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Sample records for impaired drug-binding capacity

  1. 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.

  2. 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

  3. Progressively impaired proteasomal capacity during terminal plasma cell differentiation

    PubMed Central

    Cenci, Simone; Mezghrani, Alexandre; Cascio, Paolo; Bianchi, Giada; Cerruti, Fulvia; Fra, Anna; Lelouard, Hugues; Masciarelli, Silvia; Mattioli, Laura; Oliva, Laura; Orsi, Andrea; Pasqualetto, Elena; Pierre, Philippe; Ruffato, Elena; Tagliavacca, Luigina; Sitia, Roberto

    2006-01-01

    After few days of intense immunoglobulin (Ig) secretion, most plasma cells undergo apoptosis, thus ending the humoral immune response. We asked whether intrinsic factors link plasma cell lifespan to Ig secretion. Here we show that in the late phases of plasmacytic differentiation, when antibody production becomes maximal, proteasomal activity decreases. The excessive load for the reduced proteolytic capacity correlates with accumulation of polyubiquitinated proteins, stabilization of endogenous proteasomal substrates (including Xbp1s, IκBα, and Bax), onset of apoptosis, and sensitization to proteasome inhibitors (PI). These events can be reproduced by expressing Ig-μ chain in nonlymphoid cells. Our results suggest that a developmental program links plasma cell death to protein production, and help explaining the peculiar sensitivity of normal and malignant plasma cells to PI. PMID:16498407

  4. 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…

  5. Impaired working memory capacity is not caused by failures of selective attention in schizophrenia.

    PubMed

    Erickson, Molly A; Hahn, Britta; Leonard, Carly J; Robinson, Benjamin; Gray, Brad; Luck, Steven J; Gold, James

    2015-03-01

    The cognitive impairments associated with schizophrenia have long been known to involve deficits in working memory (WM) capacity. To date, however, the causes of WM capacity deficits remain unknown. The present study examined selective attention impairments as a putative contributor to observed capacity deficits in this population. To test this hypothesis, we used an experimental paradigm that assesses the role of selective attention in WM encoding and has been shown to involve the prefrontal cortex and the basal ganglia. In experiment 1, participants were required to remember the locations of 3 or 5 target items (red circles). In another condition, 3-target items were accompanied by 2 distractor items (yellow circles), which participants were instructed to ignore. People with schizophrenia (PSZ) exhibited significant impairment in memory for the locations of target items, consistent with reduced WM capacity, but PSZ and healthy control subjects did not differ in their ability to filter the distractors. This pattern was replicated in experiment 2 for distractors that were more salient. Taken together, these results demonstrate that reduced WM capacity in PSZ is not attributable to a failure of filtering irrelevant distractors.

  6. Exercise training reverses impaired skeletal muscle metabolism induced by artificial selection for low aerobic capacity

    PubMed Central

    Lessard, Sarah J.; Rivas, Donato A.; Stephenson, Erin J.; Yaspelkis, Ben B.; Koch, Lauren G.; Britton, Steven L.

    2011-01-01

    We have used a novel model of genetically imparted endurance exercise capacity and metabolic health to study the genetic and environmental contributions to skeletal muscle glucose and lipid metabolism. We hypothesized that metabolic abnormalities associated with low intrinsic running capacity would be ameliorated by exercise training. Selective breeding for 22 generations resulted in rat models with a fivefold difference in intrinsic aerobic capacity. Low (LCR)- and high (HCR)-capacity runners remained sedentary (SED) or underwent 6 wk of exercise training (EXT). Insulin-stimulated glucose transport, insulin signal transduction, and rates of palmitate oxidation were lower in LCR SED vs. HCR SED (P < 0.05). Decreases in glucose and lipid metabolism were associated with decreased β2-adrenergic receptor (β2-AR), and reduced expression of Nur77 target proteins that are critical regulators of muscle glucose and lipid metabolism [uncoupling protein-3 (UCP3), fatty acid transporter (FAT)/CD36; P < 0.01 and P < 0.05, respectively]. EXT reversed the impairments to glucose and lipid metabolism observed in the skeletal muscle of LCR, while increasing the expression of β2-AR, Nur77, GLUT4, UCP3, and FAT/CD36 (P < 0.05) in this tissue. However, no metabolic improvements were observed following exercise training in HCR. Our results demonstrate that metabolic impairments resulting from genetic factors (low intrinsic aerobic capacity) can be overcome by an environmental intervention (exercise training). Furthermore, we identify Nur77 as a potential mechanism for improved skeletal muscle metabolism in response to EXT. PMID:21048074

  7. Impaired semantic knowledge underlies the reduced verbal short-term storage capacity in Alzheimer's disease.

    PubMed

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

    2009-12-01

    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 STM performance. The aim of this study was to examine the influence of semantic knowledge on verbal short-term memory storage capacity in normal aging and in AD by exploring the impact of word imageability on STM performance. Sixteen patients suffering from mild AD, 16 healthy elderly subjects and 16 young subjects performed an immediate serial recall task using word lists containing high or low imageability words. All participant groups recalled more high imageability words than low imageability words, but the effect of word imageability on verbal STM was greater in AD patients than in both the young and the elderly control groups. More precisely, AD patients showed a marked decrease in STM performance when presented with lists of low imageability words, whereas recall of high imageability words was relatively well preserved. Furthermore, AD patients displayed an abnormal proportion of phonological errors in the low imageability condition. Overall, these results indicate that the support of semantic knowledge on STM performance was impaired for lists of low imageability words in AD patients. More generally, these findings suggest that the deterioration of semantic knowledge is partly responsible for the poor verbal short-term storage capacity observed in AD.

  8. Dietary restriction improves repopulation but impairs lymphoid differentiation capacity of hematopoietic stem cells in early aging

    PubMed Central

    Tang, Duozhuang; Tao, Si; Chen, Zhiyang; Koliesnik, Ievgen Oleksandrovich; Calmes, Philip Gerald; Hoerr, Verena; Han, Bing; Gebert, Nadja; Zörnig, Martin; Löffler, Bettina

    2016-01-01

    Dietary restriction (DR) improves health, delays tissue aging, and elongates survival in flies and worms. However, studies on laboratory mice and nonhuman primates revealed ambiguous effects of DR on lifespan despite improvements in health parameters. In this study, we analyzed consequences of adult-onset DR (24 h to 1 yr) on hematopoietic stem cell (HSC) function. DR ameliorated HSC aging phenotypes, such as the increase in number of HSCs and the skewing toward myeloid-biased HSCs during aging. Furthermore, DR increased HSC quiescence and improved the maintenance of the repopulation capacity of HSCs during aging. In contrast to these beneficial effects, DR strongly impaired HSC differentiation into lymphoid lineages and particularly inhibited the proliferation of lymphoid progenitors, resulting in decreased production of peripheral B lymphocytes and impaired immune function. The study shows that DR-dependent suppression of growth factors and interleukins mediates these divergent effects caused by DR. Supplementation of insulin-like growth factor 1 partially reverted the DR-induced quiescence of HSCs, whereas IL-6/IL-7 substitutions rescued the impairment of B lymphopoiesis exposed to DR. Together, these findings delineate positive and negative effects of long-term DR on HSC functionality involving distinct stress and growth signaling pathways. PMID:26951333

  9. Heightened muscle inflammation susceptibility may impair regenerative capacity in aging humans

    PubMed Central

    Merritt, Edward K.; Stec, Michael J.; Thalacker-Mercer, Anna; Windham, Samuel T.; Cross, James M.; Shelley, David P.; Craig Tuggle, S.; Kosek, David J.; Kim, Jeong-su

    2013-01-01

    The regenerative response of skeletal muscle to mechanically induced damage is impaired with age. Previous work in our laboratory suggests this may result from higher proinflammatory signaling in aging muscle at rest and/or a greater inflammatory response to damage. We, therefore, assessed skeletal muscle proinflammatory signaling at rest and 24 h after unaccustomed, loaded knee extension contractions that induced modest muscle damage (72% increase in serum creatine kinase) in a cohort of 87 adults across three age groups (AGE40, AGE61, and AGE76). Vastus lateralis muscle gene expression and protein cell signaling of the IL-6 and TNF-α pathways were determined by quantitative PCR and immunoblot analysis. For in vitro studies, cell signaling and fusion capacities were compared among primary myoblasts from young (AGE28) and old (AGE64) donors treated with TNF-α. Muscle expression was higher (1.5- to 2.1-fold) in AGE76 and AGE61 relative to AGE40 for several genes involved in IL-6, TNF-α, and TNF-like weak inducer of apoptosis signaling. Indexes of activation for the proinflammatory transcription factors signal transducer and activator of transcription-3 and NF-κB were highest in AGE76. Resistance loading reduced gene expression of IL-6 receptor, muscle RING finger 1, and atrogin-1, and increased TNF-like weak inducer of apoptosis receptor expression. Donor myoblasts from AGE64 showed impaired differentiation and fusion in standard media and greater NF-κB activation in response to TNF-α treatment (compared with AGE28). We show for the first time that human aging is associated with muscle inflammation susceptibility (i.e., higher basal state of proinflammatory signaling) that is present in both tissue and isolated myogenic cells and likely contributes to the impaired regenerative capacity of skeletal muscle in the older population. PMID:23681911

  10. Substrate and drug binding sites in LeuT.

    PubMed

    Nyola, Ajeeta; Karpowich, Nathan K; Zhen, Juan; Marden, Jennifer; Reith, Maarten E; Wang, Da-Neng

    2010-08-01

    LeuT is a member of the neurotransmitter/sodium symporter family, which includes the neuronal transporters for serotonin, norepinephrine, and dopamine. The original crystal structure of LeuT shows a primary leucine-binding site at the center of the protein. LeuT is inhibited by different classes of antidepressants that act as potent inhibitors of the serotonin transporter. The newly determined crystal structures of LeuT-antidepressant complexes provide opportunities to probe drug binding in the serotonin transporter, of which the exact position remains controversial. Structure of a LeuT-tryptophan complex shows an overlapping binding site with the primary substrate site. A secondary substrate binding site was recently identified, where the binding of a leucine triggers the cytoplasmic release of the primary substrate. This two binding site model presents opportunities for a better understanding of drug binding and the mechanism of inhibition for mammalian transporters.

  11. Age-related decline of autocrine pituitary adenylate cyclase-activating polypeptide impairs angiogenic capacity of rat cerebromicrovascular endothelial cells.

    PubMed

    Banki, Eszter; Sosnowska, Danuta; Tucsek, Zsuzsanna; Gautam, Tripti; Toth, Peter; Tarantini, Stefano; Tamas, Andrea; Helyes, Zsuzsanna; Reglodi, Dora; Sonntag, William E; Csiszar, Anna; Ungvari, Zoltan

    2015-06-01

    Aging impairs angiogenic capacity of cerebromicrovascular endothelial cells (CMVECs) promoting microvascular rarefaction, but the underlying mechanisms remain elusive. PACAP is an evolutionarily conserved neuropeptide secreted by endothelial cells and neurons, which confers important antiaging effects. To test the hypothesis that age-related changes in autocrine PACAP signaling contributes to dysregulation of endothelial angiogenic capacity, primary CMVECs were isolated from 3-month-old (young) and 24-month-old (aged) Fischer 344 x Brown Norway rats. In aged CMVECs, expression of PACAP was decreased, which was associated with impaired capacity to form capillary-like structures, impaired adhesiveness to collagen (assessed using electric cell-substrate impedance sensing [ECIS] technology), and increased apoptosis (caspase3 activity) when compared with young cells. Overexpression of PACAP in aged CMVECs resulted in increased formation of capillary-like structures, whereas it did not affect cell adhesion. Treatment with recombinant PACAP also significantly increased endothelial tube formation and inhibited apoptosis in aged CMVECs. In young CMVECs shRNA knockdown of autocrine PACAP expression significantly impaired tube formation capacity, mimicking the aging phenotype. Cellular and mitochondrial reactive oxygen species production (dihydroethidium and MitoSox fluorescence, respectively) were increased in aged CMVECs and were unaffected by PACAP. Collectively, PACAP exerts proangiogenic effects and age-related dysregulation of autocrine PACAP signaling may contribute to impaired angiogenic capacity of CMVECs in aging.

  12. Age-Related Decline of Autocrine Pituitary Adenylate Cyclase-Activating Polypeptide Impairs Angiogenic Capacity of Rat Cerebromicrovascular Endothelial Cells

    PubMed Central

    Banki, Eszter; Sosnowska, Danuta; Tucsek, Zsuzsanna; Gautam, Tripti; Toth, Peter; Tarantini, Stefano; Tamas, Andrea; Helyes, Zsuzsanna; Reglodi, Dora; Sonntag, William E.; Csiszar, Anna

    2015-01-01

    Aging impairs angiogenic capacity of cerebromicrovascular endothelial cells (CMVECs) promoting microvascular rarefaction, but the underlying mechanisms remain elusive. PACAP is an evolutionarily conserved neuropeptide secreted by endothelial cells and neurons, which confers important antiaging effects. To test the hypothesis that age-related changes in autocrine PACAP signaling contributes to dysregulation of endothelial angiogenic capacity, primary CMVECs were isolated from 3-month-old (young) and 24-month-old (aged) Fischer 344 x Brown Norway rats. In aged CMVECs, expression of PACAP was decreased, which was associated with impaired capacity to form capillary-like structures, impaired adhesiveness to collagen (assessed using electric cell-substrate impedance sensing [ECIS] technology), and increased apoptosis (caspase3 activity) when compared with young cells. Overexpression of PACAP in aged CMVECs resulted in increased formation of capillary-like structures, whereas it did not affect cell adhesion. Treatment with recombinant PACAP also significantly increased endothelial tube formation and inhibited apoptosis in aged CMVECs. In young CMVECs shRNA knockdown of autocrine PACAP expression significantly impaired tube formation capacity, mimicking the aging phenotype. Cellular and mitochondrial reactive oxygen species production (dihydroethidium and MitoSox fluorescence, respectively) were increased in aged CMVECs and were unaffected by PACAP. Collectively, PACAP exerts proangiogenic effects and age-related dysregulation of autocrine PACAP signaling may contribute to impaired angiogenic capacity of CMVECs in aging. PMID:25136000

  13. 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.

  14. The impact of attentional allocation capacities on nonword repetition in children with specific language impairment.

    PubMed

    Leclercq, Anne-Lise; Maillart, Christelle; Lange, Manon; Majerus, Steve

    2015-01-01

    This study aimed at directly assessing the hypothesis that attentional allocation capacity influences poor nonword repetition (NWR) performances in children with specific language impairment (SLI), using an attention demanding visual search task given concurrently with the NWR task. Twenty-one children with SLI, 21 typically developing children matched on age and 21 typically developing children matched on nonword span performed an immediate serial recall task of nonwords. The nonword lists were presented either alone or concurrently with the visual search task. Overall, results revealed a resource-sharing trade-off between the two tasks. Children with SLI were affected to the same extent as their span-matched controls by the necessity to allocate their attentional resources between the two tasks. Interestingly, nonword processing strategies seemed to differ among groups: age-matched controls allocated a larger part of their attentional resources to the encoding stage, whereas nonword recall was more attention demanding in children with SLI and younger controls.

  15. 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

  16. Financial capacity of older African Americans with amnestic mild cognitive impairment.

    PubMed

    Triebel, Kristen L; Okonkwo, Ozioma C; Martin, Roy; Griffith, Henry Randall; Crowther, Martha; Marson, Daniel C

    2010-01-01

    This study investigated financial abilities of 154 patients with mild cognitive impairment (MCI) (116 white, 38 African American) using the Financial Capacity Instrument (FCI). In a series of linear regression models, we examined the effect of race on FCI performance and identified preliminary predictor variables that mediated observed racial differences on the FCI. Prior/premorbid abilities were identified. Predictor variables examined in the models included race and other demographic factors (age, education, sex), performance on global cognitive measures (MMSE, DRS-2 Total Score), history of cardiovascular disease (hypertension, diabetes, hypercholesterolemia), and a measure of educational achievement (WRAT-3 Arithmetic). African American patients with MCI performed below white patients with MCI on 6 of the 7 FCI domains examined and on the FCI total score. WRAT-3 Arithmetic emerged as a partial mediator of group differences on the FCI, accounting for 54% of variance. In contrast, performance on global cognitive measures and history of cardiovascular disease only accounted for 14% and 2%, respectively, of the variance. Racial disparities in financial capacity seem to exist among patients with amnestic MCI. Basic academic math skills related to educational opportunity and quality of education account for a substantial proportion of the group difference in financial performance.

  17. Multidrug-resistance drug-binding peptides generated by using a phage display library.

    PubMed

    Popkov, M; Lussier, I; Medvedkine, V; Estève, P O; Alakhov, V; Mandeville, R

    1998-01-15

    A phage display library of random decapeptides was used to generate peptide ligands that can bind multidrug-resistance (MDR) drugs mimicking, in this respect, the drug-binding activity of P-glycoprotein. Seven peptide sequences were identified that specifically bound doxorubicin. Five of these sequences expressed the core consensus motif WXXW. The displacement assay showed that the phages expressing these peptides bound MDR type drugs (vinblastine, doxorubicin, verapamil, and genistein) with the same selectivity as P-glycoprotein and did not interact with non-MDR type drugs, such as arabinosylcytosine (Ara-C) and melphalan. One of the selected peptides that showed a highest capacity for the binding (VCDWWGWGIC) was synthesized and displayed competition with the phage for doxorubicin binding. The structure modeling suggested that all the selected sequences contained a hydrophobic envelope in which MDR drugs could be docked with substantial energy minimization. Western blot analysis showed that monospecific antibody obtained against the phage expressing VCDWWGWGIC peptide could specifically recognize P-glycoprotein in the membrane fraction of MDR phenotype MCF-7ADR cells. The MDR drug-binding sequences generated during this work could provide an important tool for design and screening of new chemotherapeutic agents.

  18. 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.

  19. Impaired exercise capacity and skeletal muscle function in a mouse model of pulmonary inflammation

    PubMed Central

    Tang, Kechun; Murano, George; Wagner, Harrieth; Nogueira, Leonardo; Wagner, Peter D.; Tang, Alisa; Dalton, Nancy D.; Gu, Yusu; Peterson, Kirk L.

    2013-01-01

    Pulmonary TNFα has been linked to reduced exercise capacity in a subset of patients with moderate to severe chronic obstructive pulmonary disease (COPD). We hypothesized that prolonged, high expression of pulmonary TNFα impairs cardiac and skeletal muscle function, and both contribute to exercise limitation. Using a surfactant protein C promoter-TNFα construct, TNFα was overexpressed throughout life in mouse lungs (SP-C/TNFα+). TNFα levels in wild-type (WT) female serum and lung were two- and threefold higher than in WT male mice. In SP-C/TNFα+ mice, TNFα increased similarly in both sexes. Treadmill exercise was impaired only in male SP-C/TNFα+ mice. While increases in lung volume and airspace size induced by TNFα were comparable in both sexes, pulmonary hypertension along with lower body and muscle mass were evident only in male mice. Left ventricular (LV) function (cardiac output, stroke volume, LV maximal pressure, and LV maximal pressure dP/dt) was not altered by TNFα overexpression. Fatigue measured in isolated soleus and EDL was more rapid only in soleus of male SP-C/TNFα+ mice and accompanied by a loss of oxidative IIa fibers, citrate synthase activity, and PGC-1α mRNA and increase in atrogin-1 and MuRF1 expression also only in male mice. In situ gastrocnemius fatigue resistance, reflecting both oxygen availability and contractility, was decreased similarly in female and male SP-C/TNFα+ mice. These data indicate that male, but not female, mice overexpressing pulmonary TNFα are susceptible to exercise limitation, possibly due to muscle wasting and loss of the oxidative muscle phenotype, with protection in females possibly due to estrogen. PMID:23449936

  20. Impaired colony-forming capacity of circulating endothelial progenitor cells in patients with emphysema.

    PubMed

    Kim, Eun-Kyung; Lee, Ji-Hyun; Jeong, Hye-Cheol; Oh, Doyeon; Hwang, Seong-Gyu; Cho, Yong-Wook; Lee, Seon-Ju; Oh, Yeon-Mok; Lee, Sang-Do

    2012-01-01

    Chronic obstructive pulmonary disease (COPD) is classified into emphysema and chronic bronchitis, which are thought to result from different pathophysiological pathways. Smoking-induced lung parenchymal destruction and inadequate repair are involved in the pathogenesis of emphysema. In addition, decreased expression of vascular endothelial growth factor and increased endothelial cell apoptosis in the lung may participate in emphysema pathogenesis. As stem cells, circulating endothelial progenitor cells (EPCs) may play a key role in the maintenance of vascular integrity by replacing and repairing the damaged endothelial cells in the tissues. To determine whether the lack of appropriate repair by circulating EPCs in cases of smoking-induced endothelial cell injury participates in emphysema pathogenesis, we determined the association between the colony-forming or migratory capacity of circulating EPCs and the presence of emphysema in 51 patients with COPD. The patients were divided into emphysema (n = 23) and non-emphysema groups (n = 28) based on high-resolution computed tomography. Twenty-two smokers with normal lung function and 14 normal non-smokers served as controls. Circulating EPCs isolated from patients with emphysema showed significantly lower colony-forming units (CFUs) than those from patients with non-emphysema group, smokers with normal lung function, and normal non-smokers. EPCs from patients with emphysema showed significantly lower migratory capacity than those from normal non-smoking controls (p < 0.05). On multivariate analysis, the EPC-CFU was independently associated with emphysema (OR 0.944, 95% CI = 0.903-0.987, p = 0.011). Thus, impaired functions of circulating EPCs may contribute to the development of emphysema.

  1. Reversal of the Drug Binding Pocket Defects of the AcrB Multidrug Efflux Pump Protein of Escherichia coli

    PubMed Central

    Soparkar, Ketaki; Kinana, Alfred D.; Weeks, Jon W.; Morrison, Keith D.; Nikaido, Hiroshi

    2015-01-01

    ABSTRACT The AcrB protein of Escherichia coli, together with TolC and AcrA, forms a contiguous envelope conduit for the capture and extrusion of diverse antibiotics and cellular metabolites. In this study, we sought to expand our knowledge of AcrB by conducting genetic and functional analyses. We began with an AcrB mutant bearing an F610A substitution in the drug binding pocket and obtained second-site substitutions that overcame the antibiotic hypersusceptibility phenotype conferred by the F610A mutation. Five of the seven unique single amino acid substitutions—Y49S, V127A, V127G, D153E, and G288C—mapped in the periplasmic porter domain of AcrB, with the D153E and G288C mutations mapping near and at the distal drug binding pocket, respectively. The other two substitutions—F453C and L486W—were mapped to transmembrane (TM) helices 5 and 6, respectively. The nitrocefin efflux kinetics data suggested that all periplasmic suppressors significantly restored nitrocefin binding affinity impaired by the F610A mutation. Surprisingly, despite increasing MICs of tested antibiotics and the efflux of N-phenyl-1-naphthylamine, the TM suppressors did not improve the nitrocefin efflux kinetics. These data suggest that the periplasmic substitutions act by influencing drug binding affinities for the distal binding pocket, whereas the TM substitutions may indirectly affect the conformational dynamics of the drug binding domain. IMPORTANCE The AcrB protein and its homologues confer multidrug resistance in many important human bacterial pathogens. A greater understanding of how these efflux pump proteins function will lead to the development of effective inhibitors against them. The research presented in this paper investigates drug binding pocket mutants of AcrB through the isolation and characterization of intragenic suppressor mutations that overcome the drug susceptibility phenotype of mutations affecting the drug binding pocket. The data reveal a remarkable structure

  2. 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…

  3. Functional Capacity, Muscle Fat Infiltration, Power Output, and Cognitive Impairment in Institutionalized Frail Oldest Old

    PubMed Central

    Casas-Herrero, Alvaro; Cadore, Eduardo L.; Zambom-Ferraresi, Fabricio; Idoate, Fernando; Millor, Nora; Martínez-Ramirez, Alicia; Gómez, Marisol; Rodriguez-Mañas, Leocadio; Marcellán, Teresa; de Gordoa, Ana Ruiz; Marques, Mário C.

    2013-01-01

    Abstract This study examined the neuromuscular and functional performance differences between frail oldest old with and without mild cognitive impairment (MCI). In addition, the associations between functional capacities, muscle mass, strength, and power output of the leg muscles were also examined. Forty-three elderly men and women (91.9±4.1 years) were classified into three groups—the frail group, the frail with MCI group (frail+MCI), and the non-frail group. Strength tests were performed for upper and lower limbs. Functional tests included 5-meter habitual gait, timed up-and-go (TUG), dual task performance, balance, and rise from a chair ability. Incidence of falls was assessed using questionnaires. The thigh muscle mass and attenuation were assessed using computed tomography. There were no differences between the frail and frail+MCI groups for all the functional variables analyzed, except in the cognitive score of the TUG with verbal task, which frail showed greater performance than the frail+MCI group. Significant associations were observed between the functional performance, incidence of falls, muscle mass, strength, and power in the frail and frail+MCI groups (r=−0.73 to r=0.83, p<0.01 to p<0.05). These results suggest that the frail oldest old with and without MCI have similar functional and neuromuscular outcomes. Furthermore, the functional outcomes and incidences of falls are associated with muscle mass, strength, and power in the frail elderly population. PMID:23822577

  4. Relationship between ambulatory capacity and cardiorespiratory fitness in chronic stroke: Influence of stroke-specific impairments

    PubMed Central

    Pang, Marco YC; Eng, Janice J; Dawson, Andrew S

    2016-01-01

    Study Objectives To identify in individuals with chronic stroke (1) the relationship between the maximal oxygen uptake (VO2max) during cycle ergometry and the distance covered in the Six Minute Walk Test (6MWT), and (2) the stroke-specific impairments which are important determinants for the 6MWT distance. Design Cross-sectional study using a convenience sample. Setting Exercise testing laboratory in a tertiary rehabilitation center. Participants Sixty-three older adults (mean age ± standard deviation, 65.3 ± 8.7) with an average post-stroke interval of 5.5 ± 4.9 years. Intervention Not applicable Main Outcome Measures Each subject underwent a maximal cycle ergometer test and a 6MWT. Oxygen consumption (VO2) was measured during both tests. Subjects were also evaluated for Berg Balance Scale, Modified Ashworth Scale of Spasticity, isometric knee extension strength and percent body fat. Results The 6MW distance had a low correlation with the VO2max (r=0.402). Balance, knee extension strength and spasticity were all significant determinants for the 6MWT distance, with balance being the major contributor for the 6MWT distance, accounting for 66.5% of its variance. Conclusions Factors other than the cardiorespiratory status considerably influenced the ambulatory capacity as measured by the 6MWT. The 6MWT distance alone should not be used to indicate cardiorespiratory fitness in individuals with chronic stroke. PMID:15705987

  5. XIAP inhibitors induce differentiation and impair clonogenic capacity of acute myeloid leukemia stem cells

    PubMed Central

    Moreno-Martínez, Daniel; Nomdedeu, Meritxell; Lara-Castillo, María Carmen; Etxabe, Amaia; Pratcorona, Marta; Tesi, Niccolò; Díaz-Beyá, Marina; Rozman, María; Montserrat, Emili; Urbano-Ispizua, Álvaro; Esteve, Jordi; Risueño, Ruth M.

    2014-01-01

    Acute myeloid leukemia (AML) is a neoplasia characterized by the rapid expansion of immature myeloid blasts in the bone marrow, and marked by poor prognosis and frequent relapse. As such, new therapeutic approaches are required for remission induction and prevention of relapse. Due to the higher chemotherapy sensitivity and limited life span of more differentiated AML blasts, differentiation-based therapies are a promising therapeutic approach. Based on public available gene expression profiles, a myeloid-specific differentiation-associated gene expression pattern was defined as the therapeutic target. A XIAP inhibitor (Dequalinium chloride, DQA) was identified in an in silico screening searching for small molecules that induce similar gene expression regulation. Treatment with DQA, similarly to Embelin (another XIAP inhibitor), induced cytotoxicity and differentiation in AML. XIAP inhibition differentially impaired cell viability of the most primitive AML blasts and reduced clonogenic capacity of AML cells, sparing healthy mature blood and hematopoietic stem cells. Taken together, these results suggest that XIAP constitutes a potential target for AML treatment and support the evaluation of XIAP inhibitors in clinical trials. PMID:24952669

  6. Structure and localisation of drug binding sites on neurotransmitter transporters.

    PubMed

    Ravna, Aina W; Sylte, Ingebrigt; Dahl, Svein G

    2009-10-01

    The dopamine (DAT), serotontin (SERT) and noradrenalin (NET) transporters are molecular targets for different classes of psychotropic drugs. The crystal structure of Aquifex aeolicus LeuT(Aa) was used as a template for molecular modeling of DAT, SERT and NET, and two putative drug binding sites (pocket 1 and 2) in each transporter were identified. Cocaine was docked into binding pocket 1 of DAT, corresponding to the leucine binding site in LeuT(Aa), which involved transmembrane helices (TMHs) 1, 3, 6 and 8. Clomipramine was docked into binding pocket 2 of DAT, involving TMHs 1, 3, 6, 10 and 11, and extracellular loops 4 and 6, corresponding to the clomipramine binding site in a crystal structure of a LeuT(Aa)-clomipramine complex. The structures of the proposed cocaine- and tricyclic antidepressant-binding sites may be of particular interest for the design of novel DAT interacting ligands.

  7. Comparative studies on drug binding to the purified and pharmaceutical-grade human serum albumins: Bridging between basic research and clinical applications of albumin.

    PubMed

    Ashrafi-Kooshk, Mohammad Reza; Ebrahimi, Farangis; Ranjbar, Samira; Ghobadi, Sirous; Moradi, Nastaran; Khodarahmi, Reza

    2015-09-01

    Human serum albumin (HSA), the most abundant protein in blood plasma, is a monomeric multidomain protein that possesses an extraordinary capacity for binding, so that serves as a circulating depot for endogenous and exogenous compounds. During the heat sterilization process, the structure of pharmaceutical-grade HSA may change and some of its activities may be lost. In this study, to provide deeper insight on this issue, we investigated drug-binding and some physicochemical properties of purified albumin (PA) and pharmaceutical-grade albumin (PGA) using two known drugs (indomethacin and ibuprofen). PGA displayed significantly lower drug binding capacity compared to PA. Analysis of the quenching and thermodynamic parameters indicated that intermolecular interactions between the drugs and the proteins are different from each other. Surface hydrophobicity as well as the stability of PGA decreased compared to PA, also surface hydrophobicity of PA and PGA increased upon drugs binding. Also, kinetic analysis of pseudo-esterase activities indicated that Km and Vmax parameters for PGA enzymatic activity are more and less than those of PA, respectively. This in vitro study demonstrates that the specific drug binding of PGA is significantly reduced. Such studies can act as connecting bridge between basic research discoveries and clinical applications.

  8. 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.

  9. 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

  10. Urine Concentrating Capacity, Vasopressin and Copeptin in ADPKD and IgA Nephropathy Patients with Renal Impairment

    PubMed Central

    Bakker, Stephan J. L.; Boesten, Lianne S. M.; Duit, A. A. Margreeth; Franssen, Casper F. M.; Gaillard, Carlo A. J. M.; Gansevoort, Ron T.

    2017-01-01

    Background Autosomal Dominant Polycystic Kidney Disease (ADPKD) patients have an impaired urine concentrating capacity. Increased circulating vasopressin (AVP) concentrations are supposed to play a role in the progression of ADPKD. We hypothesized that ADPKD patients have a more severely impaired urine concentrating capacity in comparison to other patients with chronic kidney disease at a similar level of kidney function, with consequently an enhanced AVP response to water deprivation with higher circulating AVP concentrations. Methods 15 ADPKD (eGFR<60) patients and 15 age-, sex- and eGFR-matched controls with IgA nephropathy (IgAN), underwent a water deprivation test to determine maximal urine concentrating capacity. Plasma and urine osmolality, urine aquaporin-2 (AQP2) and plasma AVP and copeptin (a surrogate marker for AVP) were measured at baseline and after water deprivation (average 16 hours). In ADPKD patients, height adjusted total kidney volume (hTKV) was measured by MRI. Results Maximal achieved urine concentration was lower in ADPKD compared to IgAN controls (533±138 vs. 642±148 mOsm/kg, p = 0.046), with particularly a lower maximal achieved urine urea concentration (223±74 vs. 299±72 mmol/L, p = 0.008). After water deprivation, plasma osmolality was similar in both groups although change in plasma osmolality was more profound in ADPKD due to a lower baseline plasma osmolality in comparison to IgAN controls. Copeptin and AVP increased significantly in a similar way in both groups. AVP, copeptin and urine AQP2 were inversely associated with maximal urine concentrating in both groups. Conclusions ADPKD patients have a more severely impaired maximal urine concentrating capacity with a lower maximal achieved urine urea concentration in comparison to IgAN controls with similar endogenous copeptin and AVP responses. PMID:28081165

  11. 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.

  12. 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.…

  13. 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

  14. Impaired exercise capacity after lung transplantation is related to delayed recovery of muscle strength.

    PubMed

    Walsh, James R; Chambers, Daniel C; Davis, Rebecca J; Morris, Norman R; Seale, Helen E; Yerkovich, Stephanie T; Hopkins, Peter M A

    2013-01-01

    Lung transplant recipients report reduced exercise capacity despite satisfactory graft function. We analysed changes in lung function, six-min walk distance (6MWD), and quadriceps strength in the first 26-wk post-transplant and examined what factors predict 6MWD recovery. All lung transplant recipients at a single institution between June 2007 and January 2011 were considered for inclusion. Lung function, 6MWD, and quadriceps strength corrected for body weight (QS%) were recorded pre- and two-, six-, 13-, and 26-wk post-transplant. Fifty recipients, of mean (± SD) age 42 (± 13) yr, were studied. Mean FEV1 % and 6MWD improved from 26.4% to 88.9% and from 397 to 549 m at 26 wk, respectively (both p < 0.001). QS% declined in the first two wk but had improved to above pre-transplant levels by 26 wk (p = 0.027). On multivariate analysis (n = 35), lower pre-transplant exercise capacity and greater recovery in muscle strength explained most of the improvement in exercise capacity. Delayed recovery of exercise capacity after lung transplantation is unrelated to delay in improvement in graft function, but occurs secondary to the slow recovery of muscle strength. Our findings show that additional controlled trials are needed to better understand the influence of exercise rehabilitation on improvement in exercise capacity post-transplantation.

  15. 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.

  16. Increased Left Ventricular Stiffness Impairs Exercise Capacity in Patients with Heart Failure Symptoms Despite Normal Left Ventricular Ejection Fraction

    PubMed Central

    Sinning, David; Kasner, Mario; Westermann, Dirk; Schulze, Karsten; Schultheiss, Heinz-Peter; Tschöpe, Carsten

    2011-01-01

    Aims. Several mechanisms can be involved in the development of exercise intolerance in patients with heart failure despite normal left ventricular ejection fraction (HFNEF) and may include impairment of left ventricular (LV) stiffness. We therefore investigated the influence of LV stiffness, determined by pressure-volume loop analysis obtained by conductance catheterization, on exercise capacity in HFNEF. Methods and Results. 27 HFNEF patients who showed LV diastolic dysfunction in pressure-volume (PV) loop analysis performed symptom-limited cardiopulmonary exercise testing (CPET) and were compared with 12 patients who did not show diastolic dysfunction in PV loop analysis. HFNEF patients revealed a lower peak performance (P = .046), breathing reserve (P = .006), and ventilation equivalent for carbon dioxide production at rest (P = .002). LV stiffness correlated with peak oxygen uptake (r = −0.636, P < .001), peak oxygen uptake at ventilatory threshold (r = −0.500, P = .009), and ventilation equivalent for carbon dioxide production at ventilatory threshold (r = 0.529, P = .005). Conclusions. CPET parameters such as peak oxygen uptake, peak oxygen uptake at ventilatory threshold, and ventilation equivalent for carbon dioxide production at ventilatory threshold correlate with LV stiffness. Increased LV stiffness impairs exercise capacity in HFNEF. PMID:21403885

  17. 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.

  18. 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

    2014-10-05

    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.

  19. Impact of germline and somatic missense variations on drug binding sites.

    PubMed

    Yan, C; Pattabiraman, N; Goecks, J; Lam, P; Nayak, A; Pan, Y; Torcivia-Rodriguez, J; Voskanian, A; Wan, Q; Mazumder, R

    2017-03-01

    Advancements in next-generation sequencing (NGS) technologies are generating a vast amount of data. This exacerbates the current challenge of translating NGS data into actionable clinical interpretations. We have comprehensively combined germline and somatic nonsynonymous single-nucleotide variations (nsSNVs) that affect drug binding sites in order to investigate their prevalence. The integrated data thus generated in conjunction with exome or whole-genome sequencing can be used to identify patients who may not respond to a specific drug because of alterations in drug binding efficacy due to nsSNVs in the target protein's gene. To identify the nsSNVs that may affect drug binding, protein-drug complex structures were retrieved from Protein Data Bank (PDB) followed by identification of amino acids in the protein-drug binding sites using an occluded surface method. Then, the germline and somatic mutations were mapped to these amino acids to identify which of these alter protein-drug binding sites. Using this method we identified 12 993 amino acid-drug binding sites across 253 unique proteins bound to 235 unique drugs. The integration of amino acid-drug binding sites data with both germline and somatic nsSNVs data sets revealed 3133 nsSNVs affecting amino acid-drug binding sites. In addition, a comprehensive drug target discovery was conducted based on protein structure similarity and conservation of amino acid-drug binding sites. Using this method, 81 paralogs were identified that could serve as alternative drug targets. In addition, non-human mammalian proteins bound to drugs were used to identify 142 homologs in humans that can potentially bind to drugs. In the current protein-drug pairs that contain somatic mutations within their binding site, we identified 85 proteins with significant differential gene expression changes associated with specific cancer types. Information on protein-drug binding predicted drug target proteins and prevalence of both somatic and

  20. Decreased capacity for sodium export out of Arabidopsis chloroplasts impairs salt tolerance, photosynthesis and plant performance.

    PubMed

    Müller, Maria; Kunz, Hans-Henning; Schroeder, Julian I; Kemp, Grant; Young, Howard S; Neuhaus, H Ekkehard

    2014-05-01

    Salt stress is a widespread phenomenon, limiting plant performance in large areas around the world. Although various types of plant sodium/proton antiporters have been characterized, the physiological function of NHD1 from Arabidopsis thaliana has not been elucidated in detail so far. Here we report that the NHD1-GFP fusion protein localizes to the chloroplast envelope. Heterologous expression of AtNHD1 was sufficient to complement a salt-sensitive Escherichia coli mutant lacking its endogenous sodium/proton exchangers. Transport competence of NHD1 was confirmed using recombinant, highly purified carrier protein reconstituted into proteoliposomes, proving Na(+) /H(+) antiport. In planta NHD1 expression was found to be highest in mature and senescent leaves but was not induced by sodium chloride application. When compared to wild-type controls, nhd1 T-DNA insertion mutants showed decreased biomasses and lower chlorophyll levels after sodium feeding. Interestingly, if grown on sand and supplemented with high sodium chloride, nhd1 mutants exhibited leaf tissue Na(+) levels similar to those of wild-type plants, but the Na(+) content of chloroplasts increased significantly. These high sodium levels in mutant chloroplasts resulted in markedly impaired photosynthetic performance as revealed by a lower quantum yield of photosystem II and increased non-photochemical quenching. Moreover, high Na(+) levels might hamper activity of the plastidic bile acid/sodium symporter family protein 2 (BASS2). The resulting pyruvate deficiency might cause the observed decreased phenylalanine levels in the nhd1 mutants due to lack of precursors.

  1. Cold exposure impairs dark-pulse capacity to induce REM sleep in the albino rat.

    PubMed

    Baracchi, Francesca; Zamboni, Giovanni; Cerri, Matteo; Del Sindaco, Elide; Dentico, Daniela; Jones, Christine Ann; Luppi, Marco; Perez, Emanuele; Amici, Roberto

    2008-06-01

    In the albino rat, a REM sleep (REMS) onset can be induced with a high probability and a short latency when the light is suddenly turned off (dark pulse, DP) during non-REM sleep (NREMS). The aim of this study was to investigate to what extent DP delivery could overcome the integrative thermoregulatory mechanisms that depress REMS occurrence during exposure to low ambient temperature (Ta). To this aim, the efficiency of a non-rhythmical repetitive DP (3 min each) delivery during the first 6-h light period of a 12 h:12 h light-dark cycle in inducing REMS was studied in the rat, through the analysis of electroencephalogram, electrocardiogram, hypothalamic temperature and motor activity at different Tas. The results showed that DP delivery triggers a transition from NREMS to REMS comparable to that which occurs spontaneously. However, the efficiency of DP delivery in inducing REMS was reduced during cold exposure to an extent comparable with that observed in spontaneous REMS occurrence. Such impairment was associated with low Delta activity and high sympathetic tone when DPs were delivered. Repetitive DP administration increased REMS amount during the delivery period and a subsequent negative REMS rebound was observed. In conclusion, DP delivery did not overcome the integrative thermoregulatory mechanisms that depress REMS in the cold. These results underline the crucial physiological meaning of the mutual exclusion of thermoregulatory activation and REMS occurrence, and support the hypothesis that the suspension of the central control of body temperature is a prerequisite for REMS occurrence.

  2. Lack of the transcription factor C/EBPδ impairs the intrinsic capacity of peripheral neurons for regeneration.

    PubMed

    Lopez de Heredia, Luis; Magoulas, Charalambos

    2013-01-01

    Adult neurons of the peripheral nervous system (PNS), in contrast to those of the central nervous system, have a remarkable capacity to repair themselves after injury, yet the mechanisms underlying this regenerative propensity of peripheral neurons are far from completely understood. Here we show that the transcription factor CCAAT enhancer binding protein delta (C/EBPδ) is necessary for the efficient axonal regeneration of dorsal root ganglia (DRG) neurons after sciatic nerve crush injury. Loss of C/EBPδ substantially impairs axonal growth in dissociated cultured DRG neurons. In addition, lack of C/EPBδ causes a major reduction in the regenerative response of DRG neurons to a conditioning lesion, which is a well known paradigm of injury that enhances axonal growth due to a transcription-dependent cell body response. C/EBPδ is required for the induction of selected regeneration-associated genes. For example, the expression of SPRR1A (small proline-rich repeat protein 1A) is greatly reduced in DRG neurons of C/EBPδ knockout mice during axonal regeneration compared to those in wild-type mice, while the expression of GAP-43 (growth associated protein-43) and galanin is not affected. Nevertheless, the expected prompt recovery of sciatic nerve function after injury is severely impaired in C/EBPδ knockout mice, having a delay time of approximately 1 month for reaching the full function of recovering wild-type mice, suggesting that a transcription mechanism mediated by C/EBPδ is required for efficient axonal regeneration. Taken together, our results identify C/EBPδ as a crucial component of the transcriptional regulatory machinery which underlies the intrinsic capacity of peripheral neurons for axonal regeneration.

  3. Heme oxygenase (HO)-1 induction prevents Endoplasmic Reticulum stress-mediated endothelial cell death and impaired angiogenic capacity.

    PubMed

    Maamoun, Hatem; Zachariah, Matshediso; McVey, John H; Green, Fiona R; Agouni, Abdelali

    2017-03-01

    Most of diabetic cardiovascular complications are attributed to endothelial dysfunction and impaired angiogenesis. Endoplasmic Reticulum (ER) and oxidative stresses were shown to play a pivotal role in the development of endothelial dysfunction in diabetes. Hemeoxygenase-1 (HO-1) was shown to protect against oxidative stress in diabetes; however, its role in alleviating ER stress-induced endothelial dysfunction remains not fully elucidated. We aim here to test the protective role of HO-1 against high glucose-mediated ER stress and endothelial dysfunction and understand the underlying mechanisms with special emphasis on oxidative stress, inflammation and cell death. Human Umbilical Vein Endothelial Cells (HUVECs) were grown in either physiological or intermittent high concentrations of glucose for 5days in the presence or absence of Cobalt (III) Protoporphyrin IX chloride (CoPP, HO-1 inducer) or 4-Phenyl Butyric Acid (PBA, ER stress inhibitor). Using an integrated cellular and molecular approach, we then assessed ER stress and inflammatory responses, in addition to apoptosis and angiogenic capacity in these cells. Our results show that HO-1 induction prevented high glucose-mediated increase of mRNA and protein expression of key ER stress markers. Cells incubated with high glucose exhibited high levels of oxidative stress, activation of major inflammatory and apoptotic responses [nuclear factor (NF)-κB and c-Jun N-terminal kinase (JNK)] and increased rate of apoptosis; however, cells pre-treated with CoPP or PBA were fully protected. In addition, high glucose enhanced caspases 3 and 7 cleavage and activity and augmented cleaved poly ADP ribose polymerase (PARP) expression whereas HO-1 induction prevented these effects. Finally, HO-1 induction and ER stress inhibition prevented high glucose-induced reduction in NO release and impaired the angiogenic capacity of HUVECs, and enhanced vascular endothelial growth factor (VEGF)-A expression. Altogether, we show here the

  4. 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.

  5. High-dose statin use does not impair aerobic capacity or skeletal muscle function in older adults

    PubMed Central

    Stock, Anthoney A.; Harman, S. Mitchell

    2008-01-01

    3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) are lipid-lowering agents widely employed for atherosclerosis prevention. HMG-CoA reductase blockade reduces skeletal muscle coenzyme Q10 (CoQ10) levels and mitochondrial respiratory chain activities and may produce mild to severe skeletal muscle myopathy. This study investigated whether high-dose statin treatment would result in measurably decreased exercise capacity in older men and women. Maximal oxygen consumption, aerobic endurance, oxygen uptake kinetics, maximal strength, muscular power, and muscular endurance were measured before and after 12 weeks of statin treatment (simvastatin, 80 mg/day) in nine men and one woman, ages 55–76 years, with LDL-cholesterol levels >3.3 mmol/l (mean = 4.2 ± 0.2 mmol/l). Myalgia symptoms were assessed every 4 weeks. As expected, statin treatment resulted in significant decreases in LDL- and total-cholesterol levels (P < 0.01) with no significant changes in HDL-cholesterol or triglyceride levels. No significant changes were observed in aerobic capacity, endurance, oxygen kinetics or any measures of muscle function. No subject reported symptoms of myalgia, cramps, or weakness during the study. In the absence of myalgia or myopathic symptoms, high-dose simvastatin treatment did not impair exercise capacity in hyperlipidemic older individuals. We conclude that decreases in intramuscular CoQ10, in most patients on high dose statin treatment may not be clinically relevant, due to inter-individual variability in the degree of CoQ10 depletion, sensitivity of muscle to decreases in CoQ10, or both. PMID:19424852

  6. 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…

  7. 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…

  8. 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.

  9. Ionizing radiation promotes the acquisition of a senescence-associated secretory phenotype and impairs angiogenic capacity in cerebromicrovascular endothelial cells: role of increased DNA damage and decreased DNA repair capacity in microvascular radiosensitivity.

