Biochar as potential sustainable precursors for activated carbon production: Multiple applications in environmental protection and energy storage.

PubMed

Tan, Xiao-Fei; Liu, Shao-Bo; Liu, Yun-Guo; Gu, Yan-Ling; Zeng, Guang-Ming; Hu, Xin-Jiang; Wang, Xin; Liu, Shao-Heng; Jiang, Lu-Hua

2017-03-01

There is a growing interest of the scientific community on production of activated carbon using biochar as potential sustainable precursors pyrolyzed from biomass wastes. Physical activation and chemical activation are the main methods applied in the activation process. These methods could have significantly beneficial effects on biochar chemical/physical properties, which make it suitable for multiple applications including water pollution treatment, CO 2 capture, and energy storage. The feedstock with different compositions, pyrolysis conditions and activation parameters of biochar have significant influences on the properties of resultant activated carbon. Compared with traditional activated carbon, activated biochar appears to be a new potential cost-effective and environmentally-friendly carbon materials with great application prospect in many fields. This review not only summarizes information from the current analysis of activated biochar and their multiple applications for further optimization and understanding, but also offers new directions for development of activated biochar. Copyright © 2016 Elsevier Ltd. All rights reserved.

Single cell multiplexed assay for proteolytic activity using droplet microfluidics.

PubMed

Ng, Ee Xien; Miller, Miles A; Jing, Tengyang; Chen, Chia-Hung

2016-07-15

Cellular enzymes interact in a post-translationally regulated fashion to govern individual cell behaviors, yet current platform technologies are limited in their ability to measure multiple enzyme activities simultaneously in single cells. Here, we developed multi-color Förster resonance energy transfer (FRET)-based enzymatic substrates and use them in a microfluidics platform to simultaneously measure multiple specific protease activities from water-in-oil droplets that contain single cells. By integrating the microfluidic platform with a computational analytical method, Proteolytic Activity Matrix Analysis (PrAMA), we are able to infer six different protease activity signals from individual cells in a high throughput manner (~100 cells/experimental run). We characterized protease activity profiles at single cell resolution for several cancer cell lines including breast cancer cell line MDA-MB-231, lung cancer cell line PC-9, and leukemia cell line K-562 using both live-cell and in-situ cell lysis assay formats, with special focus on metalloproteinases important in metastasis. The ability to measure multiple proteases secreted from or expressed in individual cells allows us to characterize cell heterogeneity and has potential applications including systems biology, pharmacology, cancer diagnosis and stem cell biology. Copyright © 2016 Elsevier B.V. All rights reserved.

Proteasome 20S in multiple myeloma: comparison of concentration and chymotrypsin-like activity in plasma and serum.

PubMed

Romaniuk, Wioletta; Kalita, Joanna; Ostrowska, Halina; Kloczko, Janusz

2018-03-05

The ubiquitin-proteasome system is relevant in the pathobiology of many haematological malignancies, including multiple myeloma. The assessment of proteasome concentration and chymotrypsin-like (ChT-L) activity might constitute a new approach to diagnosis, prognosis and monitoring of anticancer treatment of patients with haematological malignancies and other diseases. The aim of our study was to determine which material, plasma or serum, is better for measuring chymotrypsin-like (ChT-L) activity and proteasome concentration. We analysed proteasome concentration and chymotrypsin-like (ChT-L) activity in 70 plasma and serum samples drawn from 28 patients at different treatment stages for multiple myeloma (MM) and 31 healthy volunteers. Proteasome ChT-L activity and concentration in multiple myeloma patients were significantly higher in plasma compared to serum. In this group we observed significant and positive correlations both between the plasma and serum proteasome ChT-L activity and plasma and serum proteasome concentration. The higher values of proteasome concentration and ChT-L activity in plasma than in serum and their better correlations with parameters of tumour load and prognosis suggest that plasma constitutes a better biological material for measuring ChT-L activity and proteasome concentration than serum in multiple myeloma patients.

Emergent Literacy Supports for Students Who Are Deaf-Blind or Have Visual and Multiple Impairments: A Multiple-Case Study

ERIC Educational Resources Information Center

McKenzie, Amy R.

2009-01-01

Seven classrooms of students with deaf-blindness or visual and multiple impairments were observed to document the emergent literacy supports that were present, including environmental characteristics, strategies, or activities. The findings revealed that the majority of classrooms used emergent literacy supports that were previously documented for…

Mitochondrial DNA as an inflammatory mediator in cardiovascular diseases.

PubMed

Nakayama, Hiroyuki; Otsu, Kinya

2018-03-06

Mitochondria play a central role in multiple cellular functions, including energy production, calcium homeostasis, and cell death. Currently, growing evidence indicates the vital roles of mitochondria in triggering and maintaining inflammation. Chronic inflammation without microbial infection - termed sterile inflammation - is strongly involved in the development of heart failure. Sterile inflammation is triggered by the activation of pattern recognition receptors (PRRs) that sense endogenous ligands called damage-associated molecular patterns (DAMPs). Mitochondria release multiple DAMPs including mitochondrial DNA, peptides, and lipids, which induce inflammation via the stimulation of multiple PRRs. Among the mitochondrial DAMPs, mitochondrial DNA (mtDNA) is currently highlighted as the DAMP that mediates the activation of multiple PRRs, including Toll-like receptor 9, Nod-like receptors, and cyclic GMP-AMP synthetase/stimulator of interferon gene pathways. These PRR signalling pathways, in turn, lead to the activation of nuclear factor-κB and interferon regulatory factor, which enhances the transcriptional activity of inflammatory cytokines and interferons, and induces the recruitment of inflammatory cells. As the heart is an organ comprising abundant mitochondria for its ATP consumption (needed to maintain constant cyclic contraction and relaxation), the generation of massive amounts of mitochondrial radical oxygen species and mitochondrial DAMPs are predicted to occur and promote cardiac inflammation. Here, we will focus on the role of mtDNA in cardiac inflammation and review the mechanism and pathological significance of mtDNA-induced inflammatory responses in cardiac diseases. © 2018 The Author(s).

Attributions and self-efficacy for physical activity in multiple sclerosis.

PubMed

Nickel, D; Spink, K; Andersen, M; Knox, K

2014-01-01

Self-efficacy is an important predictor of health-related physical activity in multiple sclerosis (MS). While past experiences are believed to influence efficacy beliefs, the explanations individuals provide for these experiences also may be critical. Our objective was to test the hypothesis that perceived success or failure to accumulate 150 min of physical activity in the previous week would moderate the relationship between the attributional dimension of stability and self-efficacy to exercise in the future. Forty-two adults with MS participated in this cross-sectional descriptive study. Participants completed questions assessing physical activity, perceived outcome for meeting the recommended level of endurance activity, attributions for the outcome, and exercise self-efficacy. Results from hierarchical multiple regression revealed a significant main effect for perceived outcome predicting self-efficacy that was qualified by a significant interaction. The final model, which included perceived outcome, stability, and the interaction term, predicted 37% of the variance in exercise self-efficacy, F (3, 38) = 7.27, p = .001. Our findings suggest that the best prediction of self-efficacy in the MS population may include the interaction of specific attributional dimensions with success/failure at meeting the recommended physical activity dose. Attributions may be another target for interventions aimed at increasing the physical activity in MS.

Sexual practices among unmarried adolescents in Tanzania

PubMed Central

Kazaura, Method R; Masatu, Melkiory C

2009-01-01

Background Sexual activities are increasingly changing from the cultural point of view what they used to be. Knowledge of these practices among adolescents may be a basis to create awareness among adolescents on practices that involve risks. This study aims to assess sexual practices among unmarried adolescents in Tanzania. Methods A cross-sectional survey was conducted among in-school and out-of-school but unmarried adolescents aged 10 to 19 in five locations in Tanzania. A questionnaire was used to collect information and to characterize sexual practices among these adolescents. Results About 32% of adolescents reported being sexually active; a higher proportion being males than females. The only inquired and reported sexual practices include vaginal sex, masturbation, oral and anal sex. About 15% of sexually active adolescents reported having multiple sexual partners. Significantly more males reported having multiple partners than females. Nearly 42% of sexually active adolescents reported having used a condom during most recent sexual act. Females reported older partners at first sexual act. Conclusion Adolescents experience several sexual practices that include penetrative and non-penetrative. More males reported being sexually active than females. Despite adolescents reporting having multiple sexual partners, reported condom use during the most recent sexual act was low. We advocate for a more enhanced approach of reproductive health education that includes safer sex to adolescents without forgetting those in-schools. PMID:19804651

The Homeodomain of PDX-1 Mediates Multiple Protein-Protein Interactions in the Formation of a Transcriptional Activation Complex on the Insulin Promoter

PubMed Central

Ohneda, Kinuko; Mirmira, Raghavendra G.; Wang, Juehu; Johnson, Jeffrey D.; German, Michael S.

2000-01-01

Activation of insulin gene transcription specifically in the pancreatic β cells depends on multiple nuclear proteins that interact with each other and with sequences on the insulin gene promoter to build a transcriptional activation complex. The homeodomain protein PDX-1 exemplifies such interactions by binding to the A3/4 region of the rat insulin I promoter and activating insulin gene transcription by cooperating with the basic-helix-loop-helix (bHLH) protein E47/Pan1, which binds to the adjacent E2 site. The present study provides evidence that the homeodomain of PDX-1 acts as a protein-protein interaction domain to recruit multiple proteins, including E47/Pan1, BETA2/NeuroD1, and high-mobility group protein I(Y), to an activation complex on the E2A3/4 minienhancer. The transcriptional activity of this complex results from the clustering of multiple activation domains capable of interacting with coactivators and the basal transcriptional machinery. These interactions are not common to all homeodomain proteins: the LIM homeodomain protein Lmx1.1 can also activate the E2A3/4 minienhancer in cooperation with E47/Pan1 but does so through different interactions. Cooperation between Lmx1.1 and E47/Pan1 results not only in the aggregation of multiple activation domains but also in the unmasking of a potent activation domain on E47/Pan1 that is normally silent in non-β cells. While more than one activation complex may be capable of activating insulin gene transcription through the E2A3/4 minienhancer, each is dependent on multiple specific interactions among a unique set of nuclear proteins. PMID:10629047

Go! Including Movement during Routines and Transitions

ERIC Educational Resources Information Center

Orlowski, Marietta A.; Hart, Aaron

2010-01-01

Good schools for children ages 5 to 8 provide multiple opportunities for physical activity throughout the school day. Ideally, physical education, recess, extracurricular activities, and classroom activities together help ensure that children meet the recommended 60 minutes a day of structured activity and 60 of unstructured. Additionally, brief…

Physical activity and depressive symptoms in four ethnic groups of midlife women.

PubMed

Im, Eun-Ok; Ham, Ok Kyung; Chee, Eunice; Chee, Wonshik

2015-06-01

The purpose of this study was to determine the associations between physical activity and depression and the multiple contextual factors influencing these associations in four major ethnic groups of midlife women in the United States. This was a secondary analysis of the data from 542 midlife women. The instruments included questions on background characteristics and health and menopausal status; the Depression Index for Midlife Women (DIMW); and the Kaiser Physical Activity Survey (KPAS). The data were analyzed using chi-square tests, the ANOVA, two-way ANOVA, correlation analyses, and hierarchical multiple regression analyses. The women's depressive symptoms were negatively correlated with active living and sports/exercise physical activities whereas they were positively correlated with occupational physical activities (p < .01). Family income was the strongest predictor of their depressive symptoms. Increasing physical activity may improve midlife women's depressive symptoms, but the types of physical activity and multiple contextual factors need to be considered in intervention development. © The Author(s) 2014.

Modulation by Melatonin of the Pathogenesis of Inflammatory Autoimmune Diseases

PubMed Central

Lin, Gu-Jiun; Huang, Shing-Hwa; Chen, Shyi-Jou; Wang, Chih-Hung; Chang, Deh-Ming; Sytwu, Huey-Kang

2013-01-01

Melatonin is the major secretory product of the pineal gland during the night and has multiple activities including the regulation of circadian and seasonal rhythms, and antioxidant and anti-inflammatory effects. It also possesses the ability to modulate immune responses by regulation of the T helper 1/2 balance and cytokine production. Autoimmune diseases, which result from the activation of immune cells by autoantigens released from normal tissues, affect around 5% of the population. Activation of autoantigen-specific immune cells leads to subsequent damage of target tissues by these activated cells. Melatonin therapy has been investigated in several animal models of autoimmune disease, where it has a beneficial effect in a number of models excepting rheumatoid arthritis, and has been evaluated in clinical autoimmune diseases including rheumatoid arthritis and ulcerative colitis. This review summarizes and highlights the role and the modulatory effects of melatonin in several inflammatory autoimmune diseases including multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes mellitus, and inflammatory bowel disease. PMID:23727938

Suitability of public use secondary data sets to study multiple activities.

PubMed

Putnam, Michelle; Morrow-Howell, Nancy; Inoue, Megumi; Greenfield, Jennifer C; Chen, Huajuan; Lee, YungSoo

2014-10-01

The aims of this study were to inventory activity items within and across U.S. public use data sets, to identify gaps in represented activity domains and challenges in interpreting domains, and to assess the potential for studying multiple activity engagement among older adults using existing data. We engaged in content analysis of activity measures of 5U.S. public use data sets with nationally representative samples of older adults. Data sets included the Health & Retirement Survey (HRS), Americans' Changing Lives Survey (ACL), Midlife in the United States Survey (MIDUS), the National Health Interview Survey (NHIS), and the Panel Study of Income Dynamics survey (PSID). Two waves of each data set were analyzed. We identified 13 distinct activity domains across the 5 data sets, with substantial differences in representation of those domains among the data sets, and variance in the number and type of activity measures included in each. Our findings indicate that although it is possible to study multiple activity engagement within existing data sets, fuller sets of activity measures need to be developed in order to evaluate the portfolio of activities older adults engage in and the relationship of these portfolios to health and wellness outcomes. Importantly, clearer conceptual models of activity broadly conceived are required to guide this work. © The Author 2013. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Immunotoxicity of perfluorooctanoic acid and perfluorooctane sulfonate and the role of peroxisome proliferator-activated receptor alpha

EPA Science Inventory

Peroxisome proliferators, including perfluorooctanoic acid (PFOA), are environmentally widespread and persistent and multiple toxicities have been reported in experimental animals and humans. These compounds trigger biological activity via activation of the alpha isotype of pero...

The Commission Game: An Ethics Activity for Professional Selling Courses

ERIC Educational Resources Information Center

Milewicz, Chad

2012-01-01

The Commission Game is an experiment-based experiential learning activity designed to elicit students' sincere ethical decision making in an ambiguous sales context. The activity includes multiple relevant stakeholders as well as tangible, shared risk/reward elements. The activity's design encourages students to contemplate their own personal code…

Functional grouping and cortical–subcortical interactions in emotion: A meta-analysis of neuroimaging studies

PubMed Central

Kober, Hedy; Barrett, Lisa Feldman; Joseph, Josh; Bliss-Moreau, Eliza; Lindquist, Kristen; Wager, Tor D.

2009-01-01

We performed an updated quantitative meta-analysis of 162 neuroimaging studies of emotion using a novel multi-level kernel-based approach, focusing on locating brain regions consistently activated in emotional tasks and their functional organization into distributed functional groups, independent of semantically defined emotion category labels (e.g., “anger,” “fear”). Such brain-based analyses are critical if our ways of labeling emotions are to be evaluated and revised based on consistency with brain data. Consistent activations were limited to specific cortical sub-regions, including multiple functional areas within medial, orbital, and inferior lateral frontal cortices. Consistent with a wealth of animal literature, multiple subcortical activations were identified, including amygdala, ventral striatum, thalamus, hypothalamus, and periaqueductal gray. We used multivariate parcellation and clustering techniques to identify groups of co-activated brain regions across studies. These analyses identified six distributed functional groups, including medial and lateral frontal groups, two posterior cortical groups, and paralimbic and core limbic/brainstem groups. These functional groups provide information on potential organization of brain regions into large-scale networks. Specific follow-up analyses focused on amygdala, periaqueductal gray (PAG), and hypothalamic (Hy) activations, and identified frontal cortical areas co-activated with these core limbic structures. While multiple areas of frontal cortex co-activated with amygdala sub-regions, a specific region of dorsomedial prefrontal cortex (dmPFC, Brodmann’s Area 9/32) was the only area co-activated with both PAG and Hy. Subsequent mediation analyses were consistent with a pathway from dmPFC through PAG to Hy. These results suggest that medial frontal areas are more closely associated with core limbic activation than their lateral counterparts, and that dmPFC may play a particularly important role in the cognitive generation of emotional states. PMID:18579414

A system for diagnosis, referral, and rehabilitation of persons convicted of driving while intoxicated : a special rehabilitation program for multiple offenders

DOT National Transportation Integrated Search

1977-11-01

A rehabilitation program is presented for multiple DWI offenders. The program includes education related to alcohol use and abuse and therapeutic activities to help a client learn new techniques for living and alternatives to alcohol abuse. /Abstract...

