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Sample records for multiple functions including

  1. Functional Multiple-Set Canonical Correlation Analysis

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

    2012-01-01

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

  2. R5-SHIV induces multiple defects in T cell function during early infection of rhesus macaques including accumulation of T reg cells in lymph nodes.

    Michael Santosuosso

    2011-04-01

    Full Text Available HIV-1 is a pathogen that T cell responses fail to control. HIV-1gp120 is the surface viral envelope glycoprotein that interacts with CD4 T cells and mediates entry. HIV-1gp120 has been implicated in immune dysregulatory functions that may limit anti-HIV antigen-specific T cell responses. We hypothesized that in the context of early SHIV infection, immune dysregulation of antigen-specific T-effector cell and regulatory functions would be detectable and that these would be associated or correlated with measurable concentrations of HIV-1gp120 in lymphoid tissues.Rhesus macaques were intravaginally inoculated with a Clade C CCR5-tropic simian-human immunodeficiency virus, SHIV-1157ipd3N4. HIV-1gp120 levels, antigen-specificity, levels of apoptosis/anergy and frequency and function of Tregs were examined in lymph node and blood derived T cells at 5 and 12 weeks post inoculation.We observed reduced responses to Gag in CD4 and gp120 in CD8 lymph node-derived T cells compared to the peripheral blood at 5 weeks post-inoculation. Reduced antigen-specific responses were associated with higher levels of PD-1 on lymph node-derived CD4 T cells as compared to peripheral blood and uninfected lymph node-derived CD4 T cells. Lymph nodes contained increased numbers of Tregs as compared to peripheral blood, which positively correlated with gp120 levels; T regulatory cell depletion restored CD8 T cell responses to Gag but not to gp120. HIV gp120 was also able to induce T regulatory cell chemotaxis in a dose-dependent, CCR5-mediated manner. These studies contribute to our broader understanding of the ways in which HIV-1 dysregulates T cell function and localization during early infection.

  3. Solution of neutron slowing down equation including multiple inelastic scattering

    El-Wakil, S.A.; Saad, A.E.

    1977-01-01

    The present work is devoted the presentation of an analytical method for the calculation of elastically and inelastically slowed down neutrons in an infinite non absorbing homogeneous medium. On the basis of the Central limit theory (CLT) and the integral transform technique the slowing down equation including inelastic scattering in terms of the Green function of elastic scattering is solved. The Green function is decomposed according to the number of collisions. A formula for the flux at any lethargy O (u) after any number of collisions is derived. An equation for the asymptotic flux is also obtained

  4. Distal radioulnar joint: functional anatomy, including pathomechanics.

    Haugstvedt, J R; Langer, M F; Berger, R A

    2017-05-01

    The distal radioulnar joint allows the human to rotate the forearm to place the hand in a desired position to perform different tasks, without interfering with the grasping function of the hand. The ulna is the stable part of the forearm around which the radius rotates; the stability of the distal radioulnar joint is provided by the interaction between ligaments, muscles and bones. The stabilizing structures are the triangular fibrocartilage complex, the ulnocarpal ligament complex, the extensor carpi ulnaris tendon and tendon sheath, the pronator quadratus, the interosseous membrane and ligament, the bone itself and the joint capsule. The purpose of this review article is to present and illustrate the current understanding of the functional anatomy and pathomechanics of this joint.

  5. Plasma Cell Neoplasms (Including Multiple Myeloma)—Patient Version

    Plasma cell neoplasms occur when abnormal plasma cells form cancerous tumors. When there is only one tumor, the disease is called a plasmacytoma. When there are multiple tumors, it is called multiple myeloma. Start here to find information on plasma cell neoplasms treatment, research, and statistics.

  6. Stages of Plasma Cell Neoplasms (Including Multiple Myeloma)

    ... cancer treatment is also called biotherapy or immunotherapy. Immunomodulators are a type of biologic therapy. Thalidomide , lenalidomide , and pomalidomide are immunomodulators used to treat multiple myeloma and other plasma ...

  7. Treatment Options for Plasma Cell Neoplasms (Including Multiple Myeloma)

    ... cancer treatment is also called biotherapy or immunotherapy. Immunomodulators are a type of biologic therapy. Thalidomide , lenalidomide , and pomalidomide are immunomodulators used to treat multiple myeloma and other plasma ...

  8. Time functions function best as functions of multiple times

    Desain, P.; Honing, H.

    1992-01-01

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

  9. A review of multiple stressor studies that include ionising radiation

    Vanhoudt, Nathalie; Vandenhove, Hildegarde; Real, Almudena; Bradshaw, Clare; Stark, Karolina

    2012-01-01

    Studies were reviewed that investigated the combined effects of ionising radiation and other stressors on non-human biota. The aim was to determine the state of research in this area of science, and determine if a review of the literature might permit a gross generalization as to whether the combined effects of multi-stressors and radiation are fundamentally additive, synergistic or antagonistic. A multiple stressor database was established for different organism groups. Information was collected on species, stressors applied and effects evaluated. Studies were mostly laboratory based and investigated two-component mixtures. Interactions declared positive occurred in 58% of the studies, while 26% found negative interactions. Interactions were dependent on dose/concentration, on organism's life stage and exposure time and differed among endpoints. Except for one study, none of the studies predicted combined effects following Concentration Addition or Independent Action, and hence, no justified conclusions can be made about synergism or antagonism. - This review on multiple stressor studies involving radiation, highlights that most experimental designs used did not allow to deduce the nature of the interactive effects.

  10. Functional equation for the Mordell-Tornheim multiple zeta-function

    Okamoto, Takuya; Onozuka, Tomokazu

    2016-01-01

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

  11. Multiple imaging procedures including MRI for the bladder cancer

    Mikata, Noriharu; Suzuki, Makoto; Takeuchi, Takumi; Kunisawa, Yositaka; Fukutani, Keiko; Kawabe, Kazuki

    1986-01-01

    Endoscopic photography, double contrast cystography, transurethral echography, X-ray CT scan, and MRI (magnetic resonance imaging) were utilized for the staging diagnosis of the four patients with carcinoma of the bladder. In the first case, a 70-year-old man, since all of the five imaging procedures suggested a superficial and pedunculated tumor, his bladder cancer was considered T1. The classification of stage T3 carcinoma was made for the second 86-year-old male. Because all of his imaging examinations showed a tumor infiltrating deep muscle and penetrating the bladder wall. The third case was a 36-year-old male. His clinical stage was diagnosed as T2 or T3a by cystophotography, double contrast cystogram, ultrasonography, and X-ray CT scan. However, MRI showed only thickened bladder wall and the infiltrating tumor could not be distinguished from the hypertrophic wall. The last patient, a 85-year-old female, had a smaller Ta cancer. Her double contrast cystography revealed the small tumor at the lateral bladder wall. But, the tumor could not be detected by transaxial, sagittal and coronal scans. Multiple imaging procedures combining MRI and staging diagnosis of the bladder carcinoma were discussed. (author)

  12. [Multiple sclerosis, loss of functionality and gender].

    Bravo-González, Félix; Álvarez-Roldán, Arturo

    2017-12-01

    To identify the type of support and assistance that patients with multiple sclerosis need in order to cope with the loss of functionality, and to show how gender affects the perception of these needs. Interpretative-phenomenological qualitative study. Granada (Spain). Year: 2014. Intentional sample: 30 patients and 20 family caregivers. Data were gathered from 26 interviews and 4 focus groups. The data were coded and analysed with the NVivo programme. The multiple sclerosis patients and family caregivers had different perceptions of the loss of capacity to undertake activities of daily living. Being able to self care was considered the last vestige of autonomy. The women with multiple sclerosis tried to take on the responsibility of housework, but the male caregivers became gradually involved in these tasks. Gender roles were redefined with respect to housekeeping. The multiple sclerosis patients showed a need for emotional support. Some of the men had abandoned the stereotype of the strong male as a result of the decline in their health. Adaptations in the home took place without planning them in advance. The use of mobility devices started on an occasional basis. A fear of stigma was an obstacle for regular use of assistive technology. Health care for people with multiple sclerosis should include family caregivers. Gender influences the perception that caregivers and patients have of the assistance they require to maximise their quality of life. This flags up several intervention areas for the follow-up and long-term care of these patients by the healthcare system. Copyright © 2017 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

  13. Representations of Multiple-Valued Logic Functions

    Stankovic, Radomir S

    2012-01-01

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

  14. Model for CO2 leakage including multiple geological layers and multiple leaky wells.

    Nordbotten, Jan M; Kavetski, Dmitri; Celia, Michael A; Bachu, Stefan

    2009-02-01

    Geological storage of carbon dioxide (CO2) is likely to be an integral component of any realistic plan to reduce anthropogenic greenhouse gas emissions. In conjunction with large-scale deployment of carbon storage as a technology, there is an urgent need for tools which provide reliable and quick assessments of aquifer storage performance. Previously, abandoned wells from over a century of oil and gas exploration and production have been identified as critical potential leakage paths. The practical importance of abandoned wells is emphasized by the correlation of heavy CO2 emitters (typically associated with industrialized areas) to oil and gas producing regions in North America. Herein, we describe a novel framework for predicting the leakage from large numbers of abandoned wells, forming leakage paths connecting multiple subsurface permeable formations. The framework is designed to exploit analytical solutions to various components of the problem and, ultimately, leads to a grid-free approximation to CO2 and brine leakage rates, as well as fluid distributions. We apply our model in a comparison to an established numerical solverforthe underlying governing equations. Thereafter, we demonstrate the capabilities of the model on typical field data taken from the vicinity of Edmonton, Alberta. This data set consists of over 500 wells and 7 permeable formations. Results show the flexibility and utility of the solution methods, and highlight the role that analytical and semianalytical solutions can play in this important problem.

  15. Altered thalamic functional connectivity in multiple sclerosis

    Liu, Yaou; Liang, Peipeng; Duan, Yunyun; Huang, Jing; Ren, Zhuoqiong; Jia, Xiuqin [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Dong, Huiqing; Ye, Jing [Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Shi, Fu-Dong [Department of Neurology and Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052 (China); Butzkueven, Helmut [Department of Medicine, University of Melbourne, Parkville 3010 (Australia); Li, Kuncheng, E-mail: kunchengli55@gmail.com [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China)

    2015-04-15

    Highlights: •We demonstrated decreased connectivity between thalamus and cortical regions in MS. •Increased intra- and inter-thalamic connectivity was also observed in MS. •The increased functional connectivity is attenuated by increasing disease duration. -- Abstract: Objective: To compare thalamic functional connectivity (FC) in patients with multiple sclerosis (MS) and healthy controls (HC), and correlate these connectivity measures with other MRI and clinical variables. Methods: We employed resting-state functional MRI (fMRI) to examine changes in thalamic connectivity by comparing thirty-five patients with MS and 35 age- and sex-matched HC. Thalamic FC was investigated by correlating low frequency fMRI signal fluctuations in thalamic voxels with voxels in all other brain regions. Additionally thalamic volume fraction (TF), T2 lesion volume (T2LV), EDSS and disease duration were recorded and correlated with the FC changes. Results: MS patients were found to have a significantly lower TF than HC in bilateral thalami. Compared to HC, the MS group showed significantly decreased FC between thalamus and several brain regions including right middle frontal and parahippocampal gyri, and the left inferior parietal lobule. Increased intra- and inter-thalamic FC was observed in the MS group compared to HC. These FC alterations were not correlated with T2LV, thalamic volume or lesions. In the MS group, however, there was a negative correlation between disease duration and inter-thalamic connectivity (r = −0.59, p < 0.001). Conclusion: We demonstrated decreased FC between thalamus and several cortical regions, while increased intra- and inter-thalamic connectivity in MS patients. These complex functional changes reflect impairments and/or adaptations that are independent of T2LV, thalamic volume or presence of thalamic lesions. The negative correlation between disease duration and inter-thalamic connectivity could indicate an adaptive role of thalamus that is

  16. 42 CFR 137.327 - May multiple projects be included in a single construction project agreement?

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false May multiple projects be included in a single construction project agreement? 137.327 Section 137.327 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF...-GOVERNANCE Construction Project Assumption Process § 137.327 May multiple projects be included in a single...

  17. Plasma Cell Neoplasms (Including Multiple Myeloma)—Health Professional Version

    There are several types of plasma cell neoplasms, including monoclonal gammopathy of undetermined significance (MGUS), isolated plasmacytoma of the bone, extramedullary plasmacytoma, and multiple myeloma. Find evidence-based information on plasma cell neoplasms treatment, research, and statistics.

  18. Pulmonary function and dysfunction in multiple sclerosis.

    Smeltzer, S C; Utell, M J; Rudick, R A; Herndon, R M

    1988-11-01

    Pulmonary function was studied in 25 patients with clinically definite multiple sclerosis with a range of motor impairment. Forced vital capacity (FVC), maximal voluntary ventilation (MVV), and maximal expiratory pressure (MEP) were normal in the ambulatory patients (mean greater than or equal to 80% predicted) but reduced in bedridden patients (mean, 38.5%, 31.6%, and 36.3% predicted; FCV, MVV, and MEP, respectively) and wheelchair-bound patients with upper extremity involvement (mean, 69.4%, 50.4%, and 62.6% predicted; FVC, MVV, and MEP, respectively). Forced vital capacity, MVV, and MEP correlated with Kurtzke Expanded Disability Status scores (tau = -0.72, -0.70, and -0.65) and expiratory muscle weakness occurred most frequently. These findings demonstrate that marked expiratory weakness develops in severely paraparetic patients with multiple sclerosis and the weakness increases as the upper extremities become increasingly involved.

  19. Cerebellar abnormalities contribute to disability including cognitive impairment in multiple sclerosis.

    Katrin Weier

    Full Text Available The cerebellum is known to be involved not only in motor but also cognitive and affective processes. Structural changes in the cerebellum in relation to cognitive dysfunction are an emerging topic in the field of neuro-psychiatric disorders. In Multiple Sclerosis (MS cerebellar motor and cognitive dysfunction occur in parallel, early in the onset of the disease, and the cerebellum is one of the predilection sites of atrophy. This study is aimed at determining the relationship between cerebellar volumes, clinical cerebellar signs, cognitive functioning and fatigue in MS. Cerebellar volumetry was conducted using T1-weighted MPRAGE magnetic resonance imaging of 172 MS patients. All patients underwent a clinical and brief neuropsychological assessment (information processing speed, working memory, including fatigue testing. Patients with and without cerebellar signs differed significantly regarding normalized cerebellar total volume (nTCV, normalized brain volume (nBV and whole brain T2 lesion volume (LV. Patients with cerebellar dysfunction likewise performed worse in cognitive tests. A regression analysis indicated that age and nTCV explained 26.3% of the variance in SDMT (symbol digit modalities test performance. However, only age, T2 LV and nBV remained predictors in the full model (r(2 = 0.36. The full model for the prediction of PASAT (Paced Auditory Serial Addition Test scores (r(2 = 0.23 included age, cerebellar and T2 LV. In the case of fatigue, only age and nBV (r(2 = 0.17 emerged as significant predictors. These data support the view that cerebellar abnormalities contribute to disability, including cognitive impairment in MS. However, this contribution does not seem to be independent of, and may even be dominated by wider spread MS pathology as reflected by nBV and T2 LV.

  20. Exact multiple scattering theory of two-nucleus collisions including the Pauli principle

    Gurvitz, S.A.

    1981-01-01

    Exact equations for two-nucleus scattering are derived in which the effects of the Pauli principle are fully included. Our method exploits a modified equation for the scattering of two identical nucleons, which is obtained at the beginning. Considering proton-nucleus scattering we found that the resulting amplitude has two components, one resembling a multiple scattering series for distinguishable particles, and the other a distorted (A-1) nucleon cluster exchange. For elastic pA scattering the multiple scattering amplitude is found in the form of an optical potential expansion. We show that the Kerman-McManus-Thaler theory of the optical potential could be easily modified to include the effects of antisymmetrization of the projectile with the target nucleons. Nucleus-nucleus scattering is studied first for distinguishable target and beam nucleus. Afterwards the Pauli principle is included, where only the case of deuteron-nucleus scattering is discussed in detail. The resulting amplitude has four components. Two of them correspond to modified multiple scattering expansions and the others are distorted (A-1)- and (A-2)- nucleon cluster exchange. The result for d-A scattering is extended to the general case of nucleus-nucleus scattering. The equations are simple to use and as such constitute an improvement over existing schemes

  1. Multiple time-scale optimization scheduling for islanded microgrids including PV, wind turbine, diesel generator and batteries

    Xiao, Zhao xia; Nan, Jiakai; Guerrero, Josep M.

    2017-01-01

    A multiple time-scale optimization scheduling including day ahead and short time for an islanded microgrid is presented. In this paper, the microgrid under study includes photovoltaics (PV), wind turbine (WT), diesel generator (DG), batteries, and shiftable loads. The study considers the maximum...... efficiency operation area for the diesel engine and the cost of the battery charge/discharge cycle losses. The day-ahead generation scheduling takes into account the minimum operational cost and the maximum load satisfaction as the objective function. Short-term optimal dispatch is based on minimizing...

  2. Induced Systemic Tolerance to Multiple Stresses Including Biotic and Abiotic Factors by Rhizobacteria

    Sung-Je Yoo

    2017-06-01

    Full Text Available Recently, global warming and drastic climate change are the greatest threat to the world. The climate change can affect plant productivity by reducing plant adaptation to diverse environments including frequent high temperature; worsen drought condition and increased pathogen transmission and infection. Plants have to survive in this condition with a variety of biotic (pathogen/pest attack and abiotic stress (salt, high/low temperature, drought. Plants can interact with beneficial microbes including plant growth-promoting rhizobacteria, which help plant mitigate biotic and abiotic stress. This overview presents that rhizobacteria plays an important role in induced systemic resistance (ISR to biotic stress or induced systemic tolerance (IST to abiotic stress condition; bacterial determinants related to ISR and/or IST. In addition, we describe effects of rhizobacteria on defense/tolerance related signal pathway in plants. We also review recent information including plant resistance or tolerance against multiple stresses (bioticabiotic. We desire that this review contribute to expand understanding and knowledge on the microbial application in a constantly varying agroecosystem, and suggest beneficial microbes as one of alternative environment-friendly application to alleviate multiple stresses.

  3. Asymptotic functions and multiplication of distributions

    Todorov, T.D.

    1979-01-01

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

  4. The ALMT Gene Family Performs Multiple Functions in Plants

    Jie Liu

    2018-02-01

    Full Text Available The aluminium activated malate transporter (ALMT gene family is named after the first member of the family identified in wheat (Triticum aestivum L.. The product of this gene controls resistance to aluminium (Al toxicity. ALMT genes encode transmembrane proteins that function as anion channels and perform multiple functions involving the transport of organic anions (e.g., carboxylates and inorganic anions in cells. They share a PF11744 domain and are classified in the Fusaric acid resistance protein-like superfamily, CL0307. The proteins typically have five to seven transmembrane regions in the N-terminal half and a long hydrophillic C-terminal tail but predictions of secondary structure vary. Although widely spread in plants, relatively little information is available on the roles performed by other members of this family. In this review, we summarized functions of ALMT gene families, including Al resistance, stomatal function, mineral nutrition, microbe interactions, fruit acidity, light response and seed development.

  5. COMPASS hadron multiplicity measurements and fragmentation functions

    Stolarski, M.

    2016-01-01

    COMPASS is an experiment located at CERN SPS accelerator. For the results presented in this paper a 160 GeV positive muon beam was impinging on 6 LiD target. The COMPASS spectrometer was designed to reconstruct scattered muons and charged hadrons in a wide kinematic range. COMPASS preliminary results on hadron, pion and kaon multiplicities are presented. The hadron and pion data show a good agreement with (N)LO QCD expectations and some of these preliminary data have been already successfully incorporated in the global NLO QCD fits to world data. However, the results for kaon multiplicities, are different from the expectations of the DSS fit. There is also a tension between COMPASS and HERMES results, the only other experiment which measured kaon multiplicities in Semi-Inclusive Deep Inelastic scattering

  6. A Switching Anti-windup Design Using Multiple Lyapunov Functions

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

    2009-01-01

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

  7. The multiplicity function of galaxy systems

    Lucchin, F.

    1988-01-01

    The Press--Schechter approach to the mass function of cosmic structures is discussed by taking into account the effects of non-Guassian primordial perturbations and of the peak constraint, in the framework of the biased galaxy origin

  8. Thermoelectric material including a multiple transition metal-doped type I clathrate crystal structure

    Yang, Jihui [Lakeshore, CA; Shi, Xun [Troy, MI; Bai, Shengqiang [Shanghai, CN; Zhang, Wenqing [Shanghai, CN; Chen, Lidong [Shanghai, CN; Yang, Jiong [Shanghai, CN

    2012-01-17

    A thermoelectric material includes a multiple transition metal-doped type I clathrate crystal structure having the formula A.sub.8TM.sub.y.sub.1.sup.1TM.sub.y.sub.2.sup.2 . . . TM.sub.y.sub.n.sup.nM.sub.zX.sub.46-y.sub.1.sub.-y.sub.2.sub.- . . . -y.sub.n.sub.-z. In the formula, A is selected from the group consisting of barium, strontium, and europium; X is selected from the group consisting of silicon, germanium, and tin; M is selected from the group consisting of aluminum, gallium, and indium; TM.sup.1, TM.sup.2, and TM.sup.n are independently selected from the group consisting of 3d, 4d, and 5d transition metals; and y.sub.1, y.sub.2, y.sub.n and Z are actual compositions of TM.sup.1, TM.sup.2, TM.sup.n, and M, respectively. The actual compositions are based upon nominal compositions derived from the following equation: z=8q.sub.A-|.DELTA.q.sub.1|y.sub.1-|.DELTA.q.sub.2|y.sub.2- . . . -|.DELTA.q.sub.n|y.sub.n, wherein q.sub.A is a charge state of A, and wherein .DELTA.q.sub.1, .DELTA.q.sub.2, .DELTA.q.sub.n are, respectively, the nominal charge state of the first, second, and n-th TM.

  9. Multiple soft limits of cosmological correlation functions

    Joyce, Austin; Khoury, Justin; Simonović, Marko

    2015-01-01

    We derive novel identities satisfied by inflationary correlation functions in the limit where two external momenta are taken to be small. We derive these statements in two ways: using background-wave arguments and as Ward identities following from the fixed-time path integral. Interestingly, these identities allow us to constrain some of the O(q 2 ) components of the soft limit, in contrast to their single-soft analogues. We provide several nontrivial checks of our identities both in the context of resonant non-Gaussianities and in small sound speed models. Additionally, we extend the relation at lowest order in external momenta to arbitrarily many soft legs, and comment on the many-soft extension at higher orders in the soft momentum. Finally, we consider how higher soft limits lead to identities satisfied by correlation functions in large-scale structure

  10. New generalized functions and multiplication of distributions

    Colombeau, J.F.

    1984-01-01

    Since its conception, Quantum Field Theory is based on 'heuristic' computations (in particular products of distributions) that, despite lots of effort, remained meaningless from a mathematical viewpoint. In this book the author presents a new mathematical theory giving a rigorous mathematical sense to these heuristic computations and, from a mathematical viewpoint, to all products of distributions. This new mathematical theory is a new theory of Generalized Functions defined on any open subset Ω of Rsup(n), which are much more general than the distributions on Ω. (Auth.)

  11. GWAS of clinically defined gout and subtypes identifies multiple susceptibility loci that include urate transporter genes.

    Nakayama, Akiyoshi; Nakaoka, Hirofumi; Yamamoto, Ken; Sakiyama, Masayuki; Shaukat, Amara; Toyoda, Yu; Okada, Yukinori; Kamatani, Yoichiro; Nakamura, Takahiro; Takada, Tappei; Inoue, Katsuhisa; Yasujima, Tomoya; Yuasa, Hiroaki; Shirahama, Yuko; Nakashima, Hiroshi; Shimizu, Seiko; Higashino, Toshihide; Kawamura, Yusuke; Ogata, Hiraku; Kawaguchi, Makoto; Ohkawa, Yasuyuki; Danjoh, Inaho; Tokumasu, Atsumi; Ooyama, Keiko; Ito, Toshimitsu; Kondo, Takaaki; Wakai, Kenji; Stiburkova, Blanka; Pavelka, Karel; Stamp, Lisa K; Dalbeth, Nicola; Sakurai, Yutaka; Suzuki, Hiroshi; Hosoyamada, Makoto; Fujimori, Shin; Yokoo, Takashi; Hosoya, Tatsuo; Inoue, Ituro; Takahashi, Atsushi; Kubo, Michiaki; Ooyama, Hiroshi; Shimizu, Toru; Ichida, Kimiyoshi; Shinomiya, Nariyoshi; Merriman, Tony R; Matsuo, Hirotaka

    2017-05-01

    A genome-wide association study (GWAS) of gout and its subtypes was performed to identify novel gout loci, including those that are subtype-specific. Putative causal association signals from a GWAS of 945 clinically defined gout cases and 1213 controls from Japanese males were replicated with 1396 cases and 1268 controls using a custom chip of 1961 single nucleotide polymorphisms (SNPs). We also first conducted GWASs of gout subtypes. Replication with Caucasian and New Zealand Polynesian samples was done to further validate the loci identified in this study. In addition to the five loci we reported previously, further susceptibility loci were identified at a genome-wide significance level (pgout cases, and NIPAL1 and FAM35A for the renal underexcretion gout subtype. While NIPAL1 encodes a magnesium transporter, functional analysis did not detect urate transport via NIPAL1, suggesting an indirect association with urate handling. Localisation analysis in the human kidney revealed expression of NIPAL1 and FAM35A mainly in the distal tubules, which suggests the involvement of the distal nephron in urate handling in humans. Clinically ascertained male patients with gout and controls of Caucasian and Polynesian ancestries were also genotyped, and FAM35A was associated with gout in all cases. A meta-analysis of the three populations revealed FAM35A to be associated with gout at a genome-wide level of significance (p meta =3.58×10 -8 ). Our findings including novel gout risk loci provide further understanding of the molecular pathogenesis of gout and lead to a novel concept for the therapeutic target of gout/hyperuricaemia. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  12. Plasma Cell Neoplasms (Including Multiple Myeloma) Treatment (PDQ®)—Patient Version

    Plasma cell neoplasms occur when abnormal plasma cells or myeloma cells form tumors in the bones or soft tissues of the body. Multiple myeloma, plasmacytoma, lymphoplasmacytic lymphoma, and monoclonal gammopathy of undetermined significance (MGUS) are different types of plasma cell neoplasms. Find out about risk factors, symptoms, diagnostic tests, prognosis, and treatment for these diseases.

  13. Automatic treatment of multiple wound coils in 3D finite element problems including multiply connected regions

    Leonard, P.J.; Lai, H.C.; Eastham, J.F.; Al-Akayshee, Q.H. [Univ. of Bath (United Kingdom)

    1996-05-01

    This paper describes an efficient scheme for incorporating multiple wire wound coils into 3D finite element models. The scheme is based on the magnetic scalar representation with an additional basis for each coil. There are no restrictions on the topology of coils with respect to ferromagnetic and conductor regions. Reduced scalar regions and cuts are automatically generated.

  14. A Case Study of Tack Tiles[R] Literacy Instruction for a Student with Multiple Disabilities Including Congenital Blindness

    Klenk, Jessicia A.; Pufpaff, Lisa A.

    2011-01-01

    Research on literacy instruction for students with multiple disabilities is limited. Empirical research on braille instruction for students with multiple disabilities that include congenital blindness is virtually nonexistent. This case study offers initial insight into possible methods of early braille literacy instruction for a student with…

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

    Woods, Carol M.; Grimm, Kevin J.

    2011-01-01

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

  16. Clinical problems of multiple primary cancers including head and neck cancers. From the viewpoint of radiotherapy

    Nishio, Masamichi; Myojin, Miyako; Nishiyama, Noriaki; Taguchi, Hiroshi; Takagi, Masaru; Tanaka, Katsuhiko

    2003-01-01

    A total of 2144 head and neck cancers were treated by radiotherapy at the National Sapporo Hospital between 1974 and 2001. Of these, 313 (14.6%) were found to have other primary cancers besides head and neck cancer, in which double cancers were 79% and triple or more cancers were 21%. Frequency according to primary site of the first head and neck cancer was oral cavity: 107/603 (17.7%), epipharynx cancer: 7/117 (6.0%), oropharyngeal cancer: 63/257 (24.5%), hypopharyngeal cancer: 65/200 (32.5%), laryngeal cancer: 114/558 (20.4%), and nose/paranasal sinus: 4.9% respectively. Esophageal cancer, head and neck cancer, lung cancer and gastric cancer were very frequent as other primary sites combined with the head and neck. The first onset region was the head and neck in 233 out of 313 cases with multiple primary cancers. The five-year survival rate from the onset of head and neck cancers is 52%, 10-year: 30%, and 5-year cause-specific survival rate 82%, and 10-year: 78%, respectively. The treatment possibilities in multiple primary cancers tend to be limited because the treatment areas are sometimes overlapped. New approaches to the treatment of multiple primary cancers should be considered in the future. (author)

  17. Multiple shooting applied to robust reservoir control optimization including output constraints on coherent risk measures

    Codas, Andrés; Hanssen, Kristian G.; Foss, Bjarne

    2017-01-01

    The production life of oil reservoirs starts under significant uncertainty regarding the actual economical return of the recovery process due to the lack of oil field data. Consequently, investors and operators make management decisions based on a limited and uncertain description of the reservoir....... In this work, we propose a new formulation for robust optimization of reservoir well controls. It is inspired by the multiple shooting (MS) method which permits a broad range of parallelization opportunities and output constraint handling. This formulation exploits coherent risk measures, a concept...

  18. Fast, multiple optimizations of quadratic dose objective functions in IMRT

    Breedveld, Sebastiaan; Storchi, Pascal R M; Keijzer, Marleen; Heijmen, Ben J M

    2006-01-01

    Inverse treatment planning for intensity-modulated radiotherapy may include time consuming, multiple minimizations of an objective function. In this paper, methods are presented to speed up the process of (repeated) minimization of the well-known quadratic dose objective function, extended with a smoothing term that ensures generation of clinically acceptable beam profiles. In between two subsequent optimizations, the voxel-dependent importance factors of the quadratic terms will generally be adjusted, based on an intermediate plan evaluation. The objective function has been written in matrix-vector format, facilitating the use of a recently published, fast quadratic minimization algorithm, instead of commonly applied gradient-based methods. This format also reduces the calculation time in between subsequent minimizations, related to adjustment of the voxel-dependent importance factors. Sparse matrices are used to limit the required amount of computer memory. For three patients, comparisons have been made with a gradient method. Mean speed improvements of up to a factor of 37 have been achieved

  19. Evaluating Functional Decline in Patients with Multiple Sclerosis

    Rosenblum, Sara; Weiss, Patrice L.

    2010-01-01

    Multiple Sclerosis (MS) is a disease with a wide-ranging impact on functional status. The aim of the study was to examine the added value of simultaneously evaluating fatigue, personal ADL and handwriting performance as indicators for functional decline among patients with MS. Participants were 50 outpatients with MS and 26 matched healthy…

  20. Using piecewise sinusoidal basis functions to blanket multiple wire segments

    Lysko, AA

    2009-06-01

    Full Text Available This paper discusses application of the piecewise sinusoidal (PWS) basis function (BF) over a chain of several wire segments, for example as a multiple domain basis function. The usage of PWS BF is compared to results based on the piecewise linear...

  1. Multiple Crack Growth Prediction in AA2024-T3 Friction Stir Welded Joints, Including Manufacturing Effects

    Carlone, Pierpaolo; Citarella, Roberto; Sonne, Mads Rostgaard

    2016-01-01

    A great deal of attention is currently paid by several industries toward the friction stir welding process to realize lightweight structures. Within this aim, the realistic prediction of fatigue behavior of welded assemblies is a key factor. In this work an integrated finite element method - dual...... boundary element method (FEM-DBEM) procedure, coupling the welding process simulation to the subsequent crack growth assessment, is proposed and applied to simulate multiple crack propagation, with allowance for manufacturing effects. The friction stir butt welding process of the precipitation hardened AA...... on a notched specimen. The whole procedure was finally tested comparing simulation outcomes with experimental data. The good agreement obtained highlights the predictive capability of the method. The influence of the residual stress distribution on crack growth and the mutual interaction between propagating...

  2. The dyad palindromic glutathione transferase P enhancer binds multiple factors including AP1.

    Diccianni, M B; Imagawa, M; Muramatsu, M

    1992-10-11

    Glutathione Transferase P (GST-P) gene expression is dominantly regulated by an upstream enhancer (GPEI) consisting of a dyad of palindromically oriented imperfect TPA (12-O-tetradecanoyl-phorbol-13-acetate)-responsive elements (TRE). GPEI is active in AP1-lacking F9 cells as well in AP1-containing HeLa cells. Despite GPEI's similarity to a TRE, c-jun co-transfection has only a minimal effect on transactivation. Antisense c-jun and c-fos co-transfection experiments further demonstrate the lack of a role for AP1 in GPEI mediated trans-activation in F9 cells, although endogenously present AP1 can influence GPEI in HeLa cells. Co-transfection of delta fosB with c-jun, which forms an inactive c-Jun/delta FosB heterodimer that binds TRE sequences, inhibits GPEI-mediated transcription in AP1-lacking F9 cells as well as AP1-containing HeLa cells. These data suggest novel factor(s) other than AP1 are influencing GPEI. Binding studies reveal multiple nucleoproteins bind to GPEI. These factors are likely responsible for the high level of GPEI-mediated transcription observed in the absence of AP1 and during hepatocarcinogenesis.

  3. iStimulation: Apple iPad Use with Children Who Are Visually Impaired, Including Those with Multiple Disabilities

    Campaña, Laura V.; Ouimet, Donald A.

    2015-01-01

    Since its creation in the early 1980s, Light Box, a product developed by the American Printing House for the Blind (APH) that is designed for working on functional vision tasks with children who have visual impairments or multiple disabilities, has been an effective tool to help teach children with visual impairments to locate and track items…

  4. On Multiple Interpolation Functions of the -Genocchi Polynomials

    Jin Jeong-Hee

    2010-01-01

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

  5. GWAS of clinically defined gout and subtypes identifies multiple susceptibility loci that include urate transporter genes

    Nakayama, A.; Nakaoka, H.; Yamamoto, K.; Sakiyama, M.; Shaukat, A.; Toyoda, Y.; Okada, Y.; Kamatani, Y.; Nakamura, T.; Takada, T.; Inoue, K.; Yasujima, T.; Yuasa, H.; Shirahama, Y.; Nakashima, H.; Shimizu, S.; Higashino, T.; Kawamura, Y.; Ogata, H.; Kawaguchi, M.; Ohkawa, Y.; Danjoh, I.; Tokumasu, A.; Ooyama, K.; Ito, T.; Kondo, T.; Wakai, K.; Stiburkova, B.; Pavelka, K.; Stamp, L.K.; Dalbeth, N.; Sakurai, Y.; Suzuki, H; Hosoyamada, M.; Fujimori, S.; Yokoo, T.; Hosoya, T.; Inoue, I.; Takahashi, A.; Kubo, M.; Ooyama, H.; Shimizu, T.; Ichida, K.; Shinomiya, N.; Merriman, T.R.; Matsuo, H.; Andres, M; Joosten, L.A.; Janssen, M.C.H.; Jansen, T.L.; Liote, F.; Radstake, T.R.; Riches, P.L.; So, A.; Tauches, A.K.

    2017-01-01

    OBJECTIVE: A genome-wide association study (GWAS) of gout and its subtypes was performed to identify novel gout loci, including those that are subtype-specific. METHODS: Putative causal association signals from a GWAS of 945 clinically defined gout cases and 1213 controls from Japanese males were

  6. Using Photovoice to Include People with Profound and Multiple Learning Disabilities in Inclusive Research

    Cluley, Victoria

    2017-01-01

    Background: It is now expected that projects addressing the lives of people with learning disabilities include people with learning disabilities in the research process. In the past, such research often excluded people with learning disabilities, favouring the opinions of family members, carers and professionals. The inclusion of the voices of…

  7. Prospective evaluation of dermatologic surgery complications including patients on multiple antiplatelet and anticoagulant medications.

    Bordeaux, Jeremy S; Martires, Kathryn J; Goldberg, Dori; Pattee, Sean F; Fu, Pingfu; Maloney, Mary E

    2011-09-01

    Few prospective studies have evaluated the safety of dermatologic surgery. We sought to determine rates of bleeding, infection, flap and graft necrosis, and dehiscence in outpatient dermatologic surgery, and to examine their relationship to type of repair, anatomic location of repair, antibiotic use, antiplatelet use, or anticoagulant use. Patients presenting to University of Massachusetts Medical School Dermatology Clinic for surgery during a 15-month period were prospectively entered. Medications, procedures, and complications were recorded. Of the 1911 patients, 38% were on one anticoagulant or antiplatelet medication, and 8.0% were on two or more. Risk of hemorrhage was 0.89%. Complex repair (odds ratio [OR] = 5.80), graft repair (OR = 7.58), flap repair (OR = 11.93), and partial repair (OR = 43.13) were more likely to result in bleeding than intermediate repair. Patients on both clopidogrel and warfarin were 40 times more likely to have bleeding complications than all others (P = .03). Risk of infection was 1.3%, but was greater than 3% on the genitalia, scalp, back, and leg. Partial flap necrosis occurred in 1.7% of flaps, and partial graft necrosis occurred in 8.6% of grafts. Partial graft necrosis occurred in 20% of grafts on the scalp and 10% of grafts on the nose. All complications resolved without sequelae. The study was limited to one academic dermatology practice. The rate of complications in dermatologic surgery is low, even when multiple oral anticoagulant and antiplatelet medications are continued, and prophylactic antibiotics are not used. Closure type and use of warfarin or clopidogrel increase bleeding risk. However, these medications should be continued to avoid adverse thrombotic events. Copyright © 2011 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  8. Identification of Multiple Novel Viruses, Including a Parvovirus and a Hepevirus, in Feces of Red Foxes

    van der Giessen, Joke; Haagmans, Bart L.; Osterhaus, Albert D. M. E.; Smits, Saskia L.

    2013-01-01

    Red foxes (Vulpes vulpes) are the most widespread members of the order of Carnivora. Since they often live in (peri)urban areas, they are a potential reservoir of viruses that transmit from wildlife to humans or domestic animals. Here we evaluated the fecal viral microbiome of 13 red foxes by random PCR in combination with next-generation sequencing. Various novel viruses, including a parvovirus, bocavirus, adeno-associated virus, hepevirus, astroviruses, and picobirnaviruses, were identified. PMID:23616657

  9. GWAS of clinically defined gout and subtypes identifies multiple susceptibility loci that include urate transporter genes

    Nakayama, Akiyoshi; Nakaoka, Hirofumi; Yamamoto, Ken; Sakiyama, Masayuki; Shaukat, Amara; Toyoda, Yu; Okada, Yukinori; Kamatani, Yoichiro; Nakamura, Takahiro; Takada, Tappei; Inoue, Katsuhisa; Yasujima, Tomoya; Yuasa, Hiroaki; Shirahama, Yuko; Nakashima, Hiroshi

    2016-01-01

    Objective A genome-wide association study (GWAS) of gout and its subtypes was performed to identify novel gout loci, including those that are subtype-specific. Methods Putative causal association signals from a GWAS of 945 clinically defined gout cases and 1213 controls from Japanese males were replicated with 1396 cases and 1268 controls using a custom chip of 1961 single nucleotide polymorphisms (SNPs). We also first conducted GWASs of gout subtypes. Replication with Caucasian and New Zeala...

  10. Functional analysis screening for multiple topographies of problem behavior.

    Bell, Marlesha C; Fahmie, Tara A

    2018-04-23

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

  11. Multiple function benefit - cost comparison of conservation buffer placement strategies

    Z. Qiu; M.G. Dosskey

    2012-01-01

    Conservation buffers are considered to be effective practices for repairing impaired streams and restoring multiple ecosystem functions in degraded agricultural watersheds. Six different planning strategies for targeting their placement within watersheds were compared in terms of cost-effectiveness for environmental improvement in the 144 km² Neshanic River...

  12. Gender-related differences in functional connectivity in multiple sclerosis

    Schoonheim, M.M.; Hulst, H.E.; Landi, D.; Ciccarelli, O.; Roosendaal, S.D.; Sanz-Arigita, E.J.; Vrenken, H.; Polman, C.H.; Stam, C.J.; Barkhof, F.; Geurts, J.J.G.

    2012-01-01

    Background: Gender effects are strong in multiple sclerosis (MS), with male patients showing a worse clinical outcome than female patients. Functional reorganization of neural activity may contribute to limit disability, and possible gender differences in this process may have important clinical

  13. Predicting Protein Function via Semantic Integration of Multiple Networks.

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

    2016-01-01

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

  14. Medicare capitation model, functional status, and multiple comorbidities: model accuracy

    Noyes, Katia; Liu, Hangsheng; Temkin-Greener, Helena

    2012-01-01

    Objective This study examined financial implications of CMS-Hierarchical Condition Categories (HCC) risk-adjustment model on Medicare payments for individuals with comorbid chronic conditions. Study Design The study used 1992-2000 data from the Medicare Current Beneficiary Survey and corresponding Medicare claims. The pairs of comorbidities were formed based on the prior evidence about possible synergy between these conditions and activities of daily living (ADL) deficiencies and included heart disease and cancer, lung disease and cancer, stroke and hypertension, stroke and arthritis, congestive heart failure (CHF) and osteoporosis, diabetes and coronary artery disease, CHF and dementia. Methods For each beneficiary, we calculated the actual Medicare cost ratio as the ratio of the individual’s annualized costs to the mean annual Medicare cost of all people in the study. The actual Medicare cost ratios, by ADLs, were compared to the HCC ratios under the CMS-HCC payment model. Using multivariate regression models, we tested whether having the identified pairs of comorbidities affects the accuracy of CMS-HCC model predictions. Results The CMS-HCC model underpredicted Medicare capitation payments for patients with hypertension, lung disease, congestive heart failure and dementia. The difference between the actual costs and predicted payments was partially explained by beneficiary functional status and less than optimal adjustment for these chronic conditions. Conclusions Information about beneficiary functional status should be incorporated in reimbursement models since underpaying providers for caring for population with multiple comorbidities may provide severe disincentives for managed care plans to enroll such individuals and to appropriately manage their complex and costly conditions. PMID:18837646

  15. Function of One Regular Separable Relation Set Decided for the Minimal Covering in Multiple Valued Logic

    Liu Yu Zhen

    2016-01-01

    Full Text Available Multiple-valued logic is an important branch of the computer science and technology. Multiple-valued logic studies the theory, multiple-valued circuit & multiple-valued system, and the applications of multiple-valued logic included.In the theory of multiple-valued logic, one primary and important problem is the completeness of function sets, which can be solved depending on the decision for all the precomplete sets(also called maximal closed sets of K-valued function sets noted by PK*, and another is the decision for Sheffer function, which can be totally solved by picking out all of the minimal covering of the precomplete sets. In the function structure theory of multi-logic, decision on Sheffer function is an important role. It contains structure and decision of full multi-logic and partial multi-logic. Its decision is closely related to decision of completeness of function which can be done by deciding the minimal covering of full multi-logic and partial-logic. By theory of completeness of partial multi-logic, we prove that function of one regular separable relation is not minimal covering of PK* under the condition of m = 2, σ = e.

  16. Microvascular decompression for trigeminal neuralgia: comments on a series of 250 cases, including 10 patients with multiple sclerosis.

    Broggi, G; Ferroli, P; Franzini, A; Servello, D; Dones, I

    2000-01-01

    To examine surgical findings and results of microvascular decompression (MVD) for trigeminal neuralgia (TN), including patients with multiple sclerosis, to bring new insight about the role of microvascular compression in the pathogenesis of the disorder and the role of MVD in its treatment. Between 1990 and 1998, 250 patients affected by trigeminal neuralgia underwent MVD in the Department of Neurosurgery of the "Istituto Nazionale Neurologico C Besta" in Milan. Limiting the review to the period 1991-6, to exclude the "learning period" (the first 50 cases) and patients with less than 1 year follow up, surgical findings and results were critically analysed in 148 consecutive cases, including 10 patients with multiple sclerosis. Vascular compression of the trigeminal nerve was found in all cases. The recurrence rate was 15.3% (follow up 1-7 years, mean 38 months). In five of 10 patients with multiple sclerosis an excellent result was achieved (follow up 12-39 months, mean 24 months). Patients with TN for more than 84 months did significantly worse than those with a shorter history (p<0.05). There was no mortality and most complications occurred in the learning period. Surgical complications were not related to age of the patients. Aetiopathogenesis of trigeminal neuralgia remains a mystery. These findings suggest a common neuromodulatory role of microvascular compression in both patients with or without multiple sclerosis rather than a direct causal role. MVD was found to be a safe and effective procedure to relieve typical TN in patients of all ages. It should be proposed as first choice surgery to all patients affected by TN, even in selected cases with multiple sclerosis, to give them the opportunity of pain relief without sensory deficits.

  17. Multiple functions of the S-phase checkpoint mediator.

    Tanaka, Katsunori

    2010-01-01

    There is mounting evidence that replication defects are the major source of spontaneous genomic instability in cells, and that S-phase checkpoints are the principal defense against such instability. The S-phase checkpoint mediator protein Mrc1/Claspin mediates the checkpoint response to replication stress by facilitating phosphorylation of effector kinase by a sensor kinase. In this review, the multiple functions and the regulation of the S-phase checkpoint mediator are discussed.

  18. Towards Integration of Biological and Physiological Functions at Multiple Levels

    Taishin eNomura

    2010-12-01

    Full Text Available An aim of systems physiology today can be stated as to establish logical and quantitative bridges between phenomenological attributes of physiological entities such as cells and organs and physical attributes of biological entities, i.e., biological molecules, allowing us to describe and better understand physiological functions in terms of underlying biological functions. This article illustrates possible schema that can be used for promoting systems physiology by integrating quantitative knowledge of biological and physiological functions at multiple levels of time and space with the use of information technology infrastructure. Emphasis will be made for systematic, modular, hierarchical, and standardized descriptions of mathematical models of the functions and advantages for the use of them.

  19. Multiple-region directed functional connectivity based on phase delays.

    Goelman, Gadi; Dan, Rotem

    2017-03-01

    Network analysis is increasingly advancing the field of neuroimaging. Neural networks are generally constructed from pairwise interactions with an assumption of linear relations between them. Here, a high-order statistical framework to calculate directed functional connectivity among multiple regions, using wavelet analysis and spectral coherence has been presented. The mathematical expression for 4 regions was derived and used to characterize a quartet of regions as a linear, combined (nonlinear), or disconnected network. Phase delays between regions were used to obtain network's temporal hierarchy and directionality. The validity of the mathematical derivation along with the effects of coupling strength and noise on its outcomes were studied by computer simulations of the Kuramoto model. The simulations demonstrated correct directionality for a large range of coupling strength and low sensitivity to Gaussian noise compared with pairwise coherences. The analysis was applied to resting-state fMRI data of 40 healthy young subjects to characterize the ventral visual system, motor system and default mode network (DMN). It was shown that the ventral visual system was predominantly composed of linear networks while the motor system and the DMN were composed of combined (nonlinear) networks. The ventral visual system exhibits its known temporal hierarchy, the motor system exhibits center ↔ out hierarchy and the DMN has dorsal ↔ ventral and anterior ↔ posterior organizations. The analysis can be applied in different disciplines such as seismology, or economy and in a variety of brain data including stimulus-driven fMRI, electrophysiology, EEG, and MEG, thus open new horizons in brain research. Hum Brain Mapp 38:1374-1386, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  20. A predator-prey model with a holling type I functional response including a predator mutual interference

    Seo, G.; DeAngelis, D.L.

    2011-01-01

    The most widely used functional response in describing predator-prey relationships is the Holling type II functional response, where per capita predation is a smooth, increasing, and saturating function of prey density. Beddington and DeAngelis modified the Holling type II response to include interference of predators that increases with predator density. Here we introduce a predator-interference term into a Holling type I functional response. We explain the ecological rationale for the response and note that the phase plane configuration of the predator and prey isoclines differs greatly from that of the Beddington-DeAngelis response; for example, in having three possible interior equilibria rather than one. In fact, this new functional response seems to be quite unique. We used analytical and numerical methods to show that the resulting system shows a much richer dynamical behavior than the Beddington-DeAngelis response, or other typically used functional responses. For example, cyclic-fold, saddle-fold, homoclinic saddle connection, and multiple crossing bifurcations can all occur. We then use a smooth approximation to the Holling type I functional response with predator mutual interference to show that these dynamical properties do not result from the lack of smoothness, but rather from subtle differences in the functional responses. ?? 2011 Springer Science+Business Media, LLC.

  1. Multitasking in multiple sclerosis: can it inform vocational functioning?

    Morse, Chelsea L; Schultheis, Maria T; McKeever, Joshua D; Leist, Thomas

    2013-12-01

    To examine associations between multitasking ability defined by performance on a complex task integrating multiple cognitive domains and vocational functioning in multiple sclerosis (MS). Survey data collection. Laboratory with referrals from an outpatient clinic. Community-dwelling individuals with MS (N=30) referred between October 2011 and June 2012. Not applicable. The modified Six Elements Test (SET) to measure multitasking ability, Fatigue Severity Scale to measure fatigue, several neuropsychological measures of executive functioning, and vocational status. Among the sample, 60% of individuals have reduced their work hours because of MS symptoms (cutback employment group) and 40% had maintained their work hours. Among both groups, SET performance was significantly associated with performance on several measures of neuropsychological functioning. Individuals in the cutback employment group demonstrated significantly worse overall performance on the SET (P=.041). Logistic regression was used to evaluate associations between SET performance and vocational status, while accounting for neuropsychological performance and fatigue. The overall model was significant (χ(2)3=8.65, P=.032), with fatigue [Exp(B)=.83, P=.01] and multitasking ability [Exp(B)=.60, P=.043] retained as significant predictors. Multitasking ability may play an important role in performance at work for individuals with MS. Given that multitasking was associated with vocational functioning, future efforts should assess the usefulness of incorporating multitasking ability into rehabilitation planning. Copyright © 2013 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  2. Psychological functioning in primary progressive versus secondary progressive multiple sclerosis

    Vleugels, L; Pfennings, L E; Pouwer, F

    1998-01-01

    Psychological functioning in two types of multiple sclerosis (MS) patients is assessed: primary progressive (PP) and secondary progressive (SP) patients. On the basis of differences in clinical course and underlying pathology we hypothesized that primary progressive patients and secondary...... progressive patients might have different psychological functioning. Seventy patients treated in an MS centre were examined cross-sectionally. Forty had an SP course of MS and 30 a PP course. The 33 male and 37 female patients had a mean age of 48.4 years (SD 11.2) and mean age of onset of MS of 30.7 years...... (SD 11.1). Patients completed questionnaires measuring among others the following aspects of psychological functioning: depression (BDI, SCL-90), anxiety (STAI, SCL-90), agoraphobia (SCL-90), somatic complaints (SCL-90), hostility (SCL-90) and attitude towards handicap (GHAS). Patients with a PP...

  3. Direct fragmentation of quarkonia including Fermi motion using light-cone wave function

    Nobary, M.A. Gomshi [Razi University, Department of Physics, Faculty of Science, Kermanshah (Iran); A.E.O.I., Center for Theoretical Physics and Mathematics, Tehran (Iran); Javadi, B. [Razi University, Department of Physics, Faculty of Science, Kermanshah (Iran)

    2005-07-01

    We investigate the effect of Fermi motion on the direct fragmentation of the J/{psi} and {upsilon} states employing a light-cone wave function. Consistent with such a wave function we set up the kinematics of a heavy quark fragmenting into quarkonia such that the Fermi motion of the constituents splits into a longitudinal as well as a transverse direction and thus calculate the fragmentation functions for these states. In the framework of our investigation, we estimate that the fragmentation probabilities of J/{psi} and {upsilon} may increase at least up to 14 percent when including this degree of freedom. (orig.)

  4. Mode Shape Analysis of Multiple Cracked Functionally Graded Timoshenko Beams

    Tran Van Lien

    Full Text Available Abstract The present paper addresses free vibration of multiple cracked Timoshenko beams made of Functionally Graded Material (FGM. Cracks are modeled by rotational spring of stiffness calculated from the crack depth and material properties vary according to the power law throughout the beam thickness. Governing equations for free vibration of the beam are formulated with taking into account actual position of the neutral plane. The obtained frequency equation and mode shapes are used for analysis of the beam mode shapes in dependence on the material and crack parameters. Numerical results validate usefulness of the proposed herein theory and show that mode shapes are good indication for detecting multiple cracks in Timoshenko FGM beams.

  5. Reliability analysis of the auxiliary feedwater system of Angra-1 including common cause failures using the multiple greek letter model

    Lapa, Celso Marcelo Franklin.

    1996-05-01

    The use of redundancy to increase the reliability of industrial systems make them subject to the occurrence of common cause events. The industrial experience and the results of safety analysis studies have indicated that common cause failures are the main contributors to the unreliability of plants that have redundant systems, specially in nuclear power plants. In this Thesis procedures are developed in order to include the impact of common cause failures in the calculation of the top event occurrence probability of the Auxiliary Feedwater System in a typical two-loop Nuclear Power Plant (PWR). For this purpose the Multiple Greek Letter Model is used. (author). 14 refs., 10 figs., 11 tabs

  6. Association between functional performance and executive cognitive functions in an elderly population including patients with low ankle–brachial index

    Ferreira, Naomi Vidal; Cunha, Paulo Jannuzzi; da Costa, Danielle Irigoyen; dos Santos, Fernando; Costa, Fernando Oliveira; Consolim-Colombo, Fernanda; Irigoyen, Maria Cláudia

    2015-01-01

    Introduction Peripheral arterial disease, as measured by the ankle–brachial index (ABI), is prevalent among the elderly, and is associated with functional performance, assessed by the 6-minute walk test (6MWT). Executive cognitive function (ECF) impairments are also prevalent in this population, but no existing study has investigated the association between ECF and functional performance in an elderly population including individuals with low ABI. Aim To investigate the association between functional performance, as measured by the 6MWT, and loss in ECF, in an elderly sample including individuals with low ABI. Method The ABI group was formed by 26 elderly individuals with low ABI (mean ABI: 0.63±0.19), and the control group was formed by 40 elderly individuals with normal ABI (mean ABI: 1.08±0.07). We analyzed functional performance using the 6MWT, global cognition using the Mini-Mental State Examination (MMSE), and ECF using the Digit Span for assessing attention span and working memory, the Stroop Color Word Test (SCWT) for assessing information processing speed and inhibitory control/impulsivity, and the Controlled Oral Word Association Test (COWAT) for assessing semantic verbal fluency and phonemic verbal fluency. We also used a factor analysis on all of the ECF tests (global ECF). Results Before adjustment, the ABI group performed worse on global cognition, attention span, working memory, inhibitory control/impulsivity, semantic verbal fluency, and phonemic verbal fluency. After adjustment, the ABI group performance remained worse for working memory and semantic verbal fluency. In a simple correlation analysis including all of the subjects, the 6MWT was associated with global cognition, attention span, working memory, information processing speed, inhibitory control/impulsivity, semantic verbal fluency, and global ECF. After adjustment, all the associations remained statistically significant. Conclusion This study found an independent association between

  7. A new wall function boundary condition including heat release effect for supersonic combustion flows

    Gao, Zhen-Xun; Jiang, Chong-Wen; Lee, Chun-Hian

    2016-01-01

    Highlights: • A new wall function including heat release effect is theoretically derived. • The new wall function is a unified form holding for flows with/without combustion. • The new wall function shows good results for a supersonic combustion case. - Abstract: A new wall function boundary condition considering combustion heat release effect (denoted as CWFBC) is proposed, for efficient predictions of skin friction and heat transfer in supersonic combustion flows. Based on a standard flow model including boundary-layer combustion, the Shvab–Zeldovich coupling parameters are introduced to derive a new velocity law-of-the-wall including the influence of combustion. For the temperature law-of-the-wall, it is proposed to use the enthalpy–velocity relation, instead of the Crocco–Busemann equation, to eliminate explicit influence of chemical reactions. The obtained velocity and temperature law-of-the-walls constitute the CWFBC, which is a unified form simultaneously holding for single-species, multi-species mixing and multi-species reactive flows. The subsequent numerical simulations using this CWFBC on an experimental case indicate that the CWFBC could accurately reflect the influences on the skin friction and heat transfer by the chemical reactions and heat release, and show large improvements compared to previous WFBC. Moreover, the CWFBC can give accurate skin friction and heat flux for a coarse mesh with y"+ up to 200 for the experimental case, except for slightly larger discrepancy of the wall heat flux around ignition position.

  8. TS Fuzzy Model-Based Controller Design for a Class of Nonlinear Systems Including Nonsmooth Functions

    Vafamand, Navid; Asemani, Mohammad Hassan; Khayatiyan, Alireza

    2018-01-01

    This paper proposes a novel robust controller design for a class of nonlinear systems including hard nonlinearity functions. The proposed approach is based on Takagi-Sugeno (TS) fuzzy modeling, nonquadratic Lyapunov function, and nonparallel distributed compensation scheme. In this paper, a novel...... criterion, new robust controller design conditions in terms of linear matrix inequalities are derived. Three practical case studies, electric power steering system, a helicopter model and servo-mechanical system, are presented to demonstrate the importance of such class of nonlinear systems comprising...

  9. Comparison and clinical utility evaluation of four multiple allergen simultaneous tests including two newly introduced fully automated analyzers

    John Hoon Rim

    2016-04-01

    Full Text Available Background: We compared the diagnostic performances of two newly introduced fully automated multiple allergen simultaneous tests (MAST analyzers with two conventional MAST assays. Methods: The serum samples from a total of 53 and 104 patients were tested for food panels and inhalant panels, respectively, in four analyzers including AdvanSure AlloScreen (LG Life Science, Korea, AdvanSure Allostation Smart II (LG Life Science, PROTIA Allergy-Q (ProteomeTech, Korea, and RIDA Allergy Screen (R-Biopharm, Germany. We compared not only the total agreement percentages but also positive propensities among four analyzers. Results: Evaluation of AdvanSure Allostation Smart II as upgraded version of AdvanSure AlloScreen revealed good concordance with total agreement percentages of 93.0% and 92.2% in food and inhalant panel, respectively. Comparisons of AdvanSure Allostation Smart II or PROTIA Allergy-Q with RIDA Allergy Screen also showed good concordance performance with positive propensities of two new analyzers for common allergens (Dermatophagoides farina and Dermatophagoides pteronyssinus. The changes of cut-off level resulted in various total agreement percentage fluctuations among allergens by different analyzers, although current cut-off level of class 2 appeared to be generally suitable. Conclusions: AdvanSure Allostation Smart II and PROTIA Allergy-Q presented favorable agreement performances with RIDA Allergy Screen, although positive propensities were noticed in common allergens. Keywords: Multiple allergen simultaneous test, Automated analyzer

  10. Compound K, a Ginsenoside Metabolite, Inhibits Colon Cancer Growth via Multiple Pathways Including p53-p21 Interactions

    Eugene B. Chang

    2013-01-01

    Full Text Available Compound K (20-O-beta-D-glucopyranosyl-20(S-protopanaxadiol, CK, an intestinal bacterial metabolite of ginseng protopanaxadiol saponins, has been shown to inhibit cell growth in a variety of cancers. However, the mechanisms are not completely understood, especially in colorectal cancer (CRC. A xenograft tumor model was used first to examine the anti-CRC effect of CK in vivo. Then, multiple in vitro assays were applied to investigate the anticancer effects of CK including antiproliferation, apoptosis and cell cycle distribution. In addition, a qPCR array and western blot analysis were executed to screen and validate the molecules and pathways involved. We observed that CK significantly inhibited the growth of HCT-116 tumors in an athymic nude mouse xenograft model. CK significantly inhibited the proliferation of human CRC cell lines HCT-116, SW-480, and HT-29 in a dose- and time-dependent manner. We also observed that CK induced cell apoptosis and arrested the cell cycle in the G1 phase in HCT-116 cells. The processes were related to the upregulation of p53/p21, FoxO3a-p27/p15 and Smad3, and downregulation of cdc25A, CDK4/6 and cyclin D1/3. The major regulated targets of CK were cyclin dependent inhibitors, including p21, p27, and p15. These results indicate that CK inhibits transcriptional activation of multiple tumor-promoting pathways in CRC, suggesting that CK could be an active compound in the prevention or treatment of CRC.

  11. Assessment of patients with multiple sclerosis according to tests of the Multiple Sclerosis Functional Composite

    Anelise Ineu Figueiredo

    Full Text Available Abstract Introduction: The Multiple Sclerosis Functional Composite (MSFC is a scale that evaluates the functional and cognitive aspects of patients with multiple sclerosis (MS. Objective: To compare the performance of individuals with the relapsing-remitting form of MS (RRMS with a group of healthy subjects using the MSFC. Methods: Twenty subjects were investigated in this study, consisting of 10 patients with clinical diagnosis of RRMS and 10 controls with similar gender and age to the group with the disease. The three tests that comprise the MSFC were used for the evaluation of gait, upper limb motor function and cognition (memory and processing speed. Student's t-test was used to assess data with normal distribution and data with skewed distribution were evaluated using the Mann-Whitney test. Results: The results showed that the patients with RRMS took longer to perform the locomotion test (6.91 ± 2.35 compared to the control group (5.16 ± 1.28. The MS group (22.06 ± 5.44 also showed greater difficulty in performing a task with the dominant upper limb compared to the healthy subjects (17.79 ± 2.96. No statistically significant difference was found between the groups in the performance of cognitive tasks (p = .65. Conclusion: The use of the MSFC tests proved valuable for measuring possible motor and cognitive impairments in patients with RRMS. Thus, it is suggested that this scale is adopted in clinical practice, improving therapies for the treatment of MS patients and thereby providing them a better quality of life.

  12. Representing uncertainty in objective functions: extension to include the influence of serial correlation

    Croke, B. F.

    2008-12-01

    The role of performance indicators is to give an accurate indication of the fit between a model and the system being modelled. As all measurements have an associated uncertainty (determining the significance that should be given to the measurement), performance indicators should take into account uncertainties in the observed quantities being modelled as well as in the model predictions (due to uncertainties in inputs, model parameters and model structure). In the presence of significant uncertainty in observed and modelled output of a system, failure to adequately account for variations in the uncertainties means that the objective function only gives a measure of how well the model fits the observations, not how well the model fits the system being modelled. Since in most cases, the interest lies in fitting the system response, it is vital that the objective function(s) be designed to account for these uncertainties. Most objective functions (e.g. those based on the sum of squared residuals) assume homoscedastic uncertainties. If model contribution to the variations in residuals can be ignored, then transformations (e.g. Box-Cox) can be used to remove (or at least significantly reduce) heteroscedasticity. An alternative which is more generally applicable is to explicitly represent the uncertainties in the observed and modelled values in the objective function. Previous work on this topic addressed the modifications to standard objective functions (Nash-Sutcliffe efficiency, RMSE, chi- squared, coefficient of determination) using the optimal weighted averaging approach. This paper extends this previous work; addressing the issue of serial correlation. A form for an objective function that includes serial correlation will be presented, and the impact on model fit discussed.

  13. Progressive multiple sclerosis, cognitive function, and quality of life.

    Højsgaard Chow, Helene; Schreiber, Karen; Magyari, Melinda; Ammitzbøll, Cecilie; Börnsen, Lars; Romme Christensen, Jeppe; Ratzer, Rikke; Soelberg Sørensen, Per; Sellebjerg, Finn

    2018-02-01

    Patients with progressive multiple sclerosis (MS) often have cognitive impairment in addition to physical impairment. The burden of cognitive and physical impairment progresses over time, and may be major determinants of quality of life. The aim of this study was to assess to which degree quality of life correlates with physical and cognitive function in progressive MS. This is a retrospective study of 52 patients with primary progressive ( N  = 18) and secondary progressive MS ( N  = 34). Physical disability was assessed using the Expanded Disability Status Scale, Timed 25 Foot Walk (T25FW) test and 9-Hole Peg Test (9HPT). Cognitive function was assessed using Symbol Digit Modalities Test (SDMT), Paced Auditory Serial Addition Test, and Trail Making Test B (TRAIL-B). In addition, quality of life was assessed by the Short Form 36 (SF-36) questionnaire. Only measures of cognitive function correlated with the overall SF-36 quality of life score and the Mental Component Summary score from the SF-36. The only physical measure that correlated with a measure of quality of life was T25FW test, which correlated with the Physical Component Summary from the SF-36. We found no other significant correlations between the measures of cognitive function and the overall physical measures but interestingly, we found a possible relationship between the 9HPT score for the nondominant hand and the SDMT and TRAIL-B. Our findings support inclusion of measures of cognitive function in the assessment of patients with progressive MS as these correlated closer with quality of life than measures of physical impairment.

  14. Building a functional multiple intelligences theory to advance educational neuroscience.

    Cerruti, Carlo

    2013-01-01

    A key goal of educational neuroscience is to conduct constrained experimental research that is theory-driven and yet also clearly related to educators' complex set of questions and concerns. However, the fields of education, cognitive psychology, and neuroscience use different levels of description to characterize human ability. An important advance in research in educational neuroscience would be the identification of a cognitive and neurocognitive framework at a level of description relatively intuitive to educators. I argue that the theory of multiple intelligences (MI; Gardner, 1983), a conception of the mind that motivated a past generation of teachers, may provide such an opportunity. I criticize MI for doing little to clarify for teachers a core misunderstanding, specifically that MI was only an anatomical map of the mind but not a functional theory that detailed how the mind actually processes information. In an attempt to build a "functional MI" theory, I integrate into MI basic principles of cognitive and neural functioning, namely interregional neural facilitation and inhibition. In so doing I hope to forge a path toward constrained experimental research that bears upon teachers' concerns about teaching and learning.

  15. Probability of detection as a function of multiple influencing parameters

    Pavlovic, Mato

    2014-10-15

    Non-destructive testing is subject to measurement uncertainties. In safety critical applications the reliability assessment of its capability to detect flaws is therefore necessary. In most applications, the flaw size is the single most important parameter that influences the probability of detection (POD) of the flaw. That is why the POD is typically calculated and expressed as a function of the flaw size. The capability of the inspection system to detect flaws is established by comparing the size of reliably detected flaw with the size of the flaw that is critical for the structural integrity. Applications where several factors have an important influence on the POD are investigated in this dissertation. To devise a reliable estimation of the NDT system capability it is necessary to express the POD as a function of all these factors. A multi-parameter POD model is developed. It enables POD to be calculated and expressed as a function of several influencing parameters. The model was tested on the data from the ultrasonic inspection of copper and cast iron components with artificial flaws. Also, a technique to spatially present POD data called the volume POD is developed. The fusion of the POD data coming from multiple inspections of the same component with different sensors is performed to reach the overall POD of the inspection system.

  16. Wavefield reconstruction inversion with a multiplicative cost function

    da Silva, Nuno V.; Yao, Gang

    2018-01-01

    We present a method for the automatic estimation of the trade-off parameter in the context of wavefield reconstruction inversion (WRI). WRI formulates the inverse problem as an optimisation problem, minimising the data misfit while penalising with a wave equation constraining term. The trade-off between the two terms is balanced by a scaling factor that balances the contributions of the data-misfit term and the constraining term to the value of the objective function. If this parameter is too large then it implies penalizing for the wave equation imposing a hard constraint in the inversion. If it is too small, then this leads to a poorly constrained solution as it is essentially penalizing for the data misfit and not taking into account the physics that explains the data. This paper introduces a new approach for the formulation of WRI recasting its formulation into a multiplicative cost function. We demonstrate that the proposed method outperforms the additive cost function when the trade-off parameter is appropriately scaled in the latter, when adapting it throughout the iterations, and when the data is contaminated with Gaussian random noise. Thus this work contributes with a framework for a more automated application of WRI.

  17. Probability of detection as a function of multiple influencing parameters

    Pavlovic, Mato

    2014-01-01

    Non-destructive testing is subject to measurement uncertainties. In safety critical applications the reliability assessment of its capability to detect flaws is therefore necessary. In most applications, the flaw size is the single most important parameter that influences the probability of detection (POD) of the flaw. That is why the POD is typically calculated and expressed as a function of the flaw size. The capability of the inspection system to detect flaws is established by comparing the size of reliably detected flaw with the size of the flaw that is critical for the structural integrity. Applications where several factors have an important influence on the POD are investigated in this dissertation. To devise a reliable estimation of the NDT system capability it is necessary to express the POD as a function of all these factors. A multi-parameter POD model is developed. It enables POD to be calculated and expressed as a function of several influencing parameters. The model was tested on the data from the ultrasonic inspection of copper and cast iron components with artificial flaws. Also, a technique to spatially present POD data called the volume POD is developed. The fusion of the POD data coming from multiple inspections of the same component with different sensors is performed to reach the overall POD of the inspection system.

  18. Multiple image x-radiography for functional lung imaging

    Aulakh, G. K.; Mann, A.; Belev, G.; Wiebe, S.; Kuebler, W. M.; Singh, B.; Chapman, D.

    2018-01-01

    Detection and visualization of lung tissue structures is impaired by predominance of air. However, by using synchrotron x-rays, refraction of x-rays at the interface of tissue and air can be utilized to generate contrast which may in turn enable quantification of lung optical properties. We utilized multiple image radiography, a variant of diffraction enhanced imaging, at the Canadian light source to quantify changes in unique x-ray optical properties of lungs, namely attenuation, refraction and ultra small-angle scatter (USAXS or width) contrast ratios as a function of lung orientation in free-breathing or respiratory-gated mice before and after intra-nasal bacterial endotoxin (lipopolysaccharide) instillation. The lung ultra small-angle scatter and attenuation contrast ratios were significantly higher 9 h post lipopolysaccharide instillation compared to saline treatment whereas the refraction contrast decreased in magnitude. In ventilated mice, end-expiratory pressures result in an increase in ultra small-angle scatter contrast ratio when compared to end-inspiratory pressures. There were no detectable changes in lung attenuation or refraction contrast ratio with change in lung pressure alone. In effect, multiple image radiography can be applied towards following optical properties of lung air-tissue barrier over time during pathologies such as acute lung injury.

  19. A Unified Approach to Functional Principal Component Analysis and Functional Multiple-Set Canonical Correlation.

    Choi, Ji Yeh; Hwang, Heungsun; Yamamoto, Michio; Jung, Kwanghee; Woodward, Todd S

    2017-06-01

    Functional principal component analysis (FPCA) and functional multiple-set canonical correlation analysis (FMCCA) are data reduction techniques for functional data that are collected in the form of smooth curves or functions over a continuum such as time or space. In FPCA, low-dimensional components are extracted from a single functional dataset such that they explain the most variance of the dataset, whereas in FMCCA, low-dimensional components are obtained from each of multiple functional datasets in such a way that the associations among the components are maximized across the different sets. In this paper, we propose a unified approach to FPCA and FMCCA. The proposed approach subsumes both techniques as special cases. Furthermore, it permits a compromise between the techniques, such that components are obtained from each set of functional data to maximize their associations across different datasets, while accounting for the variance of the data well. We propose a single optimization criterion for the proposed approach, and develop an alternating regularized least squares algorithm to minimize the criterion in combination with basis function approximations to functions. We conduct a simulation study to investigate the performance of the proposed approach based on synthetic data. We also apply the approach for the analysis of multiple-subject functional magnetic resonance imaging data to obtain low-dimensional components of blood-oxygen level-dependent signal changes of the brain over time, which are highly correlated across the subjects as well as representative of the data. The extracted components are used to identify networks of neural activity that are commonly activated across the subjects while carrying out a working memory task.