    PubMed

    Ungvari, Zoltan; Podlutsky, Andrej; Sosnowska, Danuta; Tucsek, Zsuzsanna; Toth, Peter; Deak, Ferenc; Gautam, Tripti; Csiszar, Anna; Sonntag, William E

    2013-12-01

    Cerebromicrovascular rarefaction is believed to play a central role in cognitive impairment in patients receiving whole-brain irradiation therapy. To elucidate the mechanism underlying the deleterious effects of γ-irradiation on the cerebral microcirculation, rat primary cerebromicrovascular endothelial cells (CMVECs) were irradiated in vitro. We found that in CMVECs, γ-irradiation (2-8 Gy) elicited increased DNA damage, which was repaired less efficiently in CMVECs compared with neurons, microglia, and astrocytes. Increased genomic injury in CMVECs associated with increased apoptotic cell death. In the surviving cells, γ-irradiation promotes premature senescence (indicated by SA-β-galactosidase positivity and upregulation of p16 (INK4a) ), which was associated with impaired angiogenic capacity (decreased proliferation and tube-forming capacity). γ-Irradiated CMVECs acquired a senescence-associated secretory phenotype, characterized by upregulation of proinflammatory cytokines and chemokines (including IL-6, IL-1α, and MCP-1). Collectively, increased vulnerability of γ-irradiated CMVECs and their impaired angiogenic capacity likely contribute to cerebromicrovascular rarefaction and prevent regeneration of the microvasculature postirradiation. The acquisition of a senescence-associated secretory phenotype in irradiated CMVECs is biologically highly significant as changes in the cytokine microenvironment in the hippocampus may affect diverse biological processes relevant for normal neuronal function (including regulation of neurogenesis and the maintenance of the blood brain barrier).

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

    PubMed

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

    2015-09-08

    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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. Species-dependent stereoselective drug binding to albumin: a circular dichroism study.

    PubMed

    Pistolozzi, Marco; Bertucci, Carlo

    2008-03-01

    Drug binding to albumins from different mammalian species was investigated to disclose evidence of species-dependent stereoselectivity in drug-binding processes and affinities. This aspect is important for evaluating the reliability of extrapolating distribution data among species. The circular dichroism (CD) signal induced by drug binding to the albumins [human serum albumin (HSA), bovine serum albumin (BSA), rat serum albumin (RSA), and dog serum albumin (DSA)] were measured and analyzed. The binding of selected drugs and metabolites to HSA significantly differed from the binding to the other albumins in terms of affinity and conformation of the bound ligands. In particular, phenylbutazone, a marker of site one on HSA, showed a higher affinity for binding to BSA with respect to RSA, HSA, and DSA, respectively. In the case of diazepam, a marker of site two on HSA, the affinity decreased in order from HSA to DSA, RSA, and BSA. The induced CD spectra were similar in terms of energy and band signs, suggesting almost the same conformation for the bound drug to the different albumins. Stereoselectivity was high for the binding of ketoprofen to HSA and RSA. A different sign was observed for the CD spectra induced by the drug to the two albumins because of the prevalence of a different conformation of the bound drug. Interestingly, the same induced CD spectra were obtained using either the racemic form or the (S)-enantiomer. Finally, significant differences were observed in the affinity of bilirubin, being highest for BSA, then decreasing for RSA, HSA, and DSA. A more complex conformational equilibrium was observed for bound bilirubin.

  16. 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.

  17. 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.

  18. Whole body hyperthermia, but not skin hyperthermia, accelerates brain and locomotor limb circulatory strain and impairs exercise capacity in humans.

    PubMed

    Trangmar, Steven J; Chiesa, Scott T; Kalsi, Kameljit K; Secher, Niels H; González-Alonso, José

    2017-01-01

    Cardiovascular strain and hyperthermia are thought to be important factors limiting exercise capacity in heat-stressed humans, however, the contribution of elevations in skin (Tsk) versus whole body temperatures on exercise capacity has not been characterized. To ascertain their relationships with exercise capacity, blood temperature (TB), oxygen uptake (V̇O2), brain perfusion (MCA Vmean), locomotor limb hemodynamics, and hematological parameters were assessed during incremental cycling exercise with elevated skin (mild hyperthermia; HYPmild), combined core and skin temperatures (moderate hyperthermia; HYPmod), and under control conditions. Both hyperthermic conditions increased Tsk versus control (6.2 ± 0.2°C; P < 0.001), however, only HYPmod increased resting TB, leg blood flow and cardiac output (Q̇), but not MCA Vmean Throughout exercise, Tsk remained elevated in both hyperthermic conditions, whereas only TB was greater in HYPmod At exhaustion, oxygen uptake and exercise capacity were reduced in HYPmod in association with lower leg blood flow, MCA Vmean and mean arterial pressure (MAP), but similar maximal heart rate and TB The attenuated brain and leg perfusion with hyperthermia was associated with a plateau in MCA and two-legged vascular conductance (VC). Mechanistically, the falling MCA VC was coupled to reductions in PaCO2, whereas the plateau in leg vascular conductance was related to markedly elevated plasma [NA] and a plateau in plasma ATP These findings reveal that whole-body hyperthermia, but not skin hyperthermia, compromises exercise capacity in heat-stressed humans through the early attenuation of brain and active muscle blood flow.

  19. Working Memory Capacity as a Factor Influencing the Relationship between Language Outcome and Rehabilitation in Mandarin-Speaking Preschoolers with Congenital Hearing Impairment

    PubMed Central

    Lo, Ming; Chen, Pei-Hua

    2017-01-01

    Memory processes could account for a significant part of the variance in language performances of hearing-impaired children. However, the circumstance in which the performance of hearing-impaired children can be nearly the same as the performance of hearing children remains relatively little studied. Thus, a group of pre-school children with congenital, bilateral hearing loss and a group of pre-school children with normal hearing were invited to participate in this study. In addition, the hearing-impaired participants were divided into two groups according to their working memory span. A language disorder assessment test for Mandarin-speaking preschoolers was used to measure the outcomes of receptive and expressive language of the two groups of children. The results showed that the high-span group performed as good as the hearing group, while the low-span group showed lower accuracy than the hearing group. A linear mixed-effects analysis showed that not only length of rehabilitation but also the memory span affected the measure of language outcome. Furthermore, the rehabilitation length positively correlated with the measure of expressive language only among the participants of the high-span group. The pattern of the results indicates that working memory capacity is one of the factors that could support the children to acquire age-equivalent language skills. PMID:28337168

  20. 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

  1. Drug binding in human P-glycoprotein causes conformational changes in both nucleotide-binding domains.

    PubMed

    Loo, Tip W; Bartlett, M Claire; Clarke, David M

    2003-01-17

    The human multidrug resistance P-glycoprotein (P-gp, ABCB1) uses ATP to transport many structurally diverse compounds out of the cell. It is an ABC transporter with two nucleotide-binding domains (NBDs) and two transmembrane domains (TMDs). Recently, we showed that the "LSGGQ" motif in one NBD ((531)LSGGQ(535) in NBD1; (1176)LSGGQ(1180) in NBD2) is adjacent to the "Walker A" sequence ((1070)GSSGCGKS(1077) in NBD2; (427)GNSGCGKS(434) in NBD1) in the other NBD (Loo, T. W., Bartlett, M. C., and Clarke, D. M. (2002) J. Biol. Chem. 277, 41303-41306). Drug substrates can stimulate or inhibit the ATPase activity of P-gp. Here, we report the effect of drug binding on cross-linking between the LSGGQ signature and Walker A sites (Cys(431)(NBD1)/C1176C(NBD2) and Cys(1074)(NBD2)/L531C(NBD1), respectively). Seven drug substrates (calcein-AM, demecolcine, cis(Z)-flupentixol, verapamil, cyclosporin A, Hoechst 33342, and trans(E)-flupentixol) were tested for their effect on oxidative cross-linking. Substrates that stimulated the ATPase activity of P-gp (calcein-AM, demecolcine, cis(Z)-flupentixol, and verapamil) increased the rate of cross-linking between Cys(431)(NBD1-Walker A)/C1176C(NBD2-LSGGQ) and between Cys(1074)(NBD2-Walker A)/L531C(NBD1-LSGGQ) when compared with cross-linking in the absence of drug substrate. By contrast, substrates that inhibited ATPase activity (cyclosporin A, Hoechst 33342, and trans(E)-flupentixol) decreased the rate of cross-linking. These results indicate that interaction between the LSGGQ motifs and Walker A sites must be essential for coupling drug binding to ATP hydrolysis. Drug binding in the transmembrane domains can induce long range conformational changes in the NBDs, such that compounds that stimulate or inhibit ATPase activity must decrease and increase, respectively, the distance between the Walker A and LSGGQ sequences.

  2. 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

  3. Low pH conditions impair module capacity to regenerate in a calcified colonial invertebrate, the bryozoan Cryptosula pallasiana.

    PubMed

    Lombardi, Chiara; Taylor, Paul D; Cocito, Silvia; Bertolini, Camilla; Calosi, Piero

    2017-04-01

    Many aquatic animals grow into colonies of repeated, genetically identical, modules (zooids). Zooid interconnections enable colonies to behave as integrated functional units, while plastic responses to environmental changes may affect individual zooids. Plasticity includes the variable partitioning of resources to sexual reproduction, colony growth and maintenance. Maintenance often involves regeneration, which is also a routine part of the life history in some organisms, such as bryozoans. Here we investigate changes in regenerative capacity in the encrusting bryozoan Cryptosula pallasiana when cultured at different seawater pCO2 levels. The proportion of active zooids showing polypide regeneration was highest at current oceanic pH (8.1), but decreased progressively as pH declined below that value, reaching a six-fold reduction at pH 7.0. The zone of budding of new zooids at the colony periphery declined in size below pH 7.7. Under elevated pCO2 conditions, already experienced sporadically in coastal areas, skeletal corrosion was accompanied by the proportional reallocation of resources from polypide regeneration in old zooids to the budding of new zooids at the edge of the colony. Thus, future ocean acidification can affect colonial organisms by changing how they allocate resources, with potentially profound impacts on life-history patterns and ecological interactions.

  4. Impaired regenerative capacity and lower revertant fibre expansion in dystrophin-deficient mdx muscles on DBA/2 background

    PubMed Central

    Rodrigues, Merryl; Echigoya, Yusuke; Maruyama, Rika; Lim, Kenji Rowel Q.; Fukada, So-ichiro; Yokota, Toshifumi

    2016-01-01

    Duchenne muscular dystrophy, one of the most common lethal genetic disorders, is caused by mutations in the DMD gene and a lack of dystrophin protein. In most DMD patients and animal models, sporadic dystrophin-positive muscle fibres, called revertant fibres (RFs), are observed in otherwise dystrophin-negative backgrounds. RFs are thought to arise from skeletal muscle precursor cells and clonally expand with age due to the frequent regeneration of necrotic fibres. Here we examined the effects of genetic background on muscle regeneration and RF expansion by comparing dystrophin-deficient mdx mice on the C57BL/6 background (mdx-B6) with those on the DBA/2 background (mdx-DBA), which have a more severe phenotype. Interestingly, mdx-DBA muscles had significantly lower RF expansion than mdx-B6 in all age groups, including 2, 6, 12, and 18 months. The percentage of centrally nucleated fibres was also significantly lower in mdx-DBA mice compared to mdx-B6, indicating that less muscle regeneration occurs in mdx-DBA. Our study aligns with the model that RF expansion reflects the activity of precursor cells in skeletal muscles, and it serves as an index of muscle regeneration capacity. PMID:27924830

  5. Eccentric Contraction-Induced Muscle Injury: Reproducible, Quantitative, Physiological Models to Impair Skeletal Muscle's Capacity to Generate Force.

    PubMed

    Call, Jarrod A; Lowe, Dawn A

    2016-01-01

    In order to investigate the molecular and cellular mechanisms of muscle regeneration an experimental injury model is required. Advantages of eccentric contraction-induced injury are that it is a controllable, reproducible, and physiologically relevant model to cause muscle injury, with injury being defined as a loss of force generating capacity. While eccentric contractions can be incorporated into conscious animal study designs such as downhill treadmill running, electrophysiological approaches to elicit eccentric contractions and examine muscle contractility, for example before and after the injurious eccentric contractions, allows researchers to circumvent common issues in determining muscle function in a conscious animal (e.g., unwillingness to participate). Herein, we describe in vitro and in vivo methods that are reliable, repeatable, and truly maximal because the muscle contractions are evoked in a controlled, quantifiable manner independent of subject motivation. Both methods can be used to initiate eccentric contraction-induced injury and are suitable for monitoring functional muscle regeneration hours to days to weeks post-injury.

  6. Gated auditory speech perception in elderly hearing aid users and elderly normal-hearing individuals: effects of hearing impairment and cognitive capacity.

    PubMed

    Moradi, Shahram; Lidestam, Björn; Hällgren, Mathias; Rönnberg, Jerker

    2014-07-31

    This study compared elderly hearing aid (EHA) users and elderly normal-hearing (ENH) individuals on identification of auditory speech stimuli (consonants, words, and final word in sentences) that were different when considering their linguistic properties. We measured the accuracy with which the target speech stimuli were identified, as well as the isolation points (IPs: the shortest duration, from onset, required to correctly identify the speech target). The relationships between working memory capacity, the IPs, and speech accuracy were also measured. Twenty-four EHA users (with mild to moderate hearing impairment) and 24 ENH individuals participated in the present study. Despite the use of their regular hearing aids, the EHA users had delayed IPs and were less accurate in identifying consonants and words compared with the ENH individuals. The EHA users also had delayed IPs for final word identification in sentences with lower predictability; however, no significant between-group difference in accuracy was observed. Finally, there were no significant between-group differences in terms of IPs or accuracy for final word identification in highly predictable sentences. Our results also showed that, among EHA users, greater working memory capacity was associated with earlier IPs and improved accuracy in consonant and word identification. Together, our findings demonstrate that the gated speech perception ability of EHA users was not at the level of ENH individuals, in terms of IPs and accuracy. In addition, gated speech perception was more cognitively demanding for EHA users than for ENH individuals in the absence of semantic context.

  7. 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

  8. Activated hepatic stellate cells impair NK cell anti-fibrosis capacity through a TGF-β-dependent emperipolesis in HBV cirrhotic patients.

    PubMed

    Shi, Jijing; Zhao, Juanjuan; Zhang, Xin; Cheng, Yongqian; Hu, Jinhua; Li, Yuanyuan; Zhao, Xin; Shang, Qinghua; Sun, Yanling; Tu, Bo; Shi, Lei; Gao, Bin; Wang, Fu-Sheng; Zhang, Zheng

    2017-03-14

    Natural killer (NK) cells can induce liver fibrosis remission by killing hepatic stellate cells (HSCs) and producing interferon (IFN)-γ in a mouse model; however, their anti-fibrotic immune-characteristics and regulatory mechanisms by HSCs remain to be determined, especially in livers from HBV-infected liver cirrhosis (LC) patients. We analyzed frequency, phenotype and anti-fibrotic function of hepatic and peripheral NK subsets in 43 HBV-LC patients. We found that hepatic NK subsets from LC patients displayed a decreased frequency, activation status and anti-fibrotic activity compared with those from chronic hepatitis B patients, which were mainly mediated by increased intrahepatic tumour-growth factor (TGF)-β because blockade of TGF-β significantly reversed NK anti-fibrotic function in vitro. In vivo, hepatic NK cells were enriched in proximity to the α-smooth muscle actin (α-SMA+) area within mild fibrosis regions; while in severe fibrotic areas, they were either directly attached to or separated from the α-SMA+ region. NK cells from LC patients could enter HSCs to form emperipolesis (a cell-in-cell structure) and become apoptotic; anti-TGF-β treatment ameliorated this emperipolesis. This finding suggested a novel mechanism by which activated HSCs impair NK cells' anti-fibrosis capacity through a TGF-β-dependent emperipolesis in LC patients, providing an anti-fibrotic rational by enhancing NK cell activity.

  9. Activated hepatic stellate cells impair NK cell anti-fibrosis capacity through a TGF-β-dependent emperipolesis in HBV cirrhotic patients

    PubMed Central

    Shi, Jijing; Zhao, Juanjuan; Zhang, Xin; Cheng, Yongqian; Hu, Jinhua; Li, Yuanyuan; Zhao, Xin; Shang, Qinghua; Sun, Yanling; Tu, Bo; Shi, Lei; Gao, Bin; Wang, Fu-Sheng; Zhang, Zheng

    2017-01-01

    Natural killer (NK) cells can induce liver fibrosis remission by killing hepatic stellate cells (HSCs) and producing interferon (IFN)-γ in a mouse model; however, their anti-fibrotic immune-characteristics and regulatory mechanisms by HSCs remain to be determined, especially in livers from HBV-infected liver cirrhosis (LC) patients. We analyzed frequency, phenotype and anti-fibrotic function of hepatic and peripheral NK subsets in 43 HBV-LC patients. We found that hepatic NK subsets from LC patients displayed a decreased frequency, activation status and anti-fibrotic activity compared with those from chronic hepatitis B patients, which were mainly mediated by increased intrahepatic tumour-growth factor (TGF)-β because blockade of TGF-β significantly reversed NK anti-fibrotic function in vitro. In vivo, hepatic NK cells were enriched in proximity to the α-smooth muscle actin (α-SMA+) area within mild fibrosis regions; while in severe fibrotic areas, they were either directly attached to or separated from the α-SMA+ region. NK cells from LC patients could enter HSCs to form emperipolesis (a cell-in-cell structure) and become apoptotic; anti-TGF-β treatment ameliorated this emperipolesis. This finding suggested a novel mechanism by which activated HSCs impair NK cells’ anti-fibrosis capacity through a TGF-β-dependent emperipolesis in LC patients, providing an anti-fibrotic rational by enhancing NK cell activity. PMID:28291251

  10. 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.

  11. 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

  12. Drug binding and mobility relating to the thermal fluctuation in fluid lipid membranes

    NASA Astrophysics Data System (ADS)

    Okamura, Emiko; Yoshii, Noriyuki

    2008-12-01

    Drug binding and mobility in fluid lipid bilayer membranes are quantified in situ by using the multinuclear solution NMR combined with the pulsed-field-gradient technique. One-dimensional and pulsed-field-gradient F19 and H1 NMR signals of an anticancer drug, 5-fluorouracil (5FU) are analyzed at 283-313 K in the presence of large unilamellar vesicles (LUVs) of egg phosphatidylcholine (EPC) as model cell membranes. The simultaneous observation of the membrane-bound and free 5FU signals enables to quantify in what amount of 5FU is bound to the membrane and how fast 5FU is moving within the membrane in relation to the thermal fluctuation of the soft, fluid environment. It is shown that the mobility of membrane-bound 5FU is slowed down by almost two orders of magnitude and similar to the lipid movement in the membrane, the movement closely related to the intramembrane fluidity. The mobility of 5FU and EPC is, however, not similar at 313 K; the 5FU movement is enhanced in the membrane as a result of the loose binding of 5FU in the lipid matrices. The membrane-bound fraction of 5FU is ˜0.1 and almost unaltered over the temperature range examined. It is also independent of the 5FU concentration from 2 to 30 mM with respect to the 40-50 mM LUV. The free energy of the 5FU binding is estimated at -4 to -2 kJ/mol, the magnitude always close to the thermal fluctuation, 2.4-2.6 kJ/mol.

  13. An impaired health related muscular fitness contributes to a reduced walking capacity in patients with schizophrenia: a cross-sectional study

    PubMed Central

    2013-01-01

    Background Patients with schizophrenia report muscle weakness. The relation of this muscle weakness with performing daily life activities such as walking is however not yet studied. The aim of this study was to quantify walking capacity and health related muscular fitness in patients with schizophrenia compared with age-, gender and body mass index (BMI)-matched healthy controls. Secondly, we identified variables that could explain the variability in walking capacity and in health related muscular fitness in patients with schizophrenia. Methods A total of 100 patients with schizophrenia and 40 healthy volunteers were initially screened. Eighty patients with schizophrenia (36.8±10.0 years) and the 40 age-, gender- and body mass index (BMI)-matched healthy volunteers (37.1±10.3 years) were finally included. All participants performed a standing broad jump test (SBJ) and a six-minute walk test (6MWT) and filled out the International Physical Activity Questionnaire. Patients additionally had a fasting metabolic laboratory screening and were assessed for psychiatric symptoms. Results Patients with schizophrenia did have lower 6MWT (17.9%, p<0.001) [effect size (ES)=−1.01] and SBJ (14.1%, p<0.001) (ES=−0.57) scores. Patients were also less physically active (1291.0±1201.8 metabolic equivalent-minutes/week versus 2463.1±1365.3, p<0.001) (ES=−0.91) than controls. Schizophrenia patients with metabolic syndrome (MetS) (35%) had a 23.9% lower (p<0.001) SBJ-score and 22.4% (p<0.001) lower 6MWT-score than those without MetS. In multiple regression analysis, 71.8% of the variance in 6MWT was explained by muscular fitness, BMI, presence of MetS and physical activity participation, while 53.9% of the variance in SBJ-score was explained by age, illness duration, BMI and physical activity participation. Conclusions The walking capacity and health-related muscular fitness are impaired in patients with schizophrenia and both should be a major focus in daily clinical practice

  14. Drug design for protein kinases and phosphatases: flexible-receptor docking, binding affinity and specificity, and drug-binding kinetics.

    PubMed

    Wong, Chung F; Bairy, Sneha

    2013-01-01

    This article reviews some of our experiences on applying computational techniques to aid the design of drugs targeting protein kinases and phosphatases. It is not a comprehensive review. Rather, it focuses on several less explored approaches or ideas that we have experiences on. It reviews some recent improvements on the Poisson-Boltzmann/Surface Area model for calculating binding affinity and discusses ways to perform calculations that are more tolerant to statistical and systematic errors. Several new ways to incorporate protein flexibility in molecular docking and estimating binding affinity are also discussed. Its discussions also go beyond binding affinity to considering drug-binding kinetics, not only on investigating protein-ligand interactions in isolation, but also on accounting for upstream and downstream influences that can occur in cells, through kinetic modeling of cell signaling. This review also describes a quick molecular simulation method for understanding drug-binding kinetics at the molecular level, with the hope of generating guiding principles for designing drugs with the desired kinetic properties. Sources of drug-binding selectivity that appear obvious but often overlooked are also discussed.

  15. Maternal effects and population regulation: maternal density-induced reproduction suppression impairs offspring capacity in response to immediate environment in root voles Microtus oeconomus.

    PubMed

    Bian, Jiang-Hui; Du, Shou-Yang; Wu, Yan; Cao, Yi-Fan; Nie, Xu-Heng; He, Hui; You, Zhi-Bing

    2015-03-01

    FCM elevations, reproduction suppression and body mass decrease at sexual maturity in offspring. The FCM elevations and reproduction suppression were independent of offspring population density and correlated with decreased offspring quality. These findings indicate that intrinsic state alterations induced by maternal stress impair offspring capacity in response to immediate environment, and these alterations are likely mediated by maternal stress system. The maladaptive reproduction suppression seen in HL group suggests intrinsic population density as one of ecological factors generating delayed density-dependent effects.

  16. A comprehensive analysis of the influence of drug binding kinetics on drug action at molecular and systems levels.

    PubMed

    Yin, Ning; Pei, Jianfeng; Lai, Luhua

    2013-06-01

    Binding kinetics is closely related to the efficacy of drugs. Several aspects of binding kinetics, such as long residence or frequent dissociation, have been proposed to affect drug properties such as efficacy, selectivity, and multi-target potency. However, a comprehensive and balanced study of binding kinetics in various scenarios is still needed. We performed a comprehensive computational analysis of the role of drug binding kinetics in various situations such as enzyme inhibition, receptor binding, multi-target drug targeting, signal transduction pathways, and metabolic networks. Molecular studies of enzyme inhibition, receptor binding, and multi-target drugs have shown that at constant binding affinity, fast associating drugs show better enzyme inhibitory effects, earlier and higher receptor occupancy peaks, and better multi-target performances, while slow dissociating drugs show prolonged receptor occupancy, as suggested by others. Different situations exemplify slightly different kinetic-efficacy relationships, and each must be considered separately. At the systems level, binding kinetics can not only change the overall effect of drugs, but can also affect signaling dynamics. For example, in the tumor necrosis factor α-induced nuclear factor-κB pathway, inhibitor addition can delay the onset of oscillations and decrease their frequencies, with these changes varying with the binding kinetics of the inhibitor. The effects of drug binding kinetics also depend on network topology and where the target is located in the network. For successful drug discovery, both molecular binding kinetics and systems level requirements need to be considered.

  17. Drug-binding properties of rat alpha 1-foetoprotein. Binding of warfarin, phenylbutazone, azapropazone, diazepam, digitoxin and cholic acid.

    PubMed Central

    Hervé, F; Rajkowski, K; Martin, M T; Dessen, P; Cittanova, N

    1984-01-01

    As part of an investigation into whether alpha 1-foetoprotein (alpha 1-FP) plays the same transport role in foetal serum as albumin does in the adult, the binding properties of both proteins were compared with respect to the binding of a series of compounds known to be bound by albumin's specific drug-binding sites. The binding of warfarin, phenylbutazone, azapropazone, diazepam, digitoxin and cholic acid by rat alpha 1-FP and serum albumin was studied by equilibrium dialysis at 4 degrees C. Rat alpha 1-FP was shown to have neither albumin's high-affinity site II (diazepam as marker) nor its site III (digitoxin and cholic acid as markers). High-affinity binding by alpha 1-FP was found for the specific markers (warfarin, phenylbutazone, azapropazone) of albumin's drug-binding site I. However, instead of albumin's one high-affinity site/molecule, a mean value of 0.5 site/molecule was obtained with rat alpha 1-FP. Charcoal treatment at neutral pH of rat serum albumin did not affect its measured binding properties, but treatment of the alpha 1-FP led to an increased affinity for warfarin, phenylbutazone and azapropazone without a change in the measured number of sites, indicating competition for binding at this site by (an) endogenous ligand(s). These results are discussed in terms of the structures of the two proteins and with respect to the physiological implications of the differences found. PMID:6206846

  18. 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.'

  19. Profiling of drug binding proteins by monolithic affinity chromatography in combination with liquid chromatography-tandem mass spectrometry.

    PubMed

    Zhang, Xuepei; Wang, Tongdan; Zhang, Hanzhi; Han, Bing; Wang, Lishun; Kang, Jingwu

    2014-09-12

    A new approach for proteome-wide profiling drug binding proteins by using monolithic capillary affinity chromatography in combination with HPLC-MS/MS is reported. Two immunosuppresive drugs, namely FK506 and cyclosporin A, were utilized as the experimental models for proof-of-concept. The monolithic capillary affinity columns were prepared through a single-step copolymerization of the drug derivatives with glycidyl methacrylate and ethylene dimethacrylate. The capillary chromatography with the affinity monolithic column facilitates the purification of the drug binding proteins from the cell lysate. By combining the capillary affinity column purification and the shot-gun proteomic analysis, totally 33 FK506- and 32 CsA-binding proteins including all the literature reported target proteins of these two drugs were identified. Among them, two proteins, namely voltage-dependent anion-selective channel protein 1 and serine/threonine-protein phosphatase PGAM5 were verified by using the recombinant proteins. The result supports that the monolithic capillary affinity chromatography is likely to become a valuable tool for profiling of binding proteins of small molecular drugs as well as bioactive compounds.

  20. Water participation in molecular recognition and protein-ligand association: Probing the drug binding site "Sudlow I" in human serum albumin

    NASA Astrophysics Data System (ADS)

    Al-Lawatia, Najla; Steinbrecher, Thomas; Abou-Zied, Osama K.

    2012-03-01

    Human serum albumin (HSA) plays an important role in the transport and disposition of endogenous and exogenous ligands present in blood. Its capacity to reversibly bind a large variety of drugs results in its prevailing role in drug pharmacokinetics and pharmacodynamics. In this work, we used 7-hydroxyquinoline (7HQ) as a probe to study the binding nature of one of the major drug binding sites of HSA (Sudlow I) and to reveal the local environment around the probe in the binding site. The interaction between 7HQ and HSA at a physiological pH of 7.2 was investigated using steady-state and lifetime spectroscopic measurements, molecular docking and molecular dynamics (MD) simulations methods. The fluorescence results indicate a selective interaction between 7HQ and the Trp214 residue. The reduction in both the intensity and lifetime of the Trp214 fluorescence upon probe binding indicates the dominant role of static quenching. Molecular docking and MD simulations show that 7HQ binds in Sudlow site I close to Trp214, confirming the experimental results, and pinpoint the dominant role of hydrophobic interaction in the binding site. Electrostatic interactions were also found to be important in which two water molecules form strong hydrogen bonds with the polar groups of 7HQ. Detection of water in the binding site agrees with the absorption and fluorescence results that show the formation of a zwitterion tautomer of 7HQ. The unique spectral signatures of 7HQ in water make this molecule a potential probe for detecting the presence of water in nanocavities of proteins. Interaction of 7HQ with water in the binding site shows that water molecules can be crucial for molecular recognition and association in protein binding sites.

  1. 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…

  2. Impaired visual short-term memory capacity is distinctively associated with structural connectivity of the posterior thalamic radiation and the splenium of the corpus callosum in preterm-born adults.

    PubMed

    Menegaux, Aurore; Meng, Chun; Neitzel, Julia; Bäuml, Josef G; Müller, Hermann J; Bartmann, Peter; Wolke, Dieter; Wohlschläger, Afra M; Finke, Kathrin; Sorg, Christian

    2017-02-07

    Preterm birth is associated with an increased risk for lasting changes in both the cortico-thalamic system and attention; however, the link between cortico-thalamic and attention changes is as yet little understood. In preterm newborns, cortico-cortical and cortico-thalamic structural connectivity are distinctively altered, with increased local clustering for cortico-cortical and decreased integrity for cortico-thalamic connectivity. In preterm-born adults, among the various attention functions, visual short-term memory (vSTM) capacity is selectively impaired. We hypothesized distinct associations between vSTM capacity and the structural integrity of cortico-thalamic and cortico-cortical connections, respectively, in preterm-born adults. A whole-report paradigm of briefly presented letter arrays based on the computationally formalized Theory of Visual Attention (TVA) was used to quantify parameter vSTM capacity in 26 preterm- and 21 full-term-born adults. Fractional anisotropy (FA) of posterior thalamic radiations and the splenium of the corpus callosum obtained by diffusion tensor imaging were analyzed by tract-based spatial statistics and used as proxies for cortico-thalamic and cortico-cortical structural connectivity. The relationship between vSTM capacity and cortico-thalamic and cortico-cortical connectivity, respectively, was significantly modified by prematurity. In full-term-born adults, the higher FA in the right posterior thalamic radiation the higher vSTM capacity; in preterm-born adults this FA-vSTM-relationship was inversed. In the splenium, higher FA was correlated with higher vSTM capacity in preterm-born adults, whereas no significant relationship was evident in full-term-born adults. These results indicate distinct associations between cortico-thalamic and cortico-cortical integrity and vSTM capacity in preterm-and full-term-born adults. Data suggest compensatory cortico-cortical fiber re-organization for attention deficits after preterm delivery.

  3. Drug binding to human serum albumin: abridged review of results obtained with high-performance liquid chromatography and circular dichroism.

    PubMed

    Ascoli, Giorgio A; Domenici, Enrico; Bertucci, Carlo

    2006-09-01

    The drug binding to plasma and tissue proteins are fundamental factors in determining the overall pharmacological activity of a drug. Human serum albumin (HSA), together with alpha1-acid glycoprotein (AGP), are the most important plasma proteins, which act as drug carriers, with drug pharmacokinetic implications, resulting in important clinical impacts for drugs that have a relatively narrow therapeutic index. This review focuses on the combination of biochromatography and circular dichroism as an effective approach for the characterization of albumin binding sites and their enantioselectivity. Furthermore, their applications to the study of changes in the binding properties of the protein arising by the reversible or covalent binding of drugs are discussed, and examples of physiological relevance reported. Perspectives of these studies reside in supporting the development of new drugs, which require miniaturization to facilitate the screening of classes of compounds for their binding to the target protein, and a deeper characterization of the mechanisms involved in the molecular recognition processes.

  4. Effect of X-irradiation on epidermal immune function: decreased density and alloantigen-presenting capacity of Ia+ Langerhans cells and impaired production of epidermal cell-derived thymocyte activating factor (ETAF)

    SciTech Connect

    Breathnach, S.M.; Katz, S.I.

    1985-12-01

    The mechanisms involved in the modulation of cutaneous immune responses by x-irradiation on epidermal immune function. We therefore investigated the effect of x-irradiation of mice on: (a) the density of epidermal Ia+ Langerhans cells (LC) in immunofluorescence studies, (b) epidermal cell (EC) allostimulatory capacity in the allogeneic EC-lymphocyte reaction (ELR), and (c) production of epidermal cell-derived thymocyte activating factor (ETAF). C3H/He and BALB/c mice were irradiated with 900, 1800, 2700, or 3600 rad from a /sup 137/Cs source, and sacrificed 10 h or 3 days later. X-irradiation of mice 10 h previously only slightly decreased the density of epidermal Ia+ LC and did not affect the capacity of their EC to stimulate allogeneic responder lymphocytes in the ELR. X-irradiation of mice 3 days previously, however, resulted in a dose-dependent decrease in the density of Ia+ LC. This decrease was accompanied by a substantial reduction in EC allostimulatory capacity in the ELR at all doses of x-irradiation. ETAF production by cultured EC from mice x-irradiated 3 days previously was also found to be diminished at all doses of x-irradiation. Trypan blue exclusion studies demonstrated that the observed decreases in EC allostimulatory capacity and ETAF production were not the result of a generalized lethal effect of x-irradiation on EC. The reduction in EC allostimulatory capacity following in vivo x-irradiation could not be reversed by addition of exogenous ETAF or interleukin-1 in the ELR. Taken together, these results indicate that x-irradiation decreases the density of Ia+ LC, impairs LC alloantigen-presenting function, and reduces ETAF production. Thus cutaneous x-irradiation may affect inflammatory and neoplastic processes not only by its antimitotic activity, but also by a direct effect on EC which subserve immunologic functions.

  5. 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

  6. Elevated Pulmonary Arterial and Systemic Plasma Aldosterone Levels Associate with Impaired Cardiac Reserve Capacity during Exercise in Left Ventricular Systolic Heart Failure Patients: A Pilot Study

    PubMed Central

    Maron, Bradley A.; Stephens, Thomas E.; Farrell, Laurie A.; Oldham, William M.; Loscalzo, Joseph; Leopold, Jane A.; Lewis, Gregory D.

    2015-01-01

    Background Elevated levels of aldosterone are a modifiable contributor to clinical worsening in heart failure with reduced ejection fraction (HFrEF). Endothelin-1 (ET-1), which is increased in HFrEF, induces pulmonary endothelial aldosterone synthesis in vitro. However, whether transpulmonary aldosterone release occurs in humans or aldosterone relates to functional capacity in HFrEF is not known. Therefore, we aim to characterize ET-1 and transpulmonary aldosterone levels in HFrEF, and determine if aldosterone levels relate to peak volume of oxygen uptake (pVO2). Methods Data from 42 consecutive HFrEF patients and 18 controls referred for invasive cardiopulmonary exercise testing were analyzed retrospectively. Results Radial ET-1 levels were higher in HFrEF patients compared to controls (17.5 [11.5–31.4] vs. 11.5 [4.4–19.0] pg/ml, p=0.04). A significant ET-1 transpulmonary gradient (pulmonary arterial [PA] - radial arterial levels) was present in HFrEF (P<0.001), but not in controls (P=0.24). Compared to controls, aldosterone levels were increased in HFrEF patients in the PA (364 [250–489] vs. 581 [400–914] ng/dl, P<0.01) and radial compartments (366 [273–466] vs. 702 [443–1223] ng/dl, P<0.001). Akin to ET-1, a transpulmonary increase in aldosterone concentration was also observed between controls and HFrEF patients at rest (7.5 [−54–40] vs. 61.6 [−13.6–165] ng/dl, P=0.01) and peak exercise (−20.7 [−39.6–79.1] vs. +25.8 [−29.2–109.3] ng/dl, P=0.02). The adjusted pVO2 correlated inversely with aldosterone levels at peak activity in the PA (r=−0.31, P=0.01) and radial artery (r=−0.32, P=0.01). Conclusions These data provide preliminary evidence in support of increased transpulmonary aldosterone levels in HFrEF and suggest an inverse relationship between circulating aldosterone and pVO2. Future prospective studies are needed to characterize the functional effects of transpulmonary and circulating aldosterone on cardiac reserve

  7. New insights into non-enzymatic glycation of human serum albumin biopolymer: A study to unveil its impaired structure and function.

    PubMed

    Raghav, Alok; Ahmad, Jamal; Alam, Khursheed; Khan, Asad U

    2017-03-18

    Albumin glycation and subsequent formation of advanced glycation end products (AGEs) correlate with diabetes and associated complications. Human Serum Albumin (HSA) was modified with d-glucose for a 40day period under sterile conditions at 37°C. Modified samples along with native HSA (unmodified) were analyzed for impairment in biochemical characteristics ((fructosamine, carbonyl, thiol, lysine, arginine, hydroxymethyl furfural [HMF] content), electrochemical (electrical conductance), simulated gastric fluid assay, simulated intestinal fluid assay, spectroscopic properties (UV, fluorescence), optical (surface contact angle) and fluid dynamics (viscosity and Stokes radius). Impairment in drug binding capacity of glycosylated-HSA was assessed with molecular docking experiment using metformin. UV-absorbance and fluorescence measurement were performed for drug bound glycated and native-HSA. Extensively modified HSA has been used to study its relevance in diabetes mellitus. Glucose modified-HSA resulted in AGEs formation. It suggests deleterious impairment in biochemical, electrochemical, spectroscopic, optical and fluidity properties of HSA at high concentrations of glucose. The results of the present study can be useful to understand the phenomenon of proteins damage in hyperglycemic conditions.

  8. Visual Impairment

    MedlinePlus

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Visual Impairment KidsHealth > For Teens > Visual Impairment Print A ... with the brain, making vision impossible. What Is Visual Impairment? Many people have some type of visual ...

  9. Interactions of human P-glycoprotein transport substrates and inhibitors at the drug binding domain: Functional and molecular docking analyses.

    PubMed

    Kadioglu, Onat; Saeed, Mohamed E M; Valoti, Massimo; Frosini, Maria; Sgaragli, Giampietro; Efferth, Thomas

    2016-03-15

    Rhodamine 123 (R123) transport substrate sensitizes P-glycoprotein (P-gp) to inhibition by compound 2c (cis-cis) N,N-bis(cyclohexanolamine)aryl ester isomer in a concentration-dependent manner in human MDR1-gene transfected mouse T-lymphoma L5178 cells as shown previously. By contrast, epirubicin (EPI) concentration changes left unaltered 2c IC50 values of EPI efflux. To clarify this discrepancy, defined molecular docking (DMD) analyses of 12 N,N-bis(cyclohexanolamine)aryl esters, the highly flexible aryl ester analog 4, and several P-gp substrate/non-substrate inhibitors were performed on human P-gp drug- or nucleotide-binding domains (DBD or NBD). DMD measurements yielded lowest binding energy (LBE, kcal/mol) values (mean ± SD) ranging from -11.8 ± 0.54 (valspodar) to -3.98 ± 0.01 (4). Lys234, Ser952 and Tyr953 residues formed H-bonds with most of the compounds. Only 2c docked also at ATP binding site (LBE value of -6.9 ± 0.30 kcal/mol). Inhibition of P-gp-mediated R123 efflux by 12 N,N-bis(cyclohexanolamine)aryl esters and 4 significantly correlated with LBE values. DMD analysis of EPI, (3)H-1EPI, (3)H-2EPI, (14)C-1EPI, (14)C-2EPI, R123 and 2c before and after previous docking of each of them indicated that pre-docking of either 2c or EPI significantly reduced LBE of both EPI and R123, and that of both (3)H-2EPI and (14)C-2EPI, respectively. Since the clusters of DBD amino acid residues interacting with EPI were different, if EPI docked alone or after pre-docking of EPI or 2c, the existence of alternative secondary binding site for EPI on P-gp is credible. In conclusion, 2c may allocate the drug-binding pocket and reduce strong binding of EPI and R123 in agreement with P-gp inhibition experiments, where 2c reduced efflux of EPI and R123.

  10. Biopartitioning micellar chromatography with sodium dodecyl sulfate as a pseudo α(1)-acid glycoprotein to the prediction of protein-drug binding.

    PubMed

    Hadjmohammadi, Mohammadreza; Salary, Mina

    2013-01-01

    A simple and fast method is of urgent need to measure protein-drug binding affinity in order to meet the rapid development of new drugs. Biopartitioning micellar chromatography (BMC), a mode of micellar liquid chromatography (MLC) using micellar mobile phases in adequate experimental conditions, can be useful as an in vitro system in mimicking the drug-protein interactions. In this study, sodium dodecyl sulfate-micellar liquid chromatography (SDS-MLC) was used for the prediction of protein-drug binding based on the similar property of SDS micelles to α(1)-acid glycoprotein (AGP). The relationships between the BMC retention data of a heterogeneous set of 14 basic and neutral drugs and their plasma protein binding parameter were studied and the predictive ability of models was evaluated. Modeling of logk(BMC) of these compounds was established by multiple linear regression (MLR) and second-order polynomial models obtained in two different concentrations (0.07 and 0.09M) of SDS. The developed MLR models were characterized by both the descriptive and predictive ability (R(2)=0.882, R(CV)(2)=0.832 and R(2)=0.840, R(CV)(2)=0.765 for 0.07 and 0.09M SDS, respectively). The p values <0.01 also indicated that the relationships between the protein-drug binding and the logk(BMC) values were statistically significant at the 99% confidence level. The standard error of estimation showed the standard deviation of the regression to be 11.89 and 13.87 for 0.07 and 0.09M, respectively. The application of the developed model to a prediction set demonstrated that the model was also reliable with good predictive accuracy. The external and internal validation results showed that the predicted values were in good agreement with the experimental value.

  11. 20 CFR 416.945 - Your residual functional capacity.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... impairment(s), and any related symptoms, such as pain, may cause physical and mental limitations that affect... that result from your symptoms, such as pain, provided by you, your family, neighbors, friends, or... impairment(s), even those that are not severe, in determining your residual functional capacity. Pain...

  12. 20 CFR 416.945 - Your residual functional capacity.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... impairment(s), and any related symptoms, such as pain, may cause physical and mental limitations that affect... that result from your symptoms, such as pain, provided by you, your family, neighbors, friends, or... impairment(s), even those that are not severe, in determining your residual functional capacity. Pain...

  13. 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

    2016-04-04

    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.

  14. Impaired Driving

    MedlinePlus

    Impaired driving is dangerous. It's the cause of more than half of all car crashes. It means operating a ... texting Having a medical condition which affects your driving For your safety and the safety of others, ...

  15. Taste - impaired

    MedlinePlus

    ... longer. Causes of impaired taste include: Bell's palsy Common cold Flu and other viral infections Nasal infection, nasal ... your diet. For taste problems due to the common cold or flu, normal taste should return when the ...

  16. 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

  17. Enhancing climate Adaptation Capacity for Drinking Water ...

    EPA Pesticide Factsheets

    Journal article This paper considers the adaptation capacity of conventional water treatment systems. A modeling framework is used to illustrate climate adaptation mechanisms that could enable conventional treatment systems to accommodate water quality impairments.

  18. 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

  19. Physical Impairment

    NASA Astrophysics Data System (ADS)

    Trewin, Shari

    Many health conditions can lead to physical impairments that impact computer and Web access. Musculoskeletal conditions such as arthritis and cumulative trauma disorders can make movement stiff and painful. Movement disorders such as tremor, Parkinsonism and dystonia affect the ability to control movement, or to prevent unwanted movements. Often, the same underlying health condition also has sensory or cognitive effects. People with dexterity impairments may use a standard keyboard and mouse, or any of a wide range of alternative input mechanisms. Examples are given of the diverse ways that specific dexterity impairments and input mechanisms affect the fundamental actions of Web browsing. As the Web becomes increasingly sophisticated, and physically demanding, new access features at the Web browser and page level will be necessary.

  20. All Vision Impairment

    MedlinePlus

    ... Home > Statistics and Data > All Vision Impairment All Vision Impairment Vision Impairment Defined Vision impairment is defined as the ... Ethnicity 2010 U.S. Age-Specific Prevalence Rates for Vision Impairment by Age and Race/Ethnicity Table for ...

  1. Atomic modelling and systematic mutagenesis identify residues in multiple drug binding sites that are essential for drug resistance in the major Candida transporter Cdr1.

    PubMed

    Nim, Shweta; Lobato, Lucia Gonzalez; Moreno, Alexis; Chaptal, Vincent; Rawal, Manpreet Kaur; Falson, Pierre; Prasad, Rajendra

    2016-11-01

    The ABC (ATP-Binding Cassette) transporter Cdr1 (Candida drug resistance 1) protein (Cdr1p) of Candida albicans, shows promiscuity towards the substrate it exports and plays a major role in antifungal resistance. It has two transmembrane domains (TMDs) comprising of six transmembrane helices (TMH) that envisage and confer the substrate specificity and two nucleotide binding domains (NBDs), interconnected by extracellular loops (ECLs) and intracellular loops (ICLs) Cdr1p. This study explores the diverse substrate specificity spectrum to get a deeper insight into the structural and functional features of Cdr1p. By screening with the variety of compounds towards an in-house TMH 252 mutant library of Cdr1p, we establish new substrates of Cdr1p. The localization of substrate-susceptible mutants in an ABCG5/G8 homology model highlights the common and specific binding pockets inside the membrane domain, where rhodamines and tetrazoliums mainly engage the N-moiety of Cdr1p, binding between TMH 2, 11 and surrounded by TMH 1, 5. Whereas, tin chlorides involve both N and C moieties located at the interface of TMH 2, 11, 1 and 5. Further, screening of the in house TMH mutant library of Cdr1p displays the TMH12 interaction with tetrazolium chloride, trimethyltin chloride and a Ca(2+) ionophore, A23187. In silico localization reveals a binding site at the TMH 12, 9 and 10 interface, which is widely exposed to the lipid interface. Together, for the first time, our study shows the molecular localization of Cdr1p substrates-binding sites and demonstrates the participation of TMH12 in a peripheral drug binding site.

  2. Mental capacity.

    PubMed

    Williams, Ruth

    2010-02-03

    Three short videos exploring some of the different principles in the Mental Capacity Act 2009 are available on Social Care TV, an online channel intended mainly for the social care sector, although the films are relevant to any professionals whose work is affected by the act. The dramas, which are set in a residential home, a person's own home and a residential school for young people with learning difficulties, concern thedecision-making process and can be viewed at www.scie.org.uk/socialcaretv/topic.asp?guid=377dbe1b-de0c-4d66-bb87-22a243542db2.

  3. Attenuated natural killer (NK) cell activation through C-type lectin-like receptor NKp80 is due to an anomalous hemi-immunoreceptor tyrosine-based activation motif (HemITAM) with impaired Syk kinase recruitment capacity.

    PubMed

    Rückrich, Thomas; Steinle, Alexander

    2013-06-14

    Cellular cytotoxicity is the hallmark of NK cells mediating both elimination of virus-infected or malignant cells, and modulation of immune responses. NK cytotoxicity is triggered upon ligation of various activating NK cell receptors. Among these is the C-type lectin-like receptor NKp80 which is encoded in the human Natural Killer Gene Complex (NKC) adjacent to its ligand, activation-induced C-type lectin (AICL). NKp80-AICL interaction promotes cytolysis of malignant myeloid cells, but also stimulates the mutual crosstalk between NK cells and monocytes. While many activating NK cell receptors pair with ITAM-bearing adaptors, we recently reported that NKp80 signals via a hemITAM-like sequence in its cytoplasmic domain. Here we molecularly dissect the NKp80 hemITAM and demonstrate that two non-consensus amino acids, in particular arginine 6, critically impair both hemITAM phosphorylation and Syk recruitment. Impaired Syk recruitment results in a substantial attenuation of cytotoxic responses upon NKp80 ligation. Reconstituting the hemITAM consensus or Syk overexpression resulted in robust NKp80-mediated responsiveness. Collectively, our data provide a molecular rationale for the restrained activation potential of NKp80 and illustrate how subtle alterations in signaling motifs determine subsequent cellular responses. They also suggest that non-consensus alterations in the NKp80 hemITAM, as commonly present among mammalian NKp80 sequences, may have evolved to dampen NKp80-mediated cytotoxic responses toward AICL-expressing cells.