Emotionally Intense Science Activities

ERIC Educational Resources Information Center

King, Donna; Ritchie, Stephen; Sandhu, Maryam; Henderson, Senka

2015-01-01

Science activities that evoke positive emotional responses make a difference to students' emotional experience of science. In this study, we explored 8th Grade students' discrete emotions expressed during science activities in a unit on Energy. Multiple data sources including classroom videos, interviews and emotion diaries completed at the end of…

Management and integration of engineering and construction activities: Lessons learned from the AP1000{sup R} nuclear power plant China project

DOE Office of Scientific and Technical Information (OSTI.GOV)

McCullough, M. C.; Ebeling-Koning, D.; Evans, M. C.

2012-07-01

The lessons learned during the early phase of design engineering and construction activities for the AP1000 China Project can be applied to any project involving multiple disciplines and multiple organizations. Implementation of a first-of-a-kind design to directly support construction activities utilizing resources assigned to design development and design delivery creates challenges with prioritization of activities, successful closure of issues, and communication between site organizations and the home office. To ensure successful implementation, teams were assigned and developed to directly support construction activities including prioritization of activities, site communication and ensuring closure of site emergent issues. By developing these teams, themore » organization is better suited to meet the demands of the construction schedule while continuing with design evolution of a standard plant and engineering delivery for multiple projects. For a successful project, proper resource utilization and prioritization are key for overcoming obstacles and ensuring success of the engineering organization. (authors)« less

Emotional face processing and flat affect in schizophrenia: functional and structural neural correlates.

PubMed

Lepage, M; Sergerie, K; Benoit, A; Czechowska, Y; Dickie, E; Armony, J L

2011-09-01

There is a general consensus in the literature that schizophrenia causes difficulties with facial emotion perception and discrimination. Functional brain imaging studies have observed reduced limbic activity during facial emotion perception but few studies have examined the relation to flat affect severity. A total of 26 people with schizophrenia and 26 healthy controls took part in this event-related functional magnetic resonance imaging study. Sad, happy and neutral faces were presented in a pseudo-random order and participants indicated the gender of the face presented. Manual segmentation of the amygdala was performed on a structural T1 image. Both the schizophrenia group and the healthy control group rated the emotional valence of facial expressions similarly. Both groups exhibited increased brain activity during the perception of emotional faces relative to neutral ones in multiple brain regions, including multiple prefrontal regions bilaterally, the right amygdala, right cingulate cortex and cuneus. Group comparisons, however, revealed increased activity in the healthy group in the anterior cingulate, right parahippocampal gyrus and multiple visual areas. In schizophrenia, the severity of flat affect correlated significantly with neural activity in several brain areas including the amygdala and parahippocampal region bilaterally. These results suggest that many of the brain regions involved in emotional face perception, including the amygdala, are equally recruited in both schizophrenia and controls, but flat affect can also moderate activity in some other brain regions, notably in the left amygdala and parahippocampal gyrus bilaterally. There were no significant group differences in the volume of the amygdala.

Multiple myeloma phosphotyrosine proteomic profile associated with FGFR3 expression, ligand activation, and drug inhibition

PubMed Central

St-Germain, Jonathan R.; Taylor, Paul; Tong, Jiefei; Jin, Lily L.; Nikolic, Ana; Stewart, Ian I.; Ewing, Robert M.; Dharsee, Moyez; Li, Zhihua; Trudel, Suzanne; Moran, Michael F.

2009-01-01

Signaling by growth factor receptor tyrosine kinases is manifest through networks of proteins that are substrates and/or bind to the activated receptors. FGF receptor-3 (FGFR3) is a drug target in a subset of human multiple myelomas (MM) and is mutationally activated in some cervical and colon and many bladder cancers and in certain skeletal dysplasias. To define the FGFR3 network in multiple myeloma, mass spectrometry was used to identify and quantify phosphotyrosine (pY) sites modulated by FGFR3 activation and inhibition in myeloma-derived KMS11 cells. Label-free quantification of peptide ion currents indicated the activation of FGFR3 by phosphorylation of tandem tyrosines in the kinase domain activation loop when cellular pY phosphatases were inhibited by pervanadate. Among the 175 proteins that accumulated pY in response to pervanadate was a subset of 52 including FGFR3 that contained a total of 61 pY sites that were sensitive to inhibition by the FGFR3 inhibitor PD173074. The FGFR3 isoform containing the tandem pY motif in its activation loop was targeted by PD173074. Forty of the drug-sensitive pY sites, including two located within the 35-residue cytoplasmic domain of the transmembrane growth factor binding proteoglycan (and multiple myeloma biomarker) Syndecan-1/CD138, were also stimulated in cells treated with the ligand FGF1, providing additional validation of their link to FGFR3. The identification of these overlapping sets of co-modulated tyrosine phosphorylations presents an outline of an FGFR3 network in the MM model and demonstrates the potential for pharmacodynamic monitoring by label-free quantitative phospho-proteomics. PMID:19901323

The IKK complex contributes to the induction of autophagy.

PubMed

Criollo, Alfredo; Senovilla, Laura; Authier, Hélène; Maiuri, Maria Chiara; Morselli, Eugenia; Vitale, Ilio; Kepp, Oliver; Tasdemir, Ezgi; Galluzzi, Lorenzo; Shen, Shensi; Tailler, Maximilien; Delahaye, Nicolas; Tesniere, Antoine; De Stefano, Daniela; Younes, Aména Ben; Harper, Francis; Pierron, Gérard; Lavandero, Sergio; Zitvogel, Laurence; Israel, Alain; Baud, Véronique; Kroemer, Guido

2010-02-03

In response to stress, cells start transcriptional and transcription-independent programs that can lead to adaptation or death. Here, we show that multiple inducers of autophagy, including nutrient depletion, trigger the activation of the IKK (IkappaB kinase) complex that is best known for its essential role in the activation of the transcription factor NF-kappaB by stress. Constitutively active IKK subunits stimulated autophagy and transduced multiple signals that operate in starvation-induced autophagy, including the phosphorylation of AMPK and JNK1. Genetic inhibition of the nuclear translocation of NF-kappaB or ablation of the p65/RelA NF-kappaB subunit failed to suppress IKK-induced autophagy, indicating that IKK can promote the autophagic pathway in an NF-kappaB-independent manner. In murine and human cells, knockout and/or knockdown of IKK subunits (but not that of p65) prevented the induction of autophagy in response to multiple stimuli. Moreover, the knockout of IKK-beta suppressed the activation of autophagy by food deprivation or rapamycin injections in vivo, in mice. Altogether, these results indicate that IKK has a cardinal role in the stimulation of autophagy by physiological and pharmacological stimuli.

Bryophyllum pinnatum: A Great Teaching Aid.

ERIC Educational Resources Information Center

Martin, Francis L.

1983-01-01

Suggests using Bryophyllum pinnatum to illustrate botanical principles. Includes tips for keeping and maintaining the plant in the classroom and suggests several student activities, including observing root/shoot growth, investigating apical dominance, exploring multiple leaf development, and others. (JN)

A Study of Two English Language Coursebooks in Turkey: Focus on Multiple Intelligences

ERIC Educational Resources Information Center

Arikan, Arda; Soydan, Elif; Isler, Özlem

2014-01-01

This study aims to analyze two coursebooks, namely, "Texture of English 4" and "My English 5" on the basis of to what extent the activities and tasks included reflect the intelligent types proposed by multiple intelligences theory. Taking the general characteristics of the intelligences into account, a checklist has been…

An Exploratory Multiple Case Study about Using Game-Based Learning in STEM Classrooms

ERIC Educational Resources Information Center

Vu, Phu; Feinstein, Sheryl

2017-01-01

This exploratory multiple case study attempted to examine whether game-based learning activities had any impacts on students' academic performances and behaviors, and what perceptions the teachers had toward implementing games into their classrooms. Data used in this study included 101 students' pre and post-test scores, and four structured…

Using a Multiple Intelligences Assessment To Facilitate Teacher Development.

ERIC Educational Resources Information Center

Shearer, C. Branton

In phase 1 of this study, development and validation studies of a new assessment for the multiple intelligences were conducted. The second phase of the study was a pilot implementation project during a single academic year in collaboration with several public school teachers. Phase 1 involved a series of activities including initial instrument…

Coordinating a Large, Amalgamated REU Program with Multiple Funding Sources

ERIC Educational Resources Information Center

Fiorini, Eugene; Myers, Kellen; Naqvi, Yusra

2017-01-01

In this paper, we discuss the challenges of organizing a large REU program amalgamated from multiple funding sources, including diverse participants, mentors, and research projects. We detail the program's structure, activities, and recruitment, and we hope to demonstrate that the organization of this REU is not only beneficial to its…

Alemtuzumab Use in Clinical Practice: Recommendations from European Multiple Sclerosis Experts.

PubMed

Berger, Thomas; Elovaara, Irina; Fredrikson, Sten; McGuigan, Chris; Moiola, Lucia; Myhr, Kjell-Morten; Oreja-Guevara, Celia; Stoliarov, Igor; Zettl, Uwe K

2017-01-01

Alemtuzumab (Lemtrada™) is a humanized monoclonal antibody approved in more than 50 countries. Within the European Union, alemtuzumab is indicated for the treatment of adult patients with relapsing-remitting multiple sclerosis (RRMS) with active disease defined by clinical or imaging features; in the USA, the indication states that alemtuzumab should generally be reserved for the treatment of patients with relapsing forms of multiple sclerosis who have had an inadequate response to two or more disease-modifying therapies (DMTs). In clinical trials, alemtuzumab demonstrated efficacy in treatment-naïve patients with active RRMS and those relapsing on prior DMTs, with a consistent and manageable safety and tolerability profile. The European Union indication provides physicians with significant flexibility regarding treatment decisions, affording the opportunity for individualized treatment. Thus, alemtuzumab may be an appropriate treatment choice across a broad range of patients with RRMS, including, for example, treatment-naïve patients with active disease, patients with highly active disease, or for patients relapsing on prior DMTs. There are several practicalities to consider when using alemtuzumab, including the unique dosing regimen, administered via intravenous infusion on 5 consecutive days at baseline and on 3 consecutive days 12 months later, and as-needed retreatment (3 consecutive days at least 12 months after the last course) in cases of disease recurrence. Additionally, routine monthly monitoring is required for up to 48 months after the last infusion to promptly identify potentially serious autoimmune adverse events. Given these considerations, it is beneficial to gain insight into how alemtuzumab is being used in the real-world clinical setting. Here, we report recommendations from European multiple sclerosis experts regarding best practices for alemtuzumab treatment, including management of adverse events and compliance with ongoing safety monitoring requirements.

Inflammatory pathways in cervical cancer - the UCT contribution.

PubMed

Sales, Kurt Jason; Katz, Arieh Anthony

2012-03-23

Cervical cancer is the leading gynaecological malignancy in Southern Africa. The main causal factor for development of the disease is infection of the cervix with human papillomavirus. It is a multi-step disease with several contributing co-factors including multiple sexual partners, a compromised immune system and cervical inflammation caused by infections with Chlamydia trachomatis or Neisseria gonorrhoeae. Inflammation involves extensive tissue remodelling events which are orchestrated by complex networks of cytokines, chemokines and bio-active lipids working across multiple cellular compartments to maintain tissue homeostasis. Many pathological disorders or diseases, including cervical cancer, are characterised by the exacerbated activation and maintenance of inflammatory pathways. In this review we highlight our findings pertaining to activation of inflammatory pathways in cervical cancers, addressing their potential role in pathological changes of the cervix and the significance of these findings for intervention strategies.

Abstract-Reasoning Software for Coordinating Multiple Agents

NASA Technical Reports Server (NTRS)

Clement, Bradley; Barrett, Anthony; Rabideau, Gregg; Knight, Russell

2003-01-01

A computer program for scheduling the activities of multiple agents that share limited resources has been incorporated into the Automated Scheduling and Planning Environment (ASPEN) software system, aspects of which have been reported in several previous NASA Tech Briefs articles. In the original intended application, the agents would be multiple spacecraft and/or robotic vehicles engaged in scientific exploration of distant planets. The program could also be used on Earth in such diverse settings as production lines and military maneuvers. This program includes a planning/scheduling subprogram of the iterative repair type that reasons about the activities of multiple agents at abstract levels in order to greatly improve the scheduling of their use of shared resources. The program summarizes the information about the constraints on, and resource requirements of, abstract activities on the basis of the constraints and requirements that pertain to their potential refinements (decomposition into less-abstract and ultimately to primitive activities). The advantage of reasoning about summary information is that time needed to find consistent schedules is exponentially smaller than the time that would be needed for reasoning about the same tasks at the primitive level.

Exploring the facilitators and barriers to engagement in physical activity for people with multiple sclerosis.

PubMed

Kayes, Nicola M; McPherson, Kathryn M; Schluter, Philip; Taylor, Denise; Leete, Marta; Kolt, Gregory S

2011-01-01

To explore the relationship that cognitive behavioural and other previously identified variables have with physical activity engagement in people with multiple sclerosis (MS). This study adopted a cross-sectional questionnaire design. Participants were 282 individuals with MS. Outcome measures included the Physical Activity Disability Survey--Revised, Cognitive and Behavioural Responses to Symptoms Questionnaire, Barriers to Health Promoting Activities for Disabled Persons Scale, Multiple Sclerosis Self-efficacy Scale, Self-Efficacy for Chronic Diseases Scales and Chalder Fatigue Questionnaire. Multivariable stepwise regression analyses found that greater self-efficacy, greater reported mental fatigue and lower number of perceived barriers to physical activity accounted for a significant proportion of variance in physical activity behaviour, over that accounted for by illness-related variables. Although fear-avoidance beliefs accounted for a significant proportion of variance in the initial analyses, its effect was explained by other factors in the final multivariable analyses. Self-efficacy, mental fatigue and perceived barriers to physical activity are potentially modifiable variables which could be incorporated into interventions designed to improve physical activity engagement. Future research should explore whether a measurement tool tailored to capture beliefs about physical activity identified by people with MS would better predict participation in physical activity.

Activity Enhancement Based on the Chemical Equilibrium of Multiple-Subunit Nitrile Hydratase from Bordetella petrii.

PubMed

Liu, Yi; Liu, Ping; Lin, Lu; Zhao, Yueqin; Zhong, Wenjuan; Wu, Lunjie; Zhou, Zhemin; Sun, Weifeng

2016-09-01

The maturation mechanism of nitrile hydratase (NHase) of Pseudomonas putida NRRL-18668 was discovered and named as "self-subunit swapping." Since the NHase of Bordetella petrii DSM 12804 is similar to that of P. putida, the NHase maturation of B. petrii is proposed to be the same as that of P. putida. However, there is no further information on the application of NHase according to these findings. We successfully rapidly purified NHase and its activator through affinity his tag, and found that the cell extracts of NHase possessed multiple types of protein ingredients including α, β, α2β2, and α(P14K)2 who were in a state of chemical equilibrium. Furthermore, the activity was significantly enhanced through adding extra α(P14K)2 to the cell extracts of NHase according to the chemical equilibrium. Our findings are useful for the activity enhancement of multiple-subunit enzyme and for the first time significantly increased the NHase activity according to the chemical equilibrium.

Modelling and simulation of biased agonism dynamics at a G protein-coupled receptor.

PubMed

Bridge, L J; Mead, J; Frattini, E; Winfield, I; Ladds, G

2018-04-07

Theoretical models of G protein-coupled receptor (GPCR) concentration-response relationships often assume an agonist producing a single functional response via a single active state of the receptor. These models have largely been analysed assuming steady-state conditions. There is now much experimental evidence to suggest that many GPCRs can exist in multiple receptor conformations and elicit numerous functional responses, with ligands having the potential to activate different signalling pathways to varying extents-a concept referred to as biased agonism, functional selectivity or pluri-dimensional efficacy. Moreover, recent experimental results indicate a clear possibility for time-dependent bias, whereby an agonist's bias with respect to different pathways may vary dynamically. Efforts towards understanding the implications of temporal bias by characterising and quantifying ligand effects on multiple pathways will clearly be aided by extending current equilibrium binding and biased activation models to include G protein activation dynamics. Here, we present a new model of time-dependent biased agonism, based on ordinary differential equations for multiple cubic ternary complex activation models with G protein cycle dynamics. This model allows simulation and analysis of multi-pathway activation bias dynamics at a single receptor for the first time, at the level of active G protein (α GTP ), towards the analysis of dynamic functional responses. The model is generally applicable to systems with N G G proteins and N* active receptor states. Numerical simulations for N G =N * =2 reveal new insights into the effects of system parameters (including cooperativities, and ligand and receptor concentrations) on bias dynamics, highlighting new phenomena including the dynamic inter-conversion of bias direction. Further, we fit this model to 'wet' experimental data for two competing G proteins (G i and G s ) that become activated upon stimulation of the adenosine A 1 receptor with adenosine derivative compounds. Finally, we show that our model can qualitatively describe the temporal dynamics of this competing G protein activation. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

The metazoan Mediator co-activator complex as an integrative hub for transcriptional regulation.