  20. The hypocretins/orexins: integrators of multiple physiological functions

    Li, Jingcheng; Hu, Zhian; Lecea, Luis

    2014-01-01

    The hypocretins (Hcrts), also known as orexins, are two peptides derived from a single precursor produced in the posterior lateral hypothalamus. Over the past decade, the orexin system has been associated with numerous physiological functions, including sleep/arousal, energy homeostasis, endocrine, visceral functions and pathological states, such as narcolepsy and drug abuse. Here, we review the discovery of Hcrt/orexins and their receptors and propose a hypothesis as to how the orexin system orchestrates these multifaceted physiological functions. Linked ArticlesThis article is part of a themed section on Orexin Receptors. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-2 PMID:24102345

  1. Defining the breeding goal for a sheep breed including production and functional traits using market data.

    Theodoridis, A; Ragkos, A; Rose, G; Roustemis, D; Arsenos, G

    2017-11-16

    In this study, the economic values for production and functional traits of dairy sheep are estimated through the application of a profit function model using farm-level technical and economic data. The traits incorporated in the model were milk production, prolificacy, fertility, milking speed, longevity and mastitis occurrence. The economic values for these traits were derived as the approximate partial derivative of the specified profit function. A sensitivity analysis was also conducted in order to examine how potential changes in input and output prices would affect the breeding goal. The estimated economic values of the traits revealed their economic impact on the definition of the breeding goal for the specified production system. Milk production and fertility had the highest economic values (€40.30 and €20.28 per standard genetic deviation (SDa)), while, mastitis only had a low negative value of -0.57 €/SDa. Therefore, breeding for clinical mastitis will have a minor impact on farm profitability because it affects a small proportion of the flock and has low additive variance. The production traits, which include milk production, prolificacy and milking speed, contributed most to the breeding goal (70.0%), but functional traits still had a considerable share (30.0%). The results of this study highlight the importance of the knowledge of economic values of traits in the design of a breeding program. It is also suggested that the production and functional traits under consideration can be categorized as those which can be efficiently treated through genetic improvement (e.g. milk production and fertility) while others would be better dealt with through managerial interventions (e.g. mastitis occurrence). Also, sub-clinical mastitis that affects a higher proportion of flocks could have a higher contribution to breeding goals.

  2. Applicability of bioanalysis of multiple analytes in drug discovery and development: review of select case studies including assay development considerations.

    Srinivas, Nuggehally R

    2006-05-01

    The development of sound bioanalytical method(s) is of paramount importance during the process of drug discovery and development culminating in a marketing approval. Although the bioanalytical procedure(s) originally developed during the discovery stage may not necessarily be fit to support the drug development scenario, they may be suitably modified and validated, as deemed necessary. Several reviews have appeared over the years describing analytical approaches including various techniques, detection systems, automation tools that are available for an effective separation, enhanced selectivity and sensitivity for quantitation of many analytes. The intention of this review is to cover various key areas where analytical method development becomes necessary during different stages of drug discovery research and development process. The key areas covered in this article with relevant case studies include: (a) simultaneous assay for parent compound and metabolites that are purported to display pharmacological activity; (b) bioanalytical procedures for determination of multiple drugs in combating a disease; (c) analytical measurement of chirality aspects in the pharmacokinetics, metabolism and biotransformation investigations; (d) drug monitoring for therapeutic benefits and/or occupational hazard; (e) analysis of drugs from complex and/or less frequently used matrices; (f) analytical determination during in vitro experiments (metabolism and permeability related) and in situ intestinal perfusion experiments; (g) determination of a major metabolite as a surrogate for the parent molecule; (h) analytical approaches for universal determination of CYP450 probe substrates and metabolites; (i) analytical applicability to prodrug evaluations-simultaneous determination of prodrug, parent and metabolites; (j) quantitative determination of parent compound and/or phase II metabolite(s) via direct or indirect approaches; (k) applicability in analysis of multiple compounds in select

  3. Analysis of Multiple Spurious Operation Scenarios for Decay Heat Removal Function of CANDU Reactors

    Lee, Youngseung; Bae, Yeon-kyoung; Kim, Myungsu [KHNP CRI, Daejeon (Korea, Republic of)

    2016-10-15

    The worst fire broke out in the Browns Ferry Nuclear Power Plant on March 22, 1975. A fire occurrence in a nuclear power plant has recognized a latently serious incident. Nuclear power plants should achieve and maintain the safe shutdown conditions during and after the occurrence of a fire. Functions of the safe shutdown are five such as the shutdown function, the decay heat removal function, the containment function, monitoring and control function, and the supporting function for CANDU type reactors. The purpose of this paper is to analyze that the decay heat removal function of the safe shutdown functions for CANDU type reactors is achieved under the fire induced multiple spurious operation. The scenarios of the fire induced multiple spurious operations (MSO) for the systems used for the decay heat cooling were analyzed. Additionally, Integrated Severe Accident Analysis code for CANDU plants (ISAAC) for determining success criteria of thermal hydraulic analysis was used. Decay heat cooling systems of CANDU reactors are the auxiliary feedwater system, the emergency water supply system, and the shutdown cooling system. A big fire can threat the safety of nuclear power plants, and safe shutdown conditions. The regulatory body in Korea requires the fire hazard analysis including fire induced MSOs. The safe shutdown functions for CANDU reactors are the shutdown function, the decay heat removal function, the containment function, the monitoring and control function, and the supporting service function. The number of spurious operations for the auxiliary feedwater system is more than six and that for the emergency water supply system is one. Additionally, misoperations for the shutdown cooling system are more than two. Accordingly, if total nine components could be spuriously operated, the decay heat removal function would be lost entirely.

  4. Analysis of Multiple Spurious Operation Scenarios for Decay Heat Removal Function of CANDU Reactors

    Lee, Youngseung; Bae, Yeon-kyoung; Kim, Myungsu

    2016-01-01

    The worst fire broke out in the Browns Ferry Nuclear Power Plant on March 22, 1975. A fire occurrence in a nuclear power plant has recognized a latently serious incident. Nuclear power plants should achieve and maintain the safe shutdown conditions during and after the occurrence of a fire. Functions of the safe shutdown are five such as the shutdown function, the decay heat removal function, the containment function, monitoring and control function, and the supporting function for CANDU type reactors. The purpose of this paper is to analyze that the decay heat removal function of the safe shutdown functions for CANDU type reactors is achieved under the fire induced multiple spurious operation. The scenarios of the fire induced multiple spurious operations (MSO) for the systems used for the decay heat cooling were analyzed. Additionally, Integrated Severe Accident Analysis code for CANDU plants (ISAAC) for determining success criteria of thermal hydraulic analysis was used. Decay heat cooling systems of CANDU reactors are the auxiliary feedwater system, the emergency water supply system, and the shutdown cooling system. A big fire can threat the safety of nuclear power plants, and safe shutdown conditions. The regulatory body in Korea requires the fire hazard analysis including fire induced MSOs. The safe shutdown functions for CANDU reactors are the shutdown function, the decay heat removal function, the containment function, the monitoring and control function, and the supporting service function. The number of spurious operations for the auxiliary feedwater system is more than six and that for the emergency water supply system is one. Additionally, misoperations for the shutdown cooling system are more than two. Accordingly, if total nine components could be spuriously operated, the decay heat removal function would be lost entirely

  5. A nonlinear model for fluid flow in a multiple-zone composite reservoir including the quadratic gradient term

    Wang, Xiao-Lu; Fan, Xiang-Yu; Nie, Ren-Shi; Huang, Quan-Hua; He, Yong-Ming

    2013-01-01

    Based on material balance and Darcy's law, the governing equation with the quadratic pressure gradient term was deduced. Then the nonlinear model for fluid flow in a multiple-zone composite reservoir including the quadratic gradient term was established and solved using a Laplace transform. A series of standard log–log type curves of 1-zone (homogeneous), 2-zone and 3-zone reservoirs were plotted and nonlinear flow characteristics were analysed. The type curves governed by the coefficient of the quadratic gradient term (β) gradually deviate from those of a linear model with time elapsing. Qualitative and quantitative analyses were implemented to compare the solutions of the linear and nonlinear models. The results showed that differences of pressure transients between the linear and nonlinear models increase with elapsed time and β. At the end, a successful application of the theoretical model data against the field data shows that the nonlinear model will be a good tool to evaluate formation parameters more accurately. (paper)

  6. Decreasing Multicollinearity: A Method for Models with Multiplicative Functions.

    Smith, Kent W.; Sasaki, M. S.

    1979-01-01

    A method is proposed for overcoming the problem of multicollinearity in multiple regression equations where multiplicative independent terms are entered. The method is not a ridge regression solution. (JKS)

  7. Cross Talk Analysis on Multiple Coupled Transmission Lines; (The calculation of transfer functions on multiple coupled tansmission lines in an inhomogeneous dielectric medium)

    Dalby, Arne Brejning

    1994-01-01

    A flow graph relating voltages and the forward and reflected propagation modes (¿ TEM) on multiple coupled transmission lines in an inhomogeneous dielectric medium is presented. This flow graph directy gives the different transfer functions, including S-parameters, in matrix form needed to calcul......A flow graph relating voltages and the forward and reflected propagation modes (¿ TEM) on multiple coupled transmission lines in an inhomogeneous dielectric medium is presented. This flow graph directy gives the different transfer functions, including S-parameters, in matrix form needed...

  8. Enhanced peripheral visual processing in congenitally deaf humans is supported by multiple brain regions, including primary auditory cortex

    Gregory D. Scott

    2014-03-01

    Full Text Available Brain reorganization associated with altered sensory experience clarifies the critical role of neuroplasticity in development. An example is enhanced peripheral visual processing associated with congenital deafness, but the neural systems supporting this have not been fully characterized. A gap in our understanding of deafness-enhanced peripheral vision is the contribution of primary auditory cortex. Previous studies of auditory cortex that use anatomical normalization across participants were limited by inter-subject variability of Heschl’s gyrus. In addition to reorganized auditory cortex (cross-modal plasticity, a second gap in our understanding is the contribution of altered modality-specific cortices (visual intramodal plasticity in this case, as well as supramodal and multisensory cortices, especially when target detection is required across contrasts. Here we address these gaps by comparing fMRI signal change for peripheral versus perifoveal visual stimulation (11-15° vs. 2°-7° in congenitally deaf and hearing participants in a blocked experimental design with two analytical approaches: a Heschl’s gyrus region of interest analysis and a whole brain analysis. Our results using individually-defined primary auditory cortex (Heschl’s gyrus indicate that fMRI signal change for more peripheral stimuli was greater than perifoveal in deaf but not in hearing participants. Whole-brain analyses revealed differences between deaf and hearing participants for peripheral versus perifoveal visual processing in extrastriate visual cortex including primary auditory cortex, MT+/V5, superior-temporal auditory and multisensory and/or supramodal regions, such as posterior parietal cortex, frontal eye fields, anterior cingulate, and supplementary eye fields. Overall, these data demonstrate the contribution of neuroplasticity in multiple systems including primary auditory cortex, supramodal and multisensory regions, to altered visual processing in

  9. Klotho: a humeral mediator in CSF and plasma that influences longevity and susceptibility to multiple complex disorders, including depression.

    Pavlatou, M G; Remaley, A T; Gold, P W

    2016-08-30

    Klotho is a hormone secreted into human cerebrospinal fluid (CSF), plasma and urine that promotes longevity and influences the onset of several premature senescent phenotypes in mice and humans, including atherosclerosis, cardiovascular disease, stroke and osteoporosis. Preliminary studies also suggest that Klotho possesses tumor suppressor properties. Klotho's roles in these phenomena were first suggested by studies demonstrating that a defect in the Klotho gene in mice results in a significant decrease in lifespan. The Klotho-deficient mouse dies prematurely at 8-9 weeks of age. At 4-5 weeks of age, a syndrome resembling human ageing emerges consisting of atherosclerosis, osteoporosis, cognitive disturbances and alterations of hippocampal architecture. Several deficits in Klotho-deficient mice are likely to contribute to these phenomena. These include an inability to defend against oxidative stress in the central nervous system and periphery, decreased capacity to generate nitric oxide to sustain normal endothelial reactivity, defective Klotho-related mediation of glycosylation and ion channel regulation, increased insulin/insulin-like growth factor signaling and a disturbed calcium and phosphate homeostasis accompanied by altered vitamin D levels and ectopic calcification. Identifying the mechanisms by which Klotho influences multiple important pathways is an emerging field in human biology that will contribute significantly to understanding basic physiologic processes and targets for the treatment of complex diseases. Because many of the phenomena seen in Klotho-deficient mice occur in depressive illness, major depression and bipolar disorder represent illnesses potentially associated with Klotho dysregulation. Klotho's presence in CSF, blood and urine should facilitate its study in clinical populations.

  10. Etiopathophysiological assessment of cases with chronic daily headache: A functional magnetic resonance imaging included investigation

    Hashemi, Akram; Nami, Mohammad Torabi; Oghabian, Mohammad Ali; Ganjgahi, Habib; Vahabi, Zahra

    2012-01-01

    Background Chronic daily headache (CDH) has gained little attention in functional neuro-imaging. When no structural abnormality is found in CDH, defining functional correlates between activated brain regions during headache bouts may provide unique insights towards understanding the pathophysiology of this type of headache. Methods We recruited four CDH cases for comprehensive assessments, including history taking, physical examinations and neuropsychological evaluations (The Addenbrooke's Cognitive Evaluation, Beck's Anxiety and Depression Inventories, Pittsburg Sleep Quality Index and Epworth Sleepiness Scale). Visual analogue scale (VAS) was used to self-rate the intensity of headache. Patients then underwent electroencephalography (EEG), transcranial Doppler (TCD) and functional magnetic resonance imaging (fMRI) evaluations during maximal (VAS = 8-10/10) and off-headache (VAS = 0-3/10) conditions. Data were used to compare in both conditions. We also used BOLD (blood oxygen level dependent) -group level activation map fMRI to possibly locate headache-related activated brain regions. Results General and neurological examinations as well as conventional MRIs were unremarkable. Neuropsychological assessments showed moderate anxiety and depression in one patient and minimal in others. Unlike three patients, maximal and off-headache TCD evaluation in one revealed increased middle cerebral artery blood flow velocity, at the maximal pain area. Although with no seizure history, the same patient's EEG showed paroxysmal epileptic discharges during maximal headache intensity, respectively. Group level activation map fMRI showed activated classical pain matrix regions upon headache bouts (periaqueductal grey, substantia nigra and raphe nucleus), and markedly bilateral occipital lobes activation. Conclusion The EEG changes were of note. Furthermore, the increased BOLD signals in areas outside the classical pain matrix (i.e. occipital lobes) during maximal headaches may

  11. [Functional results of cryosurgical procedures in rhegmatogenous retinal detachment including macula region - our experience].

    Chrapek, O; Sín, M; Jirková, B; Jarkovský, J; Rehák, J

    2013-10-01

    Aim of this study is to evaluate retrospectively functional results of cryosurgical treatment of uncomplicated, idiopathic rhegmatogenous retinal detachment including macula region in phakic patients operated on at the Department of Ophthalmology, Faculty Hospital, Palacký University, Olomouc, Czech Republic, E.U., during the period 2002 -2013, and to evaluate the significance of the macula detachment duration for the final visual acuity. In the study group were included 56 eyes of 56 patients operated in the years 2003 - 2012 at the Department of Ophthalmology, Faculty Hospital, Palacký University, Olomouc. All patients were phakic and in all of them, the retinal detachment including the macula region was diagnosed. The mean follow-up period of the patients was 8,75 months. The initial and final visual acuity testing were performed. Comparing the initial and final visual acuity we rated the level of the visual acuity change. The result was stated as improved, if the visual acuity improved by 1 or more lines on the ETDRS chart. The result was rated as stabilized, if the visual acuity remained the same or it changed by 1 line of the ETDRS chart only. The result was evaluated as worsened, if the visual acuity decreased by 1 or more lines of the ETDRS chart. In the followed-up group, the authors compared visual acuity levels in patients with the macula detachment duration 10 days and 11 days. For the statistical evaluation of achieved results, the Mann - Whitney U test was used. The visual acuity improved in 49 (87 %), did not changed in 5 (9 %) and worsened in 2 (4 %) patients. The patients with macula detachment duration 10 days achieved statistically significant better visual acuity than patients with macula detachment duration 11 days. Patients with macula detachment duration 10 days have better prognosis for functional result than patients with macula detachment duration 11 days.

  12. Method of Fusion Diagnosis for Dam Service Status Based on Joint Distribution Function of Multiple Points

    Zhenxiang Jiang

    2016-01-01

    Full Text Available The traditional methods of diagnosing dam service status are always suitable for single measuring point. These methods also reflect the local status of dams without merging multisource data effectively, which is not suitable for diagnosing overall service. This study proposes a new method involving multiple points to diagnose dam service status based on joint distribution function. The function, including monitoring data of multiple points, can be established with t-copula function. Therefore, the possibility, which is an important fusing value in different measuring combinations, can be calculated, and the corresponding diagnosing criterion is established with typical small probability theory. Engineering case study indicates that the fusion diagnosis method can be conducted in real time and the abnormal point can be detected, thereby providing a new early warning method for engineering safety.

  13. Remodeling Functional Connectivity in Multiple Sclerosis: A Challenging Therapeutic Approach.

    Stampanoni Bassi, Mario; Gilio, Luana; Buttari, Fabio; Maffei, Pierpaolo; Marfia, Girolama A; Restivo, Domenico A; Centonze, Diego; Iezzi, Ennio

    2017-01-01

    Neurons in the central nervous system are organized in functional units interconnected to form complex networks. Acute and chronic brain damage disrupts brain connectivity producing neurological signs and/or symptoms. In several neurological diseases, particularly in Multiple Sclerosis (MS), structural imaging studies cannot always demonstrate a clear association between lesion site and clinical disability, originating the "clinico-radiological paradox." The discrepancy between structural damage and disability can be explained by a complex network perspective. Both brain networks architecture and synaptic plasticity may play important roles in modulating brain networks efficiency after brain damage. In particular, long-term potentiation (LTP) may occur in surviving neurons to compensate network disconnection. In MS, inflammatory cytokines dramatically interfere with synaptic transmission and plasticity. Importantly, in addition to acute and chronic structural damage, inflammation could contribute to reduce brain networks efficiency in MS leading to worse clinical recovery after a relapse and worse disease progression. These evidence suggest that removing inflammation should represent the main therapeutic target in MS; moreover, as synaptic plasticity is particularly altered by inflammation, specific strategies aimed at promoting LTP mechanisms could be effective for enhancing clinical recovery. Modulation of plasticity with different non-invasive brain stimulation (NIBS) techniques has been used to promote recovery of MS symptoms. Better knowledge of features inducing brain disconnection in MS is crucial to design specific strategies to promote recovery and use NIBS with an increasingly tailored approach.

  14. Remodeling Functional Connectivity in Multiple Sclerosis: A Challenging Therapeutic Approach

    Mario Stampanoni Bassi

    2017-12-01

    Full Text Available Neurons in the central nervous system are organized in functional units interconnected to form complex networks. Acute and chronic brain damage disrupts brain connectivity producing neurological signs and/or symptoms. In several neurological diseases, particularly in Multiple Sclerosis (MS, structural imaging studies cannot always demonstrate a clear association between lesion site and clinical disability, originating the “clinico-radiological paradox.” The discrepancy between structural damage and disability can be explained by a complex network perspective. Both brain networks architecture and synaptic plasticity may play important roles in modulating brain networks efficiency after brain damage. In particular, long-term potentiation (LTP may occur in surviving neurons to compensate network disconnection. In MS, inflammatory cytokines dramatically interfere with synaptic transmission and plasticity. Importantly, in addition to acute and chronic structural damage, inflammation could contribute to reduce brain networks efficiency in MS leading to worse clinical recovery after a relapse and worse disease progression. These evidence suggest that removing inflammation should represent the main therapeutic target in MS; moreover, as synaptic plasticity is particularly altered by inflammation, specific strategies aimed at promoting LTP mechanisms could be effective for enhancing clinical recovery. Modulation of plasticity with different non-invasive brain stimulation (NIBS techniques has been used to promote recovery of MS symptoms. Better knowledge of features inducing brain disconnection in MS is crucial to design specific strategies to promote recovery and use NIBS with an increasingly tailored approach.

  15. Communication: importance sampling including path correlation in semiclassical initial value representation calculations for time correlation functions.

    Pan, Feng; Tao, Guohua

    2013-03-07

    Full semiclassical (SC) initial value representation (IVR) for time correlation functions involves a double phase space average over a set of two phase points, each of which evolves along a classical path. Conventionally, the two initial phase points are sampled independently for all degrees of freedom (DOF) in the Monte Carlo procedure. Here, we present an efficient importance sampling scheme by including the path correlation between the two initial phase points for the bath DOF, which greatly improves the performance of the SC-IVR calculations for large molecular systems. Satisfactory convergence in the study of quantum coherence in vibrational relaxation has been achieved for a benchmark system-bath model with up to 21 DOF.

  16. Mortality from Musculoskeletal Disorders Including Rheumatoid Arthritis in Southern Sweden: A Multiple-cause-of-death Analysis, 1998-2014.

    Kiadaliri, Aliasghar A; Turkiewicz, Aleksandra; Englund, Martin

    2017-05-01

    To assess mortality related to musculoskeletal (MSK) disorders and rheumatoid arthritis (RA), specifically, among adults (aged ≥ 20 yrs) in southern Sweden using the multiple-cause-of-death approach. All death certificates (DC; n = 201,488) from 1998 to 2014 for adults in the region of Skåne were analyzed when mortality from MSK disorders and RA was listed as the underlying and nonunderlying cause of death (UCD/NUCD). Trends in age-standardized mortality rates (ASMR) were evaluated using joinpoint regression, and associated causes were identified by age- and sex-adjusted observed/expected ratios. MSK (RA) was mentioned on 2.8% (0.8%) of all DC and selected as UCD in 0.6% (0.2%), with higher values among women. Proportion of MSK disorder deaths from all deaths increased from 2.7% in 1998 to 3.1% in 2014, and declined from 0.9% to 0.5% for RA. The mean age at death was higher in DC with mention of MSK/RA than in DC without. The mean ASMR for MSK (RA) was 15.5 (4.3) per 100,000 person-years and declined by 1.1% (3.8%) per year during 1998-2014. When MSK/RA were UCD, pneumonia and heart failure were the main NUCD. When MSK/RA were NUCD, the leading UCD were ischemic heart disease and neoplasms. The greatest observed/expected ratios were seen for infectious diseases (including sepsis) and blood diseases. We observed significant reduction in MSK and RA mortality rates and increase in the mean age at death. Further analyses are required to investigate determinants of these improvements in MSK/RA survival and their potential effect on the Swedish healthcare systems.

  17. The multiple roles and functions of English in South Korea

    Gene Vasilopoulos

    2013-10-01

    Full Text Available In the field of language and identity, the subcategory of gender has been an area of growing interest (Pavlenko, 2001; Norton & Pavlenko, 2004; Menard-Warwick, 2008; and Higgins, 2010. Adopting the view of gender as “a system of social relationships and discursive practices” (Norton & Pavlenko, 2004, p. 504, social context is fundamental in understanding how gender relates to foreign language learning. This qualitative study focused on the extent to which gender impacts English language learning and English language use in the context of teaching English as a foreign language in South Korea. More specifically, it investigates how gender shapes self and social identity, and how these identities relate to English language learning and English language use, at present and/or in the future, in both real and/or imagined communities. Four male and four female participants were selected using purposive homogenous sampling techniques based on the criteria of having lived abroad in an English speaking community for over 5 years—a criterion which assumes the formation of self and social identity in addition to their native Korean L1. Data was collected through multiple methods including open-ended questionnaires, in-depth interviews, and focus group discussions. Interview and questionnaire data reveals gender differences in the symbolic meaning of English language, the relevance of English in self and social positioning, and the role of English in shaping future professional trajectories with males situating themselves in international contexts and females in the local.

  18. Microfluidic production of multiple emulsions and functional microcapsules

    Lee, Tae Yong; Choi, Tae Min; Shim, Tae Soup; Frijns, Raoul A.M.; Kim, Shin Hyun

    2016-01-01

    Recent advances in microfluidics have enabled the controlled production of multiple-emulsion drops with onion-like topology. The multiple-emulsion drops possess an intrinsic core-shell geometry, which makes them useful as templates to create microcapsules with a solid membrane. High flexibility

  19. Optimisation of chromatographic resolution using objective functions including both time and spectral information.

    Torres-Lapasió, J R; Pous-Torres, S; Ortiz-Bolsico, C; García-Alvarez-Coque, M C

    2015-01-16

    The optimisation of the resolution in high-performance liquid chromatography is traditionally performed attending only to the time information. However, even in the optimal conditions, some peak pairs may remain unresolved. Such incomplete resolution can be still accomplished by deconvolution, which can be carried out with more guarantees of success by including spectral information. In this work, two-way chromatographic objective functions (COFs) that incorporate both time and spectral information were tested, based on the peak purity (analyte peak fraction free of overlapping) and the multivariate selectivity (figure of merit derived from the net analyte signal) concepts. These COFs are sensitive to situations where the components that coelute in a mixture show some spectral differences. Therefore, they are useful to find out experimental conditions where the spectrochromatograms can be recovered by deconvolution. Two-way multivariate selectivity yielded the best performance and was applied to the separation using diode-array detection of a mixture of 25 phenolic compounds, which remained unresolved in the chromatographic order using linear and multi-linear gradients of acetonitrile-water. Peak deconvolution was carried out using the combination of orthogonal projection approach and alternating least squares. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Auxiliary variables in multiple imputation in regression with missing X: a warning against including too many in small sample research

    Hardt Jochen

    2012-12-01

    Full Text Available Abstract Background Multiple imputation is becoming increasingly popular. Theoretical considerations as well as simulation studies have shown that the inclusion of auxiliary variables is generally of benefit. Methods A simulation study of a linear regression with a response Y and two predictors X1 and X2 was performed on data with n = 50, 100 and 200 using complete cases or multiple imputation with 0, 10, 20, 40 and 80 auxiliary variables. Mechanisms of missingness were either 100% MCAR or 50% MAR + 50% MCAR. Auxiliary variables had low (r=.10 vs. moderate correlations (r=.50 with X’s and Y. Results The inclusion of auxiliary variables can improve a multiple imputation model. However, inclusion of too many variables leads to downward bias of regression coefficients and decreases precision. When the correlations are low, inclusion of auxiliary variables is not useful. Conclusion More research on auxiliary variables in multiple imputation should be performed. A preliminary rule of thumb could be that the ratio of variables to cases with complete data should not go below 1 : 3.

  1. Selection of multiple umbrella species for functional and taxonomic diversity to represent urban biodiversity.

    Sattler, T; Pezzatti, G B; Nobis, M P; Obrist, M K; Roth, T; Moretti, M

    2014-04-01

    Surrogates, such as umbrella species, are commonly used to reduce the complexity of quantifying biodiversity for conservation purposes. The presence of umbrella species is often indicative of high taxonomic diversity; however, functional diversity is now recognized as an important metric for biodiversity and thus should be considered when choosing umbrella species. We identified umbrella species associated with high taxonomic and functional biodiversity in urban areas in Switzerland. We analyzed 39,752 individuals of 574 animal species from 96 study plots and 1397 presences of 262 plant species from 58 plots. Thirty-one biodiversity measures of 7 taxonomic groups (plants, spiders, bees, ground beetles, lady bugs, weevils and birds) were included in within- and across-taxa analyses. Sixteen measures were taxonomical (species richness and species diversity), whereas 15 were functional (species traits including mobility, resource use, and reproduction). We used indicator value analysis to identify umbrella species associated with single or multiple biodiversity measures. Many umbrella species were indicators of high biodiversity within their own taxonomic group (from 33.3% in weevils to 93.8% in birds), to a lesser extent they were indicators across taxa. Principal component analysis revealed that umbrella species for multiple measures of biodiversity represented different aspects of biodiversity, especially with respect to measures of taxonomic and functional diversity. Thus, even umbrella species for multiple measures of biodiversity were complementary in the biodiversity aspects they represented. Thus, the choice of umbrella species based solely on taxonomic diversity is questionable and may not represent biodiversity comprehensively. Our results suggest that, depending on conservation priorities, managers should choose multiple and complementary umbrella species to assess the state of biodiversity. © 2013 Society for Conservation Biology.

  2. Pulmonary Function After Treatment for Embryonal Brain Tumors on SJMB03 That Included Craniospinal Irradiation

    Green, Daniel M.; Merchant, Thomas E.; Billups, Catherine A.; Stokes, Dennis C.; Broniscer, Alberto; Bartels, Ute; Chintagumpala, Murali; Hassall, Timothy E.; Gururangan, Sridharan; McCowage, Geoffrey B.; Heath, John A.; Cohn, Richard J.; Fisher, Michael J.; Srinivasan, Ashok; Robinson, Giles W.; Gajjar, Amar

    2015-01-01

    Purpose: The treatment of children with embryonal brain tumors (EBT) includes craniospinal irradiation (CSI). There are limited data regarding the effect of CSI on pulmonary function. Methods: Protocol SJMB03 enrolled patients 3 to 21 years of age with EBT. Pulmonary function tests (PFTs) (forced expiratory volume in 1 second [FEV 1 ] and forced vital capacity [FVC] by spirometry, total lung capacity [TLC] by nitrogen washout or plethysmography, and diffusing capacity of the lung for carbon monoxide corrected for hemoglobin [DLCO corr ]) were obtained. Differences between PFTs obtained immediately after the completion of CSI and 24 or 60 months after the completion of treatment (ACT) were compared using exact Wilcoxon signed-rank tests and repeated-measures models. Results: Between June 24, 2003, and March 1, 2010, 303 eligible patients (spine dose: ≤2345 cGy, 201; >2345 cGy, 102; proton beam, 20) were enrolled, 260 of whom had at least 1 PFT. The median age at diagnosis was 8.9 years (range, 3.1-20.4 years). The median thoracic spinal radiation dose was 23.4 Gy (interquartile range [IQR], 23.4-36.0 Gy). The median cyclophosphamide dose was 16.0 g/m 2 (IQR, 15.7-16.0 g/m 2 ). At 24 and 60 months ACT, DLCO corr was <75% predicted in 23% (27/118) and 25% (21/84) of patients, FEV 1 was <80% predicted in 20% (34/170) and 29% (32/109) of patients, FVC was <80% predicted in 27% (46/172) and 28% (30/108) of patients, and TLC was <75% predicted in 9% (13/138) and 11% (10/92) of patients. DLCO corr was significantly decreased 24 months ACT (median difference [MD] in % predicted, 3.00%; P=.028) and 60 months ACT (MD in % predicted, 6.00%; P=.033) compared with the end of radiation therapy. These significant decreases in DLCO corr were also observed in repeated-measures models (P=.011 and P=.032 at 24 and 60 months ACT, respectively). Conclusions: A significant minority of EBT survivors experience PFT deficits after CSI. Continued monitoring of this cohort

  3. Pulmonary Function After Treatment for Embryonal Brain Tumors on SJMB03 That Included Craniospinal Irradiation

    Green, Daniel M., E-mail: daniel.green@stjude.org [Department of Epidemiology and Cancer Control, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Merchant, Thomas E. [Department of Radiological Sciences, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Billups, Catherine A. [Department of Biostatistics, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Stokes, Dennis C. [Department of Pediatrics, University of Tennessee School of Medicine, Memphis, Tennessee (United States); Broniscer, Alberto [Department of Oncology, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Bartels, Ute [Department of Haematology and Oncology, The Hospital for Sick Children, Toronto, Ontario (Canada); Chintagumpala, Murali [Department of Pediatric Medicine, Texas Children' s Cancer and Hematology Centers, Baylor College of Medicine, Houston, Texas (United States); Hassall, Timothy E. [Department of Haematology and Oncology, Royal Children' s Hospital, Brisbane (Australia); Gururangan, Sridharan [Department of Pediatrics, Duke University Medical Center, Durham, North Carolina (United States); McCowage, Geoffrey B. [Department of Pediatrics, Children' s Hospital at Westmead, Sydney (Australia); Heath, John A. [Children' s Cancer Center, Royal Children' s Hospital Melbourne, Melbourne (Australia); Cohn, Richard J. [Department of Clinical Oncology, Sydney Children' s Hospital, Sydney (Australia); Fisher, Michael J. [Department of Pediatrics, Children' s Hospital of Philadelphia, Philadelphia, Pennsylvania (United States); Srinivasan, Ashok [Department of Bone Marrow Transplantation & Cellular Therapy, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Robinson, Giles W.; Gajjar, Amar [Department of Oncology, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States)

    2015-09-01

    Purpose: The treatment of children with embryonal brain tumors (EBT) includes craniospinal irradiation (CSI). There are limited data regarding the effect of CSI on pulmonary function. Methods: Protocol SJMB03 enrolled patients 3 to 21 years of age with EBT. Pulmonary function tests (PFTs) (forced expiratory volume in 1 second [FEV{sub 1}] and forced vital capacity [FVC] by spirometry, total lung capacity [TLC] by nitrogen washout or plethysmography, and diffusing capacity of the lung for carbon monoxide corrected for hemoglobin [DLCO{sub corr}]) were obtained. Differences between PFTs obtained immediately after the completion of CSI and 24 or 60 months after the completion of treatment (ACT) were compared using exact Wilcoxon signed-rank tests and repeated-measures models. Results: Between June 24, 2003, and March 1, 2010, 303 eligible patients (spine dose: ≤2345 cGy, 201; >2345 cGy, 102; proton beam, 20) were enrolled, 260 of whom had at least 1 PFT. The median age at diagnosis was 8.9 years (range, 3.1-20.4 years). The median thoracic spinal radiation dose was 23.4 Gy (interquartile range [IQR], 23.4-36.0 Gy). The median cyclophosphamide dose was 16.0 g/m{sup 2} (IQR, 15.7-16.0 g/m{sup 2}). At 24 and 60 months ACT, DLCO{sub corr} was <75% predicted in 23% (27/118) and 25% (21/84) of patients, FEV{sub 1} was <80% predicted in 20% (34/170) and 29% (32/109) of patients, FVC was <80% predicted in 27% (46/172) and 28% (30/108) of patients, and TLC was <75% predicted in 9% (13/138) and 11% (10/92) of patients. DLCO{sub corr} was significantly decreased 24 months ACT (median difference [MD] in % predicted, 3.00%; P=.028) and 60 months ACT (MD in % predicted, 6.00%; P=.033) compared with the end of radiation therapy. These significant decreases in DLCO{sub corr} were also observed in repeated-measures models (P=.011 and P=.032 at 24 and 60 months ACT, respectively). Conclusions: A significant minority of EBT survivors experience PFT deficits after CSI

  4. Nontypeable pneumococci can be divided into multiple cps types, including one type expressing the novel gene pspK.

    Park, In Ho; Kim, Kyung-Hyo; Andrade, Ana Lucia; Briles, David E; McDaniel, Larry S; Nahm, Moon H

    2012-01-01

    Although virulence of Streptococcus pneumoniae is associated with its capsule, some pathogenic S. pneumoniae isolates lack capsules and are serologically nontypeable (NT). We obtained 64 isolates that were identified as NT "pneumococci" (i.e., bacteria satisfying the conventional definition but without the multilocus sequence typing [MLST]-based definition of S. pneumoniae) by the traditional criteria. All 64 were optochin sensitive and had lytA, and 63 had ply. Twelve isolates had cpsA, suggesting the presence of a conventional but defective capsular polysaccharide synthesis (cps) locus. The 52 cpsA-negative isolates could be divided into three null capsule clades (NCC) based on aliC (aliB-like ORF1), aliD (aliB-like ORF2), and our newly discovered gene, pspK, in their cps loci. pspK encodes a protein with a long alpha-helical region containing an LPxTG motif and a YPT motif known to bind human pIgR. There were nine isolates in NCC1 (pspK(+) but negative for aliC and aliD), 32 isolates in NCC2 (aliC(+) aliD(+) but negative for pspK), and 11 in NCC3 (aliD(+) but negative for aliC and pspK). Among 52 cpsA-negative isolates, 41 were identified as S. pneumoniae by MLST analysis. All NCC1 and most NCC2 isolates were S. pneumoniae, whereas all nine NCC3 and two NCC2 isolates were not S. pneumoniae. Several NCC1 and NCC2 isolates from multiple individuals had identical MLST and cps regions, showing that unencapsulated S. pneumoniae can be infectious among humans. Furthermore, NCC1 and NCC2 S. pneumoniae isolates could colonize mice as well as encapsulated S. pneumoniae, although S. pneumoniae with an artificially disrupted cps locus did not. Moreover, an NCC1 isolate with pspK deletion did not colonize mice, suggesting that pspK is critical for colonization. Thus, PspK may provide pneumococci a means of surviving in the nasopharynx without capsule. IMPORTANCE The presence of a capsule is critical for many pathogenic bacteria, including pneumococci. Reflecting the

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

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

    2015-01-01

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

  6. Diversity and functional traits of culturable microbiome members, including cyanobacteria in the rice phyllosphere.

    Venkatachalam, S; Ranjan, K; Prasanna, R; Ramakrishnan, B; Thapa, S; Kanchan, A

    2016-07-01

    The diversity and abundance of culturable microbiome members of the rice phyllosphere was investigated using cv. Pusa Punjab Basmati 1509. Both diversity and species richness of bacteria were significantly higher in plants in pots in a semi-controlled environment than those in fields. Application of fertilisers reduced both diversity and species richness in field-grown plants under a conventional flooded system of rice intensification (SRI) and in dry-seeded rice (DSR) modes. Sequence analyses of 16S rDNA of culturable bacteria, those selected after amplified ribosomal DNA restriction analysis (ARDRA), showed the dominance of α-proteobacteria (35%) and actinobacteria (38%); Pantoea, Exiguobacterium and Bacillus were common among the culturable phyllospheric bacteria. About 34% of 83 culturable bacterial isolates had higher potential (>2 μg·ml(-1) ) for indole acetic acid production in the absence of tryptophan. Interestingly, the phyllosphere bacterial isolates from the pot experiment had significantly higher potential for nitrogen fixation than isolates from the field experiment. Enrichment for cyanobacteria showed both unicellular forms and non-heterocystous filaments under aerobic as well as anaerobic conditions. PCR-DGGE analysis of these showed that aerobic and anaerobic conditions as well as the three modes of cultivation of rice in the field strongly influenced the number and abundance of phylotypes. The adaptability and functional traits of these culturable microbiome members suggest enormous diversity in the phyllosphere, including potential for plant growth promotion, which was also significantly influenced by the different methods of growing rice. © 2016 German Botanical Society and The Royal Botanical Society of the Netherlands.

  7. Multiple exciton generation in chiral carbon nanotubes: Density functional theory based computation

    Kryjevski, Andrei; Mihaylov, Deyan; Kilina, Svetlana; Kilin, Dmitri

    2017-10-01

    We use a Boltzmann transport equation (BE) to study time evolution of a photo-excited state in a nanoparticle including phonon-mediated exciton relaxation and the multiple exciton generation (MEG) processes, such as exciton-to-biexciton multiplication and biexciton-to-exciton recombination. BE collision integrals are computed using Kadanoff-Baym-Keldysh many-body perturbation theory based on density functional theory simulations, including exciton effects. We compute internal quantum efficiency (QE), which is the number of excitons generated from an absorbed photon in the course of the relaxation. We apply this approach to chiral single-wall carbon nanotubes (SWCNTs), such as (6,2) and (6,5). We predict efficient MEG in the (6,2) and (6,5) SWCNTs within the solar spectrum range starting at the 2Eg energy threshold and with QE reaching ˜1.6 at about 3Eg, where Eg is the electronic gap.

  8. Bisphenol A affects androgen receptor function via multiple mechanisms.

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

    2013-05-25

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

  9. Multiple loci associated with renal function in African Americans.

    Daniel Shriner

    Full Text Available The incidence of chronic kidney disease varies by ethnic group in the USA, with African Americans displaying a two-fold higher rate than European Americans. One of the two defining variables underlying staging of chronic kidney disease is the glomerular filtration rate. Meta-analysis in individuals of European ancestry has identified 23 genetic loci associated with the estimated glomerular filtration rate (eGFR. We conducted a follow-up study of these 23 genetic loci using a population-based sample of 1,018 unrelated admixed African Americans. We included in our follow-up study two variants in APOL1 associated with end-stage kidney disease discovered by admixture mapping in admixed African Americans. To address confounding due to admixture, we estimated local ancestry at each marker and global ancestry. We performed regression analysis stratified by local ancestry and combined the resulting regression estimates across ancestry strata using an inverse variance-weighted fixed effects model. We found that 11 of the 24 loci were significantly associated with eGFR in our sample. The effect size estimates were not significantly different between the subgroups of individuals with two copies of African ancestry vs. two copies of European ancestry for any of the 11 loci. In contrast, allele frequencies were significantly different at 10 of the 11 loci. Collectively, the 11 loci, including four secondary signals revealed by conditional analyses, explained 14.2% of the phenotypic variance in eGFR, in contrast to the 1.4% explained by the 24 loci in individuals of European ancestry. Our findings provide insight into the genetic basis of variation in renal function among admixed African Americans.

  10. Neutron generators with size scalability, ease of fabrication and multiple ion source functionalities

    Elizondo-Decanini, Juan M

    2014-11-18

    A neutron generator is provided with a flat, rectilinear geometry and surface mounted metallizations. This construction provides scalability and ease of fabrication, and permits multiple ion source functionalities.

  11. An assessment of functioning and non-functioning distractors in multiple-choice questions: a descriptive analysis

    Mohammed Ahmed M

    2009-07-01

    Full Text Available Abstract Background Four- or five-option multiple choice questions (MCQs are the standard in health-science disciplines, both on certification-level examinations and on in-house developed tests. Previous research has shown, however, that few MCQs have three or four functioning distractors. The purpose of this study was to investigate non-functioning distractors in teacher-developed tests in one nursing program in an English-language university in Hong Kong. Methods Using item-analysis data, we assessed the proportion of non-functioning distractors on a sample of seven test papers administered to undergraduate nursing students. A total of 514 items were reviewed, including 2056 options (1542 distractors and 514 correct responses. Non-functioning options were defined as ones that were chosen by fewer than 5% of examinees and those with a positive option discrimination statistic. Results The proportion of items containing 0, 1, 2, and 3 functioning distractors was 12.3%, 34.8%, 39.1%, and 13.8% respectively. Overall, items contained an average of 1.54 (SD = 0.88 functioning distractors. Only 52.2% (n = 805 of all distractors were functioning effectively and 10.2% (n = 158 had a choice frequency of 0. Items with more functioning distractors were more difficult and more discriminating. Conclusion The low frequency of items with three functioning distractors in the four-option items in this study suggests that teachers have difficulty developing plausible distractors for most MCQs. Test items should consist of as many options as is feasible given the item content and the number of plausible distractors; in most cases this would be three. Item analysis results can be used to identify and remove non-functioning distractors from MCQs that have been used in previous tests.

  12. An assessment of functioning and non-functioning distractors in multiple-choice questions: a descriptive analysis.

    Tarrant, Marie; Ware, James; Mohammed, Ahmed M

    2009-07-07

    Four- or five-option multiple choice questions (MCQs) are the standard in health-science disciplines, both on certification-level examinations and on in-house developed tests. Previous research has shown, however, that few MCQs have three or four functioning distractors. The purpose of this study was to investigate non-functioning distractors in teacher-developed tests in one nursing program in an English-language university in Hong Kong. Using item-analysis data, we assessed the proportion of non-functioning distractors on a sample of seven test papers administered to undergraduate nursing students. A total of 514 items were reviewed, including 2056 options (1542 distractors and 514 correct responses). Non-functioning options were defined as ones that were chosen by fewer than 5% of examinees and those with a positive option discrimination statistic. The proportion of items containing 0, 1, 2, and 3 functioning distractors was 12.3%, 34.8%, 39.1%, and 13.8% respectively. Overall, items contained an average of 1.54 (SD = 0.88) functioning distractors. Only 52.2% (n = 805) of all distractors were functioning effectively and 10.2% (n = 158) had a choice frequency of 0. Items with more functioning distractors were more difficult and more discriminating. The low frequency of items with three functioning distractors in the four-option items in this study suggests that teachers have difficulty developing plausible distractors for most MCQs. Test items should consist of as many options as is feasible given the item content and the number of plausible distractors; in most cases this would be three. Item analysis results can be used to identify and remove non-functioning distractors from MCQs that have been used in previous tests.

  13. Ca analysis: an Excel based program for the analysis of intracellular calcium transients including multiple, simultaneous regression analysis.

    Greensmith, David J

    2014-01-01

    Here I present an Excel based program for the analysis of intracellular Ca transients recorded using fluorescent indicators. The program can perform all the necessary steps which convert recorded raw voltage changes into meaningful physiological information. The program performs two fundamental processes. (1) It can prepare the raw signal by several methods. (2) It can then be used to analyze the prepared data to provide information such as absolute intracellular Ca levels. Also, the rates of change of Ca can be measured using multiple, simultaneous regression analysis. I demonstrate that this program performs equally well as commercially available software, but has numerous advantages, namely creating a simplified, self-contained analysis workflow. Copyright © 2013 The Author. Published by Elsevier Ireland Ltd.. All rights reserved.

  14. Ca analysis: An Excel based program for the analysis of intracellular calcium transients including multiple, simultaneous regression analysis☆

    Greensmith, David J.

    2014-01-01

    Here I present an Excel based program for the analysis of intracellular Ca transients recorded using fluorescent indicators. The program can perform all the necessary steps which convert recorded raw voltage changes into meaningful physiological information. The program performs two fundamental processes. (1) It can prepare the raw signal by several methods. (2) It can then be used to analyze the prepared data to provide information such as absolute intracellular Ca levels. Also, the rates of change of Ca can be measured using multiple, simultaneous regression analysis. I demonstrate that this program performs equally well as commercially available software, but has numerous advantages, namely creating a simplified, self-contained analysis workflow. PMID:24125908

  15. Stepped-wedge cluster randomised controlled trials: a generic framework including parallel and multiple-level designs.

    Hemming, Karla; Lilford, Richard; Girling, Alan J

    2015-01-30

    Stepped-wedge cluster randomised trials (SW-CRTs) are being used with increasing frequency in health service evaluation. Conventionally, these studies are cross-sectional in design with equally spaced steps, with an equal number of clusters randomised at each step and data collected at each and every step. Here we introduce several variations on this design and consider implications for power. One modification we consider is the incomplete cross-sectional SW-CRT, where the number of clusters varies at each step or where at some steps, for example, implementation or transition periods, data are not collected. We show that the parallel CRT with staggered but balanced randomisation can be considered a special case of the incomplete SW-CRT. As too can the parallel CRT with baseline measures. And we extend these designs to allow for multiple layers of clustering, for example, wards within a hospital. Building on results for complete designs, power and detectable difference are derived using a Wald test and obtaining the variance-covariance matrix of the treatment effect assuming a generalised linear mixed model. These variations are illustrated by several real examples. We recommend that whilst the impact of transition periods on power is likely to be small, where they are a feature of the design they should be incorporated. We also show examples in which the power of a SW-CRT increases as the intra-cluster correlation (ICC) increases and demonstrate that the impact of the ICC is likely to be smaller in a SW-CRT compared with a parallel CRT, especially where there are multiple levels of clustering. Finally, through this unified framework, the efficiency of the SW-CRT and the parallel CRT can be compared. © 2014 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

  16. Nonadiabatic dynamics of electron transfer in solution: Explicit and implicit solvent treatments that include multiple relaxation time scales

    Schwerdtfeger, Christine A.; Soudackov, Alexander V.; Hammes-Schiffer, Sharon

    2014-01-01

    The development of efficient theoretical methods for describing electron transfer (ET) reactions in condensed phases is important for a variety of chemical and biological applications. Previously, dynamical dielectric continuum theory was used to derive Langevin equations for a single collective solvent coordinate describing ET in a polar solvent. In this theory, the parameters are directly related to the physical properties of the system and can be determined from experimental data or explicit molecular dynamics simulations. Herein, we combine these Langevin equations with surface hopping nonadiabatic dynamics methods to calculate the rate constants for thermal ET reactions in polar solvents for a wide range of electronic couplings and reaction free energies. Comparison of explicit and implicit solvent calculations illustrates that the mapping from explicit to implicit solvent models is valid even for solvents exhibiting complex relaxation behavior with multiple relaxation time scales and a short-time inertial response. The rate constants calculated for implicit solvent models with a single solvent relaxation time scale corresponding to water, acetonitrile, and methanol agree well with analytical theories in the Golden rule and solvent-controlled regimes, as well as in the intermediate regime. The implicit solvent models with two relaxation time scales are in qualitative agreement with the analytical theories but quantitatively overestimate the rate constants compared to these theories. Analysis of these simulations elucidates the importance of multiple relaxation time scales and the inertial component of the solvent response, as well as potential shortcomings of the analytical theories based on single time scale solvent relaxation models. This implicit solvent approach will enable the simulation of a wide range of ET reactions via the stochastic dynamics of a single collective solvent coordinate with parameters that are relevant to experimentally accessible

  17. Simultaneous measurements of work function and H‒ density including caesiation of a converter surface

    Cristofaro, S.; Friedl, R.; Fantz, U.

    2017-08-01

    Negative hydrogen ion sources rely on the surface conversion of neutral atomic hydrogen and positive hydrogen ions to H-. The efficiency of this process depends on the actual work function of the converter surface. By introducing caesium into the source the work function decreases, enhancing the negative ion yield. In order to study the impact of the work function on the H- surface production at similar conditions to the ones in ion sources for fusion devices like ITER and DEMO, fundamental investigations are performed in a flexible laboratory experiment. The work function of the converter surface can be absolutely measured by photoelectric effect, while a newly installed cavity ring-down spectroscopy system (CRDS) measures the H- density. The CRDS is firstly tested and characterized by investigations on H- volume production. Caesiation of a stainless steel sample is then performed in vacuum and the plasma effect on the Cs layer is investigated also for long plasma-on times. A minimum work function of (1.9±0.1) eV is reached after some minutes of plasma treatment, resulting in a reduction by a value of 0.8 eV compared to vacuum measurements. The H- density above the surface is (2.1±0.5)×1015 m-3. With further plasma exposure of the caesiated surface, the work function increases up to 3.75 eV, due to the impinging plasma particles which gradually remove the Cs layer. As a result, the H- density decreases by a factor of at least 2.

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

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

    2015-12-01

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

  19. Improvement in genetic evaluation of female fertility in dairy cattle using multiple-trait models including milk production traits

    Sun, C; Madsen, P; Lund, M S

    2010-01-01

    This study investigated the improvement in genetic evaluation of fertility traits by using production traits as secondary traits (MILK = 305-d milk yield, FAT = 305-d fat yield, and PROT = 305-d protein yield). Data including 471,742 records from first lactations of Denmark Holstein cows, covering...... the years of inseminations during first lactations from 1995 to 2004, were analyzed. Six fertility traits (i.e., interval in days from calving to first insemination, calving interval, days open, interval in days from first to last insemination, numbers of inseminations per conception, and nonreturn rate...... stability and predictive ability than single-trait models for all the fertility traits, except for nonreturn rate within 56 d after first service. The stability and predictive ability for the model including MILK or PROT were similar to the model including all 3 milk production traits and better than...

  20. Cooperative Control for Multiple Autonomous Vehicles Using Descriptor Functions

    Marta Niccolini

    2014-01-01

    Full Text Available The paper presents a novel methodology for the control management of a swarm of autonomous vehicles. The vehicles, or agents, may have different skills, and be employed for different missions. The methodology is based on the definition of descriptor functions that model the capabilities of the single agent and each task or mission. The swarm motion is controlled by minimizing a suitable norm of the error between agents’ descriptor functions and other descriptor functions which models the entire mission. The validity of the proposed technique is tested via numerical simulation, using different task assignment scenarios.

  1. Study Modules for Calculus-Based General Physics. [Includes Modules 3-5: Planar Motion; Newton's Laws; and Vector Multiplication].

    Fuller, Robert G., Ed.; And Others

    This is part of a series of 42 Calculus Based Physics (CBP) modules totaling about 1,000 pages. The modules include study guides, practice tests, and mastery tests for a full-year individualized course in calculus-based physics based on the Personalized System of Instruction (PSI). The units are not intended to be used without outside materials;…

  2. Robustness of Multiple Objective Decision Analysis Preference Functions

    Klimack, William

    2002-01-01

    .... The impact of these differences was examined to improve implementation efficiency. The robustness of the decision model was examined with respect to the preference functions to reduce the time burden imposed on the decision maker...

  3. Multiple Beneficial Lipids Including Lecithin Detected in the Edible Invasive Mollusk Crepidula fornicata from the French Northeastern Atlantic Coast

    Dagorn, Flore; Buzin, Florence; Couzinet-Mossion, Aurélie; Decottignies, Priscilla; Viau, Michèle; Rabesaotra, Vony; Barnathan, Gilles; Wielgosz-Collin, Gaëtane

    2014-01-01

    The invasive mollusk Crepidula fornicata, occurring in large amounts in bays along the French Northeastern Atlantic coasts, may have huge environmental effects in highly productive ecosystems where shellfish are exploited. The present study aims at determining the potential economic value of this marine species in terms of exploitable substances with high added value. Lipid content and phospholipid (PL) composition of this mollusk collected on the Bourgneuf Bay were studied through four seasons. Winter specimens contained the highest lipid levels (5.3% dry weight), including 69% of PLs. Phosphatidylcholine (PC) was the major PL class all year, accounting for 63.9% to 88.9% of total PLs. Consequently, the winter specimens were then investigated for PL fatty acids (FAs), and free sterols. Dimethylacetals (DMAs) were present (10.7% of PL FA + DMA mixture) revealing the occurrence of plasmalogens. More than forty FAs were identified, including 20:5n-3 (9.4%) and 22:6n-3 (7.3%) acids. Fourteen free sterols were present, including cholesterol at 31.3% of the sterol mixture and about 40% of phytosterols. These data on lipids of C. fornicata demonstrate their positive attributes for human nutrition and health. The PL mixture, rich in PC and polyunsaturated FAs, offers an interesting alternative source of high value-added marine lecithin. PMID:25532566

  4. Multiple beneficial lipids including lecithin detected in the edible invasive mollusk Crepidula fornicata from the French Northeastern Atlantic coast.

    Dagorn, Flore; Buzin, Florence; Couzinet-Mossion, Aurélie; Decottignies, Priscilla; Viau, Michèle; Rabesaotra, Vony; Barnathan, Gilles; Wielgosz-Collin, Gaëtane

    2014-12-22

    The invasive mollusk Crepidula fornicata, occurring in large amounts in bays along the French Northeastern Atlantic coasts, may have huge environmental effects in highly productive ecosystems where shellfish are exploited. The present study aims at determining the potential economic value of this marine species in terms of exploitable substances with high added value. Lipid content and phospholipid (PL) composition of this mollusk collected on the Bourgneuf Bay were studied through four seasons. Winter specimens contained the highest lipid levels (5.3% dry weight), including 69% of PLs. Phosphatidylcholine (PC) was the major PL class all year, accounting for 63.9% to 88.9% of total PLs. Consequently, the winter specimens were then investigated for PL fatty acids (FAs), and free sterols. Dimethylacetals (DMAs) were present (10.7% of PL FA + DMA mixture) revealing the occurrence of plasmalogens. More than forty FAs were identified, including 20:5n-3 (9.4%) and 22:6n-3 (7.3%) acids. Fourteen free sterols were present, including cholesterol at 31.3% of the sterol mixture and about 40% of phytosterols. These data on lipids of C. fornicata demonstrate their positive attributes for human nutrition and health. The PL mixture, rich in PC and polyunsaturated FAs, offers an interesting alternative source of high value-added marine lecithin.

  5. Functional and Structural Brain Plasticity Enhanced by Motor and Cognitive Rehabilitation in Multiple Sclerosis

    Luca Prosperini

    2015-01-01

    Full Text Available Rehabilitation is recognized to be important in ameliorating motor and cognitive functions, reducing disease burden, and improving quality of life in patients with multiple sclerosis (MS. In this systematic review, we summarize the existing evidences that motor and cognitive rehabilitation may enhance functional and structural brain plasticity in patients with MS, as assessed by means of the most advanced neuroimaging techniques, including diffusion tensor imaging and task-related and resting-state functional magnetic resonance imaging (MRI. In most cases, the rehabilitation program was based on computer-assisted/video game exercises performed in either an outpatient or home setting. Despite their heterogeneity, all the included studies describe changes in white matter microarchitecture, in task-related activation, and/or in functional connectivity following both task-oriented and selective training. When explored, relevant correlation between improved function and MRI-detected brain changes was often found, supporting the hypothesis that training-induced brain plasticity is specifically linked to the trained domain. Small sample sizes, lack of randomization and/or an active control group, as well as missed relationship between MRI-detected changes and clinical performance, are the major drawbacks of the selected studies. Knowledge gaps in this field of research are also discussed to provide a framework for future investigations.

  6. Dynamical density functional theory for arbitrary-shape colloidal fluids including inertia and hydrodynamic interactions

    Duran-Olivencia, Miguel A.; Goddard, Ben; Kalliadasis, Serafim

    2015-11-01

    Over the last few decades the classical density-functional theory (DFT) and its dynamic extensions (DDFTs) have become a remarkably powerful tool in the study of colloidal fluids. Recently there has been extensive research to generalise all previous DDFTs finally yielding a general DDFT equation (for spherical particles) which takes into account both inertia and hydrodynamic interactions (HI) which strongly influence non-equilibrium properties. The present work will be devoted to a further generalisation of such a framework to systems of anisotropic particles. To this end, the kinetic equation for the Brownian particle distribution function is derived starting from the Liouville equation and making use of Zwanzig's projection-operator techniques. By averaging over all but one particle, a DDFT equation is finally obtained with some similarities to that for spherical colloids. However, there is now an inevitable translational-rotational coupling which affects the diffusivity of asymmetric particles. Lastly, in the overdamped (high friction) limit the theory is notably simplified leading to a DDFT equation which agrees with previous derivations. We acknowledge financial support from European Research Council via Advanced Grant No. 247031.

  7. Multiple Functional Variants in cis Modulate PDYN Expression.

    Babbitt, Courtney C; Silverman, Jesse S; Haygood, Ralph; Reininga, Jennifer M; Rockman, Matthew V; Wray, Gregory A

    2010-02-01

    Understanding genetic variation and its functional consequences within cis-regulatory regions remains an important challenge in human genetics and evolution. Here, we present a fine-scale functional analysis of segregating variation within the cis-regulatory region of prodynorphin, a gene that encodes an endogenous opioid precursor with roles in cognition and disease. In order to characterize the functional consequences of segregating variation in cis in a region under balancing selection in different human populations, we examined associations between specific polymorphisms and gene expression in vivo and in vitro. We identified five polymorphisms within the 5' flanking region that affect transcript abundance: a 68-bp repeat recognized in prior studies, as well as two microsatellites and two single nucleotide polymorphisms not previously implicated as functional variants. The impact of these variants on transcription differs by brain region, sex, and cell type, implying interactions between cis genotype and the differentiated state of cells. The effects of individual variants on expression level are not additive in some combinations, implying epistatic interactions between nearby variants. These data reveal an unexpectedly complex relationship between segregating genetic variation and its expression-trait consequences and highlights the importance of close functional scrutiny of natural genetic variation within even relatively well-studied cis-regulatory regions.

  8. Pulmonary alveolar microlithiasis. A review including ultrastructural and pulmonary function studies

    Prakash, U.B.; Barham, S.S.; Rosenow, E.C.; Brown, M.L.; Payne, W.S.

    1983-01-01

    Pulmonary alveolar microlithiasis is a rare disease of unknown cause in which calcium phosphate microliths are deposited throughout the lungs. These deposits are of sufficient density to be almost diagnostic on chest roentgenograms. The Mayo Clinic experience with 8 patients is added to the approximately 120 cases reported in the world literature. The age range of all patients is from newborn to 80 years, with a mean age at diagnosis of about 35 years. No sexual predominance has been noted, but in about half of the reported cases a familial pattern has been found. The progression of the disease is generally very slow, some patients having been followed up for more than 30 years without evidence of change. No specific treatment is available. Pulmonary function studies demonstrate a tendency toward a restrictive pattern. Technetium-99m scanning and scanning and transmission electron microscopy are useful procedures for analysis of pulmonary alveolar microliths

  9. The impact of subjective cognitive fatigue and depression on cognitive function in patients with multiple sclerosis.

    Golan, Daniel; Doniger, Glen M; Wissemann, Karl; Zarif, Myassar; Bumstead, Barbara; Buhse, Marijean; Fafard, Lori; Lavi, Idit; Wilken, Jeffrey; Gudesblatt, Mark

    2018-02-01

    The association between subjective cognitive fatigue and objective cognitive dysfunction in patients with multiple sclerosis (PwMS) has been studied, with conflicting results. To explore the impact of fatigue on cognitive function, while controlling for the influence of depression, disability, comorbidities, and psychotropic medications. PwMS completed a computerized cognitive testing battery with age- and education-adjusted cognitive domain scores. Disability (Expanded Disability Status Scale (EDSS)), cognitive fatigue, and depression were concurrently evaluated. In all, 699 PwMS were included. Both cognitive fatigue and depression were significantly and negatively correlated with the same cognitive domains: information processing speed, executive function, attention, motor function, and memory (-0.15 ⩽ r ⩽ -0.14 for cognitive fatigue; -0.24 ⩽ r ⩽ -0.19 for depression). Multivariate analysis revealed significant but small independent correlations only between depression and neuropsychological test results, while cognitive fatigue had no independent correlation with objective cognitive function except for a trend toward impaired motor function in highly fatigued PwMS. Depression and cognitive fatigue accounted for no more than 6% of the variance in objective cognitive domain scores. Cognitive fatigue is not independently related to objective cognitive impairment. Depression may influence cognitive function of PwMS primarily when it is severe. Cognitive impairment in PwMS should not be ascribed to fatigue or mild depression.

  10. Multiple sclerosis impairs regional functional connectivity in the cerebellum

    Dogonowski, Anne-Marie; Andersen, Kasper Winther; Madsen, Kristoffer Hougaard

    2013-01-01

    in the cerebellum in MS. This might be caused by a functional disruption of cortico-ponto-cerebellar and spino-cerebellar inputs, since patients with higher lesion load in the left cerebellar peduncles showed a stronger reduction in cerebellar homogeneity. In patients, two clusters in the left posterior cerebellum...

  11. Tyrosine Residues Regulate Multiple Nuclear Functions of P54nrb.

    Lee, Ahn R; Hung, Wayne; Xie, Ning; Liu, Liangliang; He, Leye; Dong, Xuesen

    2017-04-01

    The non-POU-domain-containing octamer binding protein (NONO; also known as p54nrb) has various nuclear functions ranging from transcription, RNA splicing, DNA synthesis and repair. Although tyrosine phosphorylation has been proposed to account for the multi-functional properties of p54nrb, direct evidence on p54nrb as a phosphotyrosine protein remains unclear. To investigate the tyrosine phosphorylation status of p54nrb, we performed site-directed mutagenesis on the five tyrosine residues of p54nrb, replacing the tyrosine residues with phenylalanine or alanine, and immunoblotted for tyrosine phosphorylation. We then preceded with luciferase reporter assays, RNA splicing minigene assays, co-immunoprecipitation, and confocal microscopy to study the function of p54nrb tyrosine residues on transcription, RNA splicing, protein-protein interaction, and cellular localization. We found that p54nrb was not phosphorylated at tyrosine residues. Rather, it has non-specific binding affinity to anti-phosphotyrosine antibodies. However, replacement of tyrosine with phenylalanine altered p54nrb activities in transcription co-repression and RNA splicing in gene context-dependent fashions by means of differential regulation of p54nrb protein association with its interacting partners and co-regulators of transcription and splicing. These results demonstrate that tyrosine residues, regardless of phosphorylation status, are important for p54nrb function. J. Cell. Physiol. 232: 852-861, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  12. Inflation including collapse of the wave function: the quasi-de Sitter case

    Leon, Gabriel [Universidad de Buenos Aires, Ciudad Universitaria-PabI, Departamento de Fisica, Facultad de Ciencias Exactas y Naturales, Buenos Aires (Argentina); Landau, Susana J. [Universidad de Buenos Aires y IFIBA, CONICET, Ciudad Universitaria-PabI, Departamento de Fisica, Facultad de Ciencias Exactas y Naturales, Buenos Aires (Argentina); Piccirilli, Maria Pia [Universidad Nacional de La Plata, Grupo de Astrofisica, Relatividad y Cosmologia, Facultad de Ciencias Astronomicas y Geofisicas, Pcia de Buenos Aires (Argentina)

    2015-08-15

    The precise physical mechanism describing the emergence of the seeds of cosmic structure from a perfect isotropic and homogeneous universe has not been fully explained by the standard version of inflationary models. To handle this shortcoming, D. Sudarsky and collaborators have developed a proposal: the self-induced collapse hypothesis. In this scheme, the objective collapse of the inflaton wave function is responsible for the emergence of inhomogeneity and anisotropy at all scales. In previous papers, the proposal was developed with an almost exact de Sitter space-time approximation for the background that led to a perfect scale-invariant power spectrum. In the present article, we consider a full quasi-de Sitter expansion and calculate the primordial power spectrum for three different choices of the self-induced collapse. The consideration of a quasi-de Sitter background allows us to distinguish departures from an exact scale-invariant power spectrum that are due to the inclusion of the collapse hypothesis. These deviations are also different from the prediction of standard inflationary models with a running spectral index. A comparison with the primordial power spectrum and the CMB temperature fluctuation spectrum preferred by the latest observational data is also discussed. From the analysis performed in this work, it follows that most of the collapse schemes analyzed in this paper are viable candidates to explain the present observations of the CMB fluctuation spectrum. (orig.)

  13. Inflation including collapse of the wave function: the quasi-de Sitter case

    Leon, Gabriel; Landau, Susana J.; Piccirilli, Maria Pia

    2015-01-01

    The precise physical mechanism describing the emergence of the seeds of cosmic structure from a perfect isotropic and homogeneous universe has not been fully explained by the standard version of inflationary models. To handle this shortcoming, D. Sudarsky and collaborators have developed a proposal: the self-induced collapse hypothesis. In this scheme, the objective collapse of the inflaton wave function is responsible for the emergence of inhomogeneity and anisotropy at all scales. In previous papers, the proposal was developed with an almost exact de Sitter space-time approximation for the background that led to a perfect scale-invariant power spectrum. In the present article, we consider a full quasi-de Sitter expansion and calculate the primordial power spectrum for three different choices of the self-induced collapse. The consideration of a quasi-de Sitter background allows us to distinguish departures from an exact scale-invariant power spectrum that are due to the inclusion of the collapse hypothesis. These deviations are also different from the prediction of standard inflationary models with a running spectral index. A comparison with the primordial power spectrum and the CMB temperature fluctuation spectrum preferred by the latest observational data is also discussed. From the analysis performed in this work, it follows that most of the collapse schemes analyzed in this paper are viable candidates to explain the present observations of the CMB fluctuation spectrum. (orig.)

  14. Structural and functional effects of heavy metals on the nervous system, including sense organs, of fish

    Baatrup, E

    1991-01-01

    metals are well known pollutants in the aquatic environment. Their interaction with relevant chemical stimuli may interfere with the communication between fish and environment. 5. The affinity for a number of ligands and macromolecules makes heavy metals most potent neurotoxins. 6. The present Mini......1. Today, fish in the environment are inevitably exposed to chemical pollution. Although most hazardous substances are present at concentrations far below the lethal level, they may still cause serious damage to the life processes of these animals. 2. Fish depend on an intact nervous system......, including their sense organs, for mediating relevant behaviour such as food search, predator recognition, communication and orientation. 3. Unfortunately, the nervous system is most vulnerable and injuries to its elements may dramatically change the behaviour and consequently the survival of fish. 4. Heavy...

  15. New MoM code incorporating multiple domain basis functions

    Lysko, AA

    2011-08-01

    Full Text Available piecewise linear approximation of geometry. This often leads to an unnecessarily great number of unknowns used to model relatively small loop and spiral antennas, coils and other curved structures. This is because the program creates a dense mesh... to accelerate computation of the elements of the impedance matrix and showed acceleration factor exceeding an order of magnitude, subject to a high accuracy requirement. 3. On Code Functionality and Application Results The package of programs was written...

  16. Evaluation and Comparison of Multiple Test Methods, Including Real-time PCR, for Legionella Detection in Clinical Specimens

    Peci, Adriana; Winter, Anne-Luise; Gubbay, Jonathan B.

    2016-01-01

    Legionella is a Gram-negative bacterium that can cause Pontiac fever, a mild upper respiratory infection and Legionnaire’s disease, a more severe illness. We aimed to compare the performance of urine antigen, culture, and polymerase chain reaction (PCR) test methods and to determine if sputum is an acceptable alternative to the use of more invasive bronchoalveolar lavage (BAL). Data for this study included specimens tested for Legionella at Public Health Ontario Laboratories from 1st January, 2010 to 30th April, 2014, as part of routine clinical testing. We found sensitivity of urinary antigen test (UAT) compared to culture to be 87%, specificity 94.7%, positive predictive value (PPV) 63.8%, and negative predictive value (NPV) 98.5%. Sensitivity of UAT compared to PCR was 74.7%, specificity 98.3%, PPV 77.7%, and NPV 98.1%. Out of 146 patients who had a Legionella-positive result by PCR, only 66 (45.2%) also had a positive result by culture. Sensitivity for culture was the same using either sputum or BAL (13.6%); sensitivity for PCR was 10.3% for sputum and 12.8% for BAL. Both sputum and BAL yield similar results regardless testing methods (Fisher Exact p-values = 1.0, for each test). In summary, all test methods have inherent weaknesses in identifying Legionella; therefore, more than one testing method should be used. Obtaining a single specimen type from patients with pneumonia limits the ability to diagnose Legionella, particularly when urine is the specimen type submitted. Given ease of collection and similar sensitivity to BAL, clinicians are encouraged to submit sputum in addition to urine when BAL submission is not practical from patients being tested for Legionella. PMID:27630979

  17. Evaluation and comparison of multiple test methods, including real-time PCR, for Legionella detection in clinical specimens.

    Adriana Peci

    2016-08-01

    Full Text Available Legionella is a gram-negative bacterium that can cause Pontiac fever, a mild upper respiratory infection and Legionnaire’s disease, a more severe illness. We aimed to compare the performance of urine antigen, culture and PCR test methods and to determine if sputum is an alternative to the use of more invasive bronchoalveolar lavage (BAL. Data for this study included specimens tested for Legionella at PHOL from January 1, 2010 to April 30, 2014, as part of routine clinical testing. We found sensitivity of UAT compared to culture to be 87%, specificity 94.7%, positive predictive value (PPV 63.8% and negative predictive value (NPV 98.5%. Sensitivity of UAT compared to PCR was 74.7%, specificity 98.3%, PPV 77.7% and NPV 98.1%. Of 146 patients who had a Legionella positive result by PCR, only 66(45.2% also had a positive result by culture. Sensitivity for culture was the same using either sputum or BAL (13.6%; sensitivity for PCR was 10.3% for sputum and 12.8% for BAL. Both sputum and BAL yield similar results despite testing methods (Fisher Exact p-values=1.0, for each test. In summary, all test methods have inherent weaknesses in identifying Legionella; thereforemore than one testing method should be used. Obtaining a single specimen type from patients with pneumonia limits the ability to diagnose Legionella, particularly when urine is the specimen type submitted. Given ease of collection, and similar sensitivity to BAL, clinicians are encouraged to submit sputum in addition to urine when BAL submission is not practical, from patients being tested for Legionella.