  4. The BRCA1 alternative splicing variant Δ14-15 with an in-frame deletion of part of the regulatory serine-containing domain (SCD) impairs the DNA repair capacity in MCF-7 cells.

    PubMed

    Sevcik, Jan; Falk, Martin; Kleiblova, Petra; Lhota, Filip; Stefancikova, Lenka; Janatova, Marketa; Weiterova, Lenka; Lukasova, Emilie; Kozubek, Stanislav; Pohlreich, Petr; Kleibl, Zdenek

    2012-05-01

    The BRCA1 gene codes for a protein involved in the DNA double strand break (DDSB) repair. Alongside the dominant full-length splicing form of BRCA1, numerous endogenously expressed alternative splicing variants of unknown significance have been described in various tissues. Some of them retain the original BRCA1 reading frame but lack several critical BRCA1 structural domains, suggesting an altered function of the resulting protein in the BRCA1-regulated processes. To characterize the effect of the BRCA1Δ14-15 splicing variant (with an in-frame deletion affecting the regulatory serine-containing domain) on the DDSB repair, we constructed the MCF-7 clones stably expressing the analyzed variant with/without a shRNA-mediated downregulation of the endogenous full-length wild-type BRCA1 expression. Our results show that the expression of the BRCA1Δ14-15 variant delays the γ-radiation-induced DDSB repair, alters the kinetics of irradiation-induced foci formation/decomposition and reduces the non-homologous end-joining capacity in MCF-7 cells. Therefore, the BRCA1Δ14-15 is not able to functionally replace the full-length wt BRCA1 in the DDSB repair. Our findings indicate that the endogenously expressed BRCA1 alternative splicing variants may negatively influence genome stability and support the growing evidence of the pathological potential of the sequence variants generated by an altered or misregulated alternative splicing in the process of mammary malignant transformation.

  5. Cimetidine impairs nitrazepam clearance.

    PubMed

    Ochs, H R; Greenblatt, D J; Gugler, R; Müntefering, G; Locniskar, A; Abernethy, D R

    1983-08-01

    The effect of cimetidine on hepatic clearance of the benzodiazepine derivative nitrazepam was evaluated in healthy subjects. Six received a single 5- or 10-mg oral nitrazepam dose in the drug-free state and again with therapeutic cimetidine doses. Nitrazepam kinetics were determined from multiple serum concentrations measured during the 72 hr after each dose. Cimetidine had no effect on nitrazepam absorption kinetics, since peak serum nitrazepam concentration and time of peak concentration were not altered. Cimetidine did not alter nitrazepam volume of distribution, but cimetidine consistently reduced nitrazepam clearance, from a mean of 1.41 ml/min/kg in the control state to 1.17 ml/min/kg during cimetidine treatment. This resulted in prolongation of nitrazepam elimination t1/2 from 22.2 to 27.8 hr. Thus the ability of cimetidine to impair drug oxidation in man extends to the capacity for clearance of nitrazepam, a compound biotransformed mainly by nitroreduction.

  6. 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

  7. Cortical Visual Impairment

    MedlinePlus

    ... Frequently Asked Questions Español Condiciones Chinese Conditions Cortical Visual Impairment En Español Read in Chinese What is cortical visual impairment? Cortical visual impairment (CVI) is a decreased ...

  8. Comparative spectroscopic studies on drug binding characteristics and protein surface hydrophobicity of native and modified forms of bovine serum albumin: Possible relevance to change in protein structure/function upon non-enzymatic glycation

    NASA Astrophysics Data System (ADS)

    Khodarahmi, Reza; Karimi, Seyyed Arash; Ashrafi Kooshk, Mohammad Reza; Ghadami, Seyyed Abolghasem; Ghobadi, Sirous; Amani, Mojtaba

    2012-04-01

    The interaction between serum albumin (SA) and drugs has provided an interesting ground for understanding of drug effects, especially in drug distribution and drug-drug interaction on SA, in the case of multi-drug therapy. Determination of the impact of various factors on drug-protein interaction is especially important upon significant binding of drug to albumin. In the present study, the interaction of two drugs (furosemide and indomethacin) with native and modified albumins were investigated by using various spectroscopic methods. Fluorescence data indicated that 1:1 binding of drugs to bovine serum albumin (BSA) is associated with quenching of albumin intrinsic fluorescence. The Job's plot also confirmed that drug binds to BSA via mentioned stoichiometry. Analysis of the quenching and thermodynamic parameters indicated that intermolecular interactions between drug and albumin may change upon protein modification. The theoretical analyses also suggested some conformational changes of interacting side chains in subdomain IIA binding site (at the vicinity of W237), which were in good agreement with experimental data. Decrease of protein surface hydrophobicity (PSH) was also observed upon both albumin modification and drug binding.

  9. Comparative spectroscopic studies on drug binding characteristics and protein surface hydrophobicity of native and modified forms of bovine serum albumin: possible relevance to change in protein structure/function upon non-enzymatic glycation.

    PubMed

    Khodarahmi, Reza; Karimi, Seyyed Arash; Ashrafi Kooshk, Mohammad Reza; Ghadami, Seyyed Abolghasem; Ghobadi, Sirous; Amani, Mojtaba

    2012-04-01

    The interaction between serum albumin (SA) and drugs has provided an interesting ground for understanding of drug effects, especially in drug distribution and drug-drug interaction on SA, in the case of multi-drug therapy. Determination of the impact of various factors on drug-protein interaction is especially important upon significant binding of drug to albumin. In the present study, the interaction of two drugs (furosemide and indomethacin) with native and modified albumins were investigated by using various spectroscopic methods. Fluorescence data indicated that 1:1 binding of drugs to bovine serum albumin (BSA) is associated with quenching of albumin intrinsic fluorescence. The Job's plot also confirmed that drug binds to BSA via mentioned stoichiometry. Analysis of the quenching and thermodynamic parameters indicated that intermolecular interactions between drug and albumin may change upon protein modification. The theoretical analyses also suggested some conformational changes of interacting side chains in subdomain IIA binding site (at the vicinity of W237), which were in good agreement with experimental data. Decrease of protein surface hydrophobicity (PSH) was also observed upon both albumin modification and drug binding.

  10. 20 CFR 416.945 - Your residual functional capacity.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... impairment(s), and any related symptoms, such as pain, may cause physical and mental limitations that affect... that result from your symptoms, such as pain, provided by you, your family, neighbors, friends, or...), even those that are not severe, in determining your residual functional capacity. Pain or...

  11. 20 CFR 220.120 - The claimant's residual functional capacity.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 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 of.... Pain or other symptoms may cause a limitation of function beyond that which can be determined on...

  12. 20 CFR 220.120 - The claimant's residual functional capacity.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 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 of.... Pain or other symptoms may cause a limitation of function beyond that which can be determined on...

  13. 20 CFR 220.120 - The claimant's residual functional capacity.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 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 of.... Pain or other symptoms may cause a limitation of function beyond that which can be determined on...

  14. 20 CFR 404.1545 - Your residual functional capacity.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... impairment(s), and any related symptoms, such as pain, may cause physical and mental limitations that affect...), including limitations that result from your symptoms, such as pain, provided by you, your family, neighbors... that are not severe, in determining your residual functional capacity. Pain or other symptoms may...

  15. 20 CFR 416.945 - Your residual functional capacity.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... impairment(s), and any related symptoms, such as pain, may cause physical and mental limitations that affect... that result from your symptoms, such as pain, provided by you, your family, neighbors, friends, or...), even those that are not severe, in determining your residual functional capacity. Pain or...

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

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 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 of.... Pain or other symptoms may cause a limitation of function beyond that which can be determined on...

  17. CAPACITY OF PATIENTS WITH BRAIN METASTASES TO MAKE TREATMENT DECISIONS

    PubMed Central

    Triebel, Kristen L.; Gerstenecker, Adam; Meneses, Karen; Fiveash, John B.; Meyers, Christina A.; Cutter, Gary; Marson, Daniel C.; Martin, Roy C.; Eakin, Amanda; Watts, Olivia; Nabors, Louis B.

    2015-01-01

    OBJECTIVE To investigate medical decision-making capacity (MDC) in patients with brain metastasis. METHODS Participants were 41 adults with brain metastases with Karnofsky Performance Status scores ≥70 were recruited from an academic medical center and 41 demographically-matched controls recruited from the community. We evaluated MDC using the Capacity to Consent to Treatment Instrument (CCTI) and its four clinically relevant consent standards (expressing a treatment choice, appreciation, reasoning, and understanding). Capacity impairment ratings (no impairment, mild/moderate impairment, and severe impairment) on the consent standards were also assigned to each participant with brain metastasis using cutoff scores derived statistically from the performance of the control group. RESULTS The brain metastases patient group performed significantly below controls on consent standards of understanding and reasoning. Capacity compromise was defined as performance ≤1.5 standard deviations (SD) below the control group mean. Using this definition, approximately 60% of the participants with brain metastases demonstrated capacity compromise on at least one MDC standard. CONCLUSION When defining capacity compromise as performance ≤1.5 SD below the control group mean, over half of patients with brain metastases have reduced capacity to make treatment decisions. This impairment is demonstrated shortly after initial diagnosis of brain metastases and highlights the importance of routine clinical assessment of MDC following diagnosis of brain metastasis. These results also indicate a need for the development and investigation of interventions to support or improve MDC in this patient population. PMID:25613039

  18. 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.

  19. Financial capacity in older adults: a growing concern for clinicians.

    PubMed

    Gardiner, Paul A; Byrne, Gerard J; Mitchell, Leander K; Pachana, Nancy A

    2015-02-02

    Older people with cognitive impairment and/or dementia may be particularly vulnerable to diminished financial decision-making capacity. Financial capacity refers to the ability to satisfactorily manage one's financial affairs in a manner consistent with personal self-interest and values. Impairment of financial capacity makes the older individual vulnerable to financial exploitation, may negatively affect their family's financial situation and places strain on relationships within the family. Clinicians are often on the front line of responding to queries regarding decision-making capacity, and clinical evaluation options are often not well understood. Assessment of financial capacity should include formal objective assessment in addition to a clinical interview and gathering contextual data. Development of a flexible, empirically supported and clinically relevant assessment approach that spans all dimensions of financial capacity yet is simple enough to be used by non-specialist clinicians is needed.

  20. 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

  1. Impaired Waters and TMDLs

    EPA Pesticide Factsheets

    The 303(d) program provides guidance and technical resources to assist States in submitting lists of impaired waterbodies and the development of Total Maximum Daily Loads of the pollutant causing the impairment.

  2. 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.…

  3. 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

  4. 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,…

  5. Visual impairment in the hearing impaired students

    PubMed Central

    Gogate, Parikshit; Rishikeshi, Nikhil; Mehata, Reshma; Ranade, Satish; Kharat, Jitesh; Deshpande, Madan

    2009-01-01

    Background: Ocular problems are more common in children with hearing problems than in normal children. Neglected visual impairment could aggravate educational and social disability. Aim: To detect and treat visual impairment, if any, in hearing-impaired children. Setting and Design: Observational, clinical case series of hearing-impaired children in schools providing special education. Materials and Methods: Hearing-impaired children in selected schools underwent detailed visual acuity testing, refraction, external ocular examination and fundoscopy. Ocular motility testing was also performed. Teachers were sensitized and trained to help in the assessment of visual acuity using Snellen's E charts. Refractive errors and squint were treated as per standard practice. Statistical Analysis: Excel software was used for data entry and SSPS for analysis. Results: The study involved 901 hearing-impaired students between four and 21 years of age, from 14 special education schools. A quarter of them (216/901, 24%) had ocular problems. Refractive errors were the most common morbidity 167(18.5%), but only 10 children were using appropriate spectacle correction at presentation. Fifty children had visual acuity less than 20/80 at presentation; after providing refractive correction, this number reduced to three children, all of whom were provided low-vision aids. Other common conditions included strabismus in 12 (1.3%) children, and retinal pigmentary dystrophy in five (0.6%) children. Conclusion: Ocular problems are common in hearing-impaired children. Screening for ocular problems should be made mandatory in hearing-impaired children, as they use their visual sense to compensate for the poor auditory sense. PMID:19861747

  6. 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.

  7. 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

  8. 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.

  9. 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…

  10. 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…

  11. 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

  12. Capacity issues and decision-making in dementia

    PubMed Central

    Hegde, Soumya; Ellajosyula, Ratnavalli

    2016-01-01

    Capacity to make one's own decisions is fundamental to the autonomy of the individual. Capacity is a functional assessment made by a clinician to determine if a patient is capable of making a specific decision. Competency is a global assessment and legal determination made by a judge in court. Capacity evaluation for a patient with dementia is used to determine whether the patient is capable of giving informed consent, participate in research, manage their finances, live independently, make a will, and have ability to drive. Patients with dementia cannot be assumed to have impaired capacity. Even a patient with moderate or severe dementia, with obviously impaired capacity may still be able to indicate a choice and show some understanding. Four key components of decision-making in a capacity evaluation include understanding, communicating a choice, appreciation, and reasoning. Assessment of capacity requires a direct interview with the patient using open-ended questions and may include both informal and formal approaches depending on the situation and the context. A baseline cognitive evaluation with a simple test to assess executive function is often useful in capacity evaluation. All capacity evaluations are situation specific, relating to the particular decision under consideration, and are not global in scope. The clinician needs to spend adequate time with the patient and the family allaying their anxieties and also consider the sociocultural context. The area of capacity has considerable overlap with law and the clinician treating patients with dementia should understand the complexities of assessment and the implications of impaired capacity. It is also essential that the clinician be well informed and keep meticulous records. It is crucial to strike a balance between respecting the patient autonomy and acting in his/her best interest. PMID:27891023

  13. Capacity issues and decision-making in dementia.

    PubMed

    Hegde, Soumya; Ellajosyula, Ratnavalli

    2016-10-01

    Capacity to make one's own decisions is fundamental to the autonomy of the individual. Capacity is a functional assessment made by a clinician to determine if a patient is capable of making a specific decision. Competency is a global assessment and legal determination made by a judge in court. Capacity evaluation for a patient with dementia is used to determine whether the patient is capable of giving informed consent, participate in research, manage their finances, live independently, make a will, and have ability to drive. Patients with dementia cannot be assumed to have impaired capacity. Even a patient with moderate or severe dementia, with obviously impaired capacity may still be able to indicate a choice and show some understanding. Four key components of decision-making in a capacity evaluation include understanding, communicating a choice, appreciation, and reasoning. Assessment of capacity requires a direct interview with the patient using open-ended questions and may include both informal and formal approaches depending on the situation and the context. A baseline cognitive evaluation with a simple test to assess executive function is often useful in capacity evaluation. All capacity evaluations are situation specific, relating to the particular decision under consideration, and are not global in scope. The clinician needs to spend adequate time with the patient and the family allaying their anxieties and also consider the sociocultural context. The area of capacity has considerable overlap with law and the clinician treating patients with dementia should understand the complexities of assessment and the implications of impaired capacity. It is also essential that the clinician be well informed and keep meticulous records. It is crucial to strike a balance between respecting the patient autonomy and acting in his/her best interest.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. Vascular Cognitive Impairment.

    PubMed

    Dichgans, Martin; Leys, Didier

    2017-02-03

    Cerebrovascular disease typically manifests with stroke, cognitive impairment, or both. Vascular cognitive impairment refers to all forms of cognitive disorder associated with cerebrovascular disease, regardless of the specific mechanisms involved. It encompasses the full range of cognitive deficits from mild cognitive impairment to dementia. In principle, any of the multiple causes of clinical stroke can cause vascular cognitive impairment. Recent work further highlights a role of microinfarcts, microhemorrhages, strategic white matter tracts, loss of microstructural tissue integrity, and secondary neurodegeneration. Vascular brain injury results in loss of structural and functional connectivity and, hence, compromise of functional networks within the brain. Vascular cognitive impairment is common both after stroke and in stroke-free individuals presenting to dementia clinics, and vascular pathology frequently coexists with neurodegenerative pathology, resulting in mixed forms of mild cognitive impairment or dementia. Vascular dementia is now recognized as the second most common form of dementia after Alzheimer's disease, and there is increasing awareness that targeting vascular risk may help to prevent dementia, even of the Alzheimer type. Recent advances in neuroimaging, neuropathology, epidemiology, and genetics have led to a deeper understanding of how vascular disease affects cognition. These new findings provide an opportunity for the present reappraisal of vascular cognitive impairment. We further briefly address current therapeutic concepts.

  20. 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…

  1. 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. ...

  2. Speech impairment (adult)

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/003204.htm Speech impairment (adult) To use the sharing features on ... 2017, A.D.A.M., Inc. Duplication for commercial use must be authorized in writing by ADAM ...

  3. Kids' Quest: Vision Impairment

    MedlinePlus

    ... most important job. 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 ...

  4. Evaluation of hearing impairment.

    PubMed

    Zadeh, M H; Selesnick, S H

    2001-01-01

    Hearing impairment is among the most common medical condition presenting to health care professionals. Ear anatomy, physiology, and pathology resulting in hearing loss are discussed. A systematic approach to evaluation, diagnosis, and treatment is presented.

  5. 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.

  6. 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).

  7. 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).

  8. Trainable Mentally Impaired/Severely Multiply Impaired/Autistic Impaired/Severely Mentally Impaired. Product Evaluation Report 1989-1990.

    ERIC Educational Resources Information Center

    Claus, Richard N.; And Others

    The evaluation report describes special education services provided to trainable mentally impaired (TMI), autistic impaired (AI), severely multiply impaired (SXI), and severely mentally impaired (SMI) students at and through the Melvin G. Millet Learning Center (Bridgeport, Michigan). The eight program components are described individually and…

  9. The CD11a binding site of efalizumab in psoriatic skin tissue as analyzed by Multi-Epitope Ligand Cartography robot technology. Introduction of a novel biological drug-binding biochip assay.

    PubMed

    Bonnekoh, B; Böckelmann, R; Pommer, A J; Malykh, Y; Philipsen, L; Gollnick, H

    2007-01-01

    -1) as its ligand was most prevalent in the dermal vessels. T lymphocytes (for which the markers were CD3, CD8, CD4, and CD45R0) were the major cellular targets of efalizumab. In contrast, NK cells were only a minor target of efalizumab. Our study demonstrated that efalizumab represents a treatment for psoriasis that primarily targets memory CD4+ and CD8+ T cells and has a high specificity for psoriatic disease activity. Moreover, we hereby introduce the novel principle of a biological drug-binding biochip assay being especially useful for the future monitoring of psoriatic skin lesions under efalizumab treatment conditions.

  10. Panel on Capacity Building

    NASA Astrophysics Data System (ADS)

    Elhadani, D.

    The demonstration was made that space technologies are an important tool for developing countries. But the fundamental question is how those countries could integrate such technologies, in an effective an operational way, in the process of resources management and administration. Capacity building is a cornerstone in any strategy to set up a national programme or infrastructure for the use of space technologies. The proposed presentation attempts to bring the first elements on the actual uses of space technology in developing countries compared to their needs, the role of training activities and programs in the capacity building process as well as the role of international cooperation and what are the required conditions to ensure sustainability of the established capacities.

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. Social communication impairments: pragmatics.

    PubMed

    Russell, Robert L

    2007-06-01

    Social communication or pragmatic impairments are characterized and illustrated as involving inappropriate or ineffective use of language and gesture in social contexts. Three clinical vignettes illustrate different pragmatic impairments and the wealth of diagnostic information that can be garnered from observation of a child's social communication behavior. Definitions of, and developmental milestones in, domains of pragmatic competence are provided. Several screening instruments are suggested for use in assessing pragmatic competence within the time-frame of a pediatric examination. Frequent comorbid psychiatric conditions are described and a sample of current neurobiologic research is briefly summarized.

  16. 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…

  17. Sustained Attention in Children with Specific Language Impairment (SLI)

    ERIC Educational Resources Information Center

    Finneran, Denise A.; Francis, Alexander L.; Leonard, Laurence B.

    2009-01-01

    Purpose: Information-processing limitations have been associated with language problems in children with specific language impairment (SLI). These processing limitations may be associated with limitations in attentional capacity, even in the absence of clinically significant attention deficits. In this study, the authors examined the performance…

  18. The Nature of Individual Differences in Working Memory Capacity: Active Maintenance in Primary Memory and Controlled Search from Secondary Memory

    ERIC Educational Resources Information Center

    Unsworth, Nash; Engle, Randall W.

    2007-01-01

    Studies examining individual differences in working memory capacity have suggested that individuals with low working memory capacities demonstrate impaired performance on a variety of attention and memory tasks compared with individuals with high working memory capacities. This working memory limitation can be conceived of as arising from 2…

  19. Emotionally Impaired Elementary Curriculum.

    ERIC Educational Resources Information Center

    Taulbee, Dianne R.; And Others

    A curriculum is presented for teaching emotionally impaired elementary students. The curriculum document describes program management techniques, strategies for developing and maintaining teacher-student relationships, and therapy/change systems. It outlines referral and eligibility procedures and exit criteria. It contains job descriptions for…

  20. Emotionally Impaired Elementary Curriculum.

    ERIC Educational Resources Information Center

    Taulbee, Dianne R.; And Others

    The Jackson County (Michigan) Intermediate School District curriculum for teaching emotionally impaired elementary students is presented. The curriculum document describes program management techniques, strategies for developing and maintaining teacher-student relationships, and therapy/change systems. It outlines referral and eligibility…

  1. Anarthria impairs subvocal counting.

    PubMed

    Cubelli, R; Nichelli, P; Pentore, R

    1993-12-01

    We studied subvocal counting in two pure anarthric patients. Analysis showed that they performed definitively worse than normal subjects free to articulate subvocally and their scores were in the lower bounds of the performances of subjects suppressing articulation. These results suggest that subvocal counting is impaired after anarthria.

  2. Specific Language Impairment

    MedlinePlus

    ... children with true language impairments. After studying a large group of Hispanic children who speak English as a ... trying out an intervention program with a small group of bilingual first graders with SLI to find techniques and strategies to help them succeed academically. Diagnostic ...

  3. Ethical Considerations in Electronic Monitoring of the Cognitively Impaired.

    PubMed

    Yang, Y Tony; Kels, Charles G

    2017-01-01

    Cognitive impairment afflicts an estimated 16 million people in the United States. Wandering is a concerning behavior associated with cognitive impairment, as it may threaten patient safety. The risks posed by wandering place severe burdens on both professional and informal caregivers, as well as law enforcement institutions throughout the United States. As such, location trackers that could reduce this burden have become increasingly prevalent. As with many assistive technologies, the substantial promise of location trackers is counterbalanced by potential pitfalls with respect to loss of privacy and autonomy. This article reviews the ethical issues raised by electronic monitoring of cognitively impaired persons, with the goal of transcending a narrow focus on decisional capacity in favor of a patient-centered framework that is applicable and adjustable at different stages of cognitive decline. Balancing the ethical principles of beneficence and respect in treating cognitively impaired persons goes beyond the necessary step of evaluating decision-making capacity to include partnering with families, caretakers, and cognitively impaired individuals who wander in a collaborative coalition of care. An approach emphasizing the individual needs of patients and caretakers is best suited to finding solutions that implement tracking technologies in ways that both protect and empower the cognitively impaired.

  4. 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…

  5. 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…

  6. 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.

  7. Community Capacity Building

    PubMed Central

    Goytia, Crispin N.; Todaro-Rivera, Lea; Brenner, Barbara; Shepard, Peggy; Piedras, Veronica; Horowitz, Carol

    2013-01-01

    Background: Successful community–academic research partnerships require building the capacity of both community-based organizations (CBOs) and academics to conduct collaborative research of mutual interest and benefit. Yet, information about the needs and goals of research-interested CBOs is lacking. Our partnership aimed to conduct a community research needs assessment and to use results to develop future capacity-building programs for CBOs. Methods: Based on our review of the literature, informal interviews with research-interested CBOs and community-engaged research groups locally and nationally, we developed a needs assessment survey. Key domains of this survey included history and experience with research collaboration, interest in specific research topics, and preference for learning format and structure. We trained community health workers (CHWs) to recruit senior leaders from CBOs in New York City (NYC) and encourage them to complete an on-line survey. Results: Fully 54% (33/61) of CBOs completed the needs assessment. Most (69%) reported involvement with research or evaluation in the last 2 years and 33% had some funding for research. Although 75% had collaborated with academic institutions in the past, 58% did not rate this experience well. The four areas respondents prioritized for skills building were program evaluation, developing needs assessments, building surveys, and understanding statistical analyses. They were less interested in learning to build collaborations with academics. Conclusions: A formal needs assessment of research training and educational needs of CBOs revealed that most had experience, albeit negative, with academic collaborations. CBO leaders wanted to build skills to conduct and analyze assessments and program evaluations. Our community–academic partnership is using these findings to develop a research capacity-building course. Other partnerships should consider conducting such assessments to transform the capacity of CBOs to

  8. 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.

  9. Enabling Partner Capacity Building

    DTIC Science & Technology

    2013-03-01

    Market Street, Philadelphia, PA 19104, (215) 662-5606. The Commission on Higher Education is an institutional accrediting agency recognized by the U.S...valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE (DD-MM-YYYY) xx-03-2013 2. REPORT TYPE STRATEGY ...National Security Strategy emphasizes building the capacity of our allies and partner countries to share the burden of global leadership. The Army is

  10. 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.

  11. 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.

  12. Exacerbated Vulnerability in Existential Changes: The Essence of Dealing with Reduced Working Capacity

    ERIC Educational Resources Information Center

    Steingrímsdóttir, Sigrún Hulda; Halldórsdóttir, Sigríður

    2016-01-01

    The purpose of this phenomenological study was to explore people's experience of reduced working capacity and their encounters with professionals in that life situation. We collected data through in-depth interviews with eight individuals. The main finding of the current research is how illness and accident impairing work capacity "exacerbate…

  13. 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

  14. Butalbital and driving impairment.

    PubMed

    Yeakel, Jillian K; Logan, Barry K

    2013-07-01

    Butalbital (Fiorinal(®)), used in the treatment of migraines and muscle pain, is the most commonly encountered barbiturate in impaired driving cases. It has central nervous system (CNS) depressant properties, including sedation, drowsiness, and feelings of intoxication, which can contribute to driving impairment. Twenty-six driving under the influence cases are reviewed including results from field sobriety tests and toxicology testing. Blood samples were screened using enzyme multiplied immunoassay technique immunoassay, and the presence of butalbital was confirmed and quantified using gas chromatography/mass spectrometry, gas chromatography with flame ionization detection, or gas chromatography nitrogen/phosphorus detection. Butalbital concentrations ranged from 1.0 to 30.2 mg/L, with a mean and median of 16.0 mg/L. General impairment indicators in these cases included horizontal and vertical nystagmus, lack of convergence, poor motor coordination, and balance and speech problems, which are common to CNS depressant intoxication, similar to that associated with alcohol. These findings indicate the importance of toxicological testing for butalbital in cases where CNS depressants are indicated.

  15. 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…

  16. Assessment of Hearing Impaired Youth.

    ERIC Educational Resources Information Center

    Hicks, Doin E., Ed.; And Others

    1980-01-01

    The issue of Directions contains 11 articles on assessment of hearing impaired individuals. Entries have the following titles and authors: "Classroom Assessment Techniques for Hearing Impaired Students--A Literature Review" (B. McKee, M. Hausknecht); "Informal Assessment of Hearing Impaired Students In the Classroom" (B. Culhane, R. Hein);…

  17. Quantum reading capacity

    NASA Astrophysics Data System (ADS)

    Pirandola, Stefano; Lupo, Cosmo; Giovannetti, Vittorio; Mancini, Stefano; Braunstein, Samuel L.

    2011-11-01

    The readout of a classical memory can be modelled as a problem of quantum channel discrimination, where a decoder retrieves information by distinguishing the different quantum channels encoded in each cell of the memory (Pirandola 2011 Phys. Rev. Lett. 106 090504). In the case of optical memories, such as CDs and DVDs, this discrimination involves lossy bosonic channels and can be remarkably boosted by the use of nonclassical light (quantum reading). Here we generalize these concepts by extending the model of memory from single-cell to multi-cell encoding. In general, information is stored in a block of cells by using a channel-codeword, i.e. a sequence of channels chosen according to a classical code. Correspondingly, the readout of data is realized by a process of ‘parallel’ channel discrimination, where the entire block of cells is probed simultaneously and decoded via an optimal collective measurement. In the limit of a large block we define the quantum reading capacity of the memory, quantifying the maximum number of readable bits per cell. This notion of capacity is nontrivial when we suitably constrain the physical resources of the decoder. For optical memories (encoding bosonic channels), such a constraint is energetic and corresponds to fixing the mean total number of photons per cell. In this case, we are able to prove a separation between the quantum reading capacity and the maximum information rate achievable by classical transmitters, i.e. arbitrary classical mixtures of coherent states. In fact, we can easily construct nonclassical transmitters that are able to outperform any classical transmitter, thus showing that the advantages of quantum reading persist in the optimal multi-cell scenario.

  18. Decisional Capacity in Amyotrophic Lateral Sclerosis.

    PubMed

    Khin Khin, Eindra; Minor, Darlinda; Holloway, Amanda; Pelleg, Ayla

    2015-06-01

    The cognitive and behavioral changes that can be observed in the neurodegenerative terminal disease amyotrophic lateral sclerosis (ALS), once characterized as purely a motor neuron disease, have become increasingly recognized over the past century. Detecting cognitive deficits earlier and identifying continued changes at regular intervals can lead to improved care, proactive treatments, and earlier discussions about end-of-life wishes. Although medical decisional capacity is required for every treatment decision made, its importance becomes paramount when making decisions on complex medical treatments that will invariably and significantly affect quality of life or life itself. In this review, we conducted a critical analysis of the evidence-based literature on the cognitive and behavioral impairments in ALS that can compromise medical decisional capacity. We review specific ALS-related clinical scenarios in which decisional capacity is of utmost importance and discuss a practical framework for cognitive and behavioral assessment that can be routinely and efficiently used, while being mindful of the confounding factors associated with ALS. Finally, we review models for preserving patient choices that can be used in patients with ALS to help safeguard autonomy and retain dignity toward the end of life.

  19. 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

  20. VAP-CAP: A Procedure to Assess the Visual Functioning of Young Visually Impaired Children.

    ERIC Educational Resources Information Center

    Blanksby, D. C.; Langford, P. E.

    1993-01-01

    This article describes a visual assessment procedure (VAP) which evaluates capacity, attention, and processing (CAP) of infants and preschool children with visual impairments. The two-level battery considers, first, visual capacity and basic visual attention and, second, visual perceptual and cognitive abilities. A theoretical analysis of the…

  1. Heat Capacity in Proteins

    NASA Astrophysics Data System (ADS)

    Prabhu, Ninad V.; Sharp, Kim A.

    2005-05-01

    Heat capacity (Cp) is one of several major thermodynamic quantities commonly measured in proteins. With more than half a dozen definitions, it is the hardest of these quantities to understand in physical terms, but the richest in insight. There are many ramifications of observed Cp changes: The sign distinguishes apolar from polar solvation. It imparts a temperature (T) dependence to entropy and enthalpy that may change their signs and which of them dominate. Protein unfolding usually has a positive ΔCp, producing a maximum in stability and sometimes cold denaturation. There are two heat capacity contributions, from hydration and protein-protein interactions; which dominates in folding and binding is an open question. Theoretical work to date has dealt mostly with the hydration term and can account, at least semiquantitatively, for the major Cp-related features: the positive and negative Cp of hydration for apolar and polar groups, respectively; the convergence of apolar group hydration entropy at T ≈ 112°C; the decrease in apolar hydration Cp with increasing T; and the T-maximum in protein stability and cold denaturation.

  2. 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

  3. 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.

  4. 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

    2014-10-08

    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.

  5. Working Memory Contributions to Reinforcement Learning Impairments in Schizophrenia

    PubMed Central

    Brown, Jaime K.; Gold, James M.; Waltz, James A.; Frank, Michael J.

    2014-01-01

    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

  6. The influence of lung function on exercise capacity in patients with type 2 diabetes.

    PubMed

    Kitahara, Yoshihiro; Hattori, Noboru; Yokoyama, Akihito; Yamane, Kiminori; Sekikawa, Kiyokazu; Inamizu, Tsutomu; Kohno, Nobuoki

    2010-03-01

    Patients with type 2 diabetes have impaired exercise capacity. While numerous factors are known to contribute to impaired exercise capacity, the role of lung function remains unclear. We conducted the present study to investigate the influence of lung function on exercise capacity in patients with type 2 diabetes. Cardiopulmonary exercise testing was carried out in 31 male patients with type 2 diabetes without diabetic complications or cardiopulmonary diseases. Patients with abnormal spirometry results such as a percentage of predicted forced vital capacity (%FVC) < 80% and/or a ratio of forced expiratory volume in one second (FEV1) to FVC (FEV1/FVC) < 70% were excluded from the study. We used the percentage of predicted maximal oxygen uptake (%VO2max) as an index of exercise capacity. The correlations between %VO2max and lung function and other factors known to be associated with impaired exercise capacity were then assessed. Univariate analysis revealed %VO2max correlated significantly with percentage of predicted FEV1 (%FEV1), duration of type 2 diabetes, regular exercise habits, and systolic and diastolic blood pressures. In a multivariate analysis, %FEV1 and regular exercise habits were found to be independent determinants of %VO2max. A mild reduction in %FEV1, which may be a complication of diabetes, is associated with impaired exercise capacity in patients with type 2 diabetes. When evaluating spirometric values in patients with type 2 diabetes, a reduction in %FEV1 should be noted even when both %FVC and FEV1/FVC are within normal limits.

  7. Fertility impairment in radiotherapy

    PubMed Central

    Kuźba-Kryszak, Tamara; Nowikiewicz, Tomasz; Żyromska, Agnieszka

    2016-01-01

    Infertility as a result of antineoplastic therapy is becoming a very important issue due to the growing incidence of neoplastic diseases. Routinely applied antineoplastic treatments and the illness itself lead to fertility disorders. Therapeutic methods used in antineoplastic treatment may cause fertility impairment or sterilization due to permanent damage to reproductive cells. The risk of sterilization depends on the patient's sex, age during therapy, type of neoplasm, radiation dose and treatment area. It is known that chemotherapy and radiotherapy can lead to fertility impairment and the combination of these two gives an additive effect. The aim of this article is to raise the issue of infertility in these patients. It is of growing importance due to the increase in the number of children and young adults who underwent radiotherapy in the past. The progress in antineoplastic therapy improves treatment results, but at the same time requires a deeper look at existential needs of the patient. Reproductive function is an integral element of self-esteem and should be taken into account during therapy planning. PMID:27647982

  8. Continuity of Quantum Channel Capacities

    NASA Astrophysics Data System (ADS)

    Leung, Debbie; Smith, Graeme

    2009-11-01

    We prove that a broad array of capacities of a quantum channel are continuous. That is, two channels that are close with respect to the diamond norm have correspondingly similar communication capabilities. We first show that the classical capacity, quantum capacity, and private classical capacity are continuous, with the variation on arguments {\\varepsilon} apart bounded by a simple function of {\\varepsilon} and the channel’s output dimension. Our main tool is an upper bound of the variation of output entropies of many copies of two nearby channels given the same initial state; the bound is linear in the number of copies. Our second proof is concerned with the quantum capacities in the presence of free backward or two-way public classical communication. These capacities are proved continuous on the interior of the set of non-zero capacity channels by considering mutual simulation between similar channels.

  9. [Exercise capacity after heart valve replacement].

    PubMed

    Horstkotte, D; Niehues, R; Schulte, H D; Strauer, B E

    1994-01-01

    Exercise capacity following heart-valve replacement is dependent on how close to normal the artificial device can restore valve function, to what degree a preoperative impaired myocardial function and/or an increased pulmonary vascular resistance is normalized. The postoperative functional result can be determined by the subjective improvement of the patient, his functional capacity, exercise capacity, the central hemodynamics at rest and during exercise, and the systolic and diastolic function of the left and right ventricular myocardium. The subjective improvement of individual symptoms is obviously dependent on the degree of postoperative normalization of hemodynamics, especially of pressures in the pulmonary circulation. Subjective improvement can be objectified by comparing the functional capacities before and after surgery. Post-operative normalization of central hemodynamics and myocardial function does not happen immediately but within 3 to more than 12 months. A 12-month period can generally be expected in patients with mitral stenosis and increased pulmonary vascular resistance (> 400 dyn.sec.cm-5) prior to surgery. In patients with mitral and aortic regurgitation as well as with aortic stenosis and preoperative decrease of their left ventricular ejection fraction during exercise, continuous improvement of left ventricular pump function also may need up to 12 months. Physiological hemodynamic conditions generally are not restored by valve replacement. All prostheses are stenotic to forward blood flow because of the obstruction created by the narrowing of the valve area by sewing cuff and valve poppet. This may result in a hemodynamically important stenosis, especially after atrio-ventricular valve implantation, and may limit subjective and functional improvement. Exercise capacity after aortic valve replacement depends mainly on whether or not myocardial damage persists postoperatively. A workload of 1.5 w/kg body weight (BW) has been performed by 100% of

  10. [Multilingualism and specific language impairment].

    PubMed

    Arkkila, Eva; Smolander, Sini; Laasonen, Marja

    2013-01-01

    Specific language impairment is one of the most common developmental disturbances in childhood. With the increase of the foreign language population group an increasing number of children assimilating several languages and causing concern in language development attend clinical examinations. Knowledge of factors underlying the specific language impairment and the specific impairment in general, special features of language development of those learning several languages, as well as the assessment and support of the linguistic skills of a multilingual child is essential. The risk of long-term problems and marginalization is high for children having specific language impairment.

  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. 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

  13. Plasma antioxidant capacity is reduced in Asperger syndrome.

    PubMed

    Parellada, Mara; Moreno, Carmen; Mac-Dowell, Karina; Leza, Juan Carlos; Giraldez, Marisa; Bailón, Concepción; Castro, Carmen; Miranda-Azpiazu, Patricia; Fraguas, David; Arango, Celso

    2012-03-01

    Recent evidence suggests that children with autism have impaired detoxification capacity and may suffer from chronic oxidative stress. To our knowledge, there has been no study focusing on oxidative metabolism specifically in Asperger syndrome (a milder form of autism) or comparing this metabolism with other psychiatric disorders. In this study, total antioxidant status (TAOS), non-enzymatic (glutathione and homocysteine) and enzymatic (catalase, superoxide dismutase, and glutathione peroxidase) antioxidants, and lipid peroxidation were measured in plasma or erythrocyte lysates in a group of adolescent patients with Asperger syndrome, a group of adolescents with a first episode of psychosis, and a group of healthy controls at baseline and at 8-12 weeks. TAOS was also analyzed at 1 year. TAOS was reduced in Asperger individuals compared with healthy controls and psychosis patients, after covarying by age and antipsychotic treatment. This reduced antioxidant capacity did not depend on any of the individual antioxidant variables measured. Psychosis patients had increased homocysteine levels in plasma and decreased copper and ceruloplasmin at baseline. In conclusion, Asperger patients seem to have chronic low detoxifying capacity. No impaired detoxifying capacity was found in the first-episode psychosis group in the first year of illness.

  14. 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.

  15. 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…

  16. [Neuropsychological impairment in the early Alzheimer's disease].

    PubMed

    Traykov, L; Rigaud, A-S; Cesaro, P; Boller, F

    2007-01-01

    This analysis is centered on the study of cognitive disorders in Alzheimer's disease (AD), mainly for major neuro-psychological functions. We insist on the heterogeneity of the clinical picture peculiarly in the early stages of the illness, even if the deficits of episodic memory and of attentional/executive capacities are the first to deteriorate, preceding impairment in perceptual and language function and potentially having a substantial impact on the patient's capacity to cope independently. An episodic memory deficit is the hallmark of AD, but it must be stressed that this deficit may take different forms and its origin may be traced back to different cognitive mechanisms. One of the most striking aspects of episodic memory impairment in AD is the rapidity of forgetfulness on which screening and diagnostic tests of AD are based. There is some evidence that the episodic memory deficit in AD is one of learning (encoding and storage) of information rather than to a deficit of retrieval. Furthermore, episodic memory performance in AD depends on the integrity of semantic memory abilities, so giving support to a hierarchical model of organization of human memory. Finally, recent results show that an impairment of conscious recollection is responsible for the poor performance of AD patients in recognition memory. Executive deficits appear predominantly in tasks requiring cognitive flexibility and self-monitoring. With the progression of the disease, additional deficits are observed in the verbal concept formation abilities. These findings might be also very useful in the differential diagnosis between AD and the other cortical and subcortical dementias, as well as in the differentiation between AD and fronto-temporal dementia. We consider that studying early stages of the illness is necessary to delineate the diagnostic signs, to validate the new therapeutic experiments, to predict stages of decline. Recent research suggested that onset of AD is commonly preceded by

  17. The visually impaired patient.

    PubMed

    Rosenberg, Eric A; Sperazza, Laura C

    2008-05-15

    Blindness or low vision affects more than 3 million Americans 40 years and older, and this number is projected to reach 5.5 million by 2020. In addition to treating a patient's vision loss and comorbid medical issues, physicians must be aware of the physical limitations and social issues associated with vision loss to optimize health and independent living for the visually impaired patient. In the United States, the four most prevalent etiologies of vision loss in persons 40 years and older are age-related macular degeneration, cataracts, glaucoma, and diabetic retinopathy. Exudative macular degeneration is treated with laser therapy, and progression of nonexudative macular degeneration in its advanced stages may be slowed with high-dose antioxidant and zinc regimens. The value of screening for glaucoma is uncertain; management of this condition relies on topical ocular medications. Cataract symptoms include decreased visual acuity, decreased color perception, decreased contrast sensitivity, and glare disability. Lifestyle and environmental interventions can improve function in patients with cataracts, but surgery is commonly performed if the condition worsens. Diabetic retinopathy responds to tight glucose control, and severe cases marked by macular edema are treated with laser photocoagulation. Vision-enhancing devices can help magnify objects, and nonoptical interventions include special filters and enhanced lighting.

  18. VOT and hearing impairment

    NASA Astrophysics Data System (ADS)

    Lane, Harlan; Perkell, Joseph

    2001-05-01

    When deafened adults recover some hearing after receiving a cochlear implant, numerous changes in their speech occur at both phonemic and suprasegmental levels. If a change toward normative values is observed for some phonemic parameter, it may be attributed to the restored hearing; however, it may be a by-product of a suprasegmental change. Consistent with results reported for speakers with normal hearing, Lane et al. [J. Acoust. Soc. Am. 98, 3096-3106 (1995)] observed in implant users that VOT varies approximately linearly with syllable duration. Therefore, in comparing pre- and postimplant measures of VOT in five speakers, each token's VOT was adjusted for the change in syllable duration of that token relative to the mean syllable duration in a baseline session (called VOTc). Preimplant, the deaf speakers characteristically uttered plosives with abnormally short VOTc. With some hearing restored, four of the five lengthened VOTc. Changes in voiced plosives' VOTc with restored hearing were correlated with changes in SPL. Some of the reliable VOTc increases that were not correlated with SPL may have been caused by auditory validation of an internal model for phoneme production. Recent studies of VOT in hearing-impaired speakers will be reviewed in this light. [Work supported by NIDCD, NIH.

  19. Computational Medical Apportionment Determination for Impairment Ratings

    NASA Astrophysics Data System (ADS)

    Artz, Jerry; Thompson, Marten; Alchemy, Md, John; Penn, Md, Daniel

    2017-01-01

    Unique computational techniques are used to calculate apportionment percentages for Whole Person Impairment (WPI) Ratings for workers with job-related injuries/illnesses. This interdisciplinary project includes collaboration among physicists, engineers, and concerned medical professionals. Medical providers are often asked to medically determine multiple contributing factors to disease states (e.g. diabetes, obesity, arthritis, and prior injury) in the context of personal injury as it pertains to permanent impairment. The process of making this determination is referred to as ``apportionment''. The economic value of apportionment is far reaching and represents a significant impact to all stakeholders in the injury resolution and settlement arena. The process of apportionment is necessary to assign monetary value for the stakeholders when an injury occurs. The ultimate trier-of-fact is the judicial system. The medical provider's role in this capacity is to apply known medical scientific knowledge and present it in a format that is objective and reproducible for the stakeholders. In this presentation the traditional challenges of apportionment will be outlined, and a novel approach creating mathematical bounding and modeling of pathology-weighted data sets will be presented.

  20. Concrete Operations and Attentional Capacity.

    ERIC Educational Resources Information Center

    Chapman, Michael; Lindenberger, Ulman

    1989-01-01

    To test predictions regarding the attentional capacity requirements of Piaget's stage of concrete operations, a battery of concrete operational tasks and two measures of attentional capacity were administered to 120 first-, second-, and third-graders. Findings concern class inclusion, transitivity of length and weight, and multiplication of…

  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. Large capacity temporary visual memory

    PubMed Central

    Endress, Ansgar D.; Potter, Mary C.

    2014-01-01

    Visual working memory (WM) capacity is thought to be limited to three or four items. However, many cognitive activities seem to require larger temporary memory stores. Here, we provide evidence for a temporary memory store with much larger capacity than past WM capacity estimates. Further, based on previous WM research, we show that a single factor — proactive interference — is sufficient to bring capacity estimates down to the range of previous WM capacity estimates. Participants saw a rapid serial visual presentation (RSVP) of 5 to 21 pictures of familiar objects or words presented at rates of 4/s or 8/s, respectively, and thus too fast for strategies such as rehearsal. Recognition memory was tested with a single probe item. When new items were used on all trials, no fixed memory capacities were observed, with estimates of up to 9.1 retained pictures for 21-item lists, and up to 30.0 retained pictures for 100-item lists, and no clear upper bound to how many items could be retained. Further, memory items were not stored in a temporally stable form of memory, but decayed almost completely after a few minutes. In contrast, when, as in most WM experiments, a small set of items was reused across all trials, thus creating proactive interference among items, capacity remained in the range reported in previous WM experiments. These results show that humans have a large-capacity temporary memory store in the absence of proactive interference, and raise the question of whether temporary memory in everyday cognitive processing is severely limited as in WM experiments, or has the much larger capacity found in the present experiments. PMID:23937181

  3. A California generation capacity market

    SciTech Connect

    Conkling, R.L.

    1998-10-01

    California, overconfident with its new Power Exchange spot market, seems unaware that it could be afflicted by the same turmoil that bludgeoned the Midwest in June. An electricity capacity market should be put in place before crisis strikes. This article outlines a framework for adding an electricity capacity market in California. The new market would not create a new bureaucracy but would function within the state`s now operational PX and independent system operator (ISO) mechanisms. It would be an open market, in which capacity would be traded transparently, with freedom of entree for all willing sellers and all willing buyers.

  4. 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

  5. 303(d) Listed Impaired Waters

    EPA Pesticide Factsheets

    Geospatial data for 303(d) Impaired Waters are available as prepackaged national downloads or as GIS web and and data services. EPA provides geospatial data in the formats: GIS compatible shapefiles and geodatabases and ESRI and OGC web mapping.

  6. 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

  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. 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)

  9. Enhancing mobile phones for people with visual impairments through haptic icons: the effect of learning processes.

    PubMed

    Galdón, Pedro Maria; Madrid, R Ignacio; De La Rubia-Cuestas, Ernesto J; Diaz-Estrella, Antonio; Gonzalez, Lourdes

    2013-01-01

    We report the results of a study on the learnability ofhaptic icons used in a system for incoming-call identification in mobile phones. The aim was to explore the feasibility of using haptic icons to create new assistive technologies for people with visual impairments. We compared the performance and satisfaction of users with different visual capacities (visually impaired vs. sighted) and using different learning processes (unimodal vs. multimodal). A better recognition rate and user experience were observed for the visually impaired than for sighted users and for multimodal rather than unimodal learning processes.