PubMed

Malik, Sohail; Roeder, Robert G

2010-11-01

The Mediator is an evolutionarily conserved, multiprotein complex that is a key regulator of protein-coding genes. In metazoan cells, multiple pathways that are responsible for homeostasis, cell growth and differentiation converge on the Mediator through transcriptional activators and repressors that target one or more of the almost 30 subunits of this complex. Besides interacting directly with RNA polymerase II, Mediator has multiple functions and can interact with and coordinate the action of numerous other co-activators and co-repressors, including those acting at the level of chromatin. These interactions ultimately allow the Mediator to deliver outputs that range from maximal activation of genes to modulation of basal transcription to long-term epigenetic silencing.

Phosphoinositide protein kinase PDPK1 is a crucial cell signaling mediator in multiple myeloma.

PubMed

Chinen, Yoshiaki; Kuroda, Junya; Shimura, Yuji; Nagoshi, Hisao; Kiyota, Miki; Yamamoto-Sugitani, Mio; Mizutani, Shinsuke; Sakamoto, Natsumi; Ri, Masaki; Kawata, Eri; Kobayashi, Tsutomu; Matsumoto, Yosuke; Horiike, Shigeo; Iida, Shinsuke; Taniwaki, Masafumi

2014-12-15

Multiple myeloma is a cytogenetically/molecularly heterogeneous hematologic malignancy that remains mostly incurable, and the identification of a universal and relevant therapeutic target molecule is essential for the further development of therapeutic strategy. Herein, we identified that 3-phosphoinositide-dependent protein kinase 1 (PDPK1), a serine threonine kinase, is expressed and active in all eleven multiple myeloma-derived cell lines examined regardless of the type of cytogenetic abnormality, the mutation state of RAS and FGFR3 genes, or the activation state of ERK and AKT. Our results revealed that PDPK1 is a pivotal regulator of molecules that are essential for myelomagenesis, such as RSK2, AKT, c-MYC, IRF4, or cyclin Ds, and that PDPK1 inhibition caused the growth inhibition and the induction of apoptosis with the activation of BIM and BAD, and augmented the in vitro cytotoxic effects of antimyeloma agents in myeloma cells. In the clinical setting, PDPK1 was active in myeloma cells of approximately 90% of symptomatic patients at diagnosis, and the smaller population of patients with multiple myeloma exhibiting myeloma cells without active PDPK1 showed a significantly less frequent proportion of the disease stage III by the International Staging System and a significantly more favorable prognosis, including the longer overall survival period and the longer progression-free survival period by bortezomib treatment, than patients with active PDPK1, suggesting that PDPK1 activation accelerates the disease progression and the resistance to treatment in multiple myeloma. Our study demonstrates that PDPK1 is a potent and a universally targetable signaling mediator in multiple myeloma regardless of the types of cytogenetic/molecular profiles. ©2014 American Association for Cancer Research.

Glycoside hydrolases having multiple hydrolase activities

DOEpatents

Chen, Zhiwei; Friedland, Gregory D.; Chhabra, Swapnil R.; Chivian, Dylan C.; Simmons, Blake A

2017-08-08

Glycoside hydrolases having at least two different hydrolytic activities are provided. In one embodiment, an isolated recombinant hydrolase having at least two activities selected from a group including asparagine derivatives, glutamine derivatives, and histidine derivatives is provided. Further, a method of generating free sugars from a mixture comprising asparagine derivatives, glutamine derivatives, and histidine derivatives is provided.

In vitro screening for potential chemical inhibitors of deiodinase type 1 activity

EPA Science Inventory

Control of thyroid hormone (TH) signaling in vertebrates is dependent upon multiple key events including iodide uptake, hormone synthesis, metabolism and elimination, to maintain proper homeostasis of the hormones. Deiodinase enzymes interconvert THs between less active and more...

Cited1 Deficiency Suppresses Intestinal Tumorigenesis

PubMed Central

Young, Madeleine; Poetz, Oliver; Parry, Lee; Jenkins, John R.; Williams, Geraint T.; Dunwoodie, Sally L.; Watson, Alastair; Clarke, Alan R.

2013-01-01

Conditional deletion of Apc in the murine intestine alters crypt-villus architecture and function. This process is accompanied by multiple changes in gene expression, including upregulation of Cited1, whose role in colorectal carcinogenesis is unknown. Here we explore the relevance of Cited1 to intestinal tumorigenesis. We crossed Cited1 null mice with ApcMin/+ and AhCre+Apcfl/fl mice and determined the impact of Cited1 deficiency on tumour growth/initiation including tumour multiplicity, cell proliferation, apoptosis and the transcriptome. We show that Cited1 is up-regulated in both human and murine tumours, and that constitutive deficiency of Cited1 increases survival in ApcMin/+ mice from 230.5 to 515 days. However, paradoxically, Cited1 deficiency accentuated nearly all aspects of the immediate phenotype 4 days after conditional deletion of Apc, including an increase in cell death and enhanced perturbation of differentiation, including of the stem cell compartment. Transcriptome analysis revealed multiple pathway changes, including p53, PI3K and Wnt. The activation of Wnt through Cited1 deficiency correlated with increased transcription of β-catenin and increased levels of dephosphorylated β-catenin. Hence, immediately following deletion of Apc, Cited1 normally restrains the Wnt pathway at the level of β-catenin. Thus deficiency of Cited1 leads to hyper-activation of Wnt signaling and an exaggerated Wnt phenotype including elevated cell death. Cited1 deficiency decreases intestinal tumourigenesis in ApcMin/+ mice and impacts upon a number of oncogenic signaling pathways, including Wnt. This restraint imposed by Cited1 is consistent with a requirement for Cited1 to constrain Wnt activity to a level commensurate with optimal adenoma formation and maintenance, and provides one mechanism for tumour repression in the absence of Cited1. PMID:23935526

Prevalence of multiple health-related behaviors in adolescents with cancer.

PubMed

Carpentier, Melissa Y; Mullins, Larry L; Elkin, T David; Wolfe-Christensen, Cortney

2008-12-01

This preliminary study investigated prevalence rates of multiple health-related behaviors (ie, tobacco, alcohol, and other drug use; sexual risk-taking; nutrition/physical activity; overweight and dietary behaviors; sun safety) among 42 adolescents on active treatment for cancer, as compared with healthy adolescent norms. Health-related behaviors were assessed using the 2005 National Youth Risk Behavior Survey, for which healthy adolescent norms were publicly available. Adolescents with cancer reported significantly lower current and lifetime rates of tobacco, alcohol, and other drug use; fruit/vegetable consumption; physical activity; and dietary behavior, in addition to lower rates of lifetime sexual intercourse, early-onset sexual intercourse, and alcohol/drug use before last sexual intercourse, compared with healthy peers. Among those who have previously engaged in sexual intercourse, there appeared to be a trend toward increased partners, current sexual activity, and lack of protection at last episode of sexual intercourse. Adolescents with cancer also reported significantly higher rates of television watching compared with healthy peers. Adolescents on active treatment for cancer are engaging in multiple health-risk behaviors, including sedentary behavior, poor nutrition, lack of sun safety, and sexual risk-taking (eg, multiple partners, lack of protection at last sexual intercourse). Health promotion interventions are needed during active treatment to facilitate the acquisition of good health practices as adolescents transition into survivorship.

Two Persons with Multiple Disabilities Use Orientation Technology with Auditory Cues to Manage Simple Indoor Traveling

ERIC Educational Resources Information Center

Lancioni, Giulio E.; Singh, Nirbhay N.; O'Reilly, Mark F.; Sigafoos, Jeff; Campodonico, Francesca; Oliva, Doretta

2010-01-01

This study was an effort to extend the evaluation of orientation technology for promoting independent indoor traveling in persons with multiple disabilities. Two participants (adults) were included, who were to travel to activity destinations within occupational settings. The orientation system involved (a) cueing sources only at the destinations…

Multiple Measures of Outcome in Assessing a Prison-Based Drug Treatment Program

ERIC Educational Resources Information Center

Prendergast, Michael L.; Hall, Elizabeth A.; Wexler, Harry K.

2003-01-01

Evaluations of prison-based drug treatment programs typically focus on one or two dichotomous outcome variables related to recidivism. In contrast, this paper uses multiple measures of outcomes related to crime and drug use to examine the impact of prison treatment. Crime variables included self-report data of time to first illegal activity,…

Use of Activity Schedule to Promote Independent Performance of Individuals with Autism and Other Intellectual Disabilities: A Review

ERIC Educational Resources Information Center

Koyama, Takanori; Wang, Hui-Ting

2011-01-01

A literature review was conducted on the effectiveness of activity schedules. Twenty three studies that a) were peer-reviewed, b) were experimental, c) implemented activity schedule as a primary intervention, d) incorporated multiple activities, and e) aimed to teach learners to self-manage individual schedules were included in the review. The…

System, Apparatus, and Method for Active Debris Removal

NASA Technical Reports Server (NTRS)

Hickey, Christopher J. (Inventor); Spehar, Peter T. (Inventor); Griffith, Sr., Anthony D. (Inventor); Kohli, Rajiv (Inventor); Burns, Susan H. (Inventor); Gruber, David J. (Inventor); Lee, David E. (Inventor); Robinson, Travis M. (Inventor); Damico, Stephen J. (Inventor); Smith, Jason T. (Inventor)

2017-01-01

Systems, apparatuses, and methods for removal of orbital debris are provided. In one embodiment, an apparatus includes a spacecraft control unit configured to guide and navigate the apparatus to a target. The apparatus also includes a dynamic object characterization unit configured to characterize movement, and a capture feature, of the target. The apparatus further includes a capture and release unit configured to capture a target and deorbit or release the target. The collection of these apparatuses is then employed as multiple, independent and individually operated vehicles launched from a single launch vehicle for the purpose of disposing of multiple debris objects.

Self-reported physical activity correlates in Swedish adults with multiple sclerosis: a cross-sectional study.

PubMed

Anens, Elisabeth; Zetterberg, Lena; Urell, Charlotte; Emtner, Margareta; Hellström, Karin

2017-12-01

The benefits of physical activity in persons with Multiple Sclerosis (MS) are considerable. Knowledge about factors that correlate to physical activity is helpful in order to develop successful strategies to increase physical activity in persons with MS. Previous studies have focused on correlates to physical activity in MS, however falls self-efficacy, social support and enjoyment of physical activity are not much studied, as well as if the correlates differ with regard to disease severity. The aim of the study was to examine associations between physical activity and age, gender, employment, having children living at home, education, disease type, disease severity, fatigue, self-efficacy for physical activity, falls self-efficacy, social support and enjoyment of physical activity in a sample of persons with MS and in subgroups with regard to disease severity. This is a cross-sectional survey study including Swedish community living adults with MS, 287 persons, response rate 58.2%. The survey included standardized self-reported scales measuring physical activity, disease severity, fatigue, self-efficacy for physical activity, falls self-efficacy, and social support. Physical activity was measured by the Physical Activity Disability Survey - Revised. Multiple regression analyzes showed that 59% (F(6,3) = 64.9, p = 0.000) of the variation in physical activity was explained by having less severe disease (β = -0.30), being employed (β = 0.26), having high falls self-efficacy (β = 0.20), having high self-efficacy for physical activity (β = 0.17), and enjoying physical activity (β = 0.11). In persons with moderate/severe MS, self-efficacy for physical activity explained physical activity. Consistent with previous research in persons with MS in other countries this study shows that disease severity, employment and self-efficacy for physical activity are important for physical activity. Additional important factors were falls self-efficacy and enjoyment. More research is needed to confirm this and the subgroup differences.

Social Cognitive Correlates of Physical Activity in Black Individuals With Multiple Sclerosis.

PubMed

Kinnett-Hopkins, Dominique; Motl, Robert W

2016-04-01

To examine variables from social cognitive theory as correlates of physical activity in black and white individuals with multiple sclerosis (MS). Cross-sectional. National survey. Black (n=151) and white (n=185) individuals with MS were recruited through the North American Research Committee on Multiple Sclerosis Registry. Not applicable. The battery of questionnaires included information on demographic and clinical characteristics, physical activity, exercise self-efficacy, function, social support, exercise outcome expectations, and exercise goal setting and planning. Black individuals with MS reported significantly lower levels of physical activity compared with white individuals with MS. Physical activity levels were significantly correlated with self-efficacy, outcome expectations, functional limitations as impediments, and goal setting in black participants with MS. The pattern and magnitude of correlations were comparable with those observed in white participants based on Fisher z tests. Researchers should consider applying behavioral interventions that target social cognitive theory variables for increasing physical activity levels among black individuals with MS. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Multiple-stage integrating accelerometer

DOEpatents

Devaney, H.F.

1984-06-27

An accelerometer assembly is provided for use in activating a switch in response to multiple acceleration pulses in series. The accelerometer includes a housing forming a chamber. An inertial mass or piston is slidably disposed in the chamber and spring biased toward a first or reset position. A damping system is also provided to damp piston movement in response to first and subsequent acceleration pulses. Additionally, a cam, including a Z-shaped slot, and cooperating follower pin slidably received therein are mounted to the piston and the housing. The middle or cross-over leg of the Z-shaped slot cooperates with the follower pin to block or limit piston movement and prevent switch activation in response to a lone acceleration pulse. The switch of the assembly is only activated after two or more separate acceleration pulses are sensed and the piston reaches the end of the chamber opposite the reset position.

Multiple-channel detection of cellular activities by ion-sensitive transistors

NASA Astrophysics Data System (ADS)

Machida, Satoru; Shimada, Hideto; Motoyama, Yumi

2018-04-01

An ion-sensitive field-effect transistor to record cellular activities was demonstrated. This field-effect transistor (bio transistor) includes cultured cells on the gate insulator instead of gate electrode. The bio transistor converts a change in potential underneath the cells into variation of the drain current when ion channels open. The bio transistor has high detection sensitivity to even minute variations in potential utilizing a subthreshold swing region. To open ion channels, a reagent solution (acetylcholine) was added to a human-originating cell cultured on the bio transistor. The drain current was successfully decreased with the addition of acetylcholine. Moreover, we attempted to detect the opening of ion channels using a multiple-channel measurement circuit containing several bio transistors. As a consequence, the drain current distinctly decreased only after the addition of acetylcholine. We confirmed that this measurement system including bio transistors enables to observation of cellular activities sensitively and simultaneously.

Screening the ToxCast Phase 1 chemical library for inhibition of deiodinase type 1 activity

EPA Science Inventory

Thyroid hormone (TH) homeostasis is dependent upon coordination of multiple key events including iodide uptake, hormone synthesis, metabolism and elimination, to maintain proper TH signaling. Deiodinase enzymes catalyze iodide release from THs to interconvert THs between active a...

Screening the ToxCast Phase I Chemical Library for inhibition of Deiodinase Type I enzyme activity

EPA Science Inventory

Thyroid hormone (TH) signaling in vertebrates is dependent upon coordination of multiple key events including iodide uptake, hormone synthesis, metabolism and elimination, to maintain proper homeostasis of the hormones. Deiodinase enzymes interconvert THs between less active and...

Commercial Support and the Quandary of Continuing Medical Education.

ERIC Educational Resources Information Center

Schaffer, Mark H.

2000-01-01

Although commercial funding supports much continuing medical education, there is a public perception that funders may influence physician behavior. Solutions include having multiple grantors for continuing education activities, establishing clear standards for grantor behavior, and prohibiting commercial support for related social activities. (SK)

Preclinical anti-cancer activity and multiple mechanisms of action of a cationic silver complex bearing N-heterocyclic carbene ligands.

PubMed

Allison, Simon J; Sadiq, Maria; Baronou, Efstathia; Cooper, Patricia A; Dunnill, Chris; Georgopoulos, Nikolaos T; Latif, Ayşe; Shepherd, Samantha; Shnyder, Steve D; Stratford, Ian J; Wheelhouse, Richard T; Willans, Charlotte E; Phillips, Roger M

2017-09-10

Organometallic complexes offer the prospect of targeting multiple pathways that are important in cancer biology. Here, the preclinical activity and mechanism(s) of action of a silver-bis(N-heterocyclic carbine) complex (Ag8) were evaluated. Ag8 induced DNA damage via several mechanisms including topoisomerase I/II and thioredoxin reductase inhibition and induction of reactive oxygen species. DNA damage induction was consistent with cytotoxicity observed against proliferating cells and Ag8 induced cell death by apoptosis. Ag8 also inhibited DNA repair enzyme PARP1, showed preferential activity against cisplatin resistant A2780 cells and potentiated the activity of temozolomide. Ag8 was substantially less active against non-proliferating non-cancer cells and selectively inhibited glycolysis in cancer cells. Ag8 also induced significant anti-tumour effects against cells implanted intraperitoneally in hollow fibres but lacked activity against hollow fibres implanted subcutaneously. Thus, Ag8 targets multiple pathways of importance in cancer biology, is less active against non-cancer cells and shows activity in vivo in a loco-regional setting. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Comparison of FDMA and CDMA for second generation land-mobile satellite communications

NASA Technical Reports Server (NTRS)

Yongacoglu, A.; Lyons, R. G.; Mazur, B. A.