  18. Airborne electromagnetic detection of shallow seafloor topographic features, including resolution of multiple sub-parallel seafloor ridges

    Vrbancich, Julian; Boyd, Graham

    2014-05-01

    The HoistEM helicopter time-domain electromagnetic (TEM) system was flown over waters in Backstairs Passage, South Australia, in 2003 to test the bathymetric accuracy and hence the ability to resolve seafloor structure in shallow and deeper waters (extending to ~40 m depth) that contain interesting seafloor topography. The topography that forms a rock peak (South Page) in the form of a mini-seamount that barely rises above the water surface was accurately delineated along its ridge from the start of its base (where the seafloor is relatively flat) in ~30 m water depth to its peak at the water surface, after an empirical correction was applied to the data to account for imperfect system calibration, consistent with earlier studies using the same HoistEM system. A much smaller submerged feature (Threshold Bank) of ~9 m peak height located in waters of 35 to 40 m depth was also accurately delineated. These observations when checked against known water depths in these two regions showed that the airborne TEM system, following empirical data correction, was effectively operating correctly. The third and most important component of the survey was flown over the Yatala Shoals region that includes a series of sub-parallel seafloor ridges (resembling large sandwaves rising up to ~20 m from the seafloor) that branch out and gradually decrease in height as the ridges spread out across the seafloor. These sub-parallel ridges provide an interesting topography because the interpreted water depths obtained from 1D inversion of TEM data highlight the limitations of the EM footprint size in resolving both the separation between the ridges (which vary up to ~300 m) and the height of individual ridges (which vary up to ~20 m), and possibly also the limitations of assuming a 1D model in areas where the topography is quasi-2D/3D.

  19. Biallelic germline and somatic mutations in malignant mesothelioma: multiple mutations in transcription regulators including mSWI/SNF genes.

    Yoshikawa, Yoshie; Sato, Ayuko; Tsujimura, Tohru; Otsuki, Taiichiro; Fukuoka, Kazuya; Hasegawa, Seiki; Nakano, Takashi; Hashimoto-Tamaoki, Tomoko

    2015-02-01

    We detected low levels of acetylation for histone H3 tail lysines in malignant mesothelioma (MM) cell lines resistant to histone deacetylase inhibitors. To identify the possible genetic causes related to the low histone acetylation levels, whole-exome sequencing was conducted with MM cell lines established from eight patients. A mono-allelic variant of BRD1 was common to two MM cell lines with very low acetylation levels. We identified 318 homozygous protein-damaging variants/mutations (18-78 variants/mutations per patient); annotation analysis showed enrichment of the molecules associated with mammalian SWI/SNF (mSWI/SNF) chromatin remodeling complexes and co-activators that facilitate initiation of transcription. In seven of the patients, we detected a combination of variants in histone modifiers or transcription factors/co-factors, in addition to variants in mSWI/SNF. Direct sequencing showed that homozygous mutations in SMARCA4, PBRM1 and ARID2 were somatic. In one patient, homozygous germline variants were observed for SMARCC1 and SETD2 in chr3p22.1-3p14.2. These exhibited extended germline homozygosity and were in regions containing somatic mutations, leading to a loss of BAP1 and PBRM1 expression in MM cell line. Most protein-damaging variants were heterozygous in normal tissues. Heterozygous germline variants were often converted into hemizygous variants by mono-allelic deletion, and were rarely homozygous because of acquired uniparental disomy. Our findings imply that MM might develop through the somatic inactivation of mSWI/SNF complex subunits and/or histone modifiers, including BAP1, in subjects that have rare germline variants of these transcription regulators and/or transcription factors/co-factors, and in regions prone to mono-allelic deletion during oncogenesis. © 2014 UICC.

  20. Functional Disturbances Within Frontostriatal Circuits Across Multiple Childhood Psychopathologies

    Marsh, Rachel; Maia, Tiago V.; Peterson, Bradley S.

    2009-01-01

    Objective Neuroimaging studies of healthy individuals inform us about the normative maturation of the frontostriatal circuits that subserve self-regulatory control processes. Findings from these studies can be used as a reference frame against which to compare the aberrant development of these processes in individuals across a wide range of childhood psychopathologies. Method The authors reviewed extensive neuroimaging evidence for the presence of abnormalities in frontostriatal circuits in children and adults with Tourette’s syndrome and obsessive-compulsive disorder (OCD) as well as a more limited number of imaging studies of adolescents and adults with anorexia nervosa or bulimia nervosa that, together, implicate dysregulation of frontostriatal control systems in the pathogenesis of these eating disorders. Results The presence of an impaired capacity for self-regulatory control that derives from abnormal development of frontostriatal circuits likely interacts in similar ways with normally occurring somatic sensations and motor urges, intrusive thoughts, sensations of hunger, and preoccupation with body shape and weight to contribute, respectively, to the development of the tics of Tourette’s syndrome, the obsessions of OCD, the binge eating behaviors of bulimia, and the self-starvation of anorexia. Conclusions Analogous brain mechanisms in parallel frontostriatal circuits, or even in differing portions of the same frontostriatal circuit, may underlie the differing behavioral disturbances in these multiple disorders, although further research is needed to confirm this hypothesis. PMID:19448188

  1. Ras proteins have multiple functions in vegetative cells of Dictyostelium.

    Bolourani, Parvin; Spiegelman, George; Weeks, Gerald

    2010-11-01

    During the aggregation of Dictyostelium cells, signaling through RasG is more important in regulating cyclic AMP (cAMP) chemotaxis, whereas signaling through RasC is more important in regulating the cAMP relay. However, RasC is capable of substituting for RasG for chemotaxis, since rasG⁻ cells are only partially deficient in chemotaxis, whereas rasC⁻/rasG⁻ cells are totally incapable of chemotaxis. In this study we have examined the possible functional overlap between RasG and RasC in vegetative cells by comparing the vegetative cell properties of rasG⁻, rasC⁻, and rasC⁻/rasG⁻ cells. In addition, since RasD, a protein not normally found in vegetative cells, is expressed in vegetative rasG⁻ and rasC⁻/rasG⁻ cells and appears to partially compensate for the absence of RasG, we have also examined the possible functional overlap between RasG and RasD by comparing the properties of rasG⁻ and rasC⁻/rasG⁻ cells with those of the mutant cells expressing higher levels of RasD. The results of these two lines of investigation show that RasD is capable of totally substituting for RasG for cytokinesis and growth in suspension, whereas RasC is without effect. In contrast, for chemotaxis to folate, RasC is capable of partially substituting for RasG, but RasD is totally without effect. Finally, neither RasC nor RasD is able to substitute for the role that RasG plays in regulating actin distribution and random motility. These specificity studies therefore delineate three distinct and none-overlapping functions for RasG in vegetative cells.

  2. Multiple lupus-associated ITGAM variants alter Mac-1 functions on neutrophils.

    Zhou, Yebin; Wu, Jianming; Kucik, Dennis F; White, Nathan B; Redden, David T; Szalai, Alexander J; Bullard, Daniel C; Edberg, Jeffrey C

    2013-11-01

    Multiple studies have demonstrated that single-nucleotide polymorphisms (SNPs) in the ITGAM locus (including the nonsynonymous SNPs rs1143679, rs1143678, and rs1143683) are associated with systemic lupus erythematosus (SLE). ITGAM encodes the protein CD11b, a subunit of the β2 integrin Mac-1. The purpose of this study was to determine the effects of ITGAM genetic variation on the biologic functions of neutrophil Mac-1. Neutrophils from ITGAM-genotyped and -sequenced healthy donors were isolated for functional studies. The phagocytic capacity of neutrophil ITGAM variants was probed with complement-coated erythrocytes, serum-treated zymosan, heat-treated zymosan, and IgG-coated erythrocytes. The adhesion capacity of ITGAM variants, in adhering to either purified intercellular adhesion molecule 1 or tumor necrosis factor α-stimulated endothelial cells, was assessed in a flow chamber. Expression levels of total CD11b and activation of CD11b were assessed by flow cytometry. Mac-1-mediated neutrophil phagocytosis, determined in cultures with 2 different complement-coated particles, was significantly reduced in individuals with nonsynonymous variant alleles of ITGAM. This reduction in phagocytosis was related to variation at either rs1143679 (in the β-propeller region) or rs1143678/rs1143683 (highly linked SNPs in the cytoplasmic/calf-1 regions). Phagocytosis mediated by Fcγ receptors was also significantly reduced in donors with variant ITGAM alleles. Similarly, firm adhesion of neutrophils was significantly reduced in individuals with variant ITGAM alleles. These functional alterations were not attributable to differences in total receptor expression or activation. The nonsynonymous ITGAM variants rs1143679 and rs1143678/rs113683 contribute to altered Mac-1 function on neutrophils. These results underscore the need to consider multiple nonsynonymous SNPs when assessing the functional consequences of ITGAM variation on immune cell processes and the risk of SLE

  3. Functional Components of Cognitive Impairment in Multiple Sclerosis: A Cross-Sectional Investigation

    Jordi A. Matias-Guiu

    2017-11-01

    Full Text Available BackgroundCognitive impairment is frequent and disabling in multiple sclerosis (MS. Changes in information processing speed constitute the most important cognitive deficit in MS. However, given the clinical and topographical variability of the disease, cognitive impairment may vary greatly and appear in other forms in addition to slower information processing speed. Our aim was to determine the frequency of cognitive impairment, the principal cognitive domains, and components involved in MS and to identify factors associated with presence of cognitive impairment in these patients in a large series of patients.MethodsCross-sectional study of 311 patients with MS [236 with relapsing-remitting MS (RRMS, 52 with secondary progressive MS (SPMS, and 23 with primary progressive MS (PPMS]. Patients’ cognitive function was assessed with a comprehensive neuropsychological assessment protocol. Patients displaying deficits in 2 or more cognitive domains were considered to have cognitive impairment associated with MS. We conducted a principal component analysis to detect different cognitive patterns by identifying clusters of tests highly correlated to one another.ResultsCognitive impairment was detected in 41.5% of the sample, and it was more frequent in patients with SPMS and PPMS (P = 0.002. Expanded Disability Status Scale scores and education were independent predictors of cognitive impairment. Principal component analysis identified seven clusters: attention and basic executive function (including information processing speed, planning and high-level executive function, verbal memory and language, executive and visuospatial performance time, fatigue-depression, visuospatial function, and basic attention and verbal/visual working memory. Mean scoring of components 2 (high-order executive functioning and 3 (verbal memory-language was higher in patients with RRMS than in those with PPMS (component 2 and SPMS (component 3.ConclusionMS is linked to

  4. Economic values of production and functional traits, including residual feed intake, in Finnish milk production.

    Hietala, P; Wolfová, M; Wolf, J; Kantanen, J; Juga, J

    2014-02-01

    Improving the feed efficiency of dairy cattle has a substantial effect on the economic efficiency and on the reduction of harmful environmental effects of dairy production through lower feeding costs and emissions from dairy farming. To assess the economic importance of feed efficiency in the breeding goal for dairy cattle, the economic values for the current breeding goal traits and the additional feed efficiency traits for Finnish Ayrshire cattle under production circumstances in 2011 were determined. The derivation of economic values was based on a bioeconomic model in which the profit of the production system was calculated, using the generated steady state herd structure. Considering beef production from dairy farms, 2 marketing strategies for surplus calves were investigated: (A) surplus calves were sold at a young age and (B) surplus calves were fattened on dairy farms. Both marketing strategies were unprofitable when subsidies were not included in the revenues. When subsidies were taken into account, a positive profitability was observed in both marketing strategies. The marginal economic values for residual feed intake (RFI) of breeding heifers and cows were -25.5 and -55.8 €/kg of dry matter per day per cow and year, respectively. The marginal economic value for RFI of animals in fattening was -29.5 €/kg of dry matter per day per cow and year. To compare the economic importance among traits, the standardized economic weight of each trait was calculated as the product of the marginal economic value and the genetic standard deviation; the standardized economic weight expressed as a percentage of the sum of all standardized economic weights was called relative economic weight. When not accounting for subsidies, the highest relative economic weight was found for 305-d milk yield (34% in strategy A and 29% in strategy B), which was followed by protein percentage (13% in strategy A and 11% in strategy B). The third most important traits were calving

  5. A Powerful Test for Comparing Multiple Regression Functions.

    Maity, Arnab

    2012-09-01

    In this article, we address the important problem of comparison of two or more population regression functions. Recently, Pardo-Fernández, Van Keilegom and González-Manteiga (2007) developed test statistics for simple nonparametric regression models: Y(ij) = θ(j)(Z(ij)) + σ(j)(Z(ij))∊(ij), based on empirical distributions of the errors in each population j = 1, … , J. In this paper, we propose a test for equality of the θ(j)(·) based on the concept of generalized likelihood ratio type statistics. We also generalize our test for other nonparametric regression setups, e.g, nonparametric logistic regression, where the loglikelihood for population j is any general smooth function [Formula: see text]. We describe a resampling procedure to obtain the critical values of the test. In addition, we present a simulation study to evaluate the performance of the proposed test and compare our results to those in Pardo-Fernández et al. (2007).

  6. Acquisition and processing of multiple functional investigations in cardiology

    Baruthio, J.; Constantinesco, A.; Chavas, M.; Meyer, P.; Dumitresco, B.; Chambron, J.; Nikitine, S.; Voegtlin, R.

    1978-01-01

    This work is based on a acquisition and pretreating Service of data and signals resulting from several types of functional explorations in cardiology. This Service, through a specialised phone-line, is connected to the Medical Centre of Informatic where the different treatments and on occasion the recording of data are carried out. This functions according to the Real Time Executive System and the clinical results are send back to the investigation unit. The main types of cardiologic analysis as studied by the system are envisaged: measure in real time of the cardiac output and analysis of the radiocardiogram, measure and display of the thoracic potentials, spectral analysis of the vectorcardiogram, quantitative cineangiocardiography and analysis of intracardiac pressures. This system is particularly interesting in that it may treat several processes which could ask for a great capacity of storing and an important calculus power, see for instance the study of thoracic potentials. This type of analysis could not be envisaged financially with isolated calculators. The set of results obtained enables us to investigate thoroughly and precisely the cardiac performance [fr

  7. Validating archetypes for the Multiple Sclerosis Functional Composite.

    Braun, Michael; Brandt, Alexander Ulrich; Schulz, Stefan; Boeker, Martin

    2014-08-03

    Numerous information models for electronic health records, such as openEHR archetypes are available. The quality of such clinical models is important to guarantee standardised semantics and to facilitate their interoperability. However, validation aspects are not regarded sufficiently yet. The objective of this report is to investigate the feasibility of archetype development and its community-based validation process, presuming that this review process is a practical way to ensure high-quality information models amending the formal reference model definitions. A standard archetype development approach was applied on a case set of three clinical tests for multiple sclerosis assessment: After an analysis of the tests, the obtained data elements were organised and structured. The appropriate archetype class was selected and the data elements were implemented in an iterative refinement process. Clinical and information modelling experts validated the models in a structured review process. Four new archetypes were developed and publicly deployed in the openEHR Clinical Knowledge Manager, an online platform provided by the openEHR Foundation. Afterwards, these four archetypes were validated by domain experts in a team review. The review was a formalised process, organised in the Clinical Knowledge Manager. Both, development and review process turned out to be time-consuming tasks, mostly due to difficult selection processes between alternative modelling approaches. The archetype review was a straightforward team process with the goal to validate archetypes pragmatically. The quality of medical information models is crucial to guarantee standardised semantic representation in order to improve interoperability. The validation process is a practical way to better harmonise models that diverge due to necessary flexibility left open by the underlying formal reference model definitions.This case study provides evidence that both community- and tool-enabled review processes

  8. 25 CFR 1000.361 - Will the annual review include a review of the Secretary's residual trust functions?

    2010-04-01

    ... Evaluations § 1000.361 Will the annual review include a review of the Secretary's residual trust functions... Department official will be notified of the need for corrective action. The review of the Secretary's trust... 25 Indians 2 2010-04-01 2010-04-01 false Will the annual review include a review of the Secretary...

  9. Melatonin in Plants - Diversity of Levels and Multiplicity of Functions.

    Hardeland, Rüdiger

    2016-01-01

    Melatonin has been detected in numerous plant species. A particularly surprising finding concerns the highly divergent levels of melatonin that vary between species, organs and environmental conditions, from a few pg/g to over 20 μg/g, reportedly up to 200 μg/g. Highest values have been determined in oily seeds and in plant organs exposed to high UV radiation. The divergency of melatonin concentrations is discussed under various functional aspects and focused on several open questions. This comprises differences in precursor availability, catabolism, the relative contribution of isoenzymes of the melatonin biosynthetic pathway, and differences in rate limitation by either serotonin N-acetyltransferase or N-acetylserotonin O-methyltransferase. Other differences are related to the remarkable pleiotropy of melatonin, which exhibits properties as a growth regulator and morphogenetic factor, actually debated in terms of auxin-like effects, and as a signaling molecule that modulates pathways of ethylene, abscisic, jasmonic and salicylic acids and is involved in stress tolerance, pathogen defense and delay of senescence. In the context of high light/UV intensities, elevated melatonin levels exceed those required for signaling via stress-related phytohormones and may comprise direct antioxidant and photoprotectant properties, perhaps with a contribution of its oxidatively formed metabolites, such as N (1)-acetyl-N (2)-formyl-5-methoxykynuramine and its secondary products. High melatonin levels in seeds may also serve antioxidative protection and have been shown to promote seed viability and germination capacity.

  10. Estimation of Multiple Point Sources for Linear Fractional Order Systems Using Modulating Functions

    Belkhatir, Zehor; Laleg-Kirati, Taous-Meriem

    2017-01-01

    This paper proposes an estimation algorithm for the characterization of multiple point inputs for linear fractional order systems. First, using polynomial modulating functions method and a suitable change of variables the problem of estimating

  11. Multiple nutritional deficiencies in cerebral palsy compounding physical and functional impairments

    P G Hariprasad

    2017-01-01

    Full Text Available Introduction: Cerebral palsy (CP refers to a spectrum of disorders causing physical and intellectual morbidity. Macro and micro nutrient deficiencies often contribute to the subnormal physical and mental capabilities of them. Objectives: To assess the growth, nutritional status, physical and functional ability and quality of life in cerebral palsy children and to determine any relation with their gross motor and functional capabilities. Method: The study was conducted at a Tertiary Care Centre, with the participants in the age group 1-16 years. A pretested evaluation tool was prepared which included Anthropometric measurements, tests for hemoglobin and Vitamin D estimation, evidence of micronutrient deficiencies, Dietary patterns, Epidemiological factors, Functional assessment using GMFM (Gross Motor Function Measure and FIM (Functional Independent Measurement scales and Quality of life (QOL assessment. The data was statistically analyzed. Results: Out of the 41 children, 30 had quadriplegia, 3 had hemiplegia and 8 had spastic diplegia. 34 (82.9% were severely underweight, 35 (85.4% had severe stunting and 38 (92.7% had severe wasting. Micronutrient deficiencies were noted like vitamin B complex deficiency in 37 (90.2%, vitamin A deficiency in 31 (75.6%, low vitamin D levels in 27 (65.9% and insufficient levels in 9 (22%, severe anemia in 5 (12.2% and moderate anemia in 26 (63.4%.The gross motor and functional scores were suboptimum in the majority of patients and the care givers had significant impairment in the quality of life. Conclusion: Majority of children with cerebral palsy had multiple nutritional deficiencies, gross motor and functional disabilities. QOL of the children and their care givers were suboptimum. A comprehensive package that address dietary intake, correction of micronutrient deficiencies especially anemia and vitamin D deficiency, physical and emotional support is recommended for the wellbeing of the affected children.

  12. “The Relationship between Executive Functioning, Processing Speed and White Matter Integrity in Multiple Sclerosis”

    Genova, Helen M.; DeLuca, John; Chiaravalloti, Nancy; Wylie, Glenn

    2014-01-01

    The primary purpose of the current study was to examine the relationship between performance on executive tasks and white matter integrity, assessed by diffusion tensor imaging (DTI) in Multiple Sclerosis (MS). A second aim was to examine how processing speed affects the relationship between executive functioning and FA. This relationship was examined in two executive tasks that rely heavily on processing speed: the Color-Word Interference Test and Trail-Making Test (Delis-Kaplan Executive Function System). It was hypothesized that reduced fractional anisotropy (FA) is related to poor performance on executive tasks in MS, but that this relationship would be affected by the statistical correction of processing speed from the executive tasks. 15 healthy controls and 25 persons with MS participated. Regression analyses were used to examine the relationship between executive functioning and FA, both before and after processing speed was removed from the executive scores. Before processing speed was removed from the executive scores, reduced FA was associated with poor performance on Color-Word Interference Test and Trail-Making Test in a diffuse network including corpus callosum and superior longitudinal fasciculus. However, once processing speed was removed, the relationship between executive functions and FA was no longer significant on the Trail Making test, and significantly reduced and more localized on the Color-Word Interference Test. PMID:23777468

  13. Sequential optimization of matrix chain multiplication relative to different cost functions

    Chikalov, Igor; Hussain, Shahid; Moshkov, Mikhail

    2011-01-01

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

  14. Programmable release of multiple protein drugs from aptamer-functionalized hydrogels via nucleic acid hybridization.

    Battig, Mark R; Soontornworajit, Boonchoy; Wang, Yong

    2012-08-01

    Polymeric delivery systems have been extensively studied to achieve localized and controlled release of protein drugs. However, it is still challenging to control the release of multiple protein drugs in distinct stages according to the progress of disease or treatment. This study successfully demonstrates that multiple protein drugs can be released from aptamer-functionalized hydrogels with adjustable release rates at predetermined time points using complementary sequences (CSs) as biomolecular triggers. Because both aptamer-protein interactions and aptamer-CS hybridization are sequence-specific, aptamer-functionalized hydrogels constitute a promising polymeric delivery system for the programmable release of multiple protein drugs to treat complex human diseases.

  15. Using multiple schedules during functional communication training to promote rapid transfer of treatment effects.

    Fisher, Wayne W; Greer, Brian D; Fuhrman, Ashley M; Querim, Angie C

    2015-12-01

    Multiple schedules with signaled periods of reinforcement and extinction have been used to thin reinforcement schedules during functional communication training (FCT) to make the intervention more practical for parents and teachers. We evaluated whether these signals would also facilitate rapid transfer of treatment effects across settings and therapists. With 2 children, we conducted FCT in the context of mixed (baseline) and multiple (treatment) schedules introduced across settings or therapists using a multiple baseline design. Results indicated that when the multiple schedules were introduced, the functional communication response came under rapid discriminative control, and problem behavior remained at near-zero rates. We extended these findings with another individual by using a more traditional baseline in which problem behavior produced reinforcement. Results replicated those of the previous participants and showed rapid reductions in problem behavior when multiple schedules were implemented across settings. © Society for the Experimental Analysis of Behavior.

  16. Correlates of sexual function in male and female patients with multiple sclerosis.

    Lew-Starowicz, Michal; Rola, Rafal

    2014-09-01

    Many factors have been suggested to contribute to sexual dysfunction (SD) in multiple sclerosis (MS) patients, but the research on their impact on sexual functioning (SF) and sexual quality of life (SQoL) remains scant. The aim of this study was to investigate correlates of SF and SQoL in MS patients, as well as possible gender differences. 204 MS patients were interviewed, completed the questionnaires, and underwent neurological assessment. Primary outcome measures included the International Index of Erectile Function, the Female Sexual Function Questionnaire, the Sexual Quality of Life Questionnaire, the Beck Depression Inventory, and the Expanded Disability Status Scale. The course and duration of the disease did not predict patients' SF. Negative correlations were found for brainstem symptoms with orgasmic function and overall satisfaction in men and between cognitive functioning and the partner domain in women. Interestingly, brainstem symptoms correlated positively with the arousal domain in women. More than half (52.1%) of patients fulfilled Beck Depression Inventory criteria for depression, and these patients showed more SD than nondepressive individuals. The strongest negative correlations with depressive symptoms were found for desire, erectile function, and overall satisfaction with sexual life in men and for orgasm and sexual enjoyment in women. Deterioration in particular domains of SF was clearly related with diminished SQoL. The main gender difference was a strong influence of decreased desire on SQoL in women and no such correlation in men. Negative assessment of the relationship with partner significantly affected all domains of SF and SQoL in MS women and the desire domain in MS men. Several correlates of SF in MS patients were found. The role of brainstem symptoms needs further investigation. Clinicians should pay close attention to depressive symptoms and relationship factors in MS patients who suffer from SD. © 2014 International Society for

  17. A Multimodal, Nonpharmacologic Intervention Improves Mood and Cognitive Function in People with Multiple Sclerosis.

    Lee, Jennifer E; Bisht, Babita; Hall, Michael J; Rubenstein, Linda M; Louison, Rebecca; Klein, Danielle T; Wahls, Terry L

    2017-01-01

    The objective of this study was to examine whether participation in a 12-month multimodal intervention would improve mood and cognitive function in adults with progressive multiple sclerosis (MS). In this one-arm, open-label feasibility trial, participants were prescribed a home-based multimodal intervention, including (1) a modified Paleolithic diet; (2) an exercise program (stretching and strengthening of the trunk and lower limb muscles); (3) neuromuscular electrical stimulation (EStim) of trunk and lower limb muscles; and (4) stress management (meditation and self-massage). Individuals completed measures of mood (Beck Anxiety and Depression Inventories) and cognitive (Cognitive Stability Index, Cognitive Screening Test, Delis-Kaplan Executive Function System) and executive function (Wechsler Adult Intelligence Scale) at baseline and 3, 6, 9, and 12 months after the start of the intervention. Dosage of the multimodal intervention was assessed at 3, 6, 9, and 12 months. The more individuals participated in the intervention activities, the greater improvements they had from baseline to 12 months on self-report measures of anxiety (Beck Anxiety Inventory [BAI]; ps = 0.001 to 0.02), depression (Beck Depression Inventory [BDI]; ps = Mood and cognitive improvements were more closely related to a higher intake of the modified Paleolithic diet than to exercise and stress management dosage. Anxiety and depression changes were evident after just a few months, whereas changes in cognitive function were generally not observed until later in the intervention period. Mood and cognitive function changes from baseline to 12 months were significantly associated with fatigue improvements (ps = exercise, EStim, and stress management intervention like this one has the potential to improve the mood and cognitive symptoms that can lead to considerable suffering in people with MS, potentially improving quality of life and function for people with progressive MS.

  18. Mental Health in Multiple Sclerosis Patients without Limitation of Physical Function: The Role of Physical Activity

    Alexander Tallner

    2015-07-01

    Full Text Available Multiple sclerosis (MS patients, in general, show reduced physical function, physical activity, and quality of life. Positive associations between physical activity and quality of life have been reported. In particular, we were interested in the relation between physical activity and mental health in MS patients without limitation of physical function, since limitations of physical function may influence both physical activity and quality of life. Assessment comprised the Baecke questionnaire on physical activity, the Short Form 36 Health Survey (SF-36, and Beck Depression Inventory (BDI. We ranked our sample according to physical activity into four groups and performed an ANOVA to analyze the relationship between levels of physical activity and health-related quality of life (HRQoL. Then we performed a subgroup analysis and included patients with unlimited walking distance and a score of less than 18 in the BDI. Most active vs. inactive patients were compared for the mental subscales of the SF-36 and depression scores. From 632 patients, 265 met inclusion criteria and hence quartiles were filled with 67 patients each. Active and inactive patients did not differ considerably in physical function. In contrast, mental subscales of the SF-36 were higher in active patients. Remarkable and significant differences were found regarding vitality, general health perception, social functioning and mental health, all in favor of physically active patients. Our study showed that higher physical activity is still associated with higher mental health scores even if limitations of physical function are accounted for. Therefore, we believe that physical activity and exercise have considerable health benefits for MS patients.

  19. Multiple Time Series Forecasting Using Quasi-Randomized Functional Link Neural Networks

    Thierry Moudiki

    2018-03-01

    Full Text Available We are interested in obtaining forecasts for multiple time series, by taking into account the potential nonlinear relationships between their observations. For this purpose, we use a specific type of regression model on an augmented dataset of lagged time series. Our model is inspired by dynamic regression models (Pankratz 2012, with the response variable’s lags included as predictors, and is known as Random Vector Functional Link (RVFL neural networks. The RVFL neural networks have been successfully applied in the past, to solving regression and classification problems. The novelty of our approach is to apply an RVFL model to multivariate time series, under two separate regularization constraints on the regression parameters.

  20. "THE RELATION OF HYPERHOMOCYSTEINEMIA TO COGNITIVE FUNCTION AND BRAIN ATROPHY IN PATIENTS WITH MULTIPLE SCLEROSIS "

    M. Ghaffarpour

    2007-06-01

    Full Text Available Cognitive impairment may be a common even at the onset of multiple sclerosis (MS. In this case-control study, we tried to find out the probable relationship between homocysteine levels and cerebral atrophy or cognitive impairment in patients with multiple sclerosis. One hundred fifty six patients who had MS according to McDonald diagnostic criteria were included in this study. Patients’ age, gender, and educational level, MS duration and clinical type, disability, cognitive function state based on minimental state examination (MMSE, presence of hyperhomocysteinemia, and brain atrophy were evaluated. There was no statistically significant relationship between hyperhomocysteinemia and cognitive status. Total homocysteine levels had a significant correlation with MMSE score only in those patients with elementary level of education. Also total homocysteine levels and overall cerebral atrophy did not indicate significant relationship according to those independent variables mentioned above except in the patients with EDSS less than 6. When intercaudate ratio > 0.10 was applied as a criterion for cerebral atrophy, we found that hyperhomocysteinemia related significantly to intercaudate ratio > 0.10 in females, aged between 21 and 30 years, MS duration ≤ 5 years, primary progressive MS and relapsing-remitting MS clinical types, EDSS ≤ 3 and elementary level of education. We suggest applying MMSE only for the first step of cognitive function survey. In the next steps, much more exact test must be used (e.g. MSNQ. Also we can not suggest measuring plasma homocysteine level as criterion for monitoring the cognitive function in patients with MS.

  1. More Than Just Accuracy: A Novel Method to Incorporate Multiple Test Attributes in Evaluating Diagnostic Tests Including Point of Care Tests.

    Thompson, Matthew; Weigl, Bernhard; Fitzpatrick, Annette; Ide, Nicole

    2016-01-01

    Current frameworks for evaluating diagnostic tests are constrained by a focus on diagnostic accuracy, and assume that all aspects of the testing process and test attributes are discrete and equally important. Determining the balance between the benefits and harms associated with new or existing tests has been overlooked. Yet, this is critically important information for stakeholders involved in developing, testing, and implementing tests. This is particularly important for point of care tests (POCTs) where tradeoffs exist between numerous aspects of the testing process and test attributes. We developed a new model that multiple stakeholders (e.g., clinicians, patients, researchers, test developers, industry, regulators, and health care funders) can use to visualize the multiple attributes of tests, the interactions that occur between these attributes, and their impacts on health outcomes. We use multiple examples to illustrate interactions between test attributes (test availability, test experience, and test results) and outcomes, including several POCTs. The model could be used to prioritize research and development efforts, and inform regulatory submissions for new diagnostics. It could potentially provide a way to incorporate the relative weights that various subgroups or clinical settings might place on different test attributes. Our model provides a novel way that multiple stakeholders can use to visualize test attributes, their interactions, and impacts on individual and population outcomes. We anticipate that this will facilitate more informed decision making around diagnostic tests.

  2. Psychometrics of Multiple Choice Questions with Non-Functioning Distracters: Implications to Medical Education.

    Deepak, Kishore K; Al-Umran, Khalid Umran; AI-Sheikh, Mona H; Dkoli, B V; Al-Rubaish, Abdullah

    2015-01-01

    The functionality of distracters in a multiple choice question plays a very important role. We examined the frequency and impact of functioning and non-functioning distracters on psychometric properties of 5-option items in clinical disciplines. We analyzed item statistics of 1115 multiple choice questions from 15 summative assessments of undergraduate medical students and classified the items into five groups by their number of non-functioning distracters. We analyzed the effect of varying degree of non-functionality ranging from 0 to 4, on test reliability, difficulty index, discrimination index and point biserial correlation. The non-functionality of distracters inversely affected the test reliability and quality of items in a predictable manner. The non-functioning distracters made the items easier and lowered the discrimination index significantly. Three non-functional distracters in a 5-option MCQ significantly affected all psychometric properties (p psychometrically as effective as 5-option items. Our study reveals that a multiple choice question with 3 functional options provides lower most limit of item format that has adequate psychometric property. The test containing items with less number of functioning options have significantly lower reliability. The distracter function analysis and revision of nonfunctioning distracters can serve as important methods to improve the psychometrics and reliability of assessment.

  3. Multiple zeta functions and double wrapping in planar N=4 SYM

    Leurent, Sébastien; Volin, Dmytro

    2013-10-01

    Using the FiNLIE solution of the AdS/CFT Y-system, we compute the anomalous dimension of the Konishi operator in planar N=4 SYM up to eight loops, i.e. up to the leading double wrapping order. At this order a non-reducible Euler-Zagier sum, ζ1,2,8, appears for the first time. We find that at all orders in perturbation, every spectral-dependent quantity of the Y-system is expressed through multiple Hurwitz zeta functions, hence we provide a Mathematica package to manipulate these functions, including the particular case of Euler-Zagier sums. Furthermore, we conjecture that only Euler-Zagier sums can appear in the answer for the anomalous dimension at any order in perturbation theory. We also resum the leading transcendentality terms of the anomalous dimension at all orders, obtaining a simple result in terms of Bessel functions. Finally, we demonstrate that exact Bethe equations should be related to an absence of poles condition that becomes especially non-trivial at double wrapping.

  4. Volatile terpenoids: multiple functions, biosynthesis, modulation and manipulation by genetic engineering.

    Abbas, Farhat; Ke, Yanguo; Yu, Rangcai; Yue, Yuechong; Amanullah, Sikandar; Jahangir, Muhammad Muzammil; Fan, Yanping

    2017-11-01

    Terpenoids play several physiological and ecological functions in plant life through direct and indirect plant defenses and also in human society because of their enormous applications in the pharmaceutical, food and cosmetics industries. Through the aid of genetic engineering its role can by magnified to broad spectrum by improving genetic ability of crop plants, enhancing the aroma quality of fruits and flowers and the production of pharmaceutical terpenoids contents in medicinal plants. Terpenoids are structurally diverse and the most abundant plant secondary metabolites, playing an important role in plant life through direct and indirect plant defenses, by attracting pollinators and through different interactions between the plants and their environment. Terpenoids are also significant because of their enormous applications in the pharmaceutical, food and cosmetics industries. Due to their broad distribution and functional versatility, efforts are being made to decode the biosynthetic pathways and comprehend the regulatory mechanisms of terpenoids. This review summarizes the recent advances in biosynthetic pathways, including the spatiotemporal, transcriptional and post-transcriptional regulatory mechanisms. Moreover, we discuss the multiple functions of the terpene synthase genes (TPS), their interaction with the surrounding environment and the use of genetic engineering for terpenoid production in model plants. Here, we also provide an overview of the significance of terpenoid metabolic engineering in crop protection, plant reproduction and plant metabolic engineering approaches for pharmaceutical terpenoids production and future scenarios in agriculture, which call for sustainable production platforms by improving different plant traits.

  5. On functional determinants of matrix differential operators with multiple zero modes

    Falco, G.M.; Fedorenko, Andrey A; Gruzberg, Ilya A

    2017-01-01

    We generalize the method of computing functional determinants with a single excluded zero eigenvalue developed by McKane and Tarlie to differential operators with multiple zero eigenvalues. We derive general formulas for such functional determinants of $r\\times r$ matrix second order differential

  6. Linking and Psychological Functioning in a Chinese Sample: The Multiple Mediation of Response to Positive Affect

    Yang, Hongfei; Li, Juan

    2016-01-01

    The present study examined the associations between linking, response to positive affect, and psychological functioning in Chinese college students. The results of conducting multiple mediation analyses indicated that emotion- and self-focused positive rumination mediated the relationship between linking and psychological functioning, whereas…

  7. Effects of Functional Mobility Skills Training for Adults with Severe Multiple Disabilities

    Whinnery, Stacie B.; Whinnery, Keith W.

    2011-01-01

    This study investigated the effects of a functional mobility program on the functional standing and walking skills of five adults with developmental disabilities. The Mobility Opportunities Via Education (MOVE) Curriculum was implemented using a multiple-baseline across subjects design. Repeated measures were taken during baseline, intervention…

  8. Micropatterning of Functional Conductive Polymers with Multiple Surface Chemistries in Register

    Lind, Johan Ulrik; Acikgöz, Canet; Daugaard, Anders Egede

    2012-01-01

    A versatile procedure is presented for fast and efficient micropatterning of multiple types of covalently bound surface chemistry in perfect register on and between conductive polymer microcircuits. The micropatterning principle is applied to several types of native and functionalized PEDOT (poly(3...... functionalized conjugated polymer systems....

  9. Curvelet-domain multiple matching method combined with cubic B-spline function

    Wang, Tong; Wang, Deli; Tian, Mi; Hu, Bin; Liu, Chengming

    2018-05-01

    Since the large amount of surface-related multiple existed in the marine data would influence the results of data processing and interpretation seriously, many researchers had attempted to develop effective methods to remove them. The most successful surface-related multiple elimination method was proposed based on data-driven theory. However, the elimination effect was unsatisfactory due to the existence of amplitude and phase errors. Although the subsequent curvelet-domain multiple-primary separation method achieved better results, poor computational efficiency prevented its application. In this paper, we adopt the cubic B-spline function to improve the traditional curvelet multiple matching method. First, select a little number of unknowns as the basis points of the matching coefficient; second, apply the cubic B-spline function on these basis points to reconstruct the matching array; third, build constraint solving equation based on the relationships of predicted multiple, matching coefficients, and actual data; finally, use the BFGS algorithm to iterate and realize the fast-solving sparse constraint of multiple matching algorithm. Moreover, the soft-threshold method is used to make the method perform better. With the cubic B-spline function, the differences between predicted multiple and original data diminish, which results in less processing time to obtain optimal solutions and fewer iterative loops in the solving procedure based on the L1 norm constraint. The applications to synthetic and field-derived data both validate the practicability and validity of the method.

  10. DMPD: Suppressor of cytokine signaling (SOCS) 2, a protein with multiple functions. [Dynamic Macrophage Pathway CSML Database

    Full Text Available 17070092 Suppressor of cytokine signaling (SOCS) 2, a protein with multiple function...Epub 2006 Oct 27. (.png) (.svg) (.html) (.csml) Show Suppressor of cytokine signaling (SOCS) 2, a protein with multiple function...SOCS) 2, a protein with multiple functions. Authors Rico-Bautista E, Flores-Morales A, Fernandez-Perez L. Pu

  11. Availability of thermodynamic system with multiple performance parameters based on vector-universal generating function

    Cai Qi; Shang Yanlong; Chen Lisheng; Zhao Yuguang

    2013-01-01

    Vector-universal generating function was presented to analyze the availability of thermodynamic system with multiple performance parameters. Vector-universal generating function of component's performance was defined, the arithmetic model based on vector-universal generating function was derived for the thermodynamic system, and the calculation method was given for state probability of multi-state component. With the stochastic simulation of the degeneration trend of the multiple factors, the system availability with multiple performance parameters was obtained under composite factors. It is shown by an example that the results of the availability obtained by the binary availability analysis method are somewhat conservative, and the results considering parameter failure based on vector-universal generating function reflect the operation characteristics of the thermodynamic system better. (authors)

  12. Noncoding Subgenomic Flavivirus RNA: Multiple Functions in West Nile Virus Pathogenesis and Modulation of Host Responses

    Justin A. Roby

    2014-01-01

    Full Text Available Flaviviruses are a large group of positive strand RNA viruses transmitted by arthropods that include many human pathogens such as West Nile virus (WNV, Japanese encephalitis virus (JEV, yellow fever virus, dengue virus, and tick-borne encephalitis virus. All members in this genus tested so far are shown to produce a unique subgenomic flavivirus RNA (sfRNA derived from the 3' untranslated region (UTR. sfRNA is a product of incomplete degradation of genomic RNA by the cell 5'–3' exoribonuclease XRN1 which stalls at highly ordered secondary RNA structures at the beginning of the 3'UTR. Generation of sfRNA results in inhibition of XRN1 activity leading to an increase in stability of many cellular mRNAs. Mutant WNV deficient in sfRNA generation was highly attenuated displaying a marked decrease in cytopathicity in cells and pathogenicity in mice. sfRNA has also been shown to inhibit the antiviral activity of IFN-α/β by yet unknown mechanism and of the RNAi pathway by likely serving as a decoy substrate for Dicer. Thus, sfRNA is involved in modulating multiple cellular pathways to facilitate viral pathogenicity; however the overlying mechanism linking all these multiple functions of sfRNA remains to be elucidated.

  13. Multiple functions of a multi-component mating pheromone in sea lamprey Petromyzon marinus

    Johnson, N.S.; Yun, S.-S.; Buchinger, T.J.; Li, W.

    2012-01-01

    The role of the C24 sulphate in the mating pheromone component, 7α,12α,24-trihydroxy-5α-cholan-3-one 24-sulphate (3kPZS), to specifically induce upstream movement in ovulated female sea lampreys Petromyzon marinus was investigated. 7α,12α-dihydroxy-5α-cholan-3-one 24-oic acid (3kACA), a structurally similar bile acid released by spermiated males, but lacking the C24 sulphate ester, was tested in bioassays at concentrations between 10−11 and 10−14 molar (M). 3kACA did not induce upstream movement in females or additional reproductive behaviours. In contrast, spermiated male washings induced upstream movement, prolonged retention on a nest and induced an array of nesting behaviours. Differential extraction and elution by solid-phase extraction resins showed that components other than 3kPZS + 3kACA are necessary to retain females on nests and induce nest cleaning behaviours. All pheromone components, including components in addition to 3kPZS + 3kACA that retain females and induce nest cleaning behaviours were released from the anterior region of the males, as had been reported for 3kPZS. It is concluded that the sea lamprey male mating pheromone has multiple functions and is composed of multiple components.

  14. Deformable microparticles with multiple functions for drug delivery and device testing

    Thula, Taili T.

    Since the HIV epidemic of the 1990s, researchers have attempted to develop a red blood cell analog. Even though some of these substitutes are now in Phase III of clinical trials, their use is limited by side effects and short half-life in the human body. As a result, there is still a need for an effective erythrocyte analog with minimum immunogenic and side effects, so that it can be used for multiple applications. Finding new approaches to develop more efficient blood substitutes will not only bring valuable advances in the clinical approach, but also in the area of in vitro testing of medical devices. We examined the feasibility of creating a deformable multi-functional, biodegradable, biocompatible particle for applications in drug delivery and device testing. As a preliminary evaluation, we synthesized different types of microcapsules using natural and synthetic polymers, various cross-linking agents, and diverse manufacturing techniques. After fully characterizing of each system, we determined the most promising red blood cell analog in terms of deformability, stability and toxicity. We also examined the encapsulation and release of bovine serum albumin (BSA) within these deformable particles. After removal of cross-linkers, zinc- and copper-alginate microparticles surrounded by multiple polyelectrolyte layers of chitosan oligosaccharide and alginate were deformable and remained stable under physiological pressures applied by the micropipette technique. In addition, multiple coatings decreased toxicity of heavy-metal crosslinked particles. BSA encapsulation and release from chitosan-alginate microspheres were contingent on the crosslinker and number of polyelectrolyte coatings, respectively. Further rheological studies are needed to determine how closely these particles simulate the behavior of erythrocytes. Also, studies on the encapsulation and release of different proteins, including hemoglobin, are needed to establish the desired controlled release of

  15. Multiplicative interaction of functional inflammasome genetic variants in determining the risk of gout.

    McKinney, Cushla; Stamp, Lisa K; Dalbeth, Nicola; Topless, Ruth K; Day, Richard O; Kannangara, Diluk Rw; Williams, Kenneth M; Janssen, Matthijs; Jansen, Timothy L; Joosten, Leo A; Radstake, Timothy R; Riches, Philip L; Tausche, Anne-Kathrin; Lioté, Frederic; So, Alexander; Merriman, Tony R

    2015-10-13

    The acute gout flare results from a localised self-limiting innate immune response to monosodium urate (MSU) crystals deposited in joints in hyperuricaemic individuals. Activation of the caspase recruitment domain-containing protein 8 (CARD8) NOD-like receptor pyrin-containing 3 (NLRP3) inflammasome by MSU crystals and production of mature interleukin-1β (IL-1β) is central to acute gouty arthritis. However very little is known about genetic control of the innate immune response involved in acute gouty arthritis. Therefore our aim was to test functional single nucleotide polymorphism (SNP) variants in the toll-like receptor (TLR)-inflammasome-IL-1β axis for association with gout. 1,494 gout cases of European and 863 gout cases of New Zealand (NZ) Polynesian (Māori and Pacific Island) ancestry were included. Gout was diagnosed by the 1977 ARA gout classification criteria. There were 1,030 Polynesian controls and 10,942 European controls including from the publicly-available Atherosclerosis Risk in Communities (ARIC) and Framingham Heart (FHS) studies. The ten SNPs were either genotyped by Sequenom MassArray or by Affymetrix SNP array or imputed in the ARIC and FHS datasets. Allelic association was done by logistic regression adjusting by age and sex with European and Polynesian data combined by meta-analysis. Sample sets were pooled for multiplicative interaction analysis, which was also adjusted by sample set. Eleven SNPs were tested in the TLR2, CD14, IL1B, CARD8, NLRP3, MYD88, P2RX7, DAPK1 and TNXIP genes. Nominally significant (P gout were detected at CARD8 rs2043211 (OR = 1.12, P = 0.007), IL1B rs1143623 (OR = 1.10, P = 0.020) and CD14 rs2569190 (OR = 1.08; P = 0.036). There was significant multiplicative interaction between CARD8 and IL1B (P = 0.005), with the IL1B risk genotype amplifying the risk effect of CARD8. There is evidence for association of gout with functional variants in CARD8, IL1B and CD14. The gout-associated allele of IL1B increases

  16. Multiple victimization experiences of urban elementary school students: associations with psychosocial functioning and academic performance.

    Holt, Melissa K; Finkelhor, David; Kantor, Glenda Kaufman

    2007-05-01

    This study explored the victimization experiences of urban elementary school students to determine whether subsets of youth emerged with similar victimization profiles (e.g., no victimization, multiple types of victimization). It also evaluated whether multiple victimization was associated with greater psychological distress and lower academic performance. Participants were 689 fifth grade students from an urban, ethnically diverse school district in the Northeast. Youth completed self-report measures in school about bullying victimization, victimization in the home and community, and psychosocial functioning. Cluster analysis suggested the existence of three distinct youth profiles: those with minimal victimization, those victimized primarily by their peers, and those with multiple types of victimizations. As hypothesized, youth with multiple victimizations experienced more psychological distress and earned lower grades than their peers. Findings highlight the heterogeneity of youth victimization experiences and their relations to functioning, and have implications for treatment planning among practitioners working with youth.

  17. Aerobic capacity explains physical functioning and participation in patients with multiple sclerosis-related fatigue

    Emma Rosalie Driehuis; Lizanne Eva van den Akker; Vincent de Groot; Heleen Beckerman

    2018-01-01

    Objective: To investigate whether aerobic capacity explains the level of self-reported physical activity, physical functioning, and participation and autonomy in daily living in persons with multiple sclerosis-related fatigue. Design: A cross-sectional study. Patients: Sixty-two participants with multiple sclerosis-related fatigue. Methods: Aerobic capacity was measured with a leg ergometer and was expressed as maximal oxygen uptake (VO2max, in ...

  18. Efficient Time-Domain Ray-Tracing Technique for the Analysis of Ultra-Wideband Indoor Environments including Lossy Materials and Multiple Effects

    F. Saez de Adana

    2009-01-01

    Full Text Available This paper presents an efficient application of the Time-Domain Uniform Theory of Diffraction (TD-UTD for the analysis of Ultra-Wideband (UWB mobile communications for indoor environments. The classical TD-UTD formulation is modified to include the contribution of lossy materials and multiple-ray interactions with the environment. The electromagnetic analysis is combined with a ray-tracing acceleration technique to treat realistic and complex environments. The validity of this method is tested with measurements performed inside the Polytechnic building of the University of Alcala and shows good performance of the model for the analysis of UWB propagation.

  19. Stroop performance in multiple sclerosis: information processing, selective attention, or executive functioning?

    Macniven, J A B; Davis, C; Ho, M-Y; Bradshaw, C M; Szabadi, E; Constantinescu, C S

    2008-09-01

    Cognitive impairments in information processing speed, attention and executive functioning are widely reported in patients with multiple sclerosis (MS). Several studies have identified impaired performance on the Stroop test in people with MS, yet uncertainty remains over the cause of this phenomenon. In this study, 25 patients with MS were assessed with a neuropsychological test battery including a computerized Stroop test and a computerized test of information processing speed, the Graded Conditional Discrimination Tasks (GCDT). The patient group was compared with an individually age, sex and estimated premorbid IQ-matched healthy control group. The patients' reaction times (RTs) were significantly longer than those of the controls on all Stroop test trials and there was a significantly enhanced absolute (RT(incongruent)-RT(neutral)) and relative (100 x [RT(incongruent)-RT(neutral)]/RT(neutral)) Stroop interference effect for the MS group. The linear function relating RT to stimulus complexity in the GCDT was significantly steeper in the patient group, indicating slowed information processing. The results are discussed with reference to the difference engine model, a theory of diversity in speeded cognition. It is concluded that, in the assessment of people with MS, great caution must be used in the interpretation of performance on neuropsychological tests which rely on RT as the primary measure.

  20. Correlation functions with fusion-channel multiplicity in W3 Toda field theory

    Belavin, Vladimir; Estienne, Benoit; Foda, Omar; Santachiara, Raoul

    2016-01-01

    Current studies of W N Toda field theory focus on correlation functions such that the W N highest-weight representations in the fusion channels are multiplicity-free. In this work, we study W 3 Toda 4-point functions with multiplicity in the fusion channel. The conformal blocks of these 4-point functions involve matrix elements of a fully-degenerate primary field with a highest-weight in the adjoint representation of sl 3 , and a fully-degenerate primary field with a highest-weight in the fundamental representation of sl 3 . We show that, when the fusion rules do not involve multiplicities, the matrix elements of the fully-degenerate adjoint field, between two arbitrary descendant states, can be computed explicitly, on equal footing with the matrix elements of the semi-degenerate fundamental field. Using null-state conditions, we obtain a fourth-order Fuchsian differential equation for the conformal blocks. Using Okubo theory, we show that, due to the presence of multiplicities, this differential equation belongs to a class of Fuchsian equations that is different from those that have appeared so far in W N theories. We solve this equation, compute its monodromy group, and construct the monodromy-invariant correlation functions. This computation shows in detail how the ambiguities that are caused by the presence of multiplicities are fixed by requiring monodromy-invariance.

  1. Correlation functions with fusion-channel multiplicity in W{sub 3} Toda field theory

    Belavin, Vladimir [I.E. Tamm Department of Theoretical Physics, P.N. Lebedev Physical Institute,Leninsky Avenue 53, 119991 Moscow (Russian Federation); Department of Quantum Physics, Institute for Information Transmission Problems,Bolshoy Karetny per. 19, 127994 Moscow (Russian Federation); Estienne, Benoit [LPTHE, CNRS and Université Pierre et Marie Curie,Sorbonne Universités, 4 Place Jussieu, 75252 Paris Cedex 05 (France); Foda, Omar [School of Mathematics and Statistics, University of Melbourne,Parkville, Victoria 3010 (Australia); Santachiara, Raoul [LPTMS, CNRS (UMR 8626), Université Paris-Saclay,15 rue Georges Clémenceau, 91405 Orsay (France)

    2016-06-22

    Current studies of W{sub N} Toda field theory focus on correlation functions such that the W{sub N} highest-weight representations in the fusion channels are multiplicity-free. In this work, we study W{sub 3} Toda 4-point functions with multiplicity in the fusion channel. The conformal blocks of these 4-point functions involve matrix elements of a fully-degenerate primary field with a highest-weight in the adjoint representation of sl{sub 3}, and a fully-degenerate primary field with a highest-weight in the fundamental representation of sl{sub 3}. We show that, when the fusion rules do not involve multiplicities, the matrix elements of the fully-degenerate adjoint field, between two arbitrary descendant states, can be computed explicitly, on equal footing with the matrix elements of the semi-degenerate fundamental field. Using null-state conditions, we obtain a fourth-order Fuchsian differential equation for the conformal blocks. Using Okubo theory, we show that, due to the presence of multiplicities, this differential equation belongs to a class of Fuchsian equations that is different from those that have appeared so far in W{sub N} theories. We solve this equation, compute its monodromy group, and construct the monodromy-invariant correlation functions. This computation shows in detail how the ambiguities that are caused by the presence of multiplicities are fixed by requiring monodromy-invariance.

  2. Prediction of preterm birth in multiple pregnancies: development of a multivariable model including cervical length measurement at 16 to 21 weeks' gestation.

    van de Mheen, Lidewij; Schuit, Ewoud; Lim, Arianne C; Porath, Martina M; Papatsonis, Dimitri; Erwich, Jan J; van Eyck, Jim; van Oirschot, Charlotte M; Hummel, Piet; Duvekot, Johannes J; Hasaart, Tom H M; Groenwold, Rolf H H; Moons, Karl G M; de Groot, Christianne J M; Bruinse, Hein W; van Pampus, Maria G; Mol, Ben W J

    2014-04-01

    To develop a multivariable prognostic model for the risk of preterm delivery in women with multiple pregnancy that includes cervical length measurement at 16 to 21 weeks' gestation and other variables. We used data from a previous randomized trial. We assessed the association between maternal and pregnancy characteristics including cervical length measurement at 16 to 21 weeks' gestation and time to delivery using multivariable Cox regression modelling. Performance of the final model was assessed for the outcomes of preterm and very preterm delivery using calibration and discrimination measures. We studied 507 women, of whom 270 (53%) delivered models for preterm and very preterm delivery had a c-index of 0.68 (95% CI 0.63 to 0.72) and 0.68 (95% CI 0.62 to 0.75), respectively, and showed good calibration. In women with a multiple pregnancy, the risk of preterm delivery can be assessed with a multivariable model incorporating cervical length and other predictors.

  3. TRANSAT-- method for detecting the conserved helices of functional RNA structures, including transient, pseudo-knotted and alternative structures.

    Wiebe, Nicholas J P; Meyer, Irmtraud M

    2010-06-24

    The prediction of functional RNA structures has attracted increased interest, as it allows us to study the potential functional roles of many genes. RNA structure prediction methods, however, assume that there is a unique functional RNA structure and also do not predict functional features required for in vivo folding. In order to understand how functional RNA structures form in vivo, we require sophisticated experiments or reliable prediction methods. So far, there exist only a few, experimentally validated transient RNA structures. On the computational side, there exist several computer programs which aim to predict the co-transcriptional folding pathway in vivo, but these make a range of simplifying assumptions and do not capture all features known to influence RNA folding in vivo. We want to investigate if evolutionarily related RNA genes fold in a similar way in vivo. To this end, we have developed a new computational method, Transat, which detects conserved helices of high statistical significance. We introduce the method, present a comprehensive performance evaluation and show that Transat is able to predict the structural features of known reference structures including pseudo-knotted ones as well as those of known alternative structural configurations. Transat can also identify unstructured sub-sequences bound by other molecules and provides evidence for new helices which may define folding pathways, supporting the notion that homologous RNA sequence not only assume a similar reference RNA structure, but also fold similarly. Finally, we show that the structural features predicted by Transat differ from those assuming thermodynamic equilibrium. Unlike the existing methods for predicting folding pathways, our method works in a comparative way. This has the disadvantage of not being able to predict features as function of time, but has the considerable advantage of highlighting conserved features and of not requiring a detailed knowledge of the cellular

  4. Effect of yoga practices on pulmonary function tests including transfer factor of lung for carbon monoxide (TLCO) in asthma patients.

    Singh, Savita; Soni, Ritu; Singh, K P; Tandon, O P

    2012-01-01

    Prana is the energy, when the self-energizing force embraces the body with extension and expansion and control, it is pranayama. It may affect the milieu at the bronchioles and the alveoli particularly at the alveolo-capillary membrane to facilitate diffusion and transport of gases. It may also increase oxygenation at tissue level. Aim of our study is to compare pulmonary functions and diffusion capacity in patients of bronchial asthma before and after yogic intervention of 2 months. Sixty stable asthmatic-patients were randomized into two groups i.e group 1 (Yoga training group) and group 2 (control group). Each group included thirty patients. Lung functions were recorded on all patients at baseline, and then after two months. Group 1 subjects showed a statistically significant improvement (Pincreased significantly. It was concluded that pranayama & yoga breathing and stretching postures are used to increase respiratory stamina, relax the chest muscles, expand the lungs, raise energy levels, and calm the body.

  5. Multiple amino acid sequence alignment nitrogenase component 1: insights into phylogenetics and structure-function relationships.

    James B Howard

    Full Text Available Amino acid residues critical for a protein's structure-function are retained by natural selection and these residues are identified by the level of variance in co-aligned homologous protein sequences. The relevant residues in the nitrogen fixation Component 1 α- and β-subunits were identified by the alignment of 95 protein sequences. Proteins were included from species encompassing multiple microbial phyla and diverse ecological niches as well as the nitrogen fixation genotypes, anf, nif, and vnf, which encode proteins associated with cofactors differing at one metal site. After adjusting for differences in sequence length, insertions, and deletions, the remaining >85% of the sequence co-aligned the subunits from the three genotypes. Six Groups, designated Anf, Vnf , and Nif I-IV, were assigned based upon genetic origin, sequence adjustments, and conserved residues. Both subunits subdivided into the same groups. Invariant and single variant residues were identified and were defined as "core" for nitrogenase function. Three species in Group Nif-III, Candidatus Desulforudis audaxviator, Desulfotomaculum kuznetsovii, and Thermodesulfatator indicus, were found to have a seleno-cysteine that replaces one cysteinyl ligand of the 8Fe:7S, P-cluster. Subsets of invariant residues, limited to individual groups, were identified; these unique residues help identify the gene of origin (anf, nif, or vnf yet should not be considered diagnostic of the metal content of associated cofactors. Fourteen of the 19 residues that compose the cofactor pocket are invariant or single variant; the other five residues are highly variable but do not correlate with the putative metal content of the cofactor. The variable residues are clustered on one side of the cofactor, away from other functional centers in the three dimensional structure. Many of the invariant and single variant residues were not previously recognized as potentially critical and their identification

  6. Computation of transverse muon-spin relaxation functions including trapping-detrapping reactions, with application to electron-irradiated tantalum

    Doering, K.P.; Aurenz, T.; Herlach, D.; Schaefer, H.E.; Arnold, K.P.; Jacobs, W.; Orth, H.; Haas, N.; Seeger, A.; Max-Planck-Institut fuer Metallforschung, Stuttgart

    1986-01-01

    A new technique for the economical evaluation of transverse muon spin relaxation functions in situations involving μ + trapping at and detrapping from crystal defects is applied to electron-irradiated Ta exhibiting relaxation maxima at about 35 K, 100 K, and 250 K. The long-range μ + diffusion is shown to be limted by traps over the entire temperature range investigated. The (static) relaxation rates for several possible configurations of trapped muons are discussed, including the effect of the simultaneous presence of a proton in a vacancy. (orig.)

  7. Validity and Reliability of Scores Obtained on Multiple-Choice Questions: Why Functioning Distractors Matter

    Ali, Syed Haris; Carr, Patrick A.; Ruit, Kenneth G.

    2016-01-01

    Plausible distractors are important for accurate measurement of knowledge via multiple-choice questions (MCQs). This study demonstrates the impact of higher distractor functioning on validity and reliability of scores obtained on MCQs. Freeresponse (FR) and MCQ versions of a neurohistology practice exam were given to four cohorts of Year 1 medical…

  8. Accounting for multiple functions in environmental life cycle assessment of storm water management solutions

    Brudler, Sarah; Arnbjerg-Nielsen, Karsten; Rygaard, Martin

    The wide range of approaches to handle storm water runoff have varying effects on the environment. Local stormwater control measures for retention and treatment are increasingly used components in urban climate adaptation plans. Often, these solutions modify the multiple functions of urban...

  9. Multiple Sclerosis and Employment: A Research Review Based on the International Classification of Function

    Frain, Michael P.; Bishop, Malachy; Rumrill, Phillip D., Jr.; Chan, Fong; Tansey, Timothy N.; Strauser, David; Chiu, Chung-Yi

    2015-01-01

    Multiple sclerosis (MS) is an unpredictable, sometimes progressive chronic illness affecting people in the prime of their working lives. This article reviews the effects of MS on employment based on the World Health Organization's International Classification of Functioning, Disability and Health model. Correlations between employment and…

  10. Embedding multiple self-organisation functionalities in future radio access networks

    Jansen, T.; Amirijoo, M.; Türke, U.; Jorguseski, L.; Zetterberg, K.; Nascimento, J.R.V. do; Schmelz, L.C.; Turk, J.; Balan, I.

    2009-01-01

    Wireless network operators today allocate considerable manual effort in managing their networks. A viable solution for lowering the manual effort is to introduce self-organisation functionalities. In this paper we discuss the challenges that are encountered when embedding multiple self-organisation

  11. Stepwise Analysis of Differential Item Functioning Based on Multiple-Group Partial Credit Model.

    Muraki, Eiji

    1999-01-01

    Extended an Item Response Theory (IRT) method for detection of differential item functioning to the partial credit model and applied the method to simulated data using a stepwise procedure. Then applied the stepwise DIF analysis based on the multiple-group partial credit model to writing trend data from the National Assessment of Educational…

  12. Disruption of Structural and Functional Networks in Long-Standing Multiple Sclerosis

    Tewarie, P.; Steenwijk, M.D.; Tijms, B.M.; Daams, M.; Balk, L.J.; Stam, C.J.; Uitdehaag, B.M.J.; Polman, C.H.; Geurts, J.J.G.; Barkhof, F.; Pouwels, P.J.W.; Vrenken, H.; Hillebrand, A.

    2014-01-01

    Both gray matter atrophy and disruption of functional networks are important predictors for physical disability and cognitive impairment in multiple sclerosis (MS), yet their relationship is poorly understood. Graph theory provides a modality invariant framework to analyze patterns of gray matter

  13. Transfer functions of double- and multiple-cavity Fabry-Perot filters driven by Lorentzian sources.

    Marti, J; Capmany, J

    1996-12-20

    We derive expressions for the transfer functions of double- and multiple-cavity Fabry-Perot filters driven by laser sources with Lorentzian spectrum. These are of interest because of their applications in sensing and channel filtering in optical frequency-division multiplexing networks.

  14. Using Multiple Schedules during Functional Communication Training to Promote Rapid Transfer of Treatment Effects

    Fisher, Wayne W.; Greer, Brian D.; Fuhrman, Ashley M.; Querim, Angie C.

    2015-01-01

    Multiple schedules with signaled periods of reinforcement and extinction have been used to thin reinforcement schedules during functional communication training (FCT) to make the intervention more practical for parents and teachers. We evaluated whether these signals would also facilitate rapid transfer of treatment effects across settings and…

  15. The rank-heat plot is a novel way to present the results from a network meta-analysis including multiple outcomes.

    Veroniki, Areti Angeliki; Straus, Sharon E; Fyraridis, Alexandros; Tricco, Andrea C

    2016-08-01

    To present a novel and simple graphical approach to improve the presentation of the treatment ranking in a network meta-analysis (NMA) including multiple outcomes. NMA simultaneously compares many relevant interventions for a clinical condition from a network of trials, and allows ranking of the effectiveness and/or safety of each intervention. There are numerous ways to present the NMA results, which can challenge their interpretation by research users. The rank-heat plot is a novel graph that can be used to quickly recognize which interventions are most likely the best or worst interventions with respect to their effectiveness and/or safety for a single or multiple outcome(s) and may increase interpretability. Using empirical NMAs, we show that the need for a concise and informative presentation of results is imperative, particularly as the number of competing treatments and outcomes in an NMA increases. The rank-heat plot is an efficient way to present the results of ranking statistics, particularly when a large amount of data is available, and it is targeted to users from various backgrounds. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Langevin dynamics for vector variables driven by multiplicative white noise: A functional formalism

    Moreno, Miguel Vera; Arenas, Zochil González; Barci, Daniel G.

    2015-04-01

    We discuss general multidimensional stochastic processes driven by a system of Langevin equations with multiplicative white noise. In particular, we address the problem of how time reversal diffusion processes are affected by the variety of conventions available to deal with stochastic integrals. We present a functional formalism to build up the generating functional of correlation functions without any type of discretization of the Langevin equations at any intermediate step. The generating functional is characterized by a functional integration over two sets of commuting variables, as well as Grassmann variables. In this representation, time reversal transformation became a linear transformation in the extended variables, simplifying in this way the complexity introduced by the mixture of prescriptions and the associated calculus rules. The stochastic calculus is codified in our formalism in the structure of the Grassmann algebra. We study some examples such as higher order derivative Langevin equations and the functional representation of the micromagnetic stochastic Landau-Lifshitz-Gilbert equation.

  17. The Usefulness of Multilevel Hash Tables with Multiple Hash Functions in Large Databases

    A.T. Akinwale

    2009-05-01

    Full Text Available In this work, attempt is made to select three good hash functions which uniformly distribute hash values that permute their internal states and allow the input bits to generate different output bits. These functions are used in different levels of hash tables that are coded in Java Programming Language and a quite number of data records serve as primary data for testing the performances. The result shows that the two-level hash tables with three different hash functions give a superior performance over one-level hash table with two hash functions or zero-level hash table with one function in term of reducing the conflict keys and quick lookup for a particular element. The result assists to reduce the complexity of join operation in query language from O( n2 to O( 1 by placing larger query result, if any, in multilevel hash tables with multiple hash functions and generate shorter query result.

  18. IMPROVING FUNCTIONAL INDEPENDENCE OF PATIENTS WITH MULTIPLE SCLEROSIS BY PHYSICAL THERAPY AND OCCUPATIONAL THERAPY

    Ana-Maria Ticărat

    2011-06-01

    Full Text Available Introduction. Patients with multiple sclerosis can have a normal life despite of their real or possible disability and of the progressive nature of it. Scope. Patients who follow physical therapy and occupational therapy will have an increased quality of life and a greater functional independence.Methods. The randomized study was made on 7 patients with multiple sclerosis, from Oradea Day Centre, 3 times/week, ages between 35 – 55 years, functional level between mild and sever. Assessment and rehabilitation methods: inspection, BARTHEL Index. Frenkel method, brething exercises, weights exercises, gait exercises, writind exercises and games were used in the rehabilitation process. Group therapies: sociotherapy, arttherapy, music therapy. Results analysis consisted of the comparison of baseline and final means.Results. By analizing baseline and final means for Barthel Index for each functon separately, it was shown a mild improvement of functional independence for almost assessed functions, with at least 1-1,5 points.Conclusions. Persons with multiple sclerosis who follow physical therapy and occupational therapy presents a better functional independence after the treatment.

  19. Resistance training improves muscle strength and functional capacity in multiple sclerosis

    Dalgas, U; Stenager, E; Jakobsen, J

    2009-01-01

    strength and functional capacity in patients with multiple sclerosis, the effects persisting after 12 weeks of self-guided physical activity. Level of evidence: The present study provides level III evidence supporting the hypothesis that lower extremity progressive resistance training can improve muscle......OBJECTIVE: To test the hypothesis that lower extremity progressive resistance training (PRT) can improve muscle strength and functional capacity in patients with multiple sclerosis (MS) and to evaluate whether the improvements are maintained after the trial. METHODS: The present study was a 2-arm...... and was afterward encouraged to continue training. After the trial, the control group completed the PRT intervention. Both groups were tested before and after 12 weeks of the trial and at 24 weeks (follow-up), where isometric muscle strength of the knee extensors (KE MVC) and functional capacity (FS; combined score...

  20. Association between functional performance and executive cognitive functions in an elderly population including patients with low ankle–brachial index

    Ferreira NV

    2015-05-01

    Full Text Available Naomi Vidal Ferreira,1 Paulo Jannuzzi Cunha,2 Danielle Irigoyen da Costa,3 Fernando dos Santos,1 Fernando Oliveira Costa,1 Fernanda Consolim-Colombo,4 Maria Cláudia Irigoyen1 1Heart Institute, Medical School, Universidade de São Paulo, São Paulo, SP, Brazil; 2Neuroimaging in Psychiatry Laboratory, Department of Psychiatry, Medical School, Universidade de São Paulo, São Paulo, SP, Brazil; 3Rio Grande do Sul Cardiology Institute, Fundação Universitária de Cardiologia, Porto Alegre, RS, Brazil; 4Medical School, Universidade Nove de Julho, São Paulo, SP, Brazil Introduction: Peripheral arterial disease, as measured by the ankle–brachial index (ABI, is prevalent among the elderly, and is associated with functional performance, assessed by the 6-minute walk test (6MWT. Executive cognitive function (ECF impairments are also prevalent in this population, but no existing study has investigated the association between ECF and functional performance in an elderly population including individuals with low ABI.Aim: To investigate the association between functional performance, as measured by the 6MWT, and loss in ECF, in an elderly sample including individuals with low ABI.Method: The ABI group was formed by 26 elderly individuals with low ABI (mean ABI: 0.63±0.19, and the control group was formed by 40 elderly individuals with normal ABI (mean ABI: 1.08±0.07. We analyzed functional performance using the 6MWT, global cognition using the Mini-Mental State Examination (MMSE, and ECF using the Digit Span for assessing attention span and working memory, the Stroop Color Word Test (SCWT for assessing information processing speed and inhibitory control/impulsivity, and the Controlled Oral Word Association Test (COWAT for assessing semantic verbal fluency and phonemic verbal fluency. We also used a factor analysis on all of the ECF tests (global ECF.Results: Before adjustment, the ABI group performed worse on global cognition, attention span, working

  1. A Method of Calculating Functional Independence Measure at Discharge from Functional Independence Measure Effectiveness Predicted by Multiple Regression Analysis Has a High Degree of Predictive Accuracy.