  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

  11. Personality Disorders and Mindreading: Specific Impairments in Patients With Borderline Personality Disorder Compared to Other PDs.

    PubMed

    Semerari, Antonio; Colle, Livia; Pellecchia, Giovanni; Carcione, Antonino; Conti, Laura; Fiore, Donatella; Moroni, Fabio; Nicolò, Giuseppe; Procacci, Michele; Pedone, Roberto

    2015-08-01

    The capacity of understanding mental states is a complex function which involves several components. Single components can be selectively impaired in specific clinical populations. It has been suggested that impairments in mindreading are central for borderline personality disorder (BPD). However, empirical findings are inconsistent, and it is debatable whether BPD presents a specific profile of mindreading impairments. The aim of this study is to compare BPD and other PDs in mindreading. Seventy-two patients with BPD and 125 patients with other PD diagnoses were assessed using the Metacognition Assessment Interview. BPD showed difficulties in two mindreading functions, differentiation and integration, even when the severity of psychopathology was controlled. These results suggest a specific mindreading impairment in BPD and a strong relationship between these impairments and the severity of psychopathology.

  12. Impaired procedural learning in language impairment: results from probabilistic categorization.

    PubMed

    Kemeny, Ferenc; Lukacs, Agnes

    2010-03-01

    The Weather Prediction (WP) Task is a classical task of probabilistic category learning generally used for examining the dissociation of procedural and declarative memory. The current study focuses on performance of children with language impairment (LI) and compares their performance to that of typically developing (TD) children and adults with the aim of testing the procedural deficit hypothesis of LI (PDH; Ullman & Pierpont, 2005), which states that language impairment is not a specific linguistic phenomenon, but results from the dysfunction of a more general cognitive system: the procedural system. To test the generality of the procedural impairment, we needed a task that is dissimilar from language in that it does not build on sequential information. Children with language impairment show deficient learning on the Weather Prediction Task, which already appears at the early stages of the task. These results, in line with the PDH, point to the deficit of the procedural system in language impairment going beyond the language system. Whether this deficit is selective to the procedural system or is complemented by deficits in the declarative system is the subject of future studies.

  13. Impaired Pain Processing Correlates with Cognitive Impairment in Parkinson's Disease

    PubMed Central

    Okada, Akinori; Nakamura, Tomohiko; Suzuki, Junichiro; Suzuki, Masashi; Hirayama, Masaaki; Katsuno, Masahisa; Sobue, Gen

    2016-01-01

    Objective Pain and cognitive impairment are important clinical features in patients with Parkinson's disease (PD). Although pain processing is associated with the limbic system, which is also closely linked to the cognitive function, the association between pain and cognitive impairment in PD is still not well understood. The aim of the study was to investigate the association between pain processing and cognitive impairment in patients with PD. Methods Forty-three patients with PD and 22 healthy subjects were studied. Pain-related somatosensory evoked potentials (SEPs) were generated using a thin needle electrode to stimulate epidermal Aδ fibers. Cognitive impairment was evaluated using the Mini-Mental State Examination (MMSE), the Frontal Assessment Battery, and Japanese version of the Montreal Cognitive Assessment (MoCA-J), and their correlation with pain-related SEPs was investigated. Results The N1/P1 amplitude was significantly lower in PD patients than the controls. N1/P1 peak-to-peak amplitudes correlated with the MMSE (r=0.66, p<0.001) and MoCA-J scores (r=0.38, p<0.01) in patients with PD. These amplitudes also strongly correlated with the domains of attention and memory in the MMSE (attention, r=0.52, p<0.001; memory, r=0.40, p<0.01) and MoCA-J (attention, r=0.45, p<0.005; memory, r=0.48, p<0.001), but not in control subjects. Conclusion A good correlation was observed between the decreased amplitudes of pain-related SEPs and an impairment of attention and memory in patients with PD. Our results suggest that pathological abnormalities of the pain pathway are significantly linked to cognitive impairment in PD. PMID:27803403

  14. 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…

  15. 20 CFR 416.923 - Multiple impairments.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Multiple impairments. 416.923 Section 416.923... DISABLED Determining Disability and Blindness Evaluation of Disability § 416.923 Multiple impairments. In... the combined effect of all of your impairments without regard to whether any such impairment,...

  16. Gadobutrol in Renally Impaired Patients

    PubMed Central

    Michaely, Henrik J.; Aschauer, Manuela; Deutschmann, Hannes; Bongartz, Georg; Gutberlet, Matthias; Woitek, Ramona; Ertl-Wagner, Birgit; Kucharczyk, Walter; Hammerstingl, Renate; De Cobelli, Francesco; Rosenberg, Martin; Balzer, Thomas; Endrikat, Jan

    2017-01-01

    Objective The aim of this study was to assess the potential risk of gadobutrol-enhanced magnetic resonance imaging (MRI) in patients with moderate to severe renal impairment for the development of nephrogenic systemic fibrosis (NSF). Materials and Methods We performed a prospective, international, multicenter, open-label study in 55 centers. Patients with moderate to severe renal impairment scheduled for any gadobutrol-enhanced MRI were included. All patients received a single intravenous bolus injection of gadobutrol at a dose of 0.1 mmol/kg body weight. The primary target variable was the number of patients who develop NSF within a 2-year follow-up period. Results A total of 908 patients were enrolled, including 586 with moderate and 284 with severe renal impairment who are at highest risk for developing NSF. The mean time since renal disease diagnosis was 1.83 and 5.49 years in the moderate and severe renal impairment cohort, respectively. Overall, 184 patients (20.3%) underwent further contrast-enhanced MRI with other gadolinium-based contrast agents within the 2-year follow-up. No patient developed symptoms conclusive of NSF. Conclusions No safety concerns with gadobutrol in patients with moderate to severe renal impairment were identified. There were no NSF cases. PMID:27529464

  17. Capacities of quantum amplifier channels

    NASA Astrophysics Data System (ADS)

    Qi, Haoyu; Wilde, Mark M.

    2017-01-01

    Quantum amplifier channels are at the core of several physical processes. Not only do they model the optical process of spontaneous parametric down-conversion, but the transformation corresponding to an amplifier channel also describes the physics of the dynamical Casimir effect in superconducting circuits, the Unruh effect, and Hawking radiation. Here we study the communication capabilities of quantum amplifier channels. Invoking a recently established minimum output-entropy theorem for single-mode phase-insensitive Gaussian channels, we determine capacities of quantum-limited amplifier channels in three different scenarios. First, we establish the capacities of quantum-limited amplifier channels for one of the most general communication tasks, characterized by the trade-off between classical communication, quantum communication, and entanglement generation or consumption. Second, we establish capacities of quantum-limited amplifier channels for the trade-off between public classical communication, private classical communication, and secret key generation. Third, we determine the capacity region for a broadcast channel induced by the quantum-limited amplifier channel, and we also show that a fully quantum strategy outperforms those achieved by classical coherent-detection strategies. In all three scenarios, we find that the capacities significantly outperform communication rates achieved with a naive time-sharing strategy.

  18. Boomerang pillows and respiratory capacity.

    PubMed

    Roberts, K L; Brittin, M; Cook, M A; deClifford, J

    1994-05-01

    An experimental study was done to determine whether subjects placed on boomerang pillows would have lower vital capacities than subjects placed on straight pillows after 30 minutes. A sample of 42 subjects took part in the study in a nursing laboratory. A crossover design was used in which subjects were measured in both conditions. The findings indicated that there was no significant difference in the vital capacities of subjects in the two conditions. An associated finding was that the vital capacities were significantly lower in a semi-Fowler's position than in a straight chair. It was concluded that boomerang pillows are safe to use for persons without respiratory problems. Further research is needed into the effect of boomerang pillows on persons with respiratory deficits.

  19. Buffer Capacity: An Undergraduate Laboratory Experiment.

    ERIC Educational Resources Information Center

    Russo, Steven O.; Hanania, George I. H.

    1987-01-01

    Describes a quantitative experiment designed to demonstrate buffer action and the measurement of buffer capacity. Discusses how to make acetate buffers, determine their buffer capacity, plot the capacity/pH curve, and interpret the data obtained. (TW)

  20. Superadditivity of classical capacity revisited

    SciTech Connect

    Pilyavets, Oleg V.; Karpov, Evgueni A.; Schäfer, Joachim

    2014-12-04

    We introduce new type of superadditivity for classical capacity of quantum channels, which involves the properties of channels’ environment. By imposing different restrictions on the total energy contained in channels’ environment we can consider different types of superadditivity. Using lossy bosonic and additive noise quantum channels as examples, we demonstrate that their capacities can be either additive or superadditive depending on the values of channels parameters. The parameters corresponding to transition between the additive and superadditive cases are related with recently found critical and supercritical parameters for Gaussian channels.

  1. Free Energy and Heat Capacity

    SciTech Connect

    Kurata, Masaki; Devanathan, Ramaswami

    2015-10-13

    Free energy and heat capacity of actinide elements and compounds are important properties for the evaluation of the safety and reliable performance of nuclear fuel. They are essential inputs for models that describe complex phenomena that govern the behaviour of actinide compounds during nuclear fuel fabrication and irradiation. This chapter introduces various experimental methods to measure free energy and heat capacity to serve as inputs for models and to validate computer simulations. This is followed by a discussion of computer simulation of these properties, and recent simulations of thermophysical properties of nuclear fuel are briefly reviewed.

  2. Effect of risk factors on exercise capacity in NIDDM.

    PubMed

    Estacio, R O; Wolfel, E E; Regensteiner, J G; Jeffers, B; Havranek, E P; Savage, S; Schrier, R W

    1996-01-01

    Exercise capacity has been used as a noninvasive parameter for predicting cardiovascular events. It is known that diabetic patients have an impaired exercise capacity when compared with nondiabetic age-matched control subjects, but the risk factors associated with this impairment have not been thoroughly analyzed. A total of 453 male and female NIDDM patients who underwent graded exercise testing with expired gas analysis were studied to determine the possible influences of demographic and cardiac risk factors on exercise capacity. Univariate and multiple linear regression analyses were performed on baseline patient characteristics with respect to peak oxygen consumption (VO2). In the regression analyses, African-American race was strongly associated with a decrease in peak VO2; the difference in means between African-Americans and other subjects for men was -2.50 ml.kg-1.min-1 (-4.28, -0.07, 95% CI) (P < 0.006) and for women was -2.96 ml.kg-1.min-1 (-4.45, -1.47) (P < 0.0002). Univariate analyses revealed that African-American subjects had increased prevalence, longer duration, and higher systolic and diastolic hypertension than the non-Hispanic and Hispanic whites. Other independent predictors of peak VO2 (reported as change in peak VO2 in milliliters per kilogram per minute) were BMI (men: -0.39 kg/m2 [-0.52, -0.29], P < 0.0001; women: -0.39 kg/m2 [-0.48, -0.31], P < 0.0001), age (men: -0.16/year [-0.23, -0.09], P < 0.0001; women: -0.17/year [-0.24, -0.11], P < 0.0001), baseline resting systolic blood pressure (men: -0.03/mmHg [-0.06, -0.01], P < 0.05; women: -0.03/mmHg (-0.06, -0.01)f1p4< 0.05), and pack-years smoking (men: -0.04/pack-years [-0.04, -0.01], P < 0.01; women: -0.04/pack-years [-0.07, -0.01], P < 0.0001). Thus, in this large NIDDM study, weight loss, smoking cessation, and aggressive blood pressure control, particularly in African-Americans with NIDDM, would appear to be important in improving exercise capacity and potentially improving the

  3. 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.

  4. 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.

  5. Unreasonable reasons: normative judgements in the assessment of mental capacity.

    PubMed

    Banner, Natalie F

    2012-10-01

    The recent Mental Capacity Act (2005) sets out a test for assessing a person's capacity to make treatment choices. In some cases, particularly in psychiatry, it is unclear how the criteria ought to be interpreted and applied by clinicians. In this paper, I argue that this uncertainty arises because the concept of capacity employed in the Act, and the diagnostic tools developed to assist its assessment, overlook the inherent normativity of judgements made about whether a person is using or weighing information in the decision-making process. Patients may fail on this criterion to the extent that they do not appear to be handling the information given in an appropriate way, on account of a mental impairment disrupting the way the decision process ought to proceed. Using case law and clinical examples, I describe some of the normative dimensions along which judgements of incapacity can be made, namely epistemic, evaluative and affective dimensions. Such judgements are complex and the normative standards by which a clinician may determine capacity cannot be reduced to a set of criteria. Rather, in recognizing this normativity, clinicians may better understand how clinical judgements are structured and what kinds of assumption may inform their assessment.

  6. The Effect of Supercharger Capacity on Engine and Airplane Performance

    NASA Technical Reports Server (NTRS)

    Schey, O W; Gove, W D

    1930-01-01

    This report presents the results of an investigation to determine the effect of different supercharger capacities on the performance of an airplane and its engine . The tests were conducted on a DH4-M2 airplane powered with a Liberty 12 engine. In this investigation four supercharger capacities, obtained by driving a roots type supercharger at 1.615, 1.957, 2.4, and 3 time engine speed, were used to maintain sea-level pressure at the carburetor to altitudes of 7,000, 11,500, 17,000, and 22,000 feet, respectively. The performance of the airplane in climb and in level flight was determined for each of the four supercharger drive ratios and for the unsupercharged condition. The engine power was measured during these tests by means of a calibrated propeller. It was found that very little sacrifice in sea-level performance was experienced with the larger supercharger drive ratios as compared with performance obtained when using the smaller drive ratios. The results indicate that further increase in supercharger capacity over that obtained when using 3:1 drive ratio would give a slight increase in ceiling and in high-altitude performance but would considerably impair the performance for an appreciable distance below the critical altitude. As the supercharger capacity was increased, the height at which sea-level high speeds could be equaled or improved became a larger percentage of the maximum height of operation of the airplane.

  7. Self-concept, self-esteem, personality traits and psychopathological symptoms in adolescents with and without visual impairment.

    PubMed

    Garaigordobil, Maite; Bernarás, Elena

    2009-05-01

    The purpose of this study was to analyze self-concept, self-esteem, and other personality traits and psychopathological symptoms in subjects with and without visual impairment. The sample was made up of 90 participants aged 12 to 17: 61 with no impairment and 29 with visual impairment. The ANOVA showed that there were no significant differences in self-concept and self-esteem in the samples, but the visually impaired adolescents scored significantly higher in various psychopathological symptoms as well as in their capacity for kind behavior. The ANOVA revealed no gender differences in any variables in adolescents without visual impairment. However, women with visual impairment scored lower in self-esteem and higher in various psychopathological symptoms. Pearson coefficients revealed negative relations between self-concept/self-esteem and all the psychopathological symptoms, and neuroticism, as well as a positive relation with extraversion. Low psychoticism, high extraversion, and low hostility were identified as predictors of high self-concept.

  8. Single-dose pharmacokinetic studies of abiraterone acetate in men with hepatic or renal impairment.

    PubMed

    Marbury, Thomas; Lawitz, Eric; Stonerock, Robert; Gonzalez, Martha; Jiao, James; Breeding, Jim; Haqq, Christopher; Verboven, Peter; Stieltjes, Hans; Yu, Margaret; Molina, Arturo; Acharya, Milin; Chien, Caly; Tran, NamPhuong

    2014-07-01

    Three open-label, single-dose studies investigated the impact of hepatic or renal impairment on abiraterone acetate pharmacokinetics and safety/tolerability in non-cancer patients. Patients (n = 8 each group) with mild/moderate hepatic impairment or end-stage renal disease (ESRD), and age-, BMI-matched healthy controls received a single oral 1,000 mg abiraterone acetate (tablet dose); while patients (n = 8 each) with severe hepatic impairment and matched healthy controls received 125- and 2,000-mg abiraterone acetate (suspension doses), respectively (systemic exposure of abiraterone acetate suspension is approximately half to that of tablet formulation). Blood was sampled at specified timepoints up to 72 or 96 hours postdose to measure plasma abiraterone concentrations. Abiraterone exposure was comparable between healthy controls and patients with mild hepatic impairment or ESRD, but increased by 4-fold in patients with moderate hepatic impairment. Despite a 16-fold reduction in dose, abiraterone exposure in patients with severe hepatic impairment was about 22% and 44% of the Cmax and AUC∞ of healthy controls, respectively. These results suggest that abiraterone pharmacokinetics were not changed markedly in patients with ESRD or mild hepatic impairment. However, the capacity to eliminate abiraterone was substantially compromised in patients with moderate or severe hepatic impairment. A single-dose administration of abiraterone acetate was well-tolerated.

  9. A Case Study of Parental Perceptions of Literacy Skill Development for Severe Speech Impairments

    ERIC Educational Resources Information Center

    Sweat, Karen

    2014-01-01

    Students exhibiting speech deficits may not have the appropriate skills or support structures necessary to obtain adequate or acceptable literacy development as mixed results from past research have indicated that some students with speech impairments have the capacity to gain appropriate literacy skills. The purpose of the qualitative holistic…

  10. Psycholinguistic Profiling Differentiates Specific Language Impairment from Typical Development and from Attention-Deficit/Hyperactivity Disorder

    ERIC Educational Resources Information Center

    Redmond, Sean M.; Thompson, Heather L.; Goldstein, Sam

    2011-01-01

    Purpose: Practitioners must have confidence in the capacity of their language measures to discriminate developmental language disorders from typical development and from other common disorders. In this study, psycholinguistic profiles were collected from 3 groups: children with specific language impairment (SLI), children with…

  11. The Impact of Dual Tasking on Sentence Comprehension in Children with Specific Language Impairment

    ERIC Educational Resources Information Center

    Leclercq, Anne-Lise; Majerus, Steve; Prigent, Gaid; Maillart, Christelle

    2013-01-01

    Purpose: In this study, the authors assessed the hypothesis of a limitation in attentional allocation capacity as underlying poor sentence comprehension in children with specific language impairment (SLI). Method: Fifteen children with SLI, 15 age-matched controls, and 15 grammar-matched controls participated in the study. Sixty sentences were…

  12. Complex Sentence Comprehension and Working Memory in Children with Specific Language Impairment

    ERIC Educational Resources Information Center

    Montgomery, James W.; Evans, Julia L.

    2009-01-01

    Purpose: This study investigated the association of 2 mechanisms of working memory (phonological short-term memory [PSTM], attentional resource capacity/allocation) with the sentence comprehension of school-age children with specific language impairment (SLI) and 2 groups of control children. Method: Twenty-four children with SLI, 18 age-matched…

  13. Building Capacity and Sustaining Endeavors

    ERIC Educational Resources Information Center

    Kraybill, Anne; Din, Herminia

    2015-01-01

    In this article, institutional capacity and sustainability is considered. The authors explore a case study from Crystal Bridges Museum of American Art as an example of how museums can leverage not only online technologies to reach more learners regardless of geography, but to increase their reach through strategic partnerships.

  14. [Fasting and physical endurance capacity].

    PubMed

    Schürch, P M

    1993-03-01

    Fasting, or zero calorie diets are used not only by overweight people as a means of losing weight, but by athletes too. Their use is then explained on philosophical grounds, with the aim of even enhancing sports performance. The purpose of this investigation consisted of quantifying the effects of a 10-day fast on maximum performance capacity and endurance (as measured on a bicycle ergometer) of 12 female students of physical education of normal weight. The measurements included resting and exercise metabolism determinants, as well as weight and lean body mass. The main results show that after the diet period the maximum ergometric performance was lower in absolute terms as well as in relation to weight or lean body mass. Performance capacity for submaximal exercise was also reduced. Fat combustion was enhanced both at rest and during exercise. The reduction of maximum performance and endurance capacity may be explained by an enhanced muscle breakdown, an efficiency drop of muscular work, and an inadequate glycogen content of the acting muscles. Shorter fasting periods of 24-36 hours also lead to a lower performance level for exercise bouts extending from several minutes to 1-3 hours. An enhancement of fat combustion was always conspicuous. One may conclude that optimal physical performance is dependent on full hepatic and muscle glycogen stores. Glycogen concentration in the liver decreases sharply as a matter of fact after merely one day of carbohydrate shortage. Zero calorie or low carbohydrate diets are thus at variance with an optimal physical work capacity.

  15. Capacity Issue Looms for Vouchers

    ERIC Educational Resources Information Center

    Zehr, Mary Ann

    2011-01-01

    State-level momentum in support of vouchers and tax credits that help students go to private schools highlights what has been a largely theoretical issue: private school capacity to support voucher-financed enrollment. Academics say the national supply of seats in secular and religious private schools is sufficient to meet short-term demand from…

  16. Language Impairment in Autistic Children.

    ERIC Educational Resources Information Center

    Deaton, Ann Virginia

    Discussed is the language impairment of children with infantile autism. The speech patterns of autistic children, including echolalia, pronomial reversal, silent language, and voice imitation, are described. The clinical picture of the autistic child is compared to that of children with such other disorders as deafness, retardation, and…

  17. Parkinson's Disease and Cognitive Impairment

    PubMed Central

    Tang, Bei-sha

    2016-01-01

    Parkinson's disease (PD) is a progressive neurodegenerative disease primarily characterized by the hallmarks of motor symptoms, such as tremor, bradykinesia, rigidity, and postural instability. However, through clinical investigations in patients and experimental findings in animal models of Parkinson's disease for years, it is now well recognized that Parkinson's disease is more than just a motor-deficit disorder. The majority of Parkinson's disease patients suffer from nonmotor disabilities, for instance, cognitive impairment, autonomic dysfunction, sensory dysfunction, and sleep disorder. So far, anti-PD prescriptions and surgical treatments have been mainly focusing on motor dysfunctions, leaving cognitive impairment a marginal clinical field. Within the nonmotor symptoms, cognitive impairment is one of the most common and significant aspects of Parkinson's disease, and cognitive deficits such as dysexecutive syndrome and visuospatial disturbances could seriously affect the quality of life, reduce life expectancy, prolong the duration of hospitalization, and therefore increase burdens of caregiver and medical costs. In this review, we have done a retrospective study of the recent related researches on epidemiology, clinical manifestation and diagnosis, genetics, and potential treatment of cognitive deficits in Parkinson's disease, aiming to provide a summary of cognitive impairment in Parkinson's disease and make it easy for clinicians to tackle this challenging issue in their future practice. PMID:28058128

  18. Parkinson's Disease and Cognitive Impairment.

    PubMed

    Yang, Yang; Tang, Bei-Sha; Guo, Ji-Feng

    2016-01-01

    Parkinson's disease (PD) is a progressive neurodegenerative disease primarily characterized by the hallmarks of motor symptoms, such as tremor, bradykinesia, rigidity, and postural instability. However, through clinical investigations in patients and experimental findings in animal models of Parkinson's disease for years, it is now well recognized that Parkinson's disease is more than just a motor-deficit disorder. The majority of Parkinson's disease patients suffer from nonmotor disabilities, for instance, cognitive impairment, autonomic dysfunction, sensory dysfunction, and sleep disorder. So far, anti-PD prescriptions and surgical treatments have been mainly focusing on motor dysfunctions, leaving cognitive impairment a marginal clinical field. Within the nonmotor symptoms, cognitive impairment is one of the most common and significant aspects of Parkinson's disease, and cognitive deficits such as dysexecutive syndrome and visuospatial disturbances could seriously affect the quality of life, reduce life expectancy, prolong the duration of hospitalization, and therefore increase burdens of caregiver and medical costs. In this review, we have done a retrospective study of the recent related researches on epidemiology, clinical manifestation and diagnosis, genetics, and potential treatment of cognitive deficits in Parkinson's disease, aiming to provide a summary of cognitive impairment in Parkinson's disease and make it easy for clinicians to tackle this challenging issue in their future practice.

  19. Assessment of the Visually Impaired.

    ERIC Educational Resources Information Center

    Chase, Joan B.

    1985-01-01

    Assessment of visually impaired students is traced historically, and current practices in visual functioning, movement and spatial awareness, cognition, tactile performance, and emotional/social development are noted. Federal requirements for assessment are discussed and recommended assessment practices for six major assessment domains are listed.…

  20. Oceanography for the Visually Impaired

    ERIC Educational Resources Information Center

    Fraser, Kate

    2008-01-01

    Amy Bower is a physical oceanographer and senior scientist at the Woods Hole Oceanographic Institution (WHOI) in Woods Hole, Massachusetts--she has also been legally blind for 14 years. Through her partnership with the Perkins School for the Blind in Watertown, Massachusetts, the oldest K-12 school for the visually impaired in the United States,…

  1. Cognitive impairments in abstinent alcoholics.

    PubMed Central

    Fein, G; Bachman, L; Fisher, S; Davenport, L

    1990-01-01

    Impaired cognitive functioning in alcoholics is widespread during the first months of detoxification. Between half and two thirds of abstinent alcoholics exhibit cognitive impairments during this period, with residual deficits persisting for years after detoxification in some patients. The most severe deficits have been observed in visuospatial abilities, perceptual-motor integration, abstract reasoning, and new learning. The most significant predictors of cognitive dysfunction in persons recovering from alcoholism are the time elapsed since the last drink and the person's age. Surprisingly, the pattern and duration of a patient's alcohol abuse are relatively weak determinants of neuropsychological impairment during abstinence. Research investigating the hypothesis that cognitive impairments may be related to alcoholic persons resuming drinking has yielded mixed results, but a higher level of neuropsychological functioning is associated with increased rates of completing treatment programs and with greater success in the work environment after discharge from treatment. The possibility of cognitive limitations should be taken into account in planning treatment programs for alcoholism. PMID:2190421

  2. Forced vital capacity, slow vital capacity, or inspiratory vital capacity: which is the best measure of vital capacity?

    PubMed

    Chhabra, S K

    1998-01-01

    Vital capacity can be measured as forced vital capacity (FVC), slow vital capacity (SVC), and inspiratory vital capacity (IVC). Although it is well known that the latter two are generally greater, a systematic comparison of the three in subjects with different degrees of airways obstruction has not been made. Sixty asthmatics and 20 normal subjects performed maneuvers for measurement of FVC, SVC, and IVC on a dry, rolling-seal spirometer. The severity of airways obstruction in asthmatics was classified as mild, moderate, and severe. There was no significant difference between FVC, SVC, and IVC in normal subjects. However, the three measurements of vital capacity were significantly different in all subgroups of asthmatics. FVC was smaller than both SVC and IVC. The differences were more marked in patients with moderate and severe degrees of airways obstruction. The differences between SVC and IVC were small and clinically not important. Forced expiratory volume in 1 sec (FEV1) expressed as percent of FVC, SVC, and IVC, was not different in normals and asthmatics with mild airways obstruction. The ratios were significantly different in asthmatics with moderate and severe airways obstruction. FEV1/IVC ratio was the lowest in both the groups followed by FEV1/SVC and FEV1/FVC. IVC and SVC are greater than FVC in patients with airways obstruction. This difference increases as the degree of obstruction increases. The difference between SVC or IVC and FVC serves as an indicator of air trapping. Both FVC and IVC could be measured and the largest VC used to calculate the FEV1/VC ratio because this increases the sensitivity of spirometry in detecting airways obstruction.

  3. Physiologic Determinants of Exercise Capacity in Pulmonary Langerhans Cell Histiocytosis: A Multidimensional Analysis

    PubMed Central

    Fry, Stephanie; Giovannelli, Jonathan; Langlois, Carole; Bricout, Nicolas; Aguilaniu, Bernard; Bellocq, Agnes; Le Rouzic, Olivier; Dominique, Stephane; Delobbe, Alain; François, Geraldine; Tazi, Abdellatif; Wallaert, Benoit; Chenivesse, Cecile

    2017-01-01

    Background Reduced exercise capacity severely impacts quality of life in pulmonary Langerhans cell histiocytosis. Ascertaining mechanisms that impair exercise capacity is necessary to identify targets for symptomatic treatments. Methods Dyspnea, pulmonary function tests and cardiopulmonary exercise test were analysed in 62 study participants. Data were compared between subjects with impaired and normal aerobic capacity (V’O2 peak less than 84% versus 84% predicted or more). Data were reduced using a principal component analysis. Multivariate analysis included V’O2 peak as the dependent variable and principal components as covariates. Results V’O2 peak was reduced in 44 subjects (71%). Subjects with impaired aerobic capacity presented: (i) decreased FEV1, FVC, FEV1/FVC, DLCO and DLCO/VA and increased AaDO2, (ii) increased ventilatory equivalents at ventilatory threshold, VD/VT peak, AaDO2 peak and PaCO2 peak and decreased ventilatory reserve and PaO2 peak. There was no difference between groups in dyspnea scores. Principal component analysis extracted 4 principal components interpreted as follows: PC1: gas exchange; PC2: “pseudorestriction”; PC3: exercise-induced hyperpnea; PC4: air trapping. Multivariate analysis explained 65% of V’O2 peak. The 4 principal components were independently associated with V’O2 peak (βcoefficients: PC1: 9.3 [4.6; 14], PC2: 7.5 [3; 11.9], PC3: -5.3 [-9.6;-1.], PC4: -9.8 [-14,9;-4.7]). Conclusion Impaired exercise capacity is frequent in pulmonary Langerhans cell histiocytosis. It is mainly caused by pulmonary changes but is not associated with increased dyspnea intensity. Therefore, treating the lung represents a relevant approach for improving exercise capacity, even in patients experiencing mild dyspnea. PMID:28072848

  4. Sentence Repetition Accuracy in Adults with Developmental Language Impairment: Interactions of Participant Capacities and Sentence Structures

    ERIC Educational Resources Information Center

    Poll, Gerard H.; Miller, Carol A.; van Hell, Janet G.

    2016-01-01

    Purpose: We asked whether sentence repetition accuracy could be explained by interactions of participant processing limitations with the structures of the sentences. We also tested a prediction of the procedural deficit hypothesis (Ullman & Pierpont, 2005) that adjuncts are more difficult than arguments for individuals with developmental…

  5. Reduced mitochondrial oxidative capacity and increased mitochondrial uncoupling impair myocardial energetics in obesity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Obesity is a risk factor for cardiovascular disease and is strongly associated with insulin resistance and type 2 diabetes. Recent studies in obese humans and animals demonstrated increased myocardial oxygen consumption (MVO2) and reduced cardiac efficiency (CE); however, the underlying mechanisms r...

  6. Exercise capacity is not impaired after acute alcohol ingestion: a pilot study.

    PubMed

    Popovic, Dejana; Damjanovic, Svetozar S; Plecas-Solarovic, Bosiljka; Pešić, Vesna; Stojiljkovic, Stanimir; Banovic, Marko; Ristic, Arsen; Mantegazza, Valentina; Agostoni, Piergiuseppe

    2016-12-01

    The usage of alcohol is widespread, but the effects of acute alcohol ingestion on exercise performance and the stress hormone axis are not fully elucidated.We studied 10 healthy white men, nonhabitual drinkers, by Doppler echocardiography at rest, spirometry, and maximal cardiopulmonary exercise test (CPET) in two visits (2-4 days in between), one after administration of 1.5 g/kg ethanol (whisky) diluted at 15% in water, and the other after administration of an equivalent volume of water. Plasma levels of NT-pro-BNP, cortisol, and adrenocorticotropic hormone (ACTH) were also measured 10 min before the test, at maximal effort and at the third minute of recovery. Ethanol concentration was measured from resting blood samples by gas chromatography and it increased from 0.00 ± 0.00 to 1.25 ± 0.54‰ (P < 0.001). Basal echocardiographic and spirometric parameters were normal and remained so after acute alcohol intake, whereas ACTH, cortisol, and NT-pro-BNP nonsignificantly increased in all phases of the test. CPET data suggested a trend toward a slight reduction of exercise performance (peak VO2 = 3008 ± 638 vs. 2900 ± 543 ml/min, ns; peak workload = 269 ± 53 vs. 249 ± 40 W, ns; test duration 13.7 ± 2.2 vs. 13.3 ± 1.7 min, ns; VE/VCO2 22.1 ± 1.4 vs. 23.3 ± 2.9, ns). Ventilatory equivalent for carbon dioxide at rest was higher after alcohol intake (28 ± 2.5 vs. 30.4 ± 3.2, P = 0.039) and maximal respiratory exchange ratio was lower after alcohol intake (1.17 ± 0.02 vs. 1.14 ± 0.04, P = 0.04). In conclusion, we showed that acute alcohol intake in healthy white men is associated with a nonsignificant exercise performance reduction and stress hormone stimulation, with an unchanged exercise metabolism.

  7. High Capacity Phase/Amplitude Modulated Optical Communication Systems and Nonlinear Inter-Channel Impairments

    NASA Astrophysics Data System (ADS)

    Tavassoli, Vahid

    This thesis studies and mathematically models nonlinear interactions among channels of modern high bit rate (amplitude/) phase modulated optical systems. First, phase modulated analogue systems are studied and a differential receiving method is suggested with experimental validation. The main focus of the rest of the thesis is on digital advanced modulation format systems. Cross-talk due to fiber Kerr nonlinearity in two-format hybrid systems as well as 16-QAM systems is mathematically modelled and verified by simulation for different system parameters. A comparative study of differential receivers and coherent receivers is also given for hybrid systems. The model is based on mathematically proven assumptions and provides an intuitive analytical understanding of nonlinear cross-talk in such systems.

  8. Impaired insulin secretory capacity in mice lacking a functional vitamin D receptor.

    PubMed

    Zeitz, Ute; Weber, Karin; Soegiarto, Desi W; Wolf, Eckhard; Balling, Rudi; Erben, Reinhold G

    2003-03-01

    It was the aim of this study to further explore the functional role of vitamin D in the endocrine pancreas. By gene targeting, we have recently generated mice in which a lacZ reporter gene is driven by the endogenous vitamin D receptor (VDR) promoter. These mice express a functionally inactive mutant VDR. Pancreatic islets but not exocrine pancreas cells showed strong lacZ reporter gene expression in mutant mice. To rule out possible influences of hypocalcemia on pancreatic endocrine function, a rescue diet enriched with calcium, phosphorus, and lactose was fed to wild-type (WT) and VDR mutant mice. The rescue diet normalized body weight and mineral homeostasis in VDR mutants. In glucose tolerance tests, baseline blood glucose levels were unchanged in fasting VDR mutants. However, blood glucose was elevated after oral or subcutaneous glucose loading, and maximum serum insulin levels were reduced by approximately 60% in VDR mutants vs. WT mice on either diet. In addition, insulin mRNA levels were decreased in VDR mutant mice on both diets, whereas pancreatic beta cell mass, islet architecture, and islet neogenesis were normal. These findings clearly establish a molecular role of the vitamin D-responsive elements in pancreatic insulin synthesis and secretion in vivo.

  9. A dynamic test to assess learning capacity in people with severe impairments.

    PubMed

    Hessels-Schlatter, Christine

    2002-09-01

    Because traditional intelligence tests do not allow a reliable and valid estimate of the general cognitive abilities of individuals with IQs lower than 55, a dynamic test of analogical reasoning (Analogical Reasoning Learning Test-ARLT) was constructed for use with this population. The aim of the test is to distinguish individuals who could undergo more ambitious schooling and cognitive training from those who would profit little or none from such an intervention. Internal consistency and test-retest reliability of this measure are high. Discriminant and predictive validity, assessed with another learning test and with a one-month training on inductive reasoning, respectively, are satisfactory. The test is seen as a useful tool for diagnostic differentiation among low performers.

  10. Grammatical sensitivity and working memory in children with language impairment

    PubMed Central

    Marton, Klara; Campanelli, Luca; Farkas, Lajos

    2013-01-01

    Children with primary language impairment (LI) show a deficit in processing different grammatical structures, verb inflections, and syntactically complex sentences among other things (Clahsen–Hansen 1997; Leonard et al. 1997). Cross-linguistic research has shown that the pattern of performance is language-specific. We examined grammatical sensitivity to word order and agreement violations in 50 Hungarian-speaking children with and without LI. The findings suggest a strong association between sensitivity to grammatical violations and working memory capacity. Variations in working memory performance predicted grammatical sensitivity. Hungarian participants with LI exhibited a weakness in detecting both agreement and word order violations. PMID:23440891

  11. Use of a physiological profile to document motor impairment in ageing and in clinical groups.

    PubMed

    Lord, S R; Delbaere, K; Gandevia, S C

    2016-08-15

    Ageing decreases exercise performance and is frequently accompanied by reductions in cognitive performance. Deterioration in the physiological capacity to stand, locomote and exercise can manifest itself as falling over and represents a significant deterioration in sensorimotor control. In the elderly, falling leads to serious morbidity and mortality with major societal costs. Measurement of a suite of physiological capacities that are required for successful motor performance (including vision, muscle strength, proprioception and balance) has been used to produce a physiological profile assessment (PPA) which has been tracked over the age spectrum and in different diseases (e.g. multiple sclerosis, Parkinson's disease). As well as measures of specific physiological capacities, the PPA generates an overall 'score' which quantitatively measures an individual's cumulative risk of falling. The present review collates data from the PPA (and the physiological capacities it measures) as well as its use in strategies to reduce falls in the elderly and those with different diseases. We emphasise that (i) motor impairment arises via reductions in a wide range of sensorimotor abilities; (ii) the PPA approach not only gives a snapshot of the physiological capacity of an individual, but it also gives insight into the deficits among groups of individuals with particular diseases; and (iii) deficits in seemingly restricted and disparate physiological domains (e.g. vision, strength, cognition) are funnelled into impairments in tasks requiring upright balance. Motor impairments become more prevalent with ageing but careful physiological measurement and appropriate interventions offer a way to maximise health across the lifespan.

  12. 10 CFR 904.9 - Excess capacity.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Excess capacity. 904.9 Section 904.9 Energy DEPARTMENT OF... Marketing § 904.9 Excess capacity. (a) If the Uprating Program results in Excess Capacity, Western shall be entitled to such Excess Capacity to integrate the operation of the Boulder City Area Projects and...

  13. Impairment of phagocytic functions of alveolar macrophages by hydrogen peroxide

    SciTech Connect

    Oosting, R.S.; van Bree, L.; van Iwaarden, J.F.; van Golde, L.M.; Verhoef, J. )

    1990-08-01

    Hydrogen peroxide (H2O2) inhibited phagocytosis and superoxide anion production by rat alveolar macrophages. The inhibition was irreversible and concentration and exposure time dependent. The potential relationship between H2O2-induced biochemical perturbations and impaired alveolar macrophage phagocytic functions was investigated. Alveolar macrophage viability and Fc receptor binding capacity were not affected by H2O2. There was probably no correlation between a H2O2-induced rise in cytosolic (Ca2+) ((Ca2+)i) and the impairment of phagocytosis by alveolar macrophages, as was suggested by the following findings. First, the H2O2-induced rise in (Ca2+)i could be inhibited by chelation of extracellular Ca2+, whereas the H2O2-induced impairment of phagocytosis could not. Second, the H2O2-induced rise in (Ca2+)i was reversible, whereas the impairment of phagocytosis was not. And finally, a rise in (Ca2+)i by incubation of alveolar macrophages with the calcium ionophore A23187 did not affect phagocytosis. Various experiments suggested that ATP depletion may play an important role in the H2O2 toxicity for alveolar macrophages. Comparable concentrations of H2O2 caused an irreversible decrease both in cellular ATP and in phagocytosis and superoxide production by alveolar macrophages. In addition, time course of ATP depletion and induction of impaired alveolar macrophage function were similar. In view of the fact that the strong oxidant H2O2 may react with a large variety of biological substances, possible other toxic lesions may not be excluded as underlying mechanism for H2O2-induced inhibition of phagocytic functions of alveolar macrophages.

  14. Brain diabetic neurodegeneration segregates with low intrinsic aerobic capacity

    PubMed Central

    Choi, Joungil; Chandrasekaran, Krish; Demarest, Tyler G; Kristian, Tibor; Xu, Su; Vijaykumar, Kadambari; Dsouza, Kevin Geoffrey; Qi, Nathan R; Yarowsky, Paul J; Gallipoli, Rao; Koch, Lauren G; Fiskum, Gary M; Britton, Steven L; Russell, James W

    2014-01-01

    Objectives Diabetes leads to cognitive impairment and is associated with age-related neurodegenerative diseases including Alzheimer's disease (AD). Thus, understanding diabetes-induced alterations in brain function is important for developing early interventions for neurodegeneration. Low-capacity runner (LCR) rats are obese and manifest metabolic risk factors resembling human “impaired glucose tolerance” or metabolic syndrome. We examined hippocampal function in aged LCR rats compared to their high-capacity runner (HCR) rat counterparts. Methods Hippocampal function was examined using proton magnetic resonance spectroscopy and imaging, unbiased stereology analysis, and a Y maze. Changes in the mitochondrial respiratory chain function and levels of hyperphosphorylated tau and mitochondrial transcriptional regulators were examined. Results The levels of glutamate, myo-inositol, taurine, and choline-containing compounds were significantly increased in the aged LCR rats. We observed a significant loss of hippocampal neurons and impaired cognitive function in aged LCR rats. Respiratory chain function and activity were significantly decreased in the aged LCR rats. Hyperphosphorylated tau was accumulated within mitochondria and peroxisome proliferator-activated receptor-gamma coactivator 1α, the NAD+-dependent protein deacetylase sirtuin 1, and mitochondrial transcription factor A were downregulated in the aged LCR rat hippocampus. Interpretation These data provide evidence of a neurodegenerative process in the hippocampus of aged LCR rats, consistent with those seen in aged-related dementing illnesses such as AD in humans. The metabolic and mitochondrial abnormalities observed in LCR rat hippocampus are similar to well-described mechanisms that lead to diabetic neuropathy and may provide an important link between cognitive and metabolic dysfunction. PMID:25356430

  15. High capacity carbon dioxide sorbent

    DOEpatents

    Dietz, Steven Dean; Alptekin, Gokhan; Jayaraman, Ambalavanan

    2015-09-01

    The present invention provides a sorbent for the removal of carbon dioxide from gas streams, comprising: a CO.sub.2 capacity of at least 9 weight percent when measured at 22.degree. C. and 1 atmosphere; an H.sub.2O capacity of at most 15 weight percent when measured at 25.degree. C. and 1 atmosphere; and an isosteric heat of adsorption of from 5 to 8.5 kilocalories per mole of CO.sub.2. The invention also provides a carbon sorbent in a powder, a granular or a pellet form for the removal of carbon dioxide from gas streams, comprising: a carbon content of at least 90 weight percent; a nitrogen content of at least 1 weight percent; an oxygen content of at most 3 weight percent; a BET surface area from 50 to 2600 m.sup.2/g; and a DFT micropore volume from 0.04 to 0.8 cc/g.

  16. Considerations of informed consent and decision-making competence in older adults with cognitive impairment.

    PubMed

    Mayo, Ann M; Wallhagen, Margaret I

    2009-04-01

    Including older adults with cognitive impairment in research studies is necessary to ensure that interventions designed to improve care are effective for all older adults. However, issues related to capacity to consent raise many difficult questions that nurse researchers must address. Protecting vulnerable participants while simultaneously maintaining autonomy and moving important research forward can be challenging. Assessing the decision-making abilities of understanding, appreciation, reasoning, and expressing a choice is an important aspect of determining decision-making capacity. Yet although this is the prominent rational method for judging decision-making competence, it does not take into consideration the importance of culture, values, and emotions. This article focuses on the assessment of decision-making capacity to consent, recommendations for obtaining informed consent in older adults with cognitive impairment, the use of surrogate decision makers, strategies to maximize research participation, and directions for future research.

  17. Capacity is the Wrong Paradigm

    DTIC Science & Technology

    2002-01-01

    Florida Gainesville, FL 32611-6120 ABSTRACT At present, \\capacity" is the prevailing paradigm for covert channels. With respect to steganography ...INTRODUCTION Steganography is the art and science of sending a hidden message from Alice to Bob, so that an eavesdropper is not aware that this hidden...discussed a di erent new paradigm con- cerning steganography . The concern of that new paradigm was \\when is something discovered." We feel that both

  18. High Information Capacity Quantum Imaging

    DTIC Science & Technology

    2014-09-19

    High Capacity Quantum Imaging Robert W. Boyd, John C. Howell Department of Physics and Astronomy , University of Rochester, Rochester, New York, 14627...breadth of fields from magnetic resonance imaging [83] to radio astronomy [84] to entanglement characterization [85, 86]. B. Adapting Single Photon...L. Starck, and R. Ottensamer, “Compressed sensing in astronomy ,” Selected Topics in Signal Processing, IEEE Journal of 2, 718–726 (2008). [85] S. T

  19. High capacity immobilized amine sorbents

    DOEpatents

    Gray, McMahan L.; Champagne, Kenneth J.; Soong, Yee; Filburn, Thomas

    2007-10-30

    A method is provided for making low-cost CO.sub.2 sorbents that can be used in large-scale gas-solid processes. The improved method entails treating an amine to increase the number of secondary amine groups and impregnating the amine in a porous solid support. The method increases the CO.sub.2 capture capacity and decreases the cost of utilizing an amine-enriched solid sorbent in CO.sub.2 capture systems.

  20. Declining physical capacity but maintained aerobic activity in early Alzheimer's disease.

    PubMed

    Cedervall, Ylva; Kilander, Lena; Aberg, Anna Cristina

    2012-05-01

    The longitudinal influences on physical capacity and habitual aerobic activity level in the early stages of Alzheimer's disease (AD) are unclear. Therefore, changes in physical capacity and aerobic activity level were evaluated. Twenty-five individuals with AD were assessed annually for 2 years, by 10-m walk test, 6-minute walk test, and timed up-and-go (TUG) single/dual tasks. Habitual aerobic activity was assessed by diary registrations. The AD group showed a lower physical capacity than controls at baseline but comparable levels of aerobic activity. During the follow-up period, physical capacity declined in the AD group, but the aerobic activity levels changed only marginally. Our results show that in the early stages of AD, people are capable of maintaining health-promoting aerobic activity levels, despite a decline in their physical capacity. Additionally, it appears that cognitive dysfunction contributes to an impaired physical capacity. The TUG tasks might, therefore, be useful for detecting early signs of cognitive impairment.

  1. Information capacity of specific interactions

    PubMed Central

    Huntley, Miriam H.; Murugan, Arvind; Brenner, Michael P.

    2016-01-01

    Specific interactions are a hallmark feature of self-assembly and signal-processing systems in both synthetic and biological settings. Specificity between components may arise from a wide variety of physical and chemical mechanisms in diverse contexts, from DNA hybridization to shape-sensitive depletion interactions. Despite this diversity, all systems that rely on interaction specificity operate under the constraint that increasing the number of distinct components inevitably increases off-target binding. Here we introduce “capacity,” the maximal information encodable using specific interactions, to compare specificity across diverse experimental systems and to compute how specificity changes with physical parameters. Using this framework, we find that “shape” coding of interactions has higher capacity than chemical (“color”) coding because the strength of off-target binding is strongly sublinear in binding-site size for shapes while being linear for colors. We also find that different specificity mechanisms, such as shape and color, can be combined in a synergistic manner, giving a capacity greater than the sum of the parts. PMID:27155013

  2. Solubilisation capacity of Brij surfactants.

    PubMed

    Ribeiro, Maria E N P; de Moura, Carolina L; Vieira, Mariano G S; Gramosa, Nilce V; Chaibundit, Chiraphon; de Mattos, Marcos C; Attwood, David; Yeates, Stephen G; Nixon, S Keith; Ricardo, Nágila M P S

    2012-10-15

    The aim of this study was to investigate the potential of selected Brij non-ionic surfactants for enhancing the solubility of poorly water-soluble drugs. Griseofulvin was selected as a model drug candidate enabling comparisons to be made with the solubilisation capacities of other poly(ethylene oxide)-based copolymers. UV/Vis and (1)H NMR spectroscopies were used to quantify the enhancement of solubility of griseofulvin in 1 wt% aqueous micellar solutions of Brij 78 (C(18)H(37)E(20)), Brij 98 (C(18)H(35)E(20)) and Brij 700 (C(18)H(37)E(100)) (where E represents the OCH(2)CH(2) unit of the poly(ethylene oxide) chain) at 25, 37 and 40 °C. Solubilisation capacities (S(cp) expressed as mg griseofulvin per g Brij) were similar for Brij 78 and 98 (range 6-11 mg g(-1)) but lower for Brij 700 (3-4 mg g(-1)) as would be expected for the surfactant with the higher ethylene oxide content. The drug loading capacity of micelles of Brij 78 was higher than many di- and triblock copolymers with hydrophilic E-blocks specifically designed for enhancement of drug solubility.