1990-01-01

Code Division Multiple Access (CDMA) and Frequency Division Multiple Access (FDMA) (both analog and digital) systems capacities are compared on the basis of identical link availabilities and physical propagation models. Parameters are optimized for a bandwidth limited, multibeam environment. For CDMA, the benefits of voice activated carriers, antenna discrimination, polarization reuse, return link power control and multipath suppression are included in the analysis. For FDMA, the advantages of bandwidth efficient modulation/coding combinations, voice activated carriers, polarization reuse, beam placement, and frequency staggering were taken into account.

Integration and Testing Challenges of Small, Multiple Satellite Missions: Experiences From The Space Technology 5 Project

NASA Technical Reports Server (NTRS)

Sauerwein, Timothy A.; Gostomski, Thomas

2007-01-01

This brief presentation describes the mechanical and electrical integration activities and environmental testing challenges of the Space Technology 5 (ST5) Project. Lessons learned during this process are highlighted, including performing mechanical activities serially to gain efficiency through repetition and performing electrical activities based on the level of subsystem expertise available.

Disc Activities in Physical Education: A Comprehensive Approach

ERIC Educational Resources Information Center

Cramer, Stanley J.

2017-01-01

Nearly everyone who throws a disc associates the activity with fun. Over the years, multiple disc games and activities have been invented, combining fun and learning. These are games that many individuals are likely to continue playing long after they have left school and are worthy of being included in a contemporary physical education program.…

Un Marco Abierto: Un Manual de Matematicas y Ciencas Utilizando Inteligencias Multiples Disenado para Estudiantes Bilingues de Educacion General y Especial (An Open Framework: A Math and Science Manual Utilizing Multiple Intelligences Designed for Bilingual Students in General and Special Education).

ERIC Educational Resources Information Center

New York City Board of Education, Brooklyn, NY. Office of Bilingual Education.

This manual incorporates a Multiple Intelligences perspective into its presentation of themes and lesson ideas for Spanish-English bilingual elementary school students in grades 4-8 and is designed for both gifted and special education uses. Each unit includes practice activities, semantic maps to illustrate and help organize ideas as well as…

Redox flow batteries having multiple electroactive elements

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Wei; Li, Liyu; Yang, Zhenguo

Introducing multiple redox reactions with a suitable voltage range can improve the energy density of redox flow battery (RFB) systems. One example includes RFB systems utilizing multiple redox pairs in the positive half cell, the negative half cell, or in both. Such RFB systems can have a negative electrolyte, a positive electrolyte, and a membrane between the negative electrolyte and the positive electrolyte, in which at least two electrochemically active elements exist in the negative electrolyte, the positive electrolyte, or both.

Relationship between urban sprawl and physical activity, obesity, and morbidity - update and refinement.

PubMed

Ewing, Reid; Meakins, Gail; Hamidi, Shima; Nelson, Arthur C

2014-03-01

This study aims to model multiple health outcomes and behaviors in terms of the updated, refined, and validated county compactness/sprawl measures. Multiple health outcomes and behaviors are modeled using multi-level analysis. After controlling for observed confounding influences, both original and new compactness measures are negatively related to BMI, obesity, heart disease, high blood pressure, and diabetes. Indices are not significantly related to physical activity, perhaps because physical activity is not defined broadly to include active travel to work, shopping, and other destinations. Developing urban and suburban areas in a more compact manner may have some salutary effect on obesity and chronic disease trends. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

EBF factors drive expression of multiple classes of target genes governing neuronal development.

PubMed

Green, Yangsook S; Vetter, Monica L

2011-04-30

Early B cell factor (EBF) family members are transcription factors known to have important roles in several aspects of vertebrate neurogenesis, including commitment, migration and differentiation. Knowledge of how EBF family members contribute to neurogenesis is limited by a lack of detailed understanding of genes that are transcriptionally regulated by these factors. We performed a microarray screen in Xenopus animal caps to search for targets of EBF transcriptional activity, and identified candidate targets with multiple roles, including transcription factors of several classes. We determined that, among the most upregulated candidate genes with expected neuronal functions, most require EBF activity for some or all of their expression, and most have overlapping expression with ebf genes. We also found that the candidate target genes that had the most strongly overlapping expression patterns with ebf genes were predicted to be direct transcriptional targets of EBF transcriptional activity. The identification of candidate targets that are transcription factor genes, including nscl-1, emx1 and aml1, improves our understanding of how EBF proteins participate in the hierarchy of transcription control during neuronal development, and suggests novel mechanisms by which EBF activity promotes migration and differentiation. Other candidate targets, including pcdh8 and kcnk5, expand our knowledge of the types of terminal differentiated neuronal functions that EBF proteins regulate.

Lateralized hippocampal oscillations underlie distinct aspects of human spatial memory and navigation.

PubMed

Miller, Jonathan; Watrous, Andrew J; Tsitsiklis, Melina; Lee, Sang Ah; Sheth, Sameer A; Schevon, Catherine A; Smith, Elliot H; Sperling, Michael R; Sharan, Ashwini; Asadi-Pooya, Ali Akbar; Worrell, Gregory A; Meisenhelter, Stephen; Inman, Cory S; Davis, Kathryn A; Lega, Bradley; Wanda, Paul A; Das, Sandhitsu R; Stein, Joel M; Gorniak, Richard; Jacobs, Joshua

2018-06-21

The hippocampus plays a vital role in various aspects of cognition including both memory and spatial navigation. To understand electrophysiologically how the hippocampus supports these processes, we recorded intracranial electroencephalographic activity from 46 neurosurgical patients as they performed a spatial memory task. We measure signals from multiple brain regions, including both left and right hippocampi, and we use spectral analysis to identify oscillatory patterns related to memory encoding and navigation. We show that in the left but not right hippocampus, the amplitude of oscillations in the 1-3-Hz "low theta" band increases when viewing subsequently remembered object-location pairs. In contrast, in the right but not left hippocampus, low-theta activity increases during periods of navigation. The frequencies of these hippocampal signals are slower than task-related signals in the neocortex. These results suggest that the human brain includes multiple lateralized oscillatory networks that support different aspects of cognition.

High exhaust temperature, zoned, electrically-heated particulate matter filter

DOEpatents

Gonze, Eugene V.; Paratore, Jr., Michael J.; Bhatia, Garima

2015-09-22

A system includes a particulate matter (PM) filter, an electric heater, and a control circuit. The electric heater includes multiple zones, which each correspond to longitudinal zones along a length of the PM filter. A first zone includes multiple discontinuous sub-zones. The control circuit determines whether regeneration is needed based on an estimated level of loading of the PM filter and an exhaust flow rate. In response to a determination that regeneration is needed, the control circuit: controls an operating parameter of an engine to increase an exhaust temperature to a first temperature during a first period; after the first period, activates the first zone; deactivates the first zone in response to a minimum filter face temperature being reached; subsequent to deactivating the first zone, activates a second zone; and deactivates the second zone in response to the minimum filter face temperature being reached.

Recurrent TERT promoter mutations identified in a large-scale study of multiple tumour types are associated with increased TERT expression and telomerase activation.

PubMed

Huang, Dong-Sheng; Wang, Zhaohui; He, Xu-Jun; Diplas, Bill H; Yang, Rui; Killela, Patrick J; Meng, Qun; Ye, Zai-Yuan; Wang, Wei; Jiang, Xiao-Ting; Xu, Li; He, Xiang-Lei; Zhao, Zhong-Sheng; Xu, Wen-Juan; Wang, Hui-Ju; Ma, Ying-Yu; Xia, Ying-Jie; Li, Li; Zhang, Ru-Xuan; Jin, Tao; Zhao, Zhong-Kuo; Xu, Ji; Yu, Sheng; Wu, Fang; Liang, Junbo; Wang, Sizhen; Jiao, Yuchen; Yan, Hai; Tao, Hou-Quan

2015-05-01

Several somatic mutation hotspots were recently identified in the telomerase reverse transcriptase (TERT) promoter region in human cancers. Large scale studies of these mutations in multiple tumour types are limited, in particular in Asian populations. This study aimed to: analyse TERT promoter mutations in multiple tumour types in a large Chinese patient cohort, investigate novel tumour types and assess the functional significance of the mutations. TERT promoter mutation status was assessed by Sanger sequencing for 13 different tumour types and 799 tumour tissues from Chinese cancer patients. Thymic epithelial tumours, gastrointestinal leiomyoma, and gastric schwannoma were included, for which the TERT promoter has not been previously sequenced. Functional studies included TERT expression by reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR), telomerase activity by the telomeric repeat amplification protocol (TRAP) assay and promoter activity by the luciferase reporter assay. TERT promoter mutations were highly frequent in glioblastoma (83.9%), urothelial carcinoma (64.5%), oligodendroglioma (70.0%), medulloblastoma (33.3%) and hepatocellular carcinoma (31.4%). C228T and C250T were the most common mutations. In urothelial carcinoma, several novel rare mutations were identified. TERT promoter mutations were absent in gastrointestinal stromal tumour (GIST), thymic epithelial tumours, gastrointestinal leiomyoma, gastric schwannoma, cholangiocarcinoma, gastric and pancreatic cancer. TERT promoter mutations highly correlated with upregulated TERT mRNA expression and telomerase activity in adult gliomas. These mutations differentially enhanced the transcriptional activity of the TERT core promoter. TERT promoter mutations are frequent in multiple tumour types and have similar distributions in Chinese cancer patients. The functional significance of these mutations reflect the importance to telomere maintenance and hence tumourigenesis, making them potential therapeutic targets. Copyright © 2015 Elsevier Ltd. All rights reserved.

Recurrent TERT promoter mutations identified in a large-scale study of multiple tumor types are associated with increased TERT expression and telomerase activation

PubMed Central

Huang, Dong-Sheng; Wang, Zhaohui; He, Xu-Jun; Diplas, Bill H.; Yang, Rui; Killela, Patrick J.; Liang, Junbo; Meng, Qun; Ye, Zai-Yuan; Wang, Wei; Jiang, Xiao-Ting; Xu, Li; He, Xiang-Lei; Zhao, Zhong-Sheng; Xu, Wen-Juan; Wang, Hui-Ju; Ma, Ying-Yu; Xia, Ying-Jie; Li, Li; Zhang, Ru-Xuan; Jin, Tao; Zhao, Zhong-Kuo; Xu, Ji; Yu, Sheng; Wu, Fang; Wang, Si-Zhen; Jiao, Yu-Chen; Yan, Hai; Tao, Hou-Quan

2015-01-01

Background Several somatic mutation hotspots were recently identified in the TERT promoter region in human cancers. Large scale studies of these mutations in multiple tumor types are limited, in particular in Asian populations. This study aimed to: analyze TERT promoter mutations in multiple tumor types in a large Chinese patient cohort, investigate novel tumor types and assess the functional significance of the mutations. Methods TERT promoter mutation status was assessed by Sanger sequencing for 13 different tumor types and 799 tumor tissues from Chinese cancer patients. Thymic epithelial tumors, gastrointestinal leiomyoma, and gastric schwannoma were included, for which the TERT promoter has not been previously sequenced. Functional studies included TERT expression by RT-qPCR, telomerase activity by the TRAP assay, and promoter activity by the luciferase reporter assay. Results TERT promoter mutations were highly frequent in glioblastoma (83.9%), urothelial carcinoma (64.5%), oligodendroglioma (70.0%), medulloblastoma (33.3%), and hepatocellular carcinoma (31.4%). C228T and C250T were the most common mutations. In urothelial carcinoma, several novel rare mutations were identified. TERT promoter mutations were absent in GIST, thymic epithelial tumors, gastrointestinal leiomyoma, gastric schwannoma, cholangiocarcinoma, gastric and pancreatic cancer. TERT promoter mutations highly correlated with upregulated TERT mRNA expression and telomerase activity in adult gliomas. These mutations differentially enhanced the transcriptional activity of the TERT core promoter. Conclusions TERT promoter mutations are frequent in multiple tumor types and have similar distributions in Chinese cancer patients. The functional significance of these mutations reflect the importance to telomere maintenance and hence tumorigenesis, making them potential therapeutic targets. PMID:25843513

Teaching Group Work with "The Great Debaters"

ERIC Educational Resources Information Center

Moe, Jeffry; Autry, Linda; Olson, Joann S.; Johnson, Kaprea F.

2014-01-01

An experiential learning activity, based on the film "The Great Debaters" (Washington, D., 2007), was used during a group work class. Description and preliminary evaluation of the activity is provided, including analysis of participant scores on the group leader self-efficacy instrument at multiple points. Implications and future…

Reframing Notions of Identity, Learning, and Culture through the Use of Performing and Visual Arts within a Detention Center

ERIC Educational Resources Information Center

Turner, Sean Gregory

2013-01-01

This study examines a multimodal arts-based inquiry that took place within a secure detention center. The inquiry was inclusive of design, rehearsal, and production activities that culminated into a final theatre production. The methods for this study included pulling from multiple disciplines to develop multiple perspectives towards the data as…

Enhancement of ORR catalytic activity by multiple heteroatom-doped carbon materials.

PubMed

Kim, Dae-wook; Li, Oi Lun; Saito, Nagahiro

2015-01-07

Heteroatom-doped carbon matrices have been attracting significant attention due to their superior electrochemical stability, light weight and low cost. Hence, in this study, various types of heteroatom, including single dopants of N, B and P and multiple dopants of B-N and P-N with a carbon matrix were synthesized by an innovative method named the solution plasma process. The heteroatom was doped into the carbon matrix during the discharge process by continuous dissociation and recombination of precursors. The chemical bonding structure, ORR activity and electrochemical performance were compared in detail for each single dopant and multiple dopants. According to the Raman spectra, the carbon structures were deformed by the doped heteroatoms in the carbon matrix. In comparison with N-doped structures (NCNS), the ORR potential of PN-doped structures (PNCNS) was positively shifted from -0.27 V to -0.24 V. It was observed that doping with N decreased the bonding between P and C in the matrix. The multiple doping induced additional active sites for ORR which further enhanced ORR activity and stability. Therefore, PNCNS is a promising metal-free catalyst for ORR at the cathode in a fuel cell.

Fibroblast growth factors, old kids on the new block

PubMed Central

Li, Xiaokun; Wang, Cong; Xiao, Jian; McKeehan, Wallace L.; Wang, Fen

2016-01-01

The fibroblast growth factors (FGFs) are a family of cell intrinsic regulatory peptides that control a broad spectrum of cellular activities. The family includes canonic FGFs that elicit their activities by activating the FGF receptor (FGFR) tyrosine kinase and non-canonic members that elicit their activities intracellularly and via FGFR-independent mechanisms. The FGF signaling axis is highly complex due to the existence of multiple isoforms of both ligands and receptors, as well as cofactors that include the chemically heterogeneous heparan sulfate (HS) cofactors, and in the case of endocrine FGFs, the Klotho coreceptors. Resident FGF signaling controls embryonic development, maintains tissue homeostasis, promotes wound healing and tissue regeneration, and regulates functions of multiple organs. However, ectopic or aberrant FGF signaling is a culprit for various diseases, including congenital birth defects, metabolic disorder, and cancer. The molecular mechanisms by which the specificity of FGF signaling is achieved remain incompletely understood. Since its application as a druggable target has been gradually recognized by pharmaceutical companies and translational researchers, understanding the determinants of FGF signaling specificity has become even more important in order to get into the position to selectively suppress a particular pathway without affecting others to minimize side effects. PMID:26768548

Reserve-building activities in multiple sclerosis patients and healthy controls: a descriptive study.

PubMed

Schwartz, Carolyn E; Ayandeh, Armon; Ramanathan, Murali; Benedict, Ralph; Dwyer, Michael G; Weinstock-Guttman, Bianca; Zivadinov, Robert

2015-08-12

Cognitive reserve has been implicated as a possible protective factor in multiple sclerosis (MS) but to date no study has compared reserve-building activities across disease course or to healthy controls. This study aims to describe differences in reserve-building activities across the MS disease course and healthy controls. Secondary analysis of a cross-sectional cohort study that included 276 healthy controls, and subjects with clinically isolated syndrome (CIS; n = 67), relapsing-remitting MS (RRMS; n = 358) and secondary progressive MS (PMS; n = 109). Past reserve-building activities were operationalized as occupational attainment and education. Current activities comprised 6 strenuous and 6 non-strenuous activities, including 5 reserve-building activities and television-watching. Multivariate Analysis of Variance models examined group differences in past and current activities, after adjusting for covariates. There were group differences in past and current reserve-building activities. SPMS patients had lower past reserve-building activities than healthy controls. All forms of MS engaged in fewer strenuous current reserve-building pursuits than healthy controls. RRMS read less than healthy controls. SPMS engaged in fewer job-related non-strenuous activities. All MS groups watched more television than healthy controls. MS patients show significantly fewer past and present reserve-building activities. Although it is difficult to establish causality without future prospective studies, lifestyle-modifying interventions should prioritize expanding MS patients' repertoire of strenuous and non-strenuous activities.

How to Individualize Mathematics Successfully: With Materials for Implementation.

ERIC Educational Resources Information Center

Vinskey, Mildred L.