    Tokunaga, Makoto; Watanabe, Susumu; Sonoda, Shigeru

    2017-09-01

    Multiple linear regression analysis is often used to predict the outcome of stroke rehabilitation. However, the predictive accuracy may not be satisfactory. The objective of this study was to elucidate the predictive accuracy of a method of calculating motor Functional Independence Measure (mFIM) at discharge from mFIM effectiveness predicted by multiple regression analysis. The subjects were 505 patients with stroke who were hospitalized in a convalescent rehabilitation hospital. The formula "mFIM at discharge = mFIM effectiveness × (91 points - mFIM at admission) + mFIM at admission" was used. By including the predicted mFIM effectiveness obtained through multiple regression analysis in this formula, we obtained the predicted mFIM at discharge (A). We also used multiple regression analysis to directly predict mFIM at discharge (B). The correlation between the predicted and the measured values of mFIM at discharge was compared between A and B. The correlation coefficients were .916 for A and .878 for B. Calculating mFIM at discharge from mFIM effectiveness predicted by multiple regression analysis had a higher degree of predictive accuracy of mFIM at discharge than that directly predicted. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  2. A diet based on multiple functional concepts improves cardiometabolic risk parameters in healthy subjects

    Tovar Juscelino

    2012-04-01

    Full Text Available Abstract Background Different foods can modulate cardiometabolic risk factors in persons already affected by metabolic alterations. The objective of this study was to assess, in healthy overweight individuals, the impact of a diet combining multiple functional concepts on risk markers associated with cardiometabolic diseases (CMD. Methods Fourty-four healthy women and men (50-73 y.o, BMI 25-33, fasting glycemia ≤ 6.1 mmol/L participated in a randomized crossover intervention comparing a multifunctional (active diet (AD with a control diet (CD devoid of the "active" components. Each diet was consumed during 4 wk with a 4 wk washout period. AD included the following functional concepts: low glycemic impact meals, antioxidant-rich foods, oily fish as source of long-chain omega-3 fatty acids, viscous dietary fibers, soybean and whole barley kernel products, almonds, stanols and a probiotic strain (Lactobacillus plantarum Heal19/DSM15313. Results Although the aim was to improve metabolic markers without promoting body weight loss, minor weight reductions were observed with both diets (0.9-1.8 ± 0.2%; P P P P = 0.0056, LDL/HDL (-27 ± 2%; P P 1c (-2 ± 0.4%; P = 0.0013, hs-CRP (-29 ± 9%; P = 0.0497 and systolic blood pressure (-8 ± 1%¸ P = 0.0123. The differences remained significant after adjustment for weight change. After AD, the Framingham cardiovascular risk estimate was 30 ± 4% (P P Conclusion The improved biomarker levels recorded in healthy individuals following the multifunctional regime suggest preventive potential of this dietary approach against CMD.

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

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

    2013-08-01

    discrimination, including the mechanisms by which many snails determine the polarity of the trail, are yet to be experimentally determined. Given the multiple functions of trail-following we propose that future studies should adopt an integrated approach, taking into account the possibility of the simultaneous occurrence of many selectively advantageous roles of trail-following behaviour in gastropods. We also believe that future opportunities to link phenotypic and genotypic traits will make possible a new generation of research projects in which gastropod trail-following, its multitude of functions and evolutionary trade-offs can be further elucidated. © 2013 The Authors. Biological Reviews © 2013 Cambridge Philosophical Society.

  4. MiR-7 triggers cell cycle arrest at the G1/S transition by targeting multiple genes including Skp2 and Psme3.

    Noelia Sanchez

    Full Text Available MiR-7 acts as a tumour suppressor in many cancers and abrogates proliferation of CHO cells in culture. In this study we demonstrate that miR-7 targets key regulators of the G1 to S phase transition, including Skp2 and Psme3, to promote increased levels of p27(KIP and temporary growth arrest of CHO cells in the G1 phase. Simultaneously, the down-regulation of DNA repair-specific proteins via miR-7 including Rad54L, and pro-apoptotic regulators such as p53, combined with the up-regulation of anti-apoptotic factors like p-Akt, promoted cell survival while arrested in G1. Thus miR-7 can co-ordinate the levels of multiple genes and proteins to influence G1 to S phase transition and the apoptotic response in order to maintain cellular homeostasis. This work provides further mechanistic insight into the role of miR-7 as a regulator of cell growth in times of cellular stress.

  5. ON A COURNOT DUOPOLY GAME WITH DIFFERENTIATED GOODS, HETEROGENEOUS EXPECTATIONS AND A COST FUNCTION INCLUDING EMISSION COSTS

    Georges SARAFOPOULOS

    2017-07-01

    Full Text Available In this study we investigate the dynamics of a nonlinear Cournot- type duopoly game with differentiated goods, linear demand and a cost function that includes emission costs. The game is modeled with a system of two difference equations. Existence and stability of equilibria of this system are studied. We show that the model gives more complex chaotic and unpredictable trajectories as a consequence of change in the parameter of horizontal product differentiation and a higher (lower degree of product differentiation (weaker or fiercer competition destabilize (stabilize the economy. The chaotic features are justified numerically via computing Lyapunov numbers and sensitive dependence on initial conditions. Also, we show that in this case there are stable trajectories and a higher (lower degree of product differentiation does not tend to destabilize the economy.

  6. An impedance function approach for soil-structure interaction analyses including structure-to-structure interaction effects

    Gantayat, A.; Kamil, H.

    1981-01-01

    The dynamic soil-structure and structure-to-structure interaction effects may be determined in one of the two ways: by modeling the entire soil-structure system by a finite-element model, or by using a frequency-dependent (or frequency-independent) impedance function approach. In seismic design of nuclear power plant structures, the normal practice is to use the first approach because of its simplicity and easy availability of computer codes to perform such analyses. However, in the finite-element approach, because of the size and cost restrictions, the three-dimensional behavior of the entire soil-structure system and the radiation damping in soil are only approximately included by using a two-dimensional finite-element mesh. In using the impedance function approach, the soil-structure analyses can be performed in four steps: (a) determination of the dynamic properties of the fixed base superstructure, (b) determination of foundation and structure impedance matrices and input motions, (c) evaluation of foundation motion, (d) analysis of the fixed base superstructure using computed foundation motion. (orig./RW)

  7. Characterizing functional connectivity during rest in multiple sclerosis patients versus healthy volunteers using independent component analysis

    Palacio Garcia, L.; Andrzejak, R.; Prchkovska, V.; Rodrigues, P.

    2016-07-01

    It is commonly thought that our brain is not active when it does not receive any external input. However, during rest, there are still certain distant regions of the brain that are functionally correlated between them: the so-called resting-state networks. This functional connectivity of the brain is disrupted in many neurological diseases. In particular, it has been shown that one of the most studied resting-state networks (the default-mode network) is affected in multiple sclerosis, which is the most common disabling neurological condition affecting the central nervous system of young adults. In this work, I focus on the study of the differences in the resting-state networks between multiple sclerosis patients and healthy volunteers. In order to study the effects of multiple sclerosis on the functional connectivity of the brain, a numerical method known as independent component analysis (ICA) is applied. This technique divides the resting-state fMRI data into independent components. Nonetheless, noise, which could be due to head motion or physiological artifacts, may corrupt the data by indicating a false activation. Therefore, I create a web user interface that allows the user to manually classify all the independent components for a given subject. Eventually, the components classified as noise should be removed from the functional data in order to prevent them from taking part in any further analysis. (Author)

  8. A Comparative Density Functional Theory and Density Functional Tight Binding Study of Phases of Nitrogen Including a High Energy Density Material N8

    Nicholas Capel

    2015-11-01

    Full Text Available We present a comparative dispersion-corrected Density Functional Theory (DFT and Density Functional Tight Binding (DFTB-D study of several phases of nitrogen, including the well-known alpha, beta, and gamma phases as well as recently discovered highly energetic phases: covalently bound cubic gauche (cg nitrogen and molecular (vdW-bound N8 crystals. Among several tested parametrizations of N–N interactions for DFTB, we identify only one that is suitable for modeling of all these phases. This work therefore establishes the applicability of DFTB-D to studies of phases, including highly metastable phases, of nitrogen, which will be of great use for modelling of dynamics of reactions involving these phases, which may not be practical with DFT due to large required space and time scales. We also derive a dispersion-corrected DFT (DFT-D setup (atom-centered basis parameters and Grimme dispersion parameters tuned for accurate description simultaneously of several nitrogen allotropes including covalently and vdW-bound crystals and including high-energy phases.

  9. Atom localization and center-of-mass wave-function determination via multiple simultaneous quadrature measurements

    Evers, Joerg; Qamar, Shahid; Zubairy, M. Suhail

    2007-01-01

    We discuss localization and center-of-mass wave-function measurement of a quantum particle using multiple simultaneous dispersive interactions of the particle with different standing-wave fields. In particular, we consider objects with an internal structure consisting of a single ground state and several excited states. The transitions between ground and the corresponding excited states are coupled to the light fields in the dispersive limit, thus giving rise to a phase shift of the light field during the interaction. We show that multiple simultaneous measurements allow both an increase in the measurement or localization precision in a single direction and the performance of multidimensional measurements or localization. Further, we show that multiple measurements may relax the experimental requirements for each individual measurement

  10. Advanced correlation grid: Analysis and visualisation of functional connectivity among multiple spike trains.

    Masud, Mohammad Shahed; Borisyuk, Roman; Stuart, Liz

    2017-07-15

    This study analyses multiple spike trains (MST) data, defines its functional connectivity and subsequently visualises an accurate diagram of connections. This is a challenging problem. For example, it is difficult to distinguish the common input and the direct functional connection of two spike trains. The new method presented in this paper is based on the traditional pairwise cross-correlation function (CCF) and a new combination of statistical techniques. First, the CCF is used to create the Advanced Correlation Grid (ACG) correlation where both the significant peak of the CCF and the corresponding time delay are used for detailed analysis of connectivity. Second, these two features of functional connectivity are used to classify connections. Finally, the visualization technique is used to represent the topology of functional connections. Examples are presented in the paper to demonstrate the new Advanced Correlation Grid method and to show how it enables discrimination between (i) influence from one spike train to another through an intermediate spike train and (ii) influence from one common spike train to another pair of analysed spike trains. The ACG method enables scientists to automatically distinguish between direct connections from spurious connections such as common source connection and indirect connection whereas existing methods require in-depth analysis to identify such connections. The ACG is a new and effective method for studying functional connectivity of multiple spike trains. This method can identify accurately all the direct connections and can distinguish common source and indirect connections automatically. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Fitting and Phenomenology in Type IA Supernova Cosmology: Generalized Likelihood Analyses for Multiple Evolving Populations and Observations of Near-Infrared Lightcurves Including Host Galaxy Properties

    Ponder, Kara A.

    In the late 1990s, Type Ia supernovae (SNeIa) led to the discovery that the Universe is expanding at an accelerating rate due to dark energy. Since then, many different tracers of acceleration have been used to characterize dark energy, but the source of cosmic acceleration has remained a mystery. To better understand dark energy, future surveys such as the ground-based Large Synoptic Survey Telescope and the space-based Wide-Field Infrared Survey Telescope will collect thousands of SNeIa to use as a primary dark energy probe. These large surveys will be systematics limited, which makes it imperative for our insight regarding systematics to dramatically increase over the next decade for SNeIa to continue to contribute to precision cosmology. I approach this problem by improving statistical methods in the likelihood analysis and collecting near infrared (NIR) SNeIa with their host galaxies to improve the nearby data set and search for additional systematics. Using more statistically robust methods to account for systematics within the likelihood function can increase accuracy in cosmological parameters with a minimal precision loss. Though a sample of at least 10,000 SNeIa is necessary to confirm multiple populations of SNeIa, the bias in cosmology is ˜ 2 sigma with only 2,500 SNeIa. This work focused on an example systematic (host galaxy correlations), but it can be generalized for any systematic that can be represented by a distribution of multiple Gaussians. The SweetSpot survey gathered 114 low-redshift, NIR SNeIa that will act as a crucial anchor sample for the future high redshift surveys. NIR observations are not as affected by dust contamination, which may lead to increased understanding of systematics seen in optical wavelengths. We obtained spatially resolved spectra for 32 SweetSpot host galaxies to test for local host galaxy correlations. For the first time, we probe global host galaxy correlations with NIR brightnesses from the current literature

  12. Competing failure analysis in phased-mission systems with multiple functional dependence groups

    Wang, Chaonan; Xing, Liudong; Peng, Rui; Pan, Zhusheng

    2017-01-01

    A phased-mission system (PMS) involves multiple, consecutive, non-overlapping phases of operation. The system structure function and component failure behavior in a PMS can change from phase to phase, posing big challenges to the system reliability analysis. Further complicating the problem is the functional dependence (FDEP) behavior where the failure of certain component(s) causes other component(s) to become unusable or inaccessible or isolated. Previous studies have shown that FDEP can cause competitions between failure propagation and failure isolation in the time domain. While such competing failure effects have been well addressed in single-phase systems, only little work has focused on PMSs with a restrictive assumption that a single FDEP group exists in one phase of the mission. Many practical systems (e.g., computer systems and networks), however may involve multiple FDEP groups during the mission. Moreover, different FDEP groups can be dependent due to sharing some common components; they may appear in a single phase or multiple phases. This paper makes new contributions by modeling and analyzing reliability of PMSs subject to multiple FDEP groups through a Markov chain-based methodology. Propagated failures with both global and selective effects are considered. Four case studies are presented to demonstrate application of the proposed method. - Highlights: • Reliability of phased-mission systems subject to competing failure propagation and isolation effects is modeled. • Multiple independent or dependent functional dependence groups are considered. • Propagated failures with global effects and selective effects are studied. • Four case studies demonstrate generality and application of the proposed Markov-based method.

  13. Validation of the fatigue scale for motor and cognitive functions in a danish multiple sclerosis cohort

    Oervik, M. S.; Sejbaek, T.; Penner, I. K.

    2017-01-01

    Background Our objective was to validate the Danish translation of the Fatigue Scale for Motor and Cognitive Functions (FSMC) in multiple sclerosis (MS) patients. Materials and methods A Danish MS cohort (n = 84) was matched and compared to the original German validation cohort (n = 309) and a he......Background Our objective was to validate the Danish translation of the Fatigue Scale for Motor and Cognitive Functions (FSMC) in multiple sclerosis (MS) patients. Materials and methods A Danish MS cohort (n = 84) was matched and compared to the original German validation cohort (n = 309...... positive correlations between the two fatigue scales implied high convergent validity (total scores: r = 0.851, p gender). Correcting for depression did not result in any significant adjustments of the correlations...

  14. Adaptive modified function projective synchronization of multiple time-delayed chaotic Rossler system

    Sudheer, K. Sebastian; Sabir, M.

    2011-01-01

    In this Letter we consider modified function projective synchronization of unidirectionally coupled multiple time-delayed Rossler chaotic systems using adaptive controls. Recently, delay differential equations have attracted much attention in the field of nonlinear dynamics. The high complexity of the multiple time-delayed systems can provide a new architecture for enhancing message security in chaos based encryption systems. Adaptive control can be used for synchronization when the parameters of the system are unknown. Based on Lyapunov stability theory, the adaptive control law and the parameter update law are derived to make the state of two chaotic systems are function projective synchronized. Numerical simulations are presented to demonstrate the effectiveness of the proposed adaptive controllers.

  15. Awareness of single and multiple emotions in high-functioning childeren with autism

    Rieffe, C.J.; Meerum Terwogt, M.; Kotronopoulo, K.

    2007-01-01

    This study examined emotional awareness in children with autism. Twenty-two high functioning children with autism (mean age 10 years and 2 months) and 22 typically developing children, matched for age and gender, were presented with the four basic emotions (happiness, anger, sadness and fear) in single and multiple emotion tasks. Findings suggest that children with autism have difficulties identifying their own emotions and less developed emotion concepts (which causes an impaired capacity to...

  16. Activator Gcn4 employs multiple segments of Med15/Gal11, including the KIX domain, to recruit mediator to target genes in vivo.

    Jedidi, Iness; Zhang, Fan; Qiu, Hongfang; Stahl, Stephen J; Palmer, Ira; Kaufman, Joshua D; Nadaud, Philippe S; Mukherjee, Sujoy; Wingfield, Paul T; Jaroniec, Christopher P; Hinnebusch, Alan G

    2010-01-22

    Mediator is a multisubunit coactivator required for initiation by RNA polymerase II. The Mediator tail subdomain, containing Med15/Gal11, is a target of the activator Gcn4 in vivo, critical for recruitment of native Mediator or the Mediator tail subdomain present in sin4Delta cells. Although several Gal11 segments were previously shown to bind Gcn4 in vitro, the importance of these interactions for recruitment of Mediator and transcriptional activation by Gcn4 in cells was unknown. We show that interaction of Gcn4 with the Mediator tail in vitro and recruitment of this subcomplex and intact Mediator to the ARG1 promoter in vivo involve additive contributions from three different segments in the N terminus of Gal11. These include the KIX domain, which is a critical target of other activators, and a region that shares a conserved motif (B-box) with mammalian coactivator SRC-1, and we establish that B-box is a critical determinant of Mediator recruitment by Gcn4. We further demonstrate that Gcn4 binds to the Gal11 KIX domain directly and, by NMR chemical shift analysis combined with mutational studies, we identify the likely binding site for Gcn4 on the KIX surface. Gcn4 is distinctive in relying on comparable contributions from multiple segments of Gal11 for efficient recruitment of Mediator in vivo.

  17. Patients with neuromyelitis optica have a more severe disease than patients with relapsingremitting multiple sclerosis, including higher risk of dying of a demyelinating disease

    Denis Bernardi Bichuetti

    2013-05-01

    Full Text Available Although neuromyelitis optica (NMO is known to be a more severe disease than relapsing-remitting multiple sclerosis (RRMS, few studies comparing both conditions in a single center have been done. Methods: Comparison of our previously published cohort of 41 NMO patients with 177 RRMS patients followed in the same center, from 1994 to 2007. Results: Mean age of onset was 32.6 for NMO and 30.2 for RRMS (p=0.2062 with mean disease duration of 7.4 years for NMO and 10.3 years for RRMS. Patients with NMO had a higher annualized relapse rate (1.0 versus 0.8, p=0.0013 and progression index (0.9 versus 0.6, p≪0.0001, with more patients reaching expanded disability status scale (EDSS 6.0 (39 versus 17%, p=0.0036. The odds ratio for reaching EDSS 6.0 and being deceased due to NMO in comparison to RRMS were, respectively, 3.14 and 12.15. Conclusion: Patients with NMO have a more severe disease than patients with RRMS, including higher risk of dying of a demyelinating disease.

  18. Jigsaw puzzle metasurface for multiple functions: polarization conversion, anomalous reflection and diffusion.

    Zhao, Yi; Cao, Xiangyu; Gao, Jun; Liu, Xiao; Li, Sijia

    2016-05-16

    We demonstrate a simple reconfigurable metasurface with multiple functions. Anisotropic tiles are investigated and manufactured as fundamental elements. Then, the tiles are combined in a certain sequence to construct a metasurface. Each of the tiles can be adjusted independently which is like a jigsaw puzzle and the whole metasurface can achieve diverse functions by different layouts. For demonstration purposes, we realize polarization conversion, anomalous reflection and diffusion by a jigsaw puzzle metasurface with 6 × 6 pieces of anisotropic tile. Simulated and measured results prove that our method offers a simple and effective strategy for metasurface design.

  19. Charged Particles Multiplicity and Scaling Violation of Fragmentation Functions in Electron-Positron Annihilation

    Ghaffary, Tooraj

    2016-01-01

    By the use of data from the annihilation process of electron-positron in AMY detector at 60 GeV center of mass energy, charged particles multiplicity distribution is obtained and fitted with the KNO scaling. Then, momentum spectra of charged particles and momentum distribution with respect to the jet axis are obtained, and the results are compared to the different models of QCD; also, the distribution of fragmentation functions and scaling violations are studied. It is being expected that the scaling violations of the fragmentation functions of gluon jets are stronger than the quark ones. One of the reasons for such case is that splitting function of quarks is larger than splitting function of gluon.

  20. Factors predicting work outcome in Japanese patients with schizophrenia: role of multiple functioning levels

    Chika Sumiyoshi

    2015-09-01

    Full Text Available Functional outcomes in individuals with schizophrenia suggest recovery of cognitive, everyday, and social functioning. Specifically improvement of work status is considered to be most important for their independent living and self-efficacy. The main purposes of the present study were 1 to identify which outcome factors predict occupational functioning, quantified as work hours, and 2 to provide cut-offs on the scales for those factors to attain better work status. Forty-five Japanese patients with schizophrenia and 111 healthy controls entered the study. Cognition, capacity for everyday activities, and social functioning were assessed by the Japanese versions of the MATRICS Cognitive Consensus Battery (MCCB, the UCSD Performance-based Skills Assessment-Brief (UPSA-B, and the Social Functioning Scale Individuals’ version modified for the MATRICS-PASS (Modified SFS for PASS, respectively. Potential factors for work outcome were estimated by multiple linear regression analyses (predicting work hours directly and a multiple logistic regression analyses (predicting dichotomized work status based on work hours. ROC curve analyses were performed to determine cut-off points for differentiating between the better- and poor work status. The results showed that a cognitive component, comprising visual/verbal learning and emotional management, and a social functioning component, comprising independent living and vocational functioning, were potential factors for predicting work hours/status. Cut-off points obtained in ROC analyses indicated that 60–70% achievements on the measures of those factors were expected to maintain the better work status. Our findings suggest that improvement on specific aspects of cognitive and social functioning are important for work outcome in patients with schizophrenia.

  1. Factors predicting work outcome in Japanese patients with schizophrenia: role of multiple functioning levels.

    Sumiyoshi, Chika; Harvey, Philip D; Takaki, Manabu; Okahisa, Yuko; Sato, Taku; Sora, Ichiro; Nuechterlein, Keith H; Subotnik, Kenneth L; Sumiyoshi, Tomiki

    2015-09-01

    Functional outcomes in individuals with schizophrenia suggest recovery of cognitive, everyday, and social functioning. Specifically improvement of work status is considered to be most important for their independent living and self-efficacy. The main purposes of the present study were 1) to identify which outcome factors predict occupational functioning, quantified as work hours, and 2) to provide cut-offs on the scales for those factors to attain better work status. Forty-five Japanese patients with schizophrenia and 111 healthy controls entered the study. Cognition, capacity for everyday activities, and social functioning were assessed by the Japanese versions of the MATRICS Cognitive Consensus Battery (MCCB), the UCSD Performance-based Skills Assessment-Brief (UPSA-B), and the Social Functioning Scale Individuals' version modified for the MATRICS-PASS (Modified SFS for PASS), respectively. Potential factors for work outcome were estimated by multiple linear regression analyses (predicting work hours directly) and a multiple logistic regression analyses (predicting dichotomized work status based on work hours). ROC curve analyses were performed to determine cut-off points for differentiating between the better- and poor work status. The results showed that a cognitive component, comprising visual/verbal learning and emotional management, and a social functioning component, comprising independent living and vocational functioning, were potential factors for predicting work hours/status. Cut-off points obtained in ROC analyses indicated that 60-70% achievements on the measures of those factors were expected to maintain the better work status. Our findings suggest that improvement on specific aspects of cognitive and social functioning are important for work outcome in patients with schizophrenia.

  2. Multiple Past Concussions in High School Football Players: Are There Differences in Cognitive Functioning and Symptom Reporting?

    Brooks, Brian L; Mannix, Rebekah; Maxwell, Bruce; Zafonte, Ross; Berkner, Paul D; Iverson, Grant L

    2016-12-01

    There is increasing concern about the possible long-term effects of multiple concussions, particularly on the developing adolescent brain. Whether the effect of multiple concussions is detectable in high school football players has not been well studied, although the public health implications are great in this population. To determine if there are measureable differences in cognitive functioning or symptom reporting in high school football players with a history of multiple concussions. Cross-sectional study; Level of evidence, 3. Participants included 5232 male adolescent football players (mean [±SD] age, 15.5 ± 1.2 years) who completed baseline testing between 2009 and 2014. On the basis of injury history, athletes were grouped into 0 (n = 4183), 1 (n = 733), 2 (n = 216), 3 (n = 67), or ≥4 (n = 33) prior concussions. Cognitive functioning was measured by the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) battery, and symptom ratings were obtained from the Post-Concussion Symptom Scale. There were no statistically significant differences between groups (based on the number of reported concussions) regarding cognitive functioning. Athletes with ≥3 prior concussions reported more symptoms than did athletes with 0 or 1 prior injury. In multivariate analyses, concussion history was independently related to symptom reporting but less so than developmental problems (eg, attention or learning problems) or other health problems (eg, past treatment for psychiatric problems, headaches, or migraines). In the largest study to date, high school football players with multiple past concussions performed the same on cognitive testing as those with no prior concussions. Concussion history was one of several factors that were independently related to symptom reporting. © 2016 The Author(s).

  3. Optimizing Placement of Weather Stations: Exploring Objective Functions of Meaningful Combinations of Multiple Weather Variables

    Snyder, A.; Dietterich, T.; Selker, J. S.

    2017-12-01

    Many regions of the world lack ground-based weather data due to inadequate or unreliable weather station networks. For example, most countries in Sub-Saharan Africa have unreliable, sparse networks of weather stations. The absence of these data can have consequences on weather forecasting, prediction of severe weather events, agricultural planning, and climate change monitoring. The Trans-African Hydro-Meteorological Observatory (TAHMO.org) project seeks to address these problems by deploying and operating a large network of weather stations throughout Sub-Saharan Africa. To design the TAHMO network, we must determine where to place weather stations within each country. We should consider how we can create accurate spatio-temporal maps of weather data and how to balance the desired accuracy of each weather variable of interest (precipitation, temperature, relative humidity, etc.). We can express this problem as a joint optimization of multiple weather variables, given a fixed number of weather stations. We use reanalysis data as the best representation of the "true" weather patterns that occur in the region of interest. For each possible combination of sites, we interpolate the reanalysis data between selected locations and calculate the mean average error between the reanalysis ("true") data and the interpolated data. In order to formulate our multi-variate optimization problem, we explore different methods of weighting each weather variable in our objective function. These methods include systematic variation of weights to determine which weather variables have the strongest influence on the network design, as well as combinations targeted for specific purposes. For example, we can use computed evapotranspiration as a metric that combines many weather variables in a way that is meaningful for agricultural and hydrological applications. We compare the errors of the weather station networks produced by each optimization problem formulation. We also compare these

  4. A comparative study of single and multiple hand tasks using functional MRI

    Shin, Byung Suck; Lee, Ho Kyu; Park, Sung Tae; Kim, Dong Eun; Lee, Myung Jun; Choi, Choong Gon; Kim, Jae Kyun; Suh, Dae Chul; Lim, Tae Hwan

    1998-01-01

    The purpose of this study is to assess, using functional MRI and by comparing activated motor sensory areas, the independence of brain activation during single and alternative multiple hand tasks. The subjects were six healthy volunteers. Using at 1.5T Siemens system and single shot FID-EPI sequencing (T2 weighted image; TR/TE 0.96 msec/ 61msec, flip angle 90 deg, matrix size 96 x 128, slice thickness/gap 5 mm/0.8 mm, FOV 200 mm) and T1-weighted anatomic images, functional MRI was performed. The paradigm of motor tasks consisted of appositional finger movements; the first involved the separate use of the right, left, and both hands in sequence. Using cross-correlation method (threshold : 0.6) and fMRI analysis software (stimulate 5.0), functional images were obtained. The activated area of brain cortex, the number of pixel, the average percentage change in signal intensity, and correlation of the time-signal intensity curve in the activated motor area were analysed and compared between the two task groups. Statistical analysis involved the use of Wilcoxon signed-rank test. Brain activation did not differ according to whether the motor task was single or alternative. We therefore suggest that during multiple stimuli, the relevant functional area and neuronal column are activated independently. (author). 19 refs., 2 tabs., 3 figs

  5. Electrophysiological heterogeneity of pacemaker cells in the rabbit intercaval region, including the SA node: insights from recording multiple ion currents in each cell.

    Monfredi, Oliver; Tsutsui, Kenta; Ziman, Bruce; Stern, Michael D; Lakatta, Edward G; Maltsev, Victor A

    2018-03-01

    Cardiac pacemaker cells, including cells of the sinoatrial node, are heterogeneous in size, morphology, and electrophysiological characteristics. The exact extent to which these cells differ electrophysiologically is unclear yet is critical to understanding their functioning. We examined major ionic currents in individual intercaval pacemaker cells (IPCs) sampled from the paracristal, intercaval region (including the sinoatrial node) that were spontaneously beating after enzymatic isolation from rabbit hearts. The beating rate was measured at baseline and after inhibition of the Ca 2+ pump with cyclopiazonic acid. Thereafter, in each cell, we consecutively measured the density of funny current ( I f ), delayed rectifier K + current ( I K ) (a surrogate of repolarization capacity), and L-type Ca 2+ current ( I Ca,L ) using whole cell patch clamp . The ionic current densities varied to a greater extent than previously appreciated, with some IPCs demonstrating very small or zero I f . The density of none of the currents was correlated with cell size, while I Ca,L and I f densities were related to baseline beating rates. I f density was correlated with I K density but not with that of I Ca,L . Inhibition of Ca 2+ cycling had a greater beating rate slowing effect in IPCs with lower I f densities. Our numerical model simulation indicated that 1) IPCs with small (or zero) I f or small I Ca,L can operate via a major contribution of Ca 2+ clock, 2) I f -Ca 2+ -clock interplay could be important for robust pacemaking function, and 3) coupled I f - I K function could regulate maximum diastolic potential. Thus, we have demonstrated marked electrophysiological heterogeneity of IPCs. This heterogeneity is manifested in basal beating rate and response to interference of Ca 2+ cycling, which is linked to I f . NEW & NOTEWORTHY In the present study, a hitherto unrecognized range of heterogeneity of ion currents in pacemaker cells from the intercaval region is demonstrated

  6. Balance functions: Multiplicity and transverse momentum dependence of the charge dependent correlations in ALICE

    AUTHOR|(CDS)2078856; Snellings, Raimond; Christakoglou, Panos

    The measurement of charge-dependent correlations between positively and negatively charged particles as a function of pseudorapidity and azimuthal angle, known as the balance functions, provide insight to the properties of matter created in high-energy collisions. The balance functions are argued to probe the creation time of the particles and are also sensitive to the collective motion of the system. In this thesis, I present the results of the measured balance functions in p--Pb collisions at √sNN = 5.02~TeV obtained with the ALICE detector at the LHC. The results are compared with balance functions measured in pp and Pb--Pb collisions at √s=7~TeV and √sNN = 2.76~TeV$, respectively. The width of the balance functions in both pseudorapidity and azimuthal angle for non-identified charged particles decreases with increasing multiplicity in all three systems, for particles with low transverse momentum value pT < 2~GeV/c. For higher values of transverse momentum the balance functions become narrower and...

  7. The function of communities in protein interaction networks at multiple scales

    Jones Nick S

    2010-07-01

    Full Text Available Abstract Background If biology is modular then clusters, or communities, of proteins derived using only protein interaction network structure should define protein modules with similar biological roles. We investigate the link between biological modules and network communities in yeast and its relationship to the scale at which we probe the network. Results Our results demonstrate that the functional homogeneity of communities depends on the scale selected, and that almost all proteins lie in a functionally homogeneous community at some scale. We judge functional homogeneity using a novel test and three independent characterizations of protein function, and find a high degree of overlap between these measures. We show that a high mean clustering coefficient of a community can be used to identify those that are functionally homogeneous. By tracing the community membership of a protein through multiple scales we demonstrate how our approach could be useful to biologists focusing on a particular protein. Conclusions We show that there is no one scale of interest in the community structure of the yeast protein interaction network, but we can identify the range of resolution parameters that yield the most functionally coherent communities, and predict which communities are most likely to be functionally homogeneous.

  8. Exercise therapy in multiple sclerosis and its effects on function and the brain

    Dalgas, Ulrik

    2017-01-01

    to clinically relevant improvements in physical function, but should be considered an adjunct to specific task-based training. Exercise has also shown positive effects on the brain, including improvements in brain volume and cognition. In summary, exercise therapy is a safe and potent nonpharmacological...... intervention in MS, with beneficial effects on both functional capacity and the brain....

  9. Novel interstitial deletion of 10q24.3-25.1 associated with multiple congenital anomalies including lobar holoprosencephaly, cleft lip and palate, and hypoplastic kidneys.

    Peltekova, Iskra T; Hurteau-Millar, Julie; Armour, Christine M

    2014-12-01

    Chromosome 10q deletions are rare and phenotypically diverse. Such deletions differ in length and occur in numerous regions on the long arm of chromosome 10, accounting for the wide clinical variability. Commonly reported findings include dysmorphic facial features, microcephaly, developmental delay, and genitourinary abnormalities. Here, we report on a female patient with a novel interstitial 5.54 Mb deletion at 10q24.31-q25.1. This patient had findings in common with a previously reported patient with an overlapping deletion, including renal anomalies and an orofacial cleft, but also demonstrated lobar holoprosencephaly and a Dandy-Walker malformation, features which have not been previously reported with 10q deletions. An analysis of the region deleted in our patient showed numerous genes, such as KAZALD1, PAX2, SEMA4G, ACTRA1, INA, and FGF8, whose putative functions may have played a role in the phenotype seen in our patient. © 2014 Wiley Periodicals, Inc.

  10. Synthesis of Carbon Dots with Multiple Color Emission by Controlled Graphitization and Surface Functionalization.

    Miao, Xiang; Qu, Dan; Yang, Dongxue; Nie, Bing; Zhao, Yikang; Fan, Hongyou; Sun, Zaicheng

    2018-01-01

    Multiple-color-emissive carbon dots (CDots) have potential applications in various fields such as bioimaging, light-emitting devices, and photocatalysis. The majority of the current CDots to date exhibit excitation-wavelength-dependent emissions with their maximum emission limited at the blue-light region. Here, a synthesis of multiple-color-emission CDots by controlled graphitization and surface function is reported. The CDots are synthesized through controlled thermal pyrolysis of citric acid and urea. By regulating the thermal-pyrolysis temperature and ratio of reactants, the maximum emission of the resulting CDots gradually shifts from blue to red light, covering the entire light spectrum. Specifically, the emission position of the CDots can be tuned from 430 to 630 nm through controlling the extent of graphitization and the amount of surface functional groups, COOH. The relative photoluminescence quantum yields of the CDots with blue, green, and red emission reach up to 52.6%, 35.1%, and 12.9%, respectively. Furthermore, it is demonstrated that the CDots can be uniformly dispersed into epoxy resins and be fabricated as transparent CDots/epoxy composites for multiple-color- and white-light-emitting devices. This research opens a door for developing low-cost CDots as alternative phosphors for light-emitting devices. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Dual-Functional Ultrafiltration Membrane for Simultaneous Removal of Multiple Pollutants with High Performance.

    Pan, Shunlong; Li, Jiansheng; Noonan, Owen; Fang, Xiaofeng; Wan, Gaojie; Yu, Chengzhong; Wang, Lianjun

    2017-05-02

    Simultaneous removal of multiple pollutants from aqueous solution with less energy consumption is crucial in water purification. Here, a novel concept of dual-functional ultrafiltration (DFUF) membrane is demonstrated by entrapment of nanostructured adsorbents into the finger-like pores of ultrafiltration (UF) membrane rather than in the membrane matrix in previous reports of blend membranes, resulting in an exceptionally high active content and simultaneous removal of multiple pollutants from water due to the dual functions of rejection and adsorption. As a demonstration, hollow porous Zr(OH) x nanospheres (HPZNs) were immobilized in poly(ether sulfone) (PES) UF membranes through polydopamine coating with a high content of 68.9 wt %. The decontamination capacity of DFUF membranes toward multiple model pollutants (colloidal gold, polyethylene glycol (PEG), Pb(II)) was evaluated against a blend membrane. Compared to the blend membrane, the DFUF membranes showed 2.1-fold increase in the effective treatment volume for the treatment of Pb(II) contaminated water from 100 ppb to below 10 ppb (WHO drinking water standard). Simultaneously, the DFUF membranes effectively removed the colloidal gold and PEG below instrument detection limit, however the blend membrane only achieved 97.6% and 96.8% rejection for colloidal gold and PEG, respectively. Moreover, the DFUF membranes showed negligible leakage of nanoadsorbents during testing; and the membrane can be easily regenerated and reused. This study sheds new light on the design of high performance multifunction membranes for drinking water purification.

  12. Multiple logic functions from extended blockade region in a silicon quantum-dot transistor

    Lee, Youngmin; Lee, Sejoon; Im, Hyunsik; Hiramoto, Toshiro

    2015-01-01

    We demonstrate multiple logic-functions at room temperature on a unit device of the Si single electron transistor (SET). Owing to the formation of the multi-dot system, the device exhibits the enhanced Coulomb blockade characteristics (e.g., large peak-to-valley current ratio ∼200) that can improve the reliability of the SET-based logic circuits. The SET displays a unique feature useful for the logic applications; namely, the Coulomb oscillation peaks are systematically shifted by changing either of only the gate or the drain voltage. This enables the SET to act as a multi-functional one-transistor logic gate with AND, OR, NAND, and XOR functions

  13. Multiple logic functions from extended blockade region in a silicon quantum-dot transistor

    Lee, Youngmin; Lee, Sejoon, E-mail: sejoon@dongguk.edu; Im, Hyunsik [Department of Semiconductor Science, Dongguk University-Seoul, Seoul 100-715 (Korea, Republic of); Hiramoto, Toshiro [Institute of Industrial Science, University of Tokyo, Tokyo 153-8505 (Japan)

    2015-02-14

    We demonstrate multiple logic-functions at room temperature on a unit device of the Si single electron transistor (SET). Owing to the formation of the multi-dot system, the device exhibits the enhanced Coulomb blockade characteristics (e.g., large peak-to-valley current ratio ∼200) that can improve the reliability of the SET-based logic circuits. The SET displays a unique feature useful for the logic applications; namely, the Coulomb oscillation peaks are systematically shifted by changing either of only the gate or the drain voltage. This enables the SET to act as a multi-functional one-transistor logic gate with AND, OR, NAND, and XOR functions.

  14. Generalized internal multiple imaging

    Zuberi, Mohammad Akbar Hosain

    2014-12-04

    Various examples are provided for generalized internal multiple imaging (GIMI). In one example, among others, a method includes generating a higher order internal multiple image using a background Green\\'s function and rendering the higher order internal multiple image for presentation. In another example, a system includes a computing device and a generalized internal multiple imaging (GIMI) application executable in the computing device. The GIMI application includes logic that generates a higher order internal multiple image using a background Green\\'s function and logic that renders the higher order internal multiple image for display on a display device. In another example, a non-transitory computer readable medium has a program executable by processing circuitry that generates a higher order internal multiple image using a background Green\\'s function and renders the higher order internal multiple image for display on a display device.

  15. Generalized internal multiple imaging

    Zuberi, Mohammad Akbar Hosain; Alkhalifah, Tariq

    2014-01-01

    Various examples are provided for generalized internal multiple imaging (GIMI). In one example, among others, a method includes generating a higher order internal multiple image using a background Green's function and rendering the higher order internal multiple image for presentation. In another example, a system includes a computing device and a generalized internal multiple imaging (GIMI) application executable in the computing device. The GIMI application includes logic that generates a higher order internal multiple image using a background Green's function and logic that renders the higher order internal multiple image for display on a display device. In another example, a non-transitory computer readable medium has a program executable by processing circuitry that generates a higher order internal multiple image using a background Green's function and renders the higher order internal multiple image for display on a display device.

  16. Multiple-scanning-probe tunneling microscope with nanoscale positional recognition function.

    Higuchi, Seiji; Kuramochi, Hiromi; Laurent, Olivier; Komatsubara, Takashi; Machida, Shinichi; Aono, Masakazu; Obori, Kenichi; Nakayama, Tomonobu

    2010-07-01

    Over the past decade, multiple-scanning-probe microscope systems with independently controlled probes have been developed for nanoscale electrical measurements. We developed a quadruple-scanning-probe tunneling microscope (QSPTM) that can determine and control the probe position through scanning-probe imaging. The difficulty of operating multiple probes with submicrometer precision drastically increases with the number of probes. To solve problems such as determining the relative positions of the probes and avoiding of contact between the probes, we adopted sample-scanning methods to obtain four images simultaneously and developed an original control system for QSPTM operation with a function of automatic positional recognition. These improvements make the QSPTM a more practical and useful instrument since four images can now be reliably produced, and consequently the positioning of the four probes becomes easier owing to the reduced chance of accidental contact between the probes.

  17. Experimental design and multiple response optimization. Using the desirability function in analytical methods development.

    Candioti, Luciana Vera; De Zan, María M; Cámara, María S; Goicoechea, Héctor C

    2014-06-01

    A review about the application of response surface methodology (RSM) when several responses have to be simultaneously optimized in the field of analytical methods development is presented. Several critical issues like response transformation, multiple response optimization and modeling with least squares and artificial neural networks are discussed. Most recent analytical applications are presented in the context of analytLaboratorio de Control de Calidad de Medicamentos (LCCM), Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, C.C. 242, S3000ZAA Santa Fe, ArgentinaLaboratorio de Control de Calidad de Medicamentos (LCCM), Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, C.C. 242, S3000ZAA Santa Fe, Argentinaical methods development, especially in multiple response optimization procedures using the desirability function. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Aerobic capacity explains physical functioning and participation in patients with multiple sclerosis-related fatigue.

    Rosalie Driehuis, Emma; van den Akker, Lizanne Eva; de Groot, Vincent; Beckerman, Heleen

    2018-02-13

    To investigate whether aerobic capacity explains the level of self-reported physical activity, physical functioning, and participation and autonomy in daily living in persons with multiple sclerosis-related fatigue. A cross-sectional study. Sixty-two participants with multiple sclerosis-related fatigue. Aerobic capacity was measured with a leg ergometer and was expressed as maximal oxygen uptake (VO2max, in ml/kg/min). Physical activity was measured with the Physical Activity Scale for Individuals with Physical Disabilities (PASIPD), physical functioning with the Short Form 36 - physical functioning (SF36-pf), and participation and autonomy in daily living with the Impact on Participation and Autonomy questionnaire (IPA). Multiple regression analyses were performed, adjusted for potential confounders (gender, age, body mass index, educational level, and employment status). Mean maximal oxygen uptake (VO2max) was 23.9 ml/kg/min (standard deviation (SD) 6.3 ml/kg/min). There was no significant relationship between VO2max and physical activity (PASIPD): β = 0.320, 95% confidence interval (95% CI) = -0.109 to 0.749, R2 = 10.8%. Higher VO2max correlated with better physical functioning (SF36-pf): β = 1.527, 95% CI = 0.820-2.234, R2 = 25.9%, and was significantly related to IPA domains "autonomy indoors" (β = -0.043, 95% CI = -0.067 to -0.020, R2 = 20.6%), "autonomy outdoors" (β = -0.037, 95% CI = -0.062 to -0.012, R2 = 18.2%) and "social life and relationships" (β=-0.033, 95% CI = -0.060 to -0.007, R2 = 21.3%). Maximum aerobic capacity was severely reduced in persons with multiple sclerosis-related fatigue. This partly explains the limited physical functioning and restrictions in participation and autonomy indoors, outdoors and in social life and relationships in these persons.

  19. Aerobic capacity explains physical functioning and participation in patients with multiple sclerosis-related fatigue

    Emma Rosalie Driehuis

    2018-01-01

    Full Text Available Objective: To investigate whether aerobic capacity explains the level of self-reported physical activity, physical functioning, and participation and autonomy in daily living in persons with multiple sclerosis-related fatigue. Design: A cross-sectional study. Patients: Sixty-two participants with multiple sclerosis-related fatigue. Methods: Aerobic capacity was measured with a leg ergometer and was expressed as maximal oxygen uptake (VO2max, in ml/kg/min. Physical activity was measured with the Physical Activity Scale for Individuals with Physical Disabilities (PASIPD, physical functioning with the Short Form 36 – physical functioning (SF36-pf, and participation and autonomy in daily living with the Impact on Participation and Autonomy questionnaire (IPA. Multiple regression analyses were performed, adjusted for potential confounders (gender, age, body mass index, educational level, and employment status. Results: Mean maximal oxygen uptake (VO2max was 23.9 ml/kg/min (standard deviation (SD 6.3 ml/kg/min. There was no significant relationship between VO2max and physical activity (PASIPD: β = 0.320, 95% confidence interval (95% CI = –0.109 to 0.749, R2 = 10.8%. Higher VO2max correlated with better physical functioning (SF36-pf: β = 1.527, 95% CI = 0.820–2.234, R2 = 25.9%, and was significantly related to IPA domains “autonomy indoors” (β = –0.043, 95% CI = –0.067 to –0.020, R2 = 20.6%, “autonomy outdoors” (β = –0.037, 95% CI = –0.062 to –0.012, R2 = 18.2% and “social life and relationships” (β=–0.033, 95% CI = –0.060 to –0.007, R2 = 21.3%. Conclusion: Maximum aerobic capacity was severely reduced in persons with multiple sclerosis-related fatigue. This partly explains the limited physical functioning and restrictions in participation and autonomy indoors, outdoors and in social life and relationships in these persons.

  20. Comparative evaluation of Plateletworks, Multiplate analyzer and Platelet function analyzer-200 in cardiology patients.

    Kim, Jeeyong; Cho, Chi Hyun; Jung, Bo Kyeung; Nam, Jeonghun; Seo, Hong Seog; Shin, Sehyun; Lim, Chae Seung

    2018-04-14

    The objective of this study was to comparatively evaluate three commercial whole-blood platelet function analyzer systems: Platelet Function Analyzer-200 (PFA; Siemens Canada, Mississauga, Ontario, Canada), Multiplate analyzer (MP; Roche Diagnostics International Ltd., Rotkreuz, Switzerland), and Plateletworks Combo-25 kit (PLW; Helena Laboratories, Beaumont, TX, USA). Venipuncture was performed on 160 patients who visited a department of cardiology. Pairwise agreement among the three platelet function assays was assessed using Cohen's kappa coefficient and percent agreement within the reference limit. Kappa values with the same agonists were poor between PFA-collagen (COL; agonist)/adenosine diphosphate (ADP) and MP-ADP (-0.147), PFA-COL/ADP and PLW-ADP (0.089), MP-ADP and PLW-ADP (0.039), PFA-COL/ADP and MP-COL (-0.039), and between PFA-COL/ADP and PLW-COL (-0.067). Nonetheless, kappa values for the same assay principle with a different agonist were slightly higher between PFA-COL/ADP and PFA-COL/EPI (0.352), MP-ADP and MP-COL (0.235), and between PLW-ADP and PLW-COL (0.247). The range of percent agreement values was 38.7% to 73.8%. Therefore, various measurements of platelet function by more than one method were needed to obtain a reliable interpretation of platelet function considering low kappa coefficient and modest percent agreement rates among 3 different platelet function tests.

  1. Multiple Types of Memory and Everyday Functional Assessment in Older Adults

    Beaver, Jenna

    2017-01-01

    Abstract Objective Current proxy measures for assessing everyday functioning (e.g., questionnaires, performance-based measures, and direct observation) show discrepancies in their rating of functional status. The present study investigated the relationship between multiple proxy measures of functional status and content memory (i.e., memory for information), temporal order memory, and prospective memory in an older adult sample. Method A total of 197 community-dwelling older adults who did (n = 45) or did not meet (n = 152) criteria for mild cognitive impairment (MCI), completed six different assessments of functional status (two questionnaires, two performance-based tasks, and two direct observation tasks) as well as experimental measures of content memory, prospective memory, and temporal order memory. Results After controlling for demographics and content memory, the temporal order and prospective memory measures explained a significant amount of variance in all proxy functional status measures. When all variables were entered into the regression analyses, content memory and prospective memory were found to be significant predictors of all measures of functional status, whereas temporal order memory was a significant predictor for the questionnaire and direct observation measures, but not performance-based measures. Conclusion The results suggest that direct observation and questionnaire measures may be able to capture components of everyday functioning that require context and temporal sequencing abilities, such as multi-tasking, that are not as well captured in many current laboratory performance-based measures of functional status. Future research should aim to inform the development and use of maximally effective and valid proxy measures of functional ability. PMID:28334170

  2. Multiple Types of Memory and Everyday Functional Assessment in Older Adults.

    Beaver, Jenna; Schmitter-Edgecombe, Maureen

    2017-06-01

    Current proxy measures for assessing everyday functioning (e.g., questionnaires, performance-based measures, and direct observation) show discrepancies in their rating of functional status. The present study investigated the relationship between multiple proxy measures of functional status and content memory (i.e., memory for information), temporal order memory, and prospective memory in an older adult sample. A total of 197 community-dwelling older adults who did (n = 45) or did not meet (n = 152) criteria for mild cognitive impairment (MCI), completed six different assessments of functional status (two questionnaires, two performance-based tasks, and two direct observation tasks) as well as experimental measures of content memory, prospective memory, and temporal order memory. After controlling for demographics and content memory, the temporal order and prospective memory measures explained a significant amount of variance in all proxy functional status measures. When all variables were entered into the regression analyses, content memory and prospective memory were found to be significant predictors of all measures of functional status, whereas temporal order memory was a significant predictor for the questionnaire and direct observation measures, but not performance-based measures. The results suggest that direct observation and questionnaire measures may be able to capture components of everyday functioning that require context and temporal sequencing abilities, such as multi-tasking, that are not as well captured in many current laboratory performance-based measures of functional status. Future research should aim to inform the development and use of maximally effective and valid proxy measures of functional ability. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. Using Functional Electrical Stimulation Mediated by Iterative Learning Control and Robotics to Improve Arm Movement for People With Multiple Sclerosis.

    Sampson, Patrica; Freeman, Chris; Coote, Susan; Demain, Sara; Feys, Peter; Meadmore, Katie; Hughes, Ann-Marie

    2016-02-01

    Few interventions address multiple sclerosis (MS) arm dysfunction but robotics and functional electrical stimulation (FES) appear promising. This paper investigates the feasibility of combining FES with passive robotic support during virtual reality (VR) training tasks to improve upper limb function in people with multiple sclerosis (pwMS). The system assists patients in following a specified trajectory path, employing an advanced model-based paradigm termed iterative learning control (ILC) to adjust the FES to improve accuracy and maximise voluntary effort. Reaching tasks were repeated six times with ILC learning the optimum control action from previous attempts. A convenience sample of five pwMS was recruited from local MS societies, and the intervention comprised 18 one-hour training sessions over 10 weeks. The accuracy of tracking performance without FES and the amount of FES delivered during training were analyzed using regression analysis. Clinical functioning of the arm was documented before and after treatment with standard tests. Statistically significant results following training included: improved accuracy of tracking performance both when assisted and unassisted by FES; reduction in maximum amount of FES needed to assist tracking; and less impairment in the proximal arm that was trained. The system was well tolerated by all participants with no increase in muscle fatigue reported. This study confirms the feasibility of FES combined with passive robot assistance as a potentially effective intervention to improve arm movement and control in pwMS and provides the basis for a follow-up study.

  4. Multiple functional attributes of glucose-monitoring neurons in the medial orbitofrontal (ventrolateral prefrontal) cortex.

    Szabó, István; Hormay, Edina; Csetényi, Bettina; Nagy, Bernadett; Lénárd, László; Karádi, Zoltán

    2018-02-01

    Multiple functional attributes of glucose-monitoring neurons in the medial orbitofrontal (ventrolateral prefrontal) cortex. NEUROSCI BIOBEHAV REV 73(1) XXX-XXX, 2017.- Special chemosensory cells, the glucose-monitoring (GM) neurons, reportedly involved in the central feeding control, exist in the medial orbitofrontal (ventrolateral prefrontal) cortex (mVLPFC). Electrophysiological, metabolic and behavioral studies reveal complex functional attributes of these cells and raise their homeostatic significance. Single neuron recordings, by means of the multibarreled microelectrophoretic technique, elucidate differential sensitivities of limbic forebrain neurons in the rat and the rhesus monkey to glucose and other chemicals, whereas gustatory stimulations demonstrate their distinct taste responsiveness. Metabolic examinations provide evidence for alteration of blood glucose level in glucose tolerance test and elevation of plasma triglyceride concentration after destruction of the local GM cells by streptozotocin (STZ). In behavioral studies, STZ microinjection into the mVLPFC fails to interfere with the acquisition of saccharin conditioned taste avoidance, does cause, however, taste perception deficit in taste reactivity tests. Multiple functional attributes of GM neurons in the mVLPFC, within the frame of the hierarchically organized central GM neuronal network, appear to play important role in the maintenance of the homeostatic balance. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

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

    2015-02-01

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

  6. Sexual function in multiple sclerosis. A 5-year follow-up study

    Stenager, E; Stenager, E N; Jensen, K

    1996-01-01

    Sexual dysfunction is known to occur in multiple sclerosis (MS). The purpose of the study is to describe the change in sexual function and symptoms in a longitudinal study. Forty-nine patients (27 females, 22 males) with definite MS were interviewed and examined with 5 years interval. The number...... of patients with sexual dysfunction increased significantly (p = 0.009) and involved females and males equally. Males usually had 1 or two symptoms of sexual dysfunction, while females frequently had 2 or more symptoms. It is concluded that the risk of sexual dysfunction increases over time. Further studies...

  7. High-Resolution Printing of 3D Structures Using an Electrohydrodynamic Inkjet with Multiple Functional Inks.

    An, Byeong Wan; Kim, Kukjoo; Lee, Heejoo; Kim, So-Yun; Shim, Yulhui; Lee, Dae-Young; Song, Jun Yeob; Park, Jang-Ung

    2015-08-05

    Electrohydrodynamic-inkjet-printed high-resolution complex 3D structures with multiple functional inks are demonstrated. Printed 3D structures can have a variety of fine patterns, such as vertical or helix-shaped pillars and straight or rounded walls, with high aspect ratios (greater than ≈50) and narrow diameters (≈0.7 μm). Furthermore, the formation of freestanding, bridge-like Ag wire structures on plastic substrates suggests substantial potentials as high-precision, flexible 3D interconnects. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

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

    2005-07-01

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

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

    Wang, Li-Qun; Saito, Masao

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

  10. Alignment engineering in liquid crystalline elastomers: Free-form microstructures with multiple functionalities

    Zeng, Hao; Cerretti, Giacomo; Wiersma, Diederik S., E-mail: camilla.parmeggiani@lens.unifi.it, E-mail: wiersma@lens.unifi.it [European Laboratory for Non Linear Spectroscopy (LENS), University of Florence, via Nello Carrara 1, 50019 Sesto Fiorentino (Italy); Wasylczyk, Piotr [European Laboratory for Non Linear Spectroscopy (LENS), University of Florence, via Nello Carrara 1, 50019 Sesto Fiorentino (Italy); Faculty of Physics, Institute of Experimental Physics, University of Warsaw, ul. Hoza 69, Warszawa 00-681 (Poland); Martella, Daniele [European Laboratory for Non Linear Spectroscopy (LENS), University of Florence, via Nello Carrara 1, 50019 Sesto Fiorentino (Italy); Dipartimento di Chimica “Ugo Schiff,” University of Florence, via della Lastruccia 3-13, 50019 Sesto Fiorentino (Italy); Parmeggiani, Camilla, E-mail: camilla.parmeggiani@lens.unifi.it, E-mail: wiersma@lens.unifi.it [European Laboratory for Non Linear Spectroscopy (LENS), University of Florence, via Nello Carrara 1, 50019 Sesto Fiorentino (Italy); CNR-INO, via Nello Carrara 1, 50019 Sesto Fiorentino (Italy)

    2015-03-16

    We report a method to fabricate polymer microstructures with local control over the molecular orientation. Alignment control is achieved on molecular level in a structure of arbitrary form that can be from 1 to 100 μm in size, by fixing the local boundary conditions with micro-grating patterns. The method makes use of two-photon polymerization (Direct Laser Writing) and is demonstrated specifically in liquid-crystalline elastomers. This concept allows for the realization of free-form polymeric structures with multiple functionalities which are not possible to realize with existing techniques and which can be locally controlled by light in the micrometer scale.

  11. Multiple kernel learning using single stage function approximation for binary classification problems

    Shiju, S.; Sumitra, S.

    2017-12-01

    In this paper, the multiple kernel learning (MKL) is formulated as a supervised classification problem. We dealt with binary classification data and hence the data modelling problem involves the computation of two decision boundaries of which one related with that of kernel learning and the other with that of input data. In our approach, they are found with the aid of a single cost function by constructing a global reproducing kernel Hilbert space (RKHS) as the direct sum of the RKHSs corresponding to the decision boundaries of kernel learning and input data and searching that function from the global RKHS, which can be represented as the direct sum of the decision boundaries under consideration. In our experimental analysis, the proposed model had shown superior performance in comparison with that of existing two stage function approximation formulation of MKL, where the decision functions of kernel learning and input data are found separately using two different cost functions. This is due to the fact that single stage representation helps the knowledge transfer between the computation procedures for finding the decision boundaries of kernel learning and input data, which inturn boosts the generalisation capacity of the model.

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

    Zhang Benwei; Wang, Enke; Wang Xinnian

    2005-01-01

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

  13. Measurement of hadron multiplicities in deep inelastic scattering and extraction of quark fragmentation functions

    Curiel-Garcia, Quiela-Marina

    2014-01-01

    One of the goals of the COMPASS experience is the study of the nucleon spin structure. Data were taken from a polarized muon beam (160 GeV/c) scattering off a polarized target ( 6 LiD or NH 3 ). In this context, the need of a precise knowledge of quark Fragmentation Functions (final-state hadronization of quarks q into hadrons h, FFs) was raised. The FFs can be extracted from hadron multiplicities produced in Semi-Inclusive Deep Inelastic Scattering (SIDIS). This thesis presents the measurement of charged hadrons (pions and kaons) multiplicities from SIDIS data collected in 2006. The data cover a large kinematical range: Q 2 ≥1 (GeV/c)2, y belongs to [0.1,0.9], x belongs to [0.004,0.7] and W belongs to [5,17] GeV. These multiplicities provide an important input for global QCD analyses of world data at NLO, aiming at the FFs determination. (author) [fr

  14. Unpolarised transverse momentum dependent distribution and fragmentation functions from SIDIS multiplicities

    Anselmino, M.; Boglione, M.; Gonzalez, H. J.O.; Melis, S.; Prokudin, A.

    2014-01-01

    In this study, the unpolarised transverse momentum dependent distribution and fragmentation functions are extracted from HERMES and COMPASS experimental measurements of SIDIS multiplicities for charged hadron production. The data are grouped into independent bins of the kinematical variables, in which the TMD factorisation is expected to hold. A simple factorised functional form of the TMDs is adopted, with a Gaussian dependence on the intrinsic transverse momentum, which turns out to be quite adequate in shape. HERMES data do not need any normalisation correction, while fits of the COMPASS data much improve with a y-dependent overall normalisation factor. A comparison of the extracted TMDs with previous EMC and JLab data confirms the adequacy of the simple gaussian distributions. The possible role of the TMD evolution is briefly considered

  15. JDet: interactive calculation and visualization of function-related conservation patterns in multiple sequence alignments and structures.

    Muth, Thilo; García-Martín, Juan A; Rausell, Antonio; Juan, David; Valencia, Alfonso; Pazos, Florencio

    2012-02-15

    We have implemented in a single package all the features required for extracting, visualizing and manipulating fully conserved positions as well as those with a family-dependent conservation pattern in multiple sequence alignments. The program allows, among other things, to run different methods for extracting these positions, combine the results and visualize them in protein 3D structures and sequence spaces. JDet is a multiplatform application written in Java. It is freely available, including the source code, at http://csbg.cnb.csic.es/JDet. The package includes two of our recently developed programs for detecting functional positions in protein alignments (Xdet and S3Det), and support for other methods can be added as plug-ins. A help file and a guided tutorial for JDet are also available.

  16. Finger and foot tapping as alternative outcomes of upper and lower extremity function in multiple sclerosis.

    Tanigawa, Makoto; Stein, Jason; Park, John; Kosa, Peter; Cortese, Irene; Bielekova, Bibiana

    2017-01-01

    While magnetic resonance imaging contrast-enhancing lesions represent an excellent screening tool for disease-modifying treatments in relapsing-remitting multiple sclerosis (RRMS), this biomarker is insensitive for testing therapies against compartmentalized inflammation in progressive multiple sclerosis (MS). Therefore, alternative sensitive outcomes are needed. Using machine learning, clinician-acquired disability scales can be combined with timed measures of neurological functions such as walking speed (e.g. 25-foot walk; 25FW) or fine finger movements (e.g. 9-hole peg test; 9HPT) into sensitive composite clinical scales, such as the recently developed combinatorial, weight-adjusted disability scale (CombiWISE). Ideally, these complementary simplified measurements of certain neurological functions could be performed regularly at patients' homes using smartphones. We asked whether tests amenable to adaptation to smartphone technology, such as finger and foot tapping have comparable sensitivity and specificity to current non-clinician-acquired disability measures. We observed that finger and foot tapping can differentiate RRMS and progressive MS in a cross-sectional study and can also measure yearly and two-year disease progression in the latter, with better power (based on z-scores) in comparison to currently utilized 9HPT and 25FW. Replacing the 9HPT and 25FW with simplified tests broadly adaptable to smartphone technology may enhance the power of composite scales for progressive MS.

  17. Functional adaptation to loading of a single bone is neuronally regulated and involves multiple bones.

    Sample, Susannah J; Behan, Mary; Smith, Lesley; Oldenhoff, William E; Markel, Mark D; Kalscheur, Vicki L; Hao, Zhengling; Miletic, Vjekoslav; Muir, Peter

    2008-09-01

    Regulation of load-induced bone formation is considered a local phenomenon controlled by osteocytes, although it has also been hypothesized that functional adaptation may be neuronally regulated. The aim of this study was to examine bone formation in multiple bones, in response to loading of a single bone, and to determine whether adaptation may be neuronally regulated. Load-induced responses in the left and right ulnas and humeri were determined after loading of the right ulna in male Sprague-Dawley rats (69 +/- 16 days of age). After a single period of loading at -760-, -2000-, or -3750-microepsilon initial peak strain, rats were given calcein to label new bone formation. Bone formation and bone neuropeptide concentrations were determined at 10 days. In one group, temporary neuronal blocking was achieved by perineural anesthesia of the brachial plexus with bupivicaine during loading. We found right ulna loading induces adaptive responses in other bones in both thoracic limbs compared with Sham controls and that neuronal blocking during loading abrogated bone formation in the loaded ulna and other thoracic limb bones. Skeletal adaptation was more evident in distal long bones compared with proximal long bones. We also found that the single period of loading modulated bone neuropeptide concentrations persistently for 10 days. We conclude that functional adaptation to loading of a single bone in young rapidly growing rats is neuronally regulated and involves multiple bones. Persistent changes in bone neuropeptide concentrations after a single loading period suggest that plasticity exists in the innervation of bone.

  18. Solution to PDEs using radial basis function finite-differences (RBF-FD) on multiple GPUs

    Bollig, Evan F.; Flyer, Natasha; Erlebacher, Gordon

    2012-01-01

    This paper presents parallelization strategies for the radial basis function-finite difference (RBF-FD) method. As a generalized finite differencing scheme, the RBF-FD method functions without the need for underlying meshes to structure nodes. It offers high-order accuracy approximation and scales as O(N) per time step, with N being with the total number of nodes. To our knowledge, this is the first implementation of the RBF-FD method to leverage GPU accelerators for the solution of PDEs. Additionally, this implementation is the first to span both multiple CPUs and multiple GPUs. OpenCL kernels target the GPUs and inter-processor communication and synchronization is managed by the Message Passing Interface (MPI). We verify our implementation of the RBF-FD method with two hyperbolic PDEs on the sphere, and demonstrate up to 9x speedup on a commodity GPU with unoptimized kernel implementations. On a high performance cluster, the method achieves up to 7x speedup for the maximum problem size of 27,556 nodes.

  19. The Effects of Massage Therapy on Multiple Sclerosis Patients’ Quality of Life and Leg Function

    Brittany Schroeder

    2014-01-01

    Full Text Available Background. Massage therapy is a noninvasive treatment that many individuals with multiple sclerosis (MS use to supplement their conventional treatment. Objective. We hypothesize that massage therapy will improve the leg function and overall quality of life (QoL of MS patients. Design. A two-period (rest, massage crossover design was used. Twenty-four individuals with MS ranging from 3.0 to 7.0 on the Expanded Disability Status Scale (EDSS received Swedish massage treatments for four weeks. Exercise capacity and leg function as well as QoL were assessed using the Six-Minute Walk Test (6MWT and the Hamburg Quality of Life in Multiple Sclerosis (HAQUAMS instrument, respectively. Assessments were measured before and after a massage period and a rest period where no massages were employed. Results. The results displayed no significant changes in 6MWT distances or HAQUAMS scores. However, the participants perceived improvement in overall health as expressed in written comments. Conclusions. Massage is a safe, noninvasive treatment that may assist MS patients in managing the stress of their symptoms. Future studies with larger sample size and cortisol measures are warranted.

  20. Conservative two-step procedure including uterine artery embolization with embosphere and surgical myomectomy for the treatment of multiple fibroids: Preliminary experience

    Malartic, Cécile; Morel, Olivier; Fargeaudou, Yann; Le Dref, Olivier; Fazel, Afchine; Barranger, Emmanuel; Soyer, Philippe

    2012-01-01

    Objective: To evaluate the feasibility and safety of combined uterine artery embolization (UAE) using embosphere and surgical myomectomy as an alternative to radical hysterectomy in premenopausal women with multiple fibroids. Materials and methods: Mid-term clinical outcome (mean, 25 months) of 12 premenopausal women (mean age, 38 years) with multiple and large symptomatic fibroids who desired to retain their uterus and who were treated using combined UAE and surgical myomectomy were retrospectively analyzed. In all women, UAE alone was contraindicated because of large (>10 cm) or subserosal or submucosal fibroids and myomectomy alone was contraindicated because of too many (>10) fibroids. Results: UAE and surgical myomectomy were successfully performed in all women. Myomectomy was performed using laparoscopy (n = 6), open laparotomy (n = 3), hysteroscopy (n = 2), or laparoscopy and hysteroscopy (n = 1). Mean serum hemoglobin level drop was 0.97 g/dL and no blood transfusion was needed. No immediate complications were observed and all women reported resumption of normal menses. During a mean follow-up period of 25 months (range, 14–37 months), complete resolution of initial symptoms along with decrease in uterine volume (mean, 48%) was observed in all women. No further hysterectomy was required in any woman. Conclusion: In premenopausal women with multiple fibroids, the two-step procedure is safe and effective alternative to radical hysterectomy, which allows preserving the uterus. Further prospective studies, however, should be done to determine the actual benefit of this combined approach on the incidence of subsequent pregnancies.

  1. The assessment of problems in functioning and the subjective perception of these problems in people with Multiple Sclerosis : the Multiple Sclerosis Impact Profile (MSIP)

    Wynia, Klaske; Roodbol, Petrie F.; Middel, Berry

    People with Multiple Sclerosis (MS) perceive consequences of this chronic condition that are not limited to impairments in physical functioning but also have their impact on limitations in activities and restrictions in participation in life situations. There is a growing awareness among healthcare

  2. On Measurement of Efficiency of Cobb-Douglas Production Function with Additive and Multiplicative Errors

    Md. Moyazzem Hossain

    2015-02-01

    Full Text Available In developing counties, efficiency of economic development has determined by the analysis of industrial production. An examination of the characteristic of industrial sector is an essential aspect of growth studies. The most of the developed countries are highly industrialized as they brief “The more industrialization, the more development”. For proper industrialization and industrial development we have to study industrial input-output relationship that leads to production analysis. For a number of reasons econometrician’s belief that industrial production is the most important component of economic development because, if domestic industrial production increases, GDP will increase, if elasticity of labor is higher, implement rates will increase and investment will increase if elasticity of capital is higher. In this regard, this paper should be helpful in suggesting the most suitable Cobb-Douglas production function to forecast the production process for some selected manufacturing industries of developing countries like Bangladesh. This paper choose the appropriate Cobb-Douglas function which gives optimal combination of inputs, that is, the combination that enables it to produce the desired level of output with minimum cost and hence with maximum profitability for some selected manufacturing industries of Bangladesh over the period 1978-79 to 2011-2012. The estimated results shows that the estimates of both capital and labor elasticity of Cobb-Douglas production function with additive errors are more efficient than those estimates of Cobb-Douglas production function with multiplicative errors.

  3. Evaluation of the anti-inflammatory actions of various functional food materials including glucosamine on synovial cells.

    Yamagishi, Yoshie; Someya, Akimasa; Imai, Kensuke; Nagao, Junji; Nagaoka, Isao

    2017-08-01

    The anti-inflammatory actions of glucosamine (GlcN) on arthritic disorders involve the suppression of inflammatory mediator production from synovial cells. GlcN has also been reported to inhibit the activation of the p38 mitogen-activated protein kinase (MAPK) pathway. The present study aimed to determine the cooperative and anti‑inflammatory actions of functional food materials and evaluated the production of interleukin (IL)‑8 and phosphorylation of p38 MAPK in IL-1β-activated synovial cells, incubated with the combination of GlcN and various functional food materials containing L‑methionine (Met), undenatured type II collagen (UC‑II), chondroitin sulfate (CS), methylsulfonylmethane (MSM) and agaro-oligosaccharide (AO). The results indicated that Met, UC‑II, CS, MSM and AO slightly or moderately suppressed the IL-1β-stimulated IL‑8 production by human synovial MH7A cells. The same compounds further decreased the IL‑8 level lowered by GlcN. Similarly, they slightly suppressed the phosphorylation level of p38 MAPK and further reduced the phosphorylation level lowered by GlcN. These observations suggest a possibility that these functional food materials exert an anti‑inflammatory action (inhibition of IL‑8 production) in combination with GlcN by cooperatively suppressing the p38 MAPK signaling (phosphorylation).

  4. Evolutionary and molecular foundations of multiple contemporary functions of the nitroreductase superfamily.

    Akiva, Eyal; Copp, Janine N; Tokuriki, Nobuhiko; Babbitt, Patricia C

    2017-11-07

    Insight regarding how diverse enzymatic functions and reactions have evolved from ancestral scaffolds is fundamental to understanding chemical and evolutionary biology, and for the exploitation of enzymes for biotechnology. We undertook an extensive computational analysis using a unique and comprehensive combination of tools that include large-scale phylogenetic reconstruction to determine the sequence, structural, and functional relationships of the functionally diverse flavin mononucleotide-dependent nitroreductase (NTR) superfamily (>24,000 sequences from all domains of life, 54 structures, and >10 enzymatic functions). Our results suggest an evolutionary model in which contemporary subgroups of the superfamily have diverged in a radial manner from a minimal flavin-binding scaffold. We identified the structural design principle for this divergence: Insertions at key positions in the minimal scaffold that, combined with the fixation of key residues, have led to functional specialization. These results will aid future efforts to delineate the emergence of functional diversity in enzyme superfamilies, provide clues for functional inference for superfamily members of unknown function, and facilitate rational redesign of the NTR scaffold. Copyright © 2017 the Author(s). Published by PNAS.

