankle muscle proprioception, even on unstable support surface, which implies an impaired proprioceptive weighting capacity. Our findings emphasize the importance of the superior

  8. No Clear Association between Impaired Short-Term or Working Memory Storage and Time Reproduction Capacity in Adult ADHD Patients

    PubMed Central

    Mette, Christian; Grabemann, Marco; Zimmermann, Marco; Strunz, Laura; Scherbaum, Norbert; Wiltfang, Jens; Kis, Bernhard

    2015-01-01

    Objective Altered time reproduction is exhibited by patients with adult attention deficit hyperactivity disorder (ADHD). It remains unclear whether memory capacity influences the ability of adults with ADHD to reproduce time intervals. Method We conducted a behavioral study on 30 ADHD patients who were medicated with methylphenidate, 29 unmedicated adult ADHD patients and 32 healthy controls (HCs). We assessed time reproduction using six time intervals (1 s, 4 s, 6 s, 10 s, 24 s and 60 s) and assessed memory performance using the Wechsler memory scale. Results The patients with ADHD exhibited lower memory performance scores than the HCs. No significant differences in the raw scores for any of the time intervals (p > .05), with the exception of the variability at the short time intervals (1 s, 4 s and 6 s) (p < .01), were found between the groups. The overall analyses failed to reveal any significant correlations between time reproduction at any of the time intervals examined in the time reproduction task and working memory performance (p > .05). Conclusion We detected no findings indicating that working memory might influence time reproduction in adult patients with ADHD. Therefore, further studies concerning time reproduction and memory capacity among adult patients with ADHD must be performed to verify and replicate the present findings. PMID:26221955

  9. Anguillicola crassus impairs the silvering-related enhancements of the ROS defense capacity in swimbladder tissue of the European eel (Anguilla anguilla).

    PubMed

    Schneebauer, Gabriel; Hanel, Reinhold; Pelster, Bernd

    2016-10-01

    In a process called silvering, European eels prepare for their long-distance migration from European freshwater systems to the Sargasso Sea for reproduction. During this journey, eels perform extended diel vertical migrations, and the concomitant changes in hydrostatic pressure significantly affect the swimbladder, functioning as a buoyancy organ. As the swimbladder is primarily filled with oxygen, the tissue has to cope with extreme hyperoxic conditions, which typically are accompanied by the generation of reactive oxygen species (ROS) and oxidative stress. In addition, since the introduction of the parasitic nematode Anguillicola crassus in the early 1980s, swimbladder function of most of the European eels is impaired by the infection with this parasite. However, the exact pathways to detoxify ROS and how these pathways are affected by silvering or the infection are still unknown. In swimbladder and muscle tissue from uninfected and infected yellow, and from uninfected and infected silver eels, we measured the level of lipid peroxidation, which increases with ROS stress. To assess the capacity of the ROS defense systems, we analyzed the activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and glutathione reductase (GR), and determined the concentration of the antioxidant glutathione (GSH + GSSG). In swimbladder tissue, we found increased concentrations of GSH + GSSG as well as higher activities of SOD, GPx and GR, suggesting that SOD and the glutathione cycle are important for ROS detoxification. Comparing swimbladder tissue of uninfected yellow with uninfected silver eels, the concentration of GSH + GSSG and the activity of SOD were higher after silvering, corresponding with lower levels of lipid peroxidation. Whereas in yellow eels the infection with A. crassus had no effect, in silver eels the capacity to cope with ROS was significantly impaired. In muscle tissue, silvering or the infection only affected the activity of SOD

  10. The motile and invasive capacity of human endometrial stromal cells: implications for normal and impaired reproductive function.

    PubMed

    Weimar, Charlotte H E; Macklon, Nick S; Post Uiterweer, Emiel D; Brosens, Jan J; Gellersen, Birgit

    2013-01-01

    BACKGROUND Mechanisms underlying early reproductive loss in the human are beginning to be elucidated. The migratory and invasive capacity of human endometrial stromal cells (ESCs) is increasingly recognized to contribute to the intense tissue remodelling associated with embryo implantation, trophoblast invasion and endometrial regeneration. In this review, we examine the signals and mechanisms that control ESC migration and invasion and assess how deregulation of these cell functions contributes to common reproductive disorders. METHODS The PubMed database was searched for publications on motility and invasiveness of human ESCs in normal endometrial function and in reproductive disorders including implantation failure, recurrent pregnancy loss (RPL), endometriosis and adenomyosis, covering the period 2000-2012. RESULTS Increasing evidence suggests that implantation failure and RPL involve abnormal migratory responses of decidualizing ESCs to embryo and trophoblast signals. Numerous reports indicate that endometriosis, as well as adenomyosis, is associated with increased basal and stimulated invasiveness of ESCs and their progenitor cells, suggesting a link between a heightened menstrual repair response and the formation of ectopic implants. Migration and invasiveness of ESCs are controlled by a complex array of hormones, growth factors, chemokines and inflammatory mediators, and involve signalling through Rho GTPases, phosphatidylinositol-3-kinase and mitogen-activated protein kinase pathways. CONCLUSIONS Novel concepts are extending our understanding of the key functions of ESCs in effecting tissue repair imposed by cyclic menstruation and parturition. Migration of decidualizing ESCs also serves to support blastocyst implantation and embryo selection through discriminate motile responses directed by embryo quality. Targeting regulatory molecules holds promise for developing new strategies for the treatment of reproductive disorders such as endometriosis and

  11. The drug binding sites and transport mechanism of the RND pumps from Mycobacterium tuberculosis: Insights from molecular dynamics simulations.

    PubMed

    Sandhu, Padmani; Akhter, Yusuf

    2016-02-15

    RND permease superfamily drug efflux pumps are involved in multidrug transport and are attractive to study them for therapeutic purpose. In previous work we have classified 14 members of MmpL proteins belong to RND superfamily from Mycobacterium tuberculosis (Mtb) within its families [Sandhu P. and Akhter Y., 2015. Int. J. Med. Microbiol., 305:413-423]. In this study, structures of these proteins are homology modelled. The drug binding sites and channels are identified using local micro-stereochemistry and charge densities. Potential transport mechanism based on differential structural behaviour in the absence and on the binding of drug molecules is explained using the molecular dynamics simulation results. Our studies show two potential drug binding sites positioned at opposite ends of the transport tunnel leading from cytoplasmic to the periplasmic space across MmpL5 trimer. The drug binding have effects on the structural conformation of the protein leading to molecular-scale peristaltic movements. The free binding energy calculations reveal that the subsequent binding events are interdependent and may have implications on transport mechanism. Two drug binding sites and a continuous channel in the RND pump have been reported. The proposed ligand binding mechanism shows peristaltic movements in the channel leading to the drug efflux. This study would be helpful in understanding the molecular basis of drugs resistance in Mtb. PMID:26792538

  12. Digalactosyl-diacylglycerol deficiency impairs the capacity for photosynthetic intersystem electron transport and state transitions in Arabidopsis thaliana due to photosystem I acceptor-side limitations.

    PubMed

    Ivanov, Alexander G; Hendrickson, Luke; Krol, Marianna; Selstam, Eva; Oquist, Gunnar; Hurry, Vaughan; Huner, Norman P A

    2006-08-01

    Compared with wild type, the dgd1 mutant of Arabidopsis thaliana exhibited a lower amount of PSI-related Chl-protein complexes and lower abundance of the PSI-associated polypeptides, PsaA, PsaB, PsaC, PsaL and PsaH, with no changes in the levels of Lhca1-4. Functionally, the dgd1 mutant exhibited a significantly lower light-dependent, steady-state oxidation level of P700 (P700(+)) in vivo, a higher intersystem electron pool size, restricted linear electron transport and a higher rate of reduction of P700(+) in the dark, indicating an increased capacity for PSI cyclic electron transfer compared with the wild type. Concomitantly, the dgd1 mutant exhibited a higher sensitivity to and incomplete recovery of photoinhibition of PSI. Furthermore, dgd1 exhibited a lower capacity to undergo state transitions compared with the wild type, which was associated with a higher reduction state of the plastoquinone (PQ) pool. We conclude that digalactosyl-diacylglycerol (DGDG) deficiency results in PSI acceptor-side limitations that alter the flux of electrons through the photosynthetic electron chain and impair the regulation of distribution of excitation energy between the photosystems. These results are discussed in terms of thylakoid membrane domain reorganization in response to DGDG deficiency in A. thaliana. PMID:16854937

  13. Effect of bioceramic functional groups on drug binding and release kinetics

    NASA Astrophysics Data System (ADS)

    Trujillo, Christopher

    Bioceramics have been studied extensively as drug delivery systems (DDS). Those studies have aimed to tailor the drug binding and release kinetics to successfully treat infections and other diseases. This research suggests that the drug binding and release kinetics are predominantly driven by the functional groups available on the surface of a bioceramic. The goal of the present study is to explain the role of silicate and phosphate functional groups in drug binding to and release kinetics from bioceramics. alpha-cristobalite (Cris; SiO2) particles (90-150 microm) were prepared and doped with 0 microg (P-0), 39.1 microg (P-39.1), 78.2 microg (P-78.2), 165.5 microg (P-165.5) or 331 microg (P-331) of P 2O5 per gram Cris, using 85% orthophosphoric (H3PO 4) acid and thermal treatment. The material structure was analyzed using X-ray diffraction (XRD) with Rietveld Refinement and Fourier Transform Infrared (FTIR) spectroscopy with Gaussian fitting. XRD demonstrated an increase from sample P-0 (170.5373 A3) to P-331 (170.6466 A 3) in the unit cell volume as the P2O5 concentration increased in the material confirming phosphate silicate substitution in Cris. Moreover, FTIR showed the characteristic bands of phosphate functional groups of nu4 PO4/O-P-O bending, P-O-P stretching, P-O-P bending, P=O stretching, and P-O-H bending in doped Cris indicating phosphate incorporation in the silicate structure. Furthermore, FTIR showed that the nu4 PO4/O-P-O bending band around 557.6 cm-1 and P=O stretching band around 1343.9 cm-1 increased in area for samples P-39.1 to P-331 from 3.5 to 10.5 and from 10.1 to 22.4, respectively due to phosphate doping. In conjunction with the increase of the nu4 PO4/O-P-O bending band and P=O stretching band, a decrease in area of the O-Si-O bending bands around 488.1 and 629.8 cm-1 was noticed for samples P-39.1 to P-331 from 5 to 2 and from 11.8 to 5.4, respectively. Furthermore, Cris samples (200 mg, n=5 for each sample) were immersed separately in

  14. Survey of phosphorylation near drug binding sites in the Protein Data Bank (PDB) and their effects

    PubMed Central

    Smith, Kyle P.; Gifford, Kathleen M.; Waitzman, Joshua S.; Rice, Sarah E.

    2014-01-01

    While it is currently estimated that 40–50% of eukaryotic proteins are phosphorylated, little is known about the frequency and local effects of phosphorylation near pharmaceutical inhibitor binding sites. In this study, we investigated how frequently phosphorylation may affect the binding of drug inhibitors to target proteins. We examined the 453 non-redundant structures of soluble mammalian drug target proteins bound to inhibitors currently available in the Protein Data Bank (PDB). We cross-referenced these structures with phosphorylation data available from the PhosphoSitePlus database. 322/453 (71%) of drug targets have evidence of phosphorylation that has been validated by multiple methods or labs. For 132/453 (29%) of those, the phosphorylation site is within 12Å of the small molecule-binding site, where it would likely alter small molecule binding affinity. We propose a framework for distinguishing between drug-phosphorylation site interactions that are likely to alter the efficacy of drugs vs. those that are not. In addition we highlight examples of well-established drug targets, such as estrogen receptor alpha, for which phosphorylation may affect drug affinity and clinical efficacy. Our data suggest that phosphorylation may affect drug binding and efficacy for a significant fraction of drug target proteins. PMID:24833420

  15. Survey of phosphorylation near drug binding sites in the Protein Data Bank (PDB) and their effects.

    PubMed

    Smith, Kyle P; Gifford, Kathleen M; Waitzman, Joshua S; Rice, Sarah E

    2015-01-01

    While it is currently estimated that 40 to 50% of eukaryotic proteins are phosphorylated, little is known about the frequency and local effects of phosphorylation near pharmaceutical inhibitor binding sites. In this study, we investigated how frequently phosphorylation may affect the binding of drug inhibitors to target proteins. We examined the 453 non-redundant structures of soluble mammalian drug target proteins bound to inhibitors currently available in the Protein Data Bank (PDB). We cross-referenced these structures with phosphorylation data available from the PhosphoSitePlus database. Three hundred twenty-two of 453 (71%) of drug targets have evidence of phosphorylation that has been validated by multiple methods or labs. For 132 of 453 (29%) of those, the phosphorylation site is within 12 Å of the small molecule-binding site, where it would likely alter small molecule binding affinity. We propose a framework for distinguishing between drug-phosphorylation site interactions that are likely to alter the efficacy of drugs versus those that are not. In addition we highlight examples of well-established drug targets, such as estrogen receptor alpha, for which phosphorylation may affect drug affinity and clinical efficacy. Our data suggest that phosphorylation may affect drug binding and efficacy for a significant fraction of drug target proteins. PMID:24833420

  16. High-throughput screening of drug-binding dynamics to HERG improves early drug safety assessment.

    PubMed

    Di Veroli, Giovanni Y; Davies, Mark R; Zhang, Henggui; Abi-Gerges, Najah; Boyett, Mark R

    2013-01-01

    The use of computational models to predict drug-induced changes in the action potential (AP) is a promising approach to reduce drug safety attrition but requires a better representation of more complex drug-target interactions to improve the quantitative prediction. The blockade of the human ether-a-go-go-related gene (HERG) channel is a major concern for QT prolongation and Torsade de Pointes risk. We aim to develop quantitative in-silico AP predictions based on a new electrophysiological protocol (suitable for high-throughput HERG screening) and mathematical modeling of ionic currents. Electrophysiological recordings using the IonWorks device were made from HERG channels stably expressed in Chinese hamster ovary cells. A new protocol that delineates inhibition over time was applied to assess dofetilide, cisapride, and almokalant effects. Dynamic effects displayed distinct profiles for these drugs compared with concentration-effects curves. Binding kinetics to specific states were identified using a new HERG Markov model. The model was then modified to represent the canine rapid delayed rectifier K(+) current at 37°C and carry out AP predictions. Predictions were compared with a simpler model based on conductance reduction and were found to be much closer to experimental data. Improved sensitivity to concentration and pacing frequency variables was obtained when including binding kinetics. Our new electrophysiological protocol is suitable for high-throughput screening and is able to distinguish drug-binding kinetics. The association of this protocol with our modeling approach indicates that quantitative predictions of AP modulation can be obtained, which is a significant improvement compared with traditional conductance reduction methods. PMID:23103500

  17. Molecular Dynamics of Rab7::REP1::GGTase-II Ternary Complex and Identification of Their Putative Drug Binding Sites.

    PubMed

    Sindhu, Meenakshi; Saini, Vandana; Piplani, Sakshi; Kumar, A

    2013-01-01

    The structure-function correlation of membrane proteins have been a difficult task, particularly in context to transient protein complexes. The molecular simulation of ternary complex of Rab7::REP1::GGTase-II was carried out to understand the basic structural events occurring during the prenylation event of Rab proteins, using the software YASARA. The study suggested that the C-terminus of Rab7 has to be in completely extended conformation during prenylation to reach the active site of RabGGTase-II. Also, attempt was made to find putative drug binding sites on the ternary complex of Rab7::REP1::GGTase-II using Q-SiteFinder programme. The comprehensive consensus probe generated by the program revealed a total of 10 major pockets as putative drug binding sites on Rab7::REP:: GGTase-II ternary complex. These pockets were found on REP protein and GGTase protein subunits. The Rab7 was found to be devoid of any putative drug binding sites in the ternary complex. The phylogenetic analysis of 60 Rab proteins of human was carried out using PHYLIP and study indicated the close phylogenetic relationship between Rab7 and Rab9 proteins of human and hence with further in silico study, the present observations can be extrapolated to Rab9 proteins. The study paves a good platform for further experimental verifications of the findings and other in silico studies like identifying the potential drug targets by searching the putative drug binding sites, generating pharmacophoric pattern, searching or constructing suitable ligand and docking studies. PMID:23901157

  18. Effect of bioceramic functional groups on drug binding and release kinetics

    NASA Astrophysics Data System (ADS)

    Trujillo, Christopher

    Bioceramics have been studied extensively as drug delivery systems (DDS). Those studies have aimed to tailor the drug binding and release kinetics to successfully treat infections and other diseases. This research suggests that the drug binding and release kinetics are predominantly driven by the functional groups available on the surface of a bioceramic. The goal of the present study is to explain the role of silicate and phosphate functional groups in drug binding to and release kinetics from bioceramics. alpha-cristobalite (Cris; SiO2) particles (90-150 microm) were prepared and doped with 0 microg (P-0), 39.1 microg (P-39.1), 78.2 microg (P-78.2), 165.5 microg (P-165.5) or 331 microg (P-331) of P 2O5 per gram Cris, using 85% orthophosphoric (H3PO 4) acid and thermal treatment. The material structure was analyzed using X-ray diffraction (XRD) with Rietveld Refinement and Fourier Transform Infrared (FTIR) spectroscopy with Gaussian fitting. XRD demonstrated an increase from sample P-0 (170.5373 A3) to P-331 (170.6466 A 3) in the unit cell volume as the P2O5 concentration increased in the material confirming phosphate silicate substitution in Cris. Moreover, FTIR showed the characteristic bands of phosphate functional groups of nu4 PO4/O-P-O bending, P-O-P stretching, P-O-P bending, P=O stretching, and P-O-H bending in doped Cris indicating phosphate incorporation in the silicate structure. Furthermore, FTIR showed that the nu4 PO4/O-P-O bending band around 557.6 cm-1 and P=O stretching band around 1343.9 cm-1 increased in area for samples P-39.1 to P-331 from 3.5 to 10.5 and from 10.1 to 22.4, respectively due to phosphate doping. In conjunction with the increase of the nu4 PO4/O-P-O bending band and P=O stretching band, a decrease in area of the O-Si-O bending bands around 488.1 and 629.8 cm-1 was noticed for samples P-39.1 to P-331 from 5 to 2 and from 11.8 to 5.4, respectively. Furthermore, Cris samples (200 mg, n=5 for each sample) were immersed separately in

  19. Beyond capacity limitations II: Effects of lexical processes on word recall in verbal working memory tasks in children with and without specific language impairment

    PubMed Central

    Mainela-Arnold, Elina; Evans, Julia L.; Coady, Jeffry

    2010-01-01

    Purpose This study investigated the impact of lexical processes on target word recall in sentence span tasks in children with and without specific language impairment (SLI). Method Participants were 42 children (ages 8;2–12;3), 21 with SLI and 21 typically developing peers matched on age and nonverbal IQ. Children completed a sentence span task where target words to be recalled varied in word frequency and neighborhood density. Two measures of lexical processes were examined, the number of non-target competitor words activated during a gating task (lexical cohort competition) and word definitions. Results Neighborhood density had no effect on word recall for either group. However, both groups recalled significantly more high than low frequency words. Lexical cohort competition and specificity of semantic representations accounted for unique variance in the number of target word recalled in the SLI and CA groups combined. Conclusions Performance on verbal working memory span tasks for both SLI and CA children is influenced by word frequency, lexical cohorts, and semantic representations. Future studies need to examine the extent to which verbal working memory capacity is a cognitive construct independent of extant language knowledge representations. PMID:20705747

  20. A retroactive spatial cue improved VSTM capacity in mild cognitive impairment and medial temporal lobe amnesia but not in healthy older adults.

    PubMed

    Newsome, Rachel N; Duarte, Audrey; Pun, Carson; Smith, Victoria M; Ferber, Susanne; Barense, Morgan D

    2015-10-01

    Visual short-term memory (VSTM) is a vital cognitive ability, connecting visual input with conscious awareness. VSTM performance declines with mild cognitive impairment (MCI) and medial temporal lobe (MTL) amnesia. Many studies have shown that providing a spatial retrospective cue ("retrocue") improves VSTM capacity estimates for healthy young adults. However, one study has demonstrated that older adults are unable to use a retrocue to inhibit irrelevant items from memory. It is unknown whether patients with MCI and MTL amnesia will be able to use a retrocue to benefit their memory. We administered a retrocue and a baseline (simultaneous cue, "simucue") task to young adults, older adults, MCI patients, and MTL cases. Consistent with previous findings, young adults showed a retrocue benefit, whereas healthy older adults did not. In contrast, both MCI patients and MTL cases showed a retrocue benefit--the use of a retrocue brought patient performance up to the level of age-matched controls. We speculate that the patients were able to use the spatial information from the retrocue to reduce interference and facilitate binding items to their locations. PMID:26300388

  1. Impaired Endothelial Repair Capacity of Early Endothelial Progenitor Cells in Hypertensive Patients With Primary Hyperaldosteronemia: Role of 5,6,7,8-Tetrahydrobiopterin Oxidation and Endothelial Nitric Oxide Synthase Uncoupling.