  3. Auditory Short-Term Memory Capacity Correlates with Gray Matter Density in the Left Posterior STS in Cognitively Normal and Dyslexic Adults

    ERIC Educational Resources Information Center

    Richardson, Fiona M.; Ramsden, Sue; Ellis, Caroline; Burnett, Stephanie; Megnin, Odette; Catmur, Caroline; Schofield, Tom M.; Leff, Alex P.; Price, Cathy J.

    2011-01-01

    A central feature of auditory STM is its item-limited processing capacity. We investigated whether auditory STM capacity correlated with regional gray and white matter in the structural MRI images from 74 healthy adults, 40 of whom had a prior diagnosis of developmental dyslexia whereas 34 had no history of any cognitive impairment. Using…

  4. Neurosonological Examination: A Non-Invasive Approach for the Detection of Cerebrovascular Impairment in AD

    PubMed Central

    Urbanova, Barbora; Tomek, Ales; Mikulik, Robert; Magerova, Hana; Horinek, Daniel; Hort, Jakub

    2014-01-01

    There has been a growing interest in vascular impairment associated with Alzheimer’s disease (AD). This interest was stimulated by the findings of higher incidence of vascular risk factors in AD. Signs of vascular impairment were investigated notably in the field of imaging methods. Our aim was to explore ultrasonographic studies of extra- and intracranial vessels in patients with AD and mild cognitive impairment (MCI) and define implications for diagnosis, treatment, and prevention of the disease. The most frequently studied parameters with extracranial ultrasound are intima-media thickness in common carotid artery, carotid atherosclerosis, and total cerebral blood flow. The transcranial ultrasound concentrates mostly on flow velocities, pulsatility indices, cerebrovascular reserve capacity, and cerebral microembolization. Studies suggest that there is morphological and functional impairment of cerebral circulation in AD compared to healthy subjects. Ultrasound as a non-invasive method could be potentially useful in identifying individuals in a higher risk of progression of cognitive decline. PMID:24478651

  5. Flying Training Capacity Model: Initial Results

    DTIC Science & Technology

    2005-06-21

    numbers by base • FTRAP model is not versatile • Excel spreadsheets based on corporate knowledge • Requires flying training subject matter expert ( SME ... IFR & VFR operations • Capacity given in terms of runway operations per year • AETC Capacity Metrics - Graduates • Based on sortie generation • Consider...Pilots (IPs) from each course • Airspace capacities from base operations SMEs • Runway capacities • Military Operating Area capacities (including aux

  6. Mandatory notification of impaired doctors.

    PubMed

    Beran, R G

    2014-12-01

    Mandatory reporting of impaired doctors is compulsory in Australasia. Australian Health Practitioner Regulation Agency guidelines for notification claim high benchmark though the Royal Australasian College of Surgeons and the Royal Australasian College of Physicians suggest they still obstruct doctors seeking help. Western Australia excludes mandatory reporting of practitioner-patients. This study examines reporting, consequences and international experiences with notification. Depressed doctors avoid diagnosis and treatment, fearing consequences, yet are more prone to marital problems, substance dependence and needing psychotherapy. South African research confirms isolation of impaired doctors and delayed seeking help with definable characteristics of those at risk. New Zealand data acknowledge: errors occur; questionable contribution from mandatory reporting; issues concerning competence assessment; favouring reporting to senior colleagues or self-intervention to compliance with mandatory reporting. UK found an anaesthetist guilty of professional misconduct for not reporting and sanctioned doctors regarding Harold Shipman. Australians are reluctant to report, fearing legalistic intrusion into care. Australian research confirmed definable characteristics for doctors with psychiatric illness or alcohol abuse. Exposure to legal medicine evokes personal disenchantment for doctors involved. Medicine poses barriers for impaired doctors. Spanish and UK doctors do not use general practitioners and may have suboptimal care. US and European doctors self-medicate using samples. US drug-dependent doctors also prescribe for spouses. Junior doctors are losing empathy with the profession. UK doctors favour private care, avoiding public scrutiny. NZ and Brazil created specific services for doctors, which appear effective. Mandatory reporting may be counterproductive requiring reappraisal.

  7. Oculomotor Impairments in Developmental Dyspraxia.

    PubMed

    Gaymard, B; Giannitelli, M; Challes, G; Rivaud-Péchoux, S; Bonnot, O; Cohen, D; Xavier, J

    2017-04-01

    Children with developmental dyspraxia (DD) express impairments in the acquisition of various motor skills and in the development of their social cognition abilities. Although the neural bases of this condition are not fully understood, they are thought to involve frontal cortical areas, subcortical structures, and the cerebellum. Although cerebellar dysfunction is typically difficult to assess and quantify using traditional neurophysiological methods, oculomotor analysis may provide insight into specific cerebellar patterns. The aim of the present study was to investigate, in dyspraxic and typically developing subjects, various oculomotor saccade tasks specifically designed to reveal frontal and cerebellar dysfunction. In addition to evidence supporting prefrontal dysfunction, our results revealed increased variability of saccade accuracy consistent with cerebellar impairments. Furthermore, we found that dyspraxic patients showed decreased velocities of non-visually guided saccades. A closer analysis revealed significant differences in saccade velocity profiles with slightly decreased maximum saccade velocities but markedly prolonged deceleration phases. We show that this pattern was not related to a decreased state of alertness but was suggestive of cerebellar dysfunction. However, the clear predominance of this pattern in non-visually guided saccades warrants alternative hypotheses. In light of previous experimental and anatomical studies, we propose that this unusual pattern may be a consequence of impaired connections between frontal areas and cerebellar oculomotor structures.

  8. Ability of older people with dementia or cognitive impairment to manage medicine regimens: a narrative review.

    PubMed

    Elliott, Rohan A; Goeman, Dianne; Beanland, Christine; Koch, Susan

    2015-01-01

    Impaired cognition has a significant impact on a person's ability to manage their medicines. The aim of this paper is to provide a narrative review of contemporary literature on medicines management by people with dementia or cognitive impairment living in the community, methods for assessing their capacity to safely manage medicines, and strategies for supporting independent medicines management. Studies and reviews addressing medicines management by people with dementia or cognitive impairment published between 2003 and 2013 were identified via searches of Medline and other databases. The literature indicates that as cognitive impairment progresses, the ability to plan, organise, and execute medicine management tasks is impaired, leading to increased risk of unintentional non-adherence, medication errors, preventable medication-related hospital admissions and dependence on family carers or community nursing services to assist with medicines management. Impaired functional capacity may not be detected by health professionals in routine clinical encounters. Assessment of patients' (or carers') ability to safely manage medicines is not undertaken routinely, and when it is there is variability in the methods used. Self-report and informant report may be helpful, but can be unreliable or prone to bias. Measures of cognitive function are useful, but may lack sensitivity and specificity. Direct observation, using a structured, standardised performance-based tool, may help to determine whether a person is able to manage their medicines and identify barriers to adherence such as inability to open medicine packaging. A range of strategies have been used to support independent medicines management in people with cognitive impairment, but there is little high-quality research underpinning these strategies. Further studies are needed to develop and evaluate approaches to facilitate safe medicines management by older people with cognitive impairment and their carers.

  9. Cognitive Impairment, Oral Self-care Function and Dental Caries Severity in Community-dwelling Older Adults

    PubMed Central

    Chen, Xi; Clark, Jennifer JJ; Chen, Hong; Naorungroj, Supawadee

    2013-01-01

    Objective To investigate whether oral self-care function mediates the associations between cognitive impairment and caries severity in community-dwelling older adults. Background Cognitive impairment significantly affects activities of daily living and compromises oral health, systemic health and quality of life in older adults. However, the associations among cognitive impairment, oral self-care capacity and caries severity remain unclear. This increases difficulty in developing effective interventions for cognitively impaired patients. Materials and methods Medical, dental, cognitive and functional assessments were abstracted from the dental records of 600 community-dwelling elderly. 230 participants were selected using propensity score matching and categorised into normal, cognitive impairment but no dementia (CIND) and dementia groups based on their cognitive status and a diagnosis of dementia. Multivariable regressions were developed to examine the mediating effect of oral self-care function on the association between cognitive status and number of caries or retained roots. Results Cognitive impairment, oral self-care function and dental caries severity were intercorrelated. Multivariable analysis showed that without adjusting for oral self-care capacity, cognition was significantly associated with the number of caries or retained roots (p = 0.003). However, the association was not significant when oral self-care capacity was adjusted (p = 0.125). In contrast, individuals with impaired oral self-care capacity had a greater risk of having a caries or retained root (RR = 1.67, 95% CI 1.15, 2.44). Conclusion Oral care capacity mediates the association between cognition and dental caries severity in community-dwelling older adults. PMID:23758583

  10. Nature Trails for the Visually Impaired.

    ERIC Educational Resources Information Center

    Schwartz, Jonathan R.

    Many interpretive nature trails have been established for the visually impaired in recent years. The objectives of the investigation were to (a) identify what has been done in the past in the way of nature trail design for the visually impaired, (b) compare this with what professional workers for the visually impaired consider important in the…

  11. Evaluating the Visually Impaired: Neuropsychological Techniques.

    ERIC Educational Resources Information Center

    Price, J. R.; And Others

    1987-01-01

    Assessment of nonvisual neuropsychological impairments in visually impaired persons can be achieved through modification of existing intelligence, memory, sensory-motor, personality, language, and achievement tests so that they do not require vision or penalize visually impaired persons. The Halstead-Reitan and Luria-Nebraska neuropsychological…

  12. The Relationship between Visual Impairment and Gestures.

    ERIC Educational Resources Information Center

    Frame, Melissa J.

    2000-01-01

    A study found the gestural activity of 15 adolescents with visual impairments differed from that of 15 adolescents with sight. Subjects with visual impairments used more adapters (especially finger-to-hand gestures) and fewer conversational gestures. Differences in gestural activity by degree of visual impairment and grade in school were also…

  13. Conceptions of Hearing Impairment in Students.

    ERIC Educational Resources Information Center

    Alm, Irma; Ronnberg, Jerker

    1991-01-01

    Twelve students (ages 10-18) with hearing impairment and 12 normal hearing students were interviewed to determine attitudes about hearing impairment and self-concept. Results showed that school-integrated hearing-impaired students possessed a positive self-perception, but they shared normal hearing students' negative view of hearing-impaired…

  14. Communication Skills and Learning in Impaired Individuals

    ERIC Educational Resources Information Center

    Eliöz, Murat

    2016-01-01

    The purpose of this study is to compare the communication skills of individuals with different disabilities with athletes and sedentary people and to examine their learning abilities which influence the development of communication. A total of 159 male subjects 31 sedentary, 30 visually impaired, 27 hearing impaired, 40 physically impaired and 31…

  15. 20 CFR 220.104 - Multiple impairments.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Multiple impairments. 220.104 Section 220.104... DISABILITY Evaluation of Disability § 220.104 Multiple impairments. To determine whether the claimant's... impairments could be the basis of eligiblity under the law, the combined effect of all of the...

  16. Fluoroquinolone-gyrase-DNA complexes: two modes of drug binding.

    PubMed

    Mustaev, Arkady; Malik, Muhammad; Zhao, Xilin; Kurepina, Natalia; Luan, Gan; Oppegard, Lisa M; Hiasa, Hiroshi; Marks, Kevin R; Kerns, Robert J; Berger, James M; Drlica, Karl

    2014-05-02

    DNA gyrase and topoisomerase IV control bacterial DNA topology by breaking DNA, passing duplex DNA through the break, and then resealing the break. This process is subject to reversible corruption by fluoroquinolones, antibacterials that form drug-enzyme-DNA complexes in which the DNA is broken. The complexes, called cleaved complexes because of the presence of DNA breaks, have been crystallized and found to have the fluoroquinolone C-7 ring system facing the GyrB/ParE subunits. As expected from x-ray crystallography, a thiol-reactive, C-7-modified chloroacetyl derivative of ciprofloxacin (Cip-AcCl) formed cross-linked cleaved complexes with mutant GyrB-Cys(466) gyrase as evidenced by resistance to reversal by both EDTA and thermal treatments. Surprisingly, cross-linking was also readily seen with complexes formed by mutant GyrA-G81C gyrase, thereby revealing a novel drug-gyrase interaction not observed in crystal structures. The cross-link between fluoroquinolone and GyrA-G81C gyrase correlated with exceptional bacteriostatic activity for Cip-AcCl with a quinolone-resistant GyrA-G81C variant of Escherichia coli and its Mycobacterium smegmatis equivalent (GyrA-G89C). Cip-AcCl-mediated, irreversible inhibition of DNA replication provided further evidence for a GyrA-drug cross-link. Collectively these data establish the existence of interactions between the fluoroquinolone C-7 ring and both GyrA and GyrB. Because the GyrA-Gly(81) and GyrB-Glu(466) residues are far apart (17 Å) in the crystal structure of cleaved complexes, two modes of quinolone binding must exist. The presence of two binding modes raises the possibility that multiple quinolone-enzyme-DNA complexes can form, a discovery that opens new avenues for exploring and exploiting relationships between drug structure and activity with type II DNA topoisomerases.

  17. Interactive association of drugs binding to human serum albumin.

    PubMed

    Yang, Feng; Zhang, Yao; Liang, Hong

    2014-02-27

    Human serum albumin (HSA) is an abundant plasma protein, which attracts great interest in the pharmaceutical industry since it can bind a remarkable variety of drugs impacting their delivery and efficacy and ultimately altering the drug's pharmacokinetic and pharmacodynamic properties. Additionally, HSA is widely used in clinical settings as a drug delivery system due to its potential for improving targeting while decreasing the side effects of drugs. It is thus of great importance from the viewpoint of pharmaceutical sciences to clarify the structure, function, and properties of HSA-drug complexes. This review will succinctly outline the properties of binding site of drugs in IIA subdomain within the structure of HSA. We will also give an overview on the binding characterization of interactive association of drugs to human serum albumin that may potentially lead to significant clinical applications.

  18. Single water entropy: hydrophobic crossover and application to drug binding.

    PubMed

    Sasikala, Wilbee D; Mukherjee, Arnab

    2014-09-11

    Entropy of water plays an important role in both chemical and biological processes e.g. hydrophobic effect, molecular recognition etc. Here we use a new approach to calculate translational and rotational entropy of the individual water molecules around different hydrophobic and charged solutes. We show that for small hydrophobic solutes, the translational and rotational entropies of each water molecule increase as a function of its distance from the solute reaching finally to a constant bulk value. As the size of the solute increases (0.746 nm), the behavior of the translational entropy is opposite; water molecules closest to the solute have higher entropy that reduces with distance from the solute. This indicates that there is a crossover in translational entropy of water molecules around hydrophobic solutes from negative to positive values as the size of the solute is increased. Rotational entropy of water molecules around hydrophobic solutes for all sizes increases with distance from the solute, indicating the absence of crossover in rotational entropy. This makes the crossover in total entropy (translation + rotation) of water molecule happen at much larger size (>1.5 nm) for hydrophobic solutes. Translational entropy of single water molecule scales logarithmically (Str(QH) = C + kB ln V), with the volume V obtained from the ellipsoid of inertia. We further discuss the origin of higher entropy of water around water and show the possibility of recovering the entropy loss of some hypothetical solutes. The results obtained are helpful to understand water entropy behavior around various hydrophobic and charged environments within biomolecules. Finally, we show how our approach can be used to calculate the entropy of the individual water molecules in a protein cavity that may be replaced during ligand binding.

  19. Reduced aerobic capacity causes leaky ryanodine receptors that trigger arrhythmia in a rat strain artificially selected and bred for low aerobic running capacity

    PubMed Central

    Høydal, MA; Stølen, TO; Johnsen, AB; Alvez, M; Catalucci, D; Condorelli, G; Koch, LG; Britton, SL; Smith, GL; Wisløff, U

    2014-01-01

    Aim Rats selectively bred for inborn Low Capacity of Running (LCR) display a series of poor health indices where as rats selected for High Capacity of Running (HCR) display a healthy profile. We hypothesized that selection of low aerobic capacity over generations leads to a phenotype with increased diastolic Ca2+ leak that trigger arrhythmia. Methods We used rats selected for HCR (N=10) or LCR (N=10) to determine the effect of inborn aerobic capacity on Ca2+ leak and susceptibility of ventricular arrhythmia. We studied isolated FURA2/AM loaded cardiomyocytes to detect Ca2+-handling and function on an inverted epi-fluorescence microscope. To determine arrhythmogenicity we did a final experiment with electrical burst pacing in Langendorff perfused hearts. Results Ca2+-handling was impaired by reduced Ca2+ amplitude, prolonged time to 50% Ca2+ decay, and reduced sarcoplasmic reticulum (SR) Ca2+-content. Impaired Ca2+ removal was influenced by reduced SR Ca2+ ATP-ase 2a (SERCA2a) function and increased sodium/Ca2+-exchanger (NCX) in LCR rats. Diastolic Ca2 leak was 87% higher in LCR rats. The leak was reduced by CaMKII inhibition. Expression levels of phosphorylated theorine-286 CaMKII levels and increased RyR2 phosphorylation at the Serine-2814 site mechanistically support our findings of increased leak in LCR. LCR rats had significantly higher incidence of ventricular fibrillation. Conclusion Selection of inborn low aerobic capacity over generations leads to a phenotype with increased risk of ventricular fibrillation. Increased phosphorylation of CaMKII at serine-2814 at the cardiac ryanodine receptor appears as an important mechanism of impaired Ca2+ handling and diastolic Ca2+ leak that results in increased susceptibility to ventricular fibrillation. PMID:24444142

  20. Theatre fleet's vital additional capacity.

    PubMed

    2012-11-01

    Vanguard Healthcare's fleet of mobile surgical facilities has been deployed to healthcare sites throughout Europe and beyond for over a decade, providing vital additional clinical capacity when existing buildings are refurbished or upgraded, in the event of flood or fire, or simply to help hospitals cater for rising demand. It is a combination of careful planning, teamwork, and the specialist expertise of Vanguard's personnel--many with a clinical background--that ensures not only each unit's successful installation, but equally its subsequent running, servicing, and maintenance, the company explains.

  1. Developing Ministerial Collaborative Planning Capacity

    DTIC Science & Technology

    2012-03-14

    the MNSTC-I era and, its successor organization the Iraq Training and Advisory Mission for the Ministry of Interior ( ITAM -MoI) that focused on the...organization can exercise influence over.26 The training partnership between the DRMI and the MoI was one of the few success stories in ITAM -MoI’s...efforts to develop institutional capacity within the MoI. Over a nineteen-month period, the DRMI, MoI JRC, and ITAM -MoI partnered to host 14

  2. Monocyte-Derived Macrophages Are Impaired in Myelodysplastic Syndrome

    PubMed Central

    Han, Yu

    2016-01-01

    Background. The myelodysplastic syndrome (MDS) comprises a group of clonal hematopoietic stem cell diseases characterized by cytopenia, dysplasia in one or more of the major myeloid lineages, ineffective hematopoiesis, and increased risk of development of acute myeloid leukemia (AML). Macrophages are innate immune cells that ingest and degrade abnormal cells, debris, and foreign material and orchestrate inflammatory processes. We analyzed the role of macrophages from MDS patients in vitro. Methods. Macrophages were induced from peripheral blood of patients with MDS via granulocyte macrophage colony-stimulating factor (GM-CSF). Phagocytic capacity of macrophages was measured with carboxyfluorescein succinimidyl ester and fluorescent microspheres. CD206 and signal regulatory protein alpha (SIRPα) on macrophages were detected by flow cytometry. Inducible nitric oxide synthase (iNOS) was measured by ELISA method. Results. Compared with normal control group, the number of monocytes increased in MDS patients. However, the monocytes showed impaired ability to induce macrophages and the number of macrophages induced from MDS samples was lower. Further, we demonstrated that the ex vivo phagocytic function of macrophages from MDS patients was impaired and levels of reorganization receptors CD206 and SIRPα were lower. Levels of iNOS secreted by macrophages in MDS were increased. Conclusions. Monocyte-derived macrophages are impaired in myelodysplastic syndromes. PMID:28074192

  3. The effects of juvenile capsaicin desensitization in rats: behavioral impairments.

    PubMed

    Petrovszki, Zita; Adam, Gábor; Kekesi, Gabriella; Tuboly, Gábor; Morvay, Zita; Nagy, Endre; Benedek, György; Horvath, Gyöngyi

    2014-02-10

    Capsaicin desensitization leads to behavioral changes, some of which are related to schizophrenia, but investigations into these effects have been scarce. The goal of this study was to characterize the consequences of juvenile capsaicin desensitization on different functions: acute and inflammation-induced thermal and mechanical sensitivity, urinary bladder capacity and thermoregulation, and also on the potentially schizophrenia-related impairments in sensory-motor gating, motor activity and cognitive functioning. Male Wistar rats desensitized with increasing doses of subcutaneous capsaicin after weaning were investigated. Heat and mechanical pain sensitivity did not change significantly; however, morphine produced a prolonged decrease in the nociceptive response to inflammation in desensitized animals. Ultrasound examination of the bladder revealed enhanced bladder volume in treated animals. Capsaicin-treated animals had higher body temperature at 22 °C in both dark and light periods, and they also showed prolonged hyperthermia in new environmental circumstances. Warm environment induced a profound impairment of thermoregulation in desensitized animals. The treated animals also showed higher levels of activity during the active phase and at both cool and warm temperatures. The amplitude of the responses to auditory stimuli and prepulse inhibition did not differ between the two groups, but the desensitized animals showed learning impairments in the novel object recognition test. These results suggest that juvenile capsaicin desensitization leads to sustained changes in several functions that may be related to schizophrenia. We propose that capsaicin desensitization, together with other interventions, may lead to an improved chronic animal model of schizophrenia.

  4. Association of waist circumference with impaired six-minute walk in type 2 diabetes mellitus is independent of cardiac function.

    PubMed

    Wang, Ying; Yang, Hong; Nolan, Mark; Negishi, Kazuaki; Burgess, John; Marwick, Thomas H

    2016-04-01

    Subclinical left ventricular dysfunction has been associated with impaired exercise capacity in type 2 diabetes mellitus. In this community-based study of 274 asymptomatic T2DM patients (71±4 years, 55% men) with preserved ejection fraction, a comprehensive resting echocardiogram was performed to gather sensitive systolic and diastolic function parameters (including speckle tracking echocardiography), and a standard six-minute walk test was performed. Tertiles of increasing waist circumference were associated with worsening walk distance. In this community-based study, we found an association of waist circumference with impaired exercise capacity, independent of age, gender, diabetes duration, insulin and angiotensin blockade, LV mass, systolic and diastolic function.

  5. Relationships between divided attention and working memory impairment in people with schizophrenia.

    PubMed

    Gray, Bradley E; Hahn, Britta; Robinson, Benjamin; Harvey, Alex; Leonard, Carly J; Luck, Steven J; Gold, James M

    2014-11-01

    Recent studies suggest that people with schizophrenia (PSZ) have difficulty distributing their attention broadly. Other research suggests that PSZ have reduced working memory (WM) capacity. This study tested whether these findings reflect a common underlying deficit. We measured the ability to distribute attention by means of the Useful Field of View (UFOV) task, in which participants must distribute attention so that they can discriminate a foveal target and simultaneously localize a peripheral target. Participants included 50 PSZ and 52 healthy control subjects. We found that PSZ exhibited severe impairments in UFOV performance, that UFOV performance was highly correlated with WM capacity in PSZ (r = -.61), and that UFOV impairments could not be explained by either impaired low-level processing or a generalized deficit. These results suggest that a common mechanism explains deficits in the ability to distribute attention broadly, reduced WM capacity, and other aspects of impaired cognition in schizophrenia. We hypothesize that this mechanism may involve abnormal local circuit dynamics that cause a hyperfocusing of resources onto a small number of internal representations.

  6. Decision-making capacity and competency in the elderly: a clinical and neuropsychological perspective.

    PubMed

    Moberg, Paul J; Rick, Jacqueline H

    2008-01-01

    With our ageing population, the number of older adults with cognitive impairment has also increased. There is both an acute and growing need for evidence-based assessments to identify their decision making capacity and competence. In the present article we (1) present definitions of decision-making capacity and competence, (2) review cognitive functions that are central to decision-making capacity as well as the methods and procedures commonly used to assess these domains, and (3) address the communication of assessment findings to patients and their loved ones. The importance of assessing decision-making capacity in the context of specific functions and of respecting the values and interests of older adults are emphasized.

  7. Control Capacity in Complex Networks

    NASA Astrophysics Data System (ADS)

    Jia, Tao; Liu, Yang-Yu; Slotine, Jean-Jacques; Barabasi, Albert-Laszlo

    2012-02-01

    By combining tools from control theory and network science, an efficient methodology was proposed to identify the minimum sets of driver nodes, whose time-dependent control can guide the whole network to any desired final state. Yet, this minimum driver set (MDS) is usually not unique, but one can often achieve multiple potential control configurations with the same number of driver nodes. Given that some nodes may appear in some MDSs but not in other, a crucial question remain unanswered: what is the role of individual node in controlling a complex system? We first classify a node as critical, redundant, or ordinary if it appears in all, no, or some MDSs. Then we introduce the concept of control capacity as a measure of the frequency that a node is in the MDSs, which quantifies the importance of a given node in maintaining Controllability. To avoid impractical enumeration of all MDSs, we propose an algorithm that uniformly samples the MDS. We use it to explore the control capacity of nodes in complex networks and study how it is related to other characteristics of the network topology.

  8. Domains and correlates of clinical balance impairment associated with Huntington's disease.

    PubMed

    Jacobs, Jesse V; Boyd, James T; Hogarth, Penelope; Horak, Fay B

    2015-03-01

    This study sought to (a) determine the domains of clinical balance impairments associated with Huntington's disease (HD), and (b) evaluate associations between balance test scores and other disease-related impairments. Eighteen subjects with genetically definite HD and 17 age-matched control subjects were evaluated on the Mini-BESTest for their clinical balance impairments as well as the Unified HD Rating Scale (UHDRS) motor and total functional capacity scales, Activity-Specific Balance Confidence (ABC) Scale-short form, Montreal Cognitive Assessment (MoCA), and Symbol Digit Modalities Test (SDMT). Results showed that subjects with HD exhibited significantly lower total Mini-BESTest scores than subjects without HD (mean (95% CI)=76 (64-87)% with HD, 98 (96-99)% without HD; p=0.0011). Mini-BESTest item scores were significantly lower for subjects with HD on one-leg stance, postural responses, standing with eyes closed on foam, and dual-task timed up-and-go. Mini-BESTest scores significantly correlated with UHDRS motor (r(2)=0.68; p=0.00003) and total functional capacity (r(2)=0.75; p=0.000006) scores as well as with scores on the ABC short form (r(2)=0.45; p=0.0024), SDMT (r(2)=0.42; p=0.0036), and MoCA (r(2)=0.23; p=0.046) assessments. This study, therefore, demonstrates that balance impairments associated with HD span domains of anticipatory postural adjustments, postural responses, stance in challenging sensory conditions, and gait. Although preliminary, clinical balance impairment appears to be an efficient proxy evaluation of multiple HD-related factors due to associations with functional capacity, other motor impairments, balance confidence, and cognitive abilities.

  9. NEUROPSYCHOLOGICAL PERFORMANCE WITHIN-PERSON VARIABILITY IS ASSOCIATED WITH REDUCED TREATMENT CONSENT CAPACITY

    PubMed Central

    Gurrera, Ronald J.; Karel, Michele J.; Azar, Armin R.; Moye, Jennifer

    2013-01-01

    OBJECTIVES The capacity of older adults to make health care decisions is often impaired in dementia and has been linked to performance on specific neuropsychological tasks. Within-person across-test neuropsychological performance variability has been shown to predict future dementia. This study examined the relationship of within-person across-test neuropsychological performance variability to a current construct of treatment decision (consent) capacity. DESIGN Participants completed a neuropsychological test battery and a standardized capacity assessment. Standard scores were used to compute mean neuropsychological performance and within-person across-test variability. SETTING Assessments were performed in the participant’s preferred location (e.g., outpatient clinic office, senior center, or home). PARTICIPANTS Participants were recruited from the community with fliers and advertisements, and consisted of men (N=79) and women (N=80) with (N=83) or without (N=76) significant cognitive impairment. MEASUREMENTS Participants completed the MacArthur Competence Assessment Tool - Treatment (MacCAT-T) and 11 neuropsychological tests commonly used in the cognitive assessment of older individuals. RESULTS Neuropsychological performance and within-person variability were independently associated with continuous and dichotomous measures of capacity, and within-person neuropsychological variability was significantly associated with within-person decisional ability variability. Prevalence of incapacity was greater than expected in participants with and without significant cognitive impairment when decisional abilities were considered separately. CONCLUSIONS These findings are consistent with an emerging construct of consent capacity in which discrete decisional abilities are differentially associated with cognitive processes, and indicate that the sensitivity and accuracy of consent capacity assessments can be improved by evaluating decisional abilities separately. PMID

  10. Diabetes mellitus and cognitive impairments

    PubMed Central

    Saedi, Elham; Gheini, Mohammad Reza; Faiz, Firoozeh; Arami, Mohammad Ali

    2016-01-01

    There is strong evidence that diabetes mellitus increases the risk of cognitive impairment and dementia. Insulin signaling dysregulation and small vessel disease in the base of diabetes may be important contributing factors in Alzheimer’s disease and vascular dementia pathogenesis, respectively. Optimal glycemic control in type 1 diabetes and identification of diabetic risk factors and prophylactic approach in type 2 diabetes are very important in the prevention of cognitive complications. In addition, hypoglycemic attacks in children and elderly should be avoided. Anti-diabetic medications especially Insulin may have a role in the management of cognitive dysfunction and dementia but further investigation is needed to validate these findings. PMID:27660698

  11. 47 CFR 80.919 - Required capacity.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... capacity. If either the main or reserve power supply includes batteries, these batteries must have sufficient reserve capacity to permit proper operation of the required transmitter and receiver for at...

  12. U.S. Refining Capacity Utilization

    EIA Publications

    1995-01-01

    This article briefly reviews recent trends in domestic refining capacity utilization and examines in detail the differences in reported crude oil distillation capacities and utilization rates among different classes of refineries.

  13. Earnings Capacity, Economic Status, and Poverty

    ERIC Educational Resources Information Center

    Garfinkel, Irwin; Haveman, Robert

    1977-01-01

    "Earnings capacity" is suggested as an alternative to "annual money income" as an indicator of economic status. The socioeconomic and demographic determinants of poverty as measured by earnings capacity and by annual money income are compared and contrasted. (WL)

  14. Impaired Brain Creatine Kinase Activity in Huntington's Disease

    PubMed Central

    Zhang, S.F.; Hennessey, T.; Yang, L.; Starkova, N.N.; Beal, M.F.; Starkov, A.A.

    2011-01-01

    Background Huntington's disease (HD) is associated with impaired energy metabolism in the brain. Creatine kinase (CK) catalyzes ATP-dependent phosphorylation of creatine (Cr) into phosphocreatine (PCr), thereby serving as readily available high-capacity spatial and temporal ATP buffering. Objective: Substantial evidence supports a specific role of the Cr/PCr system in neurodegenerative diseases. In the brain, the Cr/PCr ATP-buffering system is established by a concerted operation of the brain-specific cytosolic enzyme BB-CK and ubiquitous mitochondrial uMt-CK. It is not yet established whether the activity of these CK isoenzymes is impaired in HD. Methods We measured PCr, Cr, ATP and ADP in brain extracts of 3 mouse models of HD – R6/2 mice, N171-82Q and HdhQ111 mice – and the activity of CK in cytosolic and mitochondrial brain fractions from the same mice. Results The PCr was significantly increased in mouse HD brain extracts as compared to nontransgenic littermates. We also found an approximately 27% decrease in CK activity in both cytosolic and mitochondrial fractions of R6/2 and N171-82Q mice, and an approximately 25% decrease in the mitochondria from HdhQ111 mice. Moreover, uMt-CK and BB-CK activities were approximately 63% lower in HD human brain samples as compared to nondiseased controls. Conclusion Our findings lend strong support to the role of impaired energy metabolism in HD, and point out the potential importance of impairment of the CK-catalyzed ATP-buffering system in the etiology of HD. PMID:21124007

  15. Rehabilitation Medicine Summit: Building Research Capacity

    ERIC Educational Resources Information Center

    Frontera, Walter R.; Fuhrer, Marcus J.; Jette, Alan M.; Chan, Leighton; Cooper, Rory A.; Duncan, Pamela W.; Kemp, John D.; Ottenbacher, Kenneth J.; Peckham, P. Hunter; Roth, Elliot J.; Tate, Denise G.

    2006-01-01

    The general objective of the "Rehabilitation Medicine Summit: Building Research Capacity" was to advance and promote research in medical rehabilitation by making recommendations to expand research capacity. The 5 elements of research capacity that guided the discussions were (a) researchers; (b) research culture, environment, and infrastructure;…

  16. 14 CFR 25 - Traffic and Capacity Elements

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 4 2012-01-01 2012-01-01 false Traffic and Capacity Elements Section 25... Traffic Reporting Requirements Section 25 Traffic and Capacity Elements General Instructions. (a) All prescribed reporting for traffic and capacity elements shall conform with the data compilation standards...

  17. 25 CFR 167.6 - Carrying capacities.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 1 2011-04-01 2011-04-01 false Carrying capacities. 167.6 Section 167.6 Indians BUREAU... Carrying capacities. (a) The Commissioner of Indian Affairs on June 26, 1943, promulgated the authorized carrying capacity for each land management district of the Navajo Reservation. (b) Recommended...

  18. 25 CFR 167.6 - Carrying capacities.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 1 2012-04-01 2011-04-01 true Carrying capacities. 167.6 Section 167.6 Indians BUREAU OF... capacities. (a) The Commissioner of Indian Affairs on June 26, 1943, promulgated the authorized carrying... carrying capacities shall be referred by the Superintendent to District Grazing Committee, Central...

  19. 25 CFR 167.6 - Carrying capacities.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 25 Indians 1 2013-04-01 2013-04-01 false Carrying capacities. 167.6 Section 167.6 Indians BUREAU... Carrying capacities. (a) The Commissioner of Indian Affairs on June 26, 1943, promulgated the authorized carrying capacity for each land management district of the Navajo Reservation. (b) Recommended...

  20. 25 CFR 167.6 - Carrying capacities.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Carrying capacities. 167.6 Section 167.6 Indians BUREAU... Carrying capacities. (a) The Commissioner of Indian Affairs on June 26, 1943, promulgated the authorized carrying capacity for each land management district of the Navajo Reservation. (b) Recommended...

  1. Compressibility and heat capacity of rotating plasma

    NASA Astrophysics Data System (ADS)

    Geyko, V. I.; Fisch, N. J.

    2017-02-01

    A rotating plasma column is shown to exhibit unusual heat capacity effects under compression. For near equilibrium thermodynamics and smooth wall conditions, the heat capacity depends on the plasma density, on the speed of the rotation, and on the mass ratio. For a certain range of parameters, the storage of energy in the electric field produces a significant increase in the heat capacity.

  2. 10 CFR 904.9 - Excess capacity.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 4 2013-01-01 2013-01-01 false Excess capacity. 904.9 Section 904.9 Energy DEPARTMENT OF ENERGY GENERAL REGULATIONS FOR THE CHARGES FOR THE SALE OF POWER FROM THE BOULDER CANYON PROJECT Power Marketing § 904.9 Excess capacity. (a) If the Uprating Program results in Excess Capacity, Western shall...

  3. 10 CFR 904.9 - Excess capacity.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 4 2014-01-01 2014-01-01 false Excess capacity. 904.9 Section 904.9 Energy DEPARTMENT OF ENERGY GENERAL REGULATIONS FOR THE CHARGES FOR THE SALE OF POWER FROM THE BOULDER CANYON PROJECT Power Marketing § 904.9 Excess capacity. (a) If the Uprating Program results in Excess Capacity, Western shall...

  4. 10 CFR 904.9 - Excess capacity.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Excess capacity. 904.9 Section 904.9 Energy DEPARTMENT OF ENERGY GENERAL REGULATIONS FOR THE CHARGES FOR THE SALE OF POWER FROM THE BOULDER CANYON PROJECT Power Marketing § 904.9 Excess capacity. (a) If the Uprating Program results in Excess Capacity, Western shall...

  5. 10 CFR 904.9 - Excess capacity.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 false Excess capacity. 904.9 Section 904.9 Energy DEPARTMENT OF ENERGY GENERAL REGULATIONS FOR THE CHARGES FOR THE SALE OF POWER FROM THE BOULDER CANYON PROJECT Power Marketing § 904.9 Excess capacity. (a) If the Uprating Program results in Excess Capacity, Western shall...

  6. 30 CFR 56.19001 - Rated capacities.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Rated capacities. 56.19001 Section 56.19001 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE... § 56.19001 Rated capacities. Hoists shall have rated capacities consistent with the loads handled...

  7. 30 CFR 57.19001 - Rated capacities.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Rated capacities. 57.19001 Section 57.19001 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE... Hoists § 57.19001 Rated capacities. Hoists shall have rated capacities consistent with the loads...

  8. 47 CFR 80.861 - Required capacity.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Required capacity. 80.861 Section 80.861... Required capacity. If the main power supply or the reserve power supply provided for the purpose of... capacity available at all times while the vessel is leaving or attempting to leave a harbor or port for...

  9. 40 CFR 35.2123 - Reserve capacity.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Reserve capacity. 35.2123 Section 35... STATE AND LOCAL ASSISTANCE Grants for Construction of Treatment Works § 35.2123 Reserve capacity. EPA will limit grant assistance for reserve capacity as follows: (a) If EPA awarded a grant for a Step...

  10. 30 CFR 77.1402 - Rated capacity.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Rated capacity. 77.1402 Section 77.1402 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE SAFETY AND HEALTH MANDATORY... § 77.1402 Rated capacity. Hoists and elevators shall have rated capacities consistent with the...

  11. 30 CFR 56.19001 - Rated capacities.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Rated capacities. 56.19001 Section 56.19001 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE... § 56.19001 Rated capacities. Hoists shall have rated capacities consistent with the loads handled...

  12. 30 CFR 56.19001 - Rated capacities.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Rated capacities. 56.19001 Section 56.19001 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE... § 56.19001 Rated capacities. Hoists shall have rated capacities consistent with the loads handled...

  13. 30 CFR 56.19001 - Rated capacities.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Rated capacities. 56.19001 Section 56.19001 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE... § 56.19001 Rated capacities. Hoists shall have rated capacities consistent with the loads handled...

  14. 40 CFR 35.2123 - Reserve capacity.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 1 2013-07-01 2013-07-01 false Reserve capacity. 35.2123 Section 35... STATE AND LOCAL ASSISTANCE Grants for Construction of Treatment Works § 35.2123 Reserve capacity. EPA will limit grant assistance for reserve capacity as follows: (a) If EPA awarded a grant for a Step...

  15. 30 CFR 57.19001 - Rated capacities.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Rated capacities. 57.19001 Section 57.19001 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE... Hoists § 57.19001 Rated capacities. Hoists shall have rated capacities consistent with the loads...

  16. 47 CFR 80.919 - Required capacity.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 5 2013-10-01 2013-10-01 false Required capacity. 80.919 Section 80.919... capacity. If either the main or reserve power supply includes batteries, these batteries must have sufficient reserve capacity to permit proper operation of the required transmitter and receiver for at...

  17. 40 CFR 35.2123 - Reserve capacity.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 1 2014-07-01 2014-07-01 false Reserve capacity. 35.2123 Section 35... STATE AND LOCAL ASSISTANCE Grants for Construction of Treatment Works § 35.2123 Reserve capacity. EPA will limit grant assistance for reserve capacity as follows: (a) If EPA awarded a grant for a Step...

  18. 24 CFR 574.410 - Capacity.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 24 Housing and Urban Development 3 2014-04-01 2013-04-01 true Capacity. 574.410 Section 574.410... Project Sponsors § 574.410 Capacity. The grantee shall ensure that any project sponsor with which the grantee contracts to carry out an activity under this part has the capacity and capability to...

  19. 40 CFR 35.2123 - Reserve capacity.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 1 2011-07-01 2011-07-01 false Reserve capacity. 35.2123 Section 35... STATE AND LOCAL ASSISTANCE Grants for Construction of Treatment Works § 35.2123 Reserve capacity. EPA will limit grant assistance for reserve capacity as follows: (a) If EPA awarded a grant for a Step...

  20. 30 CFR 77.1402 - Rated capacity.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Rated capacity. 77.1402 Section 77.1402 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE SAFETY AND HEALTH MANDATORY... § 77.1402 Rated capacity. Hoists and elevators shall have rated capacities consistent with the...

  1. 47 CFR 80.861 - Required capacity.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 5 2014-10-01 2014-10-01 false Required capacity. 80.861 Section 80.861... Required capacity. If the main power supply or the reserve power supply provided for the purpose of... capacity available at all times while the vessel is leaving or attempting to leave a harbor or port for...

  2. 47 CFR 80.861 - Required capacity.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 5 2011-10-01 2011-10-01 false Required capacity. 80.861 Section 80.861... Required capacity. If the main power supply or the reserve power supply provided for the purpose of... capacity available at all times while the vessel is leaving or attempting to leave a harbor or port for...

  3. 40 CFR 35.2123 - Reserve capacity.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 1 2012-07-01 2012-07-01 false Reserve capacity. 35.2123 Section 35... STATE AND LOCAL ASSISTANCE Grants for Construction of Treatment Works § 35.2123 Reserve capacity. EPA will limit grant assistance for reserve capacity as follows: (a) If EPA awarded a grant for a Step...

  4. 47 CFR 80.861 - Required capacity.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 5 2012-10-01 2012-10-01 false Required capacity. 80.861 Section 80.861... Required capacity. If the main power supply or the reserve power supply provided for the purpose of... capacity available at all times while the vessel is leaving or attempting to leave a harbor or port for...

  5. 47 CFR 80.861 - Required capacity.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 5 2013-10-01 2013-10-01 false Required capacity. 80.861 Section 80.861... Required capacity. If the main power supply or the reserve power supply provided for the purpose of... capacity available at all times while the vessel is leaving or attempting to leave a harbor or port for...

  6. 30 CFR 77.1402 - Rated capacity.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Rated capacity. 77.1402 Section 77.1402 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE SAFETY AND HEALTH MANDATORY... § 77.1402 Rated capacity. Hoists and elevators shall have rated capacities consistent with the...

  7. 47 CFR 80.919 - Required capacity.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 5 2011-10-01 2011-10-01 false Required capacity. 80.919 Section 80.919... capacity. If either the main or reserve power supply includes batteries, these batteries must have sufficient reserve capacity to permit proper operation of the required transmitter and receiver for at...

  8. 47 CFR 80.919 - Required capacity.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 5 2012-10-01 2012-10-01 false Required capacity. 80.919 Section 80.919... capacity. If either the main or reserve power supply includes batteries, these batteries must have sufficient reserve capacity to permit proper operation of the required transmitter and receiver for at...

  9. 47 CFR 80.919 - Required capacity.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 5 2014-10-01 2014-10-01 false Required capacity. 80.919 Section 80.919... capacity. If either the main or reserve power supply includes batteries, these batteries must have sufficient reserve capacity to permit proper operation of the required transmitter and receiver for at...

  10. 24 CFR 574.410 - Capacity.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 24 Housing and Urban Development 3 2012-04-01 2012-04-01 false Capacity. 574.410 Section 574.410... Project Sponsors § 574.410 Capacity. The grantee shall ensure that any project sponsor with which the grantee contracts to carry out an activity under this part has the capacity and capability to...

  11. 30 CFR 56.19001 - Rated capacities.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Rated capacities. 56.19001 Section 56.19001 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE... § 56.19001 Rated capacities. Hoists shall have rated capacities consistent with the loads handled...

  12. 30 CFR 77.1402 - Rated capacity.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Rated capacity. 77.1402 Section 77.1402 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE SAFETY AND HEALTH MANDATORY... § 77.1402 Rated capacity. Hoists and elevators shall have rated capacities consistent with the...

  13. 30 CFR 57.19001 - Rated capacities.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Rated capacities. 57.19001 Section 57.19001 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE... Hoists § 57.19001 Rated capacities. Hoists shall have rated capacities consistent with the loads...

  14. 24 CFR 574.410 - Capacity.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 24 Housing and Urban Development 3 2013-04-01 2013-04-01 false Capacity. 574.410 Section 574.410... Project Sponsors § 574.410 Capacity. The grantee shall ensure that any project sponsor with which the grantee contracts to carry out an activity under this part has the capacity and capability to...

  15. 30 CFR 57.19001 - Rated capacities.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Rated capacities. 57.19001 Section 57.19001 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE... Hoists § 57.19001 Rated capacities. Hoists shall have rated capacities consistent with the loads...

  16. 30 CFR 77.1402 - Rated capacity.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Rated capacity. 77.1402 Section 77.1402 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE SAFETY AND HEALTH MANDATORY... § 77.1402 Rated capacity. Hoists and elevators shall have rated capacities consistent with the...

  17. 30 CFR 57.19001 - Rated capacities.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Rated capacities. 57.19001 Section 57.19001 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE... Hoists § 57.19001 Rated capacities. Hoists shall have rated capacities consistent with the loads...

  18. Understanding Dimensions of Organizational Evaluation Capacity

    ERIC Educational Resources Information Center

    Bourgeois, Isabelle; Cousins, J. Bradley

    2013-01-01

    Organizational evaluation capacity building has been a topic of increasing interest in recent years. However, the actual dimensions of evaluation capacity have not been clearly articulated through empirical research. This study sought to address this gap by identifying the key dimensions of evaluation capacity in Canadian federal government…

  19. Partnership to build research capacity.

    PubMed

    Boland, Mary G; Kamikawa, Cindy; Inouye, Jillian; Latimer, Renee W; Marshall, Stephanie

    2010-01-01

    Today's nursing leaders are setting the stage for the next evolution--bringing together skilled clinicians and administrators with peers in education to create new approaches to leading the profession forward. Partnerships share goals, common purpose, mutual respect, willingness to negotiate and compromise, informed participation, information giving, and shared decision making. The shared practice academia effort between a public university and a private health care system situated in the island state of Hawai'i is described. The medical center and school of nursing pursued individual strategic efforts to build research capacity and used the opportunity to fund academic practice research projects. The mutual need and recognition of the high stakes involved, in concert with stable, committed leaders at all levels, were key to the early success of their efforts. Through the formal research partnership mechanism, a discrete focus was created for efforts and used to move to tactical, operational, and interpersonal integration in this relationship.