  5. Towards an integration of biodiversity-ecosystem functioning and food web theory to evaluate relationships between multiple ecosystem services

    Hines, Jes; van der Putten, W.H.; De Deyn, G.B.; Wagg, Cameron; Voigt, Winfried; Mulder, Christian; Weisser, Wolfgang W.; Engel, Jan; Melian, Carlos; Scheu, Stefan; Birkhofer, Klaus; Ebeling, Anne; Scherber, Christoph; Eisenhauer, Nico

    2015-01-01

    Ecosystem responses to changes in species diversity are often studied individually. However, changes in species diversity can simultaneously influence multiple interdependent ecosystem functions. Therefore, an important challenge is to determine when and how changes in species diversity that

  6. Disrupted Module Efficiency of Structural and Functional Brain Connectomes in Clinically Isolated Syndrome and Multiple Sclerosis

    Yaou Liu

    2018-04-01

    Full Text Available Recent studies have demonstrated disrupted topological organization of brain connectome in multiple sclerosis (MS. However, whether the communication efficiency between different functional systems is affected in the early stage of MS remained largely unknown. In this study, we constructed the structural connectivity (SC and functional connectivity (FC networks in 41 patients with clinically isolated syndrome (CIS, 32 MS patients and 35 healthy controls (HC based on diffusion and resting-state functional MRI. To quantify the communication efficiency within and between different functional systems, we proposed two measures called intra- and inter-module efficiency. Based on the module parcellation of functional backbone network, the intra- and inter-module efficiency of SC and FC networks was calculated for each participant. For the SC network, CIS showed decreased inter-module efficiency between the sensory-motor network (SMN, the visual network (VN, the default-mode network (DMN and the fronto-parietal network (FPN compared with HC, while MS showed more widespread decreased module efficiency both within and between modules relative to HC and CIS. For the FC network, no differences were found between CIS and HC, and a decreased inter-module efficiency between SMN and FPN and between VN and FPN was identified in MS, compared with HC and CIS. Moreover, both intra- and inter-module efficiency of SC network were correlated with the disability and cognitive scores in MS. Therefore, our results demonstrated early SC changes between modules in CIS, and more widespread SC alterations and inter-module FC changes were observed in MS, which were further associated with cognitive impairment and physical disability.

  7. Report of Increasing Overdose Deaths that include Acetyl Fentanyl in Multiple Counties of the Southwestern Region of the Commonwealth of Pennsylvania in 2015-2016.

    Dwyer, Jessica B; Janssen, Jennifer; Luckasevic, Todd M; Williams, Karl E

    2018-01-01

    Acetyl fentanyl is a Schedule I controlled synthetic opioid that is becoming an increasingly detected "designer drug." Routine drug screening procedures in local forensic toxicology laboratories identified a total of 41 overdose deaths associated with acetyl fentanyl within multiple counties of the southwestern region of the state of Pennsylvania. The range, median, mean, and standard deviation of blood acetyl fentanyl concentrations for these 41 cases were 0.13-2100 ng/mL, 11 ng/mL, 169.3 ng/mL, and 405.3 ng/mL, respectively. Thirty-six individuals (88%) had a confirmed history of substance abuse, and all but one case (96%) were ruled multiple drug toxicities. This report characterizes this localized trend of overdose deaths associated with acetyl fentanyl and provides further evidence supporting an alarmingly concentrated opiate and opioid epidemic of both traditional and novel drugs within this region of the United States. © 2017 American Academy of Forensic Sciences.

  8. Improving executive functioning in children with ADHD: training multiple executive functions within the context of a computer game. a randomized double-blind placebo controlled trial.

    Sebastiaan Dovis

    Full Text Available Executive functions (EFs training interventions aimed at ADHD-symptom reduction have yielded mixed results. Generally, these interventions focus on training a single cognitive domain (e.g., working memory [WM], inhibition, or cognitive-flexibility. However, evidence suggests that most children with ADHD show deficits on multiple EFs, and that these EFs are largely related to different brain regions. Therefore, training multiple EFs might be a potentially more effective strategy to reduce EF-related ADHD symptoms.Eighty-nine children with a clinical diagnosis of ADHD (aged 8-12 were randomized to either a full-active-condition where visuospatial WM, inhibition and cognitive-flexibility were trained, a partially-active-condition where inhibition and cognitive-flexibility were trained and the WM-training task was presented in placebo-mode, or to a full placebo-condition. Short-term and long-term (3-months effects of this gamified, 25-session, home-based computer-training were evaluated on multiple outcome domains.During training compliance was high (only 3% failed to meet compliance criteria. After training, only children in the full-active condition showed improvement on measures of visuospatial short-term-memory (STM and WM. Inhibitory performance and interference control only improved in the full-active- and the partially-active condition. No Treatment-condition x Time interactions were found for cognitive-flexibility, verbal WM, complex-reasoning, nor for any parent-, teacher-, or child-rated ADHD behaviors, EF-behaviors, motivational behaviors, or general problem behaviors. Nonetheless, almost all measures showed main Time-effects, including the teacher-ratings.Improvements on inhibition and visuospatial STM and WM were specifically related to the type of treatment received. However, transfer to untrained EFs and behaviors was mostly nonspecific (i.e., only interference control improved exclusively in the two EF training conditions. As such

  9. Building a functional neurocognitive theory of the multiple intelligences anatomical framework

    Carlo eCerruti

    2013-12-01

    Full Text Available A key goal of educational neuroscience is to conduct constrained experimental research that is theory-driven and yet also clearly related to educators’ complex set of questions and concerns. However, the fields of education, cognitive psychology and neuroscience use different levels of description to characterize human ability. An important advance in research in educational neuroscience would be the identification of a cognitive and neurocognitive framework at a level of description relatively intuitive to educators. I argue that the theory of multiple intelligences (Gardner, 1983, a conception of the mind that motivated a past generation of teachers, may provide such an opportunity. I criticize MI for doing little to clarify for teachers a core misunderstanding, specifically that MI was only an anatomical map of the mind but not a functional theory that detailed how the mind actually processes information. In an attempt to build a functional MI theory, I integrate into MI basic principles of cognitive and neural functioning, namely interregional neural facilitation and inhibition. In so doing I hope to forge a path towards constrained experimental research that bears upon teachers’ concerns about teaching and learning.

  10. Multiple genetic interaction experiments provide complementary information useful for gene function prediction.

    Magali Michaut

    Full Text Available Genetic interactions help map biological processes and their functional relationships. A genetic interaction is defined as a deviation from the expected phenotype when combining multiple genetic mutations. In Saccharomyces cerevisiae, most genetic interactions are measured under a single phenotype - growth rate in standard laboratory conditions. Recently genetic interactions have been collected under different phenotypic readouts and experimental conditions. How different are these networks and what can we learn from their differences? We conducted a systematic analysis of quantitative genetic interaction networks in yeast performed under different experimental conditions. We find that networks obtained using different phenotypic readouts, in different conditions and from different laboratories overlap less than expected and provide significant unique information. To exploit this information, we develop a novel method to combine individual genetic interaction data sets and show that the resulting network improves gene function prediction performance, demonstrating that individual networks provide complementary information. Our results support the notion that using diverse phenotypic readouts and experimental conditions will substantially increase the amount of gene function information produced by genetic interaction screens.

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

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

    2016-01-01

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

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

    Chelsea M. Stillman

    2016-12-01

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

  13. Functional Brain Connectivity during Multiple Motor Imagery Tasks in Spinal Cord Injury

    Alkinoos Athanasiou

    2018-01-01

    Full Text Available Reciprocal communication of the central and peripheral nervous systems is compromised during spinal cord injury due to neurotrauma of ascending and descending pathways. Changes in brain organization after spinal cord injury have been associated with differences in prognosis. Changes in functional connectivity may also serve as injury biomarkers. Most studies on functional connectivity have focused on chronic complete injury or resting-state condition. In our study, ten right-handed patients with incomplete spinal cord injury and ten age- and gender-matched healthy controls performed multiple visual motor imagery tasks of upper extremities and walking under high-resolution electroencephalography recording. Directed transfer function was used to study connectivity at the cortical source space between sensorimotor nodes. Chronic disruption of reciprocal communication in incomplete injury could result in permanent significant decrease of connectivity in a subset of the sensorimotor network, regardless of positive or negative neurological outcome. Cingulate motor areas consistently contributed the larger outflow (right and received the higher inflow (left among all nodes, across all motor imagery categories, in both groups. Injured subjects had higher outflow from left cingulate than healthy subjects and higher inflow in right cingulate than healthy subjects. Alpha networks were less dense, showing less integration and more segregation than beta networks. Spinal cord injury patients showed signs of increased local processing as adaptive mechanism. This trial is registered with NCT02443558.

  14. Feasibility study for remote assessment of cognitive function in multiple sclerosis.

    George, Michaela F; Holingue, Calliope B; Briggs, Farren B S; Shao, Xiaorong; Bellesis, Kalliope H; Whitmer, Rachel A; Schaefer, Catherine; Benedict, Ralph Hb; Barcellos, Lisa F

    2016-01-01

    Cognitive impairment is common in multiple sclerosis (MS), and affects employment and quality of life. Large studies are needed to identify risk factors for cognitive decline. Currently, a MS-validated remote assessment for cognitive function does not exist. Studies to determine feasibility of large remote cognitive function investigations in MS have not been published. To determine whether MS patients would participate in remote cognitive studies. We utilized the Modified Telephone Interview for Cognitive Status (TICS-M), a previously validated phone assessment for cognitive function in healthy elderly populations to detect mild cognitive impairment. We identified factors that influenced participation rates. We investigated the relationship between MS risk factors and TICS-M score in cases, and score differences between cases and control individuals. The TICS-M was administered to MS cases and controls. Linear and logistic regression models were utilized. 11.5% of eligible study participants did not participate in cognitive testing. MS cases, females and individuals with lower educational status were more likely to refuse (pTICS-M score among cases (pTICS-M score was significantly lower in cases compared to controls (p=0.007). Our results demonstrate convincingly that a remotely administered cognitive assessment is quite feasible for conducting large epidemiologic studies in MS, and lay the much needed foundation for future work that will utilize MS-validated cognitive measures.

  15. Gender, renal function, and outcomes on the liver transplant waiting list: assessment of revised MELD including estimated glomerular filtration rate.

    Myers, Robert P; Shaheen, Abdel Aziz M; Aspinall, Alexander I; Quinn, Robert R; Burak, Kelly W

    2011-03-01

    The Model for End-Stage Liver Disease (MELD) allocation system for liver transplantation (LT) may present a disadvantage for women by including serum creatinine, which is typically lower in females. Our objectives were to investigate gender disparities in outcomes among LT candidates and to assess a revised MELD, including estimated glomerular filtration rate (eGFR), for predicting waiting list mortality. Adults registered for LT between 2002 and 2007 were identified using the UNOS database. We compared components of MELD, MDRD-derived eGFR, and the 3-month probability of LT and death between genders. Discrimination of MELD, MELDNa, and revised models including eGFR for mortality were compared using c-statistics. A total of 40,393 patients (36% female) met the inclusion criteria; 9% died and 24% underwent LT within 3 months of listing. Compared with men, women had lower median serum creatinine (0.9 vs. 1.0 mg/dl), eGFR (72 vs. 83 ml/min/1.73 m(2)), and mean MELD (16.5 vs. 17.2; all p discrimination for 3-month mortality (c-statistics: MELD 0.896, MELD-eGFR 0.894, MELDNa 0.911, MELDNa-eGFR 0.905). Women are disadvantaged under MELD potentially due to its inclusion of creatinine. However, since including eGFR in MELD does not improve mortality prediction, alternative refinements are necessary. Copyright © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  16. Multiple gcd-closed sets and determinants of matrices associated with arithmetic functions

    Hong Siao

    2016-01-01

    Full Text Available Let f be an arithmetic function and S = {x1, …, xn} be a set of n distinct positive integers. By (f(xi, xj (resp. (f[xi, xj] we denote the n × n matrix having f evaluated at the greatest common divisor (xi, xj (resp. the least common multiple [xi, xj] of x, and xj as its (i, j-entry, respectively. The set S is said to be gcd closed if (xi, xj ∈ S for 1 ≤ i, j ≤ n. In this paper, we give formulas for the determinants of the matrices (f(xi, xj and (f[xi, xj] if S consists of multiple coprime gcd-closed sets (i.e., S equals the union of S1, …, Sk with k ≥ 1 being an integer and S1, …, Sk being gcd-closed sets such that (lcm(Si, lcm(Sj = 1 for all 1 ≤ i ≠ j ≤ k. This extends the Bourque-Ligh, Hong’s and the Hong-Loewy formulas obtained in 1993, 2002 and 2011, respectively. It also generalizes the famous Smith’s determinant.

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

    CERN. Geneva

    2015-01-01

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

  18. Development of particle multiplicity distributions using a general form of the grand canonical partition function

    Lee, S.J.; Mekjian, A.Z.

    2004-01-01

    Various phenomenological models of particle multiplicity distributions are discussed using a general form of a unified model which is based on the grand canonical partition function and Feynman's path integral approach to statistical processes. These models can be written as special cases of a more general distribution which has three control parameters which are a,x,z. The relation to these parameters to various physical quantities are discussed. A connection of the parameter a with Fisher's critical exponent τ is developed. Using this grand canonical approach, moments, cumulants and combinants are discussed and a physical interpretation of the combinants are given and their behavior connected to the critical exponent τ. Various physical phenomena such as hierarchical structure, void scaling relations, Koba-Nielson-Olesen or KNO scaling features, clan variables, and branching laws are shown in terms of this general approach. Several of these features which were previously developed in terms of the negative binomial distribution are found to be more general. Both hierarchical structure and void scaling relations depend on the Fisher exponent τ. Applications of our approach to the charged particle multiplicity distribution in jets of L3 and H1 data are given

  19. Estimation of Multiple Point Sources for Linear Fractional Order Systems Using Modulating Functions

    Belkhatir, Zehor

    2017-06-28

    This paper proposes an estimation algorithm for the characterization of multiple point inputs for linear fractional order systems. First, using polynomial modulating functions method and a suitable change of variables the problem of estimating the locations and the amplitudes of a multi-pointwise input is decoupled into two algebraic systems of equations. The first system is nonlinear and solves for the time locations iteratively, whereas the second system is linear and solves for the input’s amplitudes. Second, closed form formulas for both the time location and the amplitude are provided in the particular case of single point input. Finally, numerical examples are given to illustrate the performance of the proposed technique in both noise-free and noisy cases. The joint estimation of pointwise input and fractional differentiation orders is also presented. Furthermore, a discussion on the performance of the proposed algorithm is provided.

  20. Fisetin Acts on Multiple Pathways to Reduce the Impact of Age and Disease on CNS Function

    Maher, Pamela

    2017-01-01

    It is becoming increasingly clear that neurological diseases are multi-factorial involving disruptions in multiple cellular systems. Thus, while each disease has its own initiating mechanisms and pathologies, certain common pathways appear to be involved in most, if not all, neurological diseases described to date. Thus, it is unlikely that modulating only a single factor will be effective at either preventing disease development or slowing disease progression. A better approach is to identify small (fisetin. Fisetin not only has direct antioxidant activity but it can also increase the intracellular levels of glutathione, the major intracellular antioxidant. Fisetin can also activate key neurotrophic factor signaling pathways. In addition, it has anti-inflammatory activity against microglial cells and inhibits the activity of lipoxygenases, thereby reducing the production of pro-inflammatory eicosanoids and their by-products. This wide range of actions suggests that fisetin has the ability to reduce the impact of age-related neurological diseases on brain function. PMID:25961687

  1. Mnesic performance and executive functions in patients with multiple sclerosis (MS

    Isabel Introzzi

    2009-10-01

    Full Text Available The Episodic Memory (EM and the Executive Functions (EF are cognitive areas that are affected in patients with diagnosis of Multiple Sclerosis (MS. Nowadays there exists scarce works destined to explore the infl uence of the EF on measures of mnesic performance in MS. For this reason, we analyze the effect of the EF on the performance in a set of memory measures. We worked with a clinical group (n=36 and with a control group (n=36 compared by age and educational level. The results show that the clinical group obtained significantly low average values in all the mnesic indexes (with exception of recognition and in all the executive measures. All the executive indexes showed significant associations with some of the indexes of mnesic performance. These findings suggest that the problems in the episodic memory in EM patients could be analyzed as the manifestation of a global disorder that could be similar to the one that involves the EF.

  2. Multiple functions of the von Willebrand Factor A domain in matrilins: secretion, assembly, and proteolysis

    Kanbe Katsuaki

    2008-06-01

    Full Text Available Abstract The von Willebrand Factor A (vWF A domain is one of the most widely distributed structural modules in cell-matrix adhesive molecules such as intergrins and extracellular matrix proteins. Mutations in the vWF A domain of matrilin-3 cause multiple epiphyseal dysplasia (MED, however the pathological mechanism remains to be determined. Previously we showed that the vWF A domain in matrilin-1 mediates formation of a filamentous matrix network through metal-ion dependent adhesion sites in the domain. Here we show two new functions of the vWF A domain in cartilage-specific matrilins (1 and 3. First, vWF A domain regulates oligomerization of matrilins. Insertion of a vWF A domain into matrilin-3 converts the formation of a mixture of matrilin-3 tetramer, trimer, and dimer into a tetramer only, while deletion of a vWF A domain from matrilin-1 converts the formation of the native matrilin-1 trimer into a mixture of trimer and dimer. Second, the vWF A domain protects matrilin-1 from proteolysis. We identified a latent proteolytic site next to the vWF A2 domain in matrilin-1, which is sensitive to the inhibitors of matrix proteases. Deletion of the abutting vWF A domain results in degradation of matrilin-1, presumably by exposing the adjacent proteolytic site. In addition, we also confirmed the vWF A domain is vital for the secretion of matrilin-3. Secretion of the mutant matrilin-3 harbouring a point mutation within the vWF A domain, as occurred in MED patients, is markedly reduced and delayed, resulting from intracellular retention of the mutant matrilin-3. Taken together, our data suggest that different mutations/deletions of the vWF A domain in matrilins may lead to distinct pathological mechanisms due to the multiple functions of the vWF A domain.

  3. Reconstruction of an input function from a dynamic PET water image using multiple tissue curves

    Kudomi, Nobuyuki; Maeda, Yukito; Yamamoto, Yuka; Nishiyama, Yoshihiro

    2016-08-01

    Quantification of cerebral blood flow (CBF) is important for the understanding of normal and pathologic brain physiology. When CBF is assessed using PET with {{\\text{H}}2} 15O or C15O2, its calculation requires an arterial input function, which generally requires invasive arterial blood sampling. The aim of the present study was to develop a new technique to reconstruct an image derived input function (IDIF) from a dynamic {{\\text{H}}2} 15O PET image as a completely non-invasive approach. Our technique consisted of using a formula to express the input using tissue curve with rate constant parameter. For multiple tissue curves extracted from the dynamic image, the rate constants were estimated so as to minimize the sum of the differences of the reproduced inputs expressed by the extracted tissue curves. The estimated rates were used to express the inputs and the mean of the estimated inputs was used as an IDIF. The method was tested in human subjects (n  =  29) and was compared to the blood sampling method. Simulation studies were performed to examine the magnitude of potential biases in CBF and to optimize the number of multiple tissue curves used for the input reconstruction. In the PET study, the estimated IDIFs were well reproduced against the measured ones. The difference between the calculated CBF values obtained using the two methods was small as around  PET imaging. This suggests the possibility of using a completely non-invasive technique to assess CBF in patho-physiological studies.

  4. The emerging functionality of endogenous lectins: A primer to the concept and a case study on galectins including medical implications.

    Gabius, Hans-Joachim; Wu, Albert M

    2006-01-01

    Biochemistry textbooks commonly make it appear that it is a foregone conclusion that the hardware of biological information storage and transfer is confined to nucleotides and amino acids, the letters of the genetic code. However, the remarkable talents of a third class of biomolecules are often overlooked. For example, one of them far surpasses the building blocks of nucleic acids and proteins in terms of theoretical coding capacity by oligomer formation. Although often exclusively assigned to duties in energy metabolism, carbohydrates as part of cellular glycoconjugates (glycoproteins, proteoglycans, glycolipids) have, in fact, other important tasks. Currently, they are increasingly gaining recognition as an operative high-density information coding system. An elaborate enzymatic machinery enables cells to be versatile enough to produce a glycan profile (glycome) that is as characteristic as a fingerprint. Moreover, swift modifications during dynamic processes, such as differentiation or malignant transformation, are readily possible. The translation of the information presented in oligosaccharide determinants to biological responses is carried out by lectins. Recognition of foreign glycosignatures in innate immunity, regulation of cell-cell/matrix interactions, cell migration or growth, and intra- and intercellular glycan routing etc represent physiologically far-reaching lectin-carbohydrate functionality. The classification of endogenous lectins is guided by sequence alignments and conservation of distinct structural traits. For example, a jelly-roll-like folding pattern and maintenance of key residue positioning involved in stacking and C-H/pi-interactions as well as directional hydrogen bonds to the 1-galactoside ligands are common denominators among galectins. Biochemical and biophysical studies are beginning to unravel the intricacies of the selection of a limited set of endogenous ligands, such as certain integrins or ganglioside GM1, and combined with

  5. The Effectiveness of Combining Tangible Symbols with the Picture Exchange Communication System to Teach Requesting Skills to Children with Multiple Disabilities Including Visual Impairment

    Ali, Emad

    2009-01-01

    The Picture Exchange Communication System (PECS) is an augmentative and alternative communication program (Frost & Bondy, 2002). Although PECS has been effectively used to teach functional requesting skills for children with autism, mental retardation, visual impairment, and physical disabilities (e.g., Anderson, Moore, & Bourne, 2007; Chambers &…

  6. Effectiveness of Combining Tangible Symbols with the Picture Exchange Communication System to Teach Requesting Skills to Children with Multiple Disabilities Including Visual Impairment

    Ali, Emad; MacFarland, Stephanie Z.; Umbreit, John

    2011-01-01

    The Picture Exchange Communication System (PECS) is an augmentative and alternative communication (AAC) program used to teach functional requesting and commenting skills to people with disabilities (Bondy & Frost, 1993; Frost & Bondy, 2002). In this study, tangible symbols were added to PECS in teaching requesting to four students (ages 7-14) with…

  7. The relationship between multiple joint flexibility and functional performance in independent and physically active elderly women

    Maria Joana de Carvalho

    2007-09-01

    Full Text Available Multi-joint flexibility assessment seems to be more appropriate for analyzing the association between fl exibility and functional fitness, but there is a lack of studies to confi rm this possibility in elderly people. The present study investigated the relationship between a multiple joint fl exibility assessment and the functional performance of 30 independent and physically active elderly women (age=68±1yr. Flexibility was assessed using the Chair Sit-and-Reach Test (CSRT. Functional performance was tested by a combination of three tasks: a Step Length (SL; b Time to Put on Sneakers (TPS; c Climbing Stairs (CS. The association between fl exibility and functional performance was tested by both simple and multiple correlation techniques. Pearson’s correlation was signifi cant for TPS (r = -.37; p ABSTRACT

  8. The shaping and functional consequences of the dosage effect landscape in multiple myeloma.

    Samur, Mehmet K; Shah, Parantu K; Wang, Xujun; Minvielle, Stéphane; Magrangeas, Florence; Avet-Loiseau, Hervé; Munshi, Nikhil C; Li, Cheng

    2013-10-02

    Multiple myeloma (MM) is a malignant proliferation of plasma B cells. Based on recurrent aneuploidy such as copy number alterations (CNAs), myeloma is divided into two subtypes with different CNA patterns and patient survival outcomes. How aneuploidy events arise, and whether they contribute to cancer cell evolution are actively studied. The large amount of transcriptomic changes resultant of CNAs (dosage effect) pose big challenges for identifying functional consequences of CNAs in myeloma in terms of specific driver genes and pathways. In this study, we hypothesize that gene-wise dosage effect varies as a result from complex regulatory networks that translate the impact of CNAs to gene expression, and studying this variation can provide insights into functional effects of CNAs. We propose gene-wise dosage effect score and genome-wide karyotype plot as tools to measure and visualize concordant copy number and expression changes across cancer samples. We find that dosage effect in myeloma is widespread yet variable, and it is correlated with gene expression level and CNA frequencies in different chromosomes. Our analysis suggests that despite the enrichment of differentially expressed genes between hyperdiploid MM and non-hyperdiploid MM in the trisomy chromosomes, the chromosomal proportion of dosage sensitive genes is higher in the non-trisomy chromosomes. Dosage-sensitive genes are enriched by genes with protein translation and localization functions, and dosage resistant genes are enriched by apoptosis genes. These results point to future studies on differential dosage sensitivity and resistance of pro- and anti-proliferation pathways and their variation across patients as therapeutic targets and prognosis markers. Our findings support the hypothesis that recurrent CNAs in myeloma are selected by their functional consequences. The novel dosage effect score defined in this work will facilitate integration of copy number and expression data for identifying driver

  9. Motor imagery learning modulates functional connectivity of multiple brain systems in resting state.

    Zhang, Hang; Long, Zhiying; Ge, Ruiyang; Xu, Lele; Jin, Zhen; Yao, Li; Liu, Yijun

    2014-01-01

    Learning motor skills involves subsequent modulation of resting-state functional connectivity in the sensory-motor system. This idea was mostly derived from the investigations on motor execution learning which mainly recruits the processing of sensory-motor information. Behavioral evidences demonstrated that motor skills in our daily lives could be learned through imagery procedures. However, it remains unclear whether the modulation of resting-state functional connectivity also exists in the sensory-motor system after motor imagery learning. We performed a fMRI investigation on motor imagery learning from resting state. Based on previous studies, we identified eight sensory and cognitive resting-state networks (RSNs) corresponding to the brain systems and further explored the functional connectivity of these RSNs through the assessments, connectivity and network strengths before and after the two-week consecutive learning. Two intriguing results were revealed: (1) The sensory RSNs, specifically sensory-motor and lateral visual networks exhibited greater connectivity strengths in precuneus and fusiform gyrus after learning; (2) Decreased network strength induced by learning was proved in the default mode network, a cognitive RSN. These results indicated that resting-state functional connectivity could be modulated by motor imagery learning in multiple brain systems, and such modulation displayed in the sensory-motor, visual and default brain systems may be associated with the establishment of motor schema and the regulation of introspective thought. These findings further revealed the neural substrates underlying motor skill learning and potentially provided new insights into the therapeutic benefits of motor imagery learning.

  10. Motor Imagery Learning Modulates Functional Connectivity of Multiple Brain Systems in Resting State

    Zhang, Hang; Long, Zhiying; Ge, Ruiyang; Xu, Lele; Jin, Zhen; Yao, Li; Liu, Yijun

    2014-01-01

    Background Learning motor skills involves subsequent modulation of resting-state functional connectivity in the sensory-motor system. This idea was mostly derived from the investigations on motor execution learning which mainly recruits the processing of sensory-motor information. Behavioral evidences demonstrated that motor skills in our daily lives could be learned through imagery procedures. However, it remains unclear whether the modulation of resting-state functional connectivity also exists in the sensory-motor system after motor imagery learning. Methodology/Principal Findings We performed a fMRI investigation on motor imagery learning from resting state. Based on previous studies, we identified eight sensory and cognitive resting-state networks (RSNs) corresponding to the brain systems and further explored the functional connectivity of these RSNs through the assessments, connectivity and network strengths before and after the two-week consecutive learning. Two intriguing results were revealed: (1) The sensory RSNs, specifically sensory-motor and lateral visual networks exhibited greater connectivity strengths in precuneus and fusiform gyrus after learning; (2) Decreased network strength induced by learning was proved in the default mode network, a cognitive RSN. Conclusions/Significance These results indicated that resting-state functional connectivity could be modulated by motor imagery learning in multiple brain systems, and such modulation displayed in the sensory-motor, visual and default brain systems may be associated with the establishment of motor schema and the regulation of introspective thought. These findings further revealed the neural substrates underlying motor skill learning and potentially provided new insights into the therapeutic benefits of motor imagery learning. PMID:24465577

  11. Genetic analysis of yeast RPA1 reveals its multiple functions in DNA metabolism

    Umezu, K.; Sugawara, N.; Chen, C.; Haber, J.E.; Kolodner, R.D.

    1998-01-01

    Replication protein A (RPA) is a single-stranded DNA-binding protein identified as an essential factor for SV40 DNA replication in vitro. To understand the in vivo functions of RPA, we mutagenized the Saccharomyces cerevisiae RFA1 gene and identified 19 ultraviolet light (UV) irradiation- and methyl methane sulfonate (MMS)-sensitive mutants and 5 temperature-sensitive mutants. The UV- and MMS-sensitive mutants showed up to 10 4 to 10 5 times increased sensitivity to these agents. Some of the UV- and MMSsensitive mutants were killed by an HO-induced double-strand break atMAT. Physical analysis of recombination in one UV- and MMS-sensitive rfa1 mutant demonstrated that it was defective for mating type switching and single-strand annealing recombination. Two temperature-sensitive mutants were characterized in detail, and at the restrictive temperature were found to have an arrest phenotype and DNA content indicative of incomplete DNA replication. DNA sequence analysis indicated that most of the mutations altered amino acids that were conserved between yeast, human, and Xenopus RPA1. Taken together, we conclude that RPA1 has multiple roles in vivo and functions in DNA replication, repair, and recombination, like the single-stranded DNA-binding proteins of bacteria and phages. (author)

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

    Vernerey, Franck J.; Barthelat, Francois

    2014-08-01

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

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

    François Cesselin

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

  14. Prospective memory in multiple sclerosis: The impact of cue distinctiveness and executive functioning.

    Dagenais, Emmanuelle; Rouleau, Isabelle; Tremblay, Alexandra; Demers, Mélanie; Roger, Élaine; Jobin, Céline; Duquette, Pierre

    2016-11-01

    Prospective memory (PM), the ability to remember to do something at the appropriate time in the future, is crucial in everyday life. One way to improve PM performance is to increase the salience of a cue announcing that it is time to act. Multiple sclerosis (MS) patients often report PM failures and there is growing evidence of PM deficits among this population. However, such deficits are poorly characterized and their relation to cognitive status remains unclear. To better understand PM deficits in MS patients, this study investigated the impact of cue salience on PM, and its relation to retrospective memory (RM) and executive deficits. Thirty-nine (39) MS patients were compared to 18 healthy controls on a PM task modulating cue salience during an ongoing general knowledge test. MS patients performed worse than controls on the PM task, regardless of cue salience. MS patients' executive functions contributed significantly to the variance in PM performance, whereas age, education and RM did not. Interestingly, low- and high-executive patients' performance differed when the cue was not salient, but not when it was, suggesting that low-executive MS patients benefited more from cue salience. These findings add to the growing evidence of PM deficits in MS and highlight the contribution of executive functions to certain aspects of PM. In low-executive MS patients, high cue salience improves PM performance by reducing the detection threshold and need for environmental monitoring. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Multiple functional units in the preattentive segmentation of speech in Japanese: evidence from word illusions.

    Nakamura, Miyoko; Kolinsky, Régine

    2014-12-01

    We explored the functional units of speech segmentation in Japanese using dichotic presentation and a detection task requiring no intentional sublexical analysis. Indeed, illusory perception of a target word might result from preattentive migration of phonemes, morae, or syllables from one ear to the other. In Experiment I, Japanese listeners detected targets presented in hiragana and/or kanji. Phoneme migrations did occur, suggesting that orthography-independent sublexical constituents play some role in segmentation. However, syllable and especially mora migrations were more numerous. This pattern of results was not observed in French speakers (Experiment 2), suggesting that it reflects native segmentation in Japanese. To control for the intervention of kanji representations (many words are written in kanji, and one kanji often corresponds to one syllable), in Experiment 3, Japanese listeners were presented with target loanwords that can be written only in katakana. Again, phoneme migrations occurred, while the first mora and syllable led to similar rates of illusory percepts. No migration occurred for the second, "special" mora (/J/ or/N/), probably because this constitutes the latter part of a heavy syllable. Overall, these findings suggest that multiple units, such as morae, syllables, and even phonemes, function independently of orthographic knowledge in Japanese preattentive speech segmentation.

  16. Rehabilitation of Motor Function after Stroke: A Multiple Systematic Review Focused on Techniques to Stimulate Upper Extremity Recovery

    Hatem, Samar M.; Saussez, Geoffroy; della Faille, Margaux; Prist, Vincent; Zhang, Xue; Dispa, Delphine; Bleyenheuft, Yannick

    2016-01-01

    Stroke is one of the leading causes for disability worldwide. Motor function deficits due to stroke affect the patients' mobility, their limitation in daily life activities, their participation in society and their odds of returning to professional activities. All of these factors contribute to a low overall quality of life. Rehabilitation training is the most effective way to reduce motor impairments in stroke patients. This multiple systematic review focuses both on standard treatment methods and on innovating rehabilitation techniques used to promote upper extremity motor function in stroke patients. A total number of 5712 publications on stroke rehabilitation was systematically reviewed for relevance and quality with regards to upper extremity motor outcome. This procedure yielded 270 publications corresponding to the inclusion criteria of the systematic review. Recent technology-based interventions in stroke rehabilitation including non-invasive brain stimulation, robot-assisted training, and virtual reality immersion are addressed. Finally, a decisional tree based on evidence from the literature and characteristics of stroke patients is proposed. At present, the stroke rehabilitation field faces the challenge to tailor evidence-based treatment strategies to the needs of the individual stroke patient. Interventions can be combined in order to achieve the maximal motor function recovery for each patient. Though the efficacy of some interventions may be under debate, motor skill learning, and some new technological approaches give promising outcome prognosis in stroke motor rehabilitation. PMID:27679565

  17. Rehabilitation of motor function after stroke: a multiple systematic review focused on techniques to stimulate upper extremity recovery

    Samar M Hatem

    2016-09-01

    Full Text Available Stroke is one of the leading causes for disability worldwide. Motor function deficits due to stroke affect the patients’ mobility, their limitation in daily life activities, their participation in society and their odds of returning to professional activities. All of these factors contribute to a low overall quality of life. Rehabilitation training is the most effective way to reduce motor impairments in stroke patients. This multiple systematic review focuses both on standard treatment methods and on innovating rehabilitation techniques used to promote upper extremity motor function in stroke patients. A total number of 5712 publications on stroke rehabilitation was systematically reviewed for relevance and quality with regards to upper extremity motor outcome. This procedure yielded 270 publications corresponding to the inclusion criteria of the systematic review. Recent technology-based interventions in stroke rehabilitation including non-invasive brain stimulation, robot-assisted training and virtual reality immersion are addressed. Finally, a decisional tree based on evidence from the literature and characteristics of stroke patients is proposed.At present, the stroke rehabilitation field faces the challenge to tailor evidence-based treatment strategies to the needs of the individual stroke patient. Interventions can be combined in order to achieve the maximal motor function recovery for each patient. Though the efficacy of some interventions may be under debate, motor skill learning and some new technological approaches give promising outcome prognosis in stroke motor rehabilitation.

  18. EPR spectroscopy of MRI-related Gd(III) complexes: simultaneous analysis of multiple frequency and temperature spectra, including static and transient crystal field effects.

    Rast, S; Borel, A; Helm, L; Belorizky, E; Fries, P H; Merbach, A E

    2001-03-21

    For the first time, a very general theoretical method is proposed to interpret the full electron paramagnetic resonance (EPR) spectra at multiple temperatures and frequencies in the important case of S-state metal ions complexed in liquid solution. This method is illustrated by a careful analysis of the measured spectra of two Gd3+ (S = 7/2) complexes. It is shown that the electronic relaxation mechanisms at the origin of the EPR line shape arise from the combined effects of the modulation of the static crystal field by the random Brownian rotation of the complex and of the transient zero-field splitting. A detailed study of the static crystal field mechanism shows that, contrarily to the usual global models involving only second-order terms, the fourth and sixth order terms can play a non-negligible role. The obtained parameters are well interpreted in the framework of the physics of the various underlying relaxation processes. A better understanding of these mechanisms is highly valuable since they partly control the efficiency of paramagnetic metal ions in contrast agents for medical magnetic resonance imaging (MRI).

  19. Detection of Brain Reorganization in Pediatric Multiple Sclerosis Using Functional MRI

    2015-10-01

    including the Wechsler Intelligence Scale for Children (WISC-IV) for verbal and non-verbal intelligence; the Boston Naming Test , which evaluates a...demonstrated congruency between fMRI mappings and patient performance; 2) testing of the fMRI methods we developed for use in POMS patients was carried out...adaptive functional reorganization as a way to explain how some early-stage MS patients are able to perform well in clinical cognitive testing

  20. Relationship between muscle strength parameters and functional capacity in persons with mild to moderate degree multiple sclerosis

    Kjølhede, Tue; Vissing, Kristian; Langeskov-Christensen, Daniel

    2015-01-01

    BACKGROUND: Maximal muscle strength has been shown to be an important predictor of functional capacity for persons with multiple sclerosis (PwMS). Another muscle strength parameter known to be important for functional capacity in other patient groups is rate of force development (RFD) in knee...... is the better predictor of walking performance in persons with mild to moderate multiple sclerosis. RFD, although also important for functional capacity, is a less strong predictor. Maximal strength of the knee extensors, rather than the knee flexors, predicted performance in the stairclimb and 5STS tests....

  1. Staging of cortical and deep grey matter functional connectivity changes in multiple sclerosis.

    Meijer, Kim A; Eijlers, Anand J C; Geurts, Jeroen J G; Schoonheim, Menno M

    2018-02-01

    Functional connectivity is known to increase as well as decrease throughout the brain in multiple sclerosis (MS), which could represent different stages of the disease. In addition, functional connectivity changes could follow the atrophy pattern observed with disease progression, that is, moving from the deep grey matter towards the cortex. This study investigated when and where connectivity changes develop and explored their clinical and cognitive relevance across different MS stages. A cohort of 121 patients with early relapsing-remitting MS (RRMS), 122 with late RRMS and 53 with secondary progressive MS (SPMS) as well as 96 healthy controls underwent MRI and neuropsychological testing. Functional connectivity changes were investigated for (1) within deep grey matter connectivity, (2) connectivity between the deep grey matter and cortex and (3) within-cortex connectivity. A post hoc regional analysis was performed to identify which regions were driving the connectivity changes. Patients with late RRMS and SPMS showed increased connectivity of the deep grey matter, especially of the putamen and palladium, with other deep grey matter structures and with the cortex. Within-cortex connectivity was decreased, especially for temporal, occipital and frontal regions, but only in SPMS relative to early RRMS. Deep grey matter connectivity alterations were related to cognition and disability, whereas within-cortex connectivity was only related to disability. Increased connectivity of the deep grey matter became apparent in late RRMS and further increased in SPMS. The additive effect of cortical network degeneration, which was only seen in SPMS, may explain the sudden clinical deterioration characteristic to this phase of the disease. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  2. Evaluation of autonomic functions of patients with multiple system atrophy and Parkinson's disease by head-up tilt test.

    Watano, Chikako; Shiota, Yuri; Onoda, Keiichi; Sheikh, Abdullah Md; Mishima, Seiji; Nitta, Eri; Yano, Shozo; Yamaguchi, Shuhei; Nagai, Atsushi

    2018-02-01

    The aim of this study was to evaluate the autonomic neural function in Parkinson's disease (PD) and multiple system atrophy (MSA) with head-up tilt test and spectral analysis of cardiovascular parameters. This study included 15 patients with MSA, 15 patients with PD, and 29 healthy control (HC) subjects. High frequency power of the RR interval (RR-HF), the ratio of low frequency power of RR interval to RR-HF (RR-LF/HF) and LF power of systolic BP were used to evaluate parasympathetic, cardiac sympathetic and vasomotor sympathetic functions, respectively. Both patients with PD and MSA showed orthostatic hypotension and lower parasympathetic function (RR-HF) at tilt position as compared to HC subjects. Cardiac sympathetic function (RR-LF/HF) was significantly high in patients with PD than MSA at supine position. RR-LF/HF tended to increase in MSA and HC, but decreased in PD by tilting. Consequently, the change of the ratio due to tilting (ΔRR-LF/HF) was significantly lower in patients with PD than in HC subjects. Further analysis showed that compared to mild stage of PD, RR-LF/HF at the supine position was significantly higher in advanced stage. By tilting, it was increased in mild stage and decreased in the advanced stage of PD, causing ΔRR-LF/HF to decrease significantly in the advanced stage. Thus, we demonstrated that spectral analysis of cardiovascular parameters is useful to identify sympathetic and parasympathetic disorders in MSA and PD. High cardiac sympathetic function at the supine position, and its reduction by tilting might be a characteristic feature of PD, especially in the advanced stage.

  3. Use of International Classification of Functioning, Disability and Health (ICF) to describe patient-reported disability in multiple sclerosis and identification of relevant environmental factors.

    Khan, Fary; Pallant, Julie F

    2007-01-01

    To use the International Classification of Functioning, Disability and Health (ICF) to describe patient-reported disability in multiple sclerosis and identify relevant environmental factors. Cross-sectional survey of 101 participants in the community. Their multiple sclerosis-related problems were linked with ICF categories (second level) using a checklist, consensus between health professionals and the "linking rules". The impact of multiple sclerosis on health areas corresponding to 48 ICF categories was also assessed. A total of 170 ICF categories were identified (mean age 49 years, 72 were female). Average number of problems reported was 18. The categories include 48 (42%) for body function, 16 (34%) body structure, 68 (58%) activities and participation and 38 (51%) for environmental factors. Extreme impact in health areas corresponding to ICF categories for activities and participation were reported for mobility, work, everyday home activities, community and social activities. While those for the environmental factors (barriers) included products for mobility, attitudes of extended family, restriction accessing social security and health resources. This study is a first step in the use of the ICF in persons with multiple sclerosis and towards development of the ICF Core set for multiple sclerosis from a broader international perspective.

  4. Novel and rare functional genomic variants in multiple autoimmune syndrome and Sjögren's syndrome.

    Johar, Angad S; Mastronardi, Claudio; Rojas-Villarraga, Adriana; Patel, Hardip R; Chuah, Aaron; Peng, Kaiman; Higgins, Angela; Milburn, Peter; Palmer, Stephanie; Silva-Lara, Maria Fernanda; Velez, Jorge I; Andrews, Dan; Field, Matthew; Huttley, Gavin; Goodnow, Chris; Anaya, Juan-Manuel; Arcos-Burgos, Mauricio

    2015-06-02

    Multiple autoimmune syndrome (MAS), an extreme phenotype of autoimmune disorders, is a very well suited trait to tackle genomic variants of these conditions. Whole exome sequencing (WES) is a widely used strategy for detection of protein coding and splicing variants associated with inherited diseases. The DNA of eight patients affected by MAS [all of whom presenting with Sjögren's syndrome (SS)], four patients affected by SS alone and 38 unaffected individuals, were subject to WES. Filters to identify novel and rare functional (pathogenic-deleterious) homozygous and/or compound heterozygous variants in these patients and controls were applied. Bioinformatics tools such as the Human gene connectome as well as pathway and network analysis were applied to test overrepresentation of genes harbouring these variants in critical pathways and networks involved in autoimmunity. Eleven novel and rare functional variants were identified in cases but not in controls, harboured in: MACF1, KIAA0754, DUSP12, ICA1, CELA1, LRP1/STAT6, GRIN3B, ANKLE1, TMEM161A, and FKRP. These were subsequently subject to network analysis and their functional relatedness to genes already associated with autoimmunity was evaluated. Notably, the LRP1/STAT6 novel mutation was homozygous in one MAS affected patient and heterozygous in another. LRP1/STAT6 disclosed the strongest plausibility for autoimmunity. LRP1/STAT6 are involved in extracellular and intracellular anti-inflammatory pathways that play key roles in maintaining the homeostasis of the immune system. Further; networks, pathways, and interaction analyses showed that LRP1 is functionally related to the HLA-B and IL10 genes and it has a substantial impact within immunological pathways and/or reaction to bacterial and other foreign proteins (phagocytosis, regulation of phospholipase A2 activity, negative regulation of apoptosis and response to lipopolysaccharides). Further, ICA1 and STAT6 were also closely related to AIRE and IRF5, two very

  5. Evolution of the stellar mass function in multiple-population globular clusters

    Vesperini, Enrico; Hong, Jongsuk; Webb, Jeremy J.; D'Antona, Franca; D'Ercole, Annibale

    2018-05-01

    We present the results of a survey of N-body simulations aimed at studying the effects of the long-term dynamical evolution on the stellar mass function (MF) of multiple stellar populations in globular clusters. Our simulations show that if first-(1G) and second-generation (2G) stars have the same initial MF (IMF), the global MFs of the two populations are affected similarly by dynamical evolution and no significant differences between the 1G and 2G MFs arise during the cluster's evolution. If the two populations have different IMFs, dynamical effects do not completely erase memory of the initial differences. Should observations find differences between the global 1G and 2G MFs, these would reveal the fingerprints of differences in their IMFs. Irrespective of whether the 1G and 2G populations have the same global IMF or not, dynamical effects can produce differences between the local (measured at various distances from the cluster centre) 1G and 2G MFs; these differences are a manifestation of the process of mass segregation in populations with different initial structural properties. In dynamically old and spatially mixed clusters, however, differences between the local 1G and 2G MFs can reveal differences between the 1G and 2G global MFs. In general, for clusters with any dynamical age, large differences between the local 1G and 2G MFs are more likely to be associated with differences in the global MF. Our study also reveals a dependence of the spatial mixing rate on the stellar mass, another dynamical consequence of the multiscale nature of multiple-population clusters.

  6. Scale breaking parton fragmentation functions, analytical parametrizations and comparison with charged multiplicities in e+e- annihilation

    Perlt, H.

    1980-01-01

    Scale breaking quark and gluon fragmentation functions obtained by solving numerically Altarelli-Parisi type equations are presented. Analytical parametrizations are given for the fragmentation of u and d quarks into pions. The calculated Q 2 dependent fragmentation functions are compared with experimental data. With these scale breaking fragmentation functions the average charged multiplicity is calculated in e + e - annihilation, which rises with energy more than logarithmically and is in good agreement with experiment. (author)

  7. Multiple essential functions of Plasmodium falciparum actin-1 during malaria blood-stage development.

    Das, Sujaan; Lemgruber, Leandro; Tay, Chwen L; Baum, Jake; Meissner, Markus

    2017-08-15

    The phylum Apicomplexa includes intracellular parasites causing immense global disease burden, the deadliest of them being the human malaria parasite Plasmodium falciparum, which invades and replicates within erythrocytes. The cytoskeletal protein actin is well conserved within apicomplexans but divergent from mammalian actins, and was primarily reported to function during host cell invasion. However, novel invasion mechanisms have been described for several apicomplexans, and specific functions of the acto-myosin system are being reinvestigated. Of the two actin genes in P. falciparum, actin-1 (pfact1) is ubiquitously expressed in all life-cycle stages and is thought to be required for erythrocyte invasion, although its functions during parasite development are unknown, and definitive in vivo characterisation during invasion is lacking. Here we have used a conditional Cre-lox system to investigate the functions of PfACT1 during P. falciparum blood-stage development and host cell invasion. We demonstrate that PfACT1 is crucially required for segregation of the plastid-like organelle, the apicoplast, and for efficient daughter cell separation during the final stages of cytokinesis. Surprisingly, we observe that egress from the host cell is not an actin-dependent process. Finally, we show that parasites lacking PfACT1 are capable of microneme secretion, attachment and formation of a junction with the erythrocyte, but are incapable of host cell invasion. This study provides important mechanistic insights into the definitive essential functions of PfACT1 in P. falciparum, which are not only of biological interest, but owing to functional divergence from mammalian actins, could also form the basis for the development of novel therapeutics against apicomplexans.

  8. Wide range of interacting partners of pea Gβ subunit of G-proteins suggests its multiple functions in cell signalling.

    Bhardwaj, Deepak; Lakhanpaul, Suman; Tuteja, Narendra

    2012-09-01

    Climate change is a major concern especially in view of the increasing global population and food security. Plant scientists need to look for genetic tools whose appropriate usage can contribute to sustainable food availability. G-proteins have been identified as some of the potential genetic tools that could be useful for protecting plants from various stresses. Heterotrimeric G-proteins consisting of three subunits Gα, Gβ and Gγ are important components of a number of signalling pathways. Their structure and functions are already well studied in animals but their potential in plants is now gaining attention for their role in stress tolerance. Earlier we have reported that over expressing pea Gβ conferred heat tolerance in tobacco plants. Here we report the interacting partners (proteins) of Gβ subunit of Pisum sativum and their putative role in stress and development. Out of 90 transformants isolated from the yeast-two-hybrid (Y2H) screening, seven were chosen for further investigation due to their recurrence in multiple experiments. These interacting partners were confirmed using β-galactosidase colony filter lift and ONPG (O-nitrophenyl-β-D-galactopyranoside) assays. These partners include thioredoxin H, histidine-containing phosphotransfer protein 5-like, pathogenesis-related protein, glucan endo-beta-1, 3-glucosidase (acidic isoform), glycine rich RNA binding protein, cold and drought-regulated protein (corA gene) and soluble inorganic pyrophosphatase 1. This study suggests the role of pea Gβ subunit in stress signal transduction and development pathways owing to its capability to interact with a wide range of proteins of multiple functions. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  9. Mycobacterial UvrD1 is a Ku-dependent DNA helicase that plays a role in multiple DNA repair events, including double-strand break repair.

    Sinha, Krishna Murari; Stephanou, Nicolas C; Gao, Feng; Glickman, Michael S; Shuman, Stewart

    2007-05-18

    Mycobacterium tuberculosis and other bacterial pathogens have a Ku-dependent nonhomologous end joining pathway of DNA double-strand break repair. Here we identify mycobacterial UvrD1 as a novel interaction partner for Ku in a genome-wide yeast two-hybrid screen. UvrD1 per se is a vigorous DNA-dependent ATPase but a feeble DNA helicase. Ku stimulates UvrD1 to catalyze ATP-dependent unwinding of 3'-tailed DNAs. UvrD1, Ku, and DNA form a stable ternary complex in the absence of ATP. The Ku binding determinants are located in the distinctive C-terminal segment of UvrD1. A second mycobacterial paralog, UvrD2, is a vigorous Ku-independent DNA helicase. Ablation of UvrD1 sensitizes Mycobacterium smegmatis to killing by ultraviolet and ionizing radiation and to a single chromosomal break generated by I-SceI endonuclease. The physical and functional interactions of bacterial Ku and UvrD1 highlight the potential for cross-talk between components of nonhomologous end joining and nucleotide excision repair pathways.

  10. Multiple cluster axis II comorbidity and functional outcome in severe patients with borderline personality disorder.

    Palomares, Nerea; McMaster, Antonia; Díaz-Marsá, Marina; de la Vega, Irene; Montes, Ana; Carrasco, José Luis

    2016-11-01

    Current literature suggests that personality disorder comorbidity negatively contributes to both the severity and prognosis of other disorders; however, little literature has been devoted to its influence on borderline personality disorder (BPD). The objective of the present work is to study comorbidity with other personality disorders in a severe clinical sample of patients with BPD, and its relationship with global functionality. A sample of 65 patients with severe borderline personality disorder was included in the study. Clinical and functionality measures were applied in order to study comorbidity of BPD with other disorders and its relationship with functionality. Associations with other comorbid PDs were analyzed with t-tests and linear correlations. Most patients (87%) presented comorbidity with other PDs. Almost half of the sample (42%) presented more than two PDs, and cluster A (paranoid) and C (obsessive and avoidant) PD were more frequent than cluster B (histrionic and antisocial). Only the presence of avoidant PD predicted a worse functional outcome in the long term (U Mann Withney ppersonality disorder might negatively predict for prognosis.

  11. Functional Connectivity of Multiple Brain Regions Required for the Consolidation of Social Recognition Memory.

    Tanimizu, Toshiyuki; Kenney, Justin W; Okano, Emiko; Kadoma, Kazune; Frankland, Paul W; Kida, Satoshi

    2017-04-12

    Social recognition memory is an essential and basic component of social behavior that is used to discriminate familiar and novel animals/humans. Previous studies have shown the importance of several brain regions for social recognition memories; however, the mechanisms underlying the consolidation of social recognition memory at the molecular and anatomic levels remain unknown. Here, we show a brain network necessary for the generation of social recognition memory in mice. A mouse genetic study showed that cAMP-responsive element-binding protein (CREB)-mediated transcription is required for the formation of social recognition memory. Importantly, significant inductions of the CREB target immediate-early genes c-fos and Arc were observed in the hippocampus (CA1 and CA3 regions), medial prefrontal cortex (mPFC), anterior cingulate cortex (ACC), and amygdala (basolateral region) when social recognition memory was generated. Pharmacological experiments using a microinfusion of the protein synthesis inhibitor anisomycin showed that protein synthesis in these brain regions is required for the consolidation of social recognition memory. These findings suggested that social recognition memory is consolidated through the activation of CREB-mediated gene expression in the hippocampus/mPFC/ACC/amygdala. Network analyses suggested that these four brain regions show functional connectivity with other brain regions and, more importantly, that the hippocampus functions as a hub to integrate brain networks and generate social recognition memory, whereas the ACC and amygdala are important for coordinating brain activity when social interaction is initiated by connecting with other brain regions. We have found that a brain network composed of the hippocampus/mPFC/ACC/amygdala is required for the consolidation of social recognition memory. SIGNIFICANCE STATEMENT Here, we identify brain networks composed of multiple brain regions for the consolidation of social recognition memory. We

  12. 3-D thermal weight function method and multiple virtual crack extension technique for thermal shock problems

    Lu Yanlin; Zhou Xiao; Qu Jiadi; Dou Yikang; He Yinbiao

    2005-01-01

    An efficient scheme, 3-D thermal weight function (TWF) method, and a novel numerical technique, multiple virtual crack extension (MVCE) technique, were developed for determination of histories of transient stress intensity factor (SIF) distributions along 3-D crack fronts of a body subjected to thermal shock. The TWF is a universal function, which is dependent only on the crack configuration and body geometry. TWF is independent of time during thermal shock, so the whole history of transient SIF distributions along crack fronts can be directly calculated through integration of the products of TWF and transient temperatures and temperature gradients. The repeated determinations of the distributions of stresses (or displacements) fields for individual time instants are thus avoided in the TWF method. An expression of the basic equation for the 3-D universal weight function method for Mode I in an isotropic elastic body is derived. This equation can also be derived from Bueckner-Rice's 3-D WF formulations in the framework of transformation strain. It can be understood from this equation that the so-called thermal WF is in fact coincident with the mechanical WF except for some constants of elasticity. The details and formulations of the MVCE technique are given for elliptical cracks. The MVCE technique possesses several advantages. The specially selected linearly independent VCE modes can directly be used as shape functions for the interpolation of unknown SIFs. As a result, the coefficient matrix of the final system of equations in the MVCE method is a triple-diagonal matrix and the values of the coefficients on the main diagonal are large. The system of equations has good numerical properties. The number of linearly independent VCE modes that can be introduced in a problem is unlimited. Complex situations in which the SIFs vary dramatically along crack fronts can be numerically well simulated by the MVCE technique. An integrated system of programs for solving the

  13. Epigenetic profiling of cutaneous T-cell lymphoma: promoter hypermethylation of multiple tumor suppressor genes including BCL7a, PTPRG, and p73.

    van Doorn, Remco; Zoutman, Willem H; Dijkman, Remco; de Menezes, Renee X; Commandeur, Suzan; Mulder, Aat A; van der Velden, Pieter A; Vermeer, Maarten H; Willemze, Rein; Yan, Pearlly S; Huang, Tim H; Tensen, Cornelis P

    2005-06-10

    To analyze the occurrence of promoter hypermethylation in primary cutaneous T-cell lymphoma (CTCL) on a genome-wide scale, focusing on epigenetic alterations with pathogenetic significance. DNA isolated from biopsy specimens of 28 patients with CTCL, including aggressive CTCL entities (transformed mycosis fungoides and CD30-negative large T-cell lymphoma) and an indolent entity (CD30-positive large T-cell lymphoma), were investigated. For genome-wide DNA methylation screening, differential methylation hybridization using CpG island microarrays was applied, which allows simultaneous detection of the methylation status of 8640 CpG islands. Bisulfite sequence analysis was applied for confirmation and detection of hypermethylation of eight selected tumor suppressor genes. The DNA methylation patterns of CTCLs emerging from differential methylation hybridization analysis included 35 CpG islands hypermethylated in at least four of the 28 studied CTCL samples when compared with benign T-cell samples. Hypermethylation of the putative tumor suppressor genes BCL7a (in 48% of CTCL samples), PTPRG (27%), and thrombospondin 4 (52%) was confirmed and demonstrated to be associated with transcriptional downregulation. BCL7a was hypermethylated at a higher frequency in aggressive (64%) than in indolent (14%) CTCL entities. In addition, the promoters of the selected tumor suppressor genes p73 (48%), p16 (33%), CHFR (19%), p15 (10%), and TMS1 (10%) were hypermethylated in CTCL. Malignant T cells of patients with CTCL display widespread promoter hypermethylation associated with inactivation of several tumor suppressor genes involved in DNA repair, cell cycle, and apoptosis signaling pathways. In view of this, CTCL may be amenable to treatment with demethylating agents.

  14. Community functional responses to soil and climate at multiple spatial scales: when does intraspecific variation matter?

    Andrew Siefert

    Full Text Available Despite increasing evidence of the importance of intraspecific trait variation in plant communities, its role in community trait responses to environmental variation, particularly along broad-scale climatic gradients, is poorly understood. We analyzed functional trait variation among early-successional herbaceous plant communities (old fields across a 1200-km latitudinal extent in eastern North America, focusing on four traits: vegetative height, leaf area, specific leaf area (SLA, and leaf dry matter content (LDMC. We determined the contributions of species turnover and intraspecific variation to between-site functional dissimilarity at multiple spatial scales and community trait responses to edaphic and climatic factors. Among-site variation in community mean trait values and community trait responses to the environment were generated by a combination of species turnover and intraspecific variation, with species turnover making a greater contribution for all traits. The relative importance of intraspecific variation decreased with increasing geographic and environmental distance between sites for SLA and leaf area. Intraspecific variation was most important for responses of vegetative height and responses to edaphic compared to climatic factors. Individual species displayed strong trait responses to environmental factors in many cases, but these responses were highly variable among species and did not usually scale up to the community level. These findings provide new insights into the role of intraspecific trait variation in plant communities and the factors controlling its relative importance. The contribution of intraspecific variation to community trait responses was greatest at fine spatial scales and along edaphic gradients, while species turnover dominated at broad spatial scales and along climatic gradients.

  15. Vibration control of uncertain multiple launch rocket system using radial basis function neural network

    Li, Bo; Rui, Xiaoting

    2018-01-01

    Poor dispersion characteristics of rockets due to the vibration of Multiple Launch Rocket System (MLRS) have always restricted the MLRS development for several decades. Vibration control is a key technique to improve the dispersion characteristics of rockets. For a mechanical system such as MLRS, the major difficulty in designing an appropriate control strategy that can achieve the desired vibration control performance is to guarantee the robustness and stability of the control system under the occurrence of uncertainties and nonlinearities. To approach this problem, a computed torque controller integrated with a radial basis function neural network is proposed to achieve the high-precision vibration control for MLRS. In this paper, the vibration response of a computed torque controlled MLRS is described. The azimuth and elevation mechanisms of the MLRS are driven by permanent magnet synchronous motors and supposed to be rigid. First, the dynamic model of motor-mechanism coupling system is established using Lagrange method and field-oriented control theory. Then, in order to deal with the nonlinearities, a computed torque controller is designed to control the vibration of the MLRS when it is firing a salvo of rockets. Furthermore, to compensate for the lumped uncertainty due to parametric variations and un-modeled dynamics in the design of the computed torque controller, a radial basis function neural network estimator is developed to adapt the uncertainty based on Lyapunov stability theory. Finally, the simulated results demonstrate the effectiveness of the proposed control system and show that the proposed controller is robust with regard to the uncertainty.

  16. Cognitive function in multiple sclerosis improves with telerehabilitation: Results from a randomized controlled trial.

    Leigh E Charvet

    Full Text Available Cognitive impairment affects more than half of all individuals living with multiple sclerosis (MS. We hypothesized that training at home with an adaptive online cognitive training program would have greater cognitive benefit than ordinary computer games in cognitively-impaired adults with MS. This was a double-blind, randomized, active-placebo-controlled trial. Participants with MS were recruited through Stony Brook Medicine and randomly assigned to either the adaptive cognitive remediation (ACR program or active control of ordinary computer games for 60 hours over 12 weeks. Training was remotely-supervised and delivered through a study-provided laptop computer. A computer generated, blocked stratification table prepared by statistician provided the randomization schedule and condition was assigned by a study technician. The primary outcome, administered by study psychometrician, was measured by change in a neuropsychological composite measure from baseline to study end. An intent-to-treat analysis was employed and missing primary outcome values were imputed via Markov Chain Monte Carlo method. Participants in the ACR (n = 74 vs. active control (n = 61 training program had significantly greater improvement in the primary outcome of cognitive functioning (mean change in composite z score±SD: 0·25±0·45 vs. 0·09±0·37, p = 0·03, estimated difference = 0·16 with 95% CI: 0·02-0·30, despite greater training time in the active control condition (mean±SD:56·9 ± 34·6 vs. 37·7 ±23 ·8 hours played, p = 0·006. This study provides Class I evidence that adaptive, computer-based cognitive remediation accessed from home can improve cognitive functioning in MS. This telerehabilitation approach allowed for rapid recruitment and high compliance, and can be readily applied to other neurological conditions associated with cognitive dysfunction.Clinicaltrials.gov NCT02141386.

  17. Impact of Autologous Stem Cell Transplantation on Blood Pressure and Renal Function in Multiple Myeloma Patients.

    Balsam, Leah; Saad, Chadi; Arsene, Camelia; Fogel, Joshua

    2017-01-01

    Autologous stem cell transplantation (ASCT) reverses kidney failure in one-third of multiple myeloma (MM) patients, which may lead to blood pressure (BP) improvement. We evaluate the long term impact of ASCT on BP and renal function in MM patients. We studied 192 MM patients that underwent ASCT. We compared BP readings and glomerular filtration rate (GFR) at 4 weeks before ASCT, on day of ASCT and post-ASCT at 30, 100 and 180 days. Mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) on day of ASCT and at both 30 and 100 days post-ASCT was significantly lower as compared to pre-ASCT SBP and DBP. There was a significantly higher mean GFR at day of ASCT and 30 days post-ASCT and significantly lower mean GFR at 180 days post-ASCT as compared to pre-ASCT. White patients had similar patterns to the total group for SBP, DBP, and GFR except for SBP which was still significantly lower and GFR which was not significantly different at 180 days. African-American patients showed no significant reductions in the mean values of SBP and DBP and no significant increases for GFR in follow-up after day of ASCT. Furthermore, the mean value of GFR was significantly lower at 180 days post-ASCT. ASCT in MM patients had a positive impact on SBP and DBP and GFR but the impact was minimal for African-American patients. We recommend that clinicians consider closer follow-up of BP and kidney function and more intense therapy in African-Americans with MM. Copyright © 2017 National Medical Association. Published by Elsevier Inc. All rights reserved.

  18. Multiple-Ring Digital Communication Network

    Kirkham, Harold

    1992-01-01

    Optical-fiber digital communication network to support data-acquisition and control functions of electric-power-distribution networks. Optical-fiber links of communication network follow power-distribution routes. Since fiber crosses open power switches, communication network includes multiple interconnected loops with occasional spurs. At each intersection node is needed. Nodes of communication network include power-distribution substations and power-controlling units. In addition to serving data acquisition and control functions, each node acts as repeater, passing on messages to next node(s). Multiple-ring communication network operates on new AbNET protocol and features fiber-optic communication.

  19. On the multiple zeros of a real analytic function with applications to the averaging theory of differential equations

    García, Isaac A.; Llibre, Jaume; Maza, Susanna

    2018-06-01

    In this work we consider real analytic functions , where , Ω is a bounded open subset of , is an interval containing the origin, are parameters, and ε is a small parameter. We study the branching of the zero-set of at multiple points when the parameter ε varies. We apply the obtained results to improve the classical averaging theory for computing T-periodic solutions of λ-families of analytic T-periodic ordinary differential equations defined on , using the displacement functions defined by these equations. We call the coefficients in the Taylor expansion of in powers of ε the averaged functions. The main contribution consists in analyzing the role that have the multiple zeros of the first non-zero averaged function. The outcome is that these multiple zeros can be of two different classes depending on whether the zeros belong or not to the analytic set defined by the real variety associated to the ideal generated by the averaged functions in the Noetheriang ring of all the real analytic functions at . We bound the maximum number of branches of isolated zeros that can bifurcate from each multiple zero z 0. Sometimes these bounds depend on the cardinalities of minimal bases of the former ideal. Several examples illustrate our results and they are compared with the classical theory, branching theory and also under the light of singularity theory of smooth maps. The examples range from polynomial vector fields to Abel differential equations and perturbed linear centers.

  20. Point spread function due to multiple scattering of light in the atmosphere

    Pękala, J.; Wilczyński, H.

    2013-01-01

    The atmospheric scattering of light has a significant influence on the results of optical observations of air showers. It causes attenuation of direct light from the shower, but also contributes a delayed signal to the observed light. The scattering of light therefore should be accounted for, both in simulations of air shower detection and reconstruction of observed events. In this work a Monte Carlo simulation of multiple scattering of light has been used to determine the contribution of the scattered light in observations of a point source of light. Results of the simulations and a parameterization of the angular distribution of the scattered light contribution to the observed signal (the point spread function) are presented. -- Author-Highlights: •Analysis of atmospheric scattering of light from an isotropic point source. •Different geometries and atmospheric conditions were investigated. •A parameterization of scattered light distribution has been developed. •The parameterization allows one to easily account for the light scattering in air. •The results will be useful in analyses of observations of extensive air shower

  1. Amelioration of NK cell function driven by Vα24+ invariant NKT cell activation in multiple myeloma.

    Iyoda, Tomonori; Yamasaki, Satoru; Hidaka, Michihiro; Kawano, Fumio; Abe, Yu; Suzuki, Kenshi; Kadowaki, Norimitsu; Shimizu, Kanako; Fujii, Shin-Ichiro

    2018-02-01

    NK cells represent a first line of immune defense, but are progressively dysregulated in multiple myeloma (MM) patients. To restore and facilitate their antitumor effect, NK cells are required in sufficient quantities and must be stimulated. We initially assessed the proportions of NKT and NK cells in 34 MM patients. The frequencies of both in PBMC populations correlated with those in BMMNCs irrespective of low BMMNC numbers. We then assessed the adjunctive effect of stimulating NKT cells with CD1d and α-GalCer complexes on the NK cells. The expression of NKG2D on CD56 dim CD16 + NK cells and DNAM-1 on CD56 bright CD16 - NK cells increased after NKT cell activation. Apparently, NK cell-mediated anti-tumor effects were dependent on NKG2D and DNAM-1 ligands on myeloma cells. Thus, NK cell function in patients could be ameliorated, beyond the effect of immunosuppression, by NKT cell activation. This NKT-driven NK cell therapy could represent a potential new treatment modality. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Hanford Site Welding Program Successfully Providing A Single Site Function For Use By Multiple Contractors

    Cannell, G.R.

    2009-01-01

    The Department of Energy, Richland Operations (DOE-RL) recently restructured its Hanford work scope, awarding two new contracts over the past several months for a total of three contracts to manage the sites cleanup efforts. DOE-RL met with key contractor personnel prior to and during contract transition to ensure site welding activities had appropriate oversight and maintained code compliance. The transition also provided an opportunity to establish a single site-wide function that would provide welding and materials engineering services to the Hanford site contractors: CH2M HILL Plateau Remediation Company (CHPRC); Mission Support Alliance (MSA); Washington River Protection Solutions (WRPS); and Washington Closure Hanford (WCH). Over the years, multiple and separate welding programs (amongst the several contractors) existed at the Hanford site leading to inefficiencies resulting from duplication of administrative efforts, maintenance of welding procedures, welder performance certifications, etc. The new, single program eliminates these inefficiencies. The new program, co-managed by two of the sites' new contractors, the CHPRC ('owner' of the program and responsible for construction welding services) and the MSA (provides maintenance welding services), provides more than just the traditional construction and maintenance welding services. Also provided, are welding engineering, specialty welding development/qualification for the closure of radioactive materials containers and materials evaluation/failure analysis. The following describes the new Hanford site welding program.

  3. Multiple biomarkers biosensor with just-in-time functionalization: Application to prostate cancer detection.

    Parra-Cabrera, C; Samitier, J; Homs-Corbera, A

    2016-03-15

    We present a novel lab-on-a-chip (LOC) device for the simultaneous detection of multiple biomarkers using simple voltage measurements. The biosensor functionalization is performed in-situ, immediately before its use, facilitating reagents storage and massive devices fabrication. Sensitivity, limit of detection (LOD) and limit of quantification (LOQ) are tunable depending on the in-chip flown sample volumes. As a proof-of-concept, the system has been tested and adjusted to quantify two proteins found in blood that are susceptible to be used combined, as a screening tool, to diagnose prostate cancer (PCa): prostate-specific antigen (PSA) and spondin-2 (SPON2). This combination of biomarkers has been reported to be more specific for PCa diagnostics than the currently accepted but rather controversial PSA indicator. The range of detection for PSA and SPON2 could be adjusted to the clinically relevant range of 1 to 10 ng/ml. The system was tested for specificity to the evaluated biomarkers. This multiplex system can be modified and adapted to detect a larger quantity of biomarkers, or different ones, of relevance to other specific diseases. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. The effect of executive function on stress, depression, anxiety, and quality of life in multiple sclerosis.

    Grech, Lisa B; Kiropoulos, Litza A; Kirby, Katherine M; Butler, Ernest; Paine, Mark; Hester, Robert

    2015-01-01

    The experience of cognitive deficits and emotional dysfunction are prevalent in people with multiple sclerosis (PwMS), although research examining their interaction has provided inconsistent findings. The current study examined the ability of executive function to predict psychosocial adjustment in PwMS. One hundred and seven PwMS underwent cognitive assessment and completed measures of stress, depression, anxiety, and quality of life (QoL). There was limited support for a relationship. There was no relationship between objective cognitive tasks and state or trait anxiety, mental health QoL, overall QoL, or stress frequency. The only relationship with depression was found when the Beck Depression Inventory Fast-Screen was used, with a task of planning when the timing element was removed. A measure of error rates on a task of cognitive flexibility predicted physical health QoL, and severity, but not frequency, of stress was predicted by a task of working memory. The results of this study highlight the need for further research into the relationship between cognitive deficits and psychosocial adjustment because of the conflicting findings between studies and call for a common measurement framework for future investigation.

  5. Examination of cognitive fatigue in multiple sclerosis using functional magnetic resonance imaging and diffusion tensor imaging.

    Genova, Helen M; Rajagopalan, Venkateswaran; Deluca, John; Das, Abhijit; Binder, Allison; Arjunan, Aparna; Chiaravalloti, Nancy; Wylie, Glenn

    2013-01-01

    The present study investigated the neural correlates of cognitive fatigue in Multiple Sclerosis (MS), looking specifically at the relationship between self-reported fatigue and objective measures of cognitive fatigue. In Experiment 1, functional magnetic resonance imaging (fMRI) was used to examine where in the brain BOLD activity covaried with "state" fatigue, assessed during performance of a task designed to induce cognitive fatigue while in the scanner. In Experiment 2, diffusion tensor imaging (DTI) was used to examine where in the brain white matter damage correlated with increased "trait" fatigue in individuals with MS, assessed by the Fatigue Severity Scale (FSS) completed outside the scanning session. During the cognitively fatiguing task, the MS group had increased brain activity associated with fatigue in the caudate as compared with HCs. DTI findings revealed that reduced fractional anisotropy in the anterior internal capsule was associated with increased self-reported fatigue on the FSS. Results are discussed in terms of identifying a "fatigue-network" in MS.

  6. Examination of cognitive fatigue in multiple sclerosis using functional magnetic resonance imaging and diffusion tensor imaging.