    PubMed

    Chen, Long; Ding, Mei-Lin; Wu, Fang; He, Wen; Li, Jin; Zhang, Xiao-Yu; Xie, Wen-Li; Duan, Sheng-Zhong; Xia, Wen-Hao; Tao, Jun

    2016-02-01

    Although hyperaldosteronemia exerts detrimental impacts on vascular endothelium in addition to elevating blood pressure, the effects and molecular mechanisms of hyperaldosteronemia on early endothelial progenitor cell (EPC)-mediated endothelial repair after arterial damage are yet to be determined. The aim of this study was to investigate the endothelial repair capacity of early EPCs from hypertensive patients with primary hyperaldosteronemia (PHA). In vivo endothelial repair capacity of early EPCs from PHAs (n=20), age- and blood pressure-matched essential hypertension patients (n=20), and age-matched healthy subjects (n=20) was evaluated by transplantation into a nude mouse carotid endothelial denudation model. Endothelial function was evaluated by flow-mediated dilation of brachial artery in human subjects. In vivo endothelial repair capacity of early EPCs and flow-mediated dilation were impaired both in PHAs and in essential hypertension patients when compared with age-matched healthy subjects; however, the early EPC in vivo endothelial repair capacity and flow-mediated dilation of PHAs were impaired more severely than essential hypertension patients. Oral spironolactone improved early EPC in vivo endothelial repair capacity and flow-mediated dilation of PHAs. Increased oxidative stress, oxidative 5,6,7,8-tetrahydrobiopterin degradation, endothelial nitric oxide synthase uncoupling and decreased nitric oxide production were found in early EPCs from PHAs. Nicotinamide adenine dinucleotide phosphate oxidase subunit p47(phox) knockdown or 5,6,7,8-tetrahydrobiopterin supplementation attenuated endothelial nitric oxide synthase uncoupling and enhanced in vivo endothelial repair capacity of early EPCs from PHAs. In conclusion, PHAs exhibited more impaired endothelial repair capacity of early EPCs than did essential hypertension patients independent of blood pressure, which was associated with mineralocorticoid receptor-dependent oxidative stress and subsequently 5

  2. MiR-137 Targets Estrogen-Related Receptor Alpha and Impairs the Proliferative and Migratory Capacity of Breast Cancer Cells

    PubMed Central

    Zhao, Yuanyin; Li, Yuping; Lou, Guiyu; Zhao, Li; Xu, Zhizhen; Zhang, Yan; He, Fengtian

    2012-01-01

    ERRα is an orphan nuclear receptor emerging as a novel biomarker of breast cancer. Over-expression of ERRα in breast tumor is considered as a prognostic factor of poor clinical outcome. The mechanisms underlying the dysexpression of this nuclear receptor, however, are poorly understood. MicroRNAs (miRNAs) regulate gene expression at the post-transcriptional level and play important roles in tumor initiation and progression. In the present study, we have identified that the expression of ERRα is regulated by miR-137, a potential tumor suppressor microRNA. The bioinformatics search revealed two putative and highly conserved target-sites for miR-137 located within the ERRα 3′UTR at nt 480–486 and nt 596–602 respectively. Luciferase-reporter assay demonstrated that the two predicted target sites were authentically functional. They mediated the repression of reporter gene expression induced by miR-137 in an additive manner. Moreover, ectopic expression of miR-137 down-regulated ERRα expression at both protein level and mRNA level, and the miR-137 induced ERRα-knockdown contributed to the impaired proliferative and migratory capacity of breast cancer cells. Furthermore, transfection with miR-137mimics suppressed at least two downstream target genes of ERRα–CCNE1 and WNT11, which are important effectors of ERRα implicated in tumor proliferation and migration. Taken together, our results establish a role of miR-137 in negatively regulating ERRα expression and breast cancer cell proliferation and migration. They suggest that manipulating the expression level of ERRα by microRNAs has the potential to influence breast cancer progression. PMID:22723937

  3. Computational Assay of H7N9 Influenza Neuraminidase Reveals R292K Mutation Reduces Drug Binding Affinity

    NASA Astrophysics Data System (ADS)

    Woods, Christopher J.; Malaisree, Maturos; Long, Ben; McIntosh-Smith, Simon; Mulholland, Adrian J.

    2013-12-01

    The emergence of a novel H7N9 avian influenza that infects humans is a serious cause for concern. Of the genome sequences of H7N9 neuraminidase available, one contains a substitution of arginine to lysine at position 292, suggesting a potential for reduced drug binding efficacy. We have performed molecular dynamics simulations of oseltamivir, zanamivir and peramivir bound to H7N9, H7N9-R292K, and a structurally related H11N9 neuraminidase. They show that H7N9 neuraminidase is structurally homologous to H11N9, binding the drugs in identical modes. The simulations reveal that the R292K mutation disrupts drug binding in H7N9 in a comparable manner to that observed experimentally for H11N9-R292K. Absolute binding free energy calculations with the WaterSwap method confirm a reduction in binding affinity. This indicates that the efficacy of antiviral drugs against H7N9-R292K will be reduced. Simulations can assist in predicting disruption of binding caused by mutations in neuraminidase, thereby providing a computational `assay.'

  4. A fluorescent reporter detects details of aromatic ligand interference in drug-binding sites of human serum albumin.

    PubMed

    Dobretsov, Gennady; Smolina, Natalia; Syrejshchikova, Tatiana; Brilliantova, Varvara; Uzbekov, Marat

    2016-09-01

    Human serum albumin (HSA) transports many ligands including small aromatic molecules: metabolites, drugs etc. Phenylbutazone is an anti-inflammatory drug, which binds to the drug-binding site I of HSA. Its interaction with this site has been studied using a fluorescent dye, CAPIDAN, whose fluorescence in serum originates from HSA and is sensitive to the changes in HSA site I in some diseases. Its fluorescence in HSA solutions is strongly suppressed by phenylbutazone. This phenomenon seems to be a basic sign of a simple drug-dye competition. However, a more detailed study of the time-resolved fluorescence decay of CAPIDAN has shown that phenylbutazone lowers fluorescence without changing the total amount of bound dye. In brief, the HSA-bound dye forms three populations due to three types of environment at the binding sites. The first two populations probably have a rather strong Coulomb interaction with the positive charge of residues Arginine 218 or Arginine 222 in site I and are responsible for approximately 90% of the total fluorescence. Phenylbutazone blocks this interaction and therefore lowers this fluorescence. At the same time the binding of the third population increases considerably in the presence of phenylbutazone, and, as a result, the actual number of bound dye molecules remains almost unchanged despite the ligand competition. So, time resolved fluorescence of the reporter allows to observe details of interactions and interference of aromatic ligands in drug binding site I of HSA both in isolated HSA and in serum. PMID:27318089

  5. Effect of drug-binding-induced deformation on the vibrational spectrum of a DNA.daunomycin complex

    NASA Astrophysics Data System (ADS)

    Chen, Y. Z.; Szabó, A.; Schroeter, D. F.; Powell, J. W.; Lee, S. A.; Prohofsky, E. W.

    1997-06-01

    Vibrational frequencies of a DNA.daunomycin complex and those of a free DNA helix and an isolated daunomycin are calculated and compared with the infrared spectrum of similar systems at frequencies above 600 cm-1. Our study indicates that the binding induces a considerable change in the vibrational spectrum of both DNA and the binding drug. The frequency shifts appear to be closely related to the conformational deformation in the complex caused by drug binding. Significant frequency shift is found in the normal modes in the DNA.drug complex that are primarily vibrations localized to the sugar-phosphate backbone of the binding site. Sizable frequency change is also found in the modes associated with base atoms involved in the drug binding and in the modes in regions of the binding daunomycin that are deformed by the binding. In contrast the frequency of the modes in the region with no significant deformation is relatively unchanged. The modification of the DNA dynamical force field by the nonbonded interactions between DNA and the drug is found to have little effect on the modes in DNA above 600 cm-1. The modification to the daunomycin dynamical force field appears to be sizable since the frequency of several daunomycin modes is changed by several cm-1. The close relationship between structure and spectrum revealed in this work is of potential application in the identification of sites and types of deformation of a biomolecule from Raman and infrared spectra.

  6. Drug-binding energetics of human α-1-acid glycoprotein assessed by isothermal titration calorimetry and molecular docking simulations

    PubMed Central

    Huang, Johnny X.; Cooper, Matthew A.; Baker, Mark A.; Azad, Mohammad A.K.; Nation, Roger L.; Li, Jian; Velkov, Tony

    2012-01-01

    This study utilizes sensitive, modern isothermal titration calorimetric (ITC) methods to characterize the microscopic thermodynamic parameters that drive the binding of basic drugs to α-1-acid glycoprotein (AGP) and thereby rationalize the thermodynamic data in relation to docking models and crystallographic structures of the drug-AGP complexes. The binding of basic compounds from the tricyclic antidepressant series, together with miaserine, chlorpromazine, disopyramide and cimetidine all displayed an exothermically driven binding interaction with AGP. The impact of protonation/deprotonation events, ionic strength, temperature and the individual selectivity of the A and F1*S AGP variants on drug-binding thermodynamics were characterized. A correlation plot of the thermodynamic parameters for all of the test compounds revealed enthalpy-entropy compensation is in effect. The exothermic binding energetics of the test compounds were driven by a combination of favorable (negative) enthalpic (ΔH°) and favorable (positive) entropic (ΔS°) contributions to the Gibbs free energy (ΔG°). Collectively, the data imply that the free energies that drive drug binding to AGP and its relationship to drug-serum residency evolve from the complex interplay of enthalpic and entropic forces from interactions with explicit combinations of hydrophobic and polar side-chain sub-domains within the multi-lobed AGP ligand binding cavity. PMID:23192962

  7. Cigarette smoke induces alterations in the drug-binding properties of human serum albumin.

    PubMed

    Clerici, Marco; Colombo, Graziano; Secundo, Francesco; Gagliano, Nicoletta; Colombo, Roberto; Portinaro, Nicola; Giustarini, Daniela; Milzani, Aldo; Rossi, Ranieri; Dalle-Donne, Isabella

    2014-04-01

    Albumin is the most abundant plasma protein and serves as a transport and depot protein for numerous endogenous and exogenous compounds. Earlier we had shown that cigarette smoke induces carbonylation of human serum albumin (HSA) and alters its redox state. Here, the effect of whole-phase cigarette smoke on HSA ligand-binding properties was evaluated by equilibrium dialysis and size-exclusion HPLC or tryptophan fluorescence. The binding of salicylic acid and naproxen to cigarette smoke-oxidized HSA resulted to be impaired, unlike that of curcumin and genistein, chosen as representative ligands. Binding of the hydrophobic fluorescent probe 4,4'-bis(1-anilino-8-naphtalenesulfonic acid) (bis-ANS), intrinsic tryptophan fluorescence, and susceptibility to enzymatic proteolysis revealed slight changes in albumin conformation. These findings suggest that cigarette smoke-induced modifications of HSA may affect the binding, transport and bioavailability of specific ligands in smokers. PMID:24388826

  8. Beyond Capacity Limitations II: Effects of Lexical Processes on Word Recall in Verbal Working Memory Tasks in Children with and without Specific Language Impairment

    ERIC Educational Resources Information Center

    Mainela-Arnold, Elina; Evans, Julia L.; Coady, Jeffry

    2010-01-01

    Purpose: This study investigated the impact of lexical processes on target word recall in sentence span tasks in children with and without specific language impairment (SLI). Method: Participants were 42 children (ages 8;2-12;3 [years;months]): 21 with SLI and 21 typically developing peers matched on age and nonverbal IQ. Children completed a…

  9. Cancer ‘survivor-care’: II. Disruption of prefrontal brain activation top-down control of working memory capacity as possible mechanism for chemo-fog/brain (chemotherapy-associated cognitive impairment)

    PubMed Central

    Raffa, Robert B.

    2013-01-01

    SUMMARY What is known and Objective Cancer chemotherapy-associated cognitive impairments (termed ‘chemo-fog’ or ‘chemo-brain’), particularly in memory, have been self-reported or identified in cancer survivors previously treated with chemotherapy. While a variety of deficits have been detected, a consistent theme is a detriment in visuospatial working memory. The parietal cortex, a major site of storage of such memory, is implicated in chemotherapy-induced damage. However, if the findings of two recent publications are combined, the (pre)frontal cortex might be an equally viable target. Two recent studies, one postulating a mechanism for ‘top-down control’ of working memory capacity and another visualizing chemotherapy-induced alterations in brain activation during working memory processing, are reviewed and integrated. Comment A computational model and the proposal that the prefrontal cortex plays a role in working memory via top-down control of parietal working memory capacity is consistent with a recent demonstration of decreased frontal hyperactivation following chemotherapy. What is new and Conclusion Chemotherapy-associated impairment of visuospatial working memory might include the (pre)frontal cortex In addition to the parietal cortex. This provides new opportunity for basic science and clinical investigation. PMID:23656522

  10. The relationship between health-related quality of life and higher-level functional capacity in elderly women with mild cognitive impairment

    PubMed Central

    Kameyama, Kazuyoshi; Tsutou, Akimitsu; Fujino, Hidemi

    2016-01-01

    [Purpose] To clarify health-related quality of life (HR-QOL) in subjects with mild cognitive impairment (MCI), using EuroQOL (EQ-5D), and to investigate the relationship between HR-QOL and Tokyo Metropolitan Institute Gerontology Index of Competence (TMIG-IC) scores. [Subjects and Methods] The subjects included 25 women with MCI or frail constitutions. A variety of methods were used to assess mental states and activities of daily living (ADL). [Results] EQ-5D scores were significantly lower in the MCI group than in the normal cognitive (NC) group. Among the assessed subscales, the percentages of participants with “moderate problems” during self-care and “moderate and extreme problems” during usual activities were significantly higher in the MCI group. TMIG-IC scores were significantly lower in the MCI group than in the NC group. There was a positive correlation between TMIG-IC and EQ-5D scores in the MCI group. There were also significant positive correlations between instrumental activities of daily living and social roles between EQ-5D and TMIG-IC scores in the MCI group. [Conclusion] TMIG-IC scores may reflect cognitive disorders earlier than BI and FIM. The decline of TMIG-IC scores, especially for IADL and social roles, affects HR-QOL even in the early phases of cognitive impairment. PMID:27190474

  11. Sulfation of Lower Chlorinated Polychlorinated Biphenyls Increases Their Affinity for the Major Drug-Binding Sites of Human Serum Albumin.

    PubMed

    Rodriguez, Eric A; Li, Xueshu; Lehmler, Hans-Joachim; Robertson, Larry W; Duffel, Michael W

    2016-05-17

    The disposition of toxicants is often affected by their binding to serum proteins, of which the most abundant in humans is serum albumin (HSA). There is increasing interest in the toxicities of environmentally persistent polychlorinated biphenyls (PCBs) with lower numbers of chlorine atoms (LC-PCBs) due to their presence in both indoor and outdoor air. PCB sulfates derived from metabolic hydroxylation and sulfation of LC-PCBs have been implicated in endocrine disruption due to high affinity-binding to the thyroxine-carrying protein, transthyretin. Interactions of these sulfated metabolites of LC-PCBs with HSA, however, have not been previously explored. We have now determined the relative HSA-binding affinities for a group of LC-PCBs and their hydroxylated and sulfated derivatives by selective displacement of the fluorescent probes 5-dimethylamino-1-naphthalenesulfonamide and dansyl-l-proline from the two major drug-binding sites on HSA (previously designated as Site I and Site II). Values for half-maximal displacement of the probes indicated that the relative binding affinities were generally PCB sulfate ≥ OH-PCB > PCB, although this affinity was site- and congener-selective. Moreover, specificity for Site II increased as the numbers of chlorine atoms increased. Thus, hydroxylation and sulfation of LC-PCBs result in selective interactions with HSA which may affect their overall retention and toxicity. PMID:27116425

  12. Characterization of the comparative drug binding to intra- (liver fatty acid binding protein) and extra- (human serum albumin) cellular proteins.

    PubMed

    Rowland, Andrew; Hallifax, David; Nussio, Matthew R; Shapter, Joseph G; Mackenzie, Peter I; Brian Houston, J; Knights, Kathleen M; Miners, John O

    2015-01-01

    1. This study compared the extent, affinity, and kinetics of drug binding to human serum albumin (HSA) and liver fatty acid binding protein (LFABP) using ultrafiltration and surface plasmon resonance (SPR). 2. Binding of basic and neutral drugs to both HSA and LFABP was typically negligible. Binding of acidic drugs ranged from minor (fu > 0.8) to extensive (fu < 0.1). Of the compounds screened, the highest binding to both HSA and LFABP was observed for the acidic drugs torsemide and sulfinpyrazone, and for β-estradiol (a polar, neutral compound). 3. The extent of binding of acidic drugs to HSA was up to 40% greater than binding to LFABP. SPR experiments demonstrated comparable kinetics and affinity for the binding of representative acidic drugs (naproxen, sulfinpyrazone, and torsemide) to HSA and LFABP. 4. Simulations based on in vitro kinetic constants derived from SPR experiments and a rapid equilibrium model were undertaken to examine the impact of binding characteristics on compartmental drug distribution. Simulations provided mechanistic confirmation that equilibration of intracellular unbound drug with the extracellular unbound drug is attained rapidly in the absence of active transport mechanisms for drugs bound moderately or extensively to HSA and LFABP. PMID:25801059

  13. A novel cyclophilin from parasitic and free-living nematodes with a unique substrate- and drug-binding domain.

    PubMed

    Ma, Dong; Nelson, Laura S; LeCoz, Krystel; Poole, Catherine; Carlow, Clotilde K S

    2002-04-26

    A highly diversified member of the cyclophilin family of peptidyl-prolyl cis-trans isomerases has been isolated from the human parasite Onchocerca volvulus (OvCYP-16). This 25-kDa cyclophilin shares 43-46% similarity to other filarial cyclophilins but does not belong to any of the groups previously defined in invertebrates or vertebrates. A homolog was also isolated from Caenorhabditis elegans (CeCYP-16). Both recombinant O. volvulus and C. elegans cyclophilins were found to possess an enzyme activity with similar substrate preference and insensitivity to cyclosporin A. They represent novel cyclophilins with important differences in the composition of the drug-binding site in particular, namely, a Glu(124) (C. elegans) or Asp(123) (O. volvulus) residue present in a critical position. Site-directed mutagenesis studies and kinetic characterization demonstrated that the single residue dictates the degree of binding to substrate and cyclosporin A. CeCYP-16::GFP-expressing lines were generated with expression in the anterior and posterior distal portions of the intestine, in all larval stages and adults. An exception was found in the dauer stage, where fluorescence was observed in both the cell bodies and processes of the ventral chord motor neurons but was absent from the intestine. These studies highlight the extensive diversification of cyclophilins in an important human parasite and a closely related model organism. PMID:11847225

  14. Energetic analysis of the two controversial drug binding sites of the M2 proton channel in influenza A virus.

    PubMed

    Du, Qi-Shi; Huang, Ri-Bo; Wang, Cheng-Hua; Li, Xiao-Ming; Chou, Kuo-Chen

    2009-07-01

    Understanding the mechanism of the M2 proton channel of influenza A is crucially important to both basic research and drug discovery. Recently, the structure was determined independently by high-resolution NMR and X-ray crystallography. However, the two studies lead to completely different drug-binding mechanisms: the X-ray structure shows the drug blocking the pore from inside; whereas the NMR structure shows the drug inhibiting the channel from outside by an allosteric mechanism. Which one of the two is correct? To address this problem, we conducted an in-depth computational analysis. The conclusions drawn from various aspects, such as energetics, the channel-gating dynamic process, the pK(a) shift and its impact on the channel, and the consistency with the previous functional studies, among others, are all in favour to the allosteric mechanism revealed by the NMR structure. The findings reported here may stimulate and encourage new strategies for developing effective drugs against influenza A, particularly in dealing with the drug-resistant problems. PMID:19285514

  15. Eight-Week Training Cessation Suppresses Physiological Stress but Rapidly Impairs Health Metabolic Profiles and Aerobic Capacity in Elite Taekwondo Athletes

    PubMed Central

    Liao, Yi-Hung; Sung, Yu-Chi

    2016-01-01

    Changes in an athlete’s physiological and health metabolic profiles after detraining have not been studied in elite Taekwondo (TKD) athletes. To enable a better understanding of these physiological changes to training cessation, this study examined the effects of 8-weeks detraining on the aerobic capacity, body composition, inflammatory status and health metabolic profile in elite TKD athletes. Sixteen elite TKD athletes (age: 21.0 ± 0.8 yrs, BMI: 22.4 ± 3.9 kg/m2; Mean ± SD; 11 males and 5 females) participated in this study. Physical activity level assessment using computerized physical activity logs was performed during the competitive preparation season (i.e. one-week before national competition) and at two week intervals throughout the detraining period. Participant aerobic capacity, body fat, and blood biomarkers were measured before and after detraining, and the blood biomarker analyses included leukocyte subpopulations, blood glucose, insulin, dehydroepiandrosterone-sulfate (DHEA-S), and cortisol. Eight-week detraining increased DHEA-S/cortisol ratio (+57.3%, p = 0.004), increased insulin/cortisol ratio (+59.9%, p = 0.004), reduced aerobic power (–2.43%, p = 0.043), increased body fat accumulation (body fat%: +21.3%, p < 0.001), decreased muscle mass (muscle mass%: –4.04%, p < 0.001), and elevated HOMA-IR (the biomarker of systemic insulin resistance; +34.2%, p = 0.006). The neutrophil-to-lymphocyte ratio (NLR), a systemic inflammatory index, increased by 48.2% (p = 0.005). The change in aerobic capacity was correlated with the increased fat mass (r = –0.429, p = 0.049) but not with muscle loss. An increase in the NLR was correlated to the changes in HOMA-IR (r = 0.44, p = 0.044) and aerobic capacity (r = –0.439, p = 0.045). We demonstrate that 8-week detraining suppresses physiological stress but rapidly results in declines in athletic performance and health metabolic profiles, including reduced aerobic capacity, increased body fat, muscle

  16. Eight-Week Training Cessation Suppresses Physiological Stress but Rapidly Impairs Health Metabolic Profiles and Aerobic Capacity in Elite Taekwondo Athletes.

    PubMed

    Liao, Yi-Hung; Sung, Yu-Chi; Chou, Chun-Chung; Chen, Chung-Yu

    2016-01-01

    Changes in an athlete's physiological and health metabolic profiles after detraining have not been studied in elite Taekwondo (TKD) athletes. To enable a better understanding of these physiological changes to training cessation, this study examined the effects of 8-weeks detraining on the aerobic capacity, body composition, inflammatory status and health metabolic profile in elite TKD athletes. Sixteen elite TKD athletes (age: 21.0 ± 0.8 yrs, BMI: 22.4 ± 3.9 kg/m2; Mean ± SD; 11 males and 5 females) participated in this study. Physical activity level assessment using computerized physical activity logs was performed during the competitive preparation season (i.e. one-week before national competition) and at two week intervals throughout the detraining period. Participant aerobic capacity, body fat, and blood biomarkers were measured before and after detraining, and the blood biomarker analyses included leukocyte subpopulations, blood glucose, insulin, dehydroepiandrosterone-sulfate (DHEA-S), and cortisol. Eight-week detraining increased DHEA-S/cortisol ratio (+57.3%, p = 0.004), increased insulin/cortisol ratio (+59.9%, p = 0.004), reduced aerobic power (-2.43%, p = 0.043), increased body fat accumulation (body fat%: +21.3%, p < 0.001), decreased muscle mass (muscle mass%: -4.04%, p < 0.001), and elevated HOMA-IR (the biomarker of systemic insulin resistance; +34.2%, p = 0.006). The neutrophil-to-lymphocyte ratio (NLR), a systemic inflammatory index, increased by 48.2% (p = 0.005). The change in aerobic capacity was correlated with the increased fat mass (r = -0.429, p = 0.049) but not with muscle loss. An increase in the NLR was correlated to the changes in HOMA-IR (r = 0.44, p = 0.044) and aerobic capacity (r = -0.439, p = 0.045). We demonstrate that 8-week detraining suppresses physiological stress but rapidly results in declines in athletic performance and health metabolic profiles, including reduced aerobic capacity, increased body fat, muscle loss, insulin

  17. Ectopic lipid storage in non-alcoholic fatty liver disease is not mediated by impaired mitochondrial oxidative capacity in skeletal muscle.