  20. Working capacity and cervical dystonia.

    PubMed

    Martikainen, Kirsti K; Luukkaala, Tiina H; Marttila, Reijo J

    2010-03-01

    The objective of this questionnaire study was to assess the effect of cervical dystonia on patients' working capacity. Of the 303 working-aged members of the Finnish Dystonia Association (N = 433) who participated in the study 247 (82%) had cervical dystonia. Their median age was 50 years, the median duration of CD symptoms was 12.3 years. Most (78%) subjects were on botulinum toxin treatment. Ninety-seven (39%) had retired because of CD at a median age of 48 years; 96 (39%) of the subjects were working: 87 full-time and 9 part-time. The remaining participants were on sick leave, unemployed, studying or retired of other reasons. Retirement occurred more than ten years earlier compared with the general Finnish population. All possibilities to help CD patients to continue longer in work should be considered early.

  1. High current capacity electrical connector

    DOEpatents

    Bettis, Edward S.; Watts, Harry L.

    1976-01-13

    An electrical connector is provided for coupling high current capacity electrical conductors such as copper busses or the like. The connector is arranged in a "sandwiched" configuration in which a conductor plate contacts the busses along major surfaces thereof clamped between two stainless steel backing plates. The conductor plate is provided with a plurality of contact buttons affixed therein in a spaced array such that the caps of the buttons extend above the conductor plate surface to contact the busses. When clamping bolts provided through openings in the sandwiched arrangement are tightened, Belleville springs provided under the rim of each button cap are compressed and resiliently force the caps into contact with the busses' contacting surfaces to maintain a predetermined electrical contact area provided by the button cap tops. The contact area does not change with changing thermal or mechanical stresses applied to the coupled conductors.

  2. Storage capacity of correlated perceptrons

    NASA Astrophysics Data System (ADS)

    Malzahn, D.; Engel, A.; Kanter, I.

    1997-06-01

    We consider an ensemble of K single-layer perceptrons exposed to random inputs and investigate the conditions under which the couplings of these perceptrons can be chosen such that prescribed correlations between the outputs occur. A general formalism is introduced using a multiperceptron cost function that allows one to determine the maximal number of random inputs as a function of the desired values of the correlations. Replica-symmetric results for K=2 and K=3 are compared with properties of two-layer networks of tree-structure and fixed Boolean function between hidden units and output. The results show which correlations in the hidden layer of multilayer neural networks are crucial for the value of the storage capacity.

  3. [Pragmatic language impairment in children].

    PubMed

    Ptok, M

    2005-11-01

    When a child's language development does not follow the normal developmental course for no known reasons specific language impairment (SLI) is diagnosed. In contrast, pragmatic language impairment (PLI) refers to children who experience significant difficulties with the use of language. Clinical accounts of PLI have suggested that unlike children with more typical SLI, children with PLI have adequate syntax and phonology and are often verbally fluent. However, they may exhibit a range of linguistic and communicative deficits such as comprehension deficits for connected speech, conversational inadequacies, poor turn-taking, atypical word choices, literal interpretation of figurative language, and poor topic maintenance. There also may be fundamental deficits in social cognition, such as appreciating the thoughts and feelings of others. PLI may be found in SLI children, children with learning disabilities, autism and traumatic brain injuries. Here we review aspects of pragmatic communication skills, the development of emotion recognition, and diagnostic and therapeutic procedures. Otolaryngologists have to be aware of PLI in case children with communication problems are referred to them. This may enable a timely diagnosis and early intervention.

  4. Sleep, Torpor and Memory Impairment

    NASA Astrophysics Data System (ADS)

    Palchykova, S.; Tobler, I.

    It is now well known that daily torpor induces a sleep deficit. Djungarian hamsters emerging from this hypometabolic state spend most of the time in sleep. This sleep is characterized by high initial values of EEG slow-wave activity (SWA) that monotonically decline during recovery sleep. These features resemble the changes seen in numerous species during recovery after prolonged wakefulness or sleep deprivation (SD). When hamsters are totally or partially sleep deprived immediately after emerging from torpor, an additional increase in SWA can be induced. It has been therefore postulated, that these slow- waves are homeostatically regulated, as predicted by the two-process model of sleep regulation, and that during daily torpor a sleep deficit is accumulated as it is during prolonged waking. The predominance of SWA in the frontal EEG observed both after SD and daily torpor provides further evidence for the similarity of these conditions. It has been shown in several animal and human studies that sleep can enhance memory consolidation, and that SD leads to memory impairment. Preliminary data obtained in the Djungarian hamster showed that both SD and daily torpor result in object recognition deficits. Thus, animals subjected to SD immediately after learning, or if they underwent an episode of daily torpor between learning and retention, displayed impaired recognition memory for complex object scenes. The investigation of daily torpor can reveal mechanisms that could have important implications for hypometabolic state induction in other mammalian species, including humans.

  5. Mental fatigue impairs emotion regulation.

    PubMed

    Grillon, Christian; Quispe-Escudero, David; Mathur, Ambika; Ernst, Monique

    2015-06-01

    Because healthy physical and mental functioning depends on the ability to regulate emotions, it is important to identify moderators of such regulations. Whether mental fatigue, subsequent to the depletion of cognitive resources, impairs explicit emotion regulation to negative stimuli is currently unknown. This study explored this possibility. In a within-subject design over 2 separate sessions, healthy individuals performed easy (control session) or difficult (depletion session) cognitive tasks. Subsequently, they were presented with neutral and negative pictures, with instructions to either maintain or regulate (i.e., reduce) the emotions evoked by the pictures. Emotional reactivity was probed with the startle reflex. The negative pictures evoked a similar aversive state in the control and depletion sessions as measured by startle potentiation. However, subjects were able to down-regulate their aversive state only in the control session, not in the depletion session. These results indicate that mental fatigue following performance of cognitive tasks impairs emotion regulation without affecting emotional reactivity. These findings suggest that mental fatigue needs to be incorporated into models of emotion regulation.

  6. Ego depletion impairs implicit learning.

    PubMed

    Thompson, Kelsey R; Sanchez, Daniel J; Wesley, Abigail H; Reber, Paul J

    2014-01-01

    Implicit skill learning occurs incidentally and without conscious awareness of what is learned. However, the rate and effectiveness of learning may still be affected by decreased availability of central processing resources. Dual-task experiments have generally found impairments in implicit learning, however, these studies have also shown that certain characteristics of the secondary task (e.g., timing) can complicate the interpretation of these results. To avoid this problem, the current experiments used a novel method to impose resource constraints prior to engaging in skill learning. Ego depletion theory states that humans possess a limited store of cognitive resources that, when depleted, results in deficits in self-regulation and cognitive control. In a first experiment, we used a standard ego depletion manipulation prior to performance of the Serial Interception Sequence Learning (SISL) task. Depleted participants exhibited poorer test performance than did non-depleted controls, indicating that reducing available executive resources may adversely affect implicit sequence learning, expression of sequence knowledge, or both. In a second experiment, depletion was administered either prior to or after training. Participants who reported higher levels of depletion before or after training again showed less sequence-specific knowledge on the post-training assessment. However, the results did not allow for clear separation of ego depletion effects on learning versus subsequent sequence-specific performance. These results indicate that performance on an implicitly learned sequence can be impaired by a reduction in executive resources, in spite of learning taking place outside of awareness and without conscious intent.

  7. An index of reservoir habitat impairment

    USGS Publications Warehouse

    Miranda, L.E.; Hunt, K.M.

    2011-01-01

    Fish habitat impairment resulting from natural and anthropogenic watershed and in-lake processes has in many cases reduced the ability of reservoirs to sustain native fish assemblages and fisheries quality. Rehabilitation of impaired reservoirs is hindered by the lack of a method suitable for scoring impairment status. To address this limitation, an index of reservoir habitat impairment (IRHI) was developed by merging 14 metrics descriptive of common impairment sources, with each metric scored from 0 (no impairment) to 5 (high impairment) by fisheries scientists with local knowledge. With a plausible range of 5 to 25, distribution of the IRHI scores ranged from 5 to 23 over 482 randomly selected reservoirs dispersed throughout the USA. The IRHI reflected five impairment factors including siltation, structural habitat, eutrophication, water regime, and aquatic plants. The factors were weakly related to key reservoir characteristics including reservoir area, depth, age, and usetype, suggesting that common reservoir descriptors are poor predictors of fish habitat impairment. The IRHI is rapid and inexpensive to calculate, provides an easily understood measure of the overall habitat impairment, allows comparison of reservoirs and therefore prioritization of restoration activities, and may be used to track restoration progress. The major limitation of the IRHI is its reliance on unstandardized professional judgment rather than standardized empirical measurements. ?? 2010 US Government.

  8. Upper Limb Motor Impairment Post Stroke

    PubMed Central

    Raghavan, Preeti

    2016-01-01

    Synopsis Understanding upper limb impairment after stroke is essential to planning therapeutic efforts to restore function. However determining which upper limb impairment to treat and how is complex for two reasons: 1) the impairments are not static, i.e. as motor recovery proceeds, the type and nature of the impairments may change; therefore the treatment needs to evolve to target the impairment contributing to dysfunction at a given point in time. 2) multiple impairments may be present simultaneously, i.e., a patient may present with weakness of the arm and hand immediately after a stroke, which may not have resolved when spasticity sets in a few weeks or months later; hence there may be a layering of impairments over time making it difficult to decide what to treat first. The most useful way to understand how impairments contribute to upper limb dysfunction may be to examine them from the perspective of their functional consequences. There are three main functional consequences of impairments on upper limb function are: (1) learned nonuse, (2) learned bad-use, and (3) forgetting as determined by behavioral analysis of tasks. The impairments that contribute to each of these functional limitations are described. PMID:26522900

  9. Evaluation of impairment in the upper extremity.

    PubMed

    Swanson, A B; Göran-Hagert, C; de Groot Swanson, G

    1987-09-01

    A system for evaluation of physical impairment in the hand and upper extremity was developed and has been tested and used by many hand surgeons around the world. It was approved for international application by the International Federation of Societies for Surgery of the Hand. A method for evaluating amputation and sensory and motion impairments has been devised for the hand and upper extremity. Amputation impairment percentage values were determined for each digit or position thereof for the hand, wrist, elbow, and shoulder. By a principle of progressive multiplication of percentage values, impairment of a part can be related to the hand, upper extremity, and eventually the whole person. Sensory impairment is given 50% that of an amputation. Impairment of finger motion can result from lack of flexion (F), extension (E), or ankylosis (A). The method for evaluating flexion impairment is based on a combined angular measurement principle that was correlated with the linear measurement of Boyes. Values for flexion and ankylosis impairment were obtained from the American Medical Association guide. Values for extension impairment were derived from the formula A = E + F. Values for hyperextension were given consideration in the impairment tables. The sum of impairments as related to the whole hand equals the total impairment. The method to combine various impairments is based on the principle that each impairment acts not on the whole part (e.g., the finger) but on the remaining portion (e.g., proximal interphalangeal joint and proximally) after the preceding impairment has acted (e.g., on the distal interphalangeal joint). When there is more than one impairment to a given part, these must be combined before conversion to a larger part. The combined values determination is based on the formula "A% + B% (100% - A%) = the combined values of A% + B%." Based on this principle, the physical loss of each anatomic segment is related to the part, to the entire hand, and then to

  10. Impairment of mesenchymal stem cells derived from oral leukoplakia.

    PubMed

    Zhang, Zhihui; Song, Jiangyuan; Han, Ying; Mu, Dongdong; Su, Sha; Ji, Xiaoli; Liu, Hongwei

    2015-01-01

    Oral leukoplakia is one of the common precancerous lesions in oral mucosa. To compare the biological characteristics and regenerative capacities of mesenchymal stem cells (MSCs) from oral leukoplakia (epithelial hyperplasia and dysplasia) and normal oral mucosa, MSCs were isolated by enzyme digestion. Then these cells were identified by the expression of MSC related markers, STRO-1, CD105 and CD90, with the absent for the hematopoietic stem cell marker CD34 by flow cytometric detection. The self-renewal ability of MSCs from oral leukoplakia was enhanced, while the multipotent differentiation was descended, compared with MSCs from normal oral mucosa. Fibrin gel was used as a carrier for MSCs transplanted into immunocompromised mice to detect their regenerative capacity. The regenerative capacities of MSCs from oral leukoplakia became impaired partly. Collagen IV (Col IV) and matrix metalloproteinases-9 (MMP-9) were selected to analyze the potential mechanism for the functional changes of MSCs from oral leukoplakia by immunochemical and western blot analysis. The expression of Col IV was decreased and that of MMP-9 was increased by MSCs with the progression of oral leukoplakia, especially in MSCs from epithelial dysplasia. The imbalance between regenerative and metabolic self-regulatory functions of MSCs from oral leukoplakia may be related to the progression of this premalignant disorder.

  11. [Research progress on environmental carrying capacity].

    PubMed

    Wang, Jian; Sun, Tieheng; Li, Peijun; Li, Fayun

    2005-04-01

    To study the theories and quantification methods of environmental carrying capacity is of significance in reality for directing human beings economic behaviors and harmonizing the relationships between social development and environment. In this paper, the definition of environmental carrying capacity was introduced from the aspects of "capacity", "threshold" and "capability", with the main characteristics of objective and subjective, regional and temporal, and dynamic and adjustable, and its research progress was reviewed. On the basis of these, the quantification methods of environmental carrying capacity, including exponential assessment, carrying rate assessment, system dynamics, and multi-objective optimization, were analyzed, and the research perspectives of environmental carrying capacity were discussed.

  12. Mammalian cell culture capacity for biopharmaceutical manufacturing.

    PubMed

    Ecker, Dawn M; Ransohoff, Thomas C

    2014-01-01

    : With worldwide sales of biopharmaceuticals increasing each year and continuing growth on the horizon, the manufacture of mammalian biopharmaceuticals has become a major global enterprise. We describe the current and future industry wide supply of manufacturing capacity with regard to capacity type, distribution, and geographic location. Bioreactor capacity and the use of single-use products for biomanufacturing are also profiled. An analysis of the use of this capacity is performed, including a discussion of current trends that will influence capacity growth, availability, and utilization in the coming years.

  13. Impaired reasoning and problem-solving in individuals with language impairment due to aphasia or language delay.

    PubMed

    Baldo, Juliana V; Paulraj, Selvi R; Curran, Brian C; Dronkers, Nina F

    2015-01-01

    The precise nature of the relationship between language and thought is an intriguing and challenging area of inquiry for scientists across many disciplines. In the realm of neuropsychology, research has investigated the inter-dependence of language and thought by testing individuals with compromised language abilities and observing whether performance in other cognitive domains is diminished. One group of such individuals is patients with aphasia who have an impairment in speech and language arising from a brain injury, such as a stroke. Our previous research has shown that the degree of language impairment in these individuals is strongly associated with the degree of impairment on complex reasoning tasks, such as the Wisconsin Card Sorting Task (WCST) and Raven's Matrices. In the current study, we present new data from a large group of individuals with aphasia that show a dissociation in performance between putatively non-verbal tasks on the Wechsler Adult Intelligence Scale (WAIS) that require differing degrees of reasoning (Picture Completion vs. Picture Arrangement tasks). We also present an update and replication of our previous findings with the WCST showing that individuals with the most profound core language deficits (i.e., impaired comprehension and disordered language output) are particularly impaired on problem-solving tasks. In the second part of the paper, we present findings from a neurologically intact individual known as "Chelsea" who was not exposed to language due to an unaddressed hearing loss that was present since birth. At the age of 32, she was fitted with hearing aids and exposed to spoken and signed language for the first time, but she was only able to acquire a limited language capacity. Chelsea was tested on a series of standardized neuropsychological measures, including reasoning and problem-solving tasks. She was able to perform well on a number of visuospatial tasks but was disproportionately impaired on tasks that required reasoning

  14. Impaired reasoning and problem-solving in individuals with language impairment due to aphasia or language delay

    PubMed Central

    Baldo, Juliana V.; Paulraj, Selvi R.; Curran, Brian C.; Dronkers, Nina F.

    2015-01-01

    The precise nature of the relationship between language and thought is an intriguing and challenging area of inquiry for scientists across many disciplines. In the realm of neuropsychology, research has investigated the inter-dependence of language and thought by testing individuals with compromised language abilities and observing whether performance in other cognitive domains is diminished. One group of such individuals is patients with aphasia who have an impairment in speech and language arising from a brain injury, such as a stroke. Our previous research has shown that the degree of language impairment in these individuals is strongly associated with the degree of impairment on complex reasoning tasks, such as the Wisconsin Card Sorting Task (WCST) and Raven’s Matrices. In the current study, we present new data from a large group of individuals with aphasia that show a dissociation in performance between putatively non-verbal tasks on the Wechsler Adult Intelligence Scale (WAIS) that require differing degrees of reasoning (Picture Completion vs. Picture Arrangement tasks). We also present an update and replication of our previous findings with the WCST showing that individuals with the most profound core language deficits (i.e., impaired comprehension and disordered language output) are particularly impaired on problem-solving tasks. In the second part of the paper, we present findings from a neurologically intact individual known as “Chelsea” who was not exposed to language due to an unaddressed hearing loss that was present since birth. At the age of 32, she was fitted with hearing aids and exposed to spoken and signed language for the first time, but she was only able to acquire a limited language capacity. Chelsea was tested on a series of standardized neuropsychological measures, including reasoning and problem-solving tasks. She was able to perform well on a number of visuospatial tasks but was disproportionately impaired on tasks that required

  15. Constrained by Our Connections: White Matter's Key Role in Interindividual Variability in Visual Working Memory Capacity

    PubMed Central

    Golestani, Ali M.; Miles, Laura; Babb, James; Castellanos, F. Xavier; Malaspina, Dolores

    2014-01-01

    Visual working memory (VWM) plays an essential role in many perceptual and higher-order cognitive processes. Despite its reliance on a broad network of brain regions, VWM has a capacity limited to a few objects. This capacity varies substantially across individuals and relates closely to measures of overall cognitive function (Luck and Vogel, 2013). The mechanisms underlying these properties are not completely understood, although the amplitude of neural signal oscillations (Vogel and Machizawa, 2004) and brain activation in specific cortical regions (Todd and Marois, 2004) have been implicated. Variability in VWM performance may also reflect variability in white matter structural properties. However, data based primarily on diffusion tensor imaging approaches remain inconclusive. Here, we investigate the relationship between white matter and VWM capacity in human subjects using an advanced diffusion imaging technique, diffusion kurtosis imaging. Diffusion kurtosis imaging provides several novel quantitative white mater metrics, among them the axonal water fraction (faxon), an index of axonal density and caliber. Our results show that 59% of individual variability in VWM capacity may be explained by variations in faxon within a widely distributed network of white matter tracts. Increased faxon associates with increased VWM capacity. An additional 12% in VWM capacity variance may be explained by diffusion properties of the extra-axonal space. These data demonstrate, for the first time, the key role of white matter in limiting VWM capacity in the healthy adult brain and suggest that white matter may represent an important therapeutic target in disorders of impaired VWM and cognition. PMID:25378158

  16. Everyday Functioning in Huntington's Disease: A Laboratory-Based Study of Financial Management Capacity.

    PubMed

    Sheppard, David P; Pirogovsky-Turk, Eva; Woods, Steven Paul; Holden, Heather M; Nicoll, Diane R; Filoteo, J Vincent; Corey-Bloom, Jody; Gilbert, Paul E

    2017-01-01

    One important limitation of prior studies examining functional decline in Huntington's disease (HD) has been the reliance on self-reported measures of ability. Since report-based methods can be biased by lack of insight, depression, and cognitive impairment, contrasting self-reported ability with measures that assess capacity may lead to a more comprehensive estimation of real-world functioning. The present study examined self-reported ability to perform instrumental activities of daily living (iADLs) and performance-based financial management capacity in 20 patients diagnosed with mild-moderate Huntington's disease (HD) and 20 demographically similar healthy adults. HD patients reported significantly greater declines in their ability to manage finances. On the capacity measure of financial management, HD patients performed significantly below healthy adults. Additionally, in the HD group there were no significant correlations between self-reported ability and capacity measures of financial management. HD patients endorsed declines in global iADL ability and exhibited deficits in functional capacity when performing a financial management task. Capacity measures may aid in assessing the extent to which HD patients accurately estimate real-world iADL performance, and the present findings suggest that such measures of capacity may be related to the cognitive, but not motor or affective, symptoms of HD.

  17. 20 CFR 416.921 - What we mean by a not severe impairment(s) in an adult.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false What we mean by a not severe impairment(s) in an adult. 416.921 Section 416.921 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SUPPLEMENTAL... Disability § 416.921 What we mean by a not severe impairment(s) in an adult. (a) Non-severe impairment(s)....

  18. 20 CFR 416.921 - What we mean by a not severe impairment(s) in an adult.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 2 2012-04-01 2012-04-01 false What we mean by a not severe impairment(s) in an adult. 416.921 Section 416.921 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SUPPLEMENTAL... Disability § 416.921 What we mean by a not severe impairment(s) in an adult. (a) Non-severe impairment(s)....

  19. 20 CFR 416.921 - What we mean by a not severe impairment(s) in an adult.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false What we mean by a not severe impairment(s) in an adult. 416.921 Section 416.921 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SUPPLEMENTAL... Disability § 416.921 What we mean by a not severe impairment(s) in an adult. (a) Non-severe impairment(s)....

  20. 20 CFR 416.921 - What we mean by a not severe impairment(s) in an adult.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 2 2013-04-01 2013-04-01 false What we mean by a not severe impairment(s) in an adult. 416.921 Section 416.921 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SUPPLEMENTAL... Disability § 416.921 What we mean by a not severe impairment(s) in an adult. (a) Non-severe impairment(s)....

  1. 20 CFR 416.921 - What we mean by a not severe impairment(s) in an adult.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 2 2014-04-01 2014-04-01 false What we mean by a not severe impairment(s) in an adult. 416.921 Section 416.921 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SUPPLEMENTAL... Disability § 416.921 What we mean by a not severe impairment(s) in an adult. (a) Non-severe impairment(s)....

  2. Capacity Value of Concentrating Solar Power Plants

    SciTech Connect

    Madaeni, S. H.; Sioshansi, R.; Denholm, P.

    2011-06-01

    This study estimates the capacity value of a concentrating solar power (CSP) plant at a variety of locations within the western United States. This is done by optimizing the operation of the CSP plant and by using the effective load carrying capability (ELCC) metric, which is a standard reliability-based capacity value estimation technique. Although the ELCC metric is the most accurate estimation technique, we show that a simpler capacity-factor-based approximation method can closely estimate the ELCC value. Without storage, the capacity value of CSP plants varies widely depending on the year and solar multiple. The average capacity value of plants evaluated ranged from 45%?90% with a solar multiple range of 1.0-1.5. When introducing thermal energy storage (TES), the capacity value of the CSP plant is more difficult to estimate since one must account for energy in storage. We apply a capacity-factor-based technique under two different market settings: an energy-only market and an energy and capacity market. Our results show that adding TES to a CSP plant can increase its capacity value significantly at all of the locations. Adding a single hour of TES significantly increases the capacity value above the no-TES case, and with four hours of storage or more, the average capacity value at all locations exceeds 90%.

  3. Assessing urban adaptive capacity to climate change.

    PubMed

    Araya-Muñoz, Dahyann; Metzger, Marc J; Stuart, Neil; Wilson, A Meriwether W; Alvarez, Luis

    2016-12-01

    Despite the growing number of studies focusing on urban vulnerability to climate change, adaptive capacity, which is a key component of the IPCC definition of vulnerability, is rarely assessed quantitatively. We examine the capacity of adaptation in the Concepción Metropolitan Area, Chile. A flexible methodology based on spatial fuzzy modelling was developed to standardise and aggregate, through a stepwise approach, seventeen indicators derived from widely available census statistical data into an adaptive capacity index. The results indicate that all the municipalities in the CMA increased their level of adaptive capacity between 1992 and 2002. However, the relative differences between municipalities did not change significantly over the studied timeframe. Fuzzy overlay allowed us to standardise and to effectively aggregate indicators with differing ranges and granularities of attribute values into an overall index. It also provided a conceptually sound and reproducible means of exploring the interplay of many indicators that individually influence adaptive capacity. Furthermore, it captured the complex, aggregated and continued nature of the adaptive capacity, favouring to deal with gaps of data and knowledge associated with the concept of adaptive capacity. The resulting maps can help identify municipalities where adaptive capacity is weak and identify which components of adaptive capacity need strengthening. Identification of these capacity conditions can stimulate dialogue amongst policymakers and stakeholders regarding how to manage urban areas and how to prioritise resources for urban development in ways that can also improve adaptive capacity and thus reduce vulnerability to climate change.

  4. Inferential functioning in visually impaired children.

    PubMed

    Puche-Navarro, Rebeca; Millán, Rafael

    2007-01-01

    The current study explores the inferential abilities of visually impaired children in a task presented in two formats, manipulative and verbal. The results showed that in the group of visually impaired children, just as with children with normal sight, there was a wide range of inference types. It was found that the visually impaired children perform slightly better in the use of inductive and relational inferences in the verbal format, while in the manipulative format children with normal sight perform better. These results suggest that in inferential functioning of young children, and especially visually impaired children, the format of the task influences performance more than the child's visual ability.

  5. Obesity and Hypertriglyceridemia Produce Cognitive Impairment

    PubMed Central

    Farr, Susan A.; Yamada, Kelvin A.; Butterfield, D. Allan; Abdul, H. Mohammad; Xu, Lin; Miller, Nicole E.; Banks, William A.; Morley, John E.

    2008-01-01

    Obesity is associated with cognitive impairments. Long-term mechanisms for this association include consequences of hyperglycemia, dyslipidemia, or other factors comprising metabolic syndrome X. We found that hypertriglyceridemia, the main dyslipidemia of metabolic syndrome X, is in part responsible for the leptin resistance seen in obesity. Here we determined whether triglycerides have an immediate and direct effect on cognition. Obese mice showed impaired acquisition in three different cognitive paradigms: the active avoidance T-maze, the Morris water maze, and a food reward lever press. These impairments were not attributable to differences in foot shock sensitivity, swim speed, swimming distance, or voluntary milk consumption. Impaired cognition in obese mice was improved by selectively lowering triglycerides with gemfibrozil. Injection into the brain of the triglyceride triolein, but not of the free fatty acid palmitate, impaired acquisition in normal body weight mice. Triolein or milk (97% of fats are triglycerides), but not skim milk (no triglycerides), impaired maintenance of the N-methyl-d-aspartate component of the hippocampal long-term synaptic potential. Measures of oxidative stress in whole brain were reduced by gemfibrozil. We conclude that triglycerides mediate cognitive impairment as seen in obesity, possibly by impairing maintenance of the N-methyl-d-aspartate component of hippocampal long-term potentiation, and that lowering triglycerides can reverse the cognitive impairment and improve oxidative stress in the brain. PMID:18276751

  6. Cognitive impairments in progression of Parkinson's disease.

    PubMed

    Stepkina, D A; Zakharov, V V; Yakhno, N N

    2010-01-01

    A total of 88 patients with progression of Parkinson's disease (PD) were studied. Cognitive impairments (CI) in PD were in most cases progressive in nature, predominantly because of increases in the severity of dysregulatory and neurodynamic disorders, impairments to visuospatial functions, and, in some cases, deficits in nominative speech function. A high frequency of transformation of moderate cognitive impairments to dementia was demonstrated over periods of 2-5 years. Predictors of the progression of CI in PD were identified: elderly age, later onset of disease, and the severity of PD. The greatest rate of progression of CI was seen in patients with initially more severe impairments of regulatory and visuospatial functions.

  7. Life Science for Visually Impaired Students.

    ERIC Educational Resources Information Center

    Malone, Larry; De Lucchi, Linda

    1979-01-01

    Describes life science activities for blind or visually impaired students including aquarium studies, plant germination, classroom animals, and outdoor activities designed with a multisensory approach. (MA)

  8. Family Members Responding to a Visual Impairment.

    ERIC Educational Resources Information Center

    Tuttle, Dean W.

    1986-01-01

    A literature review regarding family adjustment to a visually impaired family member considered the stages of denial, withdrawal, acceptance, depression, reaffirmation, coping, mobilization, and self-acceptance. (CB)

  9. Memory impairments: forgetfulness versus amnesia.

    PubMed

    Boss, B J

    1988-06-01

    Two varieties of memory disorders can be distinguished--those characterized by the phenomenon of forgetfulness and those characterized by the presence of an amnesic state. Although these two conditions may appear similar, they have different anatomical correlates and functional significance. States of forgetfulness and amnesia arise from different etiologies, have different prognoses and require different therapeutic regimes. The purpose of this article is to distinguish these two varieties of memory disorders and contrast them as to anatomical features, functional differences, etiologies, prognoses and therapeutic management regimes. This should assist the neuroscience nurse to better understand relevant nursing assessment features and plan appropriate therapeutic nursing interventions for the client. Teaching protocols for families and significant others as well as clients with memory impairments should also be enhanced.

  10. Specific Language Impairment Across Languages.

    PubMed

    Leonard, Laurence B

    2014-03-01

    Children with specific language impairment (SLI) have a significant and longstanding deficit in spoken language ability that adversely affects their social and academic well-being. Studies of children with SLI in a wide variety of languages reveal diverse symptoms, most of which seem to reflect weaknesses in grammatical computation and phonological short-term memory. The symptoms of the disorder are sensitive to the type of language being acquired, with extraordinary weaknesses seen in those areas of language that are relatively challenging for younger typically developing children. Although these children's deficits warrant clinical and educational attention, their weaknesses might reflect the extreme end of a language aptitude continuum rather than a distinct, separable condition.

  11. Cognitive Impairment in Multiple Sclerosis

    PubMed Central

    Lovera, Jesus; Kovner, Blake

    2012-01-01

    Cognitive Impairment (CI) is a serious complication of MS, and the domains affected are well established but new affected domains such as theory of mind are still being identified. The evidence that some disease modifying therapies (DMTs) may improve and prevent the development of CI in MS is not solid. Recent studies on the prevalence CI in MS, although not as solid as studies completed prior to DMT introduction, suggest that CI remains a problem even among people on DMTs and even at the very earliest stages of MS. Functional MRI studies and studies using diffusion tractography show that the impact of lesions on cognition depends on the particular cortical networks affected and their plasticity. Cognitive rehabilitation and L-amphetamine appear promising treatments, cholinesterase inhibitors and memantine have failed, and data on Ginkgo and exercise are limited. We need more work to understand and develop treatment for CI in MS. PMID:22791241

  12. Assessing cognitive impairment following stroke.

    PubMed

    McDonnell, Michelle N; Bryan, Janet; Smith, Ashleigh E; Esterman, Adrian J

    2011-11-01

    The assessment of cognitive function is often neglected following stroke, with no consensus on the optimal method to assess poststroke cognition. We evaluated the ability of a brief protocol to detect cognitive impairment in community-dwelling people with chronic stroke compared to healthy controls and its ability to detect changes in cognition in stroke participants undergoing an exercise intervention. Four tests of cognition were able to detect differences between the groups in the domains of executive function, memory, and information-processing speed. Stroke survivors undergoing exercise over a 5-month period showed significantly improved memory and speed of information processing. Results suggest that exercise may have the potential to improve cognition in long-term stroke survivors and that these tests are sensitive measures of poststroke cognition.

  13. Assessment of Capacity to Consent to Research Among Psychiatric Outpatients: Prevalence and Associated Factors.

    PubMed

    Morán-Sánchez, Inés; Luna, Aurelio; Pérez-Cárceles, Maria D

    2016-03-01

    Mental capacity is an emerging ethical legal concept in psychiatric settings but its relation to clinical parameters remains yet uncertain. The aim of this study is to evaluate the association between capacity to consent research and different psychiatric disorders and to characterize predictors of impairments in research decision-making capacity across diagnostic groups in a cross-sectional study. 139 consecutively referred outpatients with DSM-IV TR diagnoses of psychotic, mood and anxiety disorders were interviewed and a binary judgment of incapacity was made guided by the MacArthur competence assessment tool for consent research (MacCAT-CR). Demographics and clinical information were assessed by cases notes. Patients with anxiety disorders performed the best on the MacCAT-CR, and patients with psychotic disorders had the worst performance, however, there was considerable heterogeneity within each group. Cognitive impairment and global functioning were strongly correlated with MacCAT-CR subscales scores. 30.6% participants lacked research-related decisional capacity. Low Understanding score OR 0.07 (IC 95% 0.01-0.32) and Low Reasoning score OR 0.30 (IC 95% 0.11-0.82) were the factors most closely associated with lack of capacity. No absolute statements about decisional capacity can be driven merely due to the diagnosis. We found several risk factors which may be considered to decide which populations may require more thorough capacity assessments. The issues under consideration in the present study are by no means unique to people with psychiatric conditions. Ignoring this caveat, risks further inappropriate stigmatization of those with serious mental illness.

  14. Conceptual Challenges and Practical Approaches to Screening Capacity for Self-care and Protection in Vulnerable Older Adults

    PubMed Central

    Naik, Aanand D.; Teal, Cayla R.; Pavlik, Valory N.; Dyer, Carmel B.; McCullough, Laurence B.

    2008-01-01

    Identifying impairments in the capacity to make and execute decisions is critical to the assessment and remediation of elder self-neglect. Few capacity assessment tools are available for use outside of health care settings and none have been validated in the context of elder self-neglect. Health and social services professionals are in need of validated tools to assess capacity for self-care and self protection during initial evaluations of older adults with suspected self-neglect syndrome. Currently, legal and medical declarations of incapacity and guardianship rely on clinical evaluations and instruments developed to assess only decision-making capacity. This paper first describes the conceptual and methodological challenges to assessing the capacity to make and execute decisions regarding safe and independent living. Second, the paper describes the pragmatic obstacles to developing a screening tool for the capacity for self-care and self protection (SC&P). Finally, the paper outlines the process for validation and field testing of the screening tool. A valid and feasible screening tool can then be used during field assessments by social services professionals to screen for potential impairments in the capacity for self-care and protection in vulnerable older adults. PMID:19016970

  15. Thresholds for impaired species recovery

    PubMed Central

    Hutchings, Jeffrey A.

    2015-01-01

    Studies on small and declining populations dominate research in conservation biology. This emphasis reflects two overarching frameworks: the small-population paradigm focuses on correlates of increased extinction probability; the declining-population paradigm directs attention to the causes and consequences of depletion. Neither, however, particularly informs research on the determinants, rate or uncertainty of population increase. By contrast, Allee effects (positive associations between population size and realized per capita population growth rate, rrealized, a metric of average individual fitness) offer a theoretical and empirical basis for identifying numerical and temporal thresholds at which recovery is unlikely or uncertain. Following a critique of studies on Allee effects, I quantify population-size minima and subsequent trajectories of marine fishes that have and have not recovered following threat mitigation. The data suggest that threat amelioration, albeit necessary, can be insufficient to effect recovery for populations depleted to less than 10% of maximum abundance (Nmax), especially when they remain depleted for lengthy periods of time. Comparing terrestrial and aquatic vertebrates, life-history analyses suggest that population-size thresholds for impaired recovery are likely to be comparatively low for marine fishes but high for marine mammals. Articulation of a ‘recovering population paradigm’ would seem warranted. It might stimulate concerted efforts to identify generic impaired recovery thresholds across species. It might also serve to reduce the confusion of terminology, and the conflation of causes and consequences with patterns currently evident in the literature on Allee effects, thus strengthening communication among researchers and enhancing the practical utility of recovery-oriented research to conservation practitioners and resource managers. PMID:26213739

  16. Novelties that change carrying capacity.

    PubMed

    Erwin, Douglas H

    2012-09-01

    Comparative developmental studies have revealed a rich array of details about the patterns and processes of morphological change in animals and increasingly in plants. But, applying these insights to the study of major episodes of evolutionary innovation requires understanding how these novel morphologies become established and sufficiently abundant (either as individuals within a species or as a clade of species) to be preserved in the fossil record, and, in many cases, to influence ecological processes. Evolutionary novelties may: (1) disappear without changing the species; (2) be associated with the generation (through selection or drift) of a new species; and if the latter (3) may or may not become ecologically significant. Only the latter are commonly preserved in the fossil record. These alternatives mirror the distinction among historians of technology between innovation and invention. Here, I argue that specific sorts of evolutionary inventions drive ecological transformation, essentially constructing an environment for themselves and ancillary organisms through ecological spillover effects, increasing the "carrying capacity" of an ecosystem.

  17. Advancing leadership capacity in nursing.

    PubMed

    Scott, Elaine S; Miles, Jane

    2013-01-01

    To address the potential shortage of nurse leaders, the profession must evaluate current strategies in both education and practice. While many new graduates dream of becoming a nurse practitioner or nurse anesthetist, few transition into practice with the goal of becoming a nurse leader. To increase the number of nurses capable of leadership, the profession must address 2 critical issues. First, effort must be made to augment faculty and students' conceptualization of nursing such that leadership is seen as a dimension of practice for all nurses, not just those in formal leadership roles. In so doing, leadership identity development would be seen as a part of becoming an expert nurse. Second, a comprehensive conceptual framework for lifelong leadership development of nurses needs to be designed. This framework should allow for baseline leadership capacity building in all nurses and advanced leadership development for those in formal administrative and advanced practice roles. The knowledge and skill requirements for quality improvement and patient safety have been explored and recommendations made for Quality and Safety Education for Nurses, but parallel work needs to be done to outline educational content, objectives, and effective pedagogy for advancing leadership development in nursing students at all levels.

  18. Elevated mitochondrial oxidative stress impairs metabolic adaptations to exercise in skeletal muscle.

    PubMed

    Crane, Justin D; Abadi, Arkan; Hettinga, Bart P; Ogborn, Daniel I; MacNeil, Lauren G; Steinberg, Gregory R; Tarnopolsky, Mark A

    2013-01-01

    Mitochondrial oxidative stress is a complex phenomenon that is inherently tied to energy provision and is implicated in many metabolic disorders. Exercise training increases mitochondrial oxidative capacity in skeletal muscle yet it remains unclear if oxidative stress plays a role in regulating these adaptations. We demonstrate that the chronic elevation in mitochondrial oxidative stress present in Sod2 (+/-) mice impairs the functional and biochemical mitochondrial adaptations to exercise. Following exercise training Sod2 (+/-) mice fail to increase maximal work capacity, mitochondrial enzyme activity and mtDNA copy number, despite a normal augmentation of mitochondrial proteins. Additionally, exercised Sod2 (+/-) mice cannot compensate for their higher amount of basal mitochondrial oxidative damage and exhibit poor electron transport chain complex assembly that accounts for their compromised adaptation. Overall, these results demonstrate that chronic skeletal muscle mitochondrial oxidative stress does not impact exercise induced mitochondrial biogenesis, but impairs the resulting mitochondrial protein function and can limit metabolic plasticity.

  19. Diminished Schwann cell repair responses underlie age-associated impaired axonal regeneration

    PubMed Central

    Painter, Michio W.; Brosius Lutz, Amanda; Cheng, Yung-Chih; Latremoliere, Alban; Duong, Kelly; Miller, Christine M.; Posada, Sean; Cobos, Enrique J.; Zhang, Alice X.; Wagers, Amy J.; Havton, Leif A.; Barres, Ben; Omura, Takao

    2014-01-01

    SUMMARY The regenerative capacity of the peripheral nervous system declines with age. Why this occurs, however, is unknown. We demonstrate that 24-month old mice exhibit an impairment of functional recovery after nerve injury compared to 2-month old animals. We find no difference in the intrinsic growth capacity between aged and young sensory neurons in vitro nor in their ability to activate growth-associated transcriptional programs after injury. Instead, using age-mismatched nerve transplants in vivo, we show that the extent of functional recovery depends on the age of the nerve graft, and not the age of the host. Molecular interrogation of the sciatic nerve reveals that aged Schwann cells (SCs) fail to rapidly activate a transcriptional repair program after injury. Functionally, aged SCs exhibit impaired de-differentiation, myelin clearance and macrophage recruitment. These results suggest that the age-associated decline in axonal regeneration results from diminished Schwann cell plasticity, leading to slower myelin clearance. PMID:25033179

  20. Effects of diffusion impairment on O2 and CO2 time courses in pulmonary capillaries.

    NASA Technical Reports Server (NTRS)

    Wagner, P. D.; West, J. B.

    1972-01-01

    Simultaneous time courses for O2 and CO2 exchange along the capillary have been calculated for homogeneous lungs, allowing for O2-CO2 interactions, dissolved O2, and chemical reaction rates. As diffusing capacity (Dl) was reduced, the transfer of CO2 and O2 was impaired by similar amounts, in spite of the 20-fold greater diffusing capacity for CO2. The reason why CO2 is affected so much is that the slope of the content against partial pressure is so much greater in blood than tissue for this gas. Because of the shapes of their respective dissociation curves, O2 transfer was most affected at normal ventilation-perfusion ratios, whereas CO2 was most affected at high ratios. Exercise exaggerated the impairment of transfer of both gases.

  1. 20 CFR 416.998 - If you become disabled by another impairment(s).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... INCOME FOR THE AGED, BLIND, AND DISABLED Determining Disability and Blindness Continuing Or Stopping Disability Or Blindness § 416.998 If you become disabled by another impairment(s). If a new severe...

  2. 20 CFR 416.998 - If you become disabled by another impairment(s).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... INCOME FOR THE AGED, BLIND, AND DISABLED Determining Disability and Blindness Continuing Or Stopping Disability Or Blindness § 416.998 If you become disabled by another impairment(s). If a new severe...

  3. 20 CFR 416.998 - If you become disabled by another impairment(s).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... INCOME FOR THE AGED, BLIND, AND DISABLED Determining Disability and Blindness Continuing Or Stopping Disability Or Blindness § 416.998 If you become disabled by another impairment(s). If a new severe...

  4. 20 CFR 416.998 - If you become disabled by another impairment(s).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... INCOME FOR THE AGED, BLIND, AND DISABLED Determining Disability and Blindness Continuing Or Stopping Disability Or Blindness § 416.998 If you become disabled by another impairment(s). If a new severe...

  5. 20 CFR 416.998 - If you become disabled by another impairment(s).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... INCOME FOR THE AGED, BLIND, AND DISABLED Determining Disability and Blindness Continuing Or Stopping Disability Or Blindness § 416.998 If you become disabled by another impairment(s). If a new severe...

  6. [Regeneration capacity of skeletal muscle].

    PubMed

    Wernig, A

    2003-07-01

    The organotypic stem cell of skeletal muscle has previously been known as satellite cell. They allow muscle fiber growth during ontogenesis, enable fiber hypertrophy and are responsible for the very efficient repair of muscle fibers. This efficient apparatus is to some degree counterbalanced by an enormous use of the satellite cell pool: fiber atrophy probably is accompanied by loss of myonuclei such that every reversal of atrophy is bound to use new myonuclei i.e. satellite cells. How often in life does this occur? Hard to say. Moreover, the potent repair capacity is challenged by an unexpected vulnerability of skeletal muscle fibers: Passive stretching of contracted muscles may cause multiple "microdamage," disruption of contractile elements or tiny areas of true necrosis (focal necrosis). How often does this happen? Well, for many of us at least once per year when we go up and down mountains during vacation time, followed by sour muscles. Others may decide to change his/her (locomotor) behaviour by severe onset of jogging; it may happen that they suffer kidney failure on Monday due to muscle microdamage and the transfer of myoproteins into the serum over weekend. Also 20 minutes of stepping up and down something like a chair will do: There is a remarkable increase in kreatin kinase and other muscle derived proteins which lasts for days and is bound to reflect some muscle damage. How about sportsmen and worker who repeatedly use their muscles in such a way? We don't have answers yet to most of these questions, but considerable amount of information has been collected over the last years both in animal and--less--in human. What is common in all cases of growth and repair is the proliferation of the satellite cells and their consequent incorporation and fusion with the parent fiber. This way focal damage is repaired often without visible reminders. We would run out of satellite cells were they not stem cells: After division one daughter remains a satellite cell

  7. North Dakota Refining Capacity Study

    SciTech Connect

    Dennis Hill; Kurt Swenson; Carl Tuura; Jim Simon; Robert Vermette; Gilberto Marcha; Steve Kelly; David Wells; Ed Palmer; Kuo Yu; Tram Nguyen; Juliam Migliavacca

    2011-01-05

    According to a 2008 report issued by the United States Geological Survey, North Dakota and Montana have an estimated 3.0 to 4.3 billion barrels of undiscovered, technically recoverable oil in an area known as the Bakken Formation. With the size and remoteness of the discovery, the question became 'can a business case be made for increasing refining capacity in North Dakota?' And, if so what is the impact to existing players in the region. To answer the question, a study committee comprised of leaders in the region's petroleum industry were brought together to define the scope of the study, hire a consulting firm and oversee the study. The study committee met frequently to provide input on the findings and modify the course of the study, as needed. The study concluded that the Petroleum Area Defense District II (PADD II) has an oversupply of gasoline. With that in mind, a niche market, naphtha, was identified. Naphtha is used as a diluent used for pipelining the bitumen (heavy crude) from Canada to crude markets. The study predicted there will continue to be an increase in the demand for naphtha through 2030. The study estimated the optimal configuration for the refinery at 34,000 barrels per day (BPD) producing 15,000 BPD of naphtha and a 52 percent refinery charge for jet and diesel yield. The financial modeling assumed the sponsor of a refinery would invest its own capital to pay for construction costs. With this assumption, the internal rate of return is 9.2 percent which is not sufficient to attract traditional investment given the risk factor of the project. With that in mind, those interested in pursuing this niche market will need to identify incentives to improve the rate of return.

  8. Dating human cultural capacity using phylogenetic principles.

    PubMed

    Lind, J; Lindenfors, P; Ghirlanda, S; Lidén, K; Enquist, M

    2013-01-01

    Humans have genetically based unique abilities making complex culture possible; an assemblage of traits which we term "cultural capacity". The age of this capacity has for long been subject to controversy. We apply phylogenetic principles to date this capacity, integrating evidence from archaeology, genetics, paleoanthropology, and linguistics. We show that cultural capacity is older than the first split in the modern human lineage, and at least 170,000 years old, based on data on hyoid bone morphology, FOXP2 alleles, agreement between genetic and language trees, fire use, burials, and the early appearance of tools comparable to those of modern hunter-gatherers. We cannot exclude that Neanderthals had cultural capacity some 500,000 years ago. A capacity for complex culture, therefore, must have existed before complex culture itself. It may even originated long before. This seeming paradox is resolved by theoretical models suggesting that cultural evolution is exceedingly slow in its initial stages.

  9. Heat Capacity of 1D Molecular Chains

    NASA Astrophysics Data System (ADS)

    Bagatskii, M. I.; Barabashko, M. S.; Sumarokov, V. V.; Jeżowski, A.; Stachowiak, P.

    2017-04-01

    The heat capacity of 1D chains of nitrogen and methane molecules (adsorbed in the outer grooves of bundles of closed-cap single-walled carbon nanotubes) has been studied in the temperature ranges 2-40 and 2-60 K, respectively. The temperature dependence of the heat capacity of 1D chains of nitrogen molecules below 3 K is close to a linear. It was found that the rotational heat capacity of methane molecules is a significant part of the total heat capacity of the chains throughout the whole investigated temperature range, whereas in the case of nitrogen, the librations are significant only above 15 K. The dependence of the heat capacity for methane below 10 K indicates the presence of a Schottky anomaly caused by the tunneling between the lowest energy levels of the CH4 molecule rotational spectra. Characteristic features observed in the temperature dependence of the heat capacity of 1D methane crystals are also discussed.

  10. Writing Motivation of Students with Language Impairments

    ERIC Educational Resources Information Center

    Brouwer, Kyle L.