    Helen M Genova

    Full Text Available The present study investigated the neural correlates of cognitive fatigue in Multiple Sclerosis (MS, looking specifically at the relationship between self-reported fatigue and objective measures of cognitive fatigue. In Experiment 1, functional magnetic resonance imaging (fMRI was used to examine where in the brain BOLD activity covaried with "state" fatigue, assessed during performance of a task designed to induce cognitive fatigue while in the scanner. In Experiment 2, diffusion tensor imaging (DTI was used to examine where in the brain white matter damage correlated with increased "trait" fatigue in individuals with MS, assessed by the Fatigue Severity Scale (FSS completed outside the scanning session. During the cognitively fatiguing task, the MS group had increased brain activity associated with fatigue in the caudate as compared with HCs. DTI findings revealed that reduced fractional anisotropy in the anterior internal capsule was associated with increased self-reported fatigue on the FSS. Results are discussed in terms of identifying a "fatigue-network" in MS.

  7. Simple index of functional connectivity at rest in Multiple Sclerosis fatigue.

    Buyukturkoglu, Korhan; Porcaro, Camillo; Cottone, Carlo; Cancelli, Andrea; Inglese, Matilde; Tecchio, Franca

    2017-05-01

    To investigate the EEG-derived functional connectivity at rest (FCR) patterns of fatigued Multiple Sclerosis (MS) patients in order to find good parameters for a future EEG-Neurofeedback intervention to reduce their fatigue symptoms. We evaluated FCR between hemispheric homologous areas, via spectral coherence between pairs of corresponding left and right bipolar derivations, in the Theta, Alpha and Beta bands. We estimated FCR in 18MS patients with different levels of fatigue and minimal clinical severity and in 11 age and gender matched healthy controls. We used correlation analysis to assess the relationship between the fatigue scores and the FCR values differing between fatigued MS patients and controls. Among FCR values differing between fatigued MS patients and controls, fatigue symptoms increased with higher Beta temporo-parietal FCR (p=0.00004). Also, positive correlations were found between the fatigue levels and the fronto-frontal FCR in Beta and Theta bands (p=0.0002 and p=0.001 respectively). We propose that a future EEG-Neurofeedback system against MS fatigue would train patients to decrease voluntarily the beta coherence between the homologous temporo-parietal areas. We extracted a feature for building an EEG-Neurofeedback system against fatigue in MS. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  8. A de novo 1q22q23.1 Interstitial Microdeletion in a Girl with Intellectual Disability and Multiple Congenital Anomalies Including Congenital Heart Defect.

    Aleksiūnienė, Beata; Preiksaitiene, Egle; Morkūnienė, Aušra; Ambrozaitytė, Laima; Utkus, Algirdas

    2018-01-01

    Many studies have shown that molecular karyotyping is an effective diagnostic tool in individuals with developmental delay/intellectual disability. We report on a de novo interstitial 1q22q23.1 microdeletion, 1.6 Mb in size, detected in a patient with short stature, microcephaly, hypoplastic corpus callosum, cleft palate, minor facial anomalies, congenital heart defect, camptodactyly of the 4-5th fingers, and intellectual disability. Chromosomal microarray analysis revealed a 1.6-Mb deletion in the 1q22q23.1 region, arr[GRCh37] 1q22q23.1(155630752_157193893)×1. Real-time PCR analysis confirmed its de novo origin. The deleted region encompasses 50 protein-coding genes, including the morbid genes APOA1BP, ARHGEF2, LAMTOR2, LMNA, NTRK1, PRCC, RIT1, SEMA4A, and YY1AP1. Although the unique phenotype observed in our patient can arise from the haploinsufficiency of the dosage-sensitive LMNA gene, the dosage imbalance of other genes implicated in the rearrangement could also contribute to the phenotype. Further studies are required for the delineation of the phenotype associated with this rare chromosomal alteration and elucidation of the critical genes for manifestation of the specific clinical features. © 2018 S. Karger AG, Basel.

  9. Health effects of an increased protein intake on kidney function and colorectal cancer risk factors, including the role of animal and plant protein sources – the PREVIEW project

    Møller, Grith

    intake, including the role of animal and plant protein in pre-diabetic, overweight or obese individuals on health outcomes: markers of kidney function and putative risk factors for colorectal cancer as well as insulin sensitivity and kidney function in healthy individuals. The thesis is based on PREVIEW......, especially plant protein, on insulin sensitivity and kidney function. In paper II, the aim of the study was to assess the effect after one year of a higher protein intake on kidney function, measured by in creatinine clearance. This was investigated in pre-diabetic older adults based on a sub-group of 310...... pre-diabetic individuals included in the PREVIEW RCT. We found that a higher protein intake was associated with a significant increase in urea to creatinine ratio and serum urea after one year. There were no associations between increased protein intake and creatinine clearance, estimated glomerular...

  10. A differential transformation approach for solving functional differential equations with multiple delays

    Rebenda, Josef; Šmarda, Zdeněk

    2017-07-01

    In the paper an efficient semi-analytical approach based on the method of steps and the differential transformation is proposed for numerical approximation of solutions of functional differential models of delayed and neutral type on a finite interval of arbitrary length, including models with several constant delays. Algorithms for both commensurate and non-commensurate delays are described, applications are shown in examples. Validity and efficiency of the presented algorithms is compared with the variational iteration method, the Adomian decomposition method and the polynomial least squares method numerically. Matlab package DDE23 is used to produce reference numerical values.

  11. Physical function and pain after surgical or conservative management of multiple rib fractures - a follow-up study.

    Fagevik Olsén, Monika; Slobo, Margareta; Klarin, Lena; Caragounis, Eva-Corina; Pazooki, David; Granhed, Hans

    2016-10-28

    There is scarce knowledge of physical function and pain due to multiple rib fractures following trauma. The purpose of this follow-up was to assess respiratory and physical function, pain, range of movement and kinesiophobia in patients with multiple rib fractures who had undergone stabilizing surgery and compare with conservatively managed patients. A consecutive series of 31 patients with multiple rib fractures who had undergone stabilizing surgery were assessed >1 year after the trauma concerning respiratory and physical function, pain, range of movement in the shoulders and thorax, shoulder function and kinesiophobia. For comparison, 30 patients who were treated conservatively were evaluated with the same outcome measures. The results concerning pain, lung function, shoulder function and level of physical activity were similar in the two groups. The patients who had undergone surgery had a significantly larger range of motion in the thorax (p pain, better thoracic range of motion and physical function which would indicate that surgery is preferable. If operation technique could improve in the future with a less invasive approach, it would presumably decrease post-operative pain and the benefit of surgery would be greater than the morbidity of surgery. Patients undergoing surgery have a similar long-term recovery to those who are treated conservatively except for a better range of motion in the thorax and fewer limitations in physical function. Surgery seems to be beneficial for some patients, the question remains which patients. FoU i Sverige (R&D in Sweden), No 106121.

  12. A non-linear regression analysis program for describing electrophysiological data with multiple functions using Microsoft Excel.

    Brown, Angus M

    2006-04-01

    The objective of this present study was to demonstrate a method for fitting complex electrophysiological data with multiple functions using the SOLVER add-in of the ubiquitous spreadsheet Microsoft Excel. SOLVER minimizes the difference between the sum of the squares of the data to be fit and the function(s) describing the data using an iterative generalized reduced gradient method. While it is a straightforward procedure to fit data with linear functions, and we have previously demonstrated a method of non-linear regression analysis of experimental data based upon a single function, it is more complex to fit data with multiple functions, usually requiring specialized expensive computer software. In this paper we describe an easily understood program for fitting experimentally acquired data, in this case the stimulus-evoked compound action potential from the mouse optic nerve, with multiple Gaussian functions. The program is flexible and can be applied to describe data with a wide variety of user-input functions.

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

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

    2014-07-01

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

  14. Multiple factors, including non-motor impairments, influence decision making with regard to exercise participation in Parkinson's disease: a qualitative enquiry.

    O'Brien, Christine; Clemson, Lindy; Canning, Colleen G

    2016-01-01

    To explore how the meaning of exercise and other factors interact and influence the exercise behaviour of individuals with Parkinson's disease (PD) enrolled in a 6-month minimally supervised exercise program to prevent falls, regardless of whether they completed the prescribed exercise or not. This qualitative study utilised in-depth semi-structured interviews analysed using grounded theory methodology. Four main themes were constructed from the data: adapting to change and loss, the influence of others, making sense of the exercise experience and hope for a more active future. Participation in the PD-specific physiotherapy program involving group exercise provided an opportunity for participants to reframe their identity of their "active" self. Three new influences on exercise participation were identified and explored: non-motor impairments of apathy and fatigue, the belief in a finite energy quota, and the importance of feedback. A model was developed incorporating the themes and influences to explain decision-making for exercise participation in this group. Complex and interacting issues, including non-motor impairments, need to be considered in order to enhance the development and ongoing implementation of effective exercise programmes for people with PD. Exercise participation can assist individuals to reframe their identity as they are faced with losses associated with Parkinson's disease and ageing. Non-motor impairments of apathy and fatigue may influence exercise participation in people with Parkinson's disease. Particular attention needs to be paid to the provision of feedback in exercise programs for people with Parkinson's disease as it important for their decision-making about continuing exercise.

  15. Overlapping effector interfaces define the multiple functions of the HIV-1 Nef polyproline helix

    Kuo Lillian S

    2012-05-01

    Full Text Available Abstract Background HIV-1 Nef is a multifunctional protein required for full pathogenicity of the virus. As Nef has no known enzymatic activity, it necessarily functions through protein-protein interaction interfaces. A critical Nef protein interaction interface is centered on its polyproline segment (P69VRPQVPLRP78 which contains the helical SH3 domain binding protein motif, PXXPXR. We hypothesized that any Nef-SH3 domain interactions would be lost upon mutation of the prolines or arginine of PXXPXR. Further, mutation of the non-motif “X” residues, (Q73, V74, and L75 would give altered patterns of inhibition for different Nef/SH3 domain protein interactions. Results We found that mutations of either of the prolines or the arginine of PXXPXR are defective for Nef-Hck binding, Nef/activated PAK2 complex formation and enhancement of virion infectivity (EVI. Mutation of the non-motif “X” residues (Q, V and L gave similar patterns of inhibition for Nef/activated PAK2 complex formation and EVI which were distinct from the pattern for Hck binding. These results implicate an SH3 domain containing protein other than Hck for Nef/activated PAK2 complex formation and EVI. We have also mutated Nef residues at the N-and C-terminal ends of the polyproline segment to explore interactions outside of PXXPXR. We discovered a new locus GFP/F (G67, F68, P69 and F90 that is required for Nef/activated PAK2 complex formation and EVI. MHC Class I (MHCI downregulation was only partially inhibited by mutating the PXXPXR motif residues, but was fully inhibited by mutating the C-terminal P78. Further, we observed that MHCI downregulation strictly requires G67 and F68. Our mutational analysis confirms the recently reported structure of the complex between Nef, AP-1 μ1 and the cytoplasmic tail of MHCI, but does not support involvement of an SH3 domain protein in MHCI downregulation. Conclusion Nef has evolved to be dependent on interactions with multiple SH3 domain

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

    Natalia O. Kalinina

    2018-02-01

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

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

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

    2018-01-01

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

  18. [Correlation between demyelinating lesions and executive function decline in a sample of Mexican patients with multiple sclerosis].

    Aldrete Cortez, V R; Duriez-Sotelo, E; Carrillo-Mora, P; Pérez-Zuno, J A

    2013-09-01

    Multiple Sclerosis (MS) is characterised by several neurological symptoms including cognitive impairment, which has recently been the subject of considerable study. At present, evidence pointing to a correlation between lesion characteristics and specific cognitive impairment is not conclusive. To investigate the presence of a correlation between the characteristics of demyelinating lesions and performance of basic executive functions in a sample of MS patients. We included 21 adult patients with scores of 0 to 5 on the Kurtzke scale and no exacerbations of the disease in at least 3 months prior to the evaluation date. They completed the Stroop test and the Wisconsin Card Sorting Test (WCST). The location of the lesions was determined using magnetic resonance imaging (MRI) performed by a blinded expert in neuroimaging. Demyelinating lesions were more frequently located in the frontal and occipital lobes. The Stroop test showed that as cognitive demand increased on each of the sections in the test, reaction time and number of errors increased. On the WCST, 33.33% of patients registered as having moderate cognitive impairment. No correlation could be found between demyelinating lesion characteristics (location, size, and number) and patients' scores on the tests. Explanations of the causes of cognitive impairment in MS should examine a variety of biological, psychological, and social factors instead of focusing solely on demyelinating lesions. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  19. Method to map one-dimensional electronic wave function by using multiple Brillouin zone angle resolved photoemission

    Dong-Wook Lee

    2010-10-01

    Full Text Available Angle resolved photoemission spectroscopy (ARPES is a powerful tool to investigate electronic structures in solids and has been widely used in studying various materials. The electronic structure information by ARPES is obtained in the momentum space. However, in the case of one-dimensional system, we here show that we extract the real space information from ARPES data taken over multiple Brillouin zones (BZs. Intensities in the multiple BZs are proportional to the photoemission matrix element which contains information on the coefficient of the Bloch wave function. It is shown that the Bloch wave function coefficients can be extracted from ARPES data, which allows us to construct the real space wave function. As a test, we use ARPES data from proto-typical one-dimensional system SrCuO2 and construct the real space wave function.

  20. Pittsburgh compound-B PET white matter imaging and cognitive function in late multiple sclerosis.

    Zeydan, Burcu; Lowe, Val J; Schwarz, Christopher G; Przybelski, Scott A; Tosakulwong, Nirubol; Zuk, Samantha M; Senjem, Matthew L; Gunter, Jeffrey L; Roberts, Rosebud O; Mielke, Michelle M; Benarroch, Eduardo E; Rodriguez, Moses; Machulda, Mary M; Lesnick, Timothy G; Knopman, David S; Petersen, Ronald C; Jack, Clifford R; Kantarci, Kejal; Kantarci, Orhun H

    2018-05-01

    There is growing interest in white matter (WM) imaging with positron emission tomography (PET). We studied the association of cognitive function in late multiple sclerosis (MS) with cortical and WM Pittsburgh compound-B PET (PiB-PET) binding. In the population-based Mayo Clinic Study of Aging, 24 of 4869 participants had MS (12 underwent PiB-PET). Controls were age and sex matched (5:1). We used automated or semi-automated processing for quantitative image analyses and conditional logistic regression for group differences. MS patients had lower memory ( p = 0.03) and language ( p = 0.02) performance; smaller thalamic volumes ( p = 0.003); and thinner temporal ( p = 0.001) and frontal ( p = 0.045) cortices on magnetic resonance imaging (MRI) than controls. There was no difference in global cortical PiB standardized uptake value ratios between MS and controls ( p = 0.35). PiB uptake was lower in areas of WM hyperintensities compared to normal-appearing white matter (NAWM) in MS ( p = 0.0002). Reduced PiB uptake in both the areas of WM hyperintensities ( r = 0.65; p = 0.02) and NAWM ( r = 0.69; p = 0.01) was associated with decreased visuospatial performance in MS. PiB uptake in the cortex in late MS is not different from normal age-matched controls. PiB uptake in the WM in late MS may be a marker of the large network structures' integrity such as those involved in visuospatial performance.

  1. Structural networks involved in attention and executive functions in multiple sclerosis

    Sara Llufriu

    2017-01-01

    Full Text Available Attention and executive deficits are disabling symptoms in multiple sclerosis (MS that have been related to disconnection mechanisms. We aimed to investigate changes in structural connectivity in MS and their association with attention and executive performance applying an improved framework that combines high order probabilistic tractography and anatomical exclusion criteria postprocessing. We compared graph theory metrics of structural networks and fractional anisotropy (FA of white matter (WM connections or edges between 72 MS subjects and 38 healthy volunteers (HV and assessed their correlation with cognition. Patients displayed decreased network transitivity, global efficiency and increased path length compared with HV (p < 0.05, corrected. Also, nodal strength was decreased in 26 of 84 gray matter regions. The distribution of nodes with stronger connections or hubs of the network was similar among groups except for the right pallidum and left insula, which became hubs in patients. MS subjects presented reduced edge FA widespread in the network, while FA was increased in 24 connections (p < 0.05, corrected. Decreased integrity of frontoparietal networks, deep gray nuclei and insula correlated with worse attention and executive performance (r between 0.38 and 0.55, p < 0.05, corrected. Contrarily, higher strength in the right transverse temporal cortex and increased FA of several connections (mainly from cingulate, frontal and occipital cortices were associated with worse functioning (r between −0.40 and −0.47, p < 0.05 corrected. In conclusion, structural brain connectivity is disturbed in MS due to widespread impairment of WM connections and gray matter structures. The increased edge connectivity suggests the presence of reorganization mechanisms at the structural level. Importantly, attention and executive performance relates to frontoparietal networks, deep gray nuclei and insula. These results support the relevance of

  2. Functioning glucagonoma associated with primary hyperparathyroidism: multiple endocrine neoplasia type 1 or incidental association?

    Erdas, Enrico; Mariotti, Stefano; Pomata, Mariano; Aste, Nicola; Pilloni, Luca; Nicolosi, Angelo; Licheri, Sergio; Cappai, Antonello; Mastinu, Marco; Cetani, Filomena; Pardi, Elena

    2012-01-01

    Diagnosis of multiple endocrine neoplasia type 1 (MEN1) is commonly based on clinical criteria, and confirmed by genetic testing. In patients without known MEN1-related germline mutations, the possibility of a casual association between two or more endocrine tumors cannot be excluded and subsequent management may be difficult to plan. We describe a very uncommon case of functioning glucagonoma associated with primary hyperparathyroidism (pHPT) in which genetic testing failed to detect germline mutations of MEN-1 and other known genes responsible for MEN1. The patient, a 65-year old woman, had been suffering for more than 1 year from weakness, progressive weight loss, angular cheilitis, glossitis and, more recently, skin rashes on the perineum, perioral skin and groin folds. After multidisciplinary investigations, functioning glucagonoma and asymptomatic pHPT were diagnosed and, since family history was negative, sporadic MEN1 was suspected. However, genetic testing revealed neither MEN-1 nor other gene mutations responsible for rarer cases of MEN1 (CDKN1B/p27 and other cyclin-dependent kinase inhibitor genes CDKN1A/p15, CDKN2C/p18, CDKN2B/p21). The patient underwent distal splenopancreatectomy and at the 4-month follow-up she showed complete remission of symptoms. Six months later, a thyroid nodule, suspected to be a malignant neoplasia, and two hyperfunctioning parathyroid glands were detected respectively by ultrasound with fine needle aspiration cytology and 99m Tc-sestamibi scan with SPECT acquisition. Total thyroidectomy was performed, whereas selective parathyroidectomy was preferred to a more extensive procedure because the diagnosis of MEN1 was not supported by genetic analysis and intraoperative intact parathyroid hormone had revealed “adenoma-like” kinetics after the second parathyroid resection. Thirty-nine and 25 months after respectively the first and the second operation, the patient is well and shows no signs or symptoms of recurrence. Despite

  3. Functioning glucagonoma associated with primary hyperparathyroidism: multiple endocrine neoplasia type 1 or incidental association?

    Erdas Enrico

    2012-12-01

    Full Text Available Abstract Background Diagnosis of multiple endocrine neoplasia type 1 (MEN1 is commonly based on clinical criteria, and confirmed by genetic testing. In patients without known MEN1-related germline mutations, the possibility of a casual association between two or more endocrine tumors cannot be excluded and subsequent management may be difficult to plan. We describe a very uncommon case of functioning glucagonoma associated with primary hyperparathyroidism (pHPT in which genetic testing failed to detect germline mutations of MEN-1 and other known genes responsible for MEN1. Case presentation The patient, a 65-year old woman, had been suffering for more than 1 year from weakness, progressive weight loss, angular cheilitis, glossitis and, more recently, skin rashes on the perineum, perioral skin and groin folds. After multidisciplinary investigations, functioning glucagonoma and asymptomatic pHPT were diagnosed and, since family history was negative, sporadic MEN1 was suspected. However, genetic testing revealed neither MEN-1 nor other gene mutations responsible for rarer cases of MEN1 (CDKN1B/p27 and other cyclin-dependent kinase inhibitor genes CDKN1A/p15, CDKN2C/p18, CDKN2B/p21. The patient underwent distal splenopancreatectomy and at the 4-month follow-up she showed complete remission of symptoms. Six months later, a thyroid nodule, suspected to be a malignant neoplasia, and two hyperfunctioning parathyroid glands were detected respectively by ultrasound with fine needle aspiration cytology and 99mTc-sestamibi scan with SPECT acquisition. Total thyroidectomy was performed, whereas selective parathyroidectomy was preferred to a more extensive procedure because the diagnosis of MEN1 was not supported by genetic analysis and intraoperative intact parathyroid hormone had revealed “adenoma-like” kinetics after the second parathyroid resection. Thirty-nine and 25 months after respectively the first and the second operation, the patient is well

  4. The clinical obesity maintenance model: an integration of psychological constructs including mood, emotional regulation, disordered overeating, habitual cluster behaviours, health literacy and cognitive function.

    Raman, Jayanthi; Smith, Evelyn; Hay, Phillipa

    2013-01-01

    Psychological distress and deficits in executive functioning are likely to be important barriers to effective weight loss maintenance. The purpose of this paper is twofold. First, in the light of recent evidence in the fields of neuropsychology and obesity, particularly on the deficits in the executive function in overweight and obese individuals, a conceptual and theoretical framework of obesity maintenance is introduced by way of a clinical obesity maintenance model (COMM). It is argued that psychological variables, that of habitual cluster Behaviors, emotional dysregulation, mood, and health literacy, interact with executive functioning and impact on the overeating/binge eating behaviors of obese individuals. Second, cognizant of this model, it is argued that the focus of obesity management should be extended to include a broader range of maintaining mechanisms, including but not limited to cognitive deficits. Finally, a discussion on potential future directions in research and practice using the COMM is provided.

  5. The Clinical Obesity Maintenance Model: An Integration of Psychological Constructs including Mood, Emotional Regulation, Disordered Overeating, Habitual Cluster Behaviours, Health Literacy and Cognitive Function

    Jayanthi Raman

    2013-01-01

    Full Text Available Psychological distress and deficits in executive functioning are likely to be important barriers to effective weight loss maintenance. The purpose of this paper is twofold. First, in the light of recent evidence in the fields of neuropsychology and obesity, particularly on the deficits in the executive function in overweight and obese individuals, a conceptual and theoretical framework of obesity maintenance is introduced by way of a clinical obesity maintenance model (COMM. It is argued that psychological variables, that of habitual cluster Behaviors, emotional dysregulation, mood, and health literacy, interact with executive functioning and impact on the overeating/binge eating behaviors of obese individuals. Second, cognizant of this model, it is argued that the focus of obesity management should be extended to include a broader range of maintaining mechanisms, including but not limited to cognitive deficits. Finally, a discussion on potential future directions in research and practice using the COMM is provided.

  6. Multiple loss-of-function mechanisms contribute to SCN5A-related familial sick sinus syndrome.

    Junhong Gui

    2010-06-01

    Full Text Available To identify molecular mechanisms underlying SCN5A-related sick sinus syndrome (SSS, a rare type of SSS, in parallel experiments we elucidated the electrophysiological properties and the cell surface localization of thirteen human Na(v1.5 (hNa(v1.5 mutant channels previously linked to this disease.Mutant hNa(v1.5 channels expressed by HEK293 cells and Xenopus oocytes were investigated by whole-cell patch clamp and two-microelectrode voltage clamp, respectively. HEK293 cell surface biotinylation experiments quantified the fraction of correctly targeted channel proteins. Our data suggested three distinct mutant channel subtypes: Group 1 mutants (L212P, P1298L, DelF1617, R1632H gave peak current densities and cell surface targeting indistinguishable from wild-type hNa(v1.5. Loss-of-function of these mutants resulted from altered channel kinetics, including a negative shift of steady-state inactivation and a reduced voltage dependency of open-state inactivation. Group 2 mutants (E161K, T220I, D1275N gave significantly reduced whole-cell currents due to impaired cell surface localization (D1275N, altered channel properties at unchanged cell surface localization (T220I, or a combination of both (E161K. Group 3 mutant channels were non-functional, due to an almost complete lack of protein at the plasma membrane (T187I, W1421X, K1578fs/52, R1623X or a probable gating/permeation defect with normal surface localisation (R878C, G1408R.This study indicates that multiple molecular mechanisms, including gating abnormalities, trafficking defects, or a combination of both, are responsible for SCN5A-related familial SSS.

  7. Afferent thermosensory function in relapsing-remitting multiple sclerosis following exercise-induced increases in body temperature.

    Filingeri, Davide; Chaseling, Georgia; Hoang, Phu; Barnett, Michael; Davis, Scott L; Jay, Ollie

    2017-08-01

    What is the central question of this study? Between 60 and 80% of multiple sclerosis (MS) patients experience transient worsening of symptoms with increased body temperature (heat sensitivity). As sensory abnormalities are common in MS, we asked whether afferent thermosensory function is altered in MS following exercise-induced increases in body temperature. What is the main finding and its importance? Increases in body temperature of as little as ∼0.4°C were sufficient to decrease cold, but not warm, skin thermosensitivity (∼10%) in MS, across a wider temperature range than in age-matched healthy individuals. These findings provide new evidence on the impact of heat sensitivity on afferent function in MS, which could be useful for clinical evaluation of this neurological disease. In multiple sclerosis (MS), increases in body temperature result in transient worsening of clinical symptoms (heat sensitivity or Uhthoff's phenomenon). Although the impact of heat sensitivity on efferent physiological function has been investigated, the effects of heat stress on afferent sensory function in MS are unknown. Hence, we quantified afferent thermosensory function in MS following exercise-induced increases in body temperature with a new quantitative sensory test. Eight relapsing-remitting MS patients (three men and five women; 51.4 ± 9.1 years of age; Expanded Disability Status Scale score 2.8 ± 1.1) and eight age-matched control (CTR) subjects (five men and three women; 47.4 ± 9.1 years of age) rated the perceived magnitude of two cold (26 and 22°C) and two warm stimuli (34 and 38°C) applied to the dorsum of the hand before and after 30 min cycling in the heat (30°C air; 30% relative humidity). Exercise produced similar increases in mean body temperature in MS [+0.39°C (95% CI: +0.21, +0.53) P = 0.001] and CTR subjects [+0.41°C (95% CI: +0.25, +0.58) P = 0.001]. These changes were sufficient to decrease thermosensitivity significantly to all cold [26

  8. Development of a comprehensive survey of sexuality issues including a self-report version of the International Spinal Cord Injury sexual function basic data sets.

    New, P W; Currie, K E

    2016-08-01

    Questionnaire development, validation and completion. Develop comprehensive survey of sexuality issues including validated self-report versions of the International Spinal Cord Injury male sexual function and female sexual and reproductive function basic data sets (SR-iSCI-sexual function). People with spinal cord damage (SCD) living in the community, Australia from August 2013 to June 2014. An iterative process involving rehabilitation medicine clinicians, a nurse specialising in sexuality issues in SCD and people with SCD who developed a comprehensive survey that included the SR-iSCI-sexual function. Participants recruitment through spinal rehabilitation review clinic and community organisations that support people with SCD. Surveys completed by 154 people. Most were male (n=101, 65.6%). Respondents' median age was 50 years (interquartile range (IQR) 38-58), and they were a median of 10 years (IQR 4-20) after the onset of SCD. Sexual problems unrelated to SCD were reported by 12 (8%) respondents, and 114 (n=75.5%) reported sexual problems because of SCD. Orgasms were much less likely (χ(2)=13.1, P=0.006) to be normal in males (n=5, 5%) compared with females (n=11, 22%). Males had significantly worse (χ(2)=26.0, P=0.001) psychogenic genital functioning (normal n=9, 9%) than females (normal n=13, 26%) and worse (χ(2)=10.8, P=0.013) reflex genital functioning. Normal ejaculation was reported in only three (3%) men. Most (n=26, 52%) women reported reduced or absent menstruation pattern since SCD. The SR-iSCI-sexual function provides a useful tool for researchers and clinicians to collect information regarding patient-reported sexual functioning after SCD and to facilitate comparative studies.

  9. Exercise, Diet, and Stress Management as Mediators between Functional Disability and Health-Related Quality of Life in Multiple Sclerosis

    Sung, Connie; Chiu, Chung-Yi; Lee, Eun-Jeong; Bezyak, Jill; Chan, Fong; Muller, Veronica

    2013-01-01

    The main objective of this study was to examine the mediational and moderational effect of exercise, diet, and stress management on the relationship between functional disability and health-related quality of life. Quantitative descriptive research design using multiple regression and correlation techniques was used. Participants were 215…

  10. Functional Magnetic Resonance Imaging with Concurrent Urodynamic Testing Identifies Brain Structures Involved in Micturition Cycle in Patients with Multiple Sclerosis.

    Khavari, Rose; Karmonik, Christof; Shy, Michael; Fletcher, Sophie; Boone, Timothy

    2017-02-01

    Neurogenic lower urinary tract dysfunction, which is common in patients with multiple sclerosis, has a significant impact on quality of life. In this study we sought to determine brain activity processes during the micturition cycle in female patients with multiple sclerosis and neurogenic lower urinary tract dysfunction. We report brain activity on functional magnetic resonance imaging and simultaneous urodynamic testing in 23 ambulatory female patients with multiple sclerosis. Individual functional magnetic resonance imaging activation maps at strong desire to void and at initiation of voiding were calculated and averaged at Montreal Neuroimaging Institute. Areas of significant activation were identified in these average maps. Subgroup analysis was performed in patients with elicitable neurogenic detrusor overactivity or detrusor-sphincter dyssynergia. Group analysis of all patients at strong desire to void yielded areas of activation in regions associated with executive function (frontal gyrus), emotional regulation (cingulate gyrus) and motor control (putamen, cerebellum and precuneus). Comparison of the average change in activation between previously reported healthy controls and patients with multiple sclerosis showed predominantly stronger, more focal activation in the former and lower, more diffused activation in the latter. Patients with multiple sclerosis who had demonstrable neurogenic detrusor overactivity and detrusor-sphincter dyssynergia showed a trend toward distinct brain activation at full urge and at initiation of voiding respectively. We successfully studied brain activation during the entire micturition cycle in female patients with neurogenic lower urinary tract dysfunction and multiple sclerosis using a concurrent functional magnetic resonance imaging/urodynamic testing platform. Understanding the central neural processes involved in specific parts of micturition in patients with neurogenic lower urinary tract dysfunction may identify areas

  11. Functional analyses of multiple lichenin-degrading enzymes from the rumen bacterium Ruminococcus albus 8.

    Iakiviak, Michael; Mackie, Roderick I; Cann, Isaac K O

    2011-11-01

    Ruminococcus albus 8 is a fibrolytic ruminal bacterium capable of utilization of various plant cell wall polysaccharides. A bioinformatic analysis of a partial genome sequence of R. albus revealed several putative enzymes likely to hydrolyze glucans, including lichenin, a mixed-linkage polysaccharide of glucose linked together in β-1,3 and β-1,4 glycosidic bonds. In the present study, we demonstrate the capacity of four glycoside hydrolases (GHs), derived from R. albus, to hydrolyze lichenin. Two of the genes encoded GH family 5 enzymes (Ra0453 and Ra2830), one gene encoded a GH family 16 enzyme (Ra0505), and the last gene encoded a GH family 3 enzyme (Ra1595). Each gene was expressed in Escherichia coli, and the recombinant protein was purified to near homogeneity. Upon screening on a wide range of substrates, Ra0453, Ra2830, and Ra0505 displayed different hydrolytic properties, as they released unique product profiles. The Ra1595 protein, predicted to function as a β-glucosidase, preferred cleavage of a nonreducing end glucose when linked by a β-1,3 glycosidic bond to the next glucose residue. The major product of Ra0505 hydrolysis of lichenin was predicted to be a glucotriose that was degraded only by Ra0453 to glucose and cellobiose. Most importantly, the four enzymes functioned synergistically to hydrolyze lichenin to glucose, cellobiose, and cellotriose. This lichenin-degrading enzyme mix should be of utility as an additive to feeds administered to monogastric animals, especially those high in fiber.

  12. Multiple functions and essential roles of nuclear receptor coactivators of bHLH-PAS family.

    Pecenova, L; Farkas, Robert

    2016-07-01

    Classical non-peptide hormones, such as steroids, retinoids, thyroid hormones, vitamin D3 and their derivatives including prostaglandins, benzoates, oxysterols, and bile acids, are collectively designated as small lipophilic ligands, acting via binding to the nuclear receptors (NRs). The NRs form a large superfamily of transcription factors that participate virtually in every key biological process. They control various aspects of animal development, fertility, gametogenesis, and numerous metabolic pathways, and can be misregulated in many types of cancers. Their enormous functional plasticity, as transcription factors, relates in part to NR-mediated interactions with plethora of coregulatory proteins upon ligand binding to their ligand binding domains (LBD), or following covalent modification. Here, we review some general views of a specific group of NR coregulators, so-called nuclear receptor coactivators (NRCs) or steroid receptor coactivators (SRCs) and highlight some of their unique functions/roles, which are less extensively mentioned and discussed in other reviews. We also try to pinpoint few neglected moments in the cooperative action of SRCs, which may also indicate their variable roles in the hormone-independent signaling pathways.

  13. Characterization of Genotoxic Response to 15 Multiwalled Carbon Nanotubes with Variable Physicochemical Properties Including Surface Functionalizations in the FE1-Muta(TM) Mouse Lung Epithelial Cell Line

    Jackson, Petra; Kling, Kirsten; Jensen, Keld Alstrup

    2015-01-01

    Carbon nanotubes vary greatly in physicochemical properties. We compared cytotoxic and genotoxic response to 15 multiwalled carbon nanotubes (MWCNT) with varying physicochemical properties to identify drivers of toxic responses. The studied MWCNT included OECD Working Party on Manufactured...... Nanomaterials (WPMN) (NM-401, NM-402, and NM-403), materials (NRCWE-026 and MWCNT-XNRI-7), and three sets of surface-modified MWCNT grouped by physical characteristics (thin, thick, and short I-III, respectively). Each Groups I-III included pristine, hydroxylated and carboxylated MWCNT. Group III also included...... an amino-functionalized MWCNT. The level of surface functionalization of the MWCNT was low. The level and type of elemental impurities of the MWCNT varied by...

  14. Static Posturography and Falls According to Pyramidal, Sensory and Cerebellar Functional Systems in People with Multiple Sclerosis

    Kalron, Alon; Givon, Uri; Frid, Lior; Dolev, Mark; Achiron, Anat

    2016-01-01

    Balance impairment is common in people with multiple sclerosis (PwMS) and frequently impacts quality of life by decreasing mobility and increasing the risk of falling. However, there are only scarce data examining the contribution of specific neurological functional systems on balance measures in MS. Therefore, the primary aim of our study was to examine the differences in posturography parameters and fall incidence according to the pyramidal, cerebellar and sensory systems functional systems in PwMS. The study included 342 PwMS, 211 women and mean disease duration of 8.2 (S.D = 8.3) years. The study sample was divided into six groups according to the pyramidal, cerebellar and sensory functional system scores, derived from the Expanded Disability Status Scale (EDSS) data. Static postural control parameters were obtained from the Zebris FDM-T Treadmill (zebris® Medical GmbH, Germany). Participants were defined as "fallers" and "non-fallers" based on their fall history. Our findings revealed a trend that PwMS affected solely in the pyramidal system, have reduced stability compared to patients with cerebellar and sensory dysfunctions. Moreover, the addition of sensory impairments to pyramidal dysfunction does not exacerbate postural control. The patients in the pure sensory group demonstrated increased stability compared to each of the three combined groups; pyramidal-cerebellar, pyramidal-sensory and pyramidal-cerebellar-sensory groups. As for fall status, the percentage of fallers in the pure pyramidal, cerebellar and sensory groups were 44.3%, 33.3% and 19.5%, respectively. As for the combined functional system groups, the percentage of fallers in the pyramidal-cerebellar, pyramidal-sensory and pyramidal-cerebellar-sensory groups were 59.7%, 40.7% and 65%, respectively. This study confirms that disorders in neurological functional systems generate different effects on postural control and incidence of falls in the MS population. From a clinical standpoint, the

  15. Static Posturography and Falls According to Pyramidal, Sensory and Cerebellar Functional Systems in People with Multiple Sclerosis.

    Kalron, Alon; Givon, Uri; Frid, Lior; Dolev, Mark; Achiron, Anat

    2016-01-01

    Balance impairment is common in people with multiple sclerosis (PwMS) and frequently impacts quality of life by decreasing mobility and increasing the risk of falling. However, there are only scarce data examining the contribution of specific neurological functional systems on balance measures in MS. Therefore, the primary aim of our study was to examine the differences in posturography parameters and fall incidence according to the pyramidal, cerebellar and sensory systems functional systems in PwMS. The study included 342 PwMS, 211 women and mean disease duration of 8.2 (S.D = 8.3) years. The study sample was divided into six groups according to the pyramidal, cerebellar and sensory functional system scores, derived from the Expanded Disability Status Scale (EDSS) data. Static postural control parameters were obtained from the Zebris FDM-T Treadmill (zebris® Medical GmbH, Germany). Participants were defined as "fallers" and "non-fallers" based on their fall history. Our findings revealed a trend that PwMS affected solely in the pyramidal system, have reduced stability compared to patients with cerebellar and sensory dysfunctions. Moreover, the addition of sensory impairments to pyramidal dysfunction does not exacerbate postural control. The patients in the pure sensory group demonstrated increased stability compared to each of the three combined groups; pyramidal-cerebellar, pyramidal-sensory and pyramidal-cerebellar-sensory groups. As for fall status, the percentage of fallers in the pure pyramidal, cerebellar and sensory groups were 44.3%, 33.3% and 19.5%, respectively. As for the combined functional system groups, the percentage of fallers in the pyramidal-cerebellar, pyramidal-sensory and pyramidal-cerebellar-sensory groups were 59.7%, 40.7% and 65%, respectively. This study confirms that disorders in neurological functional systems generate different effects on postural control and incidence of falls in the MS population. From a clinical standpoint, the

  16. Molecular cloning and functional characterization of multiple NADPH-cytochrome P450 reductases from Andrographis paniculata.

    Lin, Huixin; Wang, Jian; Qi, Mengdie; Guo, Juan; Rong, Qixian; Tang, Jinfu; Wu, Yisheng; Ma, Xiaojing; Huang, Luqi

    2017-09-01

    Andrographis paniculata (Burm.f.) Wall. ex Nees is widely used as medicinal herb in Southern and Southeastern Asia and andrographolide is its main medicinal constituent. Based on the structure of andrographolide, it has been proposed that cytochrome P450 enzymes play vital roles on its biosynthesis. NADPH:cytochrome P450 reductase (CPR) is the most important redox partner of multiple P450s. In this study, three CPRs were identified in the genomic data of A. paniculata (namely ApCPR1, ApCPR2, and ApCPR3), and their coding regions were cloned. They varied from 62% to 70% identities to each other at the amino acid sequence level. ApCPR1 belongs to Class I of dicotyledonous CPR while both ApCPR2 and ApCPR3 are grouped to Class II. The recombinant enzymes ApCPR1 and ApCPR2 reduced cytochrome c and ferricyanide in an NADPH-dependent manner. In yeast, they supported the activity of CYP76AH1, a ferruginol-forming enzyme. However, ApCPR3 did not show any enzymatic activities either in vitro or in vivo. Quantitative real-time PCR analysis showed that both ApCPR1 and ApCPR2 expressed in all tissues examined, but ApCPR2 showed higher expression in leaves. Expression of ApCPR2 was inducible by MeJA and its pattern matched with andrographolide accumulation. Present investigation suggested ApCPR2 involves in the biosynthesis of secondary metabolites including andrographolide. Copyright © 2017. Published by Elsevier B.V.

  17. Episodic memory function is associated with multiple measures of white matter integrity in cognitive aging

    Samuel Neal Lockhart

    2012-03-01

    Full Text Available Previous neuroimaging research indicates that white matter injury and integrity, measured respectively by white matter hyperintensities (WMH and fractional anisotropy (FA obtained from diffusion tensor imaging, differ with aging and cerebrovascular disease and are associated with episodic memory deficits in cognitively normal older adults. However, knowledge about tract-specific relationships between WMH, FA, and episodic memory in aging remains limited. We hypothesized that white matter connections between frontal cortex and subcortical structures as well as connections between frontal and temporo-parietal cortex would be most affected. In the current study, we examined relationships between WMH, FA and episodic memory in 15 young adults, 13 elders with minimal WMH and 15 elders with extensive WMH, using an episodic recognition memory test for object-color associations. Voxel-based statistics were used to identify voxel clusters where white matter measures were specifically associated with variations in episodic memory performance, and white matter tracts intersecting these clusters were analyzed to examine white matter-memory relationships. White matter injury and integrity measures were significantly associated with episodic memory in extensive regions of white matter, located predominantly in frontal, parietal, and subcortical regions. Template based tractography indicated that white matter injury, as measured by WMH, in the uncinate and inferior longitudinal fasciculi were significantly negatively associated with episodic memory performance. Other tracts such as thalamo-frontal projections, superior longitudinal fasciculus, and dorsal cingulum bundle demonstrated strong negative associations as well. The results suggest that white matter injury to multiple pathways, including connections of frontal and temporal cortex and frontal-subcortical white matter tracts, plays a critical role in memory differences seen in older individuals.

  18. Constraints on signaling network logic reveal functional subgraphs on Multiple Myeloma OMIC data.

    Miannay, Bertrand; Minvielle, Stéphane; Magrangeas, Florence; Guziolowski, Carito

    2018-03-21

    The integration of gene expression profiles (GEPs) and large-scale biological networks derived from pathways databases is a subject which is being widely explored. Existing methods are based on network distance measures among significantly measured species. Only a small number of them include the directionality and underlying logic existing in biological networks. In this study we approach the GEP-networks integration problem by considering the network logic, however our approach does not require a prior species selection according to their gene expression level. We start by modeling the biological network representing its underlying logic using Logic Programming. This model points to reachable network discrete states that maximize a notion of harmony between the molecular species active or inactive possible states and the directionality of the pathways reactions according to their activator or inhibitor control role. Only then, we confront these network states with the GEP. From this confrontation independent graph components are derived, each of them related to a fixed and optimal assignment of active or inactive states. These components allow us to decompose a large-scale network into subgraphs and their molecular species state assignments have different degrees of similarity when compared to the same GEP. We apply our method to study the set of possible states derived from a subgraph from the NCI-PID Pathway Interaction Database. This graph links Multiple Myeloma (MM) genes to known receptors for this blood cancer. We discover that the NCI-PID MM graph had 15 independent components, and when confronted to 611 MM GEPs, we find 1 component as being more specific to represent the difference between cancer and healthy profiles.

  19. Burke-Fahn-Marsden dystonia severity, Gross Motor, Manual Ability, and Communication Function Classification scales in childhood hyperkinetic movement disorders including cerebral palsy: a 'Rosetta Stone' study.

    Elze, Markus C; Gimeno, Hortensia; Tustin, Kylee; Baker, Lesley; Lumsden, Daniel E; Hutton, Jane L; Lin, Jean-Pierre S-M

    2016-02-01

    Hyperkinetic movement disorders (HMDs) can be assessed using impairment-based scales or functional classifications. The Burke-Fahn-Marsden Dystonia Rating Scale-movement (BFM-M) evaluates dystonia impairment, but may not reflect functional ability. The Gross Motor Function Classification System (GMFCS), Manual Ability Classification System (MACS), and Communication Function Classification System (CFCS) are widely used in the literature on cerebral palsy to classify functional ability, but not in childhood movement disorders. We explore the concordance of these three functional scales in a large sample of paediatric HMDs and the impact of dystonia severity on these scales. Children with HMDs (n=161; median age 10y 3mo, range 2y 6mo-21y) were assessed using the BFM-M, GMFCS, MACS, and CFCS from 2007 to 2013. This cross-sectional study contrasts the information provided by these scales. All four scales were strongly associated (all Spearman's rank correlation coefficient rs >0.72, pdisorders including cerebral palsy can be effectively evaluated using these scales. © 2015 Mac Keith Press.

  20. Lidar inelastic multiple-scattering parameters of cirrus particle ensembles determined with geometrical-optics crystal phase functions.

    Reichardt, J; Hess, M; Macke, A

    2000-04-20

    Multiple-scattering correction factors for cirrus particle extinction coefficients measured with Raman and high spectral resolution lidars are calculated with a radiative-transfer model. Cirrus particle-ensemble phase functions are computed from single-crystal phase functions derived in a geometrical-optics approximation. Seven crystal types are considered. In cirrus clouds with height-independent particle extinction coefficients the general pattern of the multiple-scattering parameters has a steep onset at cloud base with values of 0.5-0.7 followed by a gradual and monotonic decrease to 0.1-0.2 at cloud top. The larger the scattering particles are, the more gradual is the rate of decrease. Multiple-scattering parameters of complex crystals and of imperfect hexagonal columns and plates can be well approximated by those of projected-area equivalent ice spheres, whereas perfect hexagonal crystals show values as much as 70% higher than those of spheres. The dependencies of the multiple-scattering parameters on cirrus particle spectrum, base height, and geometric depth and on the lidar parameters laser wavelength and receiver field of view, are discussed, and a set of multiple-scattering parameter profiles for the correction of extinction measurements in homogeneous cirrus is provided.

  1. Deletion of GLUT1 and GLUT3 Reveals Multiple Roles for Glucose Metabolism in Platelet and Megakaryocyte Function

    Trevor P. Fidler

    2017-07-01

    Full Text Available Anucleate platelets circulate in the blood to facilitate thrombosis and diverse immune functions. Platelet activation leading to clot formation correlates with increased glycogenolysis, glucose uptake, glucose oxidation, and lactic acid production. Simultaneous deletion of glucose transporter (GLUT 1 and GLUT3 (double knockout [DKO] specifically in platelets completely abolished glucose uptake. In DKO platelets, mitochondrial oxidative metabolism of non-glycolytic substrates, such as glutamate, increased. Thrombosis and platelet activation were decreased through impairment at multiple activation nodes, including Ca2+ signaling, degranulation, and integrin activation. DKO mice developed thrombocytopenia, secondary to impaired pro-platelet formation from megakaryocytes, and increased platelet clearance resulting from cytosolic calcium overload and calpain activation. Systemic treatment with oligomycin, inhibiting mitochondrial metabolism, induced rapid clearance of platelets, with circulating counts dropping to zero in DKO mice, but not wild-type mice, demonstrating an essential role for energy metabolism in platelet viability. Thus, substrate metabolism is essential for platelet production, activation, and survival.

  2. The use of regression analysis in determining reference intervals for low hematocrit and thrombocyte count in multiple electrode aggregometry and platelet function analyzer 100 testing of platelet function.

    Kuiper, Gerhardus J A J M; Houben, Rik; Wetzels, Rick J H; Verhezen, Paul W M; Oerle, Rene van; Ten Cate, Hugo; Henskens, Yvonne M C; Lancé, Marcus D

    2017-11-01

    Low platelet counts and hematocrit levels hinder whole blood point-of-care testing of platelet function. Thus far, no reference ranges for MEA (multiple electrode aggregometry) and PFA-100 (platelet function analyzer 100) devices exist for low ranges. Through dilution methods of volunteer whole blood, platelet function at low ranges of platelet count and hematocrit levels was assessed on MEA for four agonists and for PFA-100 in two cartridges. Using (multiple) regression analysis, 95% reference intervals were computed for these low ranges. Low platelet counts affected MEA in a positive correlation (all agonists showed r 2 ≥ 0.75) and PFA-100 in an inverse correlation (closure times were prolonged with lower platelet counts). Lowered hematocrit did not affect MEA testing, except for arachidonic acid activation (ASPI), which showed a weak positive correlation (r 2 = 0.14). Closure time on PFA-100 testing was inversely correlated with hematocrit for both cartridges. Regression analysis revealed different 95% reference intervals in comparison with originally established intervals for both MEA and PFA-100 in low platelet or hematocrit conditions. Multiple regression analysis of ASPI and both tests on the PFA-100 for combined low platelet and hematocrit conditions revealed that only PFA-100 testing should be adjusted for both thrombocytopenia and anemia. 95% reference intervals were calculated using multiple regression analysis. However, coefficients of determination of PFA-100 were poor, and some variance remained unexplained. Thus, in this pilot study using (multiple) regression analysis, we could establish reference intervals of platelet function in anemia and thrombocytopenia conditions on PFA-100 and in thrombocytopenia conditions on MEA.

  3. Comparison of multiple linear regression and artificial neural network in developing the objective functions of the orthopaedic screws.

    Hsu, Ching-Chi; Lin, Jinn; Chao, Ching-Kong

    2011-12-01

    Optimizing the orthopaedic screws can greatly improve their biomechanical performances. However, a methodical design optimization approach requires a long time to search the best design. Thus, the surrogate objective functions of the orthopaedic screws should be accurately developed. To our knowledge, there is no study to evaluate the strengths and limitations of the surrogate methods in developing the objective functions of the orthopaedic screws. Three-dimensional finite element models for both the tibial locking screws and the spinal pedicle screws were constructed and analyzed. Then, the learning data were prepared according to the arrangement of the Taguchi orthogonal array, and the verification data were selected with use of a randomized selection. Finally, the surrogate objective functions were developed by using either the multiple linear regression or the artificial neural network. The applicability and accuracy of those surrogate methods were evaluated and discussed. The multiple linear regression method could successfully construct the objective function of the tibial locking screws, but it failed to develop the objective function of the spinal pedicle screws. The artificial neural network method showed a greater capacity of prediction in developing the objective functions for the tibial locking screws and the spinal pedicle screws than the multiple linear regression method. The artificial neural network method may be a useful option for developing the objective functions of the orthopaedic screws with a greater structural complexity. The surrogate objective functions of the orthopaedic screws could effectively decrease the time and effort required for the design optimization process. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  4. Dynamic Interaction of Stress Granules, DDX3X, and IKK-α Mediates Multiple Functions in Hepatitis C Virus Infection.

    Pène, Véronique; Li, Qisheng; Sodroski, Catherine; Hsu, Ching-Sheng; Liang, T Jake

    2015-05-01

    The ubiquitous ATP-dependent RNA helicase DDX3X is involved in many cellular functions, including innate immunity, and is a pivotal host factor for hepatitis C virus (HCV) infection. Recently, we showed that DDX3X specifically recognizes the HCV 3' untranslated region (UTR), leading to the activation of IKK-α and a cascade of lipogenic signaling to facilitate lipid droplet biogenesis and viral assembly (Q. Li, V. Pene, S. Krishnamurthy, H. Cha, and T. J. Liang, Nat Med 19:722-729, 2013, http://dx.doi.org/10.1038/nm.3190). The interaction of DDX3X with HCV core protein seems to be dispensable for its proviral role. In this study, through systematic imaging and biochemical and virologic approaches, we identified a dynamic association between DDX3X and various cellular compartments and viral elements mediating multiple functions of DDX3X in productive HCV infection. Upon HCV infection, the HCV 3'UTR interacts with DDX3X and IKK-α, which redistribute to speckle-like cytoplasmic structures shown to be stress granules (SGs). As viral proteins accumulate in infected cells, DDX3X granules together with SG-associated proteins redistribute and colocalize with HCV core protein around lipid droplets (LDs). IKK-α, however, does not relocate to the LD but translocates to the nucleus. In HCV-infected cells, various HCV nonstructural proteins also interact or colocalize with DDX3X in close proximity to SGs and LDs, consistent with the tight juxtaposition of the replication complex and the assembly site at the surface of LDs. Short interfering RNA (siRNA)-mediated silencing of DDX3X and multiple SG components markedly inhibits HCV infection. Our data suggest that DDX3X initiates a multifaceted cellular program involving dynamic associations with HCV RNA and proteins, IKK-α, SG, and LD surfaces for its crucial role in the HCV life cycle. IMPORTANCE DDX3X is a proviral host factor for HCV infection. Recently, we showed that DDX3X binds to the HCV 3'UTR, activating IKK-α and

  5. The epigenetic modifier PRDM5 functions as a tumor suppressor through modulating WNT/β-catenin signaling and is frequently silenced in multiple tumors.

    Xing-sheng Shu

    Full Text Available BACKGROUND: PRDM (PRDI-BF1 and RIZ domain containing proteins are zinc finger proteins involved in multiple cellular regulations by acting as epigenetic modifiers. We studied a recently identified PRDM member PRDM5 for its epigenetic abnormality and tumor suppressive functions in multiple tumorigeneses. METHODOLOGY/PRINCIPAL FINDINGS: Semi-quantitative RT-PCR showed that PRDM5 was broadly expressed in human normal tissues, but frequently silenced or downregulated in multiple carcinoma cell lines due to promoter CpG methylation, including 80% (4/5 nasopharyngeal, 44% (8/18 esophageal, 76% (13/17 gastric, 50% (2/4 cervical, and 25% (3/12 hepatocellular carcinoma cell lines, but not in any immortalized normal epithelial cell lines. PRDM5 expression could be restored by 5-aza-2'-deoxycytidine demethylation treatment in silenced cell lines. PRDM5 methylation was frequently detected by methylation-specific PCR (MSP in multiple primary tumors, including 93% (43/46 nasopharyngeal, 58% (25/43 esophageal, 88% (37/42 gastric and 63% (29/46 hepatocellular tumors. PRDM5 was further found a stress-responsive gene, but its response was impaired when the promoter was methylated. Ectopic PRDM5 expression significantly inhibited tumor cell clonogenicity, accompanied by the inhibition of TCF/β-catenin-dependent transcription and downregulation of CDK4, TWIST1 and MDM2 oncogenes, while knocking down of PRDM5 expression lead to increased cell proliferation. ChIP assay showed that PRDM5 bound to its target gene promoters and suppressed their transcription. An inverse correlation between the expression of PRDM5 and activated β-catenin was also observed in cell lines. CONCLUSIONS/SIGNIFICANCE: PRDM5 functions as a tumor suppressor at least partially through antagonizing aberrant WNT/β-catenin signaling and oncogene expression. Frequent epigenetic silencing of PRDM5 is involved in multiple tumorigeneses, which could serve as a tumor biomarker.

  6. FSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Guidance on the scientific requirements for health claims related to functions of the ne rvous system, including psycholog ical functions

    Tetens, Inge

    The European Food Safety Authority (EFSA) asked the Panel on Dietetic Products, Nutrition and Allergies to draft guidance on scientific requirements for health claims related to functions of the nervous system, including psychological functions. This guidance has been drawn from scientific opinions......, and was released for public consultation from 17 October 2011 to 16 December 2011....

  7. Impact of cognitive function and dysarthria on spoken language and perceived speech severity in multiple sclerosis

    Feenaughty, Lynda

    Purpose: The current study sought to investigate the separate effects of dysarthria and cognitive status on global speech timing, speech hesitation, and linguistic complexity characteristics and how these speech behaviors impose on listener impressions for three connected speech tasks presumed to differ in cognitive-linguistic demand for four carefully defined speaker groups; 1) MS with cognitive deficits (MSCI), 2) MS with clinically diagnosed dysarthria and intact cognition (MSDYS), 3) MS without dysarthria or cognitive deficits (MS), and 4) healthy talkers (CON). The relationship between neuropsychological test scores and speech-language production and perceptual variables for speakers with cognitive deficits was also explored. Methods: 48 speakers, including 36 individuals reporting a neurological diagnosis of MS and 12 healthy talkers participated. The three MS groups and control group each contained 12 speakers (8 women and 4 men). Cognitive function was quantified using standard clinical tests of memory, information processing speed, and executive function. A standard z-score of ≤ -1.50 indicated deficits in a given cognitive domain. Three certified speech-language pathologists determined the clinical diagnosis of dysarthria for speakers with MS. Experimental speech tasks of interest included audio-recordings of an oral reading of the Grandfather passage and two spontaneous speech samples in the form of Familiar and Unfamiliar descriptive discourse. Various measures of spoken language were of interest. Suprasegmental acoustic measures included speech and articulatory rate. Linguistic speech hesitation measures included pause frequency (i.e., silent and filled pauses), mean silent pause duration, grammatical appropriateness of pauses, and interjection frequency. For the two discourse samples, three standard measures of language complexity were obtained including subordination index, inter-sentence cohesion adequacy, and lexical diversity. Ten listeners

  8. Right parietal cortex and calculation processing: intraoperative functional mapping of multiplication and addition in patients affected by a brain tumor.

    Della Puppa, Alessandro; De Pellegrin, Serena; d'Avella, Elena; Gioffrè, Giorgio; Munari, Marina; Saladini, Marina; Salillas, Elena; Scienza, Renato; Semenza, Carlo

    2013-11-01

    The role of parietal areas in number processing is well known. The significance of intraoperative functional mapping of these areas has been only partially explored, however, and only a few discordant data are available in the surgical literature with regard to the right parietal lobe. The purpose of this study was to evaluate the clinical impact of simple calculation in cortical electrostimulation of right-handed patients affected by a right parietal brain tumor. Calculation mapping in awake surgery was performed in 3 right-handed patients affected by high-grade gliomas located in the right parietal lobe. Preoperatively, none of the patients presented with calculation deficits. In all 3 cases, after sensorimotor and language mapping, cortical and intraparietal sulcus areas involved in single-digit multiplication and addition calculations were mapped using bipolar electrostimulation. In all patients, different sites of the right parietal cortex, mainly in the inferior lobule, were detected as being specifically related to calculation (multiplication or addition). In 2 patients the intraparietal sulcus was functionally specific for multiplication. No functional sites for language were detected. All sites functional for calculation were spared during tumor resection, which was complete in all cases without postoperative neurological deficits. These findings provide intraoperative data in support of an anatomofunctional organization for multiplication and addition within the right parietal area. Furthermore, the study shows the potential clinical relevance of intraoperative mapping of calculation in patients undergoing surgery in the right parietal area. Further and larger studies are needed to confirm these data and assess whether mapped areas are effectively essential for function.

  9. Multiple Functions of the New Cytokine-Based Antimicrobial Peptide Thymic Stromal Lymphopoietin (TSLP

    Louise Bjerkan

    2016-07-01

    Full Text Available Thymic stromal lymphopoietin (TSLP is a pleiotropic cytokine, hitherto mostly known to be involved in inflammatory responses and immunoregulation. The human tslp gene gives rise to two transcription and translation variants: a long form (lfTSLP that is induced by inflammation, and a short, constitutively-expressed form (sfTSLP, that appears to be downregulated by inflammation. The TSLP forms can be produced by a number of cell types, including epithelial and dendritic cells (DCs. lfTSLP can activate mast cells, DCs, and T cells through binding to the lfTSLP receptor (TSLPR and has a pro-inflammatory function. In contrast, sfTSLP inhibits cytokine secretion of DCs, but the receptor mediating this effect is unknown. Our recent studies have demonstrated that both forms of TSLP display potent antimicrobial activity, exceeding that of many other known antimicrobial peptides (AMPs, with sfTSLP having the strongest effect. The AMP activity is primarily mediated by the C-terminal region of the protein and is localized within a 34-mer peptide (MKK34 that spans the C-terminal α-helical region in TSLP. Fluorescent studies of peptide-treated bacteria, electron microscopy, and liposome leakage models showed that MKK34 exerted membrane-disrupting effects comparable to those of LL-37. Expression of TSLP in skin, oral mucosa, salivary glands, and intestine is part of the defense barrier that aids in the control of both commensal and pathogenic microbes.

  10. Predicting Multiple Functions of Sustainable Flood Retention Basins under Uncertainty via Multi-Instance Multi-Label Learning

    Qinli Yang

    2015-03-01

    Full Text Available The ambiguity of diverse functions of sustainable flood retention basins (SFRBs may lead to conflict and risk in water resources planning and management. How can someone provide an intuitive yet efficient strategy to uncover and distinguish the multiple potential functions of SFRBs under uncertainty? In this study, by exploiting both input and output uncertainties of SFRBs, the authors developed a new data-driven framework to automatically predict the multiple functions of SFRBs by using multi-instance multi-label (MIML learning. A total of 372 sustainable flood retention basins, characterized by 40 variables associated with confidence levels, were surveyed in Scotland, UK. A Gaussian model with Monte Carlo sampling was used to capture the variability of variables (i.e., input uncertainty, and the MIML-support vector machine (SVM algorithm was subsequently applied to predict the potential functions of SFRBs that have not yet been assessed, allowing for one basin belonging to different types (i.e., output uncertainty. Experiments demonstrated that the proposed approach enables effective automatic prediction of the potential functions of SFRBs (e.g., accuracy >93%. The findings suggest that the functional uncertainty of SFRBs under investigation can be better assessed in a more comprehensive and cost-effective way, and the proposed data-driven approach provides a promising method of doing so for water resources management.

  11. Multiple diabetic complications, as well as impaired physical and mental function, are associated with declining balance function in older persons with diabetes mellitus

    Hong XF

    2017-01-01

    Full Text Available Xiufang Hong,1,2 Xujiao Chen,2 Jiaojiao Chu,2 Shanshan Shen,2 Qichen Chai,2 Gaobo Lou,2 Lingyan Chen2 1Zhejiang Chinese Medical University, 2Department of Geriatrics, Zhejiang Hospital, Hangzhou, Zhejiang, People’s Republic of China Objective: To investigate whether there is a difference in balance function between older persons with and without diabetes mellitus (DM, and to identify whether mediating factors, such as diabetic complications, Instrumental Activities of Daily Living (IADL score, Mini-Mental State Examination (MMSE score, as well as hemoglobin A1c (HbA1c, fasting plasma glucose (FPG, serum total cholesterol (TC, triglycerides (TG, and low-density lipoprotein (LDL, are associated with balance function in older persons with DM.Methods: In this cross-sectional study, a total of 208 older persons were divided into a DM group (n=80 and a control group who did not have DM (n=128. Balance function was evaluated with the Tinetti performance-oriented mobility assessment (POMA, which includes balance and gait subscales. Activities of daily living (ADL, IADL, and the MMSE were also measured. Fall incidents in last 12 months, the use of walking aids, fear of falling, comorbidities, and polypharmacy were recorded. Diabetic complications were recorded, and HbA1c, FPG, TC, TG, and LDL were measured in the patients of the DM group.Results: Fall incidents in last 12 months were higher in the DM group than in the control group (P<0.01. POMA score as well as ADL and IADL scores were lower in the diabetic group than the control group (P<0.05. Within the diabetic group, the POMA score was positively related to the ADL score (odds ratio [OR], 11.7; 95% confidence interval [CI], 3.076–44.497; P<0.01, IADL score (OR, 16.286; 95% CI, 4.793–55.333; P<0.01, and MMSE score (OR, 10.524; 95% CI, 2.764–40.074; P<0.01, but was negatively related to age (OR, 7.707; 95% CI, 2.035–29.185; P<0.01 and diabetic complication (OR, 6.667; 95% CI, 2.279–19

  12. Use of multiple functional traits of protozoa for bioassessment of marine pollution.

    Zhong, Xiaoxiao; Xu, Guangjian; Xu, Henglong

    2017-06-30

    Ecological parameters based on multiply functional traits have many advantages for monitoring programs by reducing "signal to noise" ratios of observed species data. To identify potential indicators for bioassessment of marine pollution in function space, the functional patterns of protozoan communities and relationships with environmental changes were studied in coastal waters of the Yellow Sea during a 1-year period. The results showed that: (1) the spatial variability in functional trait distributions of the protozoa was significantly associated with changes in environmental variables, especially chemical oxygen demand (COD) and nutrients on spatial scale; (2) the functional traits, especially food resources and feeding type, were significantly correlated with COD and nutrients; and (3) the functional diversity indices were generally related to nutrients or COD. Based on the results, we suggest that the functional traits and diversity indices of protozoan communities may be used as more effective indicators for bioassessment of marine pollution. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Monitoring the Effect of Facilitation Physiotherapy in Multiple Sclerosis using Functional Magnetic Resonance Imaging

    Procházková, M.; Řasová, K.; Tintěra, J.; Martinková, Patrícia; Procházka, A.

    2014-01-01

    Roč. 20, č. 7 (2014), s. 1003-1004 ISSN 1352-4585. [RIMS 2014. Annual Conference on Rehabilitation in Multiple Sclerosis /19./. 06.06.2014-07.06.2014, Brighton] Institutional support: RVO:67985807 Subject RIV: BB - Applied Statistics, Operational Research

  14. Visual impairments in people with severe and profound multiple disabilities: An inventory of visual functioning

    van den Broek, E.G.C.; Janssen, C.G.C.; van Ramshorst, T.; Deen, L.

    2006-01-01

    Background: The prevalence of visual impairments in people with severe and profound multiple disabilities (SPMD) is the subject of considerable debate and is difficult to assess. Methods: In a typical Dutch care organization, all clients with SPMD (n = 76) participated in the study and specific

  15. Intellectual Enrichment Is Linked to Cerebral Efficiency in Multiple Sclerosis: Functional Magnetic Resonance Imaging Evidence for Cognitive Reserve

    Sumowski, James F.; Wylie, Glenn R.; DeLuca, John; Chiaravalloti, Nancy

    2010-01-01

    The cognitive reserve hypothesis helps to explain the incomplete relationship between brain disease and cognitive status in people with neurologic diseases, including Alzheimer's; disease and multiple sclerosis. Lifetime intellectual enrichment (estimated with education or vocabulary knowledge) lessens the negative impact of brain disease on…

  16. Existence, Multiplicity, and Stability of Positive Solutions of a Predator-Prey Model with Dinosaur Functional Response

    Xiaozhou Feng

    2017-01-01

    Full Text Available We investigate the property of positive solutions of a predator-prey model with Dinosaur functional response under Dirichlet boundary conditions. Firstly, using the comparison principle and fixed point index theory, the sufficient conditions and necessary conditions on coexistence of positive solutions of a predator-prey model with Dinosaur functional response are established. Secondly, by virtue of bifurcation theory, perturbation theory of eigenvalues, and the fixed point index theory, we establish the bifurcation of positive solutions of the model and obtain the stability and multiplicity of the positive solution under certain conditions. Furthermore, the local uniqueness result is studied when b and d are small enough. Finally, we investigate the multiplicity, uniqueness, and stability of positive solutions when k>0 is sufficiently large.

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

    Zhan Gang

    2016-01-01

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

  18. Including screening in van der Waals corrected density functional theory calculations: The case of atoms and small molecules physisorbed on graphene

    Silvestrelli, Pier Luigi; Ambrosetti, Alberto [Dipartimento di Fisica e Astronomia, Università di Padova, via Marzolo 8, I–35131 Padova, Italy and DEMOCRITOS National Simulation Center of the Italian Istituto Officina dei Materiali (IOM) of the Italian National Research Council (CNR), Trieste (Italy)

    2014-03-28

    The Density Functional Theory (DFT)/van der Waals-Quantum Harmonic Oscillator-Wannier function (vdW-QHO-WF) method, recently developed to include the vdW interactions in approximated DFT by combining the quantum harmonic oscillator model with the maximally localized Wannier function technique, is applied to the cases of atoms and small molecules (X=Ar, CO, H{sub 2}, H{sub 2}O) weakly interacting with benzene and with the ideal planar graphene surface. Comparison is also presented with the results obtained by other DFT vdW-corrected schemes, including PBE+D, vdW-DF, vdW-DF2, rVV10, and by the simpler Local Density Approximation (LDA) and semilocal generalized gradient approximation approaches. While for the X-benzene systems all the considered vdW-corrected schemes perform reasonably well, it turns out that an accurate description of the X-graphene interaction requires a proper treatment of many-body contributions and of short-range screening effects, as demonstrated by adopting an improved version of the DFT/vdW-QHO-WF method. We also comment on the widespread attitude of relying on LDA to get a rough description of weakly interacting systems.

  19. Continuity in Λ-variation of functions of several variables and convergence of multiple Fourier series

    Bakhvalov, A N

    2002-01-01

    The behaviour of rectangular partial sums of the Fourier series of functions of several variables having bounded Λ-variation is considered. It is proved that if a continuous function is also continuous in harmonic variation, then its Fourier series uniformly converges in the sense of Pringsheim. On the other hand, it is demonstrated that in dimensions greater than 2 there always exists a continuous function of bounded harmonic variation with Fourier series divergent over cubes at the origin

  20. Effect of halloysite nanotubes on the structure and function of important multiple blood components

    Wu, Keke; Feng, Ru; Jiao, Yanpeng; Zhou, Changren

    2017-01-01

    Many researchers have investigated the application of halloysite nanotubes (HNTs) in biomedicine, because of their special nanoscale hollow tubular structure. Although the cytocompatibility of HNTs has been studied, their blood compatibility has not been systematically investigated. In this work, the effect of HNTs on the structure and function of different blood components has been studied, including the morphology and hemolysis of red blood cells (RBCs). Based on scanning electron microscopy (SEM) observations, optical density test and flow cytometry analysis, we found that HNTs can affect the morphology and membrane integrity of RBCs in phosphate buffered saline (PBS) in a content-dependent way. In particular, based on UV–vis absorption spectra, fluorescence spectra and circular dichroism (CD) spectra, HNTs can alter the secondary structure and conformation of human fibrinogen and γ-globulins. In addition, the detection of biomarker molecules C3a and C5a in plasma suggests that HNTs can trigger complement activation. In the blood clotting assay, HNTs were found to significantly prolong the activated partial thromboplastin time (APTT), shorten the prothrombin time (PT) of platelet-poor plasma (PPP), and change the thromboelastography (TEG) parameters of whole blood coagulation. Furthermore, confocal laser scanning microscopy and flow cytometry analysis were used to test intracellular uptake by macrophages, and the cellular uptake of HNTs in the RAW 264.7 was found to be content-dependent, but not time-dependent. These findings provide insight for the potential use of HNTs as biofriendly nanocontainers for biomaterials in vivo. - Highlights: • Comprehensive study of blood compatibility halloysite nanotubes (HNTs) is processed. • We examine and analyze the effect of HNTs on conformation changes of three plasma proteins. • We prove HNTs can affect blood components at high content but little at low content. • We prove HNTs could be used as biomaterials

  1. Effect of halloysite nanotubes on the structure and function of important multiple blood components.

    Wu, Keke; Feng, Ru; Jiao, Yanpeng; Zhou, Changren

    2017-06-01

    Many researchers have investigated the application of halloysite nanotubes (HNTs) in biomedicine, because of their special nanoscale hollow tubular structure. Although the cytocompatibility of HNTs has been studied, their blood compatibility has not been systematically investigated. In this work, the effect of HNTs on the structure and function of different blood components has been studied, including the morphology and hemolysis of red blood cells (RBCs). Based on scanning electron microscopy (SEM) observations, optical density test and flow cytometry analysis, we found that HNTs can affect the morphology and membrane integrity of RBCs in phosphate buffered saline (PBS) in a content-dependent way. In particular, based on UV-vis absorption spectra, fluorescence spectra and circular dichroism (CD) spectra, HNTs can alter the secondary structure and conformation of human fibrinogen and γ-globulins. In addition, the detection of biomarker molecules C3a and C5a in plasma suggests that HNTs can trigger complement activation. In the blood clotting assay, HNTs were found to significantly prolong the activated partial thromboplastin time (APTT), shorten the prothrombin time (PT) of platelet-poor plasma (PPP), and change the thromboelastography (TEG) parameters of whole blood coagulation. Furthermore, confocal laser scanning microscopy and flow cytometry analysis were used to test intracellular uptake by macrophages, and the cellular uptake of HNTs in the RAW 264.7 was found to be content-dependent, but not time-dependent. These findings provide insight for the potential use of HNTs as biofriendly nanocontainers for biomaterials in vivo. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Effect of halloysite nanotubes on the structure and function of important multiple blood components

    Wu, Keke; Feng, Ru; Jiao, Yanpeng, E-mail: tjiaoyp@jnu.edu.cn; Zhou, Changren

    2017-06-01

    Many researchers have investigated the application of halloysite nanotubes (HNTs) in biomedicine, because of their special nanoscale hollow tubular structure. Although the cytocompatibility of HNTs has been studied, their blood compatibility has not been systematically investigated. In this work, the effect of HNTs on the structure and function of different blood components has been studied, including the morphology and hemolysis of red blood cells (RBCs). Based on scanning electron microscopy (SEM) observations, optical density test and flow cytometry analysis, we found that HNTs can affect the morphology and membrane integrity of RBCs in phosphate buffered saline (PBS) in a content-dependent way. In particular, based on UV–vis absorption spectra, fluorescence spectra and circular dichroism (CD) spectra, HNTs can alter the secondary structure and conformation of human fibrinogen and γ-globulins. In addition, the detection of biomarker molecules C3a and C5a in plasma suggests that HNTs can trigger complement activation. In the blood clotting assay, HNTs were found to significantly prolong the activated partial thromboplastin time (APTT), shorten the prothrombin time (PT) of platelet-poor plasma (PPP), and change the thromboelastography (TEG) parameters of whole blood coagulation. Furthermore, confocal laser scanning microscopy and flow cytometry analysis were used to test intracellular uptake by macrophages, and the cellular uptake of HNTs in the RAW 264.7 was found to be content-dependent, but not time-dependent. These findings provide insight for the potential use of HNTs as biofriendly nanocontainers for biomaterials in vivo. - Highlights: • Comprehensive study of blood compatibility halloysite nanotubes (HNTs) is processed. • We examine and analyze the effect of HNTs on conformation changes of three plasma proteins. • We prove HNTs can affect blood components at high content but little at low content. • We prove HNTs could be used as biomaterials

  3. A Meta-analysis of Multiple Myeloma Risk Regions in African and European Ancestry Populations Identifies Putatively Functional Loci.