Presented is a method for individualizing mathematics which utilizes the "Learning Activities Package" (LAP). LAP is a self-contained unit based on specific behavioral objectives which contains a pretest, a posttest, examples, explanations, and activities. The topics covered include but are not limited to: multiplication and division by powers of…

76 FR 35950 - Agency Information Collection (Disability Benefits Questionnaires-Group 3) Activity Under OMB Review

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-20

... Collection (Disability Benefits Questionnaires--Group 3) Activity Under OMB Review AGENCY: Veterans Benefits... Questionnaire, VA Form 21-0960C-5. b. Headaches (Including Migraine Headaches), Disability Benefits Questionnaire, VA Form 21-0960C-8. c. Multiple Sclerosis (MS), Disability Benefits Questionnaire, VA Form 21...

Understanding Students' Competition Preference in Multiple-Mice Supported Classroom

ERIC Educational Resources Information Center

Chang, Ben; Chuang, Min-Tun; Ho, Spes

2013-01-01

Competition has been prevalent in all types of childhood activities including playing, learning, and living. Studies have shown that a well-designed competitive activity can motivate students to perform at an increased level. However, there have been few research studies on the relationship between learners' preferences and performance in relation…

Activity-dependent plasticity in spinal cord injury

PubMed Central

Lynskey, James V.; Belanger, Adam; Jung, Ranu

2008-01-01

The adult mammalian central nervous system (CNS) is capable of considerable plasticity, both in health and disease. After spinal neurotrauma, the degrees and extent of neuroplasticity and recovery depend on multiple factors, including the level and extent of injury, postinjury medical and surgical care, and rehabilitative interventions. Rehabilitation strategies focus less on repairing lost connections and more on influencing CNS plasticity for regaining function. Current evidence indicates that strategies for rehabilitation, including passive exercise, active exercise with some voluntary control, and use of neuroprostheses, can enhance sensorimotor recovery after spinal cord injury (SCI) by promoting adaptive structural and functional plasticity while mitigating maladaptive changes at multiple levels of the neuraxis. In this review, we will discuss CNS plasticity that occurs both spontaneously after SCI and in response to rehabilitative therapies. PMID:18566941

Subtle Nonlinearity in Popular Album Charts

NASA Astrophysics Data System (ADS)

Bentley, R. Alexander; Maschner, Herbert D. G.

Large-scale patterns of culture change may be explained by models of self organized criticality, or alternatively, by multiplicative processes. We speculate that popular album activity may be similar to critical models of extinction in that interconnected agents compete to survive within a limited space. Here we investigate whether popular music albums as listed on popular album charts display evidence of self-organized criticality, including a self-affine time series of activity and power-law distributions of lifetimes and exit activity in the chart. We find it difficult to distinguish between multiplicative growth and critical model hypotheses for these data. However, aspects of criticality may be masked by the selective sampling that a "Top 200" listing necessarily implies.

Laterally injected light-emitting diode and laser diode

DOEpatents

Miller, Mary A.; Crawford, Mary H.; Allerman, Andrew A.

2015-06-16

A p-type superlattice is used to laterally inject holes into an III-nitride multiple quantum well active layer, enabling efficient light extraction from the active area. Laterally-injected light-emitting diodes and laser diodes can enable brighter, more efficient devices that impact a wide range of wavelengths and applications. For UV wavelengths, applications include fluorescence-based biological sensing, epoxy curing, and water purification. For visible devices, applications include solid state lighting and projection systems.

Bioterrorism and Biocrimes: The Illicit Use of Biological Agents Since 1900

DTIC Science & Technology

2001-02-01

to white supremacist groups, including the Aryan Nation and the Christian Identity movement, he 5 involve allegations of covert state activities ...toxin to poison livestock in what is now Kenya. The full extent of these activities is not known. Polish Resistance: Multiple reports suggest that...thorough reporting of Aum’s biological warfare activities . See page 47 for additional details. Table 1: Confirmed cases of illicit biological agent activity

Exploring Physical Activity Behaviour of Persons with Multiple Sclerosis: A Qualitative Pilot Study

PubMed Central

Resnik, Linda; Allen, Susan

2015-01-01

Purpose Identify facilitators and barriers to physical activity (PA), and explore the utility of Social Cognitive Theory (SCT) and Transactional Model of Stress and Coping (TMSC) in understanding PA behaviour among persons with multiple sclerosis (MS). Methods Thirteen participants from a clinical trial were interviewed and classified as physically active, sometimes active, or inactive based on the Health-Promoting Lifestyle Profile-II. Interviews were analysed using analytical induction, which consisted of coding data into pre-established categories and then exploring similarities and differences between groups. Pre-established coding categories were constructs from SCT (i.e. environment, expectations, self-efficacy, and self-regulation) and TMSC (i.e. stress appraisal and coping style). Results Inactive and active participants differed in their self-regulation skills, self-efficacy, and coping styles. Common barriers to PA included symptoms and the physical and social environment. Facilitators of PA included strong self-regulation skills, confidence to overcome symptoms to engage in PA (i.e. barrier self-efficacy), and positive coping styles. Conclusion Results from this pilot study suggest that PA interventions will need to implement multiple strategies that target self-efficacy, social environment, and coping styles. We found SCT and TMSC useful in understanding PA behaviour among persons with MS; however, a limitation to these theories is that they are not explicit in the relationship between health and cognitions. Future research will need to explore how to incorporate models of health and function into existing behaviour change theories. PMID:19479491

How Do Multiple Text Resources Influence Learning To Read American History in Fifth Grade?: NRRC Ongoing Research.

ERIC Educational Resources Information Center

VanSledright, Bruce A.

1995-01-01

A naturalistic study explored a classroom in which multiple history text resources were present and actively used by fifth-grade students. The teacher used the textbook and supplemented it with a wide assortment of trade books. Students worked in small groups of 3 to 5 students. Data included field notes of classroom observations and in-depth…

Metformin targets multiple signaling pathways in cancer.

PubMed

Lei, Yong; Yi, Yanhua; Liu, Yang; Liu, Xia; Keller, Evan T; Qian, Chao-Nan; Zhang, Jian; Lu, Yi

2017-01-26

Metformin, an inexpensive and well-tolerated oral agent commonly used in the first-line treatment of type 2 diabetes, has become the focus of intense research as a candidate anticancer agent. Here, we discuss the potential of metformin in cancer therapeutics, particularly its functions in multiple signaling pathways, including AMP-activated protein kinase, mammalian target of rapamycin, insulin-like growth factor, c-Jun N-terminal kinase/mitogen-activated protein kinase (p38 MAPK), human epidermal growth factor receptor-2, and nuclear factor kappaB pathways. In addition, cutting-edge targeting of cancer stem cells by metformin is summarized.

[Impact of physical activity level on alexithymia and coping strategies in an over-40 multiple sclerosis population: a pilot study].

PubMed

Mosson, M; Peter, L; Montel, S

2014-01-01

The aim of this study was to evaluate the impact of physical activity on alexithymia and coping strategies among people with multiple sclerosis aged over 40. The hypotheses were that physical activity should have a protective effect on alexithymia, and more particularly, on "emotional identification" and could influence coping strategies because it can be considered as a distractive coping strategy. Thirty-seven patients aged 40 years or older were asked to complete a form including an identification sheet and standardized questionnaires: the Bermond-Vorst Alexithymia Questionnaire (version B), the Coping with Health Injuries and Problem Questionnaire, the Fatigue Impact Scale, and the Hospital Anxiety and Depression Scale. The participants with a high or moderate level of physical activity used "information research" as a coping strategy better than those who had a lower level of physical activity. They also analyzed their emotions better. The results revealed an association between these variables and anxiety, depression and fatigue. This study provides insight for future research about the impact of physical activity on multiple sclerosis. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Multiple pilomatrixomas in a survivor of WNT-activated medulloblastoma leading to the discovery of a germline APC mutation and the diagnosis of familial adenomatous polyposis.

PubMed

Bendelsmith, Charles R; Skrypek, Mary M; Patel, Sachin R; Pond, Dinel A; Linabery, Amy M; Bendel, Anne E

2018-01-01

Because children diagnosed with WNT-activated medulloblastoma have a 10-year overall survival rate of 95%, active long-term follow-up is critically important in reducing mortality from other causes. Here, we describe an 11-year-old adopted female who developed multiple pilomatrixomas 3 years after diagnosis of WNT-activated medulloblastoma, an unusual finding that prompted deeper clinical investigation. A heterozygous germline APC gene mutation was discovered, consistent with familial adenomatous polyposis. Screening endoscopy revealed numerous precancerous polyps that were excised. This case highlights the importance of long-term follow-up of pediatric cancer survivors, including attention to unexpected symptoms, which might unveil an underlying cancer predisposition syndrome. © 2017 Wiley Periodicals, Inc.

"This Is Still a Work in Progress": Common Ground, Littleton, New Hampshire.

ERIC Educational Resources Information Center

Hall, Mair; Walker, Pam

This site-visit report describes Common Ground, a program located in New Hampshire that supports 52 people with developmental disabilities, including some with severe and multiple impairments, in a broad range of individualized, integrated daytime activities, including supported and competitive employment, self-employment, volunteer work, and the…

Developing effective interuniversity partnerships and community-based research to address health disparities.

PubMed

Carey, Timothy S; Howard, Daniel L; Goldmon, Moses; Roberson, James T; Godley, Paul A; Ammerman, Alice

2005-11-01

Health disparities are an enormous challenge to American society. Addressing these disparities is a priority for U.S. society and especially for institutions of higher learning, with their threefold mission of education, service, and research. Collaboration across multiple intellectual disciplines will be critical as universities address health disparities. In addition, universities must collaborate with communities, with state partners, and with each other. Development of these collaborations must be sensitive to the history and unique characteristics of each academic institution and population. The authors describe the challenges of all three types of collaboration, but primarily focus on collaboration between research-intensive universities and historically black colleges and universities. The authors describe a four-year collaboration between Shaw University and the University of North Carolina at Chapel Hill (UNC-CH). These universities strategically developed multiple research initiatives to address health disparities, building on modest early success and personal relationships. These activities included participation by Shaw faculty in faculty development activities, multiple collaborative pilot studies, and joint participation in securing grants from the Agency for Health care Research and Quality of the federal Department of Health and Human Services and the National Institutes of Health, including a P-60 Project EXPORT center grant. These multiple activities were sometimes led by UNC-CH, sometimes by Shaw University. Open discussion of problems as they arose, realistic expectations, and mutual recognition of the strengths of each institution and its faculty have been critical in achieving successful collaboration to date.

Developing Effective Interuniversity Partnerships and Community-Based Research to Address Health Disparities

PubMed Central

Carey, Timothy S.; Howard, Daniel L.; Goldmon, Moses; Roberson, James T.; Godley, Paul A.; Ammerman, Alice

2009-01-01

Health disparities are an enormous challenge to American society. Addressing these disparities is a priority for U.S. society and especially for institutions of higher learning, with their threefold mission of education, service, and research. Collaboration across multiple intellectual disciplines will be critical as universities address health disparities. In addition, universities must collaborate with communities, with state partners, and with each other. Development of these collaborations must be sensitive to the history and unique characteristics of each academic institution and population. The authors describe the challenges of all three types of collaboration, but primarily focus on collaboration between research-intensive universities and historically black colleges and universities. The authors describe a four-year collaboration between Shaw University and the University of North Carolina at Chapel Hill (UNC-CH). These universities strategically developed multiple research initiatives to address health disparities, building on modest early success and personal relationships. These activities included participation by Shaw faculty in faculty development activities, multiple collaborative pilot studies, and joint participation in securing grants from the Agency for Health care Research and Quality of the federal Department of Health and Human Services and the National Institutes of Health, including a P-60 Project EXPORT center grant. These multiple activities were sometimes led by UNC-CH, sometimes by Shaw University. Open discussion of problems as they arose, realistic expectations, and mutual recognition of the strengths of each institution and its faculty have been critical in achieving successful collaboration to date. PMID:16249303

Microfabricated injectable drug delivery system

DOEpatents

Krulevitch, Peter A.; Wang, Amy W.

2002-01-01

A microfabricated, fully integrated drug delivery system capable of secreting controlled dosages of multiple drugs over long periods of time (up to a year). The device includes a long and narrow shaped implant with a sharp leading edge for implantation under the skin of a human in a manner analogous to a sliver. The implant includes: 1) one or more micromachined, integrated, zero power, high and constant pressure generating osmotic engine; 2) low power addressable one-shot shape memory polymer (SMP) valves for switching on the osmotic engine, and for opening drug outlet ports; 3) microfabricated polymer pistons for isolating the pressure source from drug-filled microchannels; 4) multiple drug/multiple dosage capacity, and 5) anisotropically-etched, atomically-sharp silicon leading edge for penetrating the skin during implantation. The device includes an externally mounted controller for controlling on-board electronics which activates the SMP microvalves, etc. of the implant.

Using community insight to understand physical activity adoption in overweight and obese African American and Hispanic women: A qualitative study

USDA-ARS?s Scientific Manuscript database

Ecologic models suggest that multiple levels of influencing factors are important for determining physical activity participation and include individual, social, and environmental factors. The purpose of this qualitative study was to use an ecologic framework to gain a deeper understanding of the un...

Antimicrobial activities of natural antimicrobial compounds against susceptible and antibiotic-resistant pathogens in the absence and presence of food

USDA-ARS?s Scientific Manuscript database

In an effort to improve microbial food safety, we are studying the antimicrobial activities of different classes of natural compounds including plant essential oils, apple, grape, olive, and tea extracts, bioactive components, and seashell-derived chitosans against multiple foodborne pathogens in cu...

"I'd Rather Watch TV": An Examination of Physical Activity in Adults with Mental Retardation

ERIC Educational Resources Information Center

Frey, Georgia C.; Buchanan, Alice M.; Rosser Sandt, Dawn D.

2005-01-01

Interpretive ethnography was used as a framework to examine perceptions of physical activity behavior of 12 adults with mild mental retardation. Four parents and two job supervisors also agreed to participate. Multiple data sources included in-depth interviews, diaries, accelerometry, and informal observations. Participants reported many physical…

The Game of Social Life: An Assessment of a Multidimensional Poverty Simulation

ERIC Educational Resources Information Center

Bramesfeld, Kosha D.; Good, Arla

2015-01-01

This article presents the development of a new simulation activity, the Game of Social Life. The activity introduces students to concepts of social stratification based on multiple dimensions of poverty, including inequalities related to housing, education, occupational status, social power, and health outcomes. The game was administered to…

POLYBROMINATED DEPHENYL ETHERS (PBDES) AND ORTHO-SUBSTITUTED POLYCHLORINATED BIPHENYLS (PCBS) AS NEUROENDOCRINE DISRUPTORS OF VASOPRESSIN RELEASE: EFFECTS DURING PHYSIOLOGICAL ACTIVATION IN VITRO AND STRUCTURE-ACTIVITY RELATIONSHIPS

EPA Science Inventory

The neuropeptide, vasopressin (VP) is synthesized in magnocellular neuroendocrine cells (MNCs) located within the supraoptic (SON) and paraventricular (PVN) nuclei of the mammalian hypothalamus. VP has multiple functions including maintenance of body fluid homeostasis, cardiovasc...

An Examination of the Addition of Video Informed Reflective Practice to the Active Support Toolkit

ERIC Educational Resources Information Center

Baker, Peter; Appleton, Philippa; Williams, Rosie

2017-01-01

Background: This study evaluated a package of Active Support (AS), which included standard training with additional video informed reflective practice. Materials & Methods: The training package was implemented as part of a service improvement initiative in four residential intellectual disability homes, using a concurrent multiple baseline…

Distinct representations of subtraction and multiplication in the neural systems for numerosity and language

PubMed Central

Prado, Jérôme; Mutreja, Rachna; Zhang, Hongchuan; Mehta, Rucha; Desroches, Amy S.; Minas, Jennifer E.; Booth, James R.

2010-01-01

It has been proposed that recent cultural inventions such as symbolic arithmetic recycle evolutionary older neural mechanisms. A central assumption of this hypothesis is that the degree to which a pre-existing mechanism is recycled depends upon the degree of similarity between its initial function and the novel task. To test this assumption, we investigated whether the brain region involved in magnitude comparison in the intraparietal sulcus (IPS), localized by a numerosity comparison task, is recruited to a greater degree by arithmetic problems that involve number comparison (single-digit subtractions) than by problems that involve retrieving facts from memory (single-digit multiplications). Our results confirmed that subtractions are associated with greater activity in the IPS than multiplications, whereas multiplications elicit greater activity than subtractions in regions involved in verbal processing including the middle temporal gyrus and inferior frontal gyrus that were localized by a phonological processing task. Pattern analyses further indicated that the neural mechanisms more active for subtraction than multiplication in the IPS overlap with those involved in numerosity comparison, and that the strength of this overlap predicts inter-individual performance in the subtraction task. These findings provide novel evidence that elementary arithmetic relies on the co-option of evolutionary older neural circuits. PMID:21246667

Current test results for the Athena radar responsive tag

NASA Astrophysics Data System (ADS)

Ormesher, Richard C.; Martinez, Ana; Plummer, Kenneth W.; Erlandson, David; Delaware, Sheri; Clark, David R.