    2012-01-01

    This study compared the writing motivation of students with language impairments (LI) and their typically developing (TD) peers. For the study 272 students (33 students with language impairments, 242 TD peers) aged 8-10 years, in 11 elementary schools, were sampled. The two groups completed self-report measures of writing motivation and 20…

  11. Cognitive impairment in COPD: a systematic review*

    PubMed Central

    Torres-Sánchez, Irene; Rodríguez-Alzueta, Elisabeth; Cabrera-Martos, Irene; López-Torres, Isabel; Moreno-Ramírez, Maria Paz; Valenza, Marie Carmen

    2015-01-01

    The objectives of this study were to characterize and clarify the relationships between the various cognitive domains affected in COPD patients and the disease itself, as well as to determine the prevalence of impairment in the various cognitive domains in such patients. To that end, we performed a systematic review using the following databases: PubMed, Scopus, and ScienceDirect. We included articles that provided information on cognitive impairment in COPD patients. The review of the findings of the articles showed a significant relationship between COPD and cognitive impairment. The most widely studied cognitive domains are memory and attention. Verbal memory and learning constitute the second most commonly impaired cognitive domain in patients with COPD. The prevalence of impairment in visuospatial memory and intermediate visual memory is 26.9% and 19.2%, respectively. We found that cognitive impairment is associated with the profile of COPD severity and its comorbidities. The articles reviewed demonstrated that there is considerable impairment of the cognitive domains memory and attention in patients with COPD. Future studies should address impairments in different cognitive domains according to the disease stage in patients with COPD. PMID:25909154

  12. Visual Impairment in Infants and Young Children.

    ERIC Educational Resources Information Center

    Teplin, Stuart W.

    1995-01-01

    This article reviews the structure, development, function, and assessment of the visual system and then considers: common eye problems of young children with visual impairment; impacts of severe impairment on child development; and the roles of early intervention professionals, ophthalmologists, and pediatricians in working with these children and…

  13. Statistics on Children with Visual Impairments.

    ERIC Educational Resources Information Center

    Viisola, Michelle

    This report summarizes statistical data relating to children with visual impairments, including incidence, causes, and education. Data include: (1) prevalence estimates that indicate 1 percent of persons under the age of 18 in the United States have a visual impairment that cannot be corrected with glasses; (2) the leading cause of childhood…

  14. Pegasus Project for the Hearing-Impaired.

    ERIC Educational Resources Information Center

    Krahe, Jane M.

    The Pegasus Project offered nine gifted hearing impaired students (11-15 years old) a summer enrichment experience with hearing peers. Courses included computer programming, literature, fine arts, physical and biological sciences, math enrichment, and sign language. All hearing impaired students also attended a special class on issues for the…

  15. The Physical Environment and the Visually Impaired.

    ERIC Educational Resources Information Center

    Braf, Per-Gunnar

    Reported are results of a project carried out at the Swedish Institute for the Handicapped to determine needs of the visually impaired in the planning and adaptation of buildings and other forms of physical environment. Chapter 1 considers implications of impaired vision and includes definitions, statistics, and problems of the visually impaired…

  16. Library Automation Design for Visually Impaired People

    ERIC Educational Resources Information Center

    Yurtay, Nilufer; Bicil, Yucel; Celebi, Sait; Cit, Guluzar; Dural, Deniz

    2011-01-01

    Speech synthesis is a technology used in many different areas in computer science. This technology can bring a solution to reading activity of visually impaired people due to its text to speech conversion. Based on this problem, in this study, a system is designed needed for a visually impaired person to make use of all the library facilities in…

  17. Marital Conflict, Depressive Symptoms, and Functional Impairment

    ERIC Educational Resources Information Center

    Choi, Heejeong; Marks, Nadine F

    2008-01-01

    Guided by a stress process perspective, we investigated (a) whether marital conflict might directly lead to changes in depression and functional impairment, (b) whether marital conflict might indirectly lead to changes in functional impairment via depression, and (c) whether marital conflict might indirectly lead to changes in depression via…

  18. Counseling the Chronically Health Impaired Student.

    ERIC Educational Resources Information Center

    Dale, Brian, Comp.; And Others

    The role of counselors in working with chronically health impaired students is examined, and illustrations of the Chronic Health Impaired/Sickle Cell Anemia Program in Baltimore (MD) are presented. The importance of setting goals with the student is underlined, as is the necessity for counselors to have proper flexibility and time to devote to…

  19. Alcohol and the Physically Impaired: Special Focus.

    ERIC Educational Resources Information Center

    Boros, Alexander, Ed.

    1989-01-01

    The articles in this special issue explore the connections between the dual disabilities of alcohol abuse and physical impairment, and reflect progress made in exploring the causes and treatments of alcohol abuse among the physically impaired. Selected articles include: "Results of a Model Intervention Program for Physically Impaired…

  20. Dual-Retrieval Models and Neurocognitive Impairment

    ERIC Educational Resources Information Center

    Brainerd, C. J.; Reyna, V. F.; Gomes, C. F. A.; Kenney, A. E.; Gross, C. J.; Taub, E. S.; Spreng, R. N.

    2014-01-01

    Advances in dual-retrieval models of recall make it possible to use clinical data to test theoretical hypotheses about mild cognitive impairment (MCI) and Alzheimer's dementia (AD), the most common forms of neurocognitive impairment. Hypotheses about the nature of the episodic memory declines in these diseases, about decline versus sparing of…

  1. Spatial Coding of Individuals with Visual Impairments

    ERIC Educational Resources Information Center

    Papadopoulos, Konstantinos; Koustriava, Eleni; Kartasidou, Lefkothea

    2012-01-01

    The aim of this study is to examine the ability of children and adolescents with visual impairments to code and represent near space. Moreover, it examines the impact of the strategies they use and individual differences in their performance. A total of 30 individuals with visual impairments up to the age of 18 were given eight different object…

  2. The Effect of Impaired Angiogenesis on Intestinal Function Following Massive Small Bowel Resection

    PubMed Central

    Diaz-Miron, Jose; Sun, Raphael; Choi, Pamela; Sommovilla, Joshua; Guo, Jun; Erwin, Christopher R.; Mei, Junjie; Worthen, G. Scott; Warner, Brad W.

    2015-01-01

    Purpose Intestinal adaptation involves villus lengthening, crypt deepening, and increased capillary density following small bowel resection (SBR). Mice lacking the proangiogenic chemokine CXCL5 have normal structural adaptation but impaired angiogenesis. This work evaluates the impact of incomplete adaptive angiogenesis on the functional capacity of the intestine after SBR. Methods CXCL5 knockout (KO) and C57BL/6 wild-type (WT) mice underwent 50% SBR. Magnetic resonance imaging measured weekly body composition. Intestinal absorptive capacity was evaluated through fecal fat analysis. Gene expression profiles for select macronutrient transporters were measured via RT-PCR. Postoperative crypt and villus measurements assessed for structural adaptation. Submucosal capillary density was measured through CD31 immunohistochemistry. Results Comparable postoperative weight gain occurred initially. Diminished weight gain, impaired fat absorption, and elevated steatorrhea occurred in KO mice after instituting high-fat diet. Greater postoperative upregulation of ABCA1 fat transporter occurred in WT mice, while PEPT1 protein transporter was significantly downregulated in KO mice. KO mice had impaired angiogenesis but intact structural adaptation. Conclusion After SBR, KO mice display an inefficient intestinal absorption profile with perturbed macronutrient transporter expression, impaired fat absorption, and slower postoperative weight gain. In addition to longer villi and deeper crypts, an intact angiogenic response may be required to achieve functional adaptation to SBR. PMID:25818317

  3. Large capacity cryopropellant orbital storage facility

    NASA Technical Reports Server (NTRS)

    Schuster, J. R.

    1987-01-01

    A comprehensive study was performed to develop the major features of a large capacity orbital propellant storage facility for the space-based cryogenic orbital transfer vehicle. Projected propellant usage and delivery schedules can be accommodated by two orbital tank sets of 100,000 lb storage capacity, with advanced missions expected to require increased capacity. Information is given on tank pressurization schemes, propellant transfer configurations, pump specifications, the refrigeration system, and flight tests.

  4. Impaired killing of Candida albicans by granulocytes mobilized for transfusion purposes: a role for granule components

    PubMed Central

    Gazendam, Roel P.; van de Geer, Annemarie; van Hamme, John L.; Tool, Anton T.J.; van Rees, Dieke J.; Aarts, Cathelijn E.M.; van den Biggelaar, Maartje; van Alphen, Floris; Verkuijlen, Paul; Meijer, Alexander B.; Janssen, Hans; Roos, Dirk; van den Berg, Timo K.; Kuijpers, Taco W.

    2016-01-01

    Granulocyte transfusions are used to treat neutropenic patients with life-threatening bacterial or fungal infections that do not respond to anti-microbial drugs. Donor neutrophils that have been mobilized with granulocyte-colony stimulating factor (G-CSF) and dexamethasone are functional in terms of antibacterial activity, but less is known about their fungal killing capacity. We investigated the neutrophil-mediated cytotoxic response against C. albicans and A. fumigatus in detail. Whereas G-CSF/dexamethasone-mobilized neutrophils appeared less mature as compared to neutrophils from untreated controls, these cells exhibited normal ROS production by the NADPH oxidase system and an unaltered granule mobilization capacity upon stimulation. G-CSF/dexamethasone-mobilized neutrophils efficiently inhibited A. fumigatus germination and killed Aspergillus and Candida hyphae, but the killing of C. albicans yeasts was distinctly impaired. Following normal Candida phagocytosis, analysis by mass spectrometry of purified phagosomes after fusion with granules demonstrated that major constituents of the antimicrobial granule components, including major basic protein (MBP), were reduced. Purified MBP showed candidacidal activity, and neutrophil-like Crisp-Cas9 NB4-KO-MBP differentiated into phagocytes were impaired in Candida killing. Together, these findings indicate that G-CSF/dexamethasone-mobilized neutrophils for transfusion purposes have a selectively impaired capacity to kill Candida yeasts, as a consequence of an altered neutrophil granular content. PMID:26802050

  5. From the prodrome to chronic schizophrenia: the neurobiology underlying psychotic symptoms and cognitive impairments.

    PubMed

    Howes, O D; Fusar-Poli, P; Bloomfield, M; Selvaraj, S; McGuire, P

    2012-01-01

    Schizophrenia is a chronic psychotic disorder that remains a considerable cause of global disease burden. Cognitive impairments are common and contribute significantly to the morbidity of the disorder. Over the last two decades or so molecular imaging studies have refined understanding of the pathophysiology underlying the development of psychosis and cognitive impairments. Firstly they have consistently implicated presynaptic dopaminergic dysfunction in the disorder, finding that dopamine synthesis capacity, dopamine release and baseline dopamine levels are increased in the illness. Secondly recent findings show that dopamine synthesis capacity is elevated in those that go on to develop psychosis in the following year, but not in those that do not, and appears to increase further with the development of psychosis. Thirdly evidence links greater dopamine synthesis capacity to poorer cognitive performance and altered frontal cortical function measured using functional imaging during cognitive tasks. Finally they have provided data on the nature of other neurofunctional alterations in the disorder, in particular in the serotonergic system and neuroinflammation. We review these findings and discuss their implications for understanding the neurobiology of psychosis and cognitive impairments in schizophrenia.

  6. Impaired killing of Candida albicans by granulocytes mobilized for transfusion purposes: a role for granule components.

    PubMed

    Gazendam, Roel P; van de Geer, Annemarie; van Hamme, John L; Tool, Anton T J; van Rees, Dieke J; Aarts, Cathelijn E M; van den Biggelaar, Maartje; van Alphen, Floris; Verkuijlen, Paul; Meijer, Alexander B; Janssen, Hans; Roos, Dirk; van den Berg, Timo K; Kuijpers, Taco W

    2016-05-01

    Granulocyte transfusions are used to treat neutropenic patients with life-threatening bacterial or fungal infections that do not respond to anti-microbial drugs. Donor neutrophils that have been mobilized with granulocyte-colony stimulating factor (G-CSF) and dexamethasone are functional in terms of antibacterial activity, but less is known about their fungal killing capacity. We investigated the neutrophil-mediated cytotoxic response against C. albicans and A. fumigatus in detail. Whereas G-CSF/dexamethasone-mobilized neutrophils appeared less mature as compared to neutrophils from untreated controls, these cells exhibited normal ROS production by the NADPH oxidase system and an unaltered granule mobilization capacity upon stimulation. G-CSF/dexamethasone-mobilized neutrophils efficiently inhibited A. fumigatus germination and killed Aspergillus and Candida hyphae, but the killing of C. albicans yeasts was distinctly impaired. Following normal Candida phagocytosis, analysis by mass spectrometry of purified phagosomes after fusion with granules demonstrated that major constituents of the antimicrobial granule components, including major basic protein (MBP), were reduced. Purified MBP showed candidacidal activity, and neutrophil-like Crisp-Cas9 NB4-KO-MBP differentiated into phagocytes were impaired in Candida killing. Together, these findings indicate that G-CSF/dexamethasone-mobilized neutrophils for transfusion purposes have a selectively impaired capacity to kill Candida yeasts, as a consequence of an altered neutrophil granular content.

  7. Lactate rescues neuronal sodium homeostasis during impaired energy metabolism

    PubMed Central

    Karus, Claudia; Ziemens, Daniel; Rose, Christine R

    2015-01-01

    Recently, we established that recurrent activity evokes network sodium oscillations in neurons and astrocytes in hippocampal tissue slices. Interestingly, metabolic integrity of astrocytes was essential for the neurons' capacity to maintain low sodium and to recover from sodium loads, indicating an intimate metabolic coupling between the 2 cell types. Here, we studied if lactate can support neuronal sodium homeostasis during impaired energy metabolism by analyzing whether glucose removal, pharmacological inhibition of glycolysis and/or addition of lactate affect cellular sodium regulation. Furthermore, we studied the effect of lactate on sodium regulation during recurrent network activity and upon inhibition of the glial Krebs cycle by sodium-fluoroacetate. Our results indicate that lactate is preferentially used by neurons. They demonstrate that lactate supports neuronal sodium homeostasis and rescues the effects of glial poisoning by sodium-fluoroacetate. Altogether, they are in line with the proposed transfer of lactate from astrocytes to neurons, the so-called astrocyte-neuron-lactate shuttle. PMID:26039160

  8. New strategies for Alzheimer's disease and cognitive impairment.

    PubMed

    Maiese, Kenneth; Chong, Zhao Zhong; Hou, Jinling; Shang, Yan Chen

    2009-01-01

    Approximately five million people suffer with Alzheimer's disease (AD) and more than twenty-four million people are diagnosed with AD, pre-senile dementia, and other disorders of cognitive loss worldwide. Furthermore, the annual cost per patient with AD can approach $200,000 with an annual population aggregate cost of $100 billion. Yet, complete therapeutic prevention or reversal of neurovascular injury during AD and cognitive loss is not achievable despite the current understanding of the cellular pathways that modulate nervous system injury during these disorders. As a result, identification of novel therapeutic targets for the treatment of neurovascular injury would be extremely beneficial to reduce or eliminate disability from diseases that lead to cognitive loss or impairment. Here we describe the capacity of intrinsic cellular mechanisms for the novel pathways of erythropoietin and forkhead transcription factors that may offer not only new strategies for disorders such as AD and cognitive loss, but also function as biomarkers for disease onset and progression.

  9. DNA-repair in mild cognitive impairment and Alzheimer's disease.

    PubMed

    Bucholtz, Nina; Demuth, Ilja

    2013-10-01

    While the pathogenesis of the sporadic form of Alzheimer disease (late onset Alzheimer disease, LOAD) is not fully understood, it seems to be clear that a combination of genetic and environmental factors are involved and influence the course of the disease. Among these factors, elevated levels of oxidative stress have been recognized and individual differences in the capacity to deal with DNA damage caused by its effects have been the subject of numerous studies. This review summarizes the research on DNA repair proteins and genes in the context of LOAD pathogenesis and its possible prodromal stage, mild cognitive impairment (MCI). The current status of the research in this field is discussed with respect to methodological issues which might have compromised the outcome of some studies and future directions of investigation on this subject are depicted.

  10. Impaired goal-directed behavioural control in human impulsivity

    PubMed Central

    Hogarth, Lee; Chase, Henry W.; Baess, Kathleen

    2010-01-01

    Two dissociable learning processes underlie instrumental behaviour. Whereas goal-directed behaviour is controlled by knowledge of the consequences, habitual behaviour is elicited directly by antecedent Pavlovian stimuli without knowledge of the consequences. Predominance of habitual control is thought to underlie psychopathological conditions associated with corticostriatal abnormalities, such as impulsivity and drug dependence. To explore this claim, smokers were assessed for nicotine dependence, impulsivity, and capacity for goal-directed control over instrumental performance in an outcome devaluation procedure. Reduced goal-directed control was selectively associated with the Motor Impulsivity factor of Barrett's Impulsivity Scale (BIS), which reflects propensity for action without thought. These data support the claim that human impulsivity is marked by impaired use of causal knowledge to make adaptive decisions. The predominance of habit learning may play a role in psychopathological conditions that are associated with trait impulsivity. PMID:21077008

  11. Ethically optimal interventions with impaired patients.

    PubMed

    Howe, Edmund G

    2014-01-01

    It may be difficult to imagine having a severe impairment such as quadriplegia or being dependent on a respirator. There is evidence that when careproviders make treatment decisions for patients who are in these situations, we imagine the patients are worse-off than they report they are -- most patients with even very severe impairments report that they greatly value being alive. This misperception may cause us to make treatment decisions for patients with impairments that we might not make for other patients. In this article I describe how to provide better care for patients who have impairments. This includes not presupposing that the patients' quality of life is decreased, considering with patients how outside factors may be limiting their functioning, and seeking to help offset these factors, if we can, when they exist, to avoid allowing patients' impairments to result in their being truly "disabled".

  12. Assured load carrying capability and capacity credit

    NASA Astrophysics Data System (ADS)

    Pape, H.

    1981-04-01

    The determination of assured load carrying capability and the capacity credit for use in planning windpowered electric generation facilities is considered. Calculation of the available capacity of thermal power plants is described and compared with calculation of available capacity for wind turbines, taking into account outages caused by the unavailability of the primary energy, wind. The assured load carrying capability of power plants is defined. An operational definition of the capacity credit of wind turbines as related to a fixed time t Epsilon T is presented and extended to the period T.

  13. Population growth and earth's human carrying capacity.

    PubMed

    Cohen, J E

    1995-07-21

    Earth's capacity to support people is determined both by natural constraints and by human choices concerning economics, environment, culture (including values and politics), and demography. Human carrying capacity is therefore dynamic and uncertain. Human choice is not captured by ecological notions of carrying capacity that are appropriate for nonhuman populations. Simple mathematical models of the relation between human population growth and human carrying capacity can account for faster-than-exponential population growth followed by a slowing population growth rate, as observed in recent human history.

  14. Capacity fade of Sony 18650 cells cycled at elevated temperatures. Part II. Capacity fade analysis

    NASA Astrophysics Data System (ADS)

    Ramadass, P.; Haran, Bala; White, Ralph; Popov, Branko N.

    A complete capacity fade analysis was carried out for Sony 18650 cells cycled at elevated temperatures. The major causes of capacity loss were identified and a complete capacity fade balance was carried out to account for the total capacity loss of Li-ion battery as a function of cycle number and temperature. The three most significant parameters that cause capacity loss were loss of secondary active material (LiCoO 2/carbon) and primary active material (Li +) and the rate capability losses. Intrinsic capacity measurements for both positive and negative electrode has been used to estimate the capacity loss due to secondary active material and a charge balance gives the capacity lost due to primary active material (Li +). Capacity fade has been quantified with secondary active material loss dominating the other losses.

  15. The effectiveness of a stimulation program on cognitive capacity among individuals older than 60.

    PubMed

    Karatay, Gülnaz; Akkuş, Yeliz

    2011-02-01

    The purpose of this study was to test the effects of a multistimulant home-based intervention program on cognitive function, anxiety, and depression among older adults with cognitive impairment. This research is quasi-experimental and was designed in an effort to increase the cognitive capacity of individuals above the age of 60 with reduced cognitive capacities. Each senior received a total of seven home visits, including intervention conversation, newspaper/ book reading, painting/handcraft activities, and physical exercise. The Mini Mental State Test scores of the participants statistically increased, whereas the Beck Anxiety and the Geriatric Depression Scale scores showed a decrease (p < .05) after the intervention. Findings demonstrate that the multistimulant approach to improve cognitive capacity among individuals older than 60 years was successful.

  16. Building capacity for dementia care in Latin America and the Caribbean

    PubMed Central

    Gonzalez, Francisco J.; Gaona, Ciro; Quintero, Marialcira; Chavez, Carlos A.; Selga, Joyce; Maestre, Gladys E.

    2015-01-01

    Latin America and the Caribbean (LAC) have limited facilities and professionals trained to diagnose, treat, and support people with dementia and other forms of cognitive impairment. The situation for people with dementia is poor, and worsening as the proportion of elderly in the general population is rapidly expanding. We reviewed existing initiatives and provided examples of actions taken to build capacity and improve the effectiveness of individuals, organizations, and national systems that provide treatment and support for people with dementia and their caregivers. Regional barriers to capacity building and the importance of public engagement are highlighted. Existing programs need to disseminate their objectives, accomplishments, limitations, and overall lessons learned in order to gain greater recognition of the need for capacity-building programs. PMID:25932285

  17. Impaired cortical mitochondrial function following TBI precedes behavioral changes

    PubMed Central

    Watson, William D.; Buonora, John E.; Yarnell, Angela M.; Lucky, Jessica J.; D’Acchille, Michaela I.; McMullen, David C.; Boston, Andrew G.; Kuczmarski, Andrew V.; Kean, William S.; Verma, Ajay; Grunberg, Neil E.; Cole, Jeffrey T.

    2014-01-01

    Traumatic brain injury (TBI) pathophysiology can be attributed to either the immediate, primary physical injury, or the delayed, secondary injury which begins minutes to hours after the initial injury and can persist for several months or longer. Because these secondary cascades are delayed and last for a significant time period post-TBI, they are primary research targets for new therapeutics. To investigate changes in mitochondrial function after a brain injury, both the cortical impact site and ipsilateral hippocampus of adult male rats 7 and 17 days after a controlled cortical impact (CCI) injury were examined. State 3, state 4, and uncoupler-stimulated rates of oxygen consumption, respiratory control ratios (RCRs) were measured and membrane potential quantified, and all were significantly decreased in 7 day post-TBI cortical mitochondria. By contrast, hippocampal mitochondria at 7 days showed only non-significant decreases in rates of oxygen consumption and membrane potential. NADH oxidase activities measured in disrupted mitochondria were normal in both injured cortex and hippocampus at 7 days post-CCI. Respiratory and phosphorylation capacities at 17 days post-CCI were comparable to naïve animals for both cortical and hippocampus mitochondria. However, unlike oxidative phosphorylation, membrane potential of mitochondria in the cortical lining of the impact site did not recover at 17 days, suggesting that while diminished cortical membrane potential at 17 days does not adversely affect mitochondrial capacity to synthesize ATP, it may negatively impact other membrane potential-sensitive mitochondrial functions. Memory status, as assessed by a passive avoidance paradigm, was not significantly impaired until 17 days after injury. These results indicate pronounced disturbances in cortical mitochondrial function 7 days after CCI which precede the behavioral impairment observed at 17 days. PMID:24550822

  18. A methoxydiphenidine-impaired driver.

    PubMed

    Stachel, Nicole; Jacobsen-Bauer, Andrea; Skopp, Gisela

    2016-03-01

    Methoxydiphenidine (MXP) was first reported in 1989 as a dissociative anesthetic but did not enter the market for pharmaceuticals. The substance re-appeared in 2013 as a new psychoactive substance. A case of driving under the influence of MXP is reported. The concentration of MXP has been determined from a serum sample (57 ng/mL) by liquid chromatography tandem mass spectrometry following liquid-liquid extraction. In addition, amphetamine, methylenedioxymethamphetamine, and its major metabolite were present in concentrations of 111, 28, and 3 ng/mL, respectively. The subject presented with amnesia, out-of-body experiences, bizarre behavior, and decreased motor abilities. At present, information on human toxicity of MXP is not available. MXP is comparable in structure as well as in action at the N-methyl-D-aspartate (NMDA) receptor to phencyclidine or ketamine. Therefore, it is likely that MXP exerts similar severe psychotropic action in man. However, there is no information on the duration and intensity of MXP's impairing effects, the interpretation of a particular concentration in the blood or serum, and its detectability in routine drug screenings. Confirmation analysis may be confined to cases where the police has specific intelligence that points to MXP use.

  19. Impaired NHEJ function in Multiple Myeloma

    PubMed Central

    Yang, Clara; Toor, Amir A.; Singh, Sheetal; Betti, Christopher; Vaughan, Andrew

    2009-01-01

    Multiple Myeloma (MM) is characterized by multiple chromosomal aberrations. To assess the contribution of DNA repair to this phenotype, ionizing radiation was used to induce DNA double strand breaks in three MM cell lines. Clonogenic survival assays showed U266 (SF4= 15.3+6.4%) and RPMI 8226 (SF4=12.6.0+1.7%) were radiation sensitive while OPM2 was resistant (SF4=78.9+4.1%). Addition of the DNA-PK inhibitor NU7026 showed the expected suppression in radiation survival in OPM2 but increased survival in both radiation sensitive cell lines. To examine NHEJ repair in these lines, the ability of protein extracts to support in vitro DNA repair was measured. Among the three MM cell lines analyzed, RPMI 8226 demonstrated impaired blunt ended DNA ligation using a ligation mediated PCR technique. In a bacterial based functional assay to rejoin a DNA break within the β-galactosidase gene, RPMI 8226 demonstrated a four fold reduction in rejoining fidelity compared to U266, with OPM2 showing an intermediate capacity. Ionizing radiation induced a robust γ-H2AX response in OPM2 but only a modest increase in each radiation sensitive cell line perhaps related to the high level of γ-H2AX in freshly plated cells. Examination of γ-H2AX foci in RPMI 8226 cells confirmed data from Western blots where a significant number of foci were present in freshly plated untreated cells which diminished over 24 h of culture. Based on the clonogenic survival and functional repair assays, all three cell lines exhibited corrupt NHEJ repair. We conclude that suppression of aberrant NHEJ function using the DNA-PK inhibitor NU7026 may facilitate access of DNA ends to an intact homologous recombination repair pathway, paradoxically increasing survival after irradiation. These data provide insight into the deregulation of DNA repair at the site of DNA breaks in MM that may underpin the characteristic genomic instability of this disease. PMID:19028508

  20. Diffusion of Impaired Driving Laws Among US States

    PubMed Central

    Silver, Diana

    2015-01-01

    Objectives. We examined internal and external determinants of state’s adoption of impaired driving laws. Methods. Data included 7 state-level, evidence-based public health laws collected from 1980 to 2010. We used event history analyses to identify predictors of first-time law adoption and subsequent adoption between state pairs. The independent variables were internal state factors, including the political environment, legislative professionalism, government capacity, state resources, legislative history, and policy-specific risk factors. The external factors were neighboring states’ history of law adoption and changes in federal law. Results. We found a strong secular trend toward an increased number of laws over time. The proportion of younger drivers and the presence of a neighboring state with similar laws were the strongest predictors of first-time law adoption. The predictors of subsequent law adoption included neighbor state adoption and previous legislative action. Alcohol laws were negatively associated with first-time adoption of impaired driving laws, suggesting substitution effects among policy choices. Conclusions. Organizations seeking to stimulate state policy changes may need to craft strategies that engage external actors, such as neighboring states, in addition to mobilizing within-state constituencies. PMID:26180969

  1. Impaired spontaneous anthropomorphizing despite intact perception and social knowledge

    PubMed Central

    Heberlein, Andrea S.; Adolphs, Ralph

    2004-01-01

    Humans spontaneously imbue the world with social meaning: we see not only emotions and intentional behaviors in humans and other animals, but also anger in the movements of thunderstorms and willful sabotage in crashing computers. Converging evidence supports a role for the amygdala, a collection of nuclei in the temporal lobe, in processing emotionally and socially relevant information. Here, we report that a patient with bilateral amygdala damage described a film of animated shapes (normally seen as full of social content) in entirely asocial, geometric terms, despite otherwise normal visual perception. Control tasks showed that the impairment did not result from a global inability to describe social stimuli or a bias in language use, nor was a similar impairment observed in eight comparison subjects with damage to orbitofrontal cortex. This finding extends the role of the amygdala to the social attributions we make even to stimuli that are not explicitly social and, in so doing, suggests that the human capacity for anthropomorphizing draws on some of the same neural systems as do basic emotional responses. PMID:15123799

  2. Impairments that Influence Physical Function among Survivors of Childhood Cancer

    PubMed Central

    Wilson, Carmen L.; Gawade, Prasad L.; Ness, Kirsten K.

    2015-01-01

    Children treated for cancer are at increased risk of developing chronic health conditions, some of which may manifest during or soon after treatment while others emerge many years after therapy. These health problems may limit physical performance and functional capacity, interfering with participation in work, social, and recreational activities. In this review, we discuss treatment-induced impairments in the endocrine, musculoskeletal, neurological, and cardiopulmonary systems and their influence on mobility and physical function. We found that cranial radiation at a young age was associated with a broad range of chronic conditions including obesity, short stature, low bone mineral density and neuromotor impairments. Anthracyclines and chest radiation are associated with both short and long-term cardiotoxicity. Although numerous chronic conditions are documented among individuals treated for childhood cancer, the impact of these conditions on mobility and function are not well characterized, with most studies limited to survivors of acute lymphoblastic leukemia and brain tumors. Moving forward, further research assessing the impact of chronic conditions on participation in work and social activities is required. Moreover, interventions to prevent or ameliorate the loss of physical function among children treated for cancer are likely to become an important area of survivorship research. PMID:25692094

  3. Effect of renal impairment on distribution of ofloxacin.

    PubMed Central

    Sanchez Navarro, A; Martinez Lanao, J; Sanchez Recio, M M; Domínguez-Gil Hurlé, A; Tabernero Romo, J M; Gomez Sanchez, J C; Terreiro Delgado, M M

    1990-01-01

    A study was made of the plasma and distribution kinetics of ofloxacin administered at a dosage of 400 mg orally to a group of healthy volunteers and a group of patients with renal impairment. Blood and blister fluid samples were taken at programmed times from all individuals included in the study. The analytical techniques for the determination of ofloxacin in both fluids were a plate diffusion method and a high-performance liquid chromatographic technique. The fitting of the experimental data to the kinetic model used was done with the help of the AUTOAN 2 and NONLIN 84 computer programs. In the groups of healthy volunteers, the elimination half-life mean values were found to be 5.1 and 5.9 h in plasma and blister fluid, respectively. The maximum concentration reached in plasma (3.9 micrograms/ml) proved to be slightly higher than that in interstitial tissue fluid (2.8 micrograms/ml). In the patients with renal impairment, the maximum concentrations in both plasma and blister fluid were significantly increased, in the order of 5 to 8 micrograms/ml in the former and 3 to 4 micrograms/ml in interstitial tissue fluid. The parameters seen to undergo an increase as a result of the renal impairment were the area under the curve of the plasma-time levels, the area under the curve of the blister fluid-time levels, and the elimination half-life in plasma and blister fluid. The degree of absorption and the access capacity of the drug to interstitial tissue fluid remained constant. PMID:2334157

  4. Emergent Biosynthetic Capacity in Simple Microbial Communities

    PubMed Central

    Chiu, Hsuan-Chao; Levy, Roie; Borenstein, Elhanan

    2014-01-01

    Microbes have an astonishing capacity to transform their environments. Yet, the metabolic capacity of a single species is limited and the vast majority of microorganisms form complex communities and join forces to exhibit capabilities far exceeding those achieved by any single species. Such enhanced metabolic capacities represent a promising route to many medical, environmental, and industrial applications and call for the development of a predictive, systems-level understanding of synergistic microbial capacity. Here we present a comprehensive computational framework, integrating high-quality metabolic models of multiple species, temporal dynamics, and flux variability analysis, to study the metabolic capacity and dynamics of simple two-species microbial ecosystems. We specifically focus on detecting emergent biosynthetic capacity – instances in which a community growing on some medium produces and secretes metabolites that are not secreted by any member species when growing in isolation on that same medium. Using this framework to model a large collection of two-species communities on multiple media, we demonstrate that emergent biosynthetic capacity is highly prevalent. We identify commonly observed emergent metabolites and metabolic reprogramming patterns, characterizing typical mechanisms of emergent capacity. We further find that emergent secretion tends to occur in two waves, the first as soon as the two organisms are introduced, and the second when the medium is depleted and nutrients become limited. Finally, aiming to identify global community determinants of emergent capacity, we find a marked association between the level of emergent biosynthetic capacity and the functional/phylogenetic distance between community members. Specifically, we demonstrate a “Goldilocks” principle, where high levels of emergent capacity are observed when the species comprising the community are functionally neither too close, nor too distant. Taken together, our results

  5. Emergent biosynthetic capacity in simple microbial communities.

    PubMed

    Chiu, Hsuan-Chao; Levy, Roie; Borenstein, Elhanan

    2014-07-01

    Microbes have an astonishing capacity to transform their environments. Yet, the metabolic capacity of a single species is limited and the vast majority of microorganisms form complex communities and join forces to exhibit capabilities far exceeding those achieved by any single species. Such enhanced metabolic capacities represent a promising route to many medical, environmental, and industrial applications and call for the development of a predictive, systems-level understanding of synergistic microbial capacity. Here we present a comprehensive computational framework, integrating high-quality metabolic models of multiple species, temporal dynamics, and flux variability analysis, to study the metabolic capacity and dynamics of simple two-species microbial ecosystems. We specifically focus on detecting emergent biosynthetic capacity--instances in which a community growing on some medium produces and secretes metabolites that are not secreted by any member species when growing in isolation on that same medium. Using this framework to model a large collection of two-species communities on multiple media, we demonstrate that emergent biosynthetic capacity is highly prevalent. We identify commonly observed emergent metabolites and metabolic reprogramming patterns, characterizing typical mechanisms of emergent capacity. We further find that emergent secretion tends to occur in two waves, the first as soon as the two organisms are introduced, and the second when the medium is depleted and nutrients become limited. Finally, aiming to identify global community determinants of emergent capacity, we find a marked association between the level of emergent biosynthetic capacity and the functional/phylogenetic distance between community members. Specifically, we demonstrate a "Goldilocks" principle, where high levels of emergent capacity are observed when the species comprising the community are functionally neither too close, nor too distant. Taken together, our results

  6. The failure of feedback on alcohol impairment to reduce impaired driving.

    PubMed Central

    Nau, P A; Van Houten, R; Rolider, A; Jonah, B A

    1993-01-01

    We examined the effects of rules to govern drinking, individual feedback on blood alcohol concentration (BAC), and public posting of group data on impaired driving on the incidence of impaired driving. Level of impairment was determined from breath samples taken from tavern patrons. Following baseline, an intervention package consisting of (a) cards to guide patrons in pacing their drinking to stay under the legal limit, (b) individual feedback on BAC, and (c) posted group feedback on the percentage of patrons driving while impaired the preceding week was introduced in two taverns. Results indicated that the intervention package did not reduce the percentage of impaired drivers departing either tavern. The addition of a brief intensive police enforcement program directed at impaired driving produced a short-term reduction in impaired driving. PMID:8407684

  7. The failure of feedback on alcohol impairment to reduce impaired driving.

    PubMed

    Nau, P A; Van Houten, R; Rolider, A; Jonah, B A

    1993-01-01

    We examined the effects of rules to govern drinking, individual feedback on blood alcohol concentration (BAC), and public posting of group data on impaired driving on the incidence of impaired driving. Level of impairment was determined from breath samples taken from tavern patrons. Following baseline, an intervention package consisting of (a) cards to guide patrons in pacing their drinking to stay under the legal limit, (b) individual feedback on BAC, and (c) posted group feedback on the percentage of patrons driving while impaired the preceding week was introduced in two taverns. Results indicated that the intervention package did not reduce the percentage of impaired drivers departing either tavern. The addition of a brief intensive police enforcement program directed at impaired driving produced a short-term reduction in impaired driving.

  8. Limited OXPHOS capacity in white adipocytes is a hallmark of obesity in laboratory mice irrespective of the glucose tolerance status

    PubMed Central

    Schöttl, Theresa; Kappler, Lisa; Fromme, Tobias; Klingenspor, Martin

    2015-01-01

    Objective Several human and rodent obesity studies speculate on a causal link between altered white adipocyte mitochondria in the obese state and changes in glucose homeostasis. We here aimed to dissect whether alterations in white adipocyte mitochondrial respiratory function are a specific phenomenon of obesity or impaired glucose tolerance or both. Methods Mature white adipocytes were purified from posterior subcutaneous and intraabdominal epididymal fat of four murine obesity models characterized by either impaired or normal oral glucose tolerance. Bioenergetic profiles, including basal, leak, and maximal respiration, were generated using high-resolution respirometry. Cell respiratory control ratios were calculated to evaluate mitochondrial respiratory function. Results Maximal respiration capacity and cell respiratory control ratios were diminished in white adipocytes of each of the four murine obesity models, both in the absence and the presence of impaired glucose tolerance. Limitation was more pronounced in adipocytes of intraabdominal versus subcutaneous fat. Conclusion Reduced mitochondrial respiratory capacity in white adipocytes is a hallmark of murine obesity irrespective of the glucose tolerance status. Impaired respiratory capacity in white adipocytes solely is not sufficient for the development of systemic glucose intolerance. PMID:26413469

  9. Storage capacity of the Tilinglike Learning Algorithm

    NASA Astrophysics Data System (ADS)

    Buhot, Arnaud; Gordon, Mirta B.

    2001-02-01

    The storage capacity of an incremental learning algorithm for the parity machine, the Tilinglike Learning Algorithm, is analytically determined in the limit of a large number of hidden perceptrons. Different learning rules for the simple perceptron are investigated. The usual Gardner-Derrida rule leads to a storage capacity close to the upper bound, which is independent of the learning algorithm considered.

  10. 15 CFR 241.1 - Capacities.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... OTHER DRY COMMODITIES, AND FOR CRANBERRIES § 241.1 Capacities. (a) The capacities of the standard barrel for fruits, vegetables, and other dry commodities, other than cranberries, and its subdivisions, are... standard cranberry barrel and its subdivisions are as follows: Size Cubic inches Bushels 1 Quarts...

  11. 15 CFR 241.1 - Capacities.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... OTHER DRY COMMODITIES, AND FOR CRANBERRIES § 241.1 Capacities. (a) The capacities of the standard barrel for fruits, vegetables, and other dry commodities, other than cranberries, and its subdivisions, are... standard cranberry barrel and its subdivisions are as follows: Size Cubic inches Bushels 1 Quarts...

  12. 15 CFR 241.1 - Capacities.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... OTHER DRY COMMODITIES, AND FOR CRANBERRIES § 241.1 Capacities. (a) The capacities of the standard barrel for fruits, vegetables, and other dry commodities, other than cranberries, and its subdivisions, are... standard cranberry barrel and its subdivisions are as follows: Size Cubic inches Bushels 1 Quarts...

  13. 15 CFR 241.1 - Capacities.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... OTHER DRY COMMODITIES, AND FOR CRANBERRIES § 241.1 Capacities. (a) The capacities of the standard barrel for fruits, vegetables, and other dry commodities, other than cranberries, and its subdivisions, are... standard cranberry barrel and its subdivisions are as follows: Size Cubic inches Bushels 1 Quarts...

  14. 15 CFR 241.1 - Capacities.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... OTHER DRY COMMODITIES, AND FOR CRANBERRIES § 241.1 Capacities. (a) The capacities of the standard barrel for fruits, vegetables, and other dry commodities, other than cranberries, and its subdivisions, are... standard cranberry barrel and its subdivisions are as follows: Size Cubic inches Bushels 1 Quarts...

  15. Vertical boring mill capacity is increased

    NASA Technical Reports Server (NTRS)

    Young, R. J.

    1968-01-01

    Commercially available vertical boring mill with a nominal capacity to 27 feet in diameter of workpiece has been modified in-shop to handle work up to 36 feet in diameter. Capacity was increased by adding extension saddles to the mill support columns on each side.

  16. The Heat Capacity of Ideal Gases

    ERIC Educational Resources Information Center

    Scott, Robert L.

    2006-01-01

    The heat capacity of an ideal gas has been shown to be calculable directly by statistical mechanics if the energies of the quantum states are known. However, unless one makes careful calculations, it is not easy for a student to understand the qualitative results. Why there are maxima (and occasionally minima) in heat capacity-temperature curves…

  17. Liberating Leadership Capacity: Pathways to Educational Wisdom

    ERIC Educational Resources Information Center

    Lambert, Linda; Zimmerman, Diane P.; Gardner, Mary E.

    2016-01-01

    During the past quarter century, conceptions of leadership have evolved in concert with breakthrough discoveries in science and generative learning. "Liberating Leadership Capacity" captures these new ideas through the integration of the authors' earlier works in constructivist leadership and leadership capacity. What emerges is a…

  18. 25 CFR 168.5 - Grazing capacity.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Grazing capacity. 168.5 Section 168.5 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER GRAZING REGULATIONS FOR THE HOPI PARTITIONED LANDS AREA § 168.5 Grazing capacity. (a) The Area Director shall prescribe the maximum number of...

  19. 25 CFR 168.5 - Grazing capacity.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 1 2011-04-01 2011-04-01 false Grazing capacity. 168.5 Section 168.5 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER GRAZING REGULATIONS FOR THE HOPI PARTITIONED LANDS AREA § 168.5 Grazing capacity. (a) The Area Director shall prescribe the maximum number of...

  20. Assessment of capacity in an aging society.

    PubMed

    Moye, Jennifer; Marson, Daniel C; Edelstein, Barry

    2013-04-01

    Over the past 40 years, the assessment and scientific study of capacity in older adults has emerged as a distinct field of clinical and research activity for psychologists. This new field reflects the convergence of several trends: the aging of American society, the growing incidence and prevalence of dementia, and the patient rights, deinstitutionalization, and disability rights movements. Because of these forces, capacity issues now permeate the fabric of everyday life, whether in the form of guardianship petitions, questions of capacity to consent to treatment, the ability to make a new will, or participation in human research. In seeking to resolve these issues, families, clinicians, and legal professionals increasingly turn to psychologists to assess a capacity and to provide empirically supported judgments that properly balance autonomy and protection for the individual. Psychologists have taken a leading role in the development of functional assessment instruments that measure important aspects of the capacity construct. In addition, psychology has been a major contributor to the scientific study of capacity. In collaboration with colleagues from medicine and law, psychologists have articulated crucial theoretical frameworks that integrate legal, clinical, and ethical dimensions of the capacity problem. This article focuses on the evolution of theory, law, science, and practice in the evaluation of capacity in older adults and its recent culmination in a series of interdisciplinary handbooks sponsored by the American Psychological Association and the American Bar Association.

  1. REDUCTION CAPACITY OF SALTSTONE AND SALTSTONE COMPONENTS

    SciTech Connect

    Roberts, K.; Kaplan, D.

    2009-11-30

    The duration that saltstone retains its ability to immobilize some key radionuclides, such as technetium (Tc), plutonium (Pu), and neptunium (Np), depends on its capacity to maintain a low redox status (or low oxidation state). The reduction capacity is a measure of the mass of reductants present in the saltstone; the reductants are the active ingredients that immobilize Tc, Pu, and Np. Once reductants are exhausted, the saltstone loses its ability to immobilize these radionuclides. The reduction capacity values reported here are based on the Ce(IV)/Fe(II) system. The Portland cement (198 {micro}eq/g) and especially the fly ash (299 {micro}eq/g) had a measurable amount of reduction capacity, but the blast furnace slag (820 {micro}eq/g) not surprisingly accounted for most of the reduction capacity. The blast furnace slag contains ferrous iron and sulfides which are strong reducing and precipitating species for a large number of solids. Three saltstone samples containing 45% slag or one sample containing 90% slag had essentially the same reduction capacity as pure slag. There appears to be some critical concentration between 10% and 45% slag in the Saltstone formulation that is needed to create the maximum reduction capacity. Values from this work supported those previously reported, namely that the reduction capacity of SRS saltstone is about 820 {micro}eq/g; this value is recommended for estimating the longevity that the Saltstone Disposal Facility will retain its ability to immobilize radionuclides.

  2. Thinking about Community Capacity Building & Asset Mapping.

    ERIC Educational Resources Information Center

    Community Building Resources, Spruce Grove (Alberta).

    This book describes the mindshift that is the key to successful community capacity building and to the development of social and economic structures that nurture local sustainability. Its focus is how the development of community, through community capacity building, connects, animates, and informs citizens. Chapter I introduces community building…

  3. Measuring Fiscal Capacity of School Systems.

    ERIC Educational Resources Information Center

    Green, Harry A.

    Ways of measuring the fiscal capacity of school systems are examined in this paper, which presents a representative tax system model. Fiscal capacity is influenced by factors other than tax base size; the "ideal" model should address adjustments for variations in cost across communities and school systems. The first section examines the…

  4. UNDERSTANDING, DERIVING, AND COMPUTING BUFFER CAPACITY

    EPA Science Inventory

    Derivation and systematic calculation of buffer capacity is a topic that seems often to be neglected in chemistry courses and given minimal treatment in most texts. However, buffer capacity is very important in the chemistry of natural waters and potable water. It affects corro...

  5. A capacity assessment towards more resilient societies

    NASA Astrophysics Data System (ADS)

    Kuhlicke, C.; Steinführer, A.

    2012-04-01

    Social capacity building for natural hazards is a topic increasingly gaining relevance not only for so-called developing countries but also for European welfare states which are continuously challenged by the social, economic and ecological impacts of natural hazards. Following an outline of recent governance changes with regard to natural hazards, we develop a heuristic model of social capacity building by taking into account a wide range of existing expertise from different fields of research. Particular attention is paid to social vulnerability and its assessment, as well as to risk communication and risk education as specific strategies of social capacity building. We propose to distinguish between interventionist and participatory approaches, thus enabling for a better understanding of existing practices of social capacity building as well as their particular strengths and weaknesses. It is from this typology the presentation will develop two kinds of operational social capacity audits; one for communities and one for organisations. These assessments aim to identify appropriate measures and strategies regarding how to enhance, develop and build different kinds of capacities. By using these assessments participants will be able to identify strong capacities and can refer to the recommendations for tips on how to improve capacities identified as weak. That way deficits and outcomes are defined by those who are most likely to be affected by a future hazard event and most likely to be implementing improvements towards resilience.

  6. Working Memory Capacity, Confidence and Scientific Thinking

    ERIC Educational Resources Information Center

    Al-Ahmadi, Fatheya; Oraif, Fatima

    2009-01-01

    Working memory capacity is now well established as a rate determining factor in much learning and assessment, especially in the sciences. Most of the research has focussed on performance in tests and examinations in subject areas. This paper outlines some exploratory work in which other outcomes are related to working memory capacity. Confidence…

  7. 25 CFR 168.5 - Grazing capacity.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 25 Indians 1 2013-04-01 2013-04-01 false Grazing capacity. 168.5 Section 168.5 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER GRAZING REGULATIONS FOR THE HOPI PARTITIONED LANDS AREA § 168.5 Grazing capacity. (a) The Area Director shall prescribe the maximum number of...

  8. 25 CFR 168.5 - Grazing capacity.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 25 Indians 1 2014-04-01 2014-04-01 false Grazing capacity. 168.5 Section 168.5 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER GRAZING REGULATIONS FOR THE HOPI PARTITIONED LANDS AREA § 168.5 Grazing capacity. (a) The Area Director shall prescribe the maximum number of...

  9. 25 CFR 168.5 - Grazing capacity.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 1 2012-04-01 2011-04-01 true Grazing capacity. 168.5 Section 168.5 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER GRAZING REGULATIONS FOR THE HOPI PARTITIONED LANDS AREA § 168.5 Grazing capacity. (a) The Area Director shall prescribe the maximum number of...

  10. Wind Capacity Credit in the United States

    SciTech Connect

    Milligan, M.; Porter, K.