    Rand, Kristin A; Song, Chi; Dean, Eric; Serie, Daniel J; Curtin, Karen; Sheng, Xin; Hu, Donglei; Huff, Carol Ann; Bernal-Mizrachi, Leon; Tomasson, Michael H; Ailawadhi, Sikander; Singhal, Seema; Pawlish, Karen; Peters, Edward S; Bock, Cathryn H; Stram, Alex; Van Den Berg, David J; Edlund, Christopher K; Conti, David V; Zimmerman, Todd; Hwang, Amie E; Huntsman, Scott; Graff, John; Nooka, Ajay; Kong, Yinfei; Pregja, Silvana L; Berndt, Sonja I; Blot, William J; Carpten, John; Casey, Graham; Chu, Lisa; Diver, W Ryan; Stevens, Victoria L; Lieber, Michael R; Goodman, Phyllis J; Hennis, Anselm J M; Hsing, Ann W; Mehta, Jayesh; Kittles, Rick A; Kolb, Suzanne; Klein, Eric A; Leske, Cristina; Murphy, Adam B; Nemesure, Barbara; Neslund-Dudas, Christine; Strom, Sara S; Vij, Ravi; Rybicki, Benjamin A; Stanford, Janet L; Signorello, Lisa B; Witte, John S; Ambrosone, Christine B; Bhatti, Parveen; John, Esther M; Bernstein, Leslie; Zheng, Wei; Olshan, Andrew F; Hu, Jennifer J; Ziegler, Regina G; Nyante, Sarah J; Bandera, Elisa V; Birmann, Brenda M; Ingles, Sue A; Press, Michael F; Atanackovic, Djordje; Glenn, Martha J; Cannon-Albright, Lisa A; Jones, Brandt; Tricot, Guido; Martin, Thomas G; Kumar, Shaji K; Wolf, Jeffrey L; Deming Halverson, Sandra L; Rothman, Nathaniel; Brooks-Wilson, Angela R; Rajkumar, S Vincent; Kolonel, Laurence N; Chanock, Stephen J; Slager, Susan L; Severson, Richard K; Janakiraman, Nalini; Terebelo, Howard R; Brown, Elizabeth E; De Roos, Anneclaire J; Mohrbacher, Ann F; Colditz, Graham A; Giles, Graham G; Spinelli, John J; Chiu, Brian C; Munshi, Nikhil C; Anderson, Kenneth C; Levy, Joan; Zonder, Jeffrey A; Orlowski, Robert Z; Lonial, Sagar; Camp, Nicola J; Vachon, Celine M; Ziv, Elad; Stram, Daniel O; Hazelett, Dennis J; Haiman, Christopher A; Cozen, Wendy

    2016-12-01

    Genome-wide association studies (GWAS) in European populations have identified genetic risk variants associated with multiple myeloma. We performed association testing of common variation in eight regions in 1,318 patients with multiple myeloma and 1,480 controls of European ancestry and 1,305 patients with multiple myeloma and 7,078 controls of African ancestry and conducted a meta-analysis to localize the signals, with epigenetic annotation used to predict functionality. We found that variants in 7p15.3, 17p11.2, 22q13.1 were statistically significantly (P ancestry and persons of European ancestry, and the variant in 3p22.1 was associated in European ancestry only. In a combined African ancestry-European ancestry meta-analysis, variation in five regions (2p23.3, 3p22.1, 7p15.3, 17p11.2, 22q13.1) was statistically significantly associated with multiple myeloma risk. In 3p22.1, the correlated variants clustered within the gene body of ULK4 Correlated variants in 7p15.3 clustered around an enhancer at the 3' end of the CDCA7L transcription termination site. A missense variant at 17p11.2 (rs34562254, Pro251Leu, OR, 1.32; P = 2.93 × 10 -7 ) in TNFRSF13B encodes a lymphocyte-specific protein in the TNF receptor family that interacts with the NF-κB pathway. SNPs correlated with the index signal in 22q13.1 cluster around the promoter and enhancer regions of CBX7 CONCLUSIONS: We found that reported multiple myeloma susceptibility regions contain risk variants important across populations, supporting the use of multiple racial/ethnic groups with different underlying genetic architecture to enhance the localization and identification of putatively functional alleles. A subset of reported risk loci for multiple myeloma has consistent effects across populations and is likely to be functional. Cancer Epidemiol Biomarkers Prev; 25(12); 1609-18. ©2016 AACR. ©2016 American Association for Cancer Research.

  4. A Generalized Logistic Regression Procedure to Detect Differential Item Functioning among Multiple Groups

    Magis, David; Raiche, Gilles; Beland, Sebastien; Gerard, Paul

    2011-01-01

    We present an extension of the logistic regression procedure to identify dichotomous differential item functioning (DIF) in the presence of more than two groups of respondents. Starting from the usual framework of a single focal group, we propose a general approach to estimate the item response functions in each group and to test for the presence…

  5. Meta-analyses of genome-wide association studies identify multiple loci associated with pulmonary function

    D.B. Hancock (Dana); M. Eijgelsheim (Mark); J.B. Wilk (Jemma); S.A. Gharib (Sina); L.R. Loehr (Laura); K. Marciante (Kristin); N. Franceschini (Nora); Y.M.T.A. van Durme; T.H. Chen; R.G. Barr (Graham); M.B. Schabath (Matthew); D.J. Couper (David); G.G. Brusselle (Guy); B.M. Psaty (Bruce); P. Tikka-Kleemola (Päivi); J.I. Rotter (Jerome); A.G. Uitterlinden (André); A. Hofman (Albert); N.M. Punjabi (Naresh); F. Rivadeneira Ramirez (Fernando); A.C. Morrison (Alanna); P.L. Enright (Paul); K.E. North (Kari); S.R. Heckbert (Susan); T. Lumley (Thomas); B.H.Ch. Stricker (Bruno); G.T. O'Connor (George); S.J. London (Stephanie)

    2010-01-01

    textabstractSpirometric measures of lung function are heritable traits that reflect respiratory health and predict morbidity and mortality. We meta-analyzed genome-wide association studies for two clinically important lung-function measures: forced expiratory volume in the first second (FEV1) and

  6. [The influence of high-tone power therapy on the functional status of patients with multiple sclerosis].

    Kubsik, Anna; Klimkiewicz, Paulina; Klimkiewicz, Robert; Jankowska, Katarzyna; Jankowska, Agnieszka; Woldańska-Okońska, Marta

    2014-07-01

    Multiple sclerosis is a chronic, inflammatory, demyelinating disease of the central nervous system, which is characterized by diverse symptomatology. Most often affects people at a young age gradually leading to their disability. Looking for new therapies to alleviate neurological deficits caused by the disease. One of the alternative methods of therapy is high - tone power therapy. The article is a comparison of high-tone power therapy and kinesis in improving patients with multiple sclerosis. The aim of this study was to evaluate the effectiveness of high-tone power therapy and exercises in kinesis on the functional status of patients with multiple sclerosis. The study involved 20 patients with multiple sclerosis, both sexes, treated at the Department of Rehabilitation and Physical Medicine in Lodz. Patients were randomly divided into two groups studied. In group high-tone power therapy applied for 60 minutes, while in group II were used exercises for kinesis. Treatment time for both groups of patients was 15 days. To assess the functional status scale was used: Expanded Disability Status Scale of Kurtzke (EDSS), as well as by Barthel ADL Index. Assessment of quality of life were made using MSQOL Questionnaire-54. For the evaluation of gait and balance using Tinetti scale, and pain VAS rated, and Laitinen. Changes in muscle tone was assessed on the basis of the Ashworth scale. Both group I and II improved on scales conducted before and after therapy. In group I, in which the applied high-tone power therapy, reported statistically significant results in 9 out of 10 tested parameters, while in group II, which was used in the exercises in kinesis an improvement in 6 out of 10 tested parameters. Correlating the results of both the test groups in relation to each other did not show statistically significant differences. High-Tone Power Therapy beneficial effect on the functional status of patients with multiple sclerosis. Obtaining results in terms of number of tested

  7. IMAGING WITH MULTIMODAL ADAPTIVE-OPTICS OPTICAL COHERENCE TOMOGRAPHY IN MULTIPLE EVANESCENT WHITE DOT SYNDROME: THE STRUCTURE AND FUNCTIONAL RELATIONSHIP.

    Labriola, Leanne T; Legarreta, Andrew D; Legarreta, John E; Nadler, Zach; Gallagher, Denise; Hammer, Daniel X; Ferguson, R Daniel; Iftimia, Nicusor; Wollstein, Gadi; Schuman, Joel S

    2016-01-01

    To elucidate the location of pathological changes in multiple evanescent white dot syndrome (MEWDS) with the use of multimodal adaptive optics (AO) imaging. A 5-year observational case study of a 24-year-old female with recurrent MEWDS. Full examination included history, Snellen chart visual acuity, pupil assessment, intraocular pressures, slit lamp evaluation, dilated fundoscopic exam, imaging with Fourier-domain optical coherence tomography (FD-OCT), blue-light fundus autofluorescence (FAF), fundus photography, fluorescein angiography, and adaptive-optics optical coherence tomography. Three distinct acute episodes of MEWDS occurred during the period of follow-up. Fourier-domain optical coherence tomography and adaptive-optics imaging showed disturbance in the photoreceptor outer segments (PR OS) in the posterior pole with each flare. The degree of disturbance at the photoreceptor level corresponded to size and extent of the visual field changes. All findings were transient with delineation of the photoreceptor recovery from the outer edges of the lesion inward. Hyperautofluorescence was seen during acute flares. Increase in choroidal thickness did occur with each active flare but resolved. Although changes in the choroid and RPE can be observed in MEWDS, Fourier-domain optical coherence tomography, and multimodal adaptive optics imaging localized the visually significant changes seen in this disease at the level of the photoreceptors. These transient retinal changes specifically occur at the level of the inner segment ellipsoid and OS/RPE line. En face optical coherence tomography imaging provides a detailed, yet noninvasive method for following the convalescence of MEWDS and provides insight into the structural and functional relationship of this transient inflammatory retinal disease.

  8. GESTATIONAL ATRAZINE EXPOSURE IN THE RAT: EFFECTS ON MAMMARY GLAND DEVELOPMENT AND FUNCTION IN MULTIPLE GENERATIONS

    The chlorotriazine herbicides currently represent the most heavily used of all agricultural pesticides, with atrazine being the most common of these chemicals. Rodent toxicology studies indicate that atrazine can disrupt endocrine function and among its effects is an increased in...

  9. Analyzing the multiple functions of stereotypical behavior for students with autism: implications for assessment and treatment.

    Kennedy, C H; Meyer, K A; Knowles, T; Shukla, S

    2000-01-01

    We studied behavioral functions associated with stereotypical responses for students with autism. In Study 1, analogue functional analyses (attention, demand, no-attention, and recreation conditions) were conducted for 5 students. Results suggested that stereotypy was multiply determined or occurred across all assessment conditions. For 2 students, stereotypy was associated with positive and negative reinforcement and the absence of environmental stimulation. For 2 other students, stereotypy occurred at high levels across all experimental conditions. For the 5th student, stereotypy was associated with negative reinforcement and the absence of environmental stimulation. In Study 2, the stereotypy of 1 student was further analyzed on a function-by-function basis. Within a concurrent-schedules procedure, alternative responses were taught to the student using functional communication training. The results of Study 2 showed that similar topographies of stereotypy, based on qualitatively different reinforcers, were reduced only when differential reinforcement contingencies for alternative forms of communication were implemented for specific response-reinforcer relations. Our results suggest that the causes of stereotypy for students with autism are complex and that the presumed association between response topography and behavioral function may be less important than previously realized.

  10. Understanding large multiprotein complexes: applying a multiple allosteric networks model to explain the function of the Mediator transcription complex.

    Lewis, Brian A

    2010-01-15

    The regulation of transcription and of many other cellular processes involves large multi-subunit protein complexes. In the context of transcription, it is known that these complexes serve as regulatory platforms that connect activator DNA-binding proteins to a target promoter. However, there is still a lack of understanding regarding the function of these complexes. Why do multi-subunit complexes exist? What is the molecular basis of the function of their constituent subunits, and how are these subunits organized within a complex? What is the reason for physical connections between certain subunits and not others? In this article, I address these issues through a model of network allostery and its application to the eukaryotic RNA polymerase II Mediator transcription complex. The multiple allosteric networks model (MANM) suggests that protein complexes such as Mediator exist not only as physical but also as functional networks of interconnected proteins through which information is transferred from subunit to subunit by the propagation of an allosteric state known as conformational spread. Additionally, there are multiple distinct sub-networks within the Mediator complex that can be defined by their connections to different subunits; these sub-networks have discrete functions that are activated when specific subunits interact with other activator proteins.

  11. Uncertainty in Measurement: A Review of Monte Carlo Simulation Using Microsoft Excel for the Calculation of Uncertainties Through Functional Relationships, Including Uncertainties in Empirically Derived Constants

    Farrance, Ian; Frenkel, Robert

    2014-01-01

    The Guide to the Expression of Uncertainty in Measurement (usually referred to as the GUM) provides the basic framework for evaluating uncertainty in measurement. The GUM however does not always provide clearly identifiable procedures suitable for medical laboratory applications, particularly when internal quality control (IQC) is used to derive most of the uncertainty estimates. The GUM modelling approach requires advanced mathematical skills for many of its procedures, but Monte Carlo simulation (MCS) can be used as an alternative for many medical laboratory applications. In particular, calculations for determining how uncertainties in the input quantities to a functional relationship propagate through to the output can be accomplished using a readily available spreadsheet such as Microsoft Excel. The MCS procedure uses algorithmically generated pseudo-random numbers which are then forced to follow a prescribed probability distribution. When IQC data provide the uncertainty estimates the normal (Gaussian) distribution is generally considered appropriate, but MCS is by no means restricted to this particular case. With input variations simulated by random numbers, the functional relationship then provides the corresponding variations in the output in a manner which also provides its probability distribution. The MCS procedure thus provides output uncertainty estimates without the need for the differential equations associated with GUM modelling. The aim of this article is to demonstrate the ease with which Microsoft Excel (or a similar spreadsheet) can be used to provide an uncertainty estimate for measurands derived through a functional relationship. In addition, we also consider the relatively common situation where an empirically derived formula includes one or more ‘constants’, each of which has an empirically derived numerical value. Such empirically derived ‘constants’ must also have associated uncertainties which propagate through the functional

  12. Uncertainty in measurement: a review of monte carlo simulation using microsoft excel for the calculation of uncertainties through functional relationships, including uncertainties in empirically derived constants.

    Farrance, Ian; Frenkel, Robert

    2014-02-01

    The Guide to the Expression of Uncertainty in Measurement (usually referred to as the GUM) provides the basic framework for evaluating uncertainty in measurement. The GUM however does not always provide clearly identifiable procedures suitable for medical laboratory applications, particularly when internal quality control (IQC) is used to derive most of the uncertainty estimates. The GUM modelling approach requires advanced mathematical skills for many of its procedures, but Monte Carlo simulation (MCS) can be used as an alternative for many medical laboratory applications. In particular, calculations for determining how uncertainties in the input quantities to a functional relationship propagate through to the output can be accomplished using a readily available spreadsheet such as Microsoft Excel. The MCS procedure uses algorithmically generated pseudo-random numbers which are then forced to follow a prescribed probability distribution. When IQC data provide the uncertainty estimates the normal (Gaussian) distribution is generally considered appropriate, but MCS is by no means restricted to this particular case. With input variations simulated by random numbers, the functional relationship then provides the corresponding variations in the output in a manner which also provides its probability distribution. The MCS procedure thus provides output uncertainty estimates without the need for the differential equations associated with GUM modelling. The aim of this article is to demonstrate the ease with which Microsoft Excel (or a similar spreadsheet) can be used to provide an uncertainty estimate for measurands derived through a functional relationship. In addition, we also consider the relatively common situation where an empirically derived formula includes one or more 'constants', each of which has an empirically derived numerical value. Such empirically derived 'constants' must also have associated uncertainties which propagate through the functional relationship

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

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

    2013-05-01

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

  14. The application of multiple biophysical cues to engineer functional neocartilage for treatment of osteoarthritis. Part I: cellular response.

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

    2015-02-01

    Osteoarthritis (OA) is a complex disease of the joint for which current treatments are unsatisfactory, thus motivating development of tissue engineering (TE)-based therapies. To date, TE strategies have had some success, developing replacement tissue constructs with biochemical properties approaching that of native cartilage. However, poor biomechanical properties and limited postimplantation integration with surrounding tissue are major shortcomings that need to be addressed. Functional tissue engineering strategies that apply physiologically relevant biophysical cues provide a platform to improve TE constructs before implantation. In the previous decade, new experimental and theoretical findings in cartilage biomechanics and electromechanics have emerged, resulting in an increased understanding of the complex interplay of multiple biophysical cues in the extracellular matrix of the tissue. The effect of biophysical stimulation on cartilage, and the resulting chondrocyte-mediated biosynthesis, remodeling, degradation, and repair, has, therefore, been extensively explored by the TE community. This article compares and contrasts the cellular response of chondrocytes to multiple biophysical stimuli, and may be read in conjunction with its companion paper that compares and contrasts the subsequent intracellular signal transduction cascades. Mechanical, magnetic, and electrical stimuli promote proliferation, differentiation, and maturation of chondrocytes within established dose parameters or "biological windows." This knowledge will provide a framework for ongoing studies incorporating multiple biophysical cues in TE functional neocartilage for treatment of OA.

  15. Dimensional feature weighting utilizing multiple kernel learning for single-channel talker location discrimination using the acoustic transfer function.

    Takashima, Ryoichi; Takiguchi, Tetsuya; Ariki, Yasuo

    2013-02-01

    This paper presents a method for discriminating the location of the sound source (talker) using only a single microphone. In a previous work, the single-channel approach for discriminating the location of the sound source was discussed, where the acoustic transfer function from a user's position is estimated by using a hidden Markov model of clean speech in the cepstral domain. In this paper, each cepstral dimension of the acoustic transfer function is newly weighted, in order to obtain the cepstral dimensions having information that is useful for classifying the user's position. Then, this paper proposes a feature-weighting method for the cepstral parameter using multiple kernel learning, defining the base kernels for each cepstral dimension of the acoustic transfer function. The user's position is trained and classified by support vector machine. The effectiveness of this method has been confirmed by sound source (talker) localization experiments performed in different room environments.

  16. Motor programme activating therapy influences adaptive brain functions in multiple sclerosis: clinical and MRI study.

    Rasova, Kamila; Prochazkova, Marie; Tintera, Jaroslav; Ibrahim, Ibrahim; Zimova, Denisa; Stetkarova, Ivana

    2015-03-01

    There is still little scientific evidence for the efficacy of neurofacilitation approaches and their possible influence on brain plasticity and adaptability. In this study, the outcome of a new kind of neurofacilitation approach, motor programme activating therapy (MPAT), was evaluated on the basis of a set of clinical functions and with MRI. Eighteen patients were examined four times with standardized clinical tests and diffusion tensor imaging to monitor changes without therapy, immediately after therapy and 1 month after therapy. Moreover, the strength of effective connectivity was analysed before and after therapy. Patients underwent a 1-h session of MPAT twice a week for 2 months. The data were analysed by nonparametric tests of association and were subsequently statistically evaluated. The therapy led to significant improvement in clinical functions, significant increment of fractional anisotropy and significant decrement of mean diffusivity, and decrement of effective connectivity at supplementary motor areas was observed immediately after the therapy. Changes in clinical functions and diffusion tensor images persisted 1 month after completing the programme. No statistically significant changes in clinical functions and no differences in MRI-diffusion tensor images were observed without physiotherapy. Positive immediate and long-term effects of MPAT on clinical and brain functions, as well as brain microstructure, were confirmed.

  17. Minimising farm crop protection pressure supported by the multiple functionalities of the DISCUSS indicator set.

    Wustenberghs, Hilde; Fevery, Davina; Lauwers, Ludwig; Marchand, Fleur; Spanoghe, Pieter

    2018-03-15

    Sustainable crop protection (SCP) has many facets. Farmers may therefore perceive transition to SCP as very complex. The Dual Indicator Set for Crop Protection Sustainability (DISCUSS) can handle this complexity. To provide targeted support throughout the transition to SCP, complexity capture must be synchronised with the time course of on-farm decision-making. Tool use must be tuned to farmer awareness and appropriate level of data in consecutive stages. This paper thus explores the potential functionalities of DISCUSS in relation to both complexity and time. Results from apple and potato crop protection show three potential functions: DISCUSS can be used as (1) a simulation tool for communication and decision support, (2) an assessment and monitoring tool, and (3) a discussion support tool for farmer groups. Analysis of these functionalities using a framework for guiding on-farm sustainability assessment and strategic decision-making shows how each functionality can support the consecutive steps of transition to SCP, i.e. using the right tool functionality at the right time. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. The Green Function cellular method and its relation to multiple scattering theory

    Butler, W.H.; Zhang, X.G.; Gonis, A.

    1992-01-01

    This paper investigates techniques for solving the wave equation which are based on the idea of obtaining exact local solutions within each potential cell, which are then joined to form a global solution. The authors derive full potential multiple scattering theory (MST) from the Lippmann-Schwinger equation and show that it as well as a closely related cellular method are techniques of this type. This cellular method appears to have all of the advantages of MST and the added advantage of having a secular matrix with only nearest neighbor interactions. Since this cellular method is easily linearized one can rigorously reduce electronic structure calculation to the problem of solving a nearest neighbor tight-binding problem

  19. Novel tumor suppressor function of glucocorticoid-induced TNF receptor GITR in multiple myeloma.

    Yang Liu

    Full Text Available Glucocorticoid-induced TNF receptor (GITR plays a crucial role in modulating immune response and inflammation, however the role of GITR in human cancers is poorly understood. In this study, we demonstrated that GITR is inactivated during tumor progression in Multiple Myeloma (MM through promoter CpG island methylation, mediating gene silencing in primary MM plasma cells and MM cell lines. Restoration of GITR expression in GITR deficient MM cells led to inhibition of MM proliferation in vitro and in vivo and induction of apoptosis. These findings were supported by the presence of induction of p21 and PUMA, two direct downstream targets of p53, together with modulation of NF-κB in GITR-overexpressing MM cells. Moreover, the unbalanced expression of GITR in clonal plasma cells correlated with MM disease progression, poor prognosis and survival. These findings provide novel insights into the pivotal role of GITR in MM pathogenesis and disease progression.

  20. Vocal fold motion impairment in patients with multiple system atrophy: evaluation of its relationship with swallowing function.

    Higo, R; Tayama, N; Watanabe, T; Nitou, T; Takeuchi, S

    2003-07-01

    Vocal fold motion impairment (VFMI), especially vocal fold abductor paralysis, is frequently seen in multiple system atrophy (MSA). Since the regulation system of laryngeal function is closely related to swallowing function, swallowing function is considered to be more involved in MSA patients with VFMI than in patients that do not have VFMI. However, the relationship between dysphagia and VFMI in MSA patients has not been systematically explored. To elucidate the relationship between VFMI and dysphagia in MSA. We evaluated swallowing function of 36 MSA patients with and without VFMI, by videofluoroscopy, and investigated the relationship between VFMI and pharyngeal swallowing function. VFMI was found in 17 patients (47.2%). Patients with VFMI had advanced severity of the disease. Although there was a tendency for bolus stasis at the pyriform sinus and the upper oesophageal sphincter opening to be more involved in patients with VFMI, statistical analysis did not show significant differences in swallowing function of MSA patients between with and without VFMI. In contrast, patients who underwent a tracheotomy ultimately required tube feeding or a laryngectomy. Appearance of VFMI is a sign of disease progression but does not necessary mean patients should change their way of taking nutrition. However, MSA patients who need a tracheotomy might have advanced to a high-risk group for dysphagia. Appropriate evaluation and treatment for VFMI and dysphagia are required to maintain patients' quality of life in MSA.

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

    Yoko Kimata-Ariga

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

  2. Multiple populations within globular clusters in Early-type galaxies Exploring their effect on stellar initial mass function estimates

    Chantereau, W.; Usher, C.; Bastian, N.

    2018-05-01

    It is now well-established that most (if not all) ancient globular clusters host multiple populations, that are characterised by distinct chemical features such as helium abundance variations along with N-C and Na-O anti-correlations, at fixed [Fe/H]. These very distinct chemical features are similar to what is found in the centres of the massive early-type galaxies and may influence measurements of the global properties of the galaxies. Additionally, recent results have suggested that M/L variations found in the centres of massive early-type galaxies might be due to a bottom-heavy stellar initial mass function. We present an analysis of the effects of globular cluster-like multiple populations on the integrated properties of early-type galaxies. In particular, we focus on spectral features in the integrated optical spectrum and the global mass-to-light ratio that have been used to infer variations in the stellar initial mass function. To achieve this we develop appropriate stellar population synthesis models and take into account, for the first time, an initial-final mass relation which takes into consideration a varying He abundance. We conclude that while the multiple populations may be present in massive early-type galaxies, they are likely not responsible for the observed variations in the mass-to-light ratio and IMF sensitive line strengths. Finally, we estimate the fraction of stars with multiple populations chemistry that come from disrupted globular clusters within massive ellipticals and find that they may explain some of the observed chemical patterns in the centres of these galaxies.

  3. Method of applying single higher order polynomial basis function over multiple domains

    Lysko, AA

    2010-03-01

    Full Text Available A novel method has been devised where one set of higher order polynomial-based basis functions can be applied over several wire segments, thus permitting to decouple the number of unknowns from the number of segments, and so from the geometrical...

  4. Binding of Multiple Features in Memory by High-Functioning Adults with Autism Spectrum Disorder

    Bowler, Dermot M.; Gaigg, Sebastian B.; Gardiner, John M.

    2014-01-01

    Diminished episodic memory and diminished use of semantic information to aid recall by individuals with autism spectrum disorder (ASD) are both thought to result from diminished relational binding of elements of complex stimuli. To test this hypothesis, we asked high-functioning adults with ASD and typical comparison participants to study grids in…

  5. Social Function in Multiple X and Y Chromosome Disorders: XXY, XYY, XXYY, XXXY

    Visootsak, Jeannie; Graham, John M., Jr.

    2009-01-01

    Klinefelter syndrome (47,XXY) was initially described in the context of its endocrinologic and physical features; however, subsequent studies have revealed specific impairments in verbal skills and social functioning. Males with sex chromosomal aneuploidies are known to have variability in their developmental profile with the majority presenting…

  6. GWIS: Genome-Wide Inferred Statistics for Functions of Multiple Phenotypes

    Nieuwboer, H.A.; Pool, R.; Dolan, C.V.; Boomsma, D.I.; Nivard, M.G.

    2016-01-01

    Here we present a method of genome-wide inferred study (GWIS) that provides an approximation of genome-wide association study (GWAS) summary statistics for a variable that is a function of phenotypes for which GWAS summary statistics, phenotypic means, and covariances are available. A GWIS can be

  7. Multiple alterations of platelet functions dominated by increased secretion in mice lacking Cdc42 in platelets

    Pleines, Irina; Eckly, Anita; Elvers, Margitta

    2010-01-01

    formation and exocytosis in various cell types, but its exact function in platelets is not established. Here, we show that the megakaryocyte/platelet-specific loss of Cdc42 leads to mild thrombocytopenia and a small increase in platelet size in mice. Unexpectedly, Cdc42-deficient platelets were able to form...

  8. Her versus his migraine: multiple sex differences in brain function and structure.

    Maleki, Nasim; Linnman, Clas; Brawn, Jennifer; Burstein, Rami; Becerra, Lino; Borsook, David

    2012-08-01

    Migraine is twice as common in females as in males, but the mechanisms behind this difference are still poorly understood. We used high-field magnetic resonance imaging in male and female age-matched interictal (migraine free) migraineurs and matched healthy controls to determine alterations in brain structure. Female migraineurs had thicker posterior insula and precuneus cortices compared with male migraineurs and healthy controls of both sexes. Furthermore, evaluation of functional responses to heat within the migraine groups indicated concurrent functional differences in male and female migraineurs and a sex-specific pattern of functional connectivity of these two regions with the rest of the brain. The results support the notion of a 'sex phenotype' in migraine and indicate that brains are differentially affected by migraine in females compared with males. Furthermore, the results also support the notion that sex differences involve both brain structure as well as functional circuits, in that emotional circuitry compared with sensory processing appears involved to a greater degree in female than male migraineurs.

  9. Multiple functions of gingival and mucoperiosteal fibroblasts in oral wound healing and repair.

    Chiquet, Matthias; Katsaros, Christos; Kletsas, Dimitris

    2015-06-01

    Fibroblasts are cells of mesenchymal origin. They are responsible for the production of most extracellular matrix in connective tissues and are essential for wound healing and repair. In recent years, it has become clear that fibroblasts from different tissues have various distinct traits. Moreover, wounds in the oral cavity heal under very special environmental conditions compared with skin wounds. Here, we reviewed the current literature on the various interconnected functions of gingival and mucoperiosteal fibroblasts during the repair of oral wounds. The MEDLINE database was searched with the following terms: (gingival OR mucoperiosteal) AND fibroblast AND (wound healing OR repair). The data gathered were used to compare oral fibroblasts with fibroblasts from other tissues in terms of their regulation and function during wound healing. Specifically, we sought answers to the following questions: (i) what is the role of oral fibroblasts in the inflammatory response in acute wounds; (ii) how do growth factors control the function of oral fibroblasts during wound healing; (iii) how do oral fibroblasts produce, remodel and interact with extracellular matrix in healing wounds; (iv) how do oral fibroblasts respond to mechanical stress; and (v) how does aging affect the fetal-like responses and functions of oral fibroblasts? The current state of research indicates that oral fibroblasts possess unique characteristics and tightly controlled specific functions in wound healing and repair. This information is essential for developing new strategies to control the intraoral wound-healing processes of the individual patient. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Evaluation of Multiple-Sampling Function used with a Microtek flatbed scanner for Radiation Dosimetry Calibration of EBT2 Film

    Chang, Liyun; Ho, Sheng-Yow; Ding, Hueisch-Jy; Hwang, Ing-Ming; Chen, Pang-Yu; Lee, Tsair-Fwu

    2016-01-01

    The radiochromic EBT2 film is a widely used quality assurance device for radiation therapy. This study evaluated the film calibration performance of the multiple-sampling function, a function of the ScanWizard Pro scanning software provided by the manufacturer, when used with Microtek 9800XL plus (9800XL + ) flatbed scanner. By using the PDD method, each one of the eight EBT2 films, four delivered by 290 monitor unit (MU) and four by 88 MU via 6-MV photon beams, was tightly sandwiched in a 30 3 -cm 3 water equivalent polystyrene phantom prior to irradiation. Before and after irradiation, all films were scanned using the Microtek 9800XL + scanner with five different modes of the multiple-sampling function, which could generate the image with the averaged result of multiple-sampling. The net optical densities (netOD) on the beam central axis of film were assigned to corresponding depth doses for calibration. For each sampling mode with either delivered MU, the depth-dose uncertainty of a single film from repeated scans and that of a single scan of the four films were analyzed. Finally, the calibration error and the combined calibration uncertainty between film determined depth-doses and delivered depth-doses were calculated and evaluated for each sampling mode. All standard deviations and the calibration error were demonstrated to be unrelated to the number of sampling lines. The calibration error of the 2-line and 16-line mode was within 3 cGy and better than that of the other modes. The combined uncertainty of the 2-line mode was the lowest, which was generally less than 6 cGy except for the delivered dose around 100 cGy. The evaluation described herein revealed that the EBT2 film calibrated with the 2-line mode has relatively lower error, scanning time and combined uncertianty. Therefore, it is recommended for routine EBT2 film calibration and verification of treatment plans.

  11. Evolution of the Black Hole Mass Function in Star Clusters from Multiple Mergers

    Christian, Pierre; Mocz, Philip; Loeb, Abraham

    2018-05-01

    We investigate the effects of black hole (BH) mergers in star clusters on the black hole mass function (BHMF). As BHs are not produced in pair-instability supernovae, it is suggested that there is a dearth of high-mass stellar BHs. This dearth generates a gap in the upper end of the BHMF. Meanwhile, parameter fitting of X-ray binaries suggests the existence of a gap in the mass function under 5 solar masses. We show, through evolving a coagulation equation, that BH mergers can appreciably fill the upper mass gap, and that the lower mass gap generates potentially observable features at larger mass scales. We also explore the importance of ejections in such systems and whether dynamical clusters can be formation sites of intermediate-mass BH seeds.

  12. Human factors considerations for training astronauts to function effectively in multiple environments

    Cohen, Malcolm M.

    1991-01-01

    This paper reviews some of the basic issues involved in training individuals to function appropriately under the several conditions that comprise the aerospace environment. The topic of transfer of training is examined in some detail, and the use of high-fidelity simulators in various training programs is discussed. Both current and classical techniques used to train astronauts are noted, and some relatively new and innovative training techniques and methods are described. Particularly, the paper discusses an important aspect of functioning appropriately in a given environment that is based on how well the operator calibrates his motor activity for that specific environment. The role of motor-sensory feedback for the acquisition of motor skills is discussed in the context of training.

  13. New Caledonian crows attend to multiple functional properties of complex tools.

    St Clair, James J H; Rutz, Christian

    2013-11-19

    The ability to attend to the functional properties of foraging tools should affect energy-intake rates, fitness components and ultimately the evolutionary dynamics of tool-related behaviour. New Caledonian crows Corvus moneduloides use three distinct tool types for extractive foraging: non-hooked stick tools, hooked stick tools and tools cut from the barbed edges of Pandanus spp. leaves. The latter two types exhibit clear functional polarity, because of (respectively) a single terminal, crow-manufactured hook and natural barbs running along one edge of the leaf strip; in each case, the 'hooks' can only aid prey capture if the tool is oriented correctly by the crow during deployment. A previous experimental study of New Caledonian crows found that subjects paid little attention to the barbs of supplied (wide) pandanus tools, resulting in non-functional tool orientation during foraging. This result is puzzling, given the presumed fitness benefits of consistently orienting tools functionally in the wild. We investigated whether the lack of discrimination with respect to (wide) pandanus tool orientation also applies to hooked stick tools. We experimentally provided subjects with naturalistic replica tools in a range of orientations and found that all subjects used these tools correctly, regardless of how they had been presented. In a companion experiment, we explored the extent to which normally co-occurring tool features (terminal hook, curvature of the tool shaft and stripped bark at the hooked end) inform tool-orientation decisions, by forcing birds to deploy 'unnatural' tools, which exhibited these traits at opposite ends. Our subjects attended to at least two of the three tool features, although, as expected, the location of the hook was of paramount importance. We discuss these results in the context of earlier research and propose avenues for future work.

  14. Binding of multiple features in memory by high-functioning adults with autism spectrum disorder

    Bowler, D. M.; Gaigg, S. B.; Gardiner, J. M.

    2014-01-01

    Diminished episodic memory and diminished use of semantic information to aid recall by individuals with autism spectrum disorder (ASD) are both thought to result from diminished relational binding of elements of complex stimuli. To test this hypothesis, we asked high-functioning adults with ASD and typical comparison participants to study grids in which some cells contained drawings of objects in non-canonical colours. Participants were told at study which features (colour, item, location) wo...

  15. Estimating the input function non-invasively for FDG-PET quantification with multiple linear regression analysis: simulation and verification with in vivo data

    Fang, Yu-Hua; Kao, Tsair; Liu, Ren-Shyan; Wu, Liang-Chih

    2004-01-01

    A novel statistical method, namely Regression-Estimated Input Function (REIF), is proposed in this study for the purpose of non-invasive estimation of the input function for fluorine-18 2-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) quantitative analysis. We collected 44 patients who had undergone a blood sampling procedure during their FDG-PET scans. First, we generated tissue time-activity curves of the grey matter and the whole brain with a segmentation technique for every subject. Summations of different intervals of these two curves were used as a feature vector, which also included the net injection dose. Multiple linear regression analysis was then applied to find the correlation between the input function and the feature vector. After a simulation study with in vivo data, the data of 29 patients were applied to calculate the regression coefficients, which were then used to estimate the input functions of the other 15 subjects. Comparing the estimated input functions with the corresponding real input functions, the averaged error percentages of the area under the curve and the cerebral metabolic rate of glucose (CMRGlc) were 12.13±8.85 and 16.60±9.61, respectively. Regression analysis of the CMRGlc values derived from the real and estimated input functions revealed a high correlation (r=0.91). No significant difference was found between the real CMRGlc and that derived from our regression-estimated input function (Student's t test, P>0.05). The proposed REIF method demonstrated good abilities for input function and CMRGlc estimation, and represents a reliable replacement for the blood sampling procedures in FDG-PET quantification. (orig.)

  16. Functional decline and herpes zoster in older people: an interplay of multiple factors.

    2015-12-01

    Herpes zoster is a frequent painful infectious disease whose incidence and severity increase with age. In older people, there is a strong bidirectional link between herpes zoster and functional decline, which refers to a decrement in ability to perform activities of daily living due to ageing and disabilities. However, the exact nature of such link remains poorly established. Based on the opinion from a multidisciplinary group of experts, we here propose a new model to account for the interplay between infection, somatic/psychiatric comorbidity, coping skills, polypharmacy, and age, which may account for the functional decline related to herpes zoster in older patients. This model integrates the risk of decompensation of underlying disease; the risk of pain becoming chronic (e.g. postherpetic neuralgia); the risk of herpes zoster non-pain complications; the detrimental impact of herpes zoster on quality of life, functioning, and mood; the therapeutic difficulties due to multimorbidity, polypharmacy, and ageing; and the role of stressful life events in the infection itself and comorbid depression. This model underlines the importance of early treatment, strengthening coping, and vaccine prevention.

  17. Population pharmacokinetics of pomalidomide in patients with relapsed or refractory multiple myeloma with various degrees of impaired renal function.

    Li, Yan; Wang, Xiaomin; O'Mara, Edward; Dimopoulos, Meletios A; Sonneveld, Pieter; Weisel, Katja C; Matous, Jeffrey; Siegel, David S; Shah, Jatin J; Kueenburg, Elisabeth; Sternas, Lars; Cavanaugh, Chloe; Zaki, Mohamed; Palmisano, Maria; Zhou, Simon

    2017-01-01

    Pomalidomide is an immunomodulatory drug for treatment of relapsed or refractory multiple myeloma (rrMM) in patients who often have comorbid renal conditions. To assess the impact of renal impairment on pomalidomide exposure, a population pharmacokinetics (PPK) model of pomalidomide in rrMM patients with various degrees of impaired renal function was developed. Intensive and sparse pomalidomide concentration data collected from two clinical studies in rrMM patients with normal renal function, moderately impaired renal function, severely impaired renal function not requiring dialysis, and with severely impaired renal function requiring dialysis were pooled over the dose range of 2 to 4 mg, to assess specifically the influence of the impaired renal function as a categorical variable and a continuous variable on pomalidomide clearance and plasma exposure. In addition, pomalidomide concentration data collected on dialysis days from both the withdrawal (arterial) side and from the returning (venous) side of the dialyzer, from rrMM patients with severely impaired renal function requiring dialysis, were used to assess the extent to which dialysis contributes to the removal of pomalidomide from blood circulation. PPK analyses demonstrated that moderate to severe renal impairment not requiring dialysis has no influence on pomalidomide clearance or plasma exposure, as compared to those patients with normal renal function, while pomalidomide exposure increased approximately 35% in patients with severe renal impairment requiring dialysis on nondialysis days. In addition, dialysis increased total body pomalidomide clearance from 5 L/h to 12 L/h, indicating that dialysis will significantly remove pomalidomide from the blood circulation. Thus, pomalidomide should be administered post-dialysis on the days of dialysis.

  18. A method for multiple sequential analyses of macrophage functions using a small single cell sample

    F.R.F. Nascimento

    2003-09-01

    Full Text Available Microbial pathogens such as bacillus Calmette-Guérin (BCG induce the activation of macrophages. Activated macrophages can be characterized by the increased production of reactive oxygen and nitrogen metabolites, generated via NADPH oxidase and inducible nitric oxide synthase, respectively, and by the increased expression of major histocompatibility complex class II molecules (MHC II. Multiple microassays have been developed to measure these parameters. Usually each assay requires 2-5 x 10(5 cells per well. In some experimental conditions the number of cells is the limiting factor for the phenotypic characterization of macrophages. Here we describe a method whereby this limitation can be circumvented. Using a single 96-well microassay and a very small number of peritoneal cells obtained from C3H/HePas mice, containing as little as <=2 x 10(5 macrophages per well, we determined sequentially the oxidative burst (H2O2, nitric oxide production and MHC II (IAk expression of BCG-activated macrophages. More specifically, with 100 µl of cell suspension it was possible to quantify H2O2 release and nitric oxide production after 1 and 48 h, respectively, and IAk expression after 48 h of cell culture. In addition, this microassay is easy to perform, highly reproducible and more economical.

  19. Method to obtain g-functions for multiple precast quadratic pile heat exchangers

    Pagola, Maria Alberdi; Jensen, Rasmus Lund; Madsen, Søren

    The average fluid temperature circulating through the ground loop is one of the main parameters required when choosing the most adequate heat pump for a ground source heat pump installation. Besides, the analysis of the fluid temperature over time will show the sustainability of the energy supply...... over the lifetime of the installation. The average fluid temperature is subjected to the type of ground heat exchangers and the thermal interactions between them, which also depend on the soil thermal properties. For the case of precast piles, the thermal interactions become significant...... as they are usually placed within short distances (0.5 to 4 metres). Fast models that can account for these interactions are required to enable feasibility studies and support the design phase. Besides, since pile heat exchangers have a main structural role, it is also relevant to develop models that can determine...... the temperature changes that the foundation might be subjected to, to assess thermo-mechanical implications. 3D finite element model (FEM) computation of the thermal behaviour of multiple pile heat exchanger foundations is not cost effective nor for feasibility studies, nor for most design applications. Therefore...

  20. Exploring resting-state EEG brain oscillatory activity in relation to cognitive functioning in multiple sclerosis.

    Keune, Philipp M; Hansen, Sascha; Weber, Emily; Zapf, Franziska; Habich, Juliane; Muenssinger, Jana; Wolf, Sebastian; Schönenberg, Michael; Oschmann, Patrick

    2017-09-01

    Neurophysiologic monitoring parameters related to cognition in Multiple Sclerosis (MS) are sparse. Previous work reported an association between magnetoencephalographic (MEG) alpha-1 activity and information processing speed. While this remains to be replicated by more available electroencephalographic (EEG) methods, also other established EEG markers, e.g. the slow-wave/fast-wave ratio (theta/beta ratio), remain to be explored in this context. Performance on standard tests addressing information processing speed and attention (Symbol-Digit Modalities Test, SDMT; Test of Attention Performance, TAP) was examined in relation to resting-state EEG alpha-1 and alpha-2 activity and the theta/beta ratio in 25MS patients. Increased global alpha-1 and alpha-2 activity and an increased frontal theta/beta ratio (pronounced slow-wave relative to fast-wave activity) were associated with lower SDMT processing speed. In an exploratory analysis, clinically impaired attention was associated with a significantly increased frontal theta/beta ratio whereas alpha power did not show sensitivity to clinical impairment. EEG global alpha power and the frontal theta/beta ratio were both associated with attention. The theta/beta ratio involved potential clinical sensitivity. Resting-state EEG recordings can be obtained during the routine clinical process. The examined resting-state measures may represent feasible monitoring parameters in MS. This notion should be explored in future intervention studies. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  1. Including pork in the Mediterranean diet for an Australian population: Protocol for a randomised controlled trial assessing cardiovascular risk and cognitive function.

    Wade, Alexandra T; Davis, Courtney R; Dyer, Kathryn A; Hodgson, Jonathan M; Woodman, Richard J; Keage, Hannah A D; Murphy, Karen J

    2017-12-22

    The Mediterranean diet is characterised by the high consumption of extra virgin olive oil, fruits, vegetables, grains, legumes and nuts; moderate consumption of fish, poultry, eggs and dairy; and low consumption of red meat and sweets. Cross sectional, longitudinal and intervention studies indicate that a Mediterranean diet may be effective for the prevention of cardiovascular disease and dementia. However, previous research suggests that an Australian population may find red meat restrictions difficult, which could affect long term sustainability of the diet. This paper outlines the protocol for a randomised controlled trial that will assess the cardiovascular and cognitive benefits of a Mediterranean diet modified to include 2-3 weekly serves of fresh, lean pork. A 24-week cross-over design trial will compare a modified Mediterranean diet with a low-fat control diet in at-risk men and women. Participants will follow each of the two diets for 8 weeks, with an 8-week washout period separating interventions. Home measured systolic blood pressure will be the primary outcome measure. Secondary outcomes will include body mass index, body composition, fasting blood lipids, C-reactive protein, fasting plasma glucose, fasting serum insulin, erythrocyte fatty acids, cognitive function, psychological health and well-being, and dementia risk. To our knowledge this research is the first to investigate whether an alternate source of protein can be included in the Mediterranean diet to increase sustainability and feasibility for a non-Mediterranean population. Findings will be significant for the prevention of cardiovascular disease and age-related decline, and may inform individuals, clinicians and public health policy. ACTRN12616001046493 . Registered 5 August 2016.

  2. Functional Outcomes of Multiple Sural Nerve Grafts for Facial Nerve Defects after Tumor-Ablative Surgery

    Myung Chul Lee

    2015-07-01

    Full Text Available BackgroundFunctional restoration of the facial expression is necessary after facial nerve resection to treat head and neck tumors. This study was conducted to evaluate the functional outcomes of patients who underwent facial nerve cable grafting immediately after tumor resection.MethodsPatients who underwent cable grafting from April 2007 to August 2011 were reviewed, in which a harvested branch of the sural nerve was grafted onto each facial nerve division. Twelve patients underwent facial nerve cable grafting after radical parotidectomy, total parotidectomy, or schwannoma resection, and the functional facial expression of each patient was evaluated using the Facial Nerve Grading Scale 2.0. The results were analyzed according to patient age, follow-up duration, and the use of postoperative radiation therapy.ResultsAmong the 12 patients who were evaluated, the mean follow-up duration was 21.8 months, the mean age at the time of surgery was 42.8 years, and the mean facial expression score was 14.6 points, indicating moderate dysfunction. Facial expression scores were not influenced by age at the time of surgery, follow-up duration, or the use of postoperative radiation therapy.ConclusionsThe results of this study indicate that facial nerve cable grafting using the sural nerve can restore facial expression. Although patients were provided with appropriate treatment, the survival rate for salivary gland cancer was poor. We conclude that immediate facial nerve reconstruction is a worthwhile procedure that improves quality of life by allowing the recovery of facial expression, even in patients who are older or may require radiation therapy.

  3. Computer Simulations Reveal Multiple Functions for Aromatic Residues in Cellulase Enzymes (Fact Sheet)

    2012-07-01

    NREL researchers use high-performance computing to demonstrate fundamental roles of aromatic residues in cellulase enzyme tunnels. National Renewable Energy Laboratory (NREL) computer simulations of a key industrial enzyme, the Trichoderma reesei Family 6 cellulase (Cel6A), predict that aromatic residues near the enzyme's active site and at the entrance and exit tunnel perform different functions in substrate binding and catalysis, depending on their location in the enzyme. These results suggest that nature employs aromatic-carbohydrate interactions with a wide variety of binding affinities for diverse functions. Outcomes also suggest that protein engineering strategies in which mutations are made around the binding sites may require tailoring specific to the enzyme family. Cellulase enzymes ubiquitously exhibit tunnels or clefts lined with aromatic residues for processing carbohydrate polymers to monomers, but the molecular-level role of these aromatic residues remains unknown. In silico mutation of the aromatic residues near the catalytic site of Cel6A has little impact on the binding affinity, but simulation suggests that these residues play a major role in the glucopyranose ring distortion necessary for cleaving glycosidic bonds to produce fermentable sugars. Removal of aromatic residues at the entrance and exit of the cellulase tunnel, however, dramatically impacts the binding affinity. This suggests that these residues play a role in acquiring cellulose chains from the cellulose crystal and stabilizing the reaction product, respectively. These results illustrate that the role of aromatic-carbohydrate interactions varies dramatically depending on the position in the enzyme tunnel. As aromatic-carbohydrate interactions are present in all carbohydrate-active enzymes, the results have implications for understanding protein structure-function relationships in carbohydrate metabolism and recognition, carbon turnover in nature, and protein engineering

  4. Modelling of coil-loaded wire antenna using composite multiple domain basis functions

    Lysko, AA

    2010-03-01

    Full Text Available - tional Electromagnetics, Artech House, 2001. 3. Rogers, S. D. and C. M. Butler, \\An e–cient curved-wire integral equation solution technique," IEEE Trans. Ant. and Propag., 70{79, Vol. 49, Jan. 2001. 4. Mosig, J. and E. Suter, \\A multilevel divide.... 8. Wan, J. X., J. Lei, and C.-H. Liang, \\An e–cient analysis of large-scale periodic microstrip antenna arrays using the characteristic basis function method," Progress In Electromagnetics Research, PIER 50, 61{81, 2005. 9. Taguchi, M., K...

  5. Multiple RNAs from the mouse carboxypeptidase M locus: functional RNAs or transcription noise?

    Castilho Beatriz A

    2009-02-01

    Full Text Available Abstract Background A major effort of the scientific community has been to obtain complete pictures of the genomes of many organisms. This has been accomplished mainly by annotation of structural and functional elements in the genome sequence, a process that has been centred in the gene concept and, as a consequence, biased toward protein coding sequences. Recently, the explosion of transcriptome data generated and the discovery of many functional non-protein coding RNAs have painted a more detailed and complex scenario for the genome. Here we analyzed the mouse carboxypeptidase M locus in this broader perspective in order to define the mouse CPM gene structure and evaluate the existence of other transcripts from the same genomic region. Results Bioinformatic analysis of nucleotide sequences that map to the mouse CPM locus suggests that, in addition to the mouse CPM mRNA, it expresses at least 33 different transcripts, many of which seem to be non-coding RNAs. We randomly chose to evaluate experimentally four of these extra transcripts. They are expressed in a tissue specific manner, indicating that they are not artefacts or transcriptional noise. Furthermore, one of these four extra transcripts shows expression patterns that differed considerably from the other ones and from the mouse CPM gene, suggesting that there may be more than one transcriptional unit in this locus. In addition, we have confirmed the mouse CPM gene RefSeq sequence by rapid amplification of cDNA ends (RACE and directional cloning. Conclusion This study supports the recent view that the majority of the genome is transcribed and that many of the resulting transcripts seem to be non-coding RNAs from introns of genes or from independent transcriptional units. Although some of the information on the transcriptome of many organisms may actually be artefacts or transcriptional noise, we argue that it can be experimentally evaluated and used to find and define biological

  6. RhoGDI: multiple functions in the regulation of Rho family GTPase activities

    Dovas, Athanassios; Couchman, John R

    2005-01-01

    necessary for the correct targeting and regulation of Rho activities by conferring cues for spatial restriction, guidance and availability to effectors. These potential functions are discussed in the context of RhoGDI-associated multimolecular complexes, the newly emerged shuttling capability...... insight as to how RhoGDI exerts its effects on nucleotide binding, the membrane association-dissociation cycling of the GTPase and how these activities are controlled. Despite the initial negative roles attributed to RhoGDI, recent evidence has come to suggest that it may also act as a positive regulator...... of activities....

  7. A multiplicative process for generating a beta-like survival function with application to the UK 2016 EU referendum results

    Fenner, Trevor; Kaufmann, Eric; Levene, Mark; Loizou, George

    Human dynamics and sociophysics suggest statistical models that may explain and provide us with better insight into social phenomena. Contextual and selection effects tend to produce extreme values in the tails of rank-ordered distributions of both census data and district-level election outcomes. Models that account for this nonlinearity generally outperform linear models. Fitting nonlinear functions based on rank-ordering census and election data therefore improves the fit of aggregate voting models. This may help improve ecological inference, as well as election forecasting in majoritarian systems. We propose a generative multiplicative decrease model that gives rise to a rank-order distribution and facilitates the analysis of the recent UK EU referendum results. We supply empirical evidence that the beta-like survival function, which can be generated directly from our model, is a close fit to the referendum results, and also may have predictive value when covariate data are available.

  8. Examining Multiple Sources of Differential Item Functioning on the Clinician & Group CAHPS® Survey

    Rodriguez, Hector P; Crane, Paul K

    2011-01-01

    Objective To evaluate psychometric properties of a widely used patient experience survey. Data Sources English-language responses to the Clinician & Group Consumer Assessment of Healthcare Providers and Systems (CG-CAHPS®) survey (n = 12,244) from a 2008 quality improvement initiative involving eight southern California medical groups. Methods We used an iterative hybrid ordinal logistic regression/item response theory differential item functioning (DIF) algorithm to identify items with DIF related to patient sociodemographic characteristics, duration of the physician–patient relationship, number of physician visits, and self-rated physical and mental health. We accounted for all sources of DIF and determined its cumulative impact. Principal Findings The upper end of the CG-CAHPS® performance range is measured with low precision. With sensitive settings, some items were found to have DIF. However, overall DIF impact was negligible, as 0.14 percent of participants had salient DIF impact. Latinos who spoke predominantly English at home had the highest prevalence of salient DIF impact at 0.26 percent. Conclusions The CG-CAHPS® functions similarly across commercially insured respondents from diverse backgrounds. Consequently, previously documented racial and ethnic group differences likely reflect true differences rather than measurement bias. The impact of low precision at the upper end of the scale should be clarified. PMID:22092021

  9. Humic acids: Structural properties and multiple functionalities for novel technological developments.

    de Melo, Bruna Alice Gomes; Motta, Fernanda Lopes; Santana, Maria Helena Andrade

    2016-05-01

    Humic acids (HAs) are macromolecules that comprise humic substances (HS), which are organic matter distributed in terrestrial soil, natural water, and sediment. HAs differ from the other HS fractions (fulvic acid and humins) in that they are soluble in alkaline media, partially soluble in water, and insoluble in acidic media. Due to their amphiphilic character, HAs form micelle-like structures in neutral to acidic conditions, which are useful in agriculture, pollution remediation, medicine and pharmaceuticals. HAs have undefined compositions that vary according to the origin, process of obtainment, and functional groups present in their structures, such as quinones, phenols, and carboxylic acids. Quinones are responsible for the formation of reactive oxygen species (ROS) in HAs, which are useful for wound healing and have fungicidal/bactericidal properties. Phenols and carboxylic acids deprotonate in neutral and alkaline media and are responsible for various other functions, such as the antioxidant and anti-inflammatory properties of HAs. In particular, the presence of phenolic groups in HAs provides antioxidant properties due to their free radical scavenging capacity. This paper describes the main multifunctionalities of HAs associated with their structures and properties, focusing on human health applications, and we note perspectives that may lead to novel technological developments. To the best of our knowledge, this is the first review to address this topic from this approach. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Kidins220/ARMS as a functional mediator of multiple receptor signalling pathways.

    Neubrand, Veronika E; Cesca, Fabrizia; Benfenati, Fabio; Schiavo, Giampietro

    2012-04-15

    An increasing body of evidence suggests that several membrane receptors--in addition to activating distinct signalling cascades--also engage in substantial crosstalk with each other, thereby adjusting their signalling outcome as a function of specific input information. However, little is known about the molecular mechanisms that control their coordination and integration of downstream signalling. A protein that is likely to have a role in this process is kinase-D-interacting substrate of 220 kDa [Kidins220, also known as ankyrin repeat-rich membrane spanning (ARMS), hereafter referred to as Kidins220/ARMS]. Kidins220/ARMS is a conserved membrane protein that is preferentially expressed in the nervous system and interacts with the microtubule and actin cytoskeleton. It interacts with neurotrophin, ephrin, vascular endothelial growth factor (VEGF) and glutamate receptors, and is a common downstream target of several trophic stimuli. Kidins220/ARMS is required for neuronal differentiation and survival, and its expression levels modulate synaptic plasticity. Kidins220/ARMS knockout mice show developmental defects mainly in the nervous and cardiovascular systems, suggesting a crucial role for this protein in modulating the cross talk between different signalling pathways. In this Commentary, we summarise existing knowledge regarding the physiological functions of Kidins220/ARMS, and highlight some interesting directions for future studies on the role of this protein in health and disease.

  11. Multiple structure-intrinsic disorder interactions regulate and coordinate Hox protein function

    Bondos, Sarah

    During animal development, Hox transcription factors determine fate of developing tissues to generate diverse organs and appendages. Hox proteins are famous for their bizarre mutant phenotypes, such as replacing antennae with legs. Clearly, the functions of individual Hox proteins must be distinct and reliable in vivo, or the organism risks malformation or death. However, within the Hox protein family, the DNA-binding homeodomains are highly conserved and the amino acids that contact DNA are nearly invariant. These observations raise the question: How do different Hox proteins correctly identify their distinct target genes using a common DNA binding domain? One possible means to modulate DNA binding is through the influence of the non-homeodomain protein regions, which differ significantly among Hox proteins. However genetic approaches never detected intra-protein interactions, and early biochemical attempts were hindered because the special features of ``intrinsically disordered'' sequences were not appreciated. We propose the first-ever structural model of a Hox protein to explain how specific contacts between distant, intrinsically disordered regions of the protein and the homeodomain regulate DNA binding and coordinate this activity with other Hox molecular functions.

  12. Epidemiological characteristics and functional disability of multiple sclerosis patients in Kosovo.

    Zeqiraj, Kamber; Kruja, Jera; Kabashi, Serbeze; Muçaj, Sefedin

    2014-01-01

    Multiple Sclerosis (MS) is a chronic recurrent neurological disease that affects the Central Nervous System. This study aims to determine epidemiological factors that affect the appearance of MS, such as: incidence, prevalence, mortality, case appearance in accordance with the disease phase RRMS, SPMS, PPMS, gender, age, age group, and EDSS. Deals with analyzing diagnosed and treated patients in the Clinic of Neurology in Prishtina during the period of 2003-2012. The research was conducted through a questionnaire applied in the diagnosed cases of MS. Information on patients was gathered from: history of illness, discharge reports and other relevant documents on MS illness. Clinical and epidemiological-descriptive study methods were used. The acquired results are shown through tables, graphics. Statistical processing was conducted with Microsoft Office Excel. From the total number of doubtful hospitalized cases of demyelinization (644) in the Clinic of Neurology in Prishtina, 412 cases (64%) were diagnosed with MS. For the period of 2003-2012 the prevalence of MS has been 19.6 of patients in 100,000 inhabitants. MS incidence rate was 0.95 of patients in 100,000 inhabitants. MS mortality rate was 0.14 of deceased in 100,000 inhabitants. The ratio female--male is 2.3:1. A larger number of patients fall within the age group of 30-39 years-old. Clinical form trends: RRSM 72.3%, SPSM 22.6%, PPSM 5.1%. The rate of EDSS 78.3% (0-3.5), 14.9% (4-6.5), 6.8% (7-9).

  13. Fine Mapping and Functional Analysis of the Multiple Sclerosis Risk Gene CD6

    Swaminathan, Bhairavi; Cuapio, Angélica; Alloza, Iraide; Matesanz, Fuencisla; Alcina, Antonio; García-Barcina, Maria; Fedetz, Maria; Fernández, Óscar; Lucas, Miguel; Órpez, Teresa; Pinto-Medel, Mª Jesus; Otaegui, David; Olascoaga, Javier; Urcelay, Elena; Ortiz, Miguel A.; Arroyo, Rafael; Oksenberg, Jorge R.; Antigüedad, Alfredo; Tolosa, Eva; Vandenbroeck, Koen

    2013-01-01

    CD6 has recently been identified and validated as risk gene for multiple sclerosis (MS), based on the association of a single nucleotide polymorphism (SNP), rs17824933, located in intron 1. CD6 is a cell surface scavenger receptor involved in T-cell activation and proliferation, as well as in thymocyte differentiation. In this study, we performed a haptag SNP screen of the CD6 gene locus using a total of thirteen tagging SNPs, of which three were non-synonymous SNPs, and replicated the recently reported GWAS SNP rs650258 in a Spanish-Basque collection of 814 controls and 823 cases. Validation of the six most strongly associated SNPs was performed in an independent collection of 2265 MS patients and 2600 healthy controls. We identified association of haplotypes composed of two non-synonymous SNPs [rs11230563 (R225W) and rs2074225 (A257V)] in the 2nd SRCR domain with susceptibility to MS (P max(T) permutation = 1×10−4). The effect of these haplotypes on CD6 surface expression and cytokine secretion was also tested. The analysis showed significantly different CD6 expression patterns in the distinct cell subsets, i.e. – CD4+ naïve cells, P = 0.0001; CD8+ naïve cells, P<0.0001; CD4+ and CD8+ central memory cells, P = 0.01 and 0.05, respectively; and natural killer T (NKT) cells, P = 0.02; with the protective haplotype (RA) showing higher expression of CD6. However, no significant changes were observed in natural killer (NK) cells, effector memory and terminally differentiated effector memory T cells. Our findings reveal that this new MS-associated CD6 risk haplotype significantly modifies expression of CD6 on CD4+ and CD8+ T cells. PMID:23638056

  14. Novel functional polymorphism in IGF-1 gene associated with multiple sclerosis: A new insight to MS.

    Shahbazi, Majid; Abdolmohammadi, Reza; Ebadi, Hamid; Farazmandfar, Touraj

    2017-04-01

    Interactions between several genes and environment may play a role in susceptibility to multiple sclerosis (MS). The IGF-1 plays a key role in proliferation, maintenance and survival of nerve cells. Therefore, we hypothesized that IGF-1 may be a target for prediction and control MS. We aimed to analysis IGF-1 gene promoter sequence, to investigate the effect of the single nucleotide variants on IGF-1 expression and its association with MS. We enrolled 339 MS patients and 431 healthy controls. A specific region in IGF-1 gene promoter was investigated by SSCP analysis. All samples were genotyped by SSP-PCR. In-vitro and in-vivo IGF-1 production was measured by ELISA assay. IGF-1 expression in PBMCs was measured using real-time PCR. We identified a T to C single nucleotide substitution at position -1089 and a C to T at position -383 from transcription start site in the IGF-1 gene promoter. There was a significant association between MS and genotypes IGF-1(-383) C/T (p=0.001) and IGF-1(-383) C/C (pMS (p=0.001). In-vitro and in-vivo IGF-1 level showed that IGF-1 production in samples with genotype IGF-1(-383) C/C significantly was less than T/T (p=0.004) but not T/C (p=0.220). According to IGF-1 roles in CNS and our results, this study suggests that low IGF-1 level may be associated with susceptibility to MS. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Role of executive functions in prospective memory in multiple sclerosis: Impact of the strength of cue-action association.

    Dagenais, Emmanuelle; Rouleau, Isabelle; Tremblay, Alexandra; Demers, Mélanie; Roger, Élaine; Jobin, Céline; Duquette, Pierre

    2016-01-01

    Patients diagnosed with multiple sclerosis (MS) often report prospective memory (PM) deficits. Although PM is important for daily functioning, it is not formally assessed in clinical practice. The aim of this study was to examine the role of executive functions in MS patients' PM revealed by the effect of strength of cue-action association on PM performance. Thirty-nine MS patients were compared to 18 healthy controls matched for age, gender, and education on a PM task modulating the strength of association between the cue and the intended action. Deficits in MS patients affecting both prospective and retrospective components of PM were confirmed using 2 × 2 × 2 mixed analyses of variance (ANOVAs). Among patients, multiple regression analyses revealed that the impairment was modulated by the efficiency of executive functions, whereas retrospective memory seemed to have little impact on PM performance, contrary to expectation. More specifically, results of 2 × 2 × 2 mixed-model analyses of covariance (ANCOVAs) showed that low-executive patients had more difficulty detecting and, especially, retrieving the appropriate action when the cue and the action were unrelated, whereas high-executive patients' performance seemed to be virtually unaffected by the cue-action association. Using an objective measure, these findings confirm the presence of PM deficits in MS. They also suggest that such deficits depend on executive functioning and can be reduced when automatic PM processes are engaged through semantic cue-action association. They underscore the importance of assessing PM in clinical settings through a cognitive evaluation and offer an interesting avenue for rehabilitation.

  16. Predictive value of different conventional and non-conventional MRI-parameters for specific domains of cognitive function in multiple sclerosis.

    Pinter, Daniela; Khalil, Michael; Pichler, Alexander; Langkammer, Christian; Ropele, Stefan; Marschik, Peter B; Fuchs, Siegrid; Fazekas, Franz; Enzinger, Christian

    2015-01-01

    While many studies correlated cognitive function with changes in brain morphology in multiple sclerosis (MS), few of them used a multi-parametric approach in a single dataset so far. We thus here assessed the predictive value of different conventional and quantitative MRI-parameters both for overall and domain-specific cognitive performance in MS patients from a single center. 69 patients (17 clinically isolated syndrome, 47 relapsing-remitting MS, 5 secondary-progressive MS) underwent the "Brief Repeatable Battery of Neuropsychological Tests" assessing overall cognition, cognitive efficiency and memory function as well as MRI at 3 Tesla to obtain T2-lesion load (T2-LL), normalized brain volume (global brain volume loss), normalized cortical volume (NCV), normalized thalamic volume (NTV), normalized hippocampal volume (NHV), normalized caudate nuclei volume (NCNV), basal ganglia R2* values (iron deposition) and magnetization transfer ratios (MTRs) for cortex and normal appearing brain tissue (NABT). Regression models including clinical, demographic variables and MRI-parameters explained 22-27% of variance of overall cognition, 17-26% of cognitive efficiency and 22-23% of memory. NCV, T2-LL and MTR of NABT were the strongest predictors of overall cognitive function. Cognitive efficiency was best predicted by NCV, T2-LL and iron deposition in the basal ganglia. NTV was the strongest predictor for memory function and NHV was particularly related to memory function. The predictive value of distinct MRI-parameters differs for specific domains of cognitive function, with a greater impact of cortical volume, focal and diffuse white matter abnormalities on overall cognitive function, an additional role of basal ganglia iron deposition on cognitive efficiency, and thalamic and hippocampal volume on memory function. This suggests the usefulness of using multiparametric MRI to assess (micro)structural correlates of different cognitive constructs.

  17. Multiple stressor effects on marine infauna: responses of estuarine taxa and functional traits to sedimentation, nutrient and metal loading

    Ellis, Joanne

    2017-09-14

    Sedimentation, nutrients and metal loading to coastal environments are increasing, associated with urbanization and global warming, hence there is a growing need to predict ecological responses to such change. Using a regression technique we predicted how maximum abundance of 20 macrobenthic taxa and 22 functional traits separately and interactively responded to these key stressors. The abundance of most taxa declined in response to sedimentation and metal loading while a unimodal response was often associated with nutrient loading. Optimum abundances for both taxa and traits occurred at relatively low stressor levels, highlighting the vulnerability of estuaries to increasing stressor loads. Individual taxa were more susceptible to stress than traits, suggesting that functional traits may be less sensitive for detecting changes in ecosystem health. Multiplicative effects were more common than additive interactions. The observed sensitivity of most taxa to increasing sedimentation and metal loading and the documented interaction effects between multiple stressors have important implications for understanding and managing the ecological consequences of eutrophication, sedimentation and contaminants on coastal ecosystems.

  18. Effects of iodinated contrast media on renal function in patients with multiple myeloma

    Jacob, H.M.

    1980-01-01

    Case histories of 89 patients with definite myoloma of the years 1959 to 1974 were investigated in a retrospective study. 41 intravenous urographies were carried out in 31 of these patients. There was no correlation between deterioration of the renal function and contrast medium application. Relevant literature on the subject has been compiled. By 1979, 19 case studies and 5 general studies had been published which have been summarized in tables in the present study. Analyses of these case histories have shown that acute renal failure was often due to other causes and not to contrast medium application. If these cases are left out of account 8 cases remain in which lethal renal failure occurred after intravenous urography of myeloma patients. The diiodinated contrast media formerly used was less well tolerated than the present triiodinated contrast media. Further risk factors were dehydratation and/or abdominal compression. Both measures are no longer employed in intravenous urography. (orig./MG) [de

  19. A semiconductor metasurface with multiple functionalities: A polarizing beam splitter with simultaneous focusing ability

    Lee, Jun Hyung; Jin Jung, Myoung; Ho Song, Seok, E-mail: shsong@hanyang.ac.kr [Department of Physics, Hanyang University, Seoul (Korea, Republic of); Woong Yoon, Jae; Magnusson, Robert [Department of Electrical Engineering, University of Texas–Arlington, Arlington, Texas 76019 (United States); Kyun Hong, Jong [Department of Electrical Engineering, Hanyang University, Seoul (Korea, Republic of)

    2014-06-09

    We propose a semiconductor metasurface that simultaneously performs two independent functions: focusing and polarization filtering. The wavefronts of the reflected and transmitted light distributions are precisely manipulated by spatial parametric variation of a subwavelength thin-film Si grating, which inherently possesses polarization filtering properties. We design a 12-μm-wide metasurface containing only nineteen Si grating ridges. Under a 10-μm-wide unpolarized Gaussian beam incidence at wavelength of 1.55 μm, the resulting device shows promising theoretical performance with high power efficiency exceeding 80% and polarization extinction ratio of ∼10 dB with focal spot diameters near 1–2 μm.

  20. Binding of multiple features in memory by high-functioning adults with autism spectrum disorder.

    Bowler, Dermot M; Gaigg, Sebastian B; Gardiner, John M

    2014-09-01

    Diminished episodic memory and diminished use of semantic information to aid recall by individuals with autism spectrum disorder (ASD) are both thought to result from diminished relational binding of elements of complex stimuli. To test this hypothesis, we asked high-functioning adults with ASD and typical comparison participants to study grids in which some cells contained drawings of objects in non-canonical colours. Participants were told at study which features (colour, item, location) would be tested in a later memory test. In a second experiment, participants studied similar grids and were told that they would be tested on object-location or object-colour combinations. Recognition of combinations was significantly diminished in ASD, which survived covarying performance on the Color Trails Test (D'Elia et al. Color trails test. Professional manual. Psychological Assessment Resources, Lutz, 1996), a test of executive difficulties. The findings raise the possibility that medial temporal as well as frontal lobe processes are dysfunctional in ASD.