2006-05-01

Sandia National Laboratories has teamed with General Atomics and Sierra Monolithics to develop the Athena tag for the Army's Radar Tag Engagement (RaTE) program. The radar-responsive Athena tag can be used for Blue Force tracking and Combat Identification (CID) as well as data collection, identification, and geolocation applications. The Athena tag is small (~4.5" x 2.4" x 4.2"), battery-powered, and has an integral antenna. Once remotely activated by a Synthetic Aperture Radar (SAR) or Moving Target Indicator (MTI) radar, the tag transponds modulated pulses to the radar at a low transmit power. The Athena tag can operate Ku-band and X-band airborne SAR and MTI radars. This paper presents results from current tag development testing activities. Topics covered include recent field tests results from the AN/APY-8 Lynx, F16/APG-66, and F15E/APG-63 V(1) radars and other Fire Control radars. Results show that the Athena tag successfully works with multiple radar platforms, in multiple radar modes, and for multiple applications. Radar-responsive tags such as Athena have numerous applications in military and government arenas. Military applications include battlefield situational awareness, combat identification, targeting, personnel recovery, and unattended ground sensors. Government applications exist in nonproliferation, counter-drug, search-and-rescue, and land-mapping activities.

Multiple Flow Loop SCADA System Implemented on the Production Prototype Loop

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baily, Scott A.; Dalmas, Dale Allen; Wheat, Robert Mitchell

2015-11-16

The following report covers FY 15 activities to develop supervisory control and data acquisition (SCADA) system for the Northstar Moly99 production prototype gas flow loop. The goal of this effort is to expand the existing system to include a second flow loop with a larger production-sized blower. Besides testing the larger blower, this system will demonstrate the scalability of our solution to multiple flow loops.

Environmental influences on physical activity in rural Midwestern adults: a qualitative approach.

PubMed

Chrisman, Matthew; Nothwehr, Faryle; Yang, Ginger; Oleson, Jacob

2015-01-01

Qualitative research can be used to examine multiple factors associated with physical activity and help practitioners identify language used by the rural adult population when discussing this behavior. Three focus groups were conducted among 19 residents of multiple towns in a rural Midwestern county to examine the language and influences on rural physical activity. Focus group members were asked to define physical activity, exercise, community, and neighborhood. They were asked about the activities they engaged in and facilitators and barriers to those activities. A guidebook was developed to capture major themes and common patterns that emerged in the responses to the topics discussed. The data were reviewed for repeated statements and points that were agreed on by multiple participants. Important factors associated with physical activity include the importance of social support and modeling physical activity behavior. Also, the influence of pets and children was important for engaging these adults in physical activity. The focus group members engaged in walking and bicycling in their neighborhood streets and community trails, and desired to see community buildings be open to the public for exercise. This study revealed contextual issues and culturally relevant language for practitioners to use in tailoring physical activity measurement tools or designing interventions for a rural adult population. Social support (specifically, seeing others being active and using pets as motivators for being active) and policy attitudes may be targeted for interventions to increase physical activity in rural adults. © 2014 Society for Public Health Education.

Environmental Influences on Physical Activity in Rural Midwestern Adults: A Qualitative Approach

PubMed Central

Chrisman, Matthew; Nothwehr, Faryle; Yang, Ginger; Oleson, Jacob

2014-01-01

Qualitative research can be used to examine multiple factors associated with physical activity and help practitioners identify language used by the rural adult population when discussing this behavior. Three focus groups were conducted among 19 residents of multiple towns in a rural Midwestern county to examine the language and influences on rural physical activity. Focus group members were asked to define physical activity, exercise, community, and neighborhood. They were asked about the activities they engaged in and facilitators and barriers to those activities. A guidebook was developed to capture major themes and common patterns that emerged in the responses to the topics discussed. The data were reviewed for repeated statements and points that were agreed on by multiple participants. Important factors associated with physical activity include the importance of social support and modeling physical activity behavior. Also, the influence of pets and children was important for engaging these adults in physical activity. The focus group members engaged in walking and bicycling in their neighborhood streets and community trails, and desired to see community buildings be open to the public for exercise. This study revealed contextual issues and culturally relevant language for practitioners to use in tailoring physical activity measurement tools or designing interventions for a rural adult population. Social support (specifically, seeing others being active and using pets as motivators for being active) and policy attitudes may be targeted for interventions to increase physical activity in rural adults. PMID:24662894

A Grounded Theory of Sexual Minority Women and Transgender Individuals' Social Justice Activism.

PubMed

Hagen, Whitney B; Hoover, Stephanie M; Morrow, Susan L

2018-01-01

Psychosocial benefits of activism include increased empowerment, social connectedness, and resilience. Yet sexual minority women (SMW) and transgender individuals with multiple oppressed statuses and identities are especially prone to oppression-based experiences, even within minority activist communities. This study sought to develop an empirical model to explain the diverse meanings of social justice activism situated in SMW and transgender individuals' social identities, values, and experiences of oppression and privilege. Using a grounded theory design, 20 SMW and transgender individuals participated in initial, follow-up, and feedback interviews. The most frequent demographic identities were queer or bisexual, White, middle-class women with advanced degrees. The results indicated that social justice activism was intensely relational, replete with multiple benefits, yet rife with experiences of oppression from within and outside of activist communities. The empirically derived model shows the complexity of SMW and transgender individuals' experiences, meanings, and benefits of social justice activism.

Phosphorylation of NHE3-S719 regulates NHE3 activity through the formation of multiple signaling complexes

PubMed Central

Sarker, Rafiquel; Cha, Boyoung; Kovbasnjuk, Olga; Cole, Robert; Gabelli, Sandra; Tse, Chung Ming; Donowitz, Mark

2017-01-01

Casein kinase 2 (CK2) binds to the NHE3 C-terminus and constitutively phosphorylates a downstream site (S719) that accounts for 40% of basal NHE3 activity. The role of CK2 in regulation of NHE3 activity in polarized Caco-2/bbe cells was further examined by mutation of NHE3-S719 to A (not phosphorylated) or D (phosphomimetic). NHE3-S719A but not -S719D had multiple changes in NHE3 activity: 1) reduced basal NHE3 activity—specifically, inhibition of the PI3K/AKT-dependent component; 2) reduced acute stimulation of NHE3 activity by LPA/LPA5R stimulation; and 3) reduced acute inhibition of NHE3 activity—specifically, elevated Ca2+ related (carbachol/Ca2+ ionophore), but there was normal inhibition by forskolin and hyperosmolarity. The S719A mutant had reduced NHE3 complex size, reduced expression in lipid rafts, increased BB mobile fraction, and reduced binding to multiple proteins that bind throughout the NHE3 intracellular C-terminus, including calcineurin homologous protein, the NHERF family and SNX27 (related PDZ domains). These studies show that phosphorylation of the NHE3 at a single amino acid in the distal part of the C-terminus affects multiple aspects of NHE3 complex formation and changes the NHE3 lipid raft distribution, which cause changes in specific aspects of basal as well as acutely stimulated and inhibited Na+/H+ exchange activity. PMID:28495796

Use of Activity Space in a Tuberculosis Outbreak: Bringing Homeless Persons Into Spatial Analyses.

PubMed

Worrell, Mary Claire; Kramer, Michael; Yamin, Aliya; Ray, Susan M; Goswami, Neela D

2017-01-01

Tuberculosis (TB) causes significant morbidity and mortality in US cities, particularly in poor, transient populations. During a TB outbreak in Fulton County, Atlanta, GA, we aimed to determine whether local maps created from multiple locations of personal activity per case would differ significantly from traditional maps created from single residential address. Data were abstracted for patients with TB disease diagnosed in 2008-2014 and receiving care at the Fulton County Health Department. Clinical and activity location data were abstracted from charts. Kernel density methods, activity space analysis, and overlay with homeless shelter locations were used to characterize case spatial distribution when using single versus multiple addresses. Data were collected for 198 TB cases, with over 30% homeless US-born cases included. Greater spatial dispersion of cases was found when utilizing multiple versus single addresses per case. Activity spaces of homeless and isoniazid (INH)-resistant cases were more spatially congruent with one another than non-homeless and INH-susceptible cases ( P < .0001 and P < .0001, respectively). Innovative spatial methods allowed us to more comprehensively capture the geography of TB-infected homeless persons, who made up a large portion of the Fulton County outbreak. We demonstrate how activity space analysis, prominent in exposure science and chronic disease, supports that routine capture of multiple location TB data may facilitate spatially different public health interventions than traditional surveillance maps. © The Author 2017. Published by Oxford University Press on behalf of Infectious Diseases Society of America.

Communicative participation restrictions in multiple sclerosis: associated variables and correlation with social functioning.

PubMed

Yorkston, Kathryn M; Baylor, Carolyn; Amtmann, Dagmar

2014-01-01

Individuals with multiple sclerosis (MS) are at risk for communication problems that may restrict their ability to take participation in important life roles such as maintenance of relationships, work, or household management. The aim of this project is to examine selected demographic and symptom-related variables that may contribute to participation restrictions. This examination is intended to aid clinicians in predicting who might be at risk for such restrictions and what variables may be targeted in interventions. Community-dwelling adults with MS (n=216) completed a survey either online or using paper forms. The survey included the 46-item version of the Communicative Participation Item Bank, demographics (age, sex, living situation, employment status, education, and time since onset of diagnosis of MS), and self-reported symptom-related variables (physical activity, emotional problems, fatigue, pain, speech severity, and cognitive/communication skills). In order to identify predictors of restrictions in communicative participation, these variables were entered into a backwards stepwise multiple linear regression analysis. Five variables (cognitive/communication skills, speech severity, speech usage, physical activity, and education) were statistically significant predictors of communication participation. In order to examine the relationship of communicative participation and social role variables, bivariate Spearman correlations were conducted. Results suggest only a fair to moderate relationship between communicative participation and measures of social roles. Communicative participation is a complex construct associated with a number of self-reported variables. Clinicians should be alert to risk factors for reduced communicative participation including reduced cognitive and speech skills, lower levels of speech usage, limitations in physical activities and higher levels of education. The reader will be able to: (a) describe the factors that may restrict participation in individuals with multiple sclerosis; (b) list measures of social functioning that may be pertinent in adults with multiple sclerosis; (c) discuss factors that can be used to predict communicative participation in multiple sclerosis. Copyright © 2014 Elsevier Inc. All rights reserved.

Detection of person borne IEDs using multiple cooperative sensors

NASA Astrophysics Data System (ADS)

MacIntosh, Scott; Deming, Ross; Hansen, Thorkild; Kishan, Neel; Tang, Ling; Shea, Jing; Lang, Stephen

2011-06-01

The use of multiple cooperative sensors for the detection of person borne IEDs is investigated. The purpose of the effort is to evaluate the performance benefits of adding multiple sensor data streams into an aided threat detection algorithm, and a quantitative analysis of which sensor data combinations improve overall detection performance. Testing includes both mannequins and human subjects with simulated suicide bomb devices of various configurations, materials, sizes and metal content. Aided threat recognition algorithms are being developed to test detection performance of individual sensors against combined fused sensors inputs. Sensors investigated include active and passive millimeter wave imaging systems, passive infrared, 3-D profiling sensors and acoustic imaging. The paper describes the experimental set-up and outlines the methodology behind a decision fusion algorithm-based on the concept of a "body model".

Coagulation and complement system in critically ill patients.

PubMed

Helling, H; Stephan, B; Pindur, G

2015-01-01

Activation of coagulation and inflammatory response including the complement system play a major role in the pathogenesis of critical illness. However, only limited data are available addressing the relationship of both pathways and its assessment of a predictive value for the clinical outcome in intense care medicine. Therefore, parameters of the coagulation and complement system were studied in patients with septicaemia and multiple trauma regarded as being exemplary for critical illness. 34 patients (mean age: 51.38 years (±16.57), 15 females, 19 males) were investigated at day 1 of admittance to the intensive care unit (ICU). Leukocytes, complement factors C3a and C5a were significantly (p <  0.0500) higher in sepsis than in trauma, whereas platelet count and plasma fibrinogen were significantly lower in multiple trauma. Activation markers of coagulation were elevated in both groups, however, thrombin-antithrombin-complex was significantly higher in multiple trauma. DIC scores of 5 were not exceeded in any of the two groups. Analysing the influences on mortality (11/34; 32.35% ), which was not different in both groups, non-survivors were significantly older, had significantly higher multiple organ failure (MOF) scores, lactate, abnormal prothrombin times and lower C1-inhibitor activities, even more pronounced in early deaths, than survivors. In septic non-survivors protein C was significantly lower than in trauma. We conclude from these data that activation of the complement system as part of the inflammatory response is a significant mechanism in septicaemia, whereas loss and consumption of blood components including parts of the coagulation and complement system is more characteristic for multiple trauma. Protein C in case of severe reduction might be of special concern for surviving in sepsis. Activation of haemostasis was occurring in both diseases, however, overt DIC was not confirmed in this study to be a leading mechanism in critically ill patients. MOF score, lactate, C1-inhibitor and prothrombin time have been the only statistically significant predictors for lethal outcome suggesting that organ function, microcirculation, haemostasis and inflammatory response are essential elements of the pathomechanism and clinical course of diseases among critically ill patients.

Deflation-activated receptors, not classical inflation-activated receptors, mediate the Hering-Breuer deflation reflex.

PubMed

Yu, Jerry

2016-11-01

Many airway sensory units respond to both lung inflation and deflation. Whether those responses to opposite stimuli come from one sensor (one-sensor theory) or more than one sensor (multiple-sensor theory) is debatable. One-sensor theory is commonly presumed in the literature. This article proposes a multiple-sensor theory in which a sensory unit contains different sensors for sensing different forces. Two major types of mechanical sensors operate in the lung: inflation- and deflation-activated receptors (DARs). Inflation-activated sensors can be further divided into slowly adapting receptors (SARs) and rapidly adapting receptors (RARs). Many SAR and RAR units also respond to lung deflation because they contain DARs. Pure DARs, which respond to lung deflation only, are rare in large animals but are easily identified in small animals. Lung deflation-induced reflex effects previously attributed to RARs should be assigned to DARs (including pure DARs and DARs associated with SARs and RARs) if the multiple-sensor theory is accepted. Thus, based on the information, it is proposed that activation of DARs can attenuate lung deflation, shorten expiratory time, increase respiratory rate, evoke inspiration, and cause airway secretion and dyspnea.

Co-immobilization of multiple enzymes by metal coordinated nucleotide hydrogel nanofibers: improved stability and an enzyme cascade for glucose detection

NASA Astrophysics Data System (ADS)

Liang, Hao; Jiang, Shuhui; Yuan, Qipeng; Li, Guofeng; Wang, Feng; Zhang, Zijie; Liu, Juewen

2016-03-01

Preserving enzyme activity and promoting synergistic activity via co-localization of multiple enzymes are key topics in bionanotechnology, materials science, and analytical chemistry. This study reports a facile method for co-immobilizing multiple enzymes in metal coordinated hydrogel nanofibers. Specifically, four types of protein enzymes, including glucose oxidase, Candida rugosa lipase, α-amylase, and horseradish peroxidase, were respectively encapsulated in a gel nanofiber made of Zn2+ and adenosine monophosphate (AMP) with a simple mixing step. Most enzymes achieved quantitative loading and retained full activity. At the same time, the entrapped enzymes were more stable against temperature variation (by 7.5 °C), protease attack, extreme pH (by 2-fold), and organic solvents. After storing for 15 days, the entrapped enzyme still retained 70% activity while the free enzyme nearly completely lost its activity. Compared to nanoparticles formed with AMP and lanthanide ions, the nanofiber gels allowed much higher enzyme activity. Finally, a highly sensitive and selective biosensor for glucose was prepared using the gel nanofiber to co-immobilize glucose oxidase and horseradish peroxidase for an enzyme cascade system. A detection limit of 0.3 μM glucose with excellent selectivity was achieved. This work indicates that metal coordinated materials using nucleotides are highly useful for interfacing with biomolecules.Preserving enzyme activity and promoting synergistic activity via co-localization of multiple enzymes are key topics in bionanotechnology, materials science, and analytical chemistry. This study reports a facile method for co-immobilizing multiple enzymes in metal coordinated hydrogel nanofibers. Specifically, four types of protein enzymes, including glucose oxidase, Candida rugosa lipase, α-amylase, and horseradish peroxidase, were respectively encapsulated in a gel nanofiber made of Zn2+ and adenosine monophosphate (AMP) with a simple mixing step. Most enzymes achieved quantitative loading and retained full activity. At the same time, the entrapped enzymes were more stable against temperature variation (by 7.5 °C), protease attack, extreme pH (by 2-fold), and organic solvents. After storing for 15 days, the entrapped enzyme still retained 70% activity while the free enzyme nearly completely lost its activity. Compared to nanoparticles formed with AMP and lanthanide ions, the nanofiber gels allowed much higher enzyme activity. Finally, a highly sensitive and selective biosensor for glucose was prepared using the gel nanofiber to co-immobilize glucose oxidase and horseradish peroxidase for an enzyme cascade system. A detection limit of 0.3 μM glucose with excellent selectivity was achieved. This work indicates that metal coordinated materials using nucleotides are highly useful for interfacing with biomolecules. Electronic supplementary information (ESI) available: Additional methods, IR and XRD spectroscopy, enzyme loading capacity, enzyme kinetic parameters, and enzyme stability data. See DOI: 10.1039/c5nr08734a

NITRIC OXIDE, MITOCHONDRIAL HYPERPOLARIZATION AND T-CELL ACTIVATION

PubMed Central

Nagy, Gyorgy; Koncz, Agnes; Fernandez, David; Perl, Andras

2007-01-01

T lymphocyte activation is associated with nitric oxide (NO) production that plays an essential role in multiple T cell functions. NO acts as a messenger, activating soluble guanyl cyclase and participating in the transduction signaling pathways involving cyclic GMP. NO modulates mitochondrial events that are involved in apoptosis and regulates mitochondrial membrane potential and mitochondrial biogenesis in many cell types, including lymphocytes. Mitochondrial hyperpolarization (MHP), an early and reversible event during both T lymphocyte activation and apoptosis, is regulated by NO. Here, we discuss recent evidence that NO-induced MHP represents a molecular switch in multiple T cell signaling pathways. Overproduction of NO in systemic lupus erythematosus (SLE) induces mitochondrial biogenesis and alters Ca2+ signaling. Thus, while NO plays a physiological role in lymphocyte cell signaling, its overproduction may disturb normal T cell function, contributing to the pathogenesis of autoimmunity. PMID:17462531

Natural health products that inhibit angiogenesis: a potential source for investigational new agents to treat cancer—Part 1

PubMed Central

Sagar, S.M.; Yance, D.; Wong, R.K.