    PubMed

    Cuthbertson, Daniel J; Irwin, Andrew; Sprung, Victoria S; Jones, Helen; Pugh, Christopher J A; Daousi, Christina; Adams, Valerie L; Bimson, William E; Shojaee-Moradie, Fariba; Richardson, Paul; Umpleby, A Margot; Wilding, John P; Kemp, Graham J

    2014-12-01

    Non-alcoholic fatty liver disease (NAFLD), characterized by lipid deposition within the liver [intrahepatocellular lipid (IHCL)], is associated with insulin resistance and the metabolic syndrome (MS). It has been suggested that impaired skeletal muscle mitochondrial function may contribute to ectopic lipid deposition, and the associated MS, by altering post-prandial energy storage. To test this hypothesis, we performed a cross-sectional study of 17 patients with NAFLD [mean±S.D.; age, 45±11 years; body mass index (BMI), 31.6±3.4 kg/m2] and 18 age- and BMI-matched healthy controls (age, 44±11 years; BMI, 30.5±5.2 kg/m2). We determined body composition by MRI, IHCL and intramyocellular (soleus and tibialis anterior) lipids (IMCLs) by proton magnetic resonance spectroscopy (1H-MRS) and skeletal muscle mitochondrial function by dynamic phosphorus magnetic resonance spectroscopy (31P-MRS) of quadriceps muscle. Although matched for BMI and total adiposity, after statistical adjustment for gender, patients with NAFLD (defined by IHCL ≥ 5.5%) had higher IHCLs (25±16% compared with 2±2%; P<0.0005) and a higher prevalence of the MS (76% compared with 28%) compared with healthy controls. Despite this, the visceral fat/subcutaneous fat ratio, IMCLs and muscle mitochondrial function were similar between the NAFLD and control groups, with no significant difference in the rate constants of post-exercise phosphocreatine (PCr) recovery (1.55±0.4 compared with 1.51±0.4 min-1), a measure of muscle mitochondrial function. In conclusion, impaired muscle mitochondrial function does not seem to underlie ectopic lipid deposition, or the accompanying features of the MS, in patients with NAFLD. PMID:24738611

  18. High IFN-γ Release and Impaired Capacity of Multi-Cytokine Secretion in IGRA Supernatants Are Associated with Active Tuberculosis.

    PubMed

    Carrère-Kremer, Séverine; Rubbo, Pierre-Alain; Pisoni, Amandine; Bendriss, Sophie; Marin, Grégory; Peries, Marianne; Bolloré, Karine; Terru, Dominique; Godreuil, Sylvain; Bourdin, Arnaud; Van de Perre, Philippe; Tuaillon, Edouard

    2016-01-01

    Interferon gamma (IFN-γ) release assays (IGRAs) detect Mycobacterium tuberculosis (Mtb) infection regardless of the active (ATB) or latent (LTBI) forms of tuberculosis (TB). In this study, Mtb-specific T cell response against region of deletion 1 (RD1) antigens were explored by a microbead multiplex assay performed in T-SPOT TB assay (T-SPOT) supernatants from 35 patients with ATB and 115 patients with LTBI. T-SPOT is positive when over 7 IFN-γ secreting cells (SC)/250 000 peripheral blood mononuclear cells (PBMC) are enumerated. However, over 100 IFN-γ SC /250 000 PBMC were more frequently observed in the ATB group compared to the LTBI group. By contrast, lower cytokine concentrations and lower cytokine productions relative to IFN-γ secretion were observed for IL 4, IL-12, TNF-α, GM-CSF, Eotaxin and IFN-α when compared to LTBI. Thus, high IFN-γ release and low cytokine secretions in relation with IFN-γ production appeared as signatures of ATB, corroborating that multicytokine Mtb-specific response against RD1 antigens reflects host capacity to contain TB reactivation. In this way, testing cytokine profile in IGRA supernatants would be helpful to improve ATB screening strategy including immunologic tests. PMID:27603919

  19. Exposure to Δ9-Tetrahydrocannabinol Impairs the Differentiation of Human Monocyte-derived Dendritic Cells and their Capacity for T cell Activation

    PubMed Central

    Castaneda, Julie T.; Kiertscher, Sylvia M.

    2015-01-01

    The capacity for human monocytes to differentiate into antigen-presenting dendritic cells (DC) can be influenced by a number of immune modulating signals. Monocytes express intracellular cannabinoid type 1 (CB1) and 2 (CB2) receptors and we demonstrate that exposure to Δ9-tetrahydrocannabinol (THC) inhibits the forskolin-induced generation of cyclic adenosine monophosphate in a CB2-specific manner. In order to examine the potential impact of cannabinoids on the generation of monocyte-derived DC, monocytes were cultured in vitro with differentiation medium alone [containing granulocyte/macrophage-colony stimulating factor (GM-CSF) and Interleukin-4 (IL-4)] or in combination with THC. The presence of THC (0.25–1.0 μg/ml) altered key features of DC differentiation, producing a concentration-dependent decrease in surface expression of CD11c, HLA-DR and costimulatory molecules (CD40 and CD86), less effective antigen uptake, and signs of functional skewing with decreased production of IL-12 but normal levels of IL-10. When examined in a mixed leukocyte reaction, DC that had been generated in the presence of THC were poor T cell activators as evidenced by their inability to generate effector/memory T cells or to stimulate robust IFN-γ responses. Some of these effects were partially restored by exposure to exogenous IL-7 and bacterial superantigen (S. aureus Cowans strain). These studies demonstrate that human monocytes express functional cannabinoid receptors and suggest that exposure to THC can alter their differentiation into functional antigen presenting cells; an effect that may be counter-balanced by the presence of other immunoregulatory factors. The impact of cannabinoids on adaptive immune responses in individuals with frequent drug exposure remains to be determined. PMID:25614186

  20. Do Aging and Dual-Tasking Impair the Capacity to Store and Retrieve Visuospatial Information Needed to Guide Perturbation-Evoked Reach-To-Grasp Reactions?

    PubMed Central

    Cheng, Kenneth C.; Pratt, Jay; Maki, Brian E.

    2013-01-01

    A recent study involving young adults showed that rapid perturbation-evoked reach-to-grasp balance-recovery reactions can be guided successfully with visuospatial-information (VSI) retained in memory despite: 1) a reduction in endpoint accuracy due to recall-delay (time between visual occlusion and perturbation-onset, PO) and 2) slowing of the reaction when performing a concurrent cognitive task during the recall-delay interval. The present study aimed to determine whether this capacity is compromised by effects of aging. Ten healthy older adults were tested with the previous protocol and compared with the previously-tested young adults. Reactions to recover balance by grasping a small handhold were evoked by unpredictable antero-posterior platform-translation (barriers deterred stepping reactions), while using liquid-crystal goggles to occlude vision post-PO and for varying recall-delay times (0-10s) prior to PO (the handhold was moved unpredictably to one of four locations 2s prior to vision-occlusion). Subjects also performed a spatial- or non-spatial-memory cognitive task during the delay-time in a subset of trials. Results showed that older adults had slower reactions than the young across all experimental conditions. Both age groups showed similar reduction in medio-lateral end-point accuracy when recall-delay was longest (10s), but differed in the effect of recall delay on vertical hand elevation. For both age groups, engaging in either the non-spatial or spatial-memory task had similar (slowing) effects on the arm reactions; however, the older adults also showed a dual-task interference effect (poorer cognitive-task performance) that was specific to the spatial-memory task. This provides new evidence that spatial working memory plays a role in the control of perturbation-evoked balance-recovery reactions. The delays in completing the reaction that occurred when performing either cognitive task suggest that such dual-task situations in daily life could

  1. Identification of tubulin drug binding sites and prediction of relative differences in binding affinities to tubulin isotypes using digital signal processing.

    PubMed

    Chen, Ke; Huzil, J Torin; Freedman, Holly; Ramachandran, Parameswaran; Antoniou, Andreas; Tuszynski, Jack A; Kurgan, Lukasz

    2008-11-01

    Microtubules are involved in numerous cellular processes including chromosome segregation during mitosis and, as a result, their constituent protein, tubulin, has become a successful target of several chemotherapeutic drugs. In general, these drugs bind indiscriminately to tubulin within both cancerous and healthy cells, resulting in unwanted side effects. However, differences between beta-tubulin isotypes expressed in a wide range of cell types may aid in the development of anti-tubulin drugs having increased specificity for only certain types of cells. Here, we describe a digital signal processing (DSP) method that is capable of predicting hot spots for the tubulin family of proteins as well as determining relative differences in binding affinities to these hot spots based only on the primary sequence of 10 human tubulin isotypes. Due to the fact that several drug binding sites have already been characterized within beta-tubulin, we are able to correlate hot spots with the binding sites for known chemotherapy drugs. We have also verified the accuracy of this method using the correlation between the binding affinities of characterized drugs and the tubulin isotypes. Additionally, the DSP method enables the rapid estimation of relative differences in binding affinities within the binding sites of tubulin isotypes that are yet to be experimentally determined. PMID:18951052

  2. Membrane-dependent effects of a cytoplasmic helix on the structure and drug binding of the influenza virus M2 protein.

    PubMed

    Cady, Sarah; Wang, Tuo; Hong, Mei

    2011-08-01

    The influenza A M2 protein forms a proton channel for virus infection and also mediates virus assembly and budding. The minimum protein length that encodes both functions contains the transmembrane (TM) domain (roughly residues 22-46) for the amantadine-sensitive proton-channel activity and an amphipathic cytoplasmic helix (roughly residues 45-62) for curvature induction and virus budding. However, structural studies involving the TM domain with or without the amphipathic helix differed on the drug-binding site. Here we use solid-state NMR spectroscopy to determine the amantadine binding site in the cytoplasmic-helix-containing M2(21-61). (13)C-(2)H distance measurements of (13)C-labeled protein and (2)H-labeled amantadine showed that in 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) bilayers, the first equivalent of drug bound S31 inside the M2(21-61) pore, similar to the behavior of M2 transmembrane peptide (M2TM) in DMPC bilayers. The nonspecific surface site of D44 observed in M2TM is disfavored in the longer peptide. Thus, the pharmacologically relevant drug-binding site in the fully functional M2(21-61) is S31 in the TM pore. Interestingly, when M2(21-61) was reconstituted into a virus-mimetic membrane containing 30% cholesterol, no chemical shift perturbation was observed for pore-lining residues, whereas M2TM in the same membrane exhibited drug-induced chemical shift changes. Reduction of the cholesterol level and the use of unsaturated phospholipids shifted the conformational equilibrium of M2TM fully to the bound state but did not rescue drug binding to M2(21-61). These results suggest that the amphipathic helix, together with cholesterol, modulates the ability of the TM helix to bind amantadine. Thus, the M2 protein interacts with the lipid membrane and small-molecule inhibitors in a complex fashion, and a careful examination of the environmental dependence of the protein conformation is required to fully understand the structure-function relation of

  3. Structural insights into differences in drug-binding selectivity between two forms of human alpha1-acid glycoprotein genetic variants, the A and F1*S forms.

    PubMed

    Nishi, Koji; Ono, Tomomi; Nakamura, Teruya; Fukunaga, Naoko; Izumi, Miyoko; Watanabe, Hiroshi; Suenaga, Ayaka; Maruyama, Toru; Yamagata, Yuriko; Curry, Stephen; Otagiri, Masaki

    2011-04-22

    Human α(1)-acid glycoprotein (hAGP) in serum functions as a carrier of basic drugs. In most individuals, hAGP exists as a mixture of two genetic variants, the F1*S and A variants, which bind drugs with different selectivities. We prepared a mutant of the A variant, C149R, and showed that its drug-binding properties were indistinguishable from those of the wild type. In this study, we determined the crystal structures of this mutant hAGP alone and complexed with disopyramide (DSP), amitriptyline (AMT), and the nonspecific drug chlorpromazine (CPZ). The crystal structures revealed that the drug-binding pocket on the A variant is located within an eight-stranded β-barrel, similar to that found in the F1*S variant and other lipocalin family proteins. However, the binding region of the A variant is narrower than that of the F1*S variant. In the crystal structures of complexes with DSP and AMT, the two aromatic rings of each drug interact with Phe-49 and Phe-112 at the bottom of the binding pocket. Although the structure of CPZ is similar to those of DSP and AMT, its fused aromatic ring system, which is extended in length by the addition of a chlorine atom, appears to dictate an alternative mode of binding, which explains its nonselective binding to the F1*S and A variant hAGPs. Modeling experiments based on the co-crystal structures suggest that, in complexes of DSP, AMT, or CPZ with the F1*S variant, Phe-114 sterically hinders interactions with DSP and AMT, but not CPZ. PMID:21349832

  4. Interpretation of Ocular Melanin Drug Binding Assays. Alternatives to the Model of Multiple Classes of Independent Sites.

    PubMed

    Manzanares, José A; Rimpelä, Anna-Kaisa; Urtti, Arto

    2016-04-01

    Melanin has a high binding affinity for a wide range of drugs. The determination of the melanin binding capacity and its binding affinity are important, e.g., in the determination of the ocular drug distribution, the prediction of drug effects in the eye, and the trans-scleral drug delivery. The binding parameters estimated from a given data set vary significantly when using different isotherms or different nonlinear fitting methods. In this work, the commonly used bi-Langmuir isotherm, which assumes two classes of independent sites, is confronted with the Sips isotherm. Direct, log-log, and Scatchard plots are used, and the interpretation of the binding curves in the latter is critically analyzed. In addition to the goodness of fit, the emphasis is placed on the physical meaning of the binding parameters. The bi-Langmuir model imposes a bimodal distribution of binding energies for the sites on the melanin granules, but the actual distribution is most likely continuous and unimodal, as assumed by the Sips isotherm. Hence, the latter describes more accurately the distribution of binding energies and also the experimental results of melanin binding to drugs and metal ions. Simulations are used to show that the existence of two classes of sites cannot be confirmed on the sole basis of the shape of the binding curve in the Scatchard plot, and that serious doubts may appear on the meaning of the binding parameters of the bi-Langmuir model. Experimental results of melanin binding to chloroquine and metoprolol are used to illustrate the importance of the choice of the binding isotherm and of the method used to evaluate the binding parameters. PMID:26820602

  5. Multi-drug resistance profile of PR20 HIV-1 protease is attributed to distorted conformational and drug binding landscape: molecular dynamics insights.

    PubMed

    Chetty, Sarentha; Bhakat, Soumendranath; Martin, Alberto J M; Soliman, Mahmoud E S

    2016-01-01

    The PR20 HIV-1 protease, a variant with 20 mutations, exhibits high levels of multi-drug resistance; however, to date, there has been no report detailing the impact of these 20 mutations on the conformational and drug binding landscape at a molecular level. In this report, we demonstrate the first account of a comprehensive study designed to elaborate on the impact of these mutations on the dynamic features as well as drug binding and resistance profile, using extensive molecular dynamics analyses. Comparative MD simulations for the wild-type and PR20 HIV proteases, starting from bound and unbound conformations in each case, were performed. Results showed that the apo conformation of the PR20 variant of the HIV protease displayed a tendency to remain in the open conformation for a longer period of time when compared to the wild type. This led to a phenomena in which the inhibitor seated at the active site of PR20 tends to diffuse away from the binding site leading to a significant change in inhibitor-protein association. Calculating the per-residue fluctuation (RMSF) and radius of gyration, further validated these findings. MM/GBSA showed that the occurrence of 20 mutations led to a drop in the calculated binding free energies (ΔGbind) by ~25.17 kcal/mol and ~5 kcal/mol for p2-NC, a natural peptide substrate, and darunavir, respectively, when compared to wild type. Furthermore, the residue interaction network showed a diminished inter-residue hydrogen bond network and changes in inter-residue connections as a result of these mutations. The increased conformational flexibility in PR20 as a result of loss of intra- and inter-molecular hydrogen bond interactions and other prominent binding forces led to a loss of protease grip on ligand. It is interesting to note that the difference in conformational flexibility between PR20 and WT conformations was much higher in the case of substrate-bound conformation as compared to DRV. Thus, developing analogues of DRV by

  6. Premelting base pair opening probability and drug binding constant of a daunomycin-poly d(GCAT).poly d(ATGC) complex.

    PubMed Central

    Chen, Y Z; Prohofsky, E W

    1994-01-01

    We calculate room temperature thermal fluctuational base pair opening probability of a daunomycin-poly d(GCAT).poly d(ATGC) complex. This system is constructed at an atomic level of detail based on x-ray analysis of a crystal structure. The base pair opening probabilities are calculated from a modified self-consistent phonon approach of anharmonic lattice dynamics theory. We find that daunomycin binding substantially enhances the thermal stability of one of the base pairs adjacent the drug because of strong hydrogen bonding between the drug and the base. The possible effect of this enhanced stability on the drug inhibition of DNA transcription and replication is discussed. We also calculate the probability of drug dissociation from the helix based on the selfconsistent calculation of the probability of the disruption of drug-base H-bonds and the unstacking probability of the drug. The calculations can be used to determine the equilibrium drug binding constant which is found to be in good agreement with observations on similar daunomycin-DNA systems. PMID:8011914

  7. Mucosal injury and. gamma. -irradiation produce persistent gastric ulcers in the rabbit. Evaluation of antiulcer drug binding to experimental ulcer sites

    SciTech Connect

    Yokel, R.A.; Dickey, K.M. )

    1991-05-01

    A method producing persistent gastric ulcers in the rhesus monkey by combined mucosal injury and {gamma}-irradiation was modified and evaluated in the rabbit. {gamma}-Irradiation (800-1000 cGy) immediately after removal of 2-mm-diameter sections of antral mucosa resulted in ulcer craters 5-7 days later. Ulcer sites were characterized by loss of the mucosa, muscularis mucosa, and much of the submucosa. The exposed submucosa was coated with fibrin and necrotic debris infiltrated with heterophils, the rabbit equivalent of neutrophils. These ulcers strongly resemble human chronic gastric ulcers. Binding of Carafate (sucralfate; Marion Laboratories, Inc., Kansas City, MO) and Maalox (magnesia-alumina oral suspension; Wm. H. Rorer, Inc., Ft. Washington, PA) to ulcer and nearby nonulcer sites in the antrum was assessed 1 hour after drug dosing. Drug binding was determined by aluminum quantitation of stomach wall punch biopsies at necropsy. Both drugs significantly increased aluminum bound to the stomach wall compared with vehicle treatment. Significantly more antiulcer drug was bound to ulcer sites than to nearby nonulcer sites only after sucralfate administration. This model of persistent gastric ulcer should be useful to further study gastric ulcer pathogenesis and treatment.

  8. Modeling of open, closed, and open-inactivated states of the hERG1 channel: structural mechanisms of the state-dependent drug binding.

    PubMed

    Durdagi, Serdar; Deshpande, Sumukh; Duff, Henry J; Noskov, Sergei Y

    2012-10-22

    The human ether-a-go-go related gene 1 (hERG1) K ion channel is a key element for the rapid component of the delayed rectified potassium current in cardiac myocytes. Since there are no crystal structures for hERG channels, creation and validation of its reliable atomistic models have been key targets in molecular cardiology for the past decade. In this study, we developed and vigorously validated models for open, closed, and open-inactivated states of hERG1 using a multistep protocol. The conserved elements were derived using multiple-template homology modeling utilizing available structures for Kv1.2, Kv1.2/2.1 chimera, and KcsA channels. Then missing elements were modeled with the ROSETTA De Novo protein-designing suite and further refined with all-atom molecular dynamics simulations. The final ensemble of models was evaluated for consistency to the reported experimental data from biochemical, biophysical, and electrophysiological studies. The closed state models were cross-validated against available experimental data on toxin footprinting with protein-protein docking using hERG state-selective toxin BeKm-1. Poisson-Boltzmann calculations were performed to determine gating charge and compare it to electrophysiological measurements. The validated structures offered us a unique chance to assess molecular mechanisms of state-dependent drug binding in three different states of the channel. PMID:22989185

  9. General transfer matrix formalism to calculate DNA–protein–drug binding in gene regulation: application to OR operator of phage λ

    PubMed Central

    Teif, Vladimir B.

    2007-01-01

    The transfer matrix methodology is proposed as a systematic tool for the statistical–mechanical description of DNA–protein–drug binding involved in gene regulation. We show that a genetic system of several cis-regulatory modules is calculable using this method, considering explicitly the site-overlapping, competitive, cooperative binding of regulatory proteins, their multilayer assembly and DNA looping. In the methodological section, the matrix models are solved for the basic types of short- and long-range interactions between DNA-bound proteins, drugs and nucleosomes. We apply the matrix method to gene regulation at the OR operator of phage λ. The transfer matrix formalism allowed the description of the λ-switch at a single-nucleotide resolution, taking into account the effects of a range of inter-protein distances. Our calculations confirm previously established roles of the contact CI–Cro–RNAP interactions. Concerning long-range interactions, we show that while the DNA loop between the OR and OL operators is important at the lysogenic CI concentrations, the interference between the adjacent promoters PR and PRM becomes more important at small CI concentrations. A large change in the expression pattern may arise in this regime due to anticooperative interactions between DNA-bound RNA polymerases. The applicability of the matrix method to more complex systems is discussed. PMID:17526526

  10. Hearing Impairments

    NASA Astrophysics Data System (ADS)

    Cavender, Anna; Ladner, Richard E.

    For many people with hearing impairments, the degree of hearing loss is only a small aspect of their disability and does not necessarily determine the types of accessibility solutions or accommodations that may be required. For some people, the ability to adjust the audio volume may be sufficient. For others, translation to a signed language may be more appropriate. For still others, access to text alternatives may be the best solution. Because of these differences, it is important for researchers in Web accessibility to understand that people with hearing impairments may have very different cultural-linguistic traditions and personal backgrounds.

  11. In Vitro Resistance Selections for Plasmodium falciparum Dihydroorotate Dehydrogenase Inhibitors Give Mutants with Multiple Point Mutations in the Drug-binding Site and Altered Growth*

    PubMed Central

    Ross, Leila S.; Gamo, Francisco Javier; Lafuente-Monasterio, Maria José; Singh, Onkar M. P.; Rowland, Paul; Wiegand, Roger C.; Wirth, Dyann F.