    2008-01-01

    The objective of this paper is to provide an analysis and comparison of recent studies on the capacity credit of wind in the United States. We offer suggestions and recommendations for future studies, based on the recent work. We examine key wind capacity studies in the United States, emphasizing those done in the past three years.

  11. 49 CFR 1572.109 - Mental capacity.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... health facility. (b) An applicant is adjudicated as lacking mental capacity if— (1) A court, board... committed to a mental health facility if he or she is formally committed to a mental health facility by a... lacking mental capacity, mental illness, and drug use. This does not include commitment to a mental...

  12. 49 CFR 1572.109 - Mental capacity.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... health facility. (b) An applicant is adjudicated as lacking mental capacity if— (1) A court, board... committed to a mental health facility if he or she is formally committed to a mental health facility by a... lacking mental capacity, mental illness, and drug use. This does not include commitment to a mental...

  13. 49 CFR 1572.109 - Mental capacity.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... health facility. (b) An applicant is adjudicated as lacking mental capacity if— (1) A court, board... committed to a mental health facility if he or she is formally committed to a mental health facility by a... lacking mental capacity, mental illness, and drug use. This does not include commitment to a mental...

  14. 49 CFR 1572.109 - Mental capacity.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... health facility. (b) An applicant is adjudicated as lacking mental capacity if— (1) A court, board... committed to a mental health facility if he or she is formally committed to a mental health facility by a... lacking mental capacity, mental illness, and drug use. This does not include commitment to a mental...

  15. 49 CFR 1572.109 - Mental capacity.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... health facility. (b) An applicant is adjudicated as lacking mental capacity if— (1) A court, board... committed to a mental health facility if he or she is formally committed to a mental health facility by a... lacking mental capacity, mental illness, and drug use. This does not include commitment to a mental...

  16. Assessment of Capacity in an Aging Society

    PubMed Central

    Moye, Jennifer; Marson, Daniel C.; Edelstein, Barry

    2014-01-01

    Over the past 40 years, the assessment and scientific study of capacity in older adults has emerged as a distinct field of clinical and research activity for psychologists. This new field reflects the convergence of several trends: the aging of American society, the growing incidence and prevalence of dementia, and the patient rights, deinstitutionalization, and disability rights movements. Because of these forces, capacity issues now permeate the fabric of everyday life, whether in the form of guardianship petitions, questions of capacity to consent to treatment, the ability to make a new will, or participation in human research. In seeking to resolve these issues, families, clinicians, and legal professionals increasingly turn to psychologists to assess a capacity and to provide empirically supported judgments that properly balance autonomy and protection for the individual. Psychologists have taken a leading role in the development of functional assessment instruments that measure important aspects of the capacity construct. In addition, psychology has been a major contributor to the scientific study of capacity. In collaboration with colleagues from medicine and law, psychologists have articulated crucial theoretical frameworks that integrate legal, clinical, and ethical dimensions of the capacity problem. This article focuses on the evolution of theory, law, science, and practice in the evaluation of capacity in older adults and its recent culmination in a series of interdisciplinary handbooks sponsored by the American Psychological Association and the American Bar Association. PMID:23586491

  17. 24 CFR 574.410 - Capacity.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 3 2010-04-01 2010-04-01 false Capacity. 574.410 Section 574.410... ASSISTANT SECRETARY FOR COMMUNITY PLANNING AND DEVELOPMENT, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT... Project Sponsors § 574.410 Capacity. The grantee shall ensure that any project sponsor with which...

  18. Heritable risk factors associated with language impairments

    PubMed Central

    Barry, J G; Yasin, I; Bishop, D V M

    2007-01-01

    There is a strong genetic contribution to children’s language and literacy impairments. The aim of this study was to determine which aspects of the phenotype are familial by comparing 34 parents of probands with language/literacy impairments and 33 parents of typically developing probands. The parents responded to questionnaires regarding previous history for language/reading impairment and participated in psychometric testing. The psychometric test battery consisted of tests assessing non-verbal IQ, short-term memory, articulation, receptive grammar, reading abilities and spelling. Self-report measures demonstrated a higher prevalence of language and literacy impairments in parents of affected probands (32%) compared with parents of unaffected probands (6%). The two groups of parents differed significantly in their performance on the non-word repetition, oromotor and digit span tasks. Non-word repetition gave the best discrimination between the parent groups even when the data from the parents who actually were impaired as ascertained by direct testing or self-report were removed from the analyses. This suggests that non-word repetition serves as a marker of a family risk for language impairment. The paper concludes with a discussion of issues associated with ascertainment of specific language impairment (SLI). PMID:17233642

  19. Correlates of functional capacity among centenarians.

    PubMed

    Martin, Peter; MacDonald, Maurice; Margrett, Jennifer; Siegler, Ilene; Poon, Leonard W; Jazwinski, S M; Green, R C; Gearing, M; Markesbery, W R; Woodard, J L; Johnson, M A; Tenover, J S; Rodgers, W L; Hausman, D B; Rott, C; Davey, A; Arnold, J

    2013-04-01

    This study investigated correlates of functional capacity among participants of the Georgia Centenarian Study. Six domains (demographics and health, positive and negative affect, personality, social and economic support, life events and coping, distal influences) were related to functional capacity for 234 centenarians and near centenarians (i.e., 98 years and older). Data were provided by proxy informants. Domain-specific multiple regression analyses suggested that younger centenarians, those living in the community and rated to be in better health were more likely to have higher functional capacity scores. Higher scores in positive affect, conscientiousness, social provisions, religious coping, and engaged lifestyle were also associated with higher levels of functional capacity. The results suggest that functional capacity levels continue to be associated with age after 100 years of life and that positive affect levels and past lifestyle activities as reported by proxies are salient factors of adaptation in very late life.

  20. Dating human cultural capacity using phylogenetic principles

    PubMed Central

    Lind, J.; Lindenfors, P.; Ghirlanda, S.; Lidén, K.; Enquist, M.

    2013-01-01

    Humans have genetically based unique abilities making complex culture possible; an assemblage of traits which we term “cultural capacity”. The age of this capacity has for long been subject to controversy. We apply phylogenetic principles to date this capacity, integrating evidence from archaeology, genetics, paleoanthropology, and linguistics. We show that cultural capacity is older than the first split in the modern human lineage, and at least 170,000 years old, based on data on hyoid bone morphology, FOXP2 alleles, agreement between genetic and language trees, fire use, burials, and the early appearance of tools comparable to those of modern hunter-gatherers. We cannot exclude that Neanderthals had cultural capacity some 500,000 years ago. A capacity for complex culture, therefore, must have existed before complex culture itself. It may even originated long before. This seeming paradox is resolved by theoretical models suggesting that cultural evolution is exceedingly slow in its initial stages. PMID:23648831

  1. Working and Net Available Shell Storage Capacity

    EIA Publications

    2016-01-01

    Working and Net Available Shell Storage Capacity is the U.S. Energy Information Administration’s (EIA) report containing storage capacity data for crude oil, petroleum products, and selected biofuels. The report includes tables detailing working and net available shell storage capacity by type of facility, product, and Petroleum Administration for Defense District (PAD District). Net available shell storage capacity is broken down further to show the percent for exclusive use by facility operators and the percent leased to others. Crude oil storage capacity data are also provided for Cushing, Oklahoma, an important crude oil market center. Data are released twice each year near the end of May (data for March 31) and near the end of November (data for September 30).

  2. Minimal Hepatic Encephalopathy Impairs Quality of Life

    PubMed Central

    Agrawal, Swastik; Umapathy, Sridharan; Dhiman, Radha K.

    2015-01-01

    Minimal hepatic encephalopathy (MHE) is the mildest form of the spectrum of neurocognitive impairment in cirrhosis. It is a frequent occurrence in patients of cirrhosis and is detectable only by specialized neurocognitive testing. MHE is a clinically significant disorder which impairs daily functioning, driving performance, work capability and learning ability. It also predisposes to the development of overt hepatic encephalopathy, increased falls and increased mortality. This results in impaired quality of life for the patient as well as significant social and economic burden for health providers and care givers. Early detection and treatment of MHE with ammonia lowering therapy can reverse MHE and improve quality of life. PMID:26041957

  3. Cognitive impairment: classification and open issues.

    PubMed

    Basso, Cristina; Limongi, Federica; Siviero, Paola; Romanato, Giovanna; Noale, Marianna; Maggi, Stefania; Battistin, Leontino; Crepaldi, Gaetano

    2007-10-01

    Several clinically-defined cognitive impairment syndromes, with differing diagnostic criteria and nomenclature, have been proposed to describe nondisabling symptomatic cognitive deficits. Incidence and prevalence rates vary as a result of different diagnostic criteria and sampling procedures across studies. The incidence rates of cognitive impairment increase with age; but no consistent data have been reported on the association with family history, age, sex, education, Apo E4 genotype, depression, and other traditional risk factors for dementia. Several studies have suggested that most patients with cognitive impairment clinically defined will progress to Alzheimer Disease (AD), but rates of conversion vary widely among studies. This review summarizes existing definitions and related epidemiological data.

  4. Relative clause reading in hearing impairment: different profiles of syntactic impairment.

    PubMed

    Szterman, Ronit; Friedmann, Naama

    2014-01-01

    Children with hearing impairment show difficulties in sentences derived by Wh-movement, such as relative clauses and Wh-questions. This study examines the nature of this deficit in 48 hearing impaired children aged 9-12 years and 38 hearing controls. The task involved reading aloud and paraphrasing of object relatives that include a noun-verb heterophonic homograph. The correct pronunciation of the homograph in these sentences depended upon the correct construction of the syntactic structure of the sentence. An analysis of the reading and paraphrasing of each participant exposed two different patterns of syntactic impairment. Some hearing-impaired children paraphrased the object relatives incorrectly but could still read the homograph, indicating impaired assignment of thematic roles alongside good syntactic structure building; other hearing-impaired children could neither read the homograph nor paraphrase the sentence, indicating a structural deficit in the syntactic tree. Further testing of these children confirmed the different impairments: some are impaired only in Wh-movement, whereas others have CP impairment. The syntactic impairment correlated with whether or not a hearing device was fitted by the age of 1 year, but not with the type of hearing device or the depth of hearing loss: children who had a hearing device fitted during the first year of life had better syntactic abilities than children whose hearing devices were fitted later.

  5. Measurement of anaerobic work capacities in humans.

    PubMed

    Green, S

    1995-01-01

    The development of simple, noninvasive tests of work capacities, underpinned primarily by anaerobic metabolism, proliferated in the early 1970s. A 30-second maximal cycle test developed at the Wingate Institute initiated efforts to develop work tests of anaerobic capacities. Such tests can be developed using any ergometer which simulates competitive conditions and enables an accurate determination of mechanical work output. A 10-second all-out test is commonly used to measure maximal work output generated primarily via the hydrolysis of high-energy phosphagens (i.e. the alactic work capacity). In contrast, a variety of constant-load and all-out tests of anaerobic (alactic plus lactic) work capacity have been proposed. It has been suggested that all-out tests provide more information about physiological capabilities and are easier to apply than constant-load tests. The optimal duration for an all-out test of anaerobic work capacity is proposed at 30 seconds, a duration which may also provide the basis for the development of accurate field tests of anaerobic capacity. There is evidence that the y-intercept of the maximal work-derivation regression is a valid work estimate of anaerobic capacity in athletes, although its utility is undermined by the number of tests required for its derivation.

  6. Personality Profiles of Physically Impaired Young Adults.

    ERIC Educational Resources Information Center

    Richman, Lynn C.; Harper, Dennis C.

    1980-01-01

    Different forms of chronic observable disability may have differing impacts on adult personality adjustment. Young adults with cleft lip/palate display fewer personality adjustment problems than those with orthopedic impairment. (Author)

  7. Climate Adaptation Capacity for Conventional Drinking Water Treatment Facilities

    NASA Astrophysics Data System (ADS)

    Levine, A.; Goodrich, J.; Yang, J.

    2013-12-01

    the capacity of treatment facilities and supporting water infrastructure to deliver safe drinking water consistently and reliably. Simulation models of water treatment facilities are used to evaluate the outcome of specific source water quality scenarios on treatment system performance and reliability. Modeling results are used to evaluate the process and operational capacity to respond to transient water quality changes and adapt to longer-term variability in water quality and availability. In some cases, changes in temperature and mineral content serve to improve the overall treatment performance. In addition, the integration of microbially enhanced treatment systems such as biological filtration can provide additional capacity. Conversely, changes in the nutrient and temperature dynamics can trigger algal and cyanobacterial blooms that can impair performance. Research needs are identified and the importance of developing more integrated modeling systems is highlighted.

  8. Photovoltaics effective capacity: Interim final report 2

    SciTech Connect

    Perez, R.; Seals, R.

    1997-11-01

    The authors provide solid evidence, based on more than 8 million data points, that regional photovoltaic (PV) effective capacity is largely unrelated to the region`s solar resource. They confirm, however, that effective capacity is strongly related to load-shape characteristics. The load-shape effective-capacity relationship appears to be valid for end-use loads as small as 100 kW, except possibly in the case of electrically heated buildings. This relationship was used as a tool to produce a US map of PV`s effective capacity. The regions of highest effective capacities include (1) the central US from the northern Great Plains to the metropolitan areas of Chicago and Detroit, down to the lower Mississippi Valley, (2) California and western Arizona, and (3) the northeast metropolitan corridor. The features of this map are considerably different from the traditional solar resource maps. They tend to reflect the socio-economic and climatic factors that indirectly drive PV`s effective capacity: e.g., commercial air-conditioning, little use of electric heat, and strong summer heat waves. The map provides a new and significant insight to a comprehensive valuation of the PV resource. The authors assembled preliminary evidence showing that end-use load type may be related to PV`s effective capacity. Highest effective capacities were found for (nonelectrically heated) office buildings, followed by hospitals. Lowest capacities were found for airports and residences. Many more data points are needed, however, to ascertain and characterize these preliminary findings.

  9. Oro-facial impairment in stroke patients.

    PubMed

    Schimmel, M; Ono, T; Lam, O L T; Müller, F

    2017-01-27

    Stroke is considered one of the leading causes of death and acquired disability with a peak prevalence over the age of 80 years. Stroke may cause debilitating neurological deficiencies that frequently result in sensory deficits, motor impairment, muscular atrophy, cognitive deficits and psychosocial impairment. Oro-facial impairment may occur due to the frequent involvement of the cranial nerves' cortical representation areas, central nervous system pathways or motoneuron pools. The aim of this narrative, non-systematic review was to discuss the implications of stroke on oro-facial functions and oral health-related quality of life (OHRQoL). Stroke patients demonstrate an impaired masticatory performance, possibly due to reduced tongue forces and disturbed oral sensitivity. Furthermore, facial asymmetry is common, but mostly discrete and lip restraining forces are reduced. Bite force is not different between the ipsi- and contra-lesional side. In contrast, the contra-lesional handgrip strength and tongue-palate contact during swallowing are significantly impaired. OHRQoL is significantly reduced mainly because of the functional impairment. It can be concluded that impaired chewing efficiency, dysphagia, facial asymmetry, reduced lip force and OHRQoL are quantifiable symptoms of oro-facial impairment following a stroke. In the absence of functional rehabilitation, these symptoms seem not to improve. Furthermore, stroke affects the upper limb and the masseter muscle differently, both, at a functional and a morphological level. The rehabilitation of stroke survivors should, therefore, also seek to improve the strength and co-ordination of the oro-facial musculature. This would in turn help improve OHRQoL and the masticatory function, subsequently preventing weight loss and malnutrition.

  10. Astronomy for the Blind and Visually Impaired

    NASA Astrophysics Data System (ADS)

    Kraus, S.

    2016-12-01

    This article presents a number of ways of communicating astronomy topics, ranging from classical astronomy to modern astrophysics, to the blind and visually impaired. A major aim of these projects is to provide access which goes beyond the use of the tactile sense to improve knowledge transfer for blind and visually impaired students. The models presented here are especially suitable for young people of secondary school age.

  11. Cognitive impairment after sudden cardiac arrest

    PubMed Central

    Jaszke-Psonka, Magdalena; Piegza, Magdalena; Pudlo, Robert; Piegza, Jacek; Badura-Brzoza, Karina; Leksowska, Aleksandra; Hese, Robert T.; Gorczyca, Piotr W.

    2016-01-01

    Aim To evaluate the incidence and severity of the impairment of selected cognitive functions in patients after sudden cardiac arrest (SCA) in comparison to patients after myocardial infarction without SCA and healthy subjects and to analyze the influence of sociodemographic and clinical parameters and the duration of cardiac arrest on the presence and severity of the described disorders. Material and methods The study group comprised 30 cardiac arrest survivors, the reference group comprised 31 survivors of myocardial infarction without cardiac arrest, and the control group comprised 30 healthy subjects. The Mini-Mental State Examination (MMSE), the Digit Span test from the Wechsler Adult Intelligence Scale, Lauretta Bender’s Visual-Motor Gestalt Test, and the Benton Visual Retention Test (BVRT) were used to assess the presence of cognitive impairment. An original questionnaire developed by the author was used for overall mental state assessment. Results The Bender test demonstrated a significant difference in the presence and severity of visual-motor skills between the study group and the control group, while BVRT and MMSE revealed increased incidence of cognitive impairment in the study group. The Bender and BVRT (D/D)/SS (version D, method D, scaled score) scales indicated cognitive impairment in 53.3% of these patients, while the BVRT (C/A)/SS test indicated cognitive impairment in 40%. For the reference group, the values were 32.3% and 12.9%, respectively. No correlation was found between the severity of cognitive impairment and the duration of cardiac arrest. Conclusions Impairment of visual-motor skills, short-term visual memory, concentration, and visual-motor coordination occurs much more frequently and is more severe in individuals after SCA than in healthy individuals. Impairment of memory trace storage and recall after delay occurs more frequently in patients after SCA than in patients after myocardial infarction without cardiac arrest and in healthy

  12. [Non-pharmacological treatment of cognitive impairment].

    PubMed

    Ramos Cordero, Primitivo; Yubero, Raquel

    2016-06-01

    This article reviews the effect of non-pharmacological therapies in persons with cognitive impairment, especially treatments aimed at brain stimulation and functional maintenance, since both pharmacological and non-pharmacological therapies affecting the cognitive and psychoaffective domains are reviewed in another article in this supplement. The article also discusses the close and reciprocal relationship between cognitive impairment, diet and nutritional status and describes the main nutritional risk factors and protective factors in cognitive decline.

  13. Cargo distributions differentiate pathological axonal transport impairments

    PubMed Central

    Mitchell, Cassie S.; Lee, Robert H.; Coulter, Wallace H.

    2012-01-01

    Axonal transport is an essential process in neurons, analogous to shipping goods, by which energetic and cellular building supplies are carried downstream (anterogradely) and wastes are carried upstream (retrogradely) by molecular motors, which act as cargo porters. Impairments in axonal transport have been linked to devastating and often lethal neurodegenerative diseases, such as Amyotrophic Lateral Sclerosis, Huntington’s, and Alzheimer’s. Axonal transport impairment types include a decrease in available motors for cargo transport (motor depletion), the presence of defective or non-functional motors (motor dilution), and the presence of increased or larger cargos (protein aggregation). An impediment to potential treatment identification has been the inability to determine what type(s) of axonal transport impairment candidates that could be present in a given disease. In this study, we utilize a computational model and common axonal transport experimental metrics to reveal the axonal transport impairment general characteristics or “signatures” that result from three general defect types of motor depletion, motor dilution, and protein aggregation. Our results not only provide a means to discern these general impairments types, they also reveal key dynamic and emergent features of axonal transport, which potentially underlie multiple impairment types. The identified characteristics, as well as the analytical method, can be used to help elucidate the axonal transport impairments observed in experimental and clinical data. For example, using the model-predicted defect signatures, we identify the defect candidates, which are most likely to be responsible for the axonal transport impairments in the G93A SOD1 mouse model of ALS. PMID:22285784

  14. Protective Effect of Tempol on Buthionine Sulfoximine-Induced Mitochondrial Impairment in Hippocampal Derived HT22 Cells

    PubMed Central

    Salvi, Ankita; Patki, Gaurav; Khan, Eisha; Asghar, Mohammad; Salim, Samina

    2016-01-01

    Using a simulated oxidative stress model of hippocampus-derived immortalized cell line (HT22), we report that prooxidant buthionine sulfoximine (BSO, 1 mM, 14 h), without adversely affecting cell viability or morphology, induced oxidative stress by inhibiting glutathione synthesis. BSO treatment also significantly reduced superoxide dismutase (SOD) activity (p < 0.05) and significantly lowered total antioxidant capacity (p < 0.001) in HT22 cells when compared to vehicle treated control cells. Antioxidant tempol, a piperidine nitroxide considered a SOD mimetic, reversed BSO-induced decline in SOD activity (p < 0.01) and also increased BSO-induced decline in total antioxidant capacity (p < 0.05). Interestingly, BSO treatment significantly reduced mitochondrial oxygen consumption (p < 0.05), decreased mitochondrial membrane potential (p < 0.05), and lowered ATP production (p < 0.05) when compared to vehicle treated control cells, collectively indicative of mitochondrial impairment. Antioxidant tempol treatment mitigated all three indicators of mitochondrial impairment. We postulate that BSO-induced oxidative stress in HT22 cells caused mitochondrial impairment, and tempol by increasing SOD activity and improving antioxidant capacity presumably protected the cells from BSO-induced mitochondrial impairment. In conclusion, present study provides an interesting simulation of oxidative stress in hippocampal cells, which will serve as an excellent model to study mitochondrial functions. PMID:27069531

  15. Rehabilitation Medicine Summit: building research capacity.

    PubMed

    Frontera, Walter R; Fuhrer, Marcus J; Jette, Alan M; Chan, Leighton; Cooper, Rory A; Duncan, Pamela W; Kemp, John D; Ottenbacher, Kenneth J; Peckham, P Hunter; Roth, Elliot J; Tate, Denise G

    2005-12-01

    The general objective of the "Rehabilitation Medicine Summit: Building Research Capacity" was to advance and promote research in medical rehabilitation by making recommendations to expand research capacity. The five elements of research capacity that guided the discussions were: 1) researchers; 2) research culture, environment, and infrastructure; 3) funding; 4) partnerships; and 5) metrics. The 100 participants included representatives of professional organizations, consumer groups, academic departments, researchers, governmental funding agencies, and the private sector. The small group discussions and plenary sessions generated an array of problems, possible solutions, and recommended actions. A post-Summit, multi-organizational initiative is called for to pursue the agendas outlined in this report.

  16. Ethylene capacity tops 77 million mty

    SciTech Connect

    Rhodes, A.K.; Knott, D.

    1995-04-17

    World ethylene production capacity is 77.8 million metric tons/year (mty). This total represents an increase of more than 6 million mty, or almost 9%, over last year`s survey. The biggest reason for the large change is more information about plants in the CIS. Also responsible for the increase in capacity is the start-up of several large ethylene plants during the past year. The paper discusses construction of ethylene plants, feedstocks, prices, new capacity, price outlook, and problems in Europe`s ethylene market.

  17. Chewing impairment and associated factors among adults

    PubMed Central

    Figueiredo, Daniela de Rossi; Peres, Marco Aurélio; Luchi, Carla Antoni; Peres, Karen Glazer

    2013-01-01

    OBJECTIVE The aim of this study was to estimate the prevalence of chewing impairment according to sex, and its associated factors in adults. METHODS A cross-sectional population-based study was carried out with 2,016 subjects aged between 20 and 59 years in Florianopolis, SC, Southern Brazil, in 2009. The sampling was undertaken in two stages, census tracts and households. The outcome 'chewing impairment' was obtained from the question "How often do you have chewing impairment due to teeth or denture problems?". Analyses were carried out with demographics and socioeconomic factors, dental services utilization, and self-related oral health using multivariable logistic regression and stratified by sex. RESULTS The response rate was 85.3% (1,720 adults). The prevalence of chewing impairment was 13,0% (95%CI 10.3;15.8) and 18,0% (95%CI 14.6;21.3) among men and women, respectively. Women and men fifty years old and over, who had ten or fewer natural teeth and those who reported toothache were more likely to have chewing impairment. The combination of tooth loss and toothache on chewing impairment was almost four times higher among women. CONCLUSIONS The magnitude of the associations among socioeconomic, demographics and self-related oral health factors was different according to sex, in general higher for women, with emphasis on toothache. The findings suggest that the impact of oral conditions varies by sex. PMID:24626541

  18. Autoimmune autonomic ganglionopathy with reversible cognitive impairment

    PubMed Central

    Gibbons, Christopher H.; Centi, Justin; Vernino, Steven; Freeman, Roy

    2012-01-01

    Background Autoimmune autonomic ganglionopathy (AAG) is a rare disorder of antibody mediated impaired transmission across the autonomic ganglia resulting in severe autonomic failure. Some patients with AAG report cognitive impairment of unclear etiology despite treatment of autonomic symptoms. Objectives To investigate the relationship between orthostatic hypotension, antibody titers and cognitive impairment in patients with AAG. Design Prospective cohort. Setting Academic medical center. Participants Three patients with AAG underwent neuropsychological testing before and after cycles of plasma exchange in both the seated and standing position to determine the effects of orthostatic hypotension and antibody titers on cognition. Main Outcome Measures Patient responses to neuropsychological tests were measured by percent change from baseline in the seated and standing positions pre- and post-plasma exchange to determine the effects of orthostatic hypotension and antibody titers on cognition. Results Orthostatic hypotension and elevated antibody titer were associated independently with neuropsychological impairment (P<0.05), particularly in domains of executive function, sustained attention, and working memory. Cognitive dysfunction improved, even in the seated normotensive position, after plasmapheresis and consequent reduction in antibody levels. Conclusion The data presented in this study demonstrate reversible cognitive impairment is independently associated with both orthostatic hypotension and elevated nicotinic acetylcholine receptor autoantibodies thereby expanding the clinical spectrum of autonomic ganglionopathy and, in so doing, providing an additional treatable cause of cognitive impairment. PMID:22158721

  19. Cognitive impairment and Alzheimer’s disease: Links with oxidative stress and cholesterol metabolism

    PubMed Central

    Sekler, Alejandra; Jiménez, José M; Rojo, Leonel; Pastene, Edgard; Fuentes, Patricio; Slachevsky, Andrea; Maccioni, Ricardo B

    2008-01-01

    Oxidative stress has been implicated in the progression of a number of neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease and amyotrophic lateral sclerosis. We carried out an in-depth study of cognitive impairment and its relationships with oxidative stress markers such as ferric-reducing ability of plasma (FRAP), plasma malondialdehyde and total antioxidative capacity (TAC), as well as cholesterol parameters, in two subsets of subjects, AD patients (n = 59) and a control group of neurologically normal subjects (n = 29), attending the University Hospital Salvador in Santiago, Chile. Cognitive impairment was assessed by a set of neuropsychological tests (Mini-Mental State Examination, Boston Naming Test, Ideomotor Praxia by imitation, Semantic Verbal Fluency of animals or words with initial A, Test of Memory Alteration, Frontal Assessment Battery), while the levels of those oxidative stress markers and cholesterol metabolism parameters were determined according with standard bioassays in fresh plasma samples of the two subgroups of patients. No significant differences were observed when the cholesterol parameters (low-, high-density lipoprotein, total cholesterol) of the AD group were compared with normal controls. Interestingly, a correlation was evidenced when the levels of cognitive impairment were analyzed with respect to the plasma antioxidant capacity (AOC) of patients. In this context, the subset of subjects exhibiting cognitive impairment were divided into two subgroups according with their Global Dementia Scale performance: a subgroup with mild AD and a subgroup with moderate to severe AD. Significant differences in AOC were found between subgroups. The different correlations between cognitive impairment of subgroups of subjects with the oxidative stress profile are discussed in the context of AD pathogenesis. PMID:19043515

  20. Representation of the Solar Capacity Value in the ReEDS Capacity Expansion Model: Preprint

    SciTech Connect

    Sigrin, B.; Sullivan, P.; Ibanez, E.; Margolis, R.

    2014-08-01

    An important emerging issue is the estimation of renewables' contributions to reliably meeting system demand, or their capacity value. While the capacity value of thermal generation can be estimated easily, assessment of wind and solar requires a more nuanced approach due to resource variability. Reliability-based methods, particularly, effective load-carrying capacity (ELCC), are considered to be the most robust techniques for addressing this resource variability. The Regional Energy Deployment System (ReEDS) capacity expansion model and other long-term electricity capacity planning models require an approach to estimating CV for generalized PV and system configurations with low computational and data requirements. In this paper we validate treatment of solar photovoltaic (PV) capacity value by ReEDS capacity expansion model by comparing model results to literature for a range of energy penetration levels. Results from the ReEDS model are found to compare well with both comparisons--despite not being resolved at an hourly scale.

  1. Best Interests in the Mental Capacity Act: Time to say Goodbye?

    PubMed Central

    2016-01-01

    Article 12 of the United Nations Convention on the Rights of Persons with Disabilities, as interpreted by the Committee on the Rights of Persons with Disabilities in General Comment No. 1, offers a vision for law’s response to capacity impairments which differs in crucial ways from that contained in the Mental Capacity Act 2005. The Committee rejects the functional test for capacity and requires that a ‘will and preferences’ paradigm must replace the ‘best interests’ paradigm and that all substitute decision-making regimes must be abolished. This article draws on the position adopted in General Comment No. 1 in evaluating the best interests standard in the Mental Capacity Act. It sets out the normative case for a stronger legislative endorsement of will and preferences and the inclusion of greater support mechanisms but rejects the contention that all substitute decision-making can, or should, be abolished. It also argues that the best interests standard in the Mental Capacity Act retains some revolutionary potential and that, pending legislative reform, this can be further developed through the courts. PMID:28007806

  2. The separate and combined effects of nicotine and alcohol on working memory capacity in nonabstinent smokers.

    PubMed

    Greenstein, Justin E; Kassel, Jon D; Wardle, Margaret C; Veilleux, Jennifer C; Evatt, Daniel P; Heinz, Adrienne J; Roesch, Linda L; Braun, Ashley R; Yates, Marisa C

    2010-04-01

    Research indicates that nicotine and alcohol are often used on the same occasion. However, the reasons for their concurrent use are not well understood. We hypothesized that one reason smokers use tobacco when they drink alcohol is to compensate for alcohol's negative effects on processing capacity with nicotine's enhancement of processing capacity. As such, the present study tested this theory by using an independent groups design to examine the separate and combined acute effects of alcohol and nicotine on working memory (WM) capacity. Nonabstinent daily smokers (n = 127) performed the counting span task (CSPAN) after consuming either an alcohol (men: 0.8 g/kg; women: 0.7 g/kg) or placebo beverage and smoking either nicotinized (1.14 mg nicotine, 15.9 mg tar) or denicotinized (.06 mg nicotine, 17.9 mg tar) cigarettes. Analyses revealed that smokers who smoked the nicotinized cigarettes performed significantly worse on the CSPAN task than smokers who smoked the denicotinized cigarettes. Although there was no main effect of alcohol on WM performance, women exhibited better WM performance than men after consuming alcohol whereas men performed better than women on the WM task after consuming the placebo beverage. Findings also revealed no interaction between the two substances on WM performance. Taken together, results suggest that nicotine impairs nonabstinent smokers' verbal WM capacity and that gender moderates the effects of alcohol on WM. Furthermore, the present findings failed to support the notion that nicotine compensates for alcohol-related decrements in working memory capacity.

  3. Decisional capacity of patients with schizophrenia to consent to research: taking stock.

    PubMed

    Appelbaum, Paul S

    2006-01-01

    With the growth in recent years of studies of decisional capacity for research among people with schizophrenia, this is an opportune time to ask three questions: What have we learned from these studies? What remains to be learned? And what normative issues still need to be resolved? Among the things learned are that patients with schizophrenia, as a group, have lower scores on measures of decisional capacity than normals, but higher performance than patients with dementia. However, performance is highly variable within the group, correlates most strongly with neuropsychological impairment, and seems susceptible in many patients to successful remediation. The issues that remain in need of exploration include the development of a brief screening instrument for decisional capacity that can be used routinely, and the identification of those patients most likely to benefit from more intensive informational procedures. Finally, among the normative issues still in need of resolution are the degree of capacity needed to consent to research participation, how to deal with fluctuating capacity during research projects, and the legitimate extent of surrogate consent for participation of incompetent patients in research.

  4. Computer analysis of slow vital capacity spirograms.

    PubMed

    Primiano, F P; Bacevice, A E; Lough, M D; Doershuk, C F

    1982-01-01

    We have developed a digital computer program which evaluates the vital capacity and its subdivisions, expiratory reserve volume and inspiratory capacity. The algorithm examines the multibreath spirogram, a continuous record of quiet breathing interspersed among repeated slow, large volume maneuvers. Quiet breaths are recognized by comparing features of each breath to the respective average and variation of these features for all breaths. A self-scaling, iterative procedure is used to identify those end-tidal points that most likely represent the subject's functional residual capacity. A least-squared error baseline is then fit through these points to partition the vital capacity. Twenty-three spirograms from patients with documented pulmonary disease were independently analyzed by the computer, a pulmonary function technician, and the laboratory supervisor. No practical differences were found among the results. However, the computer's values, in contrast to those of the technician, were reproducible on repeated trials and free of computational and transcriptional errors.

  5. The Irony of the Capac Nan.

    ERIC Educational Resources Information Center

    Johnson, Robert W.

    1992-01-01

    Presents information on the Capac Nan, the highway system of the Incas. Describes its use by the Spanish conquistadors in the destruction of the Incan empire. Includes suggested classroom uses for the article, a homework assignment, and discussion topics. (DK)

  6. 24 CFR 574.410 - Capacity.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... ASSISTANT SECRETARY FOR COMMUNITY PLANNING AND DEVELOPMENT, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT... Project Sponsors § 574.410 Capacity. The grantee shall ensure that any project sponsor with which...

  7. 7 CFR 1437.402 - Carrying capacity.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Determining Coverage of Forage Intended for Animal Consumption § 1437.402 Carrying capacity. (a) CCC will... management and maintenance practices are improvements over those practices generally associated with...

  8. Capacity of the generalized PPM channel

    NASA Technical Reports Server (NTRS)

    Hamkins, Jon; Klimesh, Matt; McEliece, Bob; Moision, Bruce

    2004-01-01

    We show the capacity of a generalized pulse-position-modulation (PPM) channel, where the input vectors may be any set that allows a transitive group of coordinate permutations, is achieved by a uniform input distribution.

  9. Some Underexamined Aspects of Evaluation Capacity Building

    ERIC Educational Resources Information Center

    Leviton, Laura C.

    2014-01-01

    Evaluation capacity building (ECB) has progressed as a concept since it was the conference theme of the American Evaluation Association in the year 2000. This commentary poses some questions about underexamined issues in ECB about organizations, evaluators, and funders.

  10. Heat Capacity of Hydrous Silicate Melts

    NASA Astrophysics Data System (ADS)

    Robert, G.; Whittington, A. G.; Stechern, A.; Behrens, H.

    2015-12-01

    We determined the heat capacities of four series of glasses and liquids of basaltic and basaltic andesite compositions including two natural remelts from Fuego volcano, Guatemala, and two Fe-free analogs. The samples are low-alkali, Ca- and Mg-rich aluminosilicates with non-bridging oxygen to tetrahedrally-coordinated cation ratios (NBO/T) ranging between 0.33 and 0.67. Differential scanning calorimetry measurements were performed at atmospheric pressure between room temperature and ≈100 K above the glass transition for hydrous samples and up to ≈1800 K for dry samples. The water contents investigated range up to 5.34 wt.% (16.4 mol%). Water does not measurably affect the heat capacity of glasses (T capacity, which generally gets larger with increasing water content and with decreasing polymerization. The onset of the glass transition in hydrous samples also occurs below the Dulong-Petit limit of 3R/g atom. We see little change in liquid heat capacity with increasing water content; hydrous liquid heat capacities are within 3-6% of the dry liquid, at low temperatures just above the glass transition. However, dry liquids show a decrease in heat capacity with increasing temperature above the glass transition, from supercooled to superliquidus temperatures. Liquid heat capacity values just above the glass transition range between 95-100 J/mol K, whereas liquid heat capacity values at superliquidus temperatures are between 85-91 J/mol K. Comparison with other studies of the heat capacity of hydrous glasses and liquids shows that the liquid heat capacity of strongly depolymerized samples (NBO/T ≥ 0.8) increases with increasing water content, whereas depolymerized samples (0.4 ≤ NBO/T ≤ 0.8) or polymerized samples (NBO/T ≤ 0.4) generally show little change or a moderate decrease in liquid heat capacity with increasing water content.

  11. Functional capacity evaluation: an empirical approach.

    PubMed

    Jette, A M

    1980-02-01

    This paper presents an empirical approach to selecting activities of daily living (ADL) to assess the functional capacity of noninstitutionalized individuals with polyarticular disability. The results of structural analyses illustrate the feasibility of substantially reducing the task of assessing functional capacity with a subset of ADL items without sacrificing the comprehensiveness of the assessment. The analyses reveal 5 common functional categories: physical mobility, transfers, home chores, kitchen chores, and personal care, which account for over 50% of the variance in the data.

  12. Heat Capacity, Body Temperature, and Hypothermia

    NASA Astrophysics Data System (ADS)

    Kimbrough, Doris R.

    1998-01-01

    Even when air and water are at the same temperature, water will "feel" distinctly colder to us. This difference is due to the much higher heat capacity of water than of air. Offered here is an interesting life science application of water's high heat capacity and its serious implications for the maintenance of body temperature and the prevention of hypothermia in warm-blooded animals.

  13. Adaptability of the oxidative capacity of motoneurons

    NASA Technical Reports Server (NTRS)

    Chalmers, G. R.; Roy, R. R.; Edgerton, V. R.

    1992-01-01

    Previous studies have demonstrated that a chronic change in neuronal activation can produce a change in soma oxidative capacity, suggesting that: (i) these 2 variables are directly related in neurons and (ii) ion pumping is an important energy requiring activity of a neuron. Most of these studies, however, have focused on reduced activation levels of sensory systems. In the present study the effect of a chronic increase or decrease in motoneuronal activity on motoneuron oxidative capacity and soma size was studied. In addition, the effect of chronic axotomy was studied as an indicator of whether cytoplasmic volume may also be related to the oxidative capacity of motoneurons. A quantitative histochemical assay for succinate dehydrogenase activity was used as a measure of motoneuron oxidative capacity in experimental models in which chronic electromyography has been used to verify neuronal activity levels. Spinal transection reduced, and spinal isolation virtually eliminated lumbar motoneuron electrical activity. Functional overload of the plantaris by removal of its major synergists was used to chronically increase neural activity of the plantaris motor pool. No change in oxidative capacity or soma size resulted from either a chronic increase or decrease in neuronal activity level. These data indicate that the chronic modulation of ionic transport and neurotransmitter turnover associated with action potentials do not induce compensatory metabolic responses in the metabolic capacity of the soma of lumbar motoneurons. Soma oxidative capacity was reduced in the axotomized motoneurons, suggesting that a combination of axoplasmic transport, intracellular biosynthesis and perhaps neurotransmitter turnover represent the major energy demands on a motoneuron. While soma oxidative capacity may be closely related to neural activity in some neural systems, e.g. visual and auditory, lumbar motoneurons appear to be much less sensitive to modulations in chronic activity levels.

  14. The heat capacity of solid antimony selenide

    NASA Astrophysics Data System (ADS)

    Pashinkin, A. S.; Malkova, A. S.; Mikhailova, M. S.

    2008-06-01

    The literature data on the heat capacity of solid antimony selenide over the temperature range 53 K- T m were analyzed. The heat capacity of Sb2Se3 was measured from 350 to 600 K on a DSM-2M calorimeter. The experimental data were used to calculate the dependence C p = a + bT + cT -2 and the thermodynamic functions of solid Sb2Se3 over the temperature range 298.15 700 K.

  15. The association between right ventricular free wall strain and exercise capacity for health check-up subjects

    PubMed Central

    Chang, Wei-Ting; Liu, Yen-Wen; Liu, Ping-Yen; Hsu, Chih-Hsin; Tsai, Wei-Chuan

    2017-01-01

    Background Right ventricular (RV) function has been found to be a major factor of exercise capacity in patients with heart failure. However, the role of RV function in exercise capacity in healthy subjects has not been well studied. This study aims to validate the role of RV strain derived from speckle tracking echocardiography for exercise capacity for health check-up subjects. Methods This study prospectively recruited subjects from a routine health examination. All of them were symptom free. RV function represented by RV strain was derived from speckle tracking echocardiography in addition to traditional echocardiography parameters. Functional capacity was determined by a symptom limited treadmill exercise test with the Bruce protocol. Results Among 164 recruited subjects (age 52.2 ±9.2 years, 66.4% male), 32 subjects represented impaired functional capacity (MET<8), which was significantly correlated with age, left ventricular mass index, left ventricular filling pressure (E/e’), global longitudinal strain of the left ventricle (LVGLS) (-16.0±2.5% vs. -18.9±3.8%, p < 0.001) and RV free wall strain (RVLS_FW) (-17.0±4.9% vs. -21.9±3.2%, p <0.001). After multivariate logistic regression, RVS_FW was an independent predictor for impaired functional capacity (OR 1.62, CI 1.32–1.98; p <0.001). Conclusions In conclusion, RV strain is independently associated with exercise capacity for health check-up subjects. RV function is an important factor for functional capacity. PMID:28288177

  16. Working Memory Capacity as a Dynamic Process

    PubMed Central

    Simmering, Vanessa R.; Perone, Sammy

    2013-01-01

    A well-known characteristic of working memory (WM) is its limited capacity. The source of such limitations, however, is a continued point of debate. Developmental research is positioned to address this debate by jointly identifying the source(s) of limitations and the mechanism(s) underlying capacity increases. Here we provide a cross-domain survey of studies and theories of WM capacity development, which reveals a complex picture: dozens of studies from 50 papers show nearly universal increases in capacity estimates with age, but marked variation across studies, tasks, and domains. We argue that the full pattern of performance cannot be captured through traditional approaches emphasizing single causes, or even multiple separable causes, underlying capacity development. Rather, we consider WM capacity as a dynamic process that emerges from a unified cognitive system flexibly adapting to the context and demands of each task. We conclude by enumerating specific challenges for researchers and theorists that will need to be met in order to move our understanding forward. PMID:23335902

  17. The prevalence and magnitude of impaired cutaneous sensation across the hand in the chronic period post-stroke.

    PubMed

    Bowden, Jocelyn L; Lin, Gaven G; McNulty, Penelope A

    2014-01-01

    Sensation is commonly impaired immediately post-stroke but little is known about the long-term changes in cutaneous sensation that have the capacity to adversely impact independence and motor-function. We investigated cutaneous sensory thresholds across the hand in the chronic post-stroke period. Cutaneous sensation was assessed in 42 community-dwelling stroke patients and compared to 36 healthy subjects. Sensation was tested with calibrated monofilaments at 6 sites on the hand that covered the median, ulnar and radial innervation territories and included both glabrous (hairless) and hairy skin. The motor-function of stroke patients was assessed with the Wolf Motor Function Test and the upper-limb motor Fugl-Meyer Assessment. Impaired cutaneous sensation was defined as monofilament thresholds >3 SD above the mean of healthy subjects and good sensation was ≤ 3 SD. Cutaneous sensation was impaired for 33% of patients and was 40-84% worse on the more-affected side compared to healthy subjects depending on the site (p<0.05). When the stroke patient data were pooled cutaneous sensation fell within the healthy range, although ∼ 1/3 of patients were classified with impaired sensation. Classification by motor-function revealed low levels of impaired sensation. The magnitude of sensory loss was only apparent when the sensory-function of stroke patients was classified as good or impaired. Sensation was most impaired on the dorsum of the hand where age-related changes in monofilament thresholds are minimal in healthy subjects. Although patients with both high and low motor-function had poor cutaneous sensation, overall patients with low motor-function had poorer cutaneous sensation than those with higher motor-function, and relationships were found between motor impairments and sensation at the fingertip and palm. These results emphasize the importance of identifying the presence and magnitude of cutaneous sensory impairments in the chronic period after stroke.

  18. Increased distractibility in schizotypy: Independent of individual differences in working memory capacity?

    PubMed

    Marsh, John E; Vachon, François; Sörqvist, Patrik

    2017-03-01

    Individuals with schizophrenia typically show increased levels of distractibility. This has been attributed to impaired working memory capacity (WMC), since lower WMC is typically associated with higher distractibility, and schizophrenia is typically associated with impoverished WMC. Here, participants performed verbal and spatial serial recall tasks that were accompanied by to-be-ignored speech tokens. For the few trials wherein one speech token was replaced with a different token, impairment was produced to task scores (a deviation effect). Participants subsequently completed a schizotypy questionnaire and a WMC measure. Higher schizotypy scores were associated with lower WMC (as measured with operation span, OSPAN), but WMC and schizotypy scores explained unique variance in relation to the mean magnitude of the deviation effect. These results suggest that schizotypy is associated with heightened domain-general distractibility, but that this is independent of its relationship with WMC.

  19. Brain metabolic correlates of decision making in amnestic mild cognitive impairment.

    PubMed

    Griffith, H Randall; Okonkwo, Ozioma C; den Hollander, Jan A; Belue, Katherine; Copeland, Jacqueline; Harrell, Lindy E; Brockington, John C; Clark, David G; Marson, Daniel C

    2010-01-01

    Persons with amnestic mild cognitive impairment (MCI) have subtle impairments in medical decision-making capacity (MDC). We examined the relationship between proton magnetic resonance spectroscopy (MRS) and MDC in MCI. Twenty-nine MCI patients and 42 controls underwent MRS to obtain ratios of N-acetylaspartate (NAA)/Creatine (Cr), Choline (Cho)/Cr, and myo-Inositol (mI)/Cr of the posterior cingulate. They also completed the Capacity to Consent to Treatment Instrument (CCTI), a vignette-based instrument measuring decisional standards of expressing choice, appreciating consequences of choice, providing rational reasons for choice, and understanding treatment choices. Patients showed abnormal MRS ratios of mI/Cr and Cho/Cr compared to controls, and impairments on the CCTI understanding and reasoning Standards. Performance on the reasoning standard of the CCTI was correlated with NAA/Cr (r = .46, p < .05). The relationship of NAA/Cr with decision-making suggests a role for posterior cortical neuronal functioning in performance of complex IADLs in MCI.

  20. CD160-associated CD8 T-cell functional impairment is independent of PD-1 expression.

    PubMed

    Viganò, Selena; Banga, Riddhima; Bellanger, Florence; Pellaton, Céline; Farina, Alex; Comte, Denis; Harari, Alexandre; Perreau, Matthieu

    2014-09-01

    Expression of co-inhibitory molecules is generally associated with T-cell dysfunction in chronic viral infections such as HIV or HCV. However, their relative contribution in the T-cell impairment remains unclear. In the present study, we have evaluated the impact of the expression of co-inhibitory molecules such as 2B4, PD-1 and CD160 on the functions of CD8 T-cells specific to influenza, EBV and CMV. We show that CD8 T-cell populations expressing CD160, but not PD-1, had reduced proliferation capacity and perforin expression, thus indicating that the functional impairment in CD160(+) CD8 T cells may be independent of PD-1 expression. The blockade of CD160/CD160-ligand interaction restored CD8 T-cell proliferation capacity, and the extent of restoration directly correlated with the ex vivo proportion of CD160(+) CD8 T cells suggesting that CD160 negatively regulates TCR-mediated signaling. Furthermore, CD160 expression was not up-regulated upon T-cell activation or proliferation as compared to PD-1. Taken together, these results provide evidence that CD160-associated CD8 T-cell functional impairment is independent of PD-1 expression.