2006-01-01

An integrative approach for managing a patient with cancer should target the multiple biochemical and physiologic pathways that support tumour development and minimize normal-tissue toxicity. Angiogenesis is a key process in the promotion of cancer. Many natural health products that inhibit angiogenesis also manifest other anticancer activities. The present article focuses on products that have a high degree of anti-angiogenic activity, but it also describes some of the many other actions of these agents that can inhibit tumour progression and reduce the risk of metastasis. Natural health products target molecular pathways other than angiogenesis, including epidermal growth factor receptor, the HER2/neu gene, the cyclooxygenase-2 enzyme, the nuclear factor kappa-B transcription factor, the protein kinases, the Bcl-2 protein, and coagulation pathways. The herbs that are traditionally used for anticancer treatment and that are anti-angiogenic through multiple interdependent processes (including effects on gene expression, signal processing, and enzyme activities) include Artemisia annua (Chinese wormwood), Viscum album (European mistletoe), Curcuma longa (curcumin), Scutellaria baicalensis (Chinese skullcap), resveratrol and proanthocyanidin (grape seed extract), Magnolia officinalis (Chinese magnolia tree), Camellia sinensis (green tea), Ginkgo biloba, quercetin, Poria cocos, Zingiber officinalis (ginger), Panax ginseng, Rabdosia rubescens hora (Rabdosia), and Chinese destagnation herbs. Quality assurance of appropriate extracts is essential prior to embarking upon clinical trials. More data are required on dose–response, appropriate combinations, and potential toxicities. Given the multiple effects of these agents, their future use for cancer therapy probably lies in synergistic combinations. During active cancer therapy, they should generally be evaluated in combination with chemotherapy and radiation. In this role, they act as modifiers of biologic response or as adaptogens, potentially enhancing the efficacy of the conventional therapies. PMID:17576437

Forest fires in Pennsylvania.

Treesearch

Donald A. Haines; William A. Main; Eugene F. McNamara

1978-01-01

Describes factors that contribute to forest fires in Pennsylvania. Includes an analysis of basic statistics; distribution of fires during normal, drought, and wet years; fire cause, fire activity by day-of-week; multiple-fire day; and fire climatology.

Activity recognition using Video Event Segmentation with Text (VEST)

NASA Astrophysics Data System (ADS)

Holloway, Hillary; Jones, Eric K.; Kaluzniacki, Andrew; Blasch, Erik; Tierno, Jorge

2014-06-01

Multi-Intelligence (multi-INT) data includes video, text, and signals that require analysis by operators. Analysis methods include information fusion approaches such as filtering, correlation, and association. In this paper, we discuss the Video Event Segmentation with Text (VEST) method, which provides event boundaries of an activity to compile related message and video clips for future interest. VEST infers meaningful activities by clustering multiple streams of time-sequenced multi-INT intelligence data and derived fusion products. We discuss exemplar results that segment raw full-motion video (FMV) data by using extracted commentary message timestamps, FMV metadata, and user-defined queries.

A Roadmap for using Agile Development in a Traditional System

NASA Technical Reports Server (NTRS)

Streiffert, Barbara; Starbird, Thomas

2006-01-01

I. Ensemble Development Group: a) Produces activity planning software for in spacecraft; b) Built on Eclipse Rich Client Platform (open source development and runtime software); c) Funded by multiple sources including the Mars Technology Program; d) Incorporated the use of Agile Development. II. Next Generation Uplink Planning System: a) Researches the Activity Planning and Sequencing Subsystem for Mars Science Laboratory (APSS); b) APSS includes Ensemble, Activity Modeling, Constraint Checking, Command Editing and Sequencing tools plus other uplink generation utilities; c) Funded by the Mars Technology Program; d) Integrates all of the tools for APSS.

Multiple Mechanisms are Responsible for Transactivation of the Epidermal Growth Factor Receptor in Mammary Epithelial Cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rodland, Karin D.; Bollinger, Nikki; Ippolito, Danielle L.

2008-11-14

REVIEW ENTIRE DOCUMENT AT: https://pnlweb.pnl.gov/projects/bsd/ERICA%20Manuscripts%20for%20Review/KD%20Rodland%20D7E80/HMEC_transactivation_ms01_15+Figs.pdf ABSTRACT: Using a single nontransformed strain of human mammary epithelial cells, we found that the ability of multiple growth factors and cytokines to induce ERK phosphorylation was dependent on EGFR activity. These included lysophosphatidic acid (LPA), uridine triphosphate, growth hormone, vascular endothelial growth factor, insulin-like growth factor-1 (IGF-1), and tumor necrosis factoralpha. In contrast, hepatocyte growth factor could stimulate ERK phosphorylation independent of EGFR activity...

Pinning down the Constitution: Interactively Teaching Congress's Power, Federalism, and Constitutional Interpretation

ERIC Educational Resources Information Center

Emenaker, Ryan

2014-01-01

"Pin-the-Tail-on-the-Constitution" is an engaged-learning activity that has been conducted in 26 classes over the past four years. The activity teaches multiple themes commonly included in a variety of courses on American politics such as federalism, congressional powers, the role of the federal courts, and the relevance of the commerce…

Using Community Insight to Understand Physical Activity Adoption in Overweight and Obese African American and Hispanic Women: A Qualitative Study

ERIC Educational Resources Information Center

Mama, Scherezade K.; McCurdy, Sheryl A.; Evans, Alexandra E.; Thompson, Deborah I.; Diamond, Pamela M.; Lee, Rebecca E.

2015-01-01

Ecologic models suggest that multiple levels of influencing factors are important for determining physical activity participation and include individual, social, and environmental factors. The purpose of this qualitative study was to use an ecologic framework to gain a deeper understanding of the underlying behavioral mechanisms that influence…

Using Word Clouds for Fast, Formative Assessment of Students' Short Written Responses

ERIC Educational Resources Information Center

Brooks, Bill J.; Gilbuena, Debra M.; Krause, Stephen J.; Koretsky, Milo D.

2014-01-01

Active learning in class helps students develop deeper understanding of chemical engineering principles. While the use of multiple-choice ConcepTests is clearly effective, we advocate for including student writing in learning activities as well. In this article, we demonstrate that word clouds can provide a quick analytical technique to assess…

Predicting Middle School Students' Use of Web 2.0 Technologies out of School Using Home and School Technological Variables

ERIC Educational Resources Information Center

Hughes, Joan E.; Read, Michelle F.; Jones, Sara; Mahometa, Michael

2015-01-01

This study used multiple regression to identify predictors of middle school students' Web 2.0 activities out of school, a construct composed of 15 technology activities. Three middle schools participated, where sixth- and seventh-grade students completed a questionnaire. Independent predictor variables included three demographic and five computer…

Inflammasome and Autophagy Regulation: A Two-way Street

PubMed Central

Qian, Sun; Fan, Jie; Billiar, Timothy R; Scott, Melanie J

2017-01-01

Inflammation plays a significant role in protecting hosts against pathogens. Inflammation induced by noninfectious endogenous agents can be detrimental and, if excessive, can result in organ and tissue damage. The inflammasome is a major innate immune pathway that can be activated via both exogenous pathogen-associated molecular patterns (PAMPs) and endogenous damage-associated molecular patterns (DAMPs). Inflammasome activation involves formation and oligomerization of a protein complex including a nucleotide oligomerization domain (NOD)-like receptor (NLR), an adaptor protein and pro-caspase-1. This then allows cleavage and activation of caspase-1, followed by downstream cleavage and release of proinflammatory cytokines interleukin (IL)-1β and IL-18 from innate immune cells. Hyperinflammation caused by unrestrained inflammasome activation is linked with multiple inflammatory diseases, including inflammatory bowel disease, Alzheimer’s disease and multiple sclerosis. So there is an understandable rush to understand mechanisms that regulate such potent inflammatory pathways. Autophagy has now been identified as a main regulator of inflammasomes. Autophagy is a vital intracellular process involved in cellular homeostasis, recycling and removal of damaged organelles (eg, mitochondria) and intracellular pathogens. Autophagy is regulated by proteins that are important in endosomal/phagosomal pathways, as well as by specific autophagy proteins coded for by autophagy-related genes. Cytosolic components are surrounded and contained by a double-membraned vesicle, which then fuses with lysosomes to enable degradation of the contents. Autophagic removal of intracellular DAMPs, inflammasome components or cytokines can reduce inflammasome activation. Similarly, inflammasomes can regulate the autophagic process, allowing for a two-way mutual regulation of inflammation that may hold the key for treatment of multiple diseases. PMID:28741645

B cell biology: implications for treatment of systemic lupus erythematosus.

PubMed

Anolik, J H

2013-04-01

B cells are critical players in the orchestration of properly regulated immune responses, normally providing protective immunity without autoimmunity. Balance in the B cell compartment is achieved through the finely regulated participation of multiple B cell populations with different antibody-dependent and independent functions. Both types of functions allow B cells to modulate other components of the innate and adaptive immune system. Autoantibody-independent B cell functions include antigen presentation, T cell activation and polarization, and dendritic cell modulation. Several of these functions are mediated by the ability of B cells to produce immunoregulatory cytokines and chemokines and by their critical contribution to lymphoid tissue development and organization including the development of ectopic tertiary lymphoid tissue. Additionally, the functional versatility of B cells enables them to play either protective or pathogenic roles in autoimmunity. In turn, B cell dysfunction has been critically implicated in the pathophysiology of systemic lupus erythematosus (SLE), a complex disease characterized by the production of autoantibodies and heterogeneous clinical involvement. Thus, the breakdown of B cell tolerance is a defining and early event in the disease process and may occur by multiple pathways, including alterations in factors that affect B cell activation thresholds, B cell longevity, and apoptotic cell processing. Once tolerance is broken, autoantibodies contribute to autoimmunity by multiple mechanisms including immune-complex mediated Type III hypersensitivity reactions, type II antibody-dependent cytotoxicity, and by instructing innate immune cells to produce pathogenic cytokines including IFNα, TNF and IL-1. The complexity of B cell functions has been highlighted by the variable success of B cell-targeted therapies in multiple autoimmune diseases, including those conventionally viewed as T cell-mediated conditions. Given the widespread utilization of B cell depletion therapy in autoimmune diseases and the need for new therapeutic approaches in SLE, a better understanding of human B cell subsets and the balance of pathogenic and regulatory functions is of the essence.

Sources of Variability in Physical Activity Among Inactive People with Multiple Sclerosis.

PubMed

Uszynski, Marcin K; Herring, Matthew P; Casey, Blathin; Hayes, Sara; Gallagher, Stephen; Motl, Robert W; Coote, Susan

2018-04-01

Evidence supports that physical activity (PA) improves symptoms of multiple sclerosis (MS). Although application of principles from Social Cognitive Theory (SCT) may facilitate positive changes in PA behaviour among people with multiple sclerosis (pwMS), the constructs often explain limited variance in PA. This study investigated the extent to which MS symptoms, including fatigue, depression, and walking limitations combined with the SCT constructs, explained more variance in PA than SCT constructs alone among pwMS. Baseline data, including objectively assessed PA, exercise self-efficacy, goal setting, outcome expectations, 6-min walk test, fatigue and depression, from 65 participants of the Step It Up randomized controlled trial completed in Ireland (2016), were included. Multiple regression models quantified variance explained in PA and independent associations of (1) SCT constructs, (2) symptoms and (3) SCT constructs and symptoms. Model 1 included exercise self-efficacy, exercise goal setting and multidimensional outcomes expectations for exercise and explained ~14% of the variance in PA (R 2 =0.144, p < 0.05). Model 2 included walking limitations, fatigue and depression and explained 20% of the variance in PA (R 2 =0.196, p < 0.01). Model 3 combined models 1 and 2 and explained variance increased to ~29% (R 2 =0.288; p<0.01). In Model 3, exercise self-efficacy (β=0.30, p < 0.05), walking limitations (β=0.32, p < 0.01), fatigue (β = -0.41, p < 0.01) and depression (β = 0.34, p < 0.05) were significantly and independently associated with PA. Findings suggest that relevant MS symptoms improved by PA, including fatigue, depression and walking limitations, and SCT constructs together explained more variance in PA than SCT constructs alone, providing support for targeting both SCT constructs and these symptoms in the multifactorial promotion of PA among pwMS.

The association between sexual satisfaction and body image in women.

PubMed

Pujols, Yasisca; Seal, Brooke N; Meston, Cindy M

2010-02-01

Although sexual functioning has been linked to sexual satisfaction, it only partially explains the degree to which women report being sexually satisfied. Other factors include quality of life, relational variables, and individual factors such as body image. Of the few studies that have investigated the link between body image and sexual satisfaction, most have considered body image to be a single construct and have shown mixed results. The present study assessed multiple body image variables in order to better understand which aspects of body image influence multiple domains of sexual satisfaction, including sexual communication, compatibility, contentment, personal concern, and relational concern in a community sample of women. Women between the ages of 18 and 49 years in sexual relationships (N = 154) participated in an Internet survey that assessed sexual functioning, five domains of sexual satisfaction, and several body image variables. Body image variables included the sexual attractiveness, weight concern, and physical condition subscales of the Body Esteem Scale, the appearance-based subscale of the Cognitive Distractions During Sexual Activity Scale, and body mass index. Total score of the Sexual Satisfaction Scale for Women was the main outcome measure. Sexual functioning was measured by a modified Female Sexual Function Index. Consistent with expectations, correlations indicated significant positive relationships between sexual functioning, sexual satisfaction, and all body image variables. A multiple regression analysis revealed that sexual satisfaction was predicted by high body esteem and low frequency of appearance-based distracting thoughts during sexual activity, even after controlling for sexual functioning status. Several aspects of body image, including weight concern, physical condition, sexual attractiveness, and thoughts about the body during sexual activity predict sexual satisfaction in women. The findings suggest that women who experience low sexual satisfaction may benefit from treatments that target these specific aspects of body image.

Co-immobilization of multiple enzymes by metal coordinated nucleotide hydrogel nanofibers: improved stability and an enzyme cascade for glucose detection.

PubMed

Liang, Hao; Jiang, Shuhui; Yuan, Qipeng; Li, Guofeng; Wang, Feng; Zhang, Zijie; Liu, Juewen

2016-03-21

Preserving enzyme activity and promoting synergistic activity via co-localization of multiple enzymes are key topics in bionanotechnology, materials science, and analytical chemistry. This study reports a facile method for co-immobilizing multiple enzymes in metal coordinated hydrogel nanofibers. Specifically, four types of protein enzymes, including glucose oxidase, Candida rugosa lipase, α-amylase, and horseradish peroxidase, were respectively encapsulated in a gel nanofiber made of Zn(2+) and adenosine monophosphate (AMP) with a simple mixing step. Most enzymes achieved quantitative loading and retained full activity. At the same time, the entrapped enzymes were more stable against temperature variation (by 7.5 °C), protease attack, extreme pH (by 2-fold), and organic solvents. After storing for 15 days, the entrapped enzyme still retained 70% activity while the free enzyme nearly completely lost its activity. Compared to nanoparticles formed with AMP and lanthanide ions, the nanofiber gels allowed much higher enzyme activity. Finally, a highly sensitive and selective biosensor for glucose was prepared using the gel nanofiber to co-immobilize glucose oxidase and horseradish peroxidase for an enzyme cascade system. A detection limit of 0.3 μM glucose with excellent selectivity was achieved. This work indicates that metal coordinated materials using nucleotides are highly useful for interfacing with biomolecules.