    2014-01-01

    Malaria is a preventable and treatable disease; yet half of the world's population lives at risk of infection, and an estimated 660,000 people die of malaria-related causes every year. Rising drug resistance threatens to make malaria untreatable, necessitating both the discovery of new antimalarial agents and the development of strategies to identify and suppress the emergence and spread of drug resistance. We focused on in-development dihydroorotate dehydrogenase (DHODH) inhibitors. Characterizing resistance pathways for antimalarial agents not yet in clinical use will increase our understanding of the potential for resistance. We identified resistance mechanisms of Plasmodium falciparum (Pf) DHODH inhibitors via in vitro resistance selections. We found 11 point mutations in the PfDHODH target. Target gene amplification and unknown mechanisms also contributed to resistance, albeit to a lesser extent. These mutant parasites were often hypersensitive to other PfDHODH inhibitors, which immediately suggested a novel combination therapy approach to preventing resistance. Indeed, a combination of wild-type and mutant-type selective inhibitors led to resistance far less often than either drug alone. The effects of point mutations in PfDHODH were corroborated with purified recombinant wild-type and mutant-type PfDHODH proteins, which showed the same trends in drug response as the cognate cell lines. Comparative growth assays demonstrated that two mutant parasites grew less robustly than their wild-type parent, and the purified protein of those mutants showed a decrease in catalytic efficiency, thereby suggesting a reason for the diminished growth rate. Co-crystallography of PfDHODH with three inhibitors suggested that hydrophobic interactions are important for drug binding and selectivity. PMID:24782313

  12. All Vision Impairment

    MedlinePlus

    ... Jobs Home > Statistics and Data > All Vision Impairment All Vision Impairment Vision Impairment Defined Vision impairment is ... being blind by the U.S. definition.) The category “All Vision Impairment” includes both low vision and blindness. ...

  13. Cognitive impairments may mimic delusions.

    PubMed

    Eterović, Marija; Kozarić-Kovačić, Dragica

    2015-12-01

    Delusions are often recognized as key to the concept of psychosis. What is delusion is one of the basic questions of psychopathology. The common denominator of definitions of delusions is the divergence between the strong conviction in the delusional belief and superior evidences to the contrary which are continually ignored. An implicit, sustainably unspoken assumption is that the person with delusional belief has cognitive capacities to process the (counter-)arguments relevant to their delusion. However, individual's cognitive capacities are not being emphasized when delusions are evaluated. Moreover, the impact of cognitive decline on formation of delusions is neglected, both in theory and practice. We elaborate that cognitive deficits may facilitate, oppose, or mimic delusions. We focus on the last, which can lead to diagnosing as delusion what could be explained by cognitive decline and better called pseudo-delusion. The risk is significant when cognition is impaired, as in demented people; an issue which has not yet been debated. True delusions are incompatible with person's cognitive capacities, i.e., if we take into account person's cognitive status, we still cannot understand how the person holds the strange belief with an extraordinary conviction. Pseudo-delusions would be beliefs, thoughts or judgments that at first seem delusional (they are false, subculturally atypical beliefs that are strongly maintained in the face of counterargument), but lose the essence of delusions after we take cognitive impairment into account. Pseudo-delusions could actually be explained or understood by person's cognitive impairments, they "fit into" them. The reported reality-based contents of delusions in the elderly, poor response to antipsychotics and lack of association with early or family history of psychiatric disorders could in part be accounted for by the bias of misdiagnosing the cognitive impairment as the delusion. Not recognizing that the cognitive impairment

  14. Deficiency of dietary niacin impaired gill immunity and antioxidant capacity, and changes its tight junction proteins via regulating NF-κB, TOR, Nrf2 and MLCK signaling pathways in young grass carp (Ctenopharyngodon idella).

    PubMed

    Li, Shun-Quan; Feng, Lin; Jiang, Wei-Dan; Liu, Yang; Jiang, Jun; Wu, Pei; Kuang, Sheng-Yao; Tang, Ling; Tang, Wu-Neng; Zhang, Yong-An; Zhou, Xiao-Qiu

    2016-08-01

    To investigate the effects of dietary niacin on gill immunity, tight junction proteins, antioxidant system and related signaling molecules mRNA expression, young grass carp (Ctenopharyngodon idella) were fed six diets containing graded levels of niacin (3.95-55.01 mg/kg diet) for 8 weeks. The study indicated that niacin deficiency decreased lysozyme and acid phosphatase activities, and complement 3 content, and caused oxidative damage that might be partly due to the decreased copper, zinc superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase and glutathione-S-transferase activities and reduced glutathione content in fish gills (P < 0.05). Moreover, the relative mRNA levels of antimicrobial peptides (liver expressed antimicrobial peptide 2 and Hepcidin), anti-inflammatory cytokines (interleukin 10 and transforming growth factor β1), tight junction proteins (Occludin, zonula occludens 1, Claudin-15 and -3), signaling molecules (inhibitor of κBα (IκBα), target of rapamycin (TOR), ribosomal protein S6 kinase 1 (S6K1) and NF-E2-related factor 2 (Nrf2)) and antioxidant enzymes were significantly decreased (P < 0.05) in niacin-deficient diet group. Conversely, the mRNA levels of pro-inflammatory cytokines (tumor necrosis factor α, interleukin 8, interferon γ2, and interleukin 1β), signaling molecules (nuclear factor kappa B p65, IκB kinase α, IκB kinase β, IκB kinase γ, Kelch-like-ECH-associated protein 1b, myosin light chain kinase and p38 mitogen-activated protein kinase (p38 MAPK) were significantly increased (P < 0.05) in fish gills fed niacin-deficient diet. Interestingly, the varying niacin levels of 3.95-55.01 mg/kg diet had no effect on the mRNA level of Kelch-like-ECH-associated protein 1a, Claudin-c and -12 in fish gills (P > 0.05). In conclusion, niacin deficiency decreased gill immunity, impaired gill antioxidant system, as well as regulated mRNA expression of gill tight junction proteins and related signaling

  15. 20 CFR 220.120 - The claimant's residual functional capacity.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... with a low back disorder may be fully capable of the physical demands consistent with those of... functional capacity. (a) General. The claimant's impairment(s), and any related symptoms, such as pain, may... limitations that go beyond the symptoms, such as pain, that are important in the diagnosis and treatment...

  16. 20 CFR 220.120 - The claimant's residual functional capacity.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... with a low back disorder may be fully capable of the physical demands consistent with those of... functional capacity. (a) General. The claimant's impairment(s), and any related symptoms, such as pain, may... limitations that go beyond the symptoms, such as pain, that are important in the diagnosis and treatment...

  17. 20 CFR 220.120 - The claimant's residual functional capacity.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... with a low back disorder may be fully capable of the physical demands consistent with those of... functional capacity. (a) General. The claimant's impairment(s), and any related symptoms, such as pain, may... limitations that go beyond the symptoms, such as pain, that are important in the diagnosis and treatment...

  18. 20 CFR 220.120 - The claimant's residual functional capacity.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... with a low back disorder may be fully capable of the physical demands consistent with those of... functional capacity. (a) General. The claimant's impairment(s), and any related symptoms, such as pain, may... limitations that go beyond the symptoms, such as pain, that are important in the diagnosis and treatment...

  19. 20 CFR 220.120 - The claimant's residual functional capacity.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... with a low back disorder may be fully capable of the physical demands consistent with those of... functional capacity. (a) General. The claimant's impairment(s), and any related symptoms, such as pain, may... limitations that go beyond the symptoms, such as pain, that are important in the diagnosis and treatment...

  20. Capacity Building of MAGDAS

    NASA Astrophysics Data System (ADS)

    Yumoto, K.

    2011-12-01

    Under the framework of the MAGDAS Project of SERC (at Kyushu University), this report will cover the three phases of "Capacity Building": (1) Development of instrument capacity, (2) Development of data analysis capacity, and (3) Development of science capacity. Capacity Building is one of the major goals of IHY and ISWI, as specified by the organizers of IHY and ISWI.

  1. Cognitive impairments in alcohol-dependent subjects.

    PubMed

    Bernardin, Florent; Maheut-Bosser, Anne; Paille, François

    2014-01-01

    Chronic excessive alcohol consumption induces cognitive impairments mainly affecting executive functions, episodic memory, and visuospatial capacities related to multiple brain lesions. These cognitive impairments not only determine everyday management of these patients, but also impact on the efficacy of management and may compromise the abstinence prognosis. Maintenance of lasting abstinence is associated with cognitive recovery in these patients, but some impairments may persist and interfere with the good conduct and the efficacy of management. It therefore appears essential to clearly define neuropsychological management designed to identify and evaluate the type and severity of alcohol-related cognitive impairments. It is also essential to develop cognitive remediation therapy so that the patient can fully benefit from the management proposed in addiction medicine units. PMID:25076914

  2. Cognitive Impairments in Alcohol-Dependent Subjects

    PubMed Central

    Bernardin, Florent; Maheut-Bosser, Anne; Paille, François

    2014-01-01

    Chronic excessive alcohol consumption induces cognitive impairments mainly affecting executive functions, episodic memory, and visuospatial capacities related to multiple brain lesions. These cognitive impairments not only determine everyday management of these patients, but also impact on the efficacy of management and may compromise the abstinence prognosis. Maintenance of lasting abstinence is associated with cognitive recovery in these patients, but some impairments may persist and interfere with the good conduct and the efficacy of management. It therefore appears essential to clearly define neuropsychological management designed to identify and evaluate the type and severity of alcohol-related cognitive impairments. It is also essential to develop cognitive remediation therapy so that the patient can fully benefit from the management proposed in addiction medicine units. PMID:25076914

  3. Mild Cognitive Impairment

    MedlinePlus

    ... Research Portfolio (IADRP) AMP-AD Detecting Cognitive Impairment Database ... Mild cognitive impairment (MCI) is a condition in which people have more memory or other thinking problems than normal for their ...

  4. Speech impairment (adult)

    MedlinePlus

    Language impairment; Impairment of speech; Inability to speak; Aphasia; Dysarthria; Slurred speech; Dysphonia voice disorders ... disorders develop gradually, but anyone can develop a speech and ... suddenly, usually in a trauma. APHASIA Alzheimer disease ...

  5. Speech impairment (adult)

    MedlinePlus

    Language impairment; Impairment of speech; Inability to speak; Aphasia; Dysarthria; Slurred speech; Dysphonia voice disorders ... Common speech and language disorders include: APHASIA Aphasia is ... understand or express spoken or written language. It commonly ...

  6. Ciliary abnormalities in senescent human fibroblasts impair proliferative capacity.

    PubMed

    Breslin, Loretta; Prosser, Suzanna L; Cuffe, Sandra; Morrison, Ciaran G

    2014-01-01

    Somatic cells senesce in culture after a finite number of divisions indefinitely arresting their proliferation. DNA damage and senescence increase the cellular number of centrosomes, the 2 microtubule organizing centers that ensure bipolar mitotic spindles. Centrosomes also provide the basal body from which primary cilia extend to sense and transduce various extracellular signals, notably Hedgehog. Primary cilium formation is facilitated by cellular quiescence a temporary cell cycle exit, but the impact of senescence on cilia is unknown. We found that senescent human fibroblasts have increased frequency and length of primary cilia. Levels of the negative ciliary regulator CP110 were reduced in senescent cells, as were levels of key elements of the Hedgehog pathway. Hedgehog inhibition reduced proliferation in young cells with increased cilium length accompanying cell cycle arrest suggesting a regulatory function for Hedgehog in primary ciliation. Depletion of CP110 in young cell populations increased ciliation frequencies and reduced cell proliferation. These data suggest that primary cilia are potentially novel determinants of the reduced cellular proliferation that initiates senescence. PMID:25486364

  7. Ciliary abnormalities in senescent human fibroblasts impair proliferative capacity

    PubMed Central

    Breslin, Loretta; Prosser, Suzanna L; Cuffe, Sandra; Morrison, Ciaran G

    2014-01-01

    Somatic cells senesce in culture after a finite number of divisions indefinitely arresting their proliferation. DNA damage and senescence increase the cellular number of centrosomes, the 2 microtubule organizing centers that ensure bipolar mitotic spindles. Centrosomes also provide the basal body from which primary cilia extend to sense and transduce various extracellular signals, notably Hedgehog. Primary cilium formation is facilitated by cellular quiescence a temporary cell cycle exit, but the impact of senescence on cilia is unknown. We found that senescent human fibroblasts have increased frequency and length of primary cilia. Levels of the negative ciliary regulator CP110 were reduced in senescent cells, as were levels of key elements of the Hedgehog pathway. Hedgehog inhibition reduced proliferation in young cells with increased cilium length accompanying cell cycle arrest suggesting a regulatory function for Hedgehog in primary ciliation. Depletion of CP110 in young cell populations increased ciliation frequencies and reduced cell proliferation. These data suggest that primary cilia are potentially novel determinants of the reduced cellular proliferation that initiates senescence. PMID:25486364

  8. Adapting for Impaired Patrons.

    ERIC Educational Resources Information Center

    Schuyler, Michael

    1999-01-01

    Describes how a library, with an MCI Corporation grant, approached the process of setting up computers for the visually impaired. Discusses preparations, which included hiring a visually-impaired user as a consultant and contacting the VIP (Visually Impaired Persons) group; equipment; problems with the graphical user interface; and training.…

  9. ABE. The Hearing Impaired.

    ERIC Educational Resources Information Center

    Carver, L. Sue

    This handbook was written to help teachers of adult basic education (ABE) adapt their teaching methods for hearing impaired persons. Written in a narrative format, the guide covers the following topics: ABE for the hearing impaired, hints for working with the hearing impaired without an interpreter, peer pairing, interpreters in the classroom…

  10. The Impaired Social Worker.

    ERIC Educational Resources Information Center

    Reamer, Frederic G.

    1992-01-01

    Discusses concept of the impaired professional; reviews research on various types of impairment (personality disorders, depression and other emotional problems, marital problems, and physical illness), prevalence and causes of impairment, and responses to it; and outlines model assessment and action plan for social workers who encounter an…

  11. Memory Impairment in Children with Language Impairment

    ERIC Educational Resources Information Center

    Baird, Gillian; Dworzynski, Katharina; Slonims, Vicky; Simonoff, Emily

    2010-01-01

    Aim: The aim of this study was to assess whether any memory impairment co-occurring with language impairment is global, affecting both verbal and visual domains, or domain specific. Method: Visual and verbal memory, learning, and processing speed were assessed in children aged 6 years to 16 years 11 months (mean 9y 9m, SD 2y 6mo) with current,…

  12. Finances in the Older Patient with Cognitive Impairment

    PubMed Central

    Widera, Eric; Steenpass, Veronika; Marson, Daniel; Sudore, Rebecca

    2013-01-01

    Financial capacity is the ability to manage money and financial assets in ways that meet a person’s needs and which are consistent with his/her values and self-interest. Financial capacity is essential for an individual to function independently in our society; however, dementia eventually leads to a complete loss of financial capacity. Many patients with cognitive impairment and their families turn to their primary care clinician for help with financial impairment, yet most clinicians do not understand their role or how to help. We review the prevalence and impact of financial incapacity in older adults with cognitive impairment. We also articulate the role of the primary clinician which includes: (1) educating older adult patients and families about the need for advance financial planning; (2) recognizing signs of possible impaired financial capacity; (3) assessing financial impairments in cognitively impaired adults; (4) recommending interventions to help patients maintain financial independence; and (5) knowing when and to whom to make medical and legal referrals. Clearly delineating the clinician’s role in financial impairment can lead to the establishment of effective financial protections and can limit the economic, psychological, and legal hardships of financial incapacity on patients with dementia and their families. PMID:21325186

  13. Programming placental nutrient transport capacity

    PubMed Central

    Fowden, A L; Ward, J W; Wooding, F P B; Forhead, A J; Constancia, M

    2006-01-01

    Many animal studies and human epidemiological findings have shown that impaired growth in utero is associated with physiological abnormalities in later life and have linked this to tissue programming during suboptimal intrauterine conditions at critical periods of development. However, few of these studies have considered the contribution of the placenta to the ensuing adult phenotype. In mammals, the major determinant of intrauterine growth is the placental nutrient supply, which, in turn, depends on the size, morphology, blood supply and transporter abundance of the placenta and on synthesis and metabolism of nutrients and hormones by the uteroplacental tissues. This review examines the regulation of placental nutrient transfer capacity and the potential programming effects of nutrition and glucocorticoid over-exposure on placental phenotype with particular emphasis on the role of the Igf2 gene in these processes. PMID:16439433

  14. Education for the Hearing Impaired (Auditorily Impaired).

    ERIC Educational Resources Information Center

    World Federation of the Deaf, Rome (Italy).

    Education for the hearing impaired is discussed in nine conference papers. J. N. Howarth describes "The Education of Deaf Children in Schools for Hearing Pupils in the United Kingdom" and A.I.Dyachkov of the U.S.S.R. outlines Didactical Principles of Educating the Deaf in the Light of their Rehabilitation Goal." Seven papers from Poland are also…

  15. Development or Impairment?

    ERIC Educational Resources Information Center

    Hakansson, Gisela

    2010-01-01

    Joanne Paradis' Keynote Article on bilingualism and specific language impairment (SLI) is an impressive overview of research in language acquisition and language impairment. Studying different populations is crucial both for theorizing about language acquisition mechanisms, and for practical purposes of diagnosing and supporting children with…

  16. Building Leadership Capacity

    ERIC Educational Resources Information Center

    Flanary, Dick

    2009-01-01

    The NASSP "Breaking Ranks" framework lays out multiple strategies for building capacity within a school, beginning with the leaders. To change an organization and increase its capacity to produce greater results, the people within the organization must change and increase their capacity. School change begins with changes in the principal, the…

  17. Type 2 diabetes mellitus and exercise impairment.

    PubMed

    Reusch, Jane E B; Bridenstine, Mark; Regensteiner, Judith G

    2013-03-01

    Limitations in physical fitness, a consistent finding in individuals with both type I and type 2 diabetes mellitus, correlate strongly with cardiovascular and all-cause mortality. These limitations may significantly contribute to the persistent excess cardiovascular mortality affecting this group. Exercise impairments in VO2 peak and VO2 kinetics manifest early on in diabetes, even with good glycemic control and in the absence of clinically apparent complications. Subclinical cardiac dysfunction is often present but does not fully explain the observed defect in exercise capacity in persons with diabetes. In part, the cardiac limitations are secondary to decreased perfusion with exercise challenge. This is a reversible defect. Similarly, in the skeletal muscle, impairments in nutritive blood flow correlate with slowed (or inefficient) exercise kinetics and decreased exercise capacity. Several correlations highlight the likelihood of endothelial-specific impairments as mediators of exercise dysfunction in diabetes, including insulin resistance, endothelial dysfunction, decreased myocardial perfusion, slowed tissue hemoglobin oxygen saturation, and impairment in mitochondrial function. Both exercise training and therapies targeted at improving insulin sensitivity and endothelial function improve physical fitness in subjects with type 2 diabetes. Optimization of exercise functions in people with diabetes has implications for diabetes prevention and reductions in mortality risk. Understanding the molecular details of endothelial dysfunction in diabetes may provide specific therapeutic targets for the remediation of this defect. Rat models to test this hypothesis are under study. PMID:23299658

  18. Impairment in Non-Word Repetition: A Marker for Language Impairment or Reading Impairment?

    ERIC Educational Resources Information Center

    Baird, Gillian; Slonims, Vicky; Simonoff, Emily; Dworzynski, Katharina

    2011-01-01

    Aim: A deficit in non-word repetition (NWR), a measure of short-term phonological memory proposed as a marker for language impairment, is found not only in language impairment but also in reading impairment. We evaluated the strength of association between language impairment and reading impairment in children with current, past, and no language…

  19. Hearing or speech impairment - resources

    MedlinePlus

    Resources - hearing or speech impairment ... The following organizations are good resources for information on hearing impairment or speech impairment: Alexander Graham Bell Association for the Deaf and Hard of Hearing -- www.agbell. ...

  20. Mild Cognitive Impairment

    MedlinePlus

    ... other people their age. This condition is called mild cognitive impairment, or MCI. People with MCI can take care of themselves and do their normal activities. MCI memory problems may include Losing things often Forgetting ...

  1. Kids' Quest: Vision Impairment

    MedlinePlus

    ... important job. Â Return to Steps World-Wide Web Search Kids Health: What is Vision Impairment What ... for the Blind (AFB) created the Braille Bug web site to teach sighted children about braille, and ...

  2. Impairments to Vision

    MedlinePlus

    ... an external Non-Government web site. Impairments to Vision Normal Vision Diabetic Retinopathy Age-related Macular Degeneration In this ... pictures, fixate on the nose to simulate the vision loss. In diabetic retinopathy, the blood vessels in ...

  3. On Gaussian feedback capacity

    NASA Technical Reports Server (NTRS)

    Dembo, Amir

    1989-01-01

    Pinsker and Ebert (1970) proved that in channels with additive Gaussian noise, feedback at most doubles the capacity. Cover and Pombra (1989) proved that feedback at most adds half a bit per transmission. Following their approach, the author proves that in the limit as signal power approaches either zero (very low SNR) or infinity (very high SNR), feedback does not increase the finite block-length capacity (which for nonstationary Gaussian channels replaces the standard notion of capacity that may not exist). Tighter upper bounds on the capacity are obtained in the process. Specializing these results to stationary channels, the author recovers some of the bounds recently obtained by Ozarow.