  1. Identifying and exploiting trait-relevant tissues with multiple functional annotations in genome-wide association studies

    Zhang, Shujun

    2018-01-01

    Genome-wide association studies (GWASs) have identified many disease associated loci, the majority of which have unknown biological functions. Understanding the mechanism underlying trait associations requires identifying trait-relevant tissues and investigating associations in a trait-specific fashion. Here, we extend the widely used linear mixed model to incorporate multiple SNP functional annotations from omics studies with GWAS summary statistics to facilitate the identification of trait-relevant tissues, with which to further construct powerful association tests. Specifically, we rely on a generalized estimating equation based algorithm for parameter inference, a mixture modeling framework for trait-tissue relevance classification, and a weighted sequence kernel association test constructed based on the identified trait-relevant tissues for powerful association analysis. We refer to our analytic procedure as the Scalable Multiple Annotation integration for trait-Relevant Tissue identification and usage (SMART). With extensive simulations, we show how our method can make use of multiple complementary annotations to improve the accuracy for identifying trait-relevant tissues. In addition, our procedure allows us to make use of the inferred trait-relevant tissues, for the first time, to construct more powerful SNP set tests. We apply our method for an in-depth analysis of 43 traits from 28 GWASs using tissue-specific annotations in 105 tissues derived from ENCODE and Roadmap. Our results reveal new trait-tissue relevance, pinpoint important annotations that are informative of trait-tissue relationship, and illustrate how we can use the inferred trait-relevant tissues to construct more powerful association tests in the Wellcome trust case control consortium study. PMID:29377896

  2. Identifying and exploiting trait-relevant tissues with multiple functional annotations in genome-wide association studies.

    Xingjie Hao

    2018-01-01

    Full Text Available Genome-wide association studies (GWASs have identified many disease associated loci, the majority of which have unknown biological functions. Understanding the mechanism underlying trait associations requires identifying trait-relevant tissues and investigating associations in a trait-specific fashion. Here, we extend the widely used linear mixed model to incorporate multiple SNP functional annotations from omics studies with GWAS summary statistics to facilitate the identification of trait-relevant tissues, with which to further construct powerful association tests. Specifically, we rely on a generalized estimating equation based algorithm for parameter inference, a mixture modeling framework for trait-tissue relevance classification, and a weighted sequence kernel association test constructed based on the identified trait-relevant tissues for powerful association analysis. We refer to our analytic procedure as the Scalable Multiple Annotation integration for trait-Relevant Tissue identification and usage (SMART. With extensive simulations, we show how our method can make use of multiple complementary annotations to improve the accuracy for identifying trait-relevant tissues. In addition, our procedure allows us to make use of the inferred trait-relevant tissues, for the first time, to construct more powerful SNP set tests. We apply our method for an in-depth analysis of 43 traits from 28 GWASs using tissue-specific annotations in 105 tissues derived from ENCODE and Roadmap. Our results reveal new trait-tissue relevance, pinpoint important annotations that are informative of trait-tissue relationship, and illustrate how we can use the inferred trait-relevant tissues to construct more powerful association tests in the Wellcome trust case control consortium study.

  3. Method of applying single higher order polynomial basis function over multiple domains

    Lysko, AA

    2010-03-01

    Full Text Available . Derivation of the computational complexity in terms of oating point operations (FLOP) showed a possible speed gain nearly an order of the number of unknowns of direct MoM. 1. INTRODUCTION The process of numerical electromagnetic modeling may be split... into several stages [1], including geometry representation/modeling, representation/modeling of the current distribution, solution of the equations, and computation of the radiation and other parameters. A dominant majority of existing theoretical frameworks...

  4. Induction of functional Fc receptors in P388 leukemia cells. Requirement for multiple differentiation signals.

    Cohen, D A; Stotelmyer, N L; Kaplan, A M

    1985-04-01

    The development of functional Fc receptors (FcR) during induced differentiation with the tumor promoter, phorbol myristate acetate (PMA), was studied in the murine tumor cell line, P388. PMA induced the appearance of FcR on the membranes of P388 cells as indicated by the binding of IgG-coated sheep red blood cells (IgG-SRBC). Concentrations of PMA as low as 1 ng/ml were sufficient to induce the expression of FcR as well as to inhibit cellular division and to induce adherence in the P388 tumor cell line; however, optimal FcR induction occurred at PMA concentrations of 10-100 ng/ml. Immunofluorescent analysis with heat-aggregated myeloma proteins indicated that PMA induced FcR which were capable of binding IgG2a and IgG2b immunoglobulins, but not IgG1. Adherence to a substratum was determined to be a second required signal for expression of FcR, since PMA induction of P388 tumor cells in teflon dishes failed to fully develop FcR and adherence of P388 cells to poly-L-lysine-coated culture dishes in the absence of PMA was insufficient for FcR expression. FcR which appeared after PMA induction were non-functional in the sense that membrane-bound IgG-SRBC were not ingested to any significant extent by the tumor cells. However, if FcR induction occurred in the presence conA-induced rat spleen cell culture supernatants, phagocytosis of membrane-bound erythrocytes occurred. These findings suggest that for the expression of FcR which are capable of particle internalization, at least three identifiable membrane-transmitted signals are required during differentiation.

  5. Evidence implicating the Ras pathway in multiple CD28 costimulatory functions in CD4+ T cells.

    Sujit V Janardhan

    Full Text Available CD28 costimulation is a critical event in the full activation of CD4(+ T cells that augments cytokine gene transcription, promotes cytokine mRNA stability, prevents induction of anergy, increases cellular metabolism, and increases cell survival. However, despite extensive biochemical analysis of the signaling events downstream of CD28, molecular pathways sufficient to functionally replace the diverse aspects of CD28-mediated costimulation in normal T cells have not been identified. Ras/MAPK signaling is a critical pathway downstream of T cell receptor stimulation, but its role in CD28-mediated costimulation has been controversial. We observed that physiologic CD28 costimulation caused a relocalization of the RasGEF RasGRP to the T cell-APC interface by confocal microscopy. In whole cell biochemical analysis, CD28 cross-linking with either anti-CD28 antibody or B7.1-Ig augmented TCR-induced Ras activation. To determine whether Ras signaling was sufficient to functionally mimic CD28 costimulation, we utilized an adenoviral vector encoding constitutively active H-Ras (61L to transduce normal, Coxsackie-Adenovirus Receptor (CAR transgenic CD4(+ T cells. Like costimulation via CD28, active Ras induced AKT, JNK and ERK phosphorylation. In addition, constitutive Ras signaling mimicked the ability of CD28 to costimulate IL-2 protein secretion, prevent anergy induction, increase glucose uptake, and promote cell survival. Importantly, we also found that active Ras mimicked the mechanism by which CD28 costimulates IL-2 production: by increasing IL-2 gene transcription, and promoting IL-2 mRNA stability. Finally, active Ras was able to induce IL-2 production when combined with ionomycin stimulation in a MEK-1-dependent fashion. Our results are consistent with a central role for Ras signaling in CD28-mediated costimulation.

  6. Perichondrium phenotype and border function are regulated by Ext1 and heparan sulfate in developing long bones: a mechanism likely deranged in Hereditary Multiple Exostoses.

    Huegel, Julianne; Mundy, Christina; Sgariglia, Federica; Nygren, Patrik; Billings, Paul C; Yamaguchi, Yu; Koyama, Eiki; Pacifici, Maurizio

    2013-05-01

    During limb skeletogenesis the cartilaginous long bone anlagen and their growth plates become delimited by perichondrium with which they interact functionally. Yet, little is known about how, despite being so intimately associated with cartilage, perichondrium acquires and maintains its distinct phenotype and exerts its border function. Because perichondrium becomes deranged and interrupted by cartilaginous outgrowths in Hereditary Multiple Exostoses (HME), a pediatric disorder caused by EXT mutations and consequent heparan sulfate (HS) deficiency, we asked whether EXT genes and HS normally have roles in establishing its phenotype and function. Indeed, conditional Ext1 ablation in perichondrium and lateral chondrocytes flanking the epiphyseal region of mouse embryo long bone anlagen - a region encompassing the groove of Ranvier - caused ectopic cartilage formation. A similar response was observed when HS function was disrupted in long bone anlagen explants by genetic, pharmacological or enzymatic means, a response preceded by ectopic BMP signaling within perichondrium. These treatments also triggered excess chondrogenesis and cartilage nodule formation and overexpression of chondrogenic and matrix genes in limb bud mesenchymal cells in micromass culture. Interestingly, the treatments disrupted the peripheral definition and border of the cartilage nodules in such a way that many nodules overgrew and fused with each other into large amorphous cartilaginous masses. Interference with HS function reduced the physical association and interactions of BMP2 with HS and increased the cell responsiveness to endogenous and exogenous BMP proteins. In sum, Ext genes and HS are needed to establish and maintain perichondrium's phenotype and border function, restrain pro-chondrogenic signaling proteins including BMPs, and restrict chondrogenesis. Alterations in these mechanisms may contribute to exostosis formation in HME, particularly at the expense of regions rich in progenitor

  7. Functional trait composition of aquatic plants can serve to disentangle multiple interacting stressors in lowland streams

    Baattrup-Pedersen, Annette, E-mail: abp@bios.au.dk [Department of Bioscience, Aarhus University, Vejlsøvej 25, P.O. Box 314, DK-8600 Silkeborg (Denmark); Göthe, Emma [Department of Bioscience, Aarhus University, Vejlsøvej 25, P.O. Box 314, DK-8600 Silkeborg (Denmark); Riis, Tenna [Department of Bioscience, Aarhus University, Ole Worms Allé 1, Building 1135, Room 217, DK-8000 Aarhus C (Denmark); O' Hare, Matthew T. [Centre for Ecology and Hydrology, Bush Estate, Penicuik EH26 0QB (United Kingdom)

    2016-02-01

    stress. The ability to disentangle several stressors is particularly important in lowland stream environments where several stressors act in concert since the impact of the most important stressor can be targeted first, which is essential to improve the ecological status. - Highlights: • Functional trait composition of aquatic plants can distinguish hydromorphological degradation from eutrophication in streams • A conceptual framework on how eutrophication and hydromorphological degradation interact on functional trait composition • Weed cutting can set aside light as a factor controlling trait-abundance pattern in eutrophic lowland streams.

  8. Functional trait composition of aquatic plants can serve to disentangle multiple interacting stressors in lowland streams

    Baattrup-Pedersen, Annette; Göthe, Emma; Riis, Tenna; O'Hare, Matthew T.

    2016-01-01

    stress. The ability to disentangle several stressors is particularly important in lowland stream environments where several stressors act in concert since the impact of the most important stressor can be targeted first, which is essential to improve the ecological status. - Highlights: • Functional trait composition of aquatic plants can distinguish hydromorphological degradation from eutrophication in streams • A conceptual framework on how eutrophication and hydromorphological degradation interact on functional trait composition • Weed cutting can set aside light as a factor controlling trait-abundance pattern in eutrophic lowland streams.

  9. On functionally-graded crashworthy shape of conical structures for multiple load cases

    Pang, Tong; Li, Yinfeng; Kang, Hehe; Sun, Guangyong; Li, Qing; Fang, Jianguang

    2017-01-01

    Many studies on energy absorbers have been focused on tapered tubes because they have significant advantages in crashworthiness and provide a desired constant load-deflection response. However, few studies have been reported on tapered tubes with nonlinearly- variable diameters along the longitudinal direction. This paper presents thin-walled Functionally graded tapered tube (FGTT) with a diameter varying nonlinearly subject to axial (0°) and oblique (10°, 20°, 30°) impacts. To explore the advantages of FGTT, conventional Straight/Conical circular tube (SCT/CCT) with the same mass are compared; and FGTTs with a gradient exponent n > 1 are found to be preferable to others in terms of energy absorption capacity under small impact angles. Then, crashworthiness analyses of different crushing distances are conducted and it is found that under a large impact angle (e.g. 20°, 30°), FGTT with a short crushing distance (e.g. 40mm) have a higher mean crashing force than long crushing distance (e.g. 120 mm), especially for n > 1. In addition, the effect of geometric parameters, such as the gradient exponent n and diameter range ΔD between top (incident) and bottom (distal) diameters of FGTTs, are also studied and it is found that the FGTT with ΔD = 40 mm and n > 1 exhibits better crashworthiness than the others under small impact angles (0°, 10°). This paper demonstrates that such FGTT structures have a certain potential to be an energy absorber.

  10. Impacts of multiple stressors on ecosystem function: Leaf decomposition in constructed urban wetlands

    Mackintosh, Teresa J.; Davis, Jenny A.; Thompson, Ross M.

    2016-01-01

    The impact of stormwater on stream biota is well documented, but less is known about the impacts on ecosystem processes, such as the breakdown of organic matter. This study sought to establish whether the degree of urbanisation affected rates of leaf-litter breakdown within constructed wetlands. A litter bag method was used to ascertain rate of decomposition along a gradient of urbanisation (total imperviousness, TI), in constructed wetlands in western and south-eastern Melbourne. A significant positive relationship between TI and breakdown rate was found in the south-eastern wetlands. The significant reduction in rate of invertebrate-mediated breakdown with increasing concentration of certain metals was consistent with other studies. However, overall there was an increase in rate of breakdown. Studies have shown that the effects of heavy metals can be negated if nutrient levels are high. Our results suggest that other parameters besides exposure to contaminants are likely to affect leaf litter breakdown. - Highlights: • There have been few studies on the effect of urbanisation on ecosystem function. • Rate of leaf litter breakdown increased moving along a gradient of urbanisation. • There was a reduction in invertebrate mediated breakdown with certain metals. • Results suggest other parameters besides contaminants affect leaf litter breakdown. - Certain heavy metals led to a decrease in leaf litter breakdown; however overall, there was a positive relationship between breakdown and increasing urbanisation.

  11. Thymosin β4: multiple functions in protection, repair and regeneration of the mammalian heart.

    Bollini, Sveva; Riley, Paul R; Smart, Nicola

    2015-01-01

    Despite recent improvements in interventional medicine, cardiovascular disease still represents the major cause of morbidity worldwide, with myocardial infarction being the most common cardiac injury. This has sustained the development of several regenerative strategies based on the use of stem cells and tissue engineering approaches in order to achieve cardiac repair and regeneration by enhancing coronary neovascularization, modulating acute inflammation and supporting myocardial regeneration to provide new functional muscle. The actin monomer binding peptide, Thymosin β4 (Tβ4), has recently been described as a powerful regenerative agent with angiogenic, anti-inflammatory and cardioprotective effects on the heart and which specifically acts on its resident cardiac progenitor cells. In this review we will discuss the state of the art regarding the many roles of Tβ4 in preserving and regenerating the mammalian heart, with specific attention to its ability to activate the quiescent adult epicardium and specific subsets of epicardial progenitor cells for repair. The therapeutic potential of Tβ4 for the treatment of cardiac failure is herein evaluated alongside existing, emerging and prospective novel treatments.

  12. On functionally-graded crashworthy shape of conical structures for multiple load cases

    Pang, Tong; Li, Yinfeng [Hunan University, Changsha (China); Kang, Hehe [Chongqing Changan Automobile Co. Ltd., Chongqing (China); Sun, Guangyong; Li, Qing [The University of Sydney, Sydney (Australia); Fang, Jianguang [University of Technology Sydney, Sydney (Australia)

    2017-06-15

    Many studies on energy absorbers have been focused on tapered tubes because they have significant advantages in crashworthiness and provide a desired constant load-deflection response. However, few studies have been reported on tapered tubes with nonlinearly- variable diameters along the longitudinal direction. This paper presents thin-walled Functionally graded tapered tube (FGTT) with a diameter varying nonlinearly subject to axial (0°) and oblique (10°, 20°, 30°) impacts. To explore the advantages of FGTT, conventional Straight/Conical circular tube (SCT/CCT) with the same mass are compared; and FGTTs with a gradient exponent n > 1 are found to be preferable to others in terms of energy absorption capacity under small impact angles. Then, crashworthiness analyses of different crushing distances are conducted and it is found that under a large impact angle (e.g. 20°, 30°), FGTT with a short crushing distance (e.g. 40mm) have a higher mean crashing force than long crushing distance (e.g. 120 mm), especially for n > 1. In addition, the effect of geometric parameters, such as the gradient exponent n and diameter range ΔD between top (incident) and bottom (distal) diameters of FGTTs, are also studied and it is found that the FGTT with ΔD = 40 mm and n > 1 exhibits better crashworthiness than the others under small impact angles (0°, 10°). This paper demonstrates that such FGTT structures have a certain potential to be an energy absorber.

  13. Multiple determinants of transfer of evaluative function after conditioning with free-operant schedules of reinforcement.

    Dack, Charlotte; Reed, Phil; McHugh, Louise

    2010-11-01

    The aim of the four present experiments was to explore how different schedules of reinforcement influence schedule-induced behavior, their impact on evaluative ratings given to conditioned stimuli associated with each schedule through evaluative conditioning, and the transfer of these evaluations through derived stimulus networks. Experiment 1 compared two contrasting response reinforcement rules (variable ratio [VR], variable interval [VI]). Experiment 2 varied the response to reinforcement rule between two schedules but equated the outcome to response rate (differential reinforcement of high rate [DRH] vs. VR). Experiment 3 compared molar and molecular aspects of contingencies of reinforcement (tandem VIVR vs. tandem VRVI). Finally, Experiment 4 employed schedules that induced low rates of responding to determine whether, under these circumstances, responses were more sensitive to the molecular aspects of a schedule (differential reinforcement of low rate [DRL] vs. VI). The findings suggest that the transfer of evaluative functions is determined mainly by differences in response rate between the schedules and the molar aspects of the schedules. However, when neither schedule was based on a strong response reinforcement rule, the transfer of evaluative judgments came under the control of the molecular aspects of the schedule.

  14. Response function of NaI(Tl) detectors and multiple backscattering of gamma rays in aluminium

    Sabharwal, Arvind D.; Singh, Manpreet; Singh, Bhajan; Sandhu, B.S.

    2008-01-01

    The response function, converting the observed pulse-height distribution of a NaI(Tl) detector to a true photon spectrum, is obtained experimentally with the help of an inverse matrix approach. The energy of gamma-ray photons continuously decreases as the number of scatterings increases in a sample having finite dimensions when one deals with the depth of the sample. The present experiments are undertaken to study the effect of target thickness on intensity distribution of gamma photons multiply backscattered from an aluminium target. A NaI(Tl) gamma-ray detector detects the photons backscattered from the aluminium target. The subtraction of analytically estimated singly scattered distribution from the observed intensity distribution (originating from interactions of primary gamma-ray photons with the target) results in multiply backscattered events. We observe that for each incident gamma photon energy, the number of multiply backscattered photons increases with increase in target thickness and then saturates at a particular target thickness called the saturation thickness (depth). Saturation thickness for multiply backscattering of gamma photons is found to decrease with increase in energy of incident gamma-ray photons

  15. Pronounced Structural and Functional Damage in Early Adult Pediatric-Onset Multiple Sclerosis with No or Minimal Clinical Disability

    Antonio Giorgio

    2017-11-01

    Full Text Available Pediatric-onset multiple sclerosis (POMS may represent a model of vulnerability to damage occurring during a period of active maturation of the human brain. Whereas adaptive mechanisms seem to take place in the POMS brain in the short-medium term, natural history studies have shown that these patients reach irreversible disability, despite slower progression, at a significantly younger age than adult-onset MS (AOMS patients. We tested for the first time whether significant brain alterations already occurred in POMS patients in their early adulthood and with no or minimal disability (n = 15 in comparison with age- and disability-matched AOMS patients (n = 14 and to normal controls (NC, n = 20. We used a multimodal MRI approach by modeling, using FSL, voxelwise measures of microstructural integrity of white matter tracts and gray matter volumes with those of intra- and internetwork functional connectivity (FC (analysis of variance, p ≤ 0.01, corrected for multiple comparisons across space. POMS patients showed, when compared with both NC and AOMS patients, altered measures of diffusion tensor imaging (reduced fractional anisotropy and/or increased diffusivities and higher probability of lesion occurrence in a clinically eloquent region for physical disability such as the posterior corona radiata. In addition, POMS patients showed, compared with the other two groups, reduced long-range FC, assessed from resting functional MRI, between default mode network and secondary visual network, whose interaction subserves important cognitive functions such as spatial attention and visual learning. Overall, this pattern of structural damage and brain connectivity disruption in early adult POMS patients with no or minimal clinical disability might explain their unfavorable clinical outcome in the long term.

  16. The influence of multiple sensory impairments on functional balance and difficulty with falls among U.S. adults.

    Wilson, Samuel J; Garner, John C; Loprinzi, Paul D

    2016-06-01

    Studies have looked at the individual associations of sensory impairment on balance, but no population-based studies have examined their combined association on balance and difficulty with falls. Thus, the purpose of this study was to examine both the independent associations and combined associations of visual impairment, peripheral neuropathy, and self-reported hearing loss with the odds of reporting difficulty with falls and functional balance. Data from the 2003-2004 National Health and Nutrition Examination Survey were used. Vision and peripheral neuropathy were objectively measured, and hearing was self-reported. Balance testing consisted of a modified Romberg test. After exclusions, 1662 (40-85years of age) participants provided complete data on the study variables. Sensory impairment was associated with perceived difficulty of falls and functional balance. Participants who presented a single sensory impairment had 29% reduced odds of having functional balance (95% CI=0.54-0.93, p=0.01) and increased odds of reporting difficulty with falls by 61% (95% CI=0.99-2.60, p=0.05). Moreover, our multisensory models showed some evidence of a dose-response relationship, in that sensory impairment of multiple sensory systems was associated with worse balance (OR =0.59, CI=0.35-1.00, p=0.05) and perceived difficulty of falls (OR =5.02, 95% CI=1.99-12.66, p=0.002) when compared to those with less sensory impairment. Multiple sensory impairment is associated with significantly higher odds of both reporting difficulty with falls and balance dysfunction, which may lead to a subsequent fall, ultimately compromising the individual's health. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. The multiple functions of the endocannabinoid system: a focus on the regulation of food intake

    Tibiriça Eduardo

    2010-01-01

    Full Text Available Abstract Background Cannabis sativa (also known as marijuana has been cultivated by man for more than 5,000 years. However, there was a rise in its use in the 20th century for recreational, religious or spiritual, and medicinal purposes. The main psychoactive constituent of cannabis, whose structure was identified in the 1960's, is Δ9-tetrahydrocannabinol. On the other hand, the discovery of cannabinoid receptors and their endogenous agonists took place only very recently. In fact, the first cannabinoid receptor (CB1 was cloned in 1990, followed 3 years later by the characterization of a second cannabinoid receptor (CB2. Since the 19th century, the use of cannabis has been reported to stimulate appetite and increase the consumption of sweet and tasty food, sometimes resulting in significant weight gain. The recent description of the endocannabinoid system, not only in the central nervous system but also in peripheral tissues, points to its involvement in the regulation of appetite, food intake and energy metabolism. Consequently, the pharmacological modulation of the over-activity of this system could be useful in the treatment of the metabolic syndrome. Conclusions The endocannabinoid system has important physiological functions not only in the central nervous system but also in peripheral tissues. The activation of central CB1 receptors, particularly in hypothalamic nuclei and in the limbic system, is involved in the regulation of feeding behavior, and especially in the control of the intake of palatable food. In the periphery, cannabinoid receptors are present in adipocytes, skeletal muscle, gastrointestinal tract and liver, modulating energy metabolism.

  18. Chapter Four : Towards an Integration of Biodiversity–Ecosystem Functioning and Food Web Theory to Evaluate Relationships between Multiple Ecosystem Services

    Hines, J.; Putten, van der W.H.; Deyn, de G.B.; Wagg, C.; Voigt, W.; Mulder, C.; Weisser, W.W.; Engel, J.; Melian, C.; Scheu, S.; Birkhofer, K.; Ebeling, A.; Scherber, C.; Eisenhauer, N.

    2015-01-01

    Ecosystem responses to changes in species diversity are often studied individually. However, changes in species diversity can simultaneously influence multiple interdependent ecosystem functions. Therefore, an important challenge is to determine when and how changes in species diversity that

  19. Pathological changes of the chemosensory function in multiple sclerosis. An MRI study

    Schmidt, F.A.; Harms, L.; Fleiner, F.; Dahlslett, B.; Goektas, Oe.; Bohner, G.; Erb, K.; Luedemann, L.

    2011-01-01

    Purpose: To examine possible causes for olfactory and gustatory dysfunction in MS patients in a prospective study with MRI. Materials and Methods: 30 MS patients (21 women, 11 men, 22 - 65 years, diameter 42 years) were examined by MRI. The olfactory bulb (OB) and olfactory brain volume was correlated with the number and volume of MS lesions in the olfactory brain and the non-olfactory brain. Olfactory testing was performed using the Threshold-Discrimination-Identification Test (TDI), and gustatory function was tested using the Taste-Strips-Test (TST). Results: 33 % of the MS patients displayed olfactory dysfunction (8 % of the control group), and 17 % displayed gustatory dysfunction (5 % of the control group). There was a correlation between the olfactory brain volume and the number (r = -0.38, p < 0.05) and volume (r = -0.38, p < 0.05) of MS lesions in the olfactory brain. The olfactory brain volume correlated with the number of MS lesions in the non-olfactory brain (r = -0.48, p < 0.05). The volume of the left OB correlated with the volume of MS lesions in the olfactory brain (r = -0.42, p < 0.05), the number (r = 0.37, p < 0.05) and volume (r = 0.4, p < 0.05) of lesions in the left part of the olfactory brain and with the TST score (r = -0.45, p < 0.05). The TST score correlated with the volume of lesions in the left (r = -0.45, p < 0.05) and right part (r = -0.53, p < 0.05) of the olfactory brain. The TST score correlated with the number of lesions in the non-olfactory brain (r = -0.48, p < 0.05). Conclusion: The correlation between a higher number and volume of MS lesions in the olfactory brain with a decreased OB and olfactory brain volume could help to explain olfactory and gustatory dysfunction in MS patients. Just the left OB correlated with the number and volume of lesions in the olfactory brain. Manual segmentation was a suitable method for measuring OB and olfactory brain volume. (orig.)

  20. Use of Multi-class Empirical Orthogonal Function for Identification of Hydrogeological Parameters and Spatiotemporal Pattern of Multiple Recharges in Groundwater Modeling

    Huang, C. L.; Hsu, N. S.; Yeh, W. W. G.; Hsieh, I. H.

    2017-12-01

    This study develops an innovative calibration method for regional groundwater modeling by using multi-class empirical orthogonal functions (EOFs). The developed method is an iterative approach. Prior to carrying out the iterative procedures, the groundwater storage hydrographs associated with the observation wells are calculated. The combined multi-class EOF amplitudes and EOF expansion coefficients of the storage hydrographs are then used to compute the initial gauss of the temporal and spatial pattern of multiple recharges. The initial guess of the hydrogeological parameters are also assigned according to in-situ pumping experiment. The recharges include net rainfall recharge and boundary recharge, and the hydrogeological parameters are riverbed leakage conductivity, horizontal hydraulic conductivity, vertical hydraulic conductivity, storage coefficient, and specific yield. The first step of the iterative algorithm is to conduct the numerical model (i.e. MODFLOW) by the initial guess / adjusted values of the recharges and parameters. Second, in order to determine the best EOF combination of the error storage hydrographs for determining the correction vectors, the objective function is devised as minimizing the root mean square error (RMSE) of the simulated storage hydrographs. The error storage hydrograph are the differences between the storage hydrographs computed from observed and simulated groundwater level fluctuations. Third, adjust the values of recharges and parameters and repeat the iterative procedures until the stopping criterion is reached. The established methodology was applied to the groundwater system of Ming-Chu Basin, Taiwan. The study period is from January 1st to December 2ed in 2012. Results showed that the optimal EOF combination for the multiple recharges and hydrogeological parameters can decrease the RMSE of the simulated storage hydrographs dramatically within three calibration iterations. It represents that the iterative approach that

  1. Evaluation of Multiple-Sampling Function used with a Microtek flatbed scanner for Radiation Dosimetry Calibration of EBT2 Film

    Chang, Liyun [Department of Medical Imaging and Radiological Sciences, I-Shou University, Kaohsiung 82445, Taiwan (China); Ho, Sheng-Yow [Department of Nursing, Chang Jung Christian University, Tainan 71101, Taiwan (China); Department of Radiation Oncology, Chi Mei Medical Center, Liouying, Tainan 73657, Taiwan (China); Ding, Hueisch-Jy [Department of Medical Imaging and Radiological Sciences, I-Shou University, Kaohsiung 82445, Taiwan (China); Hwang, Ing-Ming [Department of Medical Imaging and Radiology, Shu Zen College of Medicine and Management, Kaohsiung 82144, Taiwan (China); Chen, Pang-Yu, E-mail: pangyuchen@yahoo.com.tw [Department of Radiation Oncology, Sinlau Christian Hospital, Tainan 70142, Taiwan (China); Lee, Tsair-Fwu, E-mail: tflee@kuas.edu.tw [Medical Physics and Informatics Laboratory, Department of Electronics Engineering, National Kaohsiung University of Applied Sciences, Kaohsiung 80778, Taiwan (China)

    2016-10-01

    The radiochromic EBT2 film is a widely used quality assurance device for radiation therapy. This study evaluated the film calibration performance of the multiple-sampling function, a function of the ScanWizard Pro scanning software provided by the manufacturer, when used with Microtek 9800XL plus (9800XL{sup +}) flatbed scanner. By using the PDD method, each one of the eight EBT2 films, four delivered by 290 monitor unit (MU) and four by 88 MU via 6-MV photon beams, was tightly sandwiched in a 30{sup 3}-cm{sup 3} water equivalent polystyrene phantom prior to irradiation. Before and after irradiation, all films were scanned using the Microtek 9800XL{sup +} scanner with five different modes of the multiple-sampling function, which could generate the image with the averaged result of multiple-sampling. The net optical densities (netOD) on the beam central axis of film were assigned to corresponding depth doses for calibration. For each sampling mode with either delivered MU, the depth-dose uncertainty of a single film from repeated scans and that of a single scan of the four films were analyzed. Finally, the calibration error and the combined calibration uncertainty between film determined depth-doses and delivered depth-doses were calculated and evaluated for each sampling mode. All standard deviations and the calibration error were demonstrated to be unrelated to the number of sampling lines. The calibration error of the 2-line and 16-line mode was within 3 cGy and better than that of the other modes. The combined uncertainty of the 2-line mode was the lowest, which was generally less than 6 cGy except for the delivered dose around 100 cGy. The evaluation described herein revealed that the EBT2 film calibrated with the 2-line mode has relatively lower error, scanning time and combined uncertianty. Therefore, it is recommended for routine EBT2 film calibration and verification of treatment plans.

  2. Synthesis of palladium@gold nanoalloys/nitrogen and sulphur-functionalized multiple graphene aerogel for electrochemical detection of dopamine

    Li, Ruiyi; Yang, Tingting [School of Chemical and Material Engineering, Jiangnan University, Wuxi 214122 (China); Li, Zaijun, E-mail: zaijunli@jiangnan.edu.cn [School of Chemical and Material Engineering, Jiangnan University, Wuxi 214122 (China); Key Laboratory of Food Colloids and Biotechnology, Ministry of Education, Wuxi 214122 (China); Gu, Zhiguo; Wang, Guangli; Liu, Junkang [School of Chemical and Material Engineering, Jiangnan University, Wuxi 214122 (China)

    2017-02-15

    Integration of noble metal nanomaterials on graphene nanosheets potentially paves one way to improve their electronic, chemical and electrochemical properties. The study reported synthesis of palladium@gold nanoalloys/nitrogen and sulphur-functionalized multiple graphene aerogel composite (Pd@Au/N,S-MGA). The as-prepared composite offers a well-defined three-dimensional architecture with rich of mesopores. The Pd@Au nanoalloys were dispersed on the graphene framework networks and their active sites were fully exposed. The unique structure achieves to ultra high electron/ion conductivity, electrocatalytic activity and structural stability. The sensor based on the Pd@Au/N,S-MGA creates ultrasensitive electrochemical response towards dopamine due to significantly electrochemical synergy between Pd, Au and N,S-MGA. Its differential pulse voltammetric signal linearly increases with the increase of dopamine concentration in the range from 1.0 × 10{sup −9} M to 4.0 × 10{sup −5} M with the detection limit of 3.6 × 10{sup −10} M (S/N = 3). The analytical method provides the advantage of sensitivity, reproducibility, rapidity and long-term stability. It has been successfully applied in the detection of trace dopamine in biological samples. The study also opens a window on the electronic properties of graphene aerogel and metal nanomaterials as well their nanohybrids to meet needs of further applications as nanoelectronics in diagnosis, bioanalysis and catalysis. - Graphical abstract: We reported a new palladium@gold nanoalloys/nitrogen and sulphur-functionalized multiple graphene aerogel. The sensor based on the nanohybrid exhibits ultrahigh sensitivity, reproducibility and stability to electrochemical detection of dopamine. - Highlights: • We reported Pd@A/nitrogen and sulphur-functionalized multiple graphene aerogel. • The nanohybrid offers unique three-dimensional architecture with rich of mesopores. • The architecture achieve to ultrahigh

  3. Synthesis of palladium@gold nanoalloys/nitrogen and sulphur-functionalized multiple graphene aerogel for electrochemical detection of dopamine

    Li, Ruiyi; Yang, Tingting; Li, Zaijun; Gu, Zhiguo; Wang, Guangli; Liu, Junkang

    2017-01-01

    Integration of noble metal nanomaterials on graphene nanosheets potentially paves one way to improve their electronic, chemical and electrochemical properties. The study reported synthesis of palladium@gold nanoalloys/nitrogen and sulphur-functionalized multiple graphene aerogel composite (Pd@Au/N,S-MGA). The as-prepared composite offers a well-defined three-dimensional architecture with rich of mesopores. The Pd@Au nanoalloys were dispersed on the graphene framework networks and their active sites were fully exposed. The unique structure achieves to ultra high electron/ion conductivity, electrocatalytic activity and structural stability. The sensor based on the Pd@Au/N,S-MGA creates ultrasensitive electrochemical response towards dopamine due to significantly electrochemical synergy between Pd, Au and N,S-MGA. Its differential pulse voltammetric signal linearly increases with the increase of dopamine concentration in the range from 1.0 × 10"−"9 M to 4.0 × 10"−"5 M with the detection limit of 3.6 × 10"−"1"0 M (S/N = 3). The analytical method provides the advantage of sensitivity, reproducibility, rapidity and long-term stability. It has been successfully applied in the detection of trace dopamine in biological samples. The study also opens a window on the electronic properties of graphene aerogel and metal nanomaterials as well their nanohybrids to meet needs of further applications as nanoelectronics in diagnosis, bioanalysis and catalysis. - Graphical abstract: We reported a new palladium@gold nanoalloys/nitrogen and sulphur-functionalized multiple graphene aerogel. The sensor based on the nanohybrid exhibits ultrahigh sensitivity, reproducibility and stability to electrochemical detection of dopamine. - Highlights: • We reported Pd@A/nitrogen and sulphur-functionalized multiple graphene aerogel. • The nanohybrid offers unique three-dimensional architecture with rich of mesopores. • The architecture achieve to ultrahigh electron

  4. Characterization and functional correlation of multiple imaging modalities with focal choroidal excavation

    Yun-Chen Chen

    2018-05-01

    Full Text Available Background: To investigate the clinical manifestations and imaging features of near-infrared autofluorescence (NIA, infrared reflectance (IR, fundus autofluorescence (FAF, indocyanine green angiography (ICGA and fluorescein angiography (FAG in the detection of patients with focal choroidal excavation (FCE identified by cross-sectional spectral-domain optical coherence tomography (SD-OCT. Methods: This retrospective cross-sectional study included 12 eyes of 10 Taiwanese patients with FCE diagnosed by SD-OCT. The areas and depths of FCE in serial cross-sectional and en-face OCT were compared in different imaging modalities. NIA, IR, FAF, ICGA and FAG images were obtained. Best corrected visual acuity, subjective distortion area in the Amsler grid and history of maculopathies were also recorded. Results: In areas where the choroid started to excavate as shown in SD-OCT, hypo-autofluorescence in NIA was noted. The area of hypo-fluorescence in NIA of all the FCE lesions showed good correlation with the size. The area of FCE was associated with complications such as choroidal neovascularization and central serous chorioretinopathy (p = 0.014, d.f = 1 and the volume (NIA area × Depth measured by SD-OCT × 1/3 was associated with subjective distortion strongly (p = 0.051, Spearman's correlation = 0.600. Conclusion: Among all image modalities, NIA was the most sensitive tool in area measurement of FCE and peripheral lesion detection. Also, the volume of FCE was associated with subjective distortion and the area was related to complications. Recording the area and volume of FCE could play an important role in monitoring complications. Keywords: Choroid-retina disease, Focal choroidal excavation, Near-infrared autofluorescence, Spectral-domain optical coherence tomography

  5. Impact of consensus contours from multiple PET segmentation methods on the accuracy of functional volume delineation

    Schaefer, A. [Saarland University Medical Centre, Department of Nuclear Medicine, Homburg (Germany); Vermandel, M. [U1189 - ONCO-THAI - Image Assisted Laser Therapy for Oncology, University of Lille, Inserm, CHU Lille, Lille (France); CHU Lille, Nuclear Medicine Department, Lille (France); Baillet, C. [CHU Lille, Nuclear Medicine Department, Lille (France); Dewalle-Vignion, A.S. [U1189 - ONCO-THAI - Image Assisted Laser Therapy for Oncology, University of Lille, Inserm, CHU Lille, Lille (France); Modzelewski, R.; Vera, P.; Gardin, I. [Centre Henri-Becquerel and LITIS EA4108, Rouen (France); Massoptier, L.; Parcq, C.; Gibon, D. [AQUILAB, Research and Innovation Department, Loos Les Lille (France); Fechter, T.; Nestle, U. [University Medical Center Freiburg, Department for Radiation Oncology, Freiburg (Germany); German Cancer Consortium (DKTK) Freiburg and German Cancer Research Center (DKFZ), Heidelberg (Germany); Nemer, U. [University Medical Center Freiburg, Department of Nuclear Medicine, Freiburg (Germany)

    2016-05-15

    The aim of this study was to evaluate the impact of consensus algorithms on segmentation results when applied to clinical PET images. In particular, whether the use of the majority vote or STAPLE algorithm could improve the accuracy and reproducibility of the segmentation provided by the combination of three semiautomatic segmentation algorithms was investigated. Three published segmentation methods (contrast-oriented, possibility theory and adaptive thresholding) and two consensus algorithms (majority vote and STAPLE) were implemented in a single software platform (Artiview registered). Four clinical datasets including different locations (thorax, breast, abdomen) or pathologies (primary NSCLC tumours, metastasis, lymphoma) were used to evaluate accuracy and reproducibility of the consensus approach in comparison with pathology as the ground truth or CT as a ground truth surrogate. Variability in the performance of the individual segmentation algorithms for lesions of different tumour entities reflected the variability in PET images in terms of resolution, contrast and noise. Independent of location and pathology of the lesion, however, the consensus method resulted in improved accuracy in volume segmentation compared with the worst-performing individual method in the majority of cases and was close to the best-performing method in many cases. In addition, the implementation revealed high reproducibility in the segmentation results with small changes in the respective starting conditions. There were no significant differences in the results with the STAPLE algorithm and the majority vote algorithm. This study showed that combining different PET segmentation methods by the use of a consensus algorithm offers robustness against the variable performance of individual segmentation methods and this approach would therefore be useful in radiation oncology. It might also be relevant for other scenarios such as the merging of expert recommendations in clinical routine and

  6. TALEN-mediated genetic tailoring as a tool to analyze the function of acquired mutations in multiple myeloma cells

    Wu, X; Blackburn, P R; Tschumper, R C; Ekker, S C; Jelinek, D F

    2014-01-01

    Multiple myeloma (MM) is a clonal plasma cell malignancy that is initiated by a number of mutations and the process of disease progression is characterized by further acquisition of mutations. The identification and functional characterization of these myelomagenic mutations is necessary to better understand the underlying pathogenic mechanisms in this disease. Recent advancements in next-generation sequencing have made the identification of most of these mutations a reality. However, the functional characterization of these mutations has been hampered by the lack of proper and efficient tools to dissect these mutations. Here we explored the possible utility of transcription activator-like effector nuclease (TALEN) genome engineering technology to tailoring the genome of MM cells. To test this possibility, we targeted the HPRT1 gene and found that TALENs are a very robust and efficient genome-editing tool in MM cells. Using cotransfected green fluorescent protein as an enrichment marker, single-cell subclones with desirable TALEN modifications in the HPRT1 gene were obtained in as little as 3–4 weeks of time. We believe that TALENs will greatly facilitate the functional study of somatic mutations in MM as well as other cancers

  7. Regional resources buffer the impact of functional limitations on perceived autonomy in older adults with multiple illnesses.

    Schüz, Benjamin; Westland, Josh N; Wurm, Susanne; Tesch-Römer, Clemens; Wolff, Julia K; Warner, Lisa M; Schwarzer, Ralf

    2016-03-01

    Retaining perceptions of autonomy is a key component of successful aging. Perceived autonomy refers to the capacity to make and enact self-directed decisions. These perceptions are often threatened in older adults with multiple illnesses, when functional limitations resulting from these illnesses impede the enactment of self-directed decisions. Regional resources (in Germany specifically at the level of administrative districts) might counteract these impediments of autonomy. Economically stronger districts can provide more-concrete support resources for older adults, buffering the negative effect of functional limitations on self-perceived autonomy. This study assessed participants aged over 65 with 2 or more chronic conditions. In total, N = 287 provided data (Mage = 73.3, SD = 5.07), and n = 97 were women. Gross domestic product (GDP) per capita was used as a proxy measure of administrative district wealth in Germany. Hierarchical multilevel regression analyses with cross-level interactions were conducted. Results suggest that the detrimental effect of functional limitations on perceived autonomy is less pronounced for participants residing in higher GDP districts. Conversely, for participants in lower GDP districts, the effect is exacerbated. This finding suggests that districts with greater financial resources might be better able to invest in supports that promote and facilitate autonomy and, thus, provide a buffer against threats to individual perceived autonomy. (c) 2016 APA, all rights reserved).

  8. Population pharmacokinetics of pomalidomide in patients with relapsed or refractory multiple myeloma with various degrees of impaired renal function

    Li Y

    2017-11-01

    Full Text Available Yan Li,1 Xiaomin Wang,2 Edward O’Mara,1 Meletios A Dimopoulos,3 Pieter Sonneveld,4 Katja C Weisel,5 Jeffrey Matous,6 David S Siegel,7 Jatin J Shah,8 Elisabeth Kueenburg,9 Lars Sternas,9 Chloe Cavanaugh,9 Mohamed Zaki,9 Maria Palmisano,1 Simon Zhou1 1Translational Development and Clinical Pharmacology, Celgene Corporation, Summit, NJ, USA; 2Non-Clinical Development and Drug Metabolism and Pharmacokinetics, Celgene Corporation, Summit, NJ, USA; 3Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Athens, Greece; 4Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands; 5Department of Hematology, University Hospital Tübingen, Tübingen, Germany; 6Department of Hematology/Oncology, Colorado Blood Cancer Institute, Denver, CO, USA; 7Myeloma Division, John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ, USA; 8Department of Lymphoma/Myeloma, Division of Cancer Medicine, MD Anderson Cancer Center, Houston, TX, USA; 9Global Clinical R&D, Celgene Corporation, Summit, NJ, USA Abstract: Pomalidomide is an immunomodulatory drug for treatment of relapsed or refractory multiple myeloma (rrMM in patients who often have comorbid renal conditions. To assess the impact of renal impairment on pomalidomide exposure, a population pharmacokinetics (PPK model of pomalidomide in rrMM patients with various degrees of impaired renal function was developed. Intensive and sparse pomalidomide concentration data collected from two clinical studies in rrMM patients with normal renal function, moderately impaired renal function, severely impaired renal function not requiring dialysis, and with severely impaired renal function requiring dialysis were pooled over the dose range of 2 to 4 mg, to assess specifically the influence of the impaired renal function as a categorical variable and a continuous variable on pomalidomide clearance and plasma exposure. In addition, pomalidomide

  9. Improving physical functional and quality of life in older adults with multiple sclerosis via a DVD-delivered exercise intervention: a study protocol.

    Wójcicki, Thomas R; Roberts, Sarah A; Learmonth, Yvonne C; Hubbard, Elizabeth A; Kinnett-Hopkins, Dominque; Motl, Robert W; McAuley, Edward

    2014-12-01

    There is a need to identify innovative, low-cost and broad-reaching strategies for promoting exercise and improving physical function in older adults with multiple sclerosis (MS). This randomised controlled pilot trial will test the efficacy of a 6-month, DVD-delivered exercise intervention to improve functional performance and quality of life in older adults with MS. Participants will be randomised either into a DVD-delivered exercise condition or an attentional control condition. This novel approach to programme delivery provides participants with detailed exercise instructions which are presented in a progressive manner and includes a variety of modifications to better meet varying levels of physical abilities. The targeted exercises focus on three critical elements of functional fitness: flexibility, strength and balance. It is hypothesised that participants who are randomised to the exercise DVD condition will demonstrate improvements in physical function compared with participants assigned to the attentional control condition. Data analysis will include a 2 (condition)×2 (time) mixed factor analysis of variance (ANOVA) that follows intent-to-treat principles, as well as an examination of effect sizes. Participants will take part in qualitative interviews about perspectives on physical activity and programme participation. The study protocol was approved by a university institutional review board and registered with a federal database. Participants will be asked to read and sign a detailed informed consent document and will be required to provide a physician's approval to participate in the study. The exercise DVDs include an overview of safety-related concerns and recommendations relative to exercise participation, as well as detailed instructions highlighting the proper execution of each exercise presented on screen. Following completion of this trial, data will be immediately analysed and results will be presented at scientific meetings and published in

  10. Functional nanoparticles exploit the bile acid pathway to overcome multiple barriers of the intestinal epithelium for oral insulin delivery

    Fan, Weiwei; Xia, Dengning; Zhu, Quanlei

    2018-01-01

    , especially to avoid lysosomal degradation, and basolateral release. Here, the functional material, deoxycholic acid-conjugated chitosan, is synthesized and loaded with the model protein drug insulin into deoxycholic acid-modified nanoparticles (DNPs). The DNPs designed in this study are demonstrated......Oral absorption of protein/peptide-loaded nanoparticles is often limited by multiple barriers of the intestinal epithelium. In addition to mucus translocation and apical endocytosis, highly efficient transepithelial absorption of nanoparticles requires successful intracellular trafficking...... to endolysosomal escape of DNPs. Additionally, DNPs can interact with a cytosolic ileal bile acid-binding protein that facilitates the intracellular trafficking and basolateral release of insulin. In rats, intravital two-photon microscopy also reveals that the transport of DNPs into the intestinal villi...

  11. A novel anti-EMMPRIN function-blocking antibody reduces T cell proliferation and neurotoxicity: relevance to multiple sclerosis.

    Agrawal, Smriti M; Silva, Claudia; Wang, Janet; Tong, Jade Pui-Wai; Yong, V Wee

    2012-04-05

    Extracellular matrix metalloproteinase inducer (EMMPRIN; CD147, basigin) is an inducer of the expression of several matrix metalloproteinases (MMPs). We reported previously that blocking EMMPRIN activity reduced neuroinflammation and severity of disease in an animal model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE). To improve upon EMMPRIN blockade, and to help unravel the biological functions of EMMPRIN in inflammatory disorders, we have developed several anti-EMMPRIN monoclonal antibodies. Of these monoclonal antibodies, a particular one, clone 10, was efficient in binding mouse and human cells using several methods of detection. The specificity of clone 10 was demonstrated by its lack of staining of EMMPRIN-null embryos compared to heterozygous and wild-type mouse samples. Functionally, human T cells activated with anti-CD3 and anti-CD28 elevated their expression of EMMPRIN and the treatment of these T cells with clone 10 resulted in decreased proliferation and matrix metalloproteinase- 9 (MMP-9) production. Activated human T cells were toxic to human neurons in culture and clone 10 pretreatment reduced T cell cytotoxicity correspondent with decrease of granzyme B levels within T cells. In vivo, EAE mice treated with clone 10 had a markedly reduced disease score compared to mice treated with IgM isotype control. We have produced a novel anti-EMMPRIN monoclonal antibody that blocks several aspects of T cell activity, thus highlighting the multiple roles of EMMPRIN in T cell biology. Moreover, clone 10 reduces EAE scores in mice compared to controls, and has activity on human cells, potentially allowing for the testing of anti-EMMPRIN treatment not only in EAE, but conceivably also in MS.

  12. A novel anti-EMMPRIN function-blocking antibody reduces T cell proliferation and neurotoxicity: relevance to multiple sclerosis

    Agrawal Smriti M

    2012-04-01

    Full Text Available Abstract Background Extracellular matrix metalloproteinase inducer (EMMPRIN; CD147, basigin is an inducer of the expression of several matrix metalloproteinases (MMPs. We reported previously that blocking EMMPRIN activity reduced neuroinflammation and severity of disease in an animal model of multiple sclerosis (MS, experimental autoimmune encephalomyelitis (EAE. Methods To improve upon EMMPRIN blockade, and to help unravel the biological functions of EMMPRIN in inflammatory disorders, we have developed several anti-EMMPRIN monoclonal antibodies. Results Of these monoclonal antibodies, a particular one, clone 10, was efficient in binding mouse and human cells using several methods of detection. The specificity of clone 10 was demonstrated by its lack of staining of EMMPRIN-null embryos compared to heterozygous and wild-type mouse samples. Functionally, human T cells activated with anti-CD3 and anti-CD28 elevated their expression of EMMPRIN and the treatment of these T cells with clone 10 resulted in decreased proliferation and matrix metalloproteinase- 9 (MMP-9 production. Activated human T cells were toxic to human neurons in culture and clone 10 pretreatment reduced T cell cytotoxicity correspondent with decrease of granzyme B levels within T cells. In vivo, EAE mice treated with clone 10 had a markedly reduced disease score compared to mice treated with IgM isotype control. Conclusions We have produced a novel anti-EMMPRIN monoclonal antibody that blocks several aspects of T cell activity, thus highlighting the multiple roles of EMMPRIN in T cell biology. Moreover, clone 10 reduces EAE scores in mice compared to controls, and has activity on human cells, potentially allowing for the testing of anti-EMMPRIN treatment not only in EAE, but conceivably also in MS.

  13. Fission neutron multiplicity calculations

    Maerten, H.; Ruben, A.; Seeliger, D.

    1991-01-01

    A model for calculating neutron multiplicities in nuclear fission is presented. It is based on the solution of the energy partition problem as function of mass asymmetry within a phenomenological approach including temperature-dependent microscopic energies. Nuclear structure effects on fragment de-excitation, which influence neutron multiplicities, are discussed. Temperature effects on microscopic energy play an important role in induced fission reactions. Calculated results are presented for various fission reactions induced by neutrons. Data cover the incident energy range 0-20 MeV, i.e. multiple chance fission is considered. (author). 28 refs, 13 figs

  14. THE INFLUENCE OF COMBINATION NON-MEDICAL TREATMENT INCLUDING FUNCTIONAL PROGRAMMED ELECTRICAL STIMULATION ON THE CLINICAL AND INSTRUMENTAL PARAMETERS IN PATIENTS WITH CEREBRAL PALSY WITH SPASTIC DIPLEGIA

    V. V. Eliseev

    2015-01-01

    Full Text Available Background: Cerebral palsy is the leading cause of physical disability in pediatric  age. The search for new methods and improvement of old rehabil- itation techniques is ongoing, due to low efficacy of the latter. Aim: To assess the efficacy of a func- tional programmed electrical muscle stimulation as a part  of combination treatment of patients with cerebral palsy in the form of spastic diplegia. Materials and methods: We analyzed the results of treatment of 71 children with cerebral palsy and spastic diplegia, who had  been  randomized  into two groups  depending on the type of treatment. In  the  first group,  the  patients  (n = 38 received a course of functional programmed electric stim- ulation  in combination with  other  non-medical treatment  methods.  The  second   group   (n = 33 underwent a usual  course  of electrical  stimula- tion in combination with non-medical  treatment, similar to that  in the first group. The third group (control   included   41   children   without    cere- bral palsy. Clinical and  instrumental parameters were  assessed  in all study  participants. Results: After the course of combination treatment in the group  1, the  tonus  of m. gastrocnemius was de- creased significantly by 41%, that of the posterior group  of femur muscles by 43%, adductor group of femur muscles by 36%. In the group  2, the re- spective parameters decreased by 24, 21 and 21%. Muscle power  endurance was  increased  signifi- cantly in patients of both groups: that of long back extensors by 12.5 and 6.2 sec, of m. rectus abdomi- nis by 10.6 sec and 5.2 sec, of gluteal muscles by 9.3 and 4.6 sec, of m. quadriceps  by 19.8 and 7.2 sec, of m. anterior  tibialis by 12.1 and 4.6 sec, respec- tively. After the  treatment, the  active movement volume in the large joints of lower extremities  in the group 1 patients  improved as follows: by 15.6° in hip joints, by 11.1° in knee joints and by

  15. The Armeo Spring as training tool to improve upper limb functionality in multiple sclerosis: a pilot study

    Kerkhofs Lore

    2011-01-01

    Full Text Available Abstract Background Few research in multiple sclerosis (MS has focused on physical rehabilitation of upper limb dysfunction, though the latter strongly influences independent performance of activities of daily living. Upper limb rehabilitation technology could hold promise for complementing traditional MS therapy. Consequently, this pilot study aimed to examine the feasibility of an 8-week mechanical-assisted training program for improving upper limb muscle strength and functional capacity in MS patients with evident paresis. Methods A case series was applied, with provision of a training program (3×/week, 30 minutes/session, supplementary on the customary maintaining care, by employing a gravity-supporting exoskeleton apparatus (Armeo Spring. Ten high-level disability MS patients (Expanded Disability Status Scale 7.0-8.5 actively performed task-oriented movements in a virtual real-life-like learning environment with the affected upper limb. Tests were administered before and after training, and at 2-month follow-up. Muscle strength was determined through the Motricity Index and Jamar hand-held dynamometer. Functional capacity was assessed using the TEMPA, Action Research Arm Test (ARAT and 9-Hole Peg Test (9HPT. Results Muscle strength did not change significantly. Significant gains were particularly found in functional capacity tests. After training completion, TEMPA scores improved (p = 0.02, while a trend towards significance was found for the 9HPT (p = 0.05. At follow-up, the TEMPA as well as ARAT showed greater improvement relative to baseline than after the 8-week intervention period (p = 0.01, p = 0.02 respectively. Conclusions The results of present pilot study suggest that upper limb functionality of high-level disability MS patients can be positively influenced by means of a technology-enhanced physical rehabilitation program.

  16. Abnormal functional connectivity and cortical integrity influence dominant hand motor disability in multiple sclerosis: a multimodal analysis.

    Zhong, Jidan; Nantes, Julia C; Holmes, Scott A; Gallant, Serge; Narayanan, Sridar; Koski, Lisa

    2016-12-01

    Functional reorganization and structural damage occur in the brains of people with multiple sclerosis (MS) throughout the disease course. However, the relationship between resting-state functional connectivity (FC) reorganization in the sensorimotor network and motor disability in MS is not well understood. This study used resting-state fMRI, T1-weighted and T2-weighted, and magnetization transfer (MT) imaging to investigate the relationship between abnormal FC in the sensorimotor network and upper limb motor disability in people with MS, as well as the impact of disease-related structural abnormalities within this network. Specifically, the differences in FC of the left hemisphere hand motor region between MS participants with preserved (n = 17) and impaired (n = 26) right hand function, compared with healthy controls (n = 20) was investigated. Differences in brain atrophy and MT ratio measured at the global and regional levels were also investigated between the three groups. Motor preserved MS participants had stronger FC in structurally intact visual information processing regions relative to motor impaired MS participants. Motor impaired MS participants showed weaker FC in the sensorimotor and somatosensory association cortices and more severe structural damage throughout the brain compared with the other groups. Logistic regression analysis showed that regional MTR predicted motor disability beyond the impact of global atrophy whereas regional grey matter volume did not. More importantly, as the first multimodal analysis combining resting-state fMRI, T1-weighted, T2-weighted and MTR images in MS, we demonstrate how a combination of structural and functional changes may contribute to motor impairment or preservation in MS. Hum Brain Mapp 37:4262-4275, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  17. Hyperfractionated radiotherapy and simultaneous cisplatin for stage-III and -IV carcinomas of the head and neck. Long-term results including functional outcome

    Huguenin, P.; Glanzmann, C.; Taussky, D.; Luetolf, U.M.; Schmid, S.; Moe, K.

    1998-01-01

    Purpose: To assess the survival rate, the probability of local control, the patterns of relapse and late sequelae including self-reported quality of life in patients treated with hyperfractionated radiotherapy (RT) and simultaneous CDDP chemotherapy for stage-III to stage-IV carcinomas of the head and neck. Methods: From 1988 to 1994, 64 patients (median age 55.5 years) with carcinomas of different subsites, excluding the nasopharynx, were treated in a pilot study with 1.2 Gy bid (6 h interval; total dose 74.4 Gy) and simultaneous CDDP (20 mg/m 2 daily, 5 days in week 1 and 5) and followed at regular intervals. Overall survival and local control, as well as the rates of late toxicity, were estimated using the actuarial method. Median follow-up was 3.3 years for all and 5.2 years for surviving patients. To assess the quality of life, the EORTC QLQ-C 30 questionnaire and the H and N35 module questionnaire were sent to the patients surviving with no evidence of disease or second primary tumors; they were answered by 15/23 (67%). Results: Overall survival was 37% at 5 years, whereas disease-specific survival was 59%. Twenty-three patients died from uncontrolled head and neck cancer. Second primary tumors were observed in 13 patients, most frequently in the lung. Local control without salvage surgery was 74% at 5 years for all subsites and stages, and loco-regional disease-free survival was 72%. Eleven patients developed distant metastases, which was the only site of failure in 6 cases. Salvage surgery was successful in 2 cases. The actuarial estimates of ≥grade-3 late toxicity was 4% for the mandibular bone and 23% for dysphagia, and 50% of the patients experienced a permanent xerostomy. Self-reported global quality of life in surviving patients was good (mean 68 points on a scale 0 to 100); consequences of impaired salivary function had most impact on nutritional and social aspects. Conclusions: Hyperfractionated RT with concomitant CDDP is well tolerated and highly

  18. A de novo 1.58 Mb deletion, including MAP2K6 and mapping 1.28 Mb upstream to SOX9, identified in a patient with Pierre Robin sequence and osteopenia with multiple fractures.

    Smyk, Marta; Roeder, Elizabeth; Cheung, Sau Wai; Szafranski, Przemyslaw; Stankiewicz, Paweł

    2015-08-01

    Defects of long-range regulatory elements of dosage-sensitive genes represent an under-recognized mechanism underlying genetic diseases. Haploinsufficiency of SOX9, the gene essential for development of testes and differentiation of chondrocytes, results in campomelic dysplasia, a skeletal malformation syndrome often associated with sex reversal. Chromosomal rearrangements with breakpoints mapping up to 1.6 Mb up- and downstream to SOX9, and disrupting its distant cis-regulatory elements, have been described in patients with milder forms of campomelic dysplasia, Pierre Robin sequence, and sex reversal. We present an ∼1.58 Mb deletion mapping ∼1.28 Mb upstream to SOX9 that encompasses its putative long-range cis-regulatory element(s) and MAP2K6 in a patient with Pierre Robin sequence and osteopenia with multiple fractures. Low bone mass panel testing using massively parallel sequencing of 23 nuclear genes, including COL1A1 and COL1A2 was negative. Based on the previous mouse model of Map2k6, suggesting that Sox9 is likely a downstream target of the p38 MAPK pathway, and our previous chromosome conformation capture-on-chip (4C) data showing potential interactions between SOX9 promoter and MAP2K6, we hypothesize that deletion of MAP2K6 might have affected SOX9 expression and contributed to our patient's phenotype. © 2015 Wiley Periodicals, Inc.

  19. Changes in endocrine thymus function in patients with breast cancer under the action of combined treatment including non-specific active immunotherapy

    Bendyug, G.D.

    1988-01-01

    The state of endocrine thymus function in patients with breast cancer of the 1st-4th stage and in 31 patients with precancerous diseases is studied. It is established that considerable decrease of thymus serous factor (TSF) content in all patients is observed. Radiation- and polychemotherapy carried out decreases the endocrine thymus function. Inclusions of non-specific active immunotherapy in patients' treatment promote the increase of TSF content, that increases treatment efficiency

  20. The Clinical Obesity Maintenance Model: An Integration of Psychological Constructs including Mood, Emotional Regulation, Disordered Overeating, Habitual Cluster Behaviours, Health Literacy and Cognitive Function

    Raman, Jayanthi; Smith, Evelyn; Hay, Phillipa

    2013-01-01

    Psychological distress and deficits in executive functioning are likely to be important barriers to effective weight loss maintenance. The purpose of this paper is twofold. First, in the light of recent evidence in the fields of neuropsychology and obesity, particularly on the deficits in the executive function in overweight and obese individuals, a conceptual and theoretical framework of obesity maintenance is introduced by way of a clinical obesity maintenance model (COMM). It is argued tha...

  1. Bayes multiple decision functions

    Wu, Wensong; Peña, Edsel A.

    2013-01-01

    This paper deals with the problem of simultaneously making many ($M$) binary decisions based on one realization of a random data matrix $\\mathbf{X}$. $M$ is typically large and $\\mathbf{X}$ will usually have $M$ rows associated with each of the $M$ decisions to make, but for each row the data may be low dimensional. Such problems arise in many practical areas such as the biological and medical sciences, where the available dataset is from microarrays or other high-throughput technology and wi...

  2. A potent complement factor C3 specific nanobody inhibiting multiple functions in the alternative pathway of human and murine complement.

    Jensen, Rasmus K; Pihl, Rasmus; Gadeberg, Trine A F; Jensen, Jan K; Andersen, Kasper R; Thiel, Steffen; Laursen, Nick S; Andersen, Gregers Rom

    2018-03-01

    The complement system is a complex, carefully regulated proteolytic cascade for which suppression of aberrant activation is of increasing clinical relevance and inhibition of the complement alternative pathway is a subject of intense research. Here, we describe the nanobody hC3Nb1 that binds to multiple functional states of C3 with sub-nanomolar affinity. The nanobody causes a complete shutdown of alternative pathway activity in human and murine serum when present in concentrations comparable to C3, and hC3Nb1 is shown to prevent both proconvertase assembly as well as binding of the C3 substrate to C3 convertases. Our crystal structure of the C3b-hC3Nb1 complex and functional experiments demonstrate that proconvertase formation is blocked by steric hindrance between the nanobody and an Asn-linked glycan on complement factor B. In addition, hC3Nb1 is shown to prevent factor H binding to C3b rationalizing its inhibition of factor I activity. Our results identify hC3Nb1 as a versatile, inexpensive, and powerful inhibitor of the alternative pathway in both human and murine in vitro model systems of complement activation. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

  3. A potent complement factor C3 specific nanobody inhibiting multiple functions in the alternative pathway of human and murine complement

    Jensen, Rasmus K; Pihl, Rasmus; Gadeberg, Trine A F

    2018-01-01

    The complement system is a complex, carefully regulated proteolytic cascade for which suppression of aberrant activation is of increasing clinical relevance and inhibition of the complement alternative pathway is a subject of intense research. Here, we describe the nanobody hC3Nb1 that binds...... to multiple functional states of C3 with sub-nanomolar affinity. The nanobody causes a complete shutdown of alternative pathway activity in human and murine serum when present in concentrations comparable to C3, and hC3Nb1 is shown to prevent both proconvertase assembly as well as binding of the C3 substrate...... to C3 convertases. Our crystal structure of the C3b-hC3Nb1 complex and functional experiments demonstrate that proconvertase formation is blocked by steric hindrance between the nanobody and an Asn-linked glycan on complement factor B. In addition, hC3Nb1 is shown to prevent factor H binding to C3b...

  4. Simultaneous dual-functioning InGaN/GaN multiple-quantum-well diode for transferrable optoelectronics

    Shi, Zheng; Yuan, Jialei; Zhang, Shuai; Liu, Yuhuai; Wang, Yongjin

    2017-10-01

    We propose a wafer-level procedure for the fabrication of 1.5-mm-diameter dual functioning InGaN/GaN multiple-quantum-well (MQW) diodes on a GaN-on-silicon platform for transferrable optoelectronics. Nitride semiconductor materials are grown on (111) silicon substrates with intermediate Al-composition step-graded buffer layers, and membrane-type MQW-diode architectures are obtained by a combination of silicon removal and III-nitride film backside thinning. Suspended MQW-diodes are directly transferred from silicon to foreign substrates such as metal, glass and polyethylene terephthalate by mechanically breaking the support beams. The transferred MQW-diodes display strong electroluminescence under current injection and photodetection under light irradiation. Interestingly, they demonstrate a simultaneous light-emitting light-detecting function, endowing the 1.5-mm-diameter MQW-diode with the capability of producing transferrable optoelectronics for adjustable displays, wearable optical sensors, multifunctional energy harvesting, flexible light communication and monolithic photonic circuit.

  5. Utility of a patient-reported outcome in measuring functional impairment during autologous stem cell transplant in patients with multiple myeloma.

    Shah, Nina; Shi, Qiuling; Giralt, Sergio; Williams, Loretta; Bashir, Qaiser; Qazilbash, Muzaffar; Champlin, Richard E; Cleeland, Charles S; Wang, Xin Shelley

    2018-04-01

    We aimed to determine the utility of a patient-reported outcome (PRO) as it relates to patient performed testing (PPT) for measuring functional status in multiple myeloma patients after autologous hematopoietic stem cell transplantation (auto-HCT). Symptom interference on walking (a PRO) was measured by the MD Anderson Symptom Inventory (MDASI). PPT was assessed via 6-min walk test (6MWT). Mixed effects modeling was used to examine (1) the longitudinal relationship between the MDASI score and 6MWT distance and (2) the MDASI scores between patients who did or did not complete the 6WMT. Receiver operating characteristic (ROC) curve analysis was performed to quantify the construct validity of the PRO by differentiating performance status. Seventy-nine patients were included. Mean 6MWT distance significantly correlated with MDASI-walking interference score (PRO) over the first month of auto-HCT (est = 6.09, p = 0.006). There was a significantly higher completion rate for MDASI versus 6MWT at each time point (p Patients who completed the 6MWT reported less interference on walking during the study period (est = 1.61, p patients undergoing auto-HCT. As patients with poorer functional status during therapy are less likely to complete PPT, this PRO may offer a more practical quantitative measure of functioning in patients.

  6. Problemas multiplicativos envolvendo combinatória: estratégias de resolução empregadas por alunos do Ensino Fundamental público Multiplicative problems including combinatorics: solving strategies adopted by Public Elementary School students

    Leny R. M. Teixeira

    2011-01-01

    was better in problems with two variables and factors with low values. There was no alteration in the performance among the 6th and 9th graders. In general, the difficulties found were related to: 1 intuitive models students have when dealing with multiplication (especially the one including repeated addition; 2 the semantic structure of the problem; 3 numerical preferences regarding the quantity of numerical digits, ways of representing the problem and interpretation of verbal problem statements. Because multiplication is a very complex operation involving abstract cognitive processes in its solution, we believe that the teacher needs to know them to facilitate students' learning.

  7. How does multiple trauma, traumatic brain injury (TBI) or spinal cord injury (SCI) affect male sexual functioning?

    Treacy, C.

    2015-01-01

    Sex is an important part of life for many people, therefore dealing with erectile problems, living with the effects of physical injury, changes in your appearance or side-effects of treatment can have an enormous impact on your sex life and relationships. Normal sexual behaviour and erectile function depends on a complex interaction between various body-systems, including the brain, nerves, blood-supply and hormones. All of these systems (alone or in combination) may be affected following mul...

  8. Does the think-aloud protocol reflect thinking? Exploring functional neuroimaging differences with thinking (answering multiple choice questions) versus thinking aloud

    Durning, S.J.; Artino, A.R.; Beckman, T.J.; Graner, J.; Vleuten, C.P.M. van der; Holmboe, E.; Schuwirth, L.

    2013-01-01

    Background: Whether the think-aloud protocol is a valid measure of thinking remains uncertain. Therefore, we used functional magnetic resonance imaging (fMRI) to investigate potential functional neuroanatomic differences between thinking (answering multiple-choice questions in real time) versus

  9. Cross-diagnostic validity of the SF-36 physical functioning scale in patients with stroke, multiple sclerosis and amyotrophic lateral sclerosis: a study using Rasch analysis

    Dallmeijer, Annet J.; de Groot, Vincent; Roorda, Leo D.; Schepers, Vera P. M.; Lindeman, Eline; van den Berg, Leonard H.; Beelen, Anita; Dekker, Joost

    2007-01-01

    The aim of this study was to investigate unidimensionality and differential item functioning of the SF-36 physical functioning scale (PF10) in patients with various neurological disorders. Patients: Patients post-stroke (n = 198), with multiple sclerosis (n = 151) and amyotrophic lateral sclerosis

  10. J/ψ production as a function of charged particle multiplicity in proton + proton collisions at LHC energies

    Thakur, Dhananjaya; De, Sudipan; Sahoo, Raghunath; Dansana, Soumya

    2017-01-01

    In high energy proton-proton collisions the total event multiplicity can have a substantial contribution from Multi-Parton Interactions (MPI), which is an Underlying Event observable. The sum of all processes that build up the final hadronic state in a collision is referred as the Underlying Event (UE). The Underlying Event includes fragmentation of beam remnant, multi-partonic interactions, and initial and final state radiation (ISR/FSR) associated with each interactions. In MPI, several interactions at the partonic level occurs in a single p+p collision, that leads to a strong dependence of particle production on total event multiplicity. MPI are commonly used to describe the soft underlying events such as the production of light quarks and gluons. But it is observed that it can also contribute on the hard and semi-hard scale such as the production of particles containing heavy quarks like J/ψ, open heavy flavors etc. This contribution become more and more relevant with increasing energy

  11. Generalized internal multiple imaging

    Zuberi, M. A. H.

    2014-08-05

    Internal multiples deteriorate the image when the imaging procedure assumes only single scattering, especially if the velocity model does not have sharp contrasts to reproduce such scattering in the Green’s function through forward modeling. If properly imaged, internal multiples (internally scattered energy) can enhance the seismic image. Conventionally, to image internal multiples, accurate, sharp contrasts in the velocity model are required to construct a Green’s function with all the scattered energy. As an alternative, we have developed a generalized internal multiple imaging procedure that images any order internal scattering using the background Green’s function (from the surface to each image point), constructed from a smooth velocity model, usually used for conventional imaging. For the first-order internal multiples, the approach consisted of three steps, in which we first back propagated the recorded surface seismic data using the background Green’s function, then crosscorrelated the back-propagated data with the recorded data, and finally crosscorrelated the result with the original background Green’s function.