Synaptic Activity and Bioenergy Homeostasis: Implications in Brain Trauma and Neurodegenerative Diseases

PubMed Central

Khatri, Natasha; Man, Heng-Ye

2013-01-01

Powered by glucose metabolism, the brain is the most energy-demanding organ in our body. Adequate ATP production and regulation of the metabolic processes are essential for the maintenance of synaptic transmission and neuronal function. Glutamatergic synaptic activity utilizes the largest portion of bioenergy for synaptic events including neurotransmitter synthesis, vesicle recycling, and most importantly, the postsynaptic activities leading to channel activation and rebalancing of ionic gradients. Bioenergy homeostasis is coupled with synaptic function via activities of the sodium pumps, glutamate transporters, glucose transport, and mitochondria translocation. Energy insufficiency is sensed by the AMP-activated protein kinase (AMPK), a master metabolic regulator that stimulates the catalytic process to enhance energy production. A decline in energy supply and a disruption in bioenergy homeostasis play a critical role in multiple neuropathological conditions including ischemia, stroke, and neurodegenerative diseases including Alzheimer’s disease and traumatic brain injuries. PMID:24376435

[Assessment of exposure to tobacco smoke in a selected group of patients with multiple sclerosis from the Upper Silesia region].

PubMed

Dobosz, Cezary; Tyrpień, Krystyna; Pierzchała, Krystyna

2012-01-01

In recent years, the increase in the incidence of multiple sclerosis (MS - Multiple Sclerosis) is observed. and the direct cause of the symptoms of multiple sclerosis is myelin nerves damage. It can be concluded that the environmental factor is at least partly responsible for the occurrence of this disease. For the development of this disease are responsible, in addition to genetic factors, compounds present in many parts of the environment. Many of these compounds may adversely affect the redox equilibrium of the body, exacerbating radicalgenesis and decreasing antioxidant defenses. Multiple sclerosis is usually diagnosed in early adulthood, during most daily activities. Effects of SM on living standards includes not only the medical aspect, but also social, economic and emotional aspect. Polish population is a high risk zone regarding multiple sclerosis. The aim of this study was a preliminary assessment of selected environmental exposure factors in the pathogenesis of multiple sclerosis with regard to exposure to tobacco smoke with the author's survey of patients from the region of Upper Silesia. Most MS patients (32) in the study group (suffering from MS from 2 to 44 years) are inhabitants of agglomeration of over 50 thousand citizens, from the area of Gliwice, Bytom and Zabrze (43.75%). In investigated group 46.88% MS patients from Silesia region were exposed to tobacco smoke, of which 21.88% actively smoke. Patients with MS, in order not to worsen their disease manifestation, should stop smoking and increase, if possible, any physical activities. These data will be incorporated into a wide-ranging research to clarify the role of selected environmental factors in a very complex and still not fully explored the pathogenesis of multiple sclerosis in Upper Silesia.

Forest fires in Missouri.

Treesearch

Donald A. Haines; William A. Main; John S. Crosby

1973-01-01

Describes factors that contribute to forest fires on two of the State of Missouri's Protection Districts and the Clark National Forest. Includes an analysis of fire cause, annual distribution, weather, and activity by day of week; also discusses multiple-fire day.

Can we prevent or treat multiple sclerosis by individualised vitamin D supply?

PubMed Central

2013-01-01

Apart from its principal role in bone metabolism and calcium homeostasis, vitamin D has been attributed additional effects including an immunomodulatory, anti-inflammatory, and possibly even neuroprotective capacity which implicates a possible role of vitamin D in autoimmune diseases like multiple sclerosis (MS). Indeed, several lines of evidence including epidemiologic, preclinical, and clinical data suggest that reduced vitamin D levels and/or dysregulation of vitamin D homeostasis is a risk factor for the development of multiple sclerosis on the one hand, and that vitamin D serum levels are inversely associated with disease activity and progression on the other hand. However, these data are not undisputable, and many questions regarding the preventive and therapeutic capacity of vitamin D in multiple sclerosis remain to be answered. In particular, available clinical data derived from interventional trials using vitamin D supplementation as a therapeutic approach in MS are inconclusive and partly contradictory. In this review, we summarise and critically evaluate the existing data on the possible link between vitamin D and multiple sclerosis in light of the crucial question whether optimization of vitamin D status may impact the risk and/or the course of multiple sclerosis. PMID:23356351

Physical activity and cognitive function in adults with multiple sclerosis: an integrative review.

PubMed

Morrison, Janet D; Mayer, Lori

2017-09-01

To identify and synthesize the research evidence concerning (1) the relationship between physical activity and cognitive performance in persons with multiple sclerosis (MS) and (2) to review the reported effects of physical activity interventions on neurocognitive performance conducted in this population. Relevant peer-reviewed journal articles were identified by searching PubMed, PsychINFO, and SPORTDiscus through May 2016. Full-text articles meeting the inclusion criteria were evaluated for quality using tools developed by the National Institutes of Health. Studies deemed to be of poor quality were excluded from the review. Nineteen studies meeting the inclusion/exclusion criteria were analyzed. Nine studies reported significant relationships between higher levels of physical activity or cardiorespiratory fitness and measures of cognitive function. Data extracted from 10 physical activity intervention studies reported mixed results on the effectiveness of physical activity to improve selected domains of cognitive function in persons with MS. Although correlational studies provide evidence to support a linkage between physical activity and cognitive function in persons with MS, this linkage is confounded by factors that may have influenced the studies' results. Evidence derived from intervention studies that could support a positive effect of physical activity on cognition in persons with MS is equivocal. Implications for Rehabilitation Physical activity has numerous benefits for persons with multiple sclerosis (MS) including improvements in balance, ambulation, depression, fatigue, and quality of life. Structured physical activity programs may contribute to cognitive function stability or improvement in persons with MS.

Survival and multiplication of Vibrio cholerae in the upper bowel of infant mice.

PubMed

Baselski, V S; Medina, R A; Parker, C D

1978-11-01

The survival and multiplication of Vibrio cholerae strains of varying virulence in the upper bowel of orally challenged infant mice early in infection has been examined. Analysis of changes in the apparent specific activity (counts per minute per colony-forming unit) of the cell population after 4 h compared with the inoculum indicated that strain CA401 established a viable, multiplying cell population, whereas strains VB12 (a rough variant) and 569B were subject to host bactericidal and bacteriolytic mechanisms. An analysis of parameters which may affect the specific activity is included. We have defined the infective potential of the strains in terms of the changes in specific activity. The relative infective potentials are CA401 greater than 569B greater than VB12.

Survival and multiplication of Vibrio cholerae in the upper bowel of infant mice.

PubMed Central

Baselski, V S; Medina, R A; Parker, C D

1978-01-01

The survival and multiplication of Vibrio cholerae strains of varying virulence in the upper bowel of orally challenged infant mice early in infection has been examined. Analysis of changes in the apparent specific activity (counts per minute per colony-forming unit) of the cell population after 4 h compared with the inoculum indicated that strain CA401 established a viable, multiplying cell population, whereas strains VB12 (a rough variant) and 569B were subject to host bactericidal and bacteriolytic mechanisms. An analysis of parameters which may affect the specific activity is included. We have defined the infective potential of the strains in terms of the changes in specific activity. The relative infective potentials are CA401 greater than 569B greater than VB12. PMID:730364

Ultrasensitive surveillance of sensors and processes

DOEpatents

Wegerich, Stephan W.; Jarman, Kristin K.; Gross, Kenneth C.

2001-01-01

A method and apparatus for monitoring a source of data for determining an operating state of a working system. The method includes determining a sensor (or source of data) arrangement associated with monitoring the source of data for a system, activating a method for performing a sequential probability ratio test if the data source includes a single data (sensor) source, activating a second method for performing a regression sequential possibility ratio testing procedure if the arrangement includes a pair of sensors (data sources) with signals which are linearly or non-linearly related; activating a third method for performing a bounded angle ratio test procedure if the sensor arrangement includes multiple sensors and utilizing at least one of the first, second and third methods to accumulate sensor signals and determining the operating state of the system.

Ultrasensitive surveillance of sensors and processes

DOEpatents

Wegerich, Stephan W.; Jarman, Kristin K.; Gross, Kenneth C.

1999-01-01

A method and apparatus for monitoring a source of data for determining an operating state of a working system. The method includes determining a sensor (or source of data) arrangement associated with monitoring the source of data for a system, activating a method for performing a sequential probability ratio test if the data source includes a single data (sensor) source, activating a second method for performing a regression sequential possibility ratio testing procedure if the arrangement includes a pair of sensors (data sources) with signals which are linearly or non-linearly related; activating a third method for performing a bounded angle ratio test procedure if the sensor arrangement includes multiple sensors and utilizing at least one of the first, second and third methods to accumulate sensor signals and determining the operating state of the system.

Effects of Active Videogames on Physical Activity and Related Outcomes Among Healthy Children: A Systematic Review.

PubMed

Liang, Yan; Lau, Patrick W C

2014-06-01

This review systematically evaluated the effects of active videogames (AVGs) on physical activity (PA) and related outcomes in healthy children. Electronic databases were searched to retrieve articles published from January 2000 through August 2013. Included were original studies published in English, in peer-reviewed journals, that included at least one subgroup of healthy participants not older than 18 years, and that measured at least one PA-related cognitive, psychosocial, or behavioral outcome. All study designs were included, but only intervention studies with PA comparison between groups or across time were assessed for methodological quality. Evidence strength for intervention studies was stratified by settings (including the free-living home setting, the school, community, or primary care setting with structured AVG sessions [i.e., AVG play of participants was organized by teachers or researchers], and multiple settings). Fifty-four articles were identified, including 32 studies that examined the immediate PA effects (i.e., energy expenditure and PA levels during AVG play), one survey study, and 21 intervention studies aimed to promote PA. AVGs led to light- to moderate-intensity PA among studies of immediate PA outcomes. No effect was identified of AVGs on PA in the home setting. Moderate evidence was found that structured AVG play could improve PA. Inconclusive evidence was found for the effect of AVGs on PA in multiple settings. The present review does not support using AVGs alone in the home setting to promote PA. Structured AVG play has the potential to promote PA in children.

The evolution of the natural killer complex; a comparison between mammals using new high-quality genome assemblies and targeted annotation

USDA-ARS?s Scientific Manuscript database

Natural killer (NK) cells are a diverse population of lymphocytes with a range of biological roles including essential immune functions. NK cell diversity is created by the differential expression of cell surface receptors which modulate activation and function, including multiple subfamilies of C-t...

Novel chlorinated dibenzofurans isolated from the cellular slime mold, Polysphondylium filamentosum, and their biological activities.

PubMed

Kikuchi, Haruhisa; Kubohara, Yuzuru; Nguyen, Van Hai; Katou, Yasuhiro; Oshima, Yoshiteru

2013-08-01

Cellular slime molds are expected to have the huge potential for producing secondary metabolites including polyketides, and we have studied the diversity of secondary metabolites of cellular slime molds for their potential utilization as new biological resources for natural product chemistry. From the methanol extract of fruiting bodies of Polysphondylium filamentosum, we obtained new chlorinated benzofurans Pf-1 (4) and Pf-2 (5) which display multiple biological activities; these include stalk cell differentiation-inducing activity in the well-studied cellular slime mold, Dictyostelium discoideum, and inhibitory activities on cell proliferation in mammalian cells and gene expression in Drosophila melanogaster. Copyright © 2013 Elsevier Ltd. All rights reserved.

Middle-Range Theory: Coping and Adaptation with Active Aging.

PubMed

Salazar-Barajas, Martha Elba; Salazar-González, Bertha Cecilia; Gallegos-Cabriales, Esther Carlota

2017-10-01

Various disciplines focus on a multiplicity of aspects of aging: lifestyles, personal biological factors, psychological conditions, health conditions, physical environment, and social and economic factors. The aforementioned are all related to the determinants of active aging. The aim is to describe the development of a middle-range theory based on coping and adaptation with active aging. Concepts and relationships derived from Roy's model of adaptation are included. The proposed concepts are hope, health habits, coping with aging, social relations, and active aging.

A new cognitive rehabilitation programme for patients with multiple sclerosis: the 'MS-line! Project'.

PubMed

Gich, Jordi; Freixenet, Jordi; Garcia, Rafael; Vilanova, Joan Carles; Genís, David; Silva, Yolanda; Montalban, Xavier; Ramió-Torrentà, Lluís

2015-09-01

Cognitive rehabilitation is often delayed in multiple sclerosis (MS). To develop a free and specific cognitive rehabilitation programme for MS patients to be used from early stages that does not interfere with daily living activities. MS-line!, cognitive rehabilitation materials consisting of written, manipulative and computer-based materials with difficulty levels developed by a multidisciplinary team. Mathematical, problem-solving and word-based exercises were designed. Physical materials included spatial, coordination and reasoning games. Computer-based material included logic and reasoning, working memory and processing speed games. Cognitive rehabilitation exercises that are specific for MS patients have been successfully developed. © The Author(s), 2014.

Transfer Learning for Improved Audio-Based Human Activity Recognition.

PubMed

Ntalampiras, Stavros; Potamitis, Ilyas

2018-06-25

Human activities are accompanied by characteristic sound events, the processing of which might provide valuable information for automated human activity recognition. This paper presents a novel approach addressing the case where one or more human activities are associated with limited audio data, resulting in a potentially highly imbalanced dataset. Data augmentation is based on transfer learning; more specifically, the proposed method: (a) identifies the classes which are statistically close to the ones associated with limited data; (b) learns a multiple input, multiple output transformation; and (c) transforms the data of the closest classes so that it can be used for modeling the ones associated with limited data. Furthermore, the proposed framework includes a feature set extracted out of signal representations of diverse domains, i.e., temporal, spectral, and wavelet. Extensive experiments demonstrate the relevance of the proposed data augmentation approach under a variety of generative recognition schemes.

Programmed Cell Death During Caenorhabditis elegans Development

PubMed Central

Conradt, Barbara; Wu, Yi-Chun; Xue, Ding

2016-01-01

Programmed cell death is an integral component of Caenorhabditis elegans development. Genetic and reverse genetic studies in C. elegans have led to the identification of many genes and conserved cell death pathways that are important for the specification of which cells should live or die, the activation of the suicide program, and the dismantling and removal of dying cells. Molecular, cell biological, and biochemical studies have revealed the underlying mechanisms that control these three phases of programmed cell death. In particular, the interplay of transcriptional regulatory cascades and networks involving multiple transcriptional regulators is crucial in activating the expression of the key death-inducing gene egl-1 and, in some cases, the ced-3 gene in cells destined to die. A protein interaction cascade involving EGL-1, CED-9, CED-4, and CED-3 results in the activation of the key cell death protease CED-3, which is tightly controlled by multiple positive and negative regulators. The activation of the CED-3 caspase then initiates the cell disassembly process by cleaving and activating or inactivating crucial CED-3 substrates; leading to activation of multiple cell death execution events, including nuclear DNA fragmentation, mitochondrial elimination, phosphatidylserine externalization, inactivation of survival signals, and clearance of apoptotic cells. Further studies of programmed cell death in C. elegans will continue to advance our understanding of how programmed cell death is regulated, activated, and executed in general. PMID:27516615

Endovascular treatment of chronic cerebro spinal venous insufficiency in patients with multiple sclerosis modifies circulating markers of endothelial dysfunction and coagulation activation: a prospective study.

PubMed

Napolitano, Mariasanta; Bruno, Aldo; Mastrangelo, Diego; De Vizia, Marcella; Bernardo, Benedetto; Rosa, Buonagura; De Lucia, Domenico

2014-10-01

We performed a monocentric observational prospective study to evaluate coagulation activation and endothelial dysfunction parameters in patients with multiple sclerosis undergoing endovascular treatment for cerebro-spinal-venous insufficiency. Between February 2011 and July 2012, 144 endovascular procedures in 110 patients with multiple sclerosis and chronical cerebro-spinal venous insufficiency were performed and they were prospectively analyzed. Each patient was included in the study according to previously published criteria, assessed by the investigators before enrollment. Endothelial dysfunction and coagulation activation parameters were determined before the procedure and during follow-up at 1, 3, 6, 9, 12, 15 and 18 months after treatment, respectively. After the endovascular procedure, patients were treated with standard therapies, with the addition of mesoglycan. Fifty-five percent of patients experienced a favorable outcome of multiple sclerosis within 1 month after treatment, 25% regressed in the following 3 months, 24.9% did not experience any benefit. In only 0.1% patients, acute recurrence was observed and it was treated with high-dose immunosuppressive therapy. No major complications were observed. Coagulation activation and endothelial dysfunction parameters were shown to be reduced at 1 month and stable up to 12-month follow-up, and they were furthermore associated with a good clinical outcome. Endovascular procedures performed by a qualified staff are well tolerated; they can be associated with other currently adopted treatments. Correlations between inflammation, coagulation activation and neurodegenerative disorders are here supported by the observed variations in plasma levels of markers of coagulation activation and endothelial dysfunction.

On "Stepping Back and Letting Go": The Role of Control in the Success or Failure of Social Studies Simulations

ERIC Educational Resources Information Center

Wright-Maley, Cory

2015-01-01

This comparative case study presents one key challenge that 2 experienced teachers faced when using simulations: control. Simulations are activities that place high demands on teachers, including the ability to anticipate pitfalls in advance, act in multiple capacities, shape the direction of the activity without unduly interfering, and to be…

Phenotypic Variation for