  4. Heat Capacity Analysis Report

    SciTech Connect

    A. Findikakis

    2004-11-01

    The purpose of this report is to provide heat capacity values for the host and surrounding rock layers for the waste repository at Yucca Mountain. The heat capacity representations provided by this analysis are used in unsaturated zone (UZ) flow, transport, and coupled processes numerical modeling activities, and in thermal analyses as part of the design of the repository to support the license application. Among the reports that use the heat capacity values estimated in this report are the ''Multiscale Thermohydrologic Model'' report, the ''Drift Degradation Analysis'' report, the ''Ventilation Model and Analysis Report, the Igneous Intrusion Impacts on Waste Packages and Waste Forms'' report, the ''Dike/Drift Interactions report, the Drift-Scale Coupled Processes (DST and TH Seepage) Models'' report, and the ''In-Drift Natural Convection and Condensation'' report. The specific objective of this study is to determine the rock-grain and rock-mass heat capacities for the geologic stratigraphy identified in the ''Mineralogic Model (MM3.0) Report'' (BSC 2004 [DIRS 170031], Table 1-1). This report provides estimates of the heat capacity for all stratigraphic layers except the Paleozoic, for which the mineralogic abundance data required to estimate the heat capacity are not available. The temperature range of interest in this analysis is 25 C to 325 C. This interval is broken into three separate temperature sub-intervals: 25 C to 95 C, 95 C to 114 C, and 114 C to 325 C, which correspond to the preboiling, trans-boiling, and postboiling regimes. Heat capacity is defined as the amount of energy required to raise the temperature of a unit mass of material by one degree (Nimick and Connolly 1991 [DIRS 100690], p. 5). The rock-grain heat capacity is defined as the heat capacity of the rock solids (minerals), and does not include the effect of water that exists in the rock pores. By comparison, the rock-mass heat capacity considers the heat capacity of both solids and pore

  5. Hearing Impairment and Retirement

    PubMed Central

    Fischer, Mary E; Cruickshanks, Karen J; Pinto, Alex; Klein, Barbara E K; Klein, Ronald; Dalton, Dayna S

    2013-01-01

    BACKGROUND Many factors influence the decision to retire including age, insurance and pension availability along with physical and mental health. Hearing impairment may be one such factor. PURPOSE The purpose of this study was to compare the 15 year retirement rate among subjects with and without hearing impairment. RESEARCH DESIGN Prospective, population-based study STUDY SAMPLE Subjects were participants in the Epidemiology of Hearing Loss Study (EHLS), a longitudinal investigation of age-related hearing loss. Participants who were working full- or part-time in 1993–1995 were included (n=1410, mean age=57.8 years). DATA COLLECTION AND ANALYSIS Data from four EHLS phases (1993–1995, 1998–2000, 2003–2005, and 2009–2010) were analyzed in 2010–2012. Hearing impairment was defined as a pure tone threshold average (at 0.5,1,2 and 4 kHz) greater than 25 dB HL in the worse ear. Employment status was determined at each of the four phases. Kaplan-Meier estimates of the cumulative incidence of retirement were calculated and Cox discrete-time modeling was used to determine the effect of hearing impairment on the rate of retirement. RESULTS The cumulative incidence of retirement was significantly (p < 0.02) higher in those with a hearing impairment (77%) compared to those without a hearing impairment (74%). After adjustment for age, gender, self-reported health, and history of chronic disease, there was no significant difference in the rate of retirement between those with and without a hearing impairment (Hazard Ratio (HR) = 0.9, 95% Confidence Interval (CI) = 0.7, 1.1). Similar results were observed when hearing aid users were excluded, when hearing impairment was based on the better ear thresholds, and when analyses were restricted to those less than 65 years of age and working full-time at baseline. Participants with a hearing impairment were less likely to state that the main reason for retirement was that the time seemed right. CONCLUSIONS Hearing impairment

  6. Problems of Excess Capacity

    NASA Technical Reports Server (NTRS)

    Douglas, G.

    1972-01-01

    The problems of excess capacity in the airline industry are discussed with focus on the following topics: load factors; fair rate of return on investment; service-quality rivalry among airlines; pricing (fare) policies; aircraft production; and the impacts of excess capacity on operating costs. Also included is a discussion of the interrelationships among these topics.

  7. Variable capacity gasification burner

    SciTech Connect

    Saxon, D.I.

    1985-03-05

    A variable capacity burner that may be used in gasification processes, the burner being adjustable when operating in its intended operating environment to operate at two different flow capacities, with the adjustable parts being dynamically sealed within a statically sealed structural arrangement to prevent dangerous blow-outs of the reactants to the atmosphere.

  8. Liquid heat capacity lasers

    DOEpatents

    Comaskey, Brian J.; Scheibner, Karl F.; Ault, Earl R.

    2007-05-01

    The heat capacity laser concept is extended to systems in which the heat capacity lasing media is a liquid. The laser active liquid is circulated from a reservoir (where the bulk of the media and hence waste heat resides) through a channel so configured for both optical pumping of the media for gain and for light amplification from the resulting gain.

  9. Who needs capacity?

    PubMed

    Buchanan, Alec

    2015-01-01

    The UK Law Commission's Discussion Paper, Criminal Liability: Insanity and Automatism, recommends introducing the concept of capacity to the insanity defence. The concept of capacity has an established role in those parts of the law that concern the validity of the decisions that people make, for instance in composing a will or entering into a contract. Making mental capacity a criterion for criminal responsibility in a mentally disordered defendant, however, is potentially problematic. First, the term capacity already has several different meanings in the literature on the jurisprudence of mental abnormality. Second, using the concept of capacity in the way that the Law Commission proposes poses difficulties that relate to the provision of testimony by expert witnesses. PMID:25939285

  10. Nanofluid heat capacities

    NASA Astrophysics Data System (ADS)

    Starace, Anne K.; Gomez, Judith C.; Wang, Jun; Pradhan, Sulolit; Glatzmaier, Greg C.

    2011-12-01

    Significant increases in the heat capacity of heat transfer fluids are needed not only to reduce the costs of liquid heating and cooling processes, but also to bring clean energy producing technologies like concentrating solar power (CSP) to price parity with conventional energy generation. It has been postulated that nanofluids could have higher heat capacities than conventional fluids. In this work, nano- and micron-sized particles were added to five base fluids (poly-α olefin, mineral oil, ethylene glycol, a mixture of water and ethylene glycol, and calcium nitrate tetrahydrate), and the resulting heat capacities were measured and compared with those of the neat base fluids and the weighted average of the heat capacities of the components. The particles used were inert metals and metal oxides that did not undergo any phase transitions over the temperature range studied. In the nanofluids studied here, we found no increase in heat capacity upon the addition of the particles larger than the experimental error.

  11. HEARING IMPAIRMENT IN CHILDREN

    PubMed Central

    Kohlmoos, H. W.

    1953-01-01

    Abnormal behavior in children may frequently be caused by impairment of hearing. Early detection of the impairment and of the cause are of utmost importance, not only to prevent irreversible changes where that is possible, but to permit early beginning of special training for children who are permanently deaf. Recent studies have shown that deafness of infants may follow rubella in the mother in early pregnancy, or kernicterus caused by Rh incompatibilities. Measures to control these disorders are being investigated. Adequate and careful treatment of diseases of the nose, as well as surgical drainage of infected ears when necessary, are important factors in the prevention of hearing loss in children. PMID:13009516

  12. [Working with hearing impairment: an integrated approach].

    PubMed

    van Til, Marten J; Kramer, Sophia E; Anema, Johannes R; Goverts, S T Theo

    2016-01-01

    Patients with hearing impairment are more likely to encounter health problems and difficulties at work than their colleagues with normal hearing. This is often not realised by either patients or professionals. In this article we describe three cases that illustrate how working conditions can influence the health of workers with hearing loss. We have implemented a vocational enablement protocol that follows a multidisciplinary approach in order to meet these patients' needs. Due to a mismatch between the demands of a job and an individual's auditory capacities, even a mild hearing impairment can cause serious problems if a patient works in adverse conditions. In addition, in many workplaces the ability to hear well is a safety issue. Professionals have to be aware of both possibilities. Specialized centres offer good facilities and ensure the optimal transfer of insight into the working environment by involving an occupational physician in their team. PMID:27050493

  13. Refinery Capacity Report

    EIA Publications

    2015-01-01

    Data series include fuel, electricity, and steam purchased for consumption at the refinery; refinery receipts of crude oil by method of transportation; and current and projected atmospheric crude oil distillation, downstream charge, and production capacities. Respondents are operators of all operating and idle petroleum refineries (including new refineries under construction) and refineries shut down during the previous year, located in the 50 states, the District of Columbia, Puerto Rico, the Virgin Islands, Guam, and other U.S. possessions. The Refinery Capacity Report does not contain working and shell storage capacity data. This data is now being collected twice a year as of March 31 and September 30 on the Form EIA-810, "Monthly Refinery Report", and is now released as a separate report Working and Net Available Shell Storage Capacity.

  14. Refinery Capacity Report

    EIA Publications

    2016-01-01

    Data series include fuel, electricity, and steam purchased for consumption at the refinery; refinery receipts of crude oil by method of transportation; and current and projected atmospheric crude oil distillation, downstream charge, and production capacities. Respondents are operators of all operating and idle petroleum refineries (including new refineries under construction) and refineries shut down during the previous year, located in the 50 states, the District of Columbia, Puerto Rico, the Virgin Islands, Guam, and other U.S. possessions. The Refinery Capacity Report does not contain working and shell storage capacity data. This data is now being collected twice a year as of March 31 and September 30 on the Form EIA-810, "Monthly Refinery Report", and is now released as a separate report Working and Net Available Shell Storage Capacity.

  15. Knudsen heat capacity

    SciTech Connect

    Babac, Gulru; Reese, Jason M.

    2014-05-15

    We present a “Knudsen heat capacity” as a more appropriate and useful fluid property in micro/nanoscale gas systems than the constant pressure heat capacity. At these scales, different fluid processes come to the fore that are not normally observed at the macroscale. For thermodynamic analyses that include these Knudsen processes, using the Knudsen heat capacity can be more effective and physical. We calculate this heat capacity theoretically for non-ideal monatomic and diatomic gases, in particular, helium, nitrogen, and hydrogen. The quantum modification for para and ortho hydrogen is also considered. We numerically model the Knudsen heat capacity using molecular dynamics simulations for the considered gases, and compare these results with the theoretical ones.

  16. Panama Canal capacity analysis

    SciTech Connect

    Bronzini, M.S.

    1995-04-27

    Predicting the transit capacities of the various Panama Canal alternatives required analyzing data on present Canal operations, adapting and extending an existing computer simulation model, performing simulation runs for each of the alternatives, and using the simulation model outputs to develop capacity estimates. These activities are summarized in this paper. A more complete account may be found in the project final report (TAMS 1993). Some of the material in this paper also appeared in a previously published paper (Rosselli, Bronzini, and Weekly 1994).

  17. Forward capacity market CONEfusion

    SciTech Connect

    Wilson, James F.

    2010-11-15

    In ISO New England and PJM it was assumed that sponsors of new capacity projects would offer them into the newly established forward centralized capacity markets at prices based on their levelized net cost of new entry, or ''Net CONE.'' But the FCCMs have not operated in the way their proponents had expected. To clear up the CONEfusion, FCCM designs should be reconsidered to adapt them to the changing circumstances and to be grounded in realistic expectations of market conduct. (author)

  18. Language Impairment in the Attention-Deficit/Hyperactivity Disorder Context

    ERIC Educational Resources Information Center

    Redmond, Sean M.

    2016-01-01

    Purpose: Attention-deficit/hyperactivity disorder (ADHD) is a ubiquitous designation that affects the identification, assessment, treatment, and study of pediatric language impairments (LIs). Method: Current literature is reviewed in 4 areas: (a) the capacity of psycholinguistic, neuropsychological, and socioemotional behavioral indices to…

  19. Specific Language Impairment

    MedlinePlus

    ... to distinguish between children who are struggling to learn a new language and children with true language impairments. After studying a large group of Hispanic children who speak English as a second language, NIDCD-funded researchers have developed a dual ...

  20. Cognitive Impairment After Stroke

    PubMed Central

    Gauba, Charu; Chaudhari, Dinesh

    2015-01-01

    Background: Vascular dementia is extremely common and contributes to stroke-associated morbidity and mortality. The study of vascular dementia may help to plan preventive interventions. Aims: To study the frequency of cognitive impairment after stroke in a series of consecutive patients with acute stroke, along with factors which influence it. Methods: Fifty adults with acute infarct or hemorrhage (as seen on computed tomography of the brain) were included in the study. The National Institute of Health Stroke Scale (NIHSS) and Barthel’s Index scores were done. Cognitive testing was done by PGI Battery of Brain Dysfunction (PGI-BBD) and Short Form of the Informant Questionnaire on Cognitive Decline in the Elderly (SIQCODE). Statistical analysis was by Student’s t-test, Chi-square test, Fisher’s exact test, and Mann-Whitney U test. Results: Mean age of patients was 61.82 years; males and ischemic strokes predominated. Dementia was seen in 30%, cognitive impairment no dementia (CIND) in 42%, and normal cognition in 28% patients. Factors associated with vascular cognitive impairment included old age, male sex, low education, hemorrhages, recurrent or severe stroke, silent infarcts, severe cortical atrophy, and left hemispheric or subcortical involvement. Conclusions: Up to 72% of patients have some form of cognitive impairment after a stroke. Secondary stroke prevention could reduce the incidence of vascular dementia. PMID:26543693

  1. Oral Morphosyntactic Competence as a Predictor of Reading Comprehension in Children with Specific Language Impairment

    ERIC Educational Resources Information Center

    Buil-Legaz, Lucía; Aguilar-Mediavilla, Eva; Rodríguez-Ferreiro, Javier

    2016-01-01

    Background: Children with a diagnosis of specific language impairment (SLI) present impaired oral comprehension. According to the simple view of reading, general amodal linguistic capacity accounts for both oral and reading comprehension. Considering this, we should expect SLI children to display a reading comprehension deficit. However, previous…

  2. Cognitive Impairment among the Aging Population in a Community in Southwest Nigeria

    ERIC Educational Resources Information Center

    Adebiyi, Akindele O.; Ogunniyi, Adesola; Adediran, Babatunde A.; Olakehinde, Olaide O.; Siwoku, Akeem A.

    2016-01-01

    Background: Vascular risk models can be quite informative in assisting the clinician to make a prediction of an individual's risk of cognitive impairment. Thus, a simple marker is a priority for low-capacity settings. This study examines the association of selected simple to deploy vascular markers with cognitive impairment in an elderly…

  3. Uncertainty in adaptive capacity

    NASA Astrophysics Data System (ADS)

    Adger, W. Neil; Vincent, Katharine

    2005-03-01

    The capacity to adapt is a critical element of the process of adaptation: it is the vector of resources that represent the asset base from which adaptation actions can be made. Adaptive capacity can in theory be identified and measured at various scales, from the individual to the nation. The assessment of uncertainty within such measures comes from the contested knowledge domain and theories surrounding the nature of the determinants of adaptive capacity and the human action of adaptation. While generic adaptive capacity at the national level, for example, is often postulated as being dependent on health, governance and political rights, and literacy, and economic well-being, the determinants of these variables at national levels are not widely understood. We outline the nature of this uncertainty for the major elements of adaptive capacity and illustrate these issues with the example of a social vulnerability index for countries in Africa. To cite this article: W.N. Adger, K. Vincent, C. R. Geoscience 337 (2005).

  4. Grammatical Impairments in PPA

    PubMed Central

    Thompson, Cynthia K.; Mack, Jennifer E.

    2015-01-01

    Background Grammatical impairments are commonly observed in the agrammatic subtype of primary progressive aphasia (PPA-G), whereas grammatical processing is relatively preserved in logopenic (PPA-L) and semantic (PPA-S) subtypes. Aims We review research on grammatical deficits in PPA and associated neural mechanisms, with discussion focused on production and comprehension of four aspects of morphosyntactic structure: grammatical morphology, functional categories, verbs and verb argument structure, and complex syntactic structures. We also address assessment of grammatical deficits in PPA, with emphasis on behavioral tests of grammatical processing. Finally, we address research examining the effects of treatment for progressive grammatical impairments. Main Contribution PPA-G is associated with grammatical deficits that are evident across linguistic domains in both production and comprehension. PPA-G is associated with damage to regions including the left inferior frontal gyrus (IFG) and dorsal white matter tracts, which have been linked to impaired comprehension and production of complex sentences. Detailing grammatical deficits in PPA is important for estimating the trajectory of language decline and associated neuropathology. We, therefore, highlight several new assessment tools for examining different aspects of morphosyntactic processing in PPA. Conclusions Individuals with PPA-G present with agrammatic deficit patterns distinct from those associated with PPA-L and PPA-S, but similar to those seen in agrammatism resulting from stroke, and patterns of cortical atrophy and white matter changes associated with PPA-G have been identified. Methods for clinical evaluation of agrammatism, focusing on comprehension and production of grammatical morphology, functional categories, verbs and verb argument structure, and complex syntactic structures are recommended and tools for this are emerging in the literature. Further research is needed to investigate the real

  5. Auditory spatial localization: Developmental delay in children with visual impairments.

    PubMed

    Cappagli, Giulia; Gori, Monica

    2016-01-01

    For individuals with visual impairments, auditory spatial localization is one of the most important features to navigate in the environment. Many works suggest that blind adults show similar or even enhanced performance for localization of auditory cues compared to sighted adults (Collignon, Voss, Lassonde, & Lepore, 2009). To date, the investigation of auditory spatial localization in children with visual impairments has provided contrasting results. Here we report, for the first time, that contrary to visually impaired adults, children with low vision or total blindness show a significant impairment in the localization of static sounds. These results suggest that simple auditory spatial tasks are compromised in children, and that this capacity recovers over time. PMID:27002960

  6. Hearing or speech impairment - resources

    MedlinePlus

    ... resources for information on hearing impairment or speech impairment: Alexander Graham Bell Association for the Deaf and Hard of Hearing -- www.agbell.org American Speech-Language-Hearing Association -- www.asha.org/public Center for ...

  7. Chemistry for the Visually Impaired.

    ERIC Educational Resources Information Center

    Ratliff, Judy L.

    1997-01-01

    Discusses modifications to general education or introductory chemistry courses that allow visually impaired students to participate productively. Describes a strategy for teaching about elements and density, and the construction of a conductivity tester for visually impaired students. (JRH)

  8. Geothermal Plant Capacity Factors

    SciTech Connect

    Greg Mines; Jay Nathwani; Christopher Richard; Hillary Hanson; Rachel Wood

    2015-01-01

    The capacity factors recently provided by the Energy Information Administration (EIA) indicated this plant performance metric had declined for geothermal power plants since 2008. Though capacity factor is a term commonly used by geothermal stakeholders to express the ability of a plant to produce power, it is a term frequently misunderstood and in some instances incorrectly used. In this paper we discuss how this capacity factor is defined and utilized by the EIA, including discussion on the information that the EIA requests from operations in their 923 and 860 forms that are submitted both monthly and annually by geothermal operators. A discussion is also provided regarding the entities utilizing the information in the EIA reports, and how those entities can misinterpret the data being supplied by the operators. The intent of the paper is to inform the facility operators as the importance of the accuracy of the data that they provide, and the implications of not providing the correct information.

  9. Capacity Maximizing Constellations

    NASA Technical Reports Server (NTRS)

    Barsoum, Maged; Jones, Christopher

    2010-01-01

    Some non-traditional signal constellations have been proposed for transmission of data over the Additive White Gaussian Noise (AWGN) channel using such channel-capacity-approaching codes as low-density parity-check (LDPC) or turbo codes. Computational simulations have shown performance gains of more than 1 dB over traditional constellations. These gains could be translated to bandwidth- efficient communications, variously, over longer distances, using less power, or using smaller antennas. The proposed constellations have been used in a bit-interleaved coded modulation system employing state-ofthe-art LDPC codes. In computational simulations, these constellations were shown to afford performance gains over traditional constellations as predicted by the gap between the parallel decoding capacity of the constellations and the Gaussian capacity

  10. Dual capacity reciprocating compressor

    DOEpatents

    Wolfe, R.W.

    1984-10-30

    A multi-cylinder compressor particularly useful in connection with northern climate heat pumps and in which different capacities are available in accordance with reversing motor rotation is provided with an eccentric cam on a crank pin under a fraction of the connecting rods, and arranged for rotation upon the crank pin between opposite positions 180[degree] apart so that with cam rotation on the crank pin such that the crank throw is at its normal maximum value all pistons pump at full capacity, and with rotation of the crank shaft in the opposite direction the cam moves to a circumferential position on the crank pin such that the overall crank throw is zero. Pistons whose connecting rods ride on a crank pin without a cam pump their normal rate with either crank rotational direction. Thus a small clearance volume is provided for any piston that moves when in either capacity mode of operation. 6 figs.

  11. Dual capacity reciprocating compressor

    DOEpatents

    Wolfe, Robert W.

    1984-01-01

    A multi-cylinder compressor 10 particularly useful in connection with northern climate heat pumps and in which different capacities are available in accordance with reversing motor 16 rotation is provided with an eccentric cam 38 on a crank pin 34 under a fraction of the connecting rods, and arranged for rotation upon the crank pin between opposite positions 180.degree. apart so that with cam rotation on the crank pin such that the crank throw is at its normal maximum value all pistons pump at full capacity, and with rotation of the crank shaft in the opposite direction the cam moves to a circumferential position on the crank pin such that the overall crank throw is zero. Pistons 24 whose connecting rods 30 ride on a crank pin 36 without a cam pump their normal rate with either crank rotational direction. Thus a small clearance volume is provided for any piston that moves when in either capacity mode of operation.

  12. Neurological Impairment: Nomenclature and Consequences.

    ERIC Educational Resources Information Center

    Spears, Catherine E.; Weber, Robert E.

    Neurological impairment as discussed includes a range of disabilities referred to as neurological impairment: minimal brain dysfunction/damage, developmental disability, perceptual handicap, learning disability, hyperkinetic behavioral syndrome, and others. Defined are causes of neurological impairment and methods of diagnosis. Symptoms…

  13. The impaired radiologist.

    PubMed

    Magnavita, N; Magnavita, G; Bergamaschi, A

    2010-08-01

    The concept of the "impaired physician" is an oxymoron. Physicians are by definition bearers of health, which can lead to overlooking the possibility of them contracting an illness that reduces their diagnostic and therapeutic abilities, with a consequent danger to their patients' health. The clinical reasons for which a radiologist may constitute a danger to patients can be divided into two categories: infectious blood-borne diseases, which can be transmitted to the patient during interventional radiology procedures; and neurodegenerative and psychiatric disorders, including alcohol and drug abuse, which temporarily or permanently impair the faculty of judgement. All radiologists have a duty to periodically verify their own state of health and seek help as soon as possible when they fear it may be a danger. This individual responsibility towards one's own patients is flanked by the health and safety requirements provided by European regulations for radiologists who are employers, directors or department heads. The occupational health physician plays a key role in identifying and managing the impaired radiologist. PMID:20221712

  14. Diabetes and Cognitive Impairment.

    PubMed

    Zilliox, Lindsay A; Chadrasekaran, Krish; Kwan, Justin Y; Russell, James W

    2016-09-01

    Both type 1 (T1DM) and type 2 diabetes mellitus (T2DM) have been associated with reduced performance on multiple domains of cognitive function and with evidence of abnormal structural and functional brain magnetic resonance imaging (MRI). Cognitive deficits may occur at the very earliest stages of diabetes and are further exacerbated by the metabolic syndrome. The duration of diabetes and glycemic control may have an impact on the type and severity of cognitive impairment, but as yet we cannot predict who is at greatest risk of developing cognitive impairment. The pathophysiology of cognitive impairment is multifactorial, although dysfunction in each interconnecting pathway ultimately leads to discordance in metabolic signaling. The pathophysiology includes defects in insulin signaling, autonomic function, neuroinflammatory pathways, mitochondrial (Mt) metabolism, the sirtuin-peroxisome proliferator-activated receptor-gamma co-activator 1α (SIRT-PGC-1α) axis, and Tau signaling. Several promising therapies have been identified in pre-clinical studies, but remain to be validated in clinical trials. PMID:27491830

  15. Attentional control mediates the relationship between social anhedonia and social impairment

    PubMed Central

    Tully, Laura M.; Lincoln, Sarah Hope; Hooker, Christine I.

    2014-01-01

    Social anhedonia (SA), a trait-like disinterest in social contact and diminished capacity to experience pleasure from social interactions, is consistently associated with social impairments in both healthy and clinical populations. However, the mechanisms underlying the relationship between SA and social impairment are poorly understood. Attentional control, selecting and focusing on relevant information and inhibiting irrelevant, may be one such mechanism. We examined individual differences in SA, attentional control, and social impairment in 108 healthy adults. High SA related to low attentional control and high social impairment. Moreover, attentional control mediated the relationship between SA and social impairment, establishing attentional control as one mechanism underlying aberrations in the fundamental human need for social contact. Although both attentional deficits and social impairment have been separately noted in SA, the relationship between SA, attentional control and social impairment in this non-clinical sample reflects a novel contribution. PMID:25538647

  16. Flood Bypass Capacity Optimization

    NASA Astrophysics Data System (ADS)

    Siclari, A.; Hui, R.; Lund, J. R.

    2015-12-01

    Large river flows can damage adjacent flood-prone areas, by exceeding river channel and levee capacities. Particularly large floods are difficult to contain in leveed river banks alone. Flood bypasses often can efficiently reduce flood risks, where excess river flow is diverted over a weir to bypasses, that incur much less damage and cost. Additional benefits of bypasses include ecosystem protection, agriculture, groundwater recharge and recreation. Constructing or expanding an existing bypass costs in land purchase easements, and levee setbacks. Accounting for such benefits and costs, this study develops a simple mathematical model for optimizing flood bypass capacity using benefit-cost and risk analysis. Application to the Yolo Bypass, an existing bypass along the Sacramento River in California, estimates optimal capacity that economically reduces flood damage and increases various benefits, especially for agriculture. Land availability is likely to limit bypass expansion. Compensation for landowners could relax such limitations. Other economic values could affect the optimal results, which are shown by sensitivity analysis on major parameters. By including land geography into the model, location of promising capacity expansions can be identified.

  17. The Moral Capacity Profile

    ERIC Educational Resources Information Center

    Wilks, Duffy; Ratheal, Juli D'Ann

    2011-01-01

    Effective counseling practice continues to be inevitably linked to underlying theories of behavioral causality. In this article, the authors present the Moral Capacity Profile of an individual from the perspective of the Amoral, Moral, Quasi-Moral/Quasi-Immoral, and Immoral Model of Behavior, a model that uniquely expands counseling's theoretical…

  18. Working Memory as a Predictor of Reading Achievement in Orally Educated Hearing-Impaired Children.

    ERIC Educational Resources Information Center

    Daneman, Meredyth; And Others

    1995-01-01

    This study found that three measures of working memory capacity (processing and storage capacity, reading and listening span, and visual shape span) were good predictors of reading achievement in 30 orally educated children (ages 5 to 14) with hearing impairments as well as in an age-matched hearing control group. Degree of hearing loss did not…

  19. Working memory contributions to reinforcement learning impairments in schizophrenia.

    PubMed

    Collins, Anne G E; Brown, Jaime K; Gold, James M; Waltz, James A; Frank, Michael J

    2014-10-01

    Previous research has shown that patients with schizophrenia are impaired in reinforcement learning tasks. However, behavioral learning curves in such tasks originate from the interaction of multiple neural processes, including the basal ganglia- and dopamine-dependent reinforcement learning (RL) system, but also prefrontal cortex-dependent cognitive strategies involving working memory (WM). Thus, it is unclear which specific system induces impairments in schizophrenia. We recently developed a task and computational model allowing us to separately assess the roles of RL (slow, cumulative learning) mechanisms versus WM (fast but capacity-limited) mechanisms in healthy adult human subjects. Here, we used this task to assess patients' specific sources of impairments in learning. In 15 separate blocks, subjects learned to pick one of three actions for stimuli. The number of stimuli to learn in each block varied from two to six, allowing us to separate influences of capacity-limited WM from the incremental RL system. As expected, both patients (n = 49) and healthy controls (n = 36) showed effects of set size and delay between stimulus repetitions, confirming the presence of working memory effects. Patients performed significantly worse than controls overall, but computational model fits and behavioral analyses indicate that these deficits could be entirely accounted for by changes in WM parameters (capacity and reliability), whereas RL processes were spared. These results suggest that the working memory system contributes strongly to learning impairments in schizophrenia. PMID:25297101

  20. The visually impaired child.

    PubMed

    Thompson, Lisa; Kaufman, Lawrence M

    2003-02-01

    This article discusses the causes of childhood blindness and how the primary care provider may begin the appropriate steps toward diagnosing and managing the visually impaired child. Community resources (see Box 3) and low-vision programs in schools should be used so that parents do not need to reinvent strategies to raise a blind child. Worldwide, childhood blindness, which places is a tremendous burden on families and communities of the third world, is mostly preventable with improved hygiene, diet, and immunization. PMID:12713115

  1. Seismic capacity of switchgear

    SciTech Connect

    Bandyopadhyay, K.; Hofmayer, C.; Kassir, M.; Pepper, S.

    1989-01-01

    As part of a component fragility program sponsored by the USNRC, BNL has collected existing information on the seismic capacity of switchgear assemblies from major manufacturers. Existing seismic test data for both low and medium voltage switchgear assemblies have been evaluated and the generic results are presented in this paper. The failure modes are identified and the corresponding generic lower bound capacity levels are established. The test response spectra have been used as a measure of the test vibration input. The results indicate that relays chatter at a very low input level at the base of the switchgear cabinet. This change of state of devices including relays have been observed. Breaker tripping occurs at a higher vibration level. Although the structural failure of internal elements have been noticed, the overall switchgear cabinet structure withstands a high vibration level. 5 refs., 2 figs., 2 tabs.

  2. Enhancing capacity management.

    PubMed

    Rees, Susan; Houlahan, Beth; Lavrenz, Dennise

    2014-03-01

    It is essential for organizations to be able to accept patients requiring care. Capacity planning and management are necessary to ensure an organization has an accepting physician/service, an available bed, and staff to care for the patient and family. This organization implemented strategies including communication plans, staffing guidelines, morning rounds, proactive planning, and an escalation process to reverse the trend of not being able to accept all patients. PMID:24531280

  3. Heat Capacity Mapping Mission

    NASA Technical Reports Server (NTRS)

    Nilsson, C. S.; Andrews, J. C.; Scully-Power, P.; Ball, S.; Speechley, G.; Latham, A. R. (Principal Investigator)

    1980-01-01

    The Tasman Front was delineated by airborne expendable bathythermograph survey; and an Heat Capacity Mapping Mission (HCMM) IR image on the same day shows the same principal features as determined from ground-truth. It is clear that digital enhancement of HCMM images is necessary to map ocean surface temperatures and when done, the Tasman Front and other oceanographic features can be mapped by this method, even through considerable scattered cloud cover.

  4. CSTI High Capacity Power

    NASA Technical Reports Server (NTRS)

    Winter, Jerry M.

    1989-01-01

    The SP-100 program was established in 1983 by DOD, DOE, and NASA as a joint program to develop the technology necessary for space nuclear power systems for military and civil application. During FY-86 and 87, the NASA SP-100 Advanced Technology Program was devised to maintain the momentum of promising technology advancement efforts started during Phase 1 of SP-100 and to strengthen, in key areas, the chances for successful development and growth capability of space nuclear reactor power systems for future space applications. In FY-88, the Advanced Technology Program was incorporated into NASA's new Civil Space Technology Initiative (CSTI). The CSTI Program was established to provide the foundation for technology development in automation and robotics, information, propulsion, and power. The CSTI High Capacity Power Program builds on the technology efforts of the SP-100 program, incorporates the previous NASA SP-100 Advanced Technology project, and provides a bridge to NASA Project Pathfinder. The elements of CSTI High Capacity Power development include Conversion Systems, Thermal Management, Power Management, System Diagnostics, and Environmental Interactions. Technology advancement in all areas, including materials, is required to assure the high reliability and 7 to 10 year lifetime demanded for future space nuclear power systems. The overall program will develop and demonstrate the technology base required to provide a wide range of modular power systems as well as allowing mission independence from solar and orbital attitude requirements. Several recent advancements in CSTI High Capacity power development will be discussed.

  5. CSTI high capacity power

    SciTech Connect

    Winter, J.M.

    1994-09-01

    The SP-100 program was established in 1983 by DOD, DOE, and NASA as a joint program to develop the technology necessary for space nuclear power systems for military and civil application. During FY86 and 87, the NASA SP-100 Advanced Technology Program was devised to maintain the momentum of promising technology advancement efforts started during Phase I of SP-100 and to strengthen, in key areas, the chances for successful development and growth capability of space nuclear reactor power systems for future space applications. In FY88, the Advanced Technology Program was incorporated into NASA`s new Civil Space Technology Initiative (CSTI). The CSTI Program was established to provide the foundation for technology development in automation and robotics, information, propulsion, and power. The CSTI High Capacity Power Program builds on the technology efforts of the SP-100 program, incorporates the previous NASA SP-100 Advanced Technology project, and provides a bridge to NASA Project Pathfinder. The elements of CSTI High Capacity Power development include Conversion Systems, Thermal Management, Power Management, System Diagnostics, and Environmental Interactions. Technology advancement in all areas, including materials, is required to assure the high reliability and 7 to 10 year lifetime demanded for future space nuclear power systems. The overall program will develop and demonstrate the technology base required to provide a wide range of modular power systems as well as allowing mission independence from solar and orbital attitude requirements. Several recent advancements in CSTI High Capacity power development will be discussed.

  6. Dimethylfumarate Impairs Neutrophil Functions.

    PubMed

    Müller, Susen; Behnen, Martina; Bieber, Katja; Möller, Sonja; Hellberg, Lars; Witte, Mareike; Hänsel, Martin; Zillikens, Detlef; Solbach, Werner; Laskay, Tamás; Ludwig, Ralf J

    2016-01-01

    Host defense against pathogens relies on neutrophil activation. Inadequate neutrophil activation is often associated with chronic inflammatory diseases. Neutrophils also constitute a significant portion of infiltrating cells in chronic inflammatory diseases, for example, psoriasis and multiple sclerosis. Fumarates improve the latter diseases, which so far has been attributed to the effects on lymphocytes and dendritic cells. Here, we focused on the effects of dimethylfumarate (DMF) on neutrophils. In vitro, DMF inhibited neutrophil activation, including changes in surface marker expression, reactive oxygen species production, formation of neutrophil extracellular traps, and migration. Phagocytic ability and autoantibody-induced, neutrophil-dependent tissue injury ex vivo was also impaired by DMF. Regarding the mode of action, DMF modulates-in a stimulus-dependent manner-neutrophil activation using the phosphoinositide 3-kinase/Akt-p38 mitogen-activated protein kinase and extracellular signal-regulated kinase 1/2 pathways. For in vivo validation, mouse models of epidermolysis bullosa acquisita, an organ-specific autoimmune disease caused by autoantibodies to type VII collagen, were employed. In the presence of DMF, blistering induced by injection of anti-type VII collagen antibodies into mice was significantly impaired. DMF treatment of mice with clinically already-manifested epidermolysis bullosa acquisita led to disease improvement. Collectively, we demonstrate a profound inhibitory activity of DMF on neutrophil functions. These findings encourage wider use of DMF in patients with neutrophil-mediated diseases. PMID:26763431

  7. Specific language impairment.

    PubMed

    Kamhi, Alan G; Clark, Mary Kristen

    2013-01-01

    The acquisition of language is one of the most important achievements in young children, in part because most children appear to acquire language with little effort. Some children are not so fortunate, however. There is a large group of children who also have difficulty learning language, but do not have obvious neurological, cognitive, sensory, emotional, or environmental deficits. Clinicians often refer to these children as language disordered or language impaired. Researchers tend to refer to these children as specific language impaired (SLI). Children with SLI have intrigued researchers for many years because there is no obvious reason for their language learning difficulties. SLI has been found to be an enduring condition that begins in early childhood and often persists into adolescence and adulthood. The language problems of children with SLI are not limited to spoken language; they also affect reading and writing and thus much of academic learning. Knowledge of the characteristics of SLI should aid physicians, pediatricians, and early childhood specialists to identify these children during the preschool years and ensure that they receive appropriate services. With high-quality language intervention and literacy instruction, most children with SLI should be able to perform and function adequately in school and beyond. PMID:23622167

  8. Psychiatric Issues in Palliative Care: Assessing Mental Capacity

    PubMed Central

    Udo, Itoro; Mohammed, Zeid; Gash, Amanda

    2013-01-01

    Issues surrounding capacity to consent to or refuse treatment are increasingly receiving clinical and legal attention. Through the use of 3 case vignettes that involve different aspects of mental health care in palliative care settings, mental capacity issues are discussed. The vignettes tackle capacity in a patient with newly developed mental illness consequent to physical illness, capacity in a patient with mental illness but without delirium and capacity in a patient with known impairment of the mind. These discussions give credence to best practice position where physicians act in the best interests of their patients at all times. It is important to emphasize that capacity decisions have to be made on a case by case basis, within the remit of legal protection. This is a fundamental requirement of the Mental Capacity Act 2005, England & Wales (MCA). The later is used as the legal basis for these discussions. The psychiatric liaison service is a useful resource to provide consultation, advice and or joint assessment to clinicians encountering complex dilemmas involving decision-making capacity. PMID:25278761

  9. Surface retention capacity calculation

    NASA Astrophysics Data System (ADS)

    David, Vaclav; Dostal, Tomas

    2010-05-01

    Flood wave transformation in the floodplain is the phenomenon which is researched within interdisciplinary project NIVA - Water Retention in Floodplains and Possibilities of Retention Capacity Increase. The project focuses on broad range of floodplain ecosystem services and mitigation of flooding is one of them. Despite main influence on flood wave transformation is due to flow retardation, retention in surface depressions within floodplain has been analyzed to get better overview of whole transformation process. Detail digital relief model (DRM) has been used for given purposes to be able to analyze terrain depressions volumes. The model was developed with use of stereophotogrammetric evaluation of airborne images with high resolution of 10 cm. It was essential for purposes of presented analysis not to apply pit removal routines which are often used for generation of DRM for hydrological modelling purposes. First, the methodology of analysis was prepared and tested on artificial surface. This surface was created using random raster generation, filtration and resampling with final resolution of 1000 x 1000 units and height of maximum 10 units above datum. The methodology itself is based on analysis of areas inundated by water at different elevation levels. Volume is than calculated for each depression using extraction of terrain elevations under corresponding water level. The method was then applied on the area of Lužnice River floodplain section to assess retention capacity of real floodplain. The floodplain had to be cut into sections perpendicular to main river orientation for analyses as the method was tested for square shaped area without any significant inclination. Results obtained by mentioned analysis are presented in this paper. Acknowledgement Presented research was accomplished within national project NIVA - Water Retention in Floodplains and Possibilities of Retention Capacity Increase, nr. QH82078. The project is funded by Ministry of Agriculture of

  10. Vascular cognitive impairment and dementia.

    PubMed

    Gorelick, Philip B; Counts, Scott E; Nyenhuis, David

    2016-05-01

    Vascular contributions to cognitive impairment are receiving heightened attention as potentially modifiable factors for dementias of later life. These factors have now been linked not only to vascular cognitive disorders but also Alzheimer's disease. In this chapter we review 3 related topics that address vascular contributions to cognitive impairment: 1. vascular pathogenesis and mechanisms; 2. neuropsychological and neuroimaging phenotypic manifestations of cerebrovascular disease; and 3. prospects for prevention of cognitive impairment of later life based on cardiovascular and stroke risk modification. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock. PMID:26704177

  11. Impaired Verb Fluency: A Sign of Mild Cognitive Impairment

    ERIC Educational Resources Information Center

    Ostberg, Per; Fernaeus, Sven-Erik; Hellstrom, Ake; Bogdanovic, Nenad; Wahlund, Lars Olof

    2005-01-01

    We assessed verb fluency vs. noun and letter-based fluency in 199 subjects referred for cognitive complaints including Subjective Cognitive Impairment, Mild Cognitive Impairment, and Alzheimer's disease. ANCOVAs and factor analyses identified verb, noun, and letter-based fluency as distinct tasks. Verb fluency performance in Mild Cognitive…

  12. Early hominin auditory capacities.

    PubMed

    Quam, Rolf; Martínez, Ignacio; Rosa, Manuel; Bonmatí, Alejandro; Lorenzo, Carlos; de Ruiter, Darryl J; Moggi-Cecchi, Jacopo; Conde Valverde, Mercedes; Jarabo, Pilar; Menter, Colin G; Thackeray, J Francis; Arsuaga, Juan Luis

    2015-09-01

    Studies of sensory capacities in past life forms have offered new insights into their adaptations and lifeways. Audition is particularly amenable to study in fossils because it is strongly related to physical properties that can be approached through their skeletal structures. We have studied the anatomy of the outer and middle ear in the early hominin taxa Australopithecus africanus and Paranthropus robustus and estimated their auditory capacities. Compared with chimpanzees, the early hominin taxa are derived toward modern humans in their slightly shorter and wider external auditory canal, smaller tympanic membrane, and lower malleus/incus lever ratio, but they remain primitive in the small size of their stapes footplate. Compared with chimpanzees, both early hominin taxa show a heightened sensitivity to frequencies between 1.5 and 3.5 kHz and an occupied band of maximum sensitivity that is shifted toward slightly higher frequencies. The results have implications for sensory ecology and communication, and suggest that the early hominin auditory pattern may have facilitated an increased emphasis on short-range vocal communication in open habitats. PMID:26601261

  13. Albermarle boosts MASC capacity

    SciTech Connect

    D`Amico, E.

    1996-07-17

    Albemarle plans to triple capacity for methylaluminum sesquichloride (MASC) at its Houston complex. The move is in response to growing demand for aluminum alkyl catalyst systems, says Greg Lambeth, product manager/organometallics North America. MASC is the key raw material for trimethylaluminum (TMA), a Ziegler-Natta cocatalyst, and for methylaluminoxane (MAO), a cocatalyst for metallocene polyolefin catalysts. {open_quotes}This is a very competitive area because of the growing importance of metallocenes in polyolefin production,{close_quotes} Lambeth says. Several companies-including Exxon Chemical, Dow Chemical, and Hoechst - have invested in metallocene catalysts this year. Others have announced plans either to convert technology from conventional Ziegler-Natta catalyst systems or to build new facilities for metallocene catalyst production. Albemarle, the largest producer of TMA and other aluminum alkyls, completed a debottlenecking project in Houston earlier this year that increased its capacity 50%. The company also expects to complete a TMA expansion project at its Orangeburg, SC facility soon.

  14. Early hominin auditory capacities

    PubMed Central

    Quam, Rolf; Martínez, Ignacio; Rosa, Manuel; Bonmatí, Alejandro; Lorenzo, Carlos; de Ruiter, Darryl J.; Moggi-Cecchi, Jacopo; Conde Valverde, Mercedes; Jarabo, Pilar; Menter, Colin G.; Thackeray, J. Francis; Arsuaga, Juan Luis

    2015-01-01

    Studies of sensory capacities in past life forms have offered new insights into their adaptations and lifeways. Audition is particularly amenable to study in fossils because it is strongly related to physical properties that can be approached through their skeletal structures. We have studied the anatomy of the outer and middle ear in the early hominin taxa Australopithecus africanus and Paranthropus robustus and estimated their auditory capacities. Compared with chimpanzees, the early hominin taxa are derived toward modern humans in their slightly shorter and wider external auditory canal, smaller tympanic membrane, and lower malleus/incus lever ratio, but they remain primitive in the small size of their stapes footplate. Compared with chimpanzees, both early hominin taxa show a heightened sensitivity to frequencies between 1.5 and 3.5 kHz and an occupied band of maximum sensitivity that is shifted toward slightly higher frequencies. The results have implications for sensory ecology and communication, and suggest that the early hominin auditory pattern may have facilitated an increased emphasis on short-range vocal communication in open habitats. PMID:26601261

  15. Astrocytes Underlie Neuroinflammatory Memory Impairment.

    PubMed

    Osso, Lindsay A; Chan, Jonah R

    2015-12-17

    Neuroinflammation is being increasingly recognized as a potential mediator of cognitive impairments in various neurological conditions. Habbas et al. demonstrate that the pro-inflammatory cytokine tumor necrosis factor alpha signals through astrocytes to alter synaptic transmission and impair cognition in a mouse model of multiple sclerosis. PMID:26687350

  16. Toward the Neural Mechanisms of Reduced Working Memory Capacity in Schizophrenia

    PubMed Central

    Leonard, Carly J.; Kaiser, Sam T.; Robinson, Benjamin M.; Kappenman, Emily S.; Hahn, Britta; Gold, James M.; Luck, Steven J.

    2013-01-01

    People with schizophrenia (PSZ) demonstrate reliable reductions in working memory (WM) capacity (i.e., the number of objects that can be held in memory). The present study asked whether WM impairments in PSZ can be explained by the same neural mechanisms that underlie individual differences in WM capacity among healthy individuals. Specifically, we examined event-related potentials in PSZ and healthy matched controls during a change detection task that required the storage of multiple objects in WM. The amplitude of contralateral delay activity (CDA), which correlates with WM capacity in healthy individuals, was larger in controls than in PSZ for memory loads of 3 and 5 objects, but larger in PSZ than in controls for a memory load of 1. This same pattern was found in the subgroups of PSZ and controls with an equivalent WM capacity. Moreover, the increase in CDA amplitude was correlated with individual differences in capacity in controls, but not in PSZ. These results demonstrate that WM impairment in PSZ is not associated with the same patterns of neural activity that characterize low WM capacity in healthy individuals. We propose that WM impairment in PSZ instead reflects a specific impairment in the ability to distribute attention broadly. PMID:22661407

  17. [Cognitive impairment of alcohol-dependent subjects].

    PubMed

    Bernardin, Florent; Maheut-Bosser, Anne; Paille, François

    2014-04-01

    Chronic excessive alcohol consumption induces multiple brain damages. Secondary cognitive disorders include executive functions, episodic memory and visuospatial capacities. The severity of these alcohol induced disorders may vary between sub-clinical manifestations (that may, nevertheless, interfere with medical management) and more important ones like Korsakoff syndrome or dementia. The latter are usually irreversible but many of these manifestations are potentially reversible with persistent abstinence. It therefore appears of particular importance to clearly define neuropsychological management in order to identify and evaluate the type and severity of alcohol-related cognitive disorders. The patients may then be offered rehabilitation for these cognitive impairments. This is the first step of a complete addiction program based especially on cognitive behavioral therapies. PMID:24855773

  18. Development of Interleukin-12-Producing Capacity throughout Childhood

    PubMed Central

    Upham, John W.; Lee, Peter T.; Holt, Barbara J.; Heaton, Tricia; Prescott, Susan L.; Sharp, Mary J.; Sly, Peter D.; Holt, Patrick G.

    2002-01-01

    Increasing evidence indicates that the capacity to induce protective Th1 immune responses is impaired in early childhood, an observation that can be partially attributed to deficiencies in antigen-presenting-cell function. Synthesis of interleukin 12 (IL-12), a key Th1-trophic cytokine, is markedly reduced in the neonatal period, though there is a paucity of knowledge concerning the ontogeny of IL-12-synthetic capacity throughout the childhood years. Hence, we examined the production of bioactive IL-12 p70 by circulating mononuclear cells in a population of healthy individuals. As expected, the capacity to synthesize IL-12 p70 in response to either lipopolysaccharide or heat-killed Staphylococcus aureus was markedly impaired at birth, even after priming of cells with gamma interferon. Surprisingly however, IL-12 p70 synthesis by peripheral blood mononuclear cells from both 5- and 12-year-old children was still substantially below that seen in adults, and this did not appear to be related to excessive production of IL-10. In contrast, dendritic cells from adults and neonates, derived from monocytes with granulocyte-macrophage colony-stimulating factor and IL-4, synthesized equivalent amounts of IL-12 p70 in response to microbial stimulation. This indicates that the impaired capacity for IL-12 synthesis in childhood is not an intrinsic property of circulating mononuclear cells but rather can be readily overcome in response to appropriate maturational stimuli. Because IL-12 arose predominantly from circulating HLA-DR+ cells that lacked B-cell- and monocyte-specific markers, we propose that the slow maturation of IL-12-synthetic capacity in the childhood years can be attributed to deficiencies in the number and/or function of dendritic cells. PMID:12438328

  19. North American fertilizer capacity data

    SciTech Connect

    Not Available

    1991-01-01

    This listing of producers and their fertilizer production capacities was compiled in January 1991 with the cooperation of the US and Canadian fertilizer industry. Capacity is only an indicator of supply. Nameplate capacity differs from planned production levels or actual production because plants often operate above or below design capacity. Unless reported otherwise, plant capacities are based on 340 days per year of operation. No adjustment is made for partial year operation. Numerical data for the production of ammonia, ammonium nitrate, nitrogen solutions, urea, phosphate rock, phosphoric acid and ammonium phosphates is included.

  20. Resilience and vision impairment in older people.

    PubMed

    Thetford, Clare; Bennett, Kate M; Hodge, Suzanne; Knox, Paul C; Robinson, Jude

    2015-12-01

    Some people fare better than others when faced with adversity; they appear to be more 'resilient'. This article explores the concept of resilience in the context of vision impairment using two linked sets of narrative interview data from 2007 to 2010. Three case studies were analysed in detail using a framework approach based upon a social-ecological model of resilience and vision impairment. Within the model a range of assets and resources are identified which influence an individual's capacity for resilience. A set of criteria were used to establish the extent to which each individual appeared to be resilient at each point in time. Analysis revealed that it is not merely the presence or absence of individual, social, and community resources - but how these resources interact with each other - that influences resilience and can create a risk to wellbeing. To possess only some of these resources is not sufficient; there is a co-dependency between these resources which requires the presence of other resources for resilience to be achieved. Resilience is not a fixed state; individuals can become more or less resilient as their circumstances and resources change over time. We suggest that the concept of resilience has much to offer the field of vision impairment as it allows the identification of enablers as well as areas of barriers to improving people's health and wellbeing and suggests further opportunities for service providers to engage with clients, even those who appear to be supported, as people's social, economic and emotional landscapes continue to change over time, rather than identifying deficit. PMID:26568213

  1. Accurate perception of negative emotions predicts functional capacity in schizophrenia.

    PubMed

    Abram, Samantha V; Karpouzian, Tatiana M; Reilly, James L; Derntl, Birgit; Habel, Ute; Smith, Matthew J

    2014-04-30

    Several studies suggest facial affect perception (FAP) deficits in schizophrenia are linked to poorer social functioning. However, whether reduced functioning is associated with inaccurate perception of specific emotional valence or a global FAP impairment remains unclear. The present study examined whether impairment in the perception of specific emotional valences (positive, negative) and neutrality were uniquely associated with social functioning, using a multimodal social functioning battery. A sample of 59 individuals with schizophrenia and 41 controls completed a computerized FAP task, and measures of functional capacity, social competence, and social attainment. Participants also underwent neuropsychological testing and symptom assessment. Regression analyses revealed that only accurately perceiving negative emotions explained significant variance (7.9%) in functional capacity after accounting for neurocognitive function and symptoms. Partial correlations indicated that accurately perceiving anger, in particular, was positively correlated with functional capacity. FAP for positive, negative, or neutral emotions were not related to social competence or social attainment. Our findings were consistent with prior literature suggesting negative emotions are related to functional capacity in schizophrenia. Furthermore, the observed relationship between perceiving anger and performance of everyday living skills is novel and warrants further exploration. PMID:24524947

  2. High capacity oil burner

    SciTech Connect

    Pedrosa, O.A. Jr.; Couto, N.C.; Fanqueiro, R.C.C.

    1983-11-01

    The present invention relates to a high capacity oil burner comprising a cylindrical atomizer completely surrounded by a protective cylindrical housing having a diameter from 2 to 3 times greater than the diameter of said atomizer; liquid fuels being injected under pressure into said atomizer and accumulating within said atomizer in a chamber for the accumulation of liquid fuels, and compressed air being injected into a chamber for the accumulation of air; cylindrical holes communicating said chamber for the accumulation of liquid fuels with the outside and cylindrical holes communicating said chamber for the accumulation of air with said cylindrical holes communicating the chamber for the accumulation of liquids with the outside so that the injection of compressed air into said liquid fuel discharge holes atomizes said fuel which is expelled to the outside through the end portions of said discharge holes which are circumferentially positioned to be burnt by a pilot flame; said protecting cylindrical housing having at its ends perforated circular rings into which water is injected under pressure to form a protecting fan-like water curtain at the rear end of the housing and a fan-like water curtain at the flame to reduce the formation of soot; the burning efficiency of said burner being superior to 30 barrels of liquid fuel per day/kg of the apparatus.

  3. First mideast capacity planned

    SciTech Connect

    Fattah, H.

    1996-11-06

    Kuwait catalyst Co.`s (KCC) plans to build a hydrodesulfurization (HDS) catalysts plant in Kuwait will mark the startup of the first refining catalysts production in the Persian Gulf region. KCC, owned by a conglomerate of Kuwait companies and governmental agencies, has licensed catalyst manufacturing technology from Japan Energy in a deal estimated at more than 7 billion ($62 million). Plant design will be based on technology from Orient Catalyst, Japan Energy`s catalysts division. Construction is expected to begin in January 1997 for production startup by January 1998. A source close to the deal says the new plant will eventually reach a capacity of 5,000 m.t./year of HDS catalysts to supply most of Kuwait`s estimated 3,500-m.t./year demand, driven primarily by Kuwait National Petroleum refineries. KCC also expects to supply demand from other catalyst consumers in the region. Alumina supply will be acquired on the open market. KCC will take all production from the plant and will be responsible for marketing.

  4. Advanced work capacity testing.

    PubMed

    Bretz, Károly J; Dános, László; Smudla, Szilvia; Pálosi, Adrienn

    2015-01-01

    The aim of this study is to describe an accurate work capacity testing which can be used in the industry, as well as in rehabilitation process. The first part of this paper is dealing with the NIOSH lifting equation, which is a tool used by occupational health and safety professionals. The second part of this paper summarizes the features and applications of the "ErgoScope" work simulator. Static and dynamic strength of upper and lower limbs, as well as whole body efforts can be measured. The equipment makes it possible to evaluate pushing, pulling, lifting and carrying activities comprising reaching, bending and stooping movements. In the third part of this paper we demonstrate handgrip force data recorded using the "ErgoScope" work simulator comparing with handgrip force data published in the literature. "ErgoScope" work simulator is capable to measure handgrip and pinch forces, suitable to evaluate fine motor skills, hand and finger dexterity, as well as reaction times. PMID:26294589

  5. Specific Language Impairment in Families: Evidence for Co-Occurrence with Reading Impairments.

    ERIC Educational Resources Information Center

    Flax, Judy F.; Realpe-Bonilla, Teresa; Hirsch, Linda S.; Brzustowicz, Linda M.; Bartlett, Christopher W.; Tallal, Paula

    2003-01-01

    Two family aggregation studies involving 25 children (ages 5-10) with specific language impairment (SLI) report the occurrence and co-occurrence of oral language impairments and reading impairments. Results indicate that when language impairments occur within families of SLI probands, these impairments generally co-occur with reading impairments.…

  6. Psychiatric Issues in Cognitive Impairment

    PubMed Central

    Aarsland, Dag; Taylor, John-Paul; Weintraub, Daniel

    2015-01-01

    Neuropsychiatric symptoms (NPS) such as depression, hallucinations and apathy commonly occur in Parkinson’s disease (PD) and have major clinical consequences including a negative impact on quality of life. This review discusses the epidemiology, clinical features, diagnostic procedures and treatment issues of NPS in PD and related disorders in the perspective of cognitive impairment, focusing on depression, anxiety, visual hallucinations, apathy, sleep disturbances, impulse control disorder and non-motor fluctuations. The majority of NPS are more common in PD patients with dementia, possibly related to shared underlying pathologies. Recent studies also suggest that NPS are associated with mild cognitive impairment in PD, in particular with the amnestic type. Accurate diagnosis of NPS is important but can be difficult, due to overlapping symptoms and similar appearance of symptoms of motor symptoms of parkinsonism, cognitive impairment, mood disorders and apathy. There are few systematic studies focusing on the management of NPS in PD with cognitive impairment. PMID:24757113

  7. [Cognitive Impairment in Multiple Sclerosis].

    PubMed

    Niino, Masaaki; Miyazaki, Yusei

    2016-04-01

    While cognitive impairment is a major symptom of multiple sclerosis (MS), it is commonly overlooked. This may be explained by the fact that it is difficult to evaluate cognitive function in patients with MS using screening batteries for the detection of dementia such as the mini-mental state examination. Further more, cognitive impairment in MS typically involves domain-specific deficits such as imparement of sustained attention and information processing speed rather than global cognitive decline. Cognitive impairment may influence the daily living and social lines of affected patients. This review discusses the characteristics of cognitive impairment, appropreate tests to evaluate its symptoms, and the current status of clinical trials for the treatment of MS. PMID:27056855

  8. [Drug-induced Cognitive Impairment].

    PubMed

    Shinohara, Moeko; Yamada, Masahito

    2016-04-01

    Elderly people are more likely than young people to develop cognitive impairments associated with medication use. One of the reasons for this is that renal and liver functions are often impaired in elderly people. Dementia and delirium (an acute confused state) are known to be associated with drug toxicity. Anticholinergic medications are common causes of both acute and chronic cognitive impairment. Psychoactive drugs, antidepressants and anticonvulsants can cause dementia and delirium. In addition, non-psychoactive drugs such as histamine H2 receptor antagonists, corticosteroids, NSAIDs (nonsteroidal anti-inflammatory agent), and cardiac medications, may cause acute or chronic cognitive impairment. Early diagnosis and withdrawal of the offending agent are essential for the prevention of drug-induced dementia and delirium. PMID:27056860

  9. Bioethics for clinicians: 3. Capacity.

    PubMed Central

    Etchells, E; Sharpe, G; Elliott, C; Singer, P A

    1996-01-01

    In the context of patient consent, "capacity" refers to the patient's ability to understand information relevant to a treatment decision and to appreciate the reasonably foreseeable consequences of a decision or lack of decision. A person may be "capable" with respect to one decision but not with respect to another. Clinicians can usually identify patients who are clearly capable or incapable, but in some cases a clinical capacity assessment is required. Such assessment may consist of cognitive status testing, general impressions of capacity or specific capacity assessment. Specific capacity assessment, in which the clinician evaluates the patient's ability to understand pertinent information and appreciate its implications, is probably the optimal method. When conducting a specific capacity assessment, the clinician must ensure that the disclosure of information is effective and must evaluate the patient's reason for his or her decision. If the assessment suggests that the patient is incapable, further assessment is generally recommended. PMID:8823211

  10. Age-dependent capacity to accelerate protein synthesis dictates the extent of compensatory growth in skeletal muscle following undernutrition

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In both humans and animals, impaired growth during early life compromises adult lean body mass and muscle strength despite skeletal muscle’s large regenerative capacity. To identify the significance of developmental age on skeletal muscle’s capacity for catch-up growth following an episode of under ...

  11. Premenstrual changes. Impaired hormonal homeostasis.

    PubMed

    Halbreich, U; Alt, I H; Paul, L

    1988-03-01

    Premenstrual changes (PMCs) in mood and behavior are very prevalent. Nonetheless, their pathophysiology is still obscure and no proven treatment is yet available. Evaluation of the plethora of available data leads to the suggestion that PMCs may result from a temporary impairment of homeostasis among a multitude of systems. This impairment is triggered by a differential pace and magnitude of change-over-time in levels of several hormones and other substances during the luteal phase. PMID:3288473

  12. Chemistry for the Visually Impaired

    NASA Astrophysics Data System (ADS)

    Ratliff, Judy L.

    1997-06-01

    Methods used to try to provide a valuable experience for visually impaired students in a general education or an introductory chemistry class are discussed. Modifications that can be made cheaply and with little time commitment which will allow visually impaired students to participate productively in the laboratory are examined. A conductivity tester that cost less than $4.00 to construct, is easy to assemble, very rugged, and provides a great deal of entertainment for sighted and non-sighted students is described.

  13. CHP Installed Capacity Optimizer Software

    Energy Science and Technology Software Center (ESTSC)

    2004-11-30

    The CHP Installed Capacity Optimizer is a Microsoft Excel spreadsheet application that determines the most economic amount of capacity of distributed generation and thermal utilization equipment (e.g., absorption chillers) to install for any user-defined set of load and cost data. Installing the optimum amount of capacity is critical to the life-cycle economic viability of a distributed generation/cooling heat and power (CHP) application. Using advanced optimization algorithms, the software accesses the loads, utility tariffs, equipment costs,more » etc., and provides to the user the most economic amount of system capacity to install.« less

  14. CHP Installed Capacity Optimizer Software

    SciTech Connect

    2004-11-30

    The CHP Installed Capacity Optimizer is a Microsoft Excel spreadsheet application that determines the most economic amount of capacity of distributed generation and thermal utilization equipment (e.g., absorption chillers) to install for any user-defined set of load and cost data. Installing the optimum amount of capacity is critical to the life-cycle economic viability of a distributed generation/cooling heat and power (CHP) application. Using advanced optimization algorithms, the software accesses the loads, utility tariffs, equipment costs, etc., and provides to the user the most economic amount of system capacity to install.

  15. Adaptive capacity and its assessment

    SciTech Connect

    Engle, Nathan L.

    2011-04-20

    This paper reviews the concept of adaptive capacity and various approaches to assessing it, particularly with respect to climate variability and change. I find that adaptive capacity is a relatively under-researched topic within the sustainability science and global change communities, particularly since it is uniquely positioned to improve linkages between vulnerability and resilience research. I identify opportunities for advancing the measurement and characterization of adaptive capacity by combining insights from both vulnerability and resilience frameworks, and I suggest several assessment approaches for possible future development that draw from both frameworks and focus on analyzing the governance, institutions, and management that have helped foster adaptive capacity in light of recent climatic events.

  16. The Capacity to Build Organizational Capacity in Schools

    ERIC Educational Resources Information Center

    King, M. Bruce; Bouchard, Kate

    2011-01-01

    Purpose: Reformers, policymakers, and researchers have given considerable attention to organizational capacity in schools, especially in those schools that perpetuate or exacerbate achievement gaps among diverse student groups and reproduce social inequalities. There is an emerging consensus about key dimensions of school capacity and how they can…

  17. Dystypia: isolated typing impairment without aphasia, apraxia or visuospatial impairment.

    PubMed

    Otsuki, Mika; Soma, Yoshiaki; Arihiro, Shoji; Watanabe, Yoshimasa; Moriwaki, Hiroshi; Naritomi, Hiroaki

    2002-01-01

    We report a 60-year-old right-handed Japanese man who showed an isolated persistent typing impairment without aphasia, agraphia, apraxia or any other neuropsychological deficit. We coined the term 'dystypia' for this peculiar neuropsychological manifestation. The symptom was caused by an infarction in the left frontal lobe involving the foot of the second frontal convolution and the frontal operculum. The patient's typing impairment was not attributable to a disturbance of the linguistic process, since he had no aphasia or agraphia. The impairment was not attributable to the impairment of the motor execution process either, since he had no apraxia. Thus, his typing impairment was deduced to be based on a disturbance of the intermediate process where the linguistic phonological information is converted into the corresponding performance. We hypothesized that there is a specific process for typing which branches from the motor programming process presented in neurolinguistic models. The foot of the left second frontal convolution and the operculum may play an important role in the manifestation of 'dystypia'. PMID:11914550

  18. Building Organizational Capacity through Trust

    ERIC Educational Resources Information Center

    Cosner, Shelby

    2009-01-01

    This article explores the cultivation of collegial trust as a central feature of the capacity-building work of 11 high school principals, nominated for their expertise with capacity building. This qualitative study examined interview data and school documents collected over 18 months. Principals regarded trust as critical and were motivated to…

  19. Enrollment Capacity and Technology Study

    ERIC Educational Resources Information Center

    Washington Higher Education Coordinating Board, 2008

    2008-01-01

    The 2007-09 Appropriations Act provided funding to the Higher Education Coordinating Board (HECB) to study the state's capital facility and technology capacity. Specifically, "...state appropriation is provided solely to implement a capital facility and technology capacity study which will compare the 10-year enrollment projections with the…

  20. Measuring Capacities for Community Resilience

    ERIC Educational Resources Information Center

    Sherrieb, Kathleen; Norris, Fran H.; Galea, Sandro

    2010-01-01

    The purpose of this study was to measure the sets of adaptive capacities for Economic Development and Social Capital in the Norris et al. (2008) community resilience model with publicly accessible population indicators. Our approach involved five steps. First, we conducted a literature review on measurements of the capacities. Second, we created…

  1. Heat capacity, configurational heat capacity and fragility of hydrous magmas

    NASA Astrophysics Data System (ADS)

    Di Genova, D.; Romano, C.; Giordano, D.; Alletti, M.

    2014-10-01

    The glassy and liquid heat capacities of four series of dry and hydrous natural glasses and magma as a function of temperature and water content (up to 19.9 mol%) were investigated using differential scanning calorimetry (DSC). The analyzed compositions are basalt, latite, trachyte and pantellerite. The results of this study indicate that the measured heat capacity of glasses (Cpg) is a linear function of composition and is well reproduced by the empirical model of Richet (1987). For the investigated glasses, the partial molar heat capacity of water can be considered as independent of composition, in agreement with Bouhifd et al. (2006). For hydrous liquids, the heat capacity (Cpliq) decreases nonlinearly with increasing water content. Previously published models, combined with the partial molar heat capacity of water from the literature, are not able to reproduce our experimental data in a satisfactory way. We estimated the partial molar heat capacity of water (CpH2O) in hydrous magma over a broad compositional range. The proposed value is 41 ± 3 J mol-1 K-1. Water strongly affects the configurational heat capacity at the glass transition temperature [Cpconf (Tg)]. An increases of Cpconf (Tg) with water content was measured for the polymerized liquids (trachyte and pantellerite), while the opposite behavior was observed for the most depolymerized liquids (basalt and latite). Structural and rheological implications of this behavior are discussed in light of the presented results.

  2. North American fertilizer capacity data

    SciTech Connect

    Not Available

    1993-02-01

    This listing of fertilizer producers and their production capacities was compiled in February 1993 with the cooperation of the US and Canadian fertilizer industry. TVA does not guarantee the completeness or accuracy of the information. Capacity is only an indicator of supply. Nameplate capacity differs from planned production levels or actual production because plants often operate above or below design capacity. Unless reported otherwise, plant capacities are based on 340 days per year of operation. No adjustment is made for partial year operation. Information is given on the following types of fertilizers: ammonia, ammonium nitrate, nitrogen solutions, urea, ammonium sulfate, phosphate rock, wet-process phosphoric acid, ammonium phosphates, concentrated superphosphates, potash, nitric acid, superphosphoric acid, upgraded phosphoric acids, normal superphosphate, elemental phosphorus, potassium sulfate, and sulfate of potash/magnesia.

  3. Heat capacity of molten halides.

    PubMed

    Redkin, Alexander A; Zaikov, Yurii P; Korzun, Iraida V; Reznitskikh, Olga G; Yaroslavtseva, Tatiana V; Kumkov, Sergey I

    2015-01-15

    The heat capacities of molten salts are very important for their practical use. Experimental investigation of this property is challenging because of the high temperatures involved and the corrosive nature of these materials. It is preferable to combine experimental investigations with empirical relationships, which allows for the evaluation of the heat capacity of molten salt mixtures. The isobaric molar heat capacities of all molten alkali and alkaline-earth halides were found to be constant for each group of salts. The value depends on the number of atoms in the salt, and the molar heat capacity per atom is constant for all molten halide salts with the exception of the lithium halides. The molar heat capacities of molten halides do not change when the anions are changed. PMID:25530462

  4. Alternative neural circuitry that might be impaired in the development of Alzheimer disease

    PubMed Central

    Avila, Jesus; Perry, George; Strange, Bryan A.; Hernandez, Felix

    2015-01-01

    It is well established that some individuals with normal cognitive capacity have abundant senile plaques in their brains. It has been proposed that those individuals are resilient or have compensation factors to prevent cognitive decline. In this comment, we explore an alternative mechanism through which cognitive capacity is maintained. This mechanism could involve the impairment of alternative neural circuitry. Also, the proportion of molecules such as Aβ or tau protein present in different areas of the brain could be important. PMID:25954151

  5. Workload capacity spaces: a unified methodology for response time measures of efficiency as workload is varied.

    PubMed

    Townsend, James T; Eidels, Ami

    2011-08-01

    Increasing the number of available sources of information may impair or facilitate performance, depending on the capacity of the processing system. Tests performed on response time distributions are proving to be useful tools in determining the workload capacity (as well as other properties) of cognitive systems. In this article, we develop a framework and relevant mathematical formulae that represent different capacity assays (Miller's race model bound, Grice's bound, and Townsend's capacity coefficient) in the same space. The new space allows a direct comparison between the distinct bounds and the capacity coefficient values and helps explicate the relationships among the different measures. An analogous common space is proposed for the AND paradigm, relating the capacity index to the Colonius-Vorberg bounds. We illustrate the effectiveness of the unified spaces by presenting data from two simulated models (standard parallel, coactive) and a prototypical visual detection experiment. A conversion table for the unified spaces is provided. PMID:21607804

  6. 20 CFR 404.1598 - If you become disabled by another impairment(s).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false If you become disabled by another impairment... Disability § 404.1598 If you become disabled by another impairment(s). If a new severe impairment(s) begins... are still disabled under § 404.1594....

  7. 20 CFR 404.1598 - If you become disabled by another impairment(s).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false If you become disabled by another impairment... Disability § 404.1598 If you become disabled by another impairment(s). If a new severe impairment(s) begins... are still disabled under § 404.1594....

  8. 20 CFR 404.1598 - If you become disabled by another impairment(s).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 2 2013-04-01 2013-04-01 false If you become disabled by another impairment... Disability § 404.1598 If you become disabled by another impairment(s). If a new severe impairment(s) begins... are still disabled under § 404.1594....

  9. 20 CFR 404.1598 - If you become disabled by another impairment(s).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 2 2012-04-01 2012-04-01 false If you become disabled by another impairment... Disability § 404.1598 If you become disabled by another impairment(s). If a new severe impairment(s) begins... are still disabled under § 404.1594....

  10. 20 CFR 404.1598 - If you become disabled by another impairment(s).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 2 2014-04-01 2014-04-01 false If you become disabled by another impairment... Disability § 404.1598 If you become disabled by another impairment(s). If a new severe impairment(s) begins... are still disabled under § 404.1594....

  11. Lacking power impairs executive functions.

    PubMed

    Smith, Pamela K; Jostmann, Nils B; Galinsky, Adam D; van Dijk, Wilco W

    2008-05-01

    Four experiments explored whether lacking power impairs executive functioning, testing the hypothesis that the cognitive presses of powerlessness increase vulnerability to performance decrements during complex executive tasks. In the first three experiments, low power impaired performance on executive-function tasks: The powerless were less effective than the powerful at updating (Experiment 1), inhibiting (Experiment 2), and planning (Experiment 3). Existing research suggests that the powerless have difficulty distinguishing between what is goal relevant and what is goal irrelevant in the environment. A fourth experiment established that the executive-function impairment associated with low power is driven by goal neglect. The current research implies that the cognitive alterations arising from powerlessness may help foster stable social hierarchies and that empowering employees may reduce costly organizational errors. PMID:18466404

  12. Legal capacity of the elderly in Greece.

    PubMed

    Giannouli, Vaitsa; Tsolaki, Magda

    2014-01-01

    Legal capacity of the elderly people in Greece is of great legal, medical and social importance, but has received little attention till now from medical literature. This paper aims to study whether elderly people with dementia are able to participate in legal contracts like sales, purchases, loans, leases, donations and testaments. We tried to introduce a new test for the above legal-financial contracts and show some preliminary findings. The test consists of six examined relevant domains concerning basic monetary skills, cash transactions, bank statement management, financial conceptual knowledge, knowledge of potential heirs (beneficiaries) and assets/estate and finally the decision making process for different dilemmas on sales, purchases, loans, leases, donations and testaments. We studied 203 people. Eighty three people were healthy, 64 with Alzheimer's disease (AD) (10 with severe AD, 22 with moderate, and 32 with mild AD), 10 with Parkinson's disease (PD), and 46 with amnestic Mild Cognitive Impairment (aMCI). Individuals were included in the study only if they were aged 60 and over and only if they had a partner or a guardian who could give information on the individual's daily living. The exclusion criteria were predefined as follows: history of any other mental health disease and/or any other serious somatic health disease except for their official diagnosis of dementia. Results showed statistically significant differences with all three groups of patients characterized as incapable for legal-financial actions. Patients with severe AD (P<0.001), patients with moderate AD (P<0.001), patients with mild AD (P<0.001), patients with PD (P<0.001) and aMCI patients (P<0.001) differed significantly from healthy controls. Further research should include more extensive sampling of elderly patients with varying demographic characteristics in Greece, to confirm and expand our initial findings. In conclusion, our new test which is based on Marson's theoretical model

  13. The effects of sleep loss on capacity and effort

    PubMed Central

    Engle-Friedman, Mindy

    2014-01-01

    Sleep loss appears to affect the capacity for performance and access to energetic resources. This paper reviews research examining the physical substrates referred to as resource capacity, the role of sleep in protecting that capacity and the reaction of the system as it attempts to respond with effort to overcome the limitations on capacity caused by sleep loss. Effort is the extent to which an organism will exert itself beyond basic levels of functioning or attempt alternative strategies to maintain performance. The purpose of this review is to bring together research across sleep disciplines to clarify the substrates that constitute and influence capacity for performance, consider how the loss of sleep influences access to those resources, examine cortical, physiological, perceptual, behavioral and subjective effort responses and consider how these responses reflect a system reacting to changes in the resource environment. When sleep deprived, the ability to perform tasks that require additional energy is impaired and the ability of the system to overcome the deficiencies caused by sleep loss is limited. Taking on tasks that require effort including school work, meal preparation, pulling off the road to nap when driving drowsy appear to be more challenging during sleep loss. Sleep loss impacts the effort-related choices we make and those choices may influence our health and safety. PMID:26483932

  14. The effects of sleep loss on capacity and effort.

    PubMed

    Engle-Friedman, Mindy

    2014-12-01

    Sleep loss appears to affect the capacity for performance and access to energetic resources. This paper reviews research examining the physical substrates referred to as resource capacity, the role of sleep in protecting that capacity and the reaction of the system as it attempts to respond with effort to overcome the limitations on capacity caused by sleep loss. Effort is the extent to which an organism will exert itself beyond basic levels of functioning or attempt alternative strategies to maintain performance. The purpose of this review is to bring together research across sleep disciplines to clarify the substrates that constitute and influence capacity for performance, consider how the loss of sleep influences access to those resources, examine cortical, physiological, perceptual, behavioral and subjective effort responses and consider how these responses reflect a system reacting to changes in the resource environment. When sleep deprived, the ability to perform tasks that require additional energy is impaired and the ability of the system to overcome the deficiencies caused by sleep loss is limited. Taking on tasks that require effort including school work, meal preparation, pulling off the road to nap when driving drowsy appear to be more challenging during sleep loss. Sleep loss impacts the effort-related choices we make and those choices may influence our health and safety. PMID:26483932

  15. Zymosan-mediated inflammation impairs in vivo reverse cholesterol transport.

    PubMed

    Malik, Priya; Berisha, Stela Z; Santore, Jennifer; Agatisa-Boyle, Colin; Brubaker, Gregory; Smith, Jonathan D

    2011-05-01

    Inflammation has been proposed to impair HDL function and reverse cholesterol transport (RCT). We investigated the effects of inflammation mediated by zymosan, a yeast glucan, on multiple steps along the RCT pathway in vivo and ex vivo. Acute inflammation with 70 mg/kg zymosan impaired RCT to plasma, liver, and feces similarly by 17-22% (P < 0.05), with no additional block at the liver. Hepatic gene expression further demonstrated no change in ABCG5, ABCB4, and ABCB11 expression but a decline in ABCG8 mRNA (32% P < 0.05). Plasma from zymosan-treated mice had a 21% decrease in cholesterol acceptor ability (P < 0.01) and a 35% decrease in ABCA1-specific efflux capacity (P < 0.01) in vitro. Zymosan treatment also decreased HDL levels and led to HDL remodeling with increased incorporation of serum amyloid A. In addition, cholesterol efflux from cultured macrophages declined with zymosan treatment in a dose dependent manner. Taken together, our results suggest that zymosan impairs in vivo RCT primarily by decreasing macrophage-derived cholesterol entering the plasma, with minimal additional blocks downstream. Our study supports the notion that RCT impairment is one of the mechanisms for the increased atherosclerotic burden observed in inflammatory conditions. PMID:21335620

  16. Neuropsychological impairments in anorexia nervosa: a spanish sample pilot study.

    PubMed

    Oltra-Cucarella, Javier; Espert, Raul; Rojo, Luís; Jacas, Carlos; Guillén, Verónica; Moreno, Sergio

    2014-01-01

    This work was aimed at obtaining a profile of neuropsychological impairments in young Spanish participants with anorexia nervosa (AN) to demonstrate that right-hemisphere and frontal capacity impairments are present not only in the acute phase but also after weight recovery in a Spanish sample compared with a healthy control group. Twelve patients with AN in the acute phase (body mass index [BMI] < 17) were compared both to 16 healthy control subjects and 12 weight-recovered AN participants (BMI ≥ 17) matched by age, IQ, and educational level by utilizing a wide neuropsychological battery. Differences were found between AN groups only for long-term verbal memory, which worsens as BMI increases. Among participants with AN as a group, results showed differences in speed of information processing, working memory, visual memory, and inhibition, unrelated to attentional capabilities. We cannot support the hypothesis of a specific right cerebral dysfunction in patients with AN. A general cognitive dysfunction, primarily in information processing, working memory, visual and verbal memory, as well as frontal impairments such as impulsivity and poor behavioral control, appeared unrelated to BMI. We support previous works affirming that neuropsychological impairments in AN are not a consequence of the illness but a risk factor for it to develop. PMID:25084841

  17. Vascular contributions to cognitive impairment

    PubMed Central

    Flores, Alan

    2015-01-01

    Summary Unlike many neurodegenerative causes of cognitive impairment and dementia, vascular damage is preventable. Despite the heterogeneity of vascular cognitive impairment (VCI) and the complexity of its clinical presentations, the potential for limiting progression and changing the trajectory of damage makes it all the more important for physicians to be educated about the syndrome and to remain vigilant when taking care of patients. In this review, we outline an approach to patients with possible VCI, summarize current treatment and prevention guidelines, and provide an overview with case examples. PMID:26124978

  18. Visitation arrangements for impaired parents.

    PubMed

    Montgomery, Stephen A; Street, David F

    2011-07-01

    Forensic mental health professionals are frequently asked to evaluate the parenting skills of divorcing parents because the court seeks help in determining the custody, visitation, and parenting time arrangements for the children. When one of the parents is impaired, the court wants to know the way to help the children have a good relationship with that parent and keep the children safe. There is little empirical research to answer such questions. In this article, the authors describe their methodology for providing useful clinical information to the court to help guide their decisions regarding visitation with impaired parents. PMID:21683915

  19. Driver Compensation: Impairment or Improvement?

    PubMed

    Young, Richard A

    2015-12-01

    Strayer et al.'s conclusion that their "cognitive distraction scale" for auditory-vocal tasks indicates "significant impairments to driving" is not supported by their data. Additional analysis demonstrates that slower brake reaction times during auditory-vocal tasks were fully compensated for by longer following distances to the lead car. Naturalistic driving data demonstrate that cellular conversation decreases crash risk, the opposite of the article's assumption. Hence, the scale's internal and external validities for indicating driving impairment are highly questionable. PMID:26534851

  20. Bilateral common carotid artery stenosis in normotensive rats impairs endothelium-dependent dilation of parenchymal arterioles.

    PubMed

    Matin, Nusrat; Fisher, Courtney; Jackson, William F; Dorrance, Anne M

    2016-05-15

    Chronic cerebral hypoperfusion is a risk factor for cognitive impairment. Reduced blood flow through the common carotid arteries induced by bilateral carotid artery stenosis (BCAS) is a physiologically relevant model of chronic cerebral hypoperfusion. We hypothesized that BCAS in 20-wk-old Wistar-Kyoto (WKY) rats would impair cognitive function and lead to reduced endothelium-dependent dilation and outward remodeling in the parenchymal arterioles (PAs). After 8 wk of BCAS, both short-term memory and spatial discrimination abilities were impaired. In vivo assessment of cerebrovascular reserve capacity showed a severe impairment after BCAS. PA endothelial function and structure were assessed by pressure myography. BCAS impaired endothelial function in PAs, as evidenced by reduced dilation to carbachol. Addition of nitric oxide synthase and cyclooxygenase inhibitors did not change carbachol-mediated dilation in either group. Inhibiting CYP epoxygenase, the enzyme that produces epoxyeicosatrienoic acid (EETs), a key determinant of endothelium-derived hyperpolarizing factor (EDHF)-mediated dilation, abolished dilation in PAs from Sham rats, but had no effect in PAs from BCAS rats. Expression of TRPV4 channels, a target for EETs, was decreased and maximal dilation to a TRPV4 agonist was attenuated after BCAS. Together these data suggest that EET-mediated dilation is impaired in PAs after BCAS. Thus impaired endothelium-dependent dilation in the PAs may be one of the contributing factors to the cognitive impairment observed after BCAS. PMID:26968546

  1. Physical impairment aware transparent optical networks

    NASA Astrophysics Data System (ADS)

    Antona, Jean-Christophe; Morea, Annalisa; Zami, Thierry; Leplingard, Florence

    2009-11-01

    As illustrated by optical fiber and optical amplification, optical telecommunications have appeared for the last ten years as one of the most promising candidates to increase the transmission capacities. More recently, the concept of optical transparency has been investigated and introduced: it consists of the optical routing of Wavelength Division Multiplexed (WDM) channels without systematic optoelectronic processing at nodes, as long as propagation impairments remain acceptable [1]. This allows achieving less power-consuming, more scalable and flexible networks, and today partial optical transparency has become a reality in deployed systems. However, because of the evolution of traffic features, optical networks are facing new challenges such as demand for higher transmitted capacity, further upgradeability, and more automation. Making all these evolutions compliant on the same current network infrastructure with a minimum of upgrades is one of the main issues for equipment vendors and operators. Hence, an automatic and efficient management of the network needs a control plan aware of the expected Quality of Transmission (QoT) of the connections to set-up with respect to numerous parameters such as: the services demanded by the customers in terms of protection/restoration; the modulation rate and format of the connection under test and also of its adjacent WDM channels; the engineering rules of the network elements traversed with an accurate knowledge of the associated physical impairments. Whatever the method and/or the technology used to collect this information, the issue about its accuracy is one of the main concerns of the network system vendors, because an inaccurate knowledge could yield a sub-optimal dimensioning and so additional costs when installing the network in the field. Previous studies [1], [2] illustrated the impact of this knowledge accuracy on the ability to predict the connection feasibility. After describing usual methods to build

  2. Human Impairment from Living near Confined Animal (Hog) Feeding Operations

    PubMed Central

    Kilburn, Kaye H.

    2012-01-01

    Problem. To determine whether neighbors around manure lagoons and massive hog confinement buildings who complained of offensive odors and symptoms had impaired brain and lung functions. Method. We compared near hog manure neighbors of lagoons to people living beyond 3 kilometers in Ohio and to unexposed people controls in a nearby state for neurophysiological, cognitive, recall and memory functions, and pulmonary performance. Results. The 25 exposed subjects averaged 4.3 neurobehavioral abnormalities, significantly different from 2.5 for local controls and 2.3 for Tennessee controls. Exposed subjects mean forced vital capacity and expiratory volume in 1 sec were reduced significantly compared to local and regional controls. Conclusions. Near neighbors of hog enclosures and manure lagoon gases had impaired neurobehavioral functions and pulmonary functions and these effects extended to nearby people thought to be controls. Hydrogen sulfide must be abated because people living near lagoons cannot avoid rotten egg gas. PMID:22496706

  3. Mental juggling: when does multitasking impair reading comprehension?

    PubMed

    Cho, Kit W; Altarriba, Jeanette; Popiel, Maximilian

    2015-01-01

    The present study investigated the conditions under which multitasking impairs reading comprehension. Participants read prose passages (the primary task), some of which required them to perform a secondary task. In Experiment 1, we compared two different types of secondary tasks (answering trivia questions and solving math problems). Reading comprehension was assessed using a multiple-choice test that measured both factual and conceptual knowledge. The results showed no observable detrimental effects associated with multitasking. In Experiment 2, the secondary task was a cognitive load task that required participants to remember a string of numbers while reading the passages. Performance on the reading comprehension test was lower in the cognitive load conditions relative to the no-load condition. The present study delineates the conditions under which multitasking can impair or have no effect on reading comprehension. These results further our understanding of our capacity to multitask and have practical implications in our technologically advanced society in which multitasking has become commonplace. PMID:25832739

  4. The diffusing capacity in adult cystic fibrosis.

    PubMed

    Espiritu, J D; Ruppel, G; Shrestha, Y; Kleinhenz, M E

    2003-06-01

    The value of adjusting the diffusing capacity for the lung volume has been demonstrated in a large number of patients with other lung diseases but has not been validated in patients with cystic fibrosis (CF). Pulmonary function test results on a cohort of 52 adult CF patients were analyzed to determine whether the diffusing capacity of carbon monoxide by single breath method (DLCO(SB)) when adjusted for alveolar volume (V(A)%), correlated with the severity of pulmonary dysfunction. The DLCO(SB) remained within the reference range except in those with severe lung impairment (61.88 +/- 15.48%). DLCO(SB) has a significant (P < 0.05) positive correlation (0.70, 0.67, 048, 0.69 and 0.31, respectively) with measures of airflow limitation (FVC%, FEV1%, FEV1/FVC%, MVV%, and sGaw) and negative correlation (-0.36 and -0.21, respectively) with measures of air trapping (RV% and RV/TLC%). DLCO(SB)/V(A) remained above 100% of predicted despite worsening lung disease and did not correlate with other measures of lung function. On the other hand, the DLCO(SB) and DLCO(SB)/V(A), when adjusted for V(A)%, decreased and were significantly correlated with worsening airflow limitation and, to a lesser extent, air trapping. The relatively preserved adjusted DLCO(SB) and DLCO(SB)/V(A) values in CF patients up until late in its course may be explained the predominant airway involvement, minimal loss of alveolar-capillary units, and enhanced V/Q relationship due to claustration in CF. PMID:12814143

  5. The Capacity Profile: A Method to Classify Additional Care Needs in Children with Neurodevelopmental Disabilities

    ERIC Educational Resources Information Center

    Meester-Delver, Anke; Beelen, Anita; Hennekam, Raoul; Nollet, Frans; Hadders-Algra, Mijna

    2007-01-01

    The aim of this study was to determine the interrater reliability and stability over time of the Capacity Profile (CAP). The CAP is a standardized method for classifying additional care needs indicated by current impairments in five domains of body functions: physical health, neuromusculoskeletal and movement-related, sensory, mental, and voice…

  6. LOW-LEVEL CARBON MONOXIDE EXPOSURE AND WORK CAPACITY AT 1600 METERS

    EPA Science Inventory

    At sea level, low-level carbon monoxide (CO) exposure impairs exercise performance. To determine if altitude residence at 1600 m augments this CO effect, two studies of graded treadmill work capacity were done. The Initial Study investigated nine, non-smoking male subjects breath...

  7. To build capacity, build confidence

    NASA Astrophysics Data System (ADS)

    Hewitson, Bruce

    2015-07-01

    The history of attempts to spread scientific know-how beyond western centres of excellence is littered with failures. Capacity building needs long-term commitment, a critical mass of trainees, and a supportive home environment.

  8. Neuropsychological assessment of mental capacity.

    PubMed

    Sullivan, Karen

    2004-09-01

    The assessment of mental capacity to assist legal determinations of competency is potentially a growth area for neuropsychology, although to date neuropsychologists have published relatively little in this area. In this paper a systematic review of methods used to assess capacity is presented, including coverage of specialized tests and interviews used for this purpose. A neuropsychological model for conducting capacity assessments is proposed. This model involves comprehensive assessment of a wide range of cognitive abilities as well as assessment of specific skills and knowledge related to the type of capacity being assessed. The purpose of proposing this model is to stimulate further discussion and debate about the contribution neuropsychologists might make in this area. PMID:15673234

  9. Capacity Markets and Market Stability

    SciTech Connect

    Stauffer, Hoff

    2006-04-15

    The good news is that market stability can be achieved through a combination of longer-term contracts, auctions for far enough in the future to permit new entry, a capacity management system, and a demand curve. The bad news is that if and when stable capacity markets are designed, the markets may seem to be relatively close to where we started - with integrated resource planning. Market ideologues will find this anathema. (author)

  10. Maximizing the optical network capacity

    PubMed Central

    Bayvel, Polina; Maher, Robert; Liga, Gabriele; Shevchenko, Nikita A.; Lavery, Domaniç; Killey, Robert I.

    2016-01-01

    Most of the digital data transmitted are carried by optical fibres, forming the great part of the national and international communication infrastructure. The information-carrying capacity of these networks has increased vastly over the past decades through the introduction of wavelength division multiplexing, advanced modulation formats, digital signal processing and improved optical fibre and amplifier technology. These developments sparked the communication revolution and the growth of the Internet, and have created an illusion of infinite capacity being available. But as the volume of data continues to increase, is there a limit to the capacity of an optical fibre communication channel? The optical fibre channel is nonlinear, and the intensity-dependent Kerr nonlinearity limit has been suggested as a fundamental limit to optical fibre capacity. Current research is focused on whether this is the case, and on linear and nonlinear techniques, both optical and electronic, to understand, unlock and maximize the capacity of optical communications in the nonlinear regime. This paper describes some of them and discusses future prospects for success in the quest for capacity. PMID:26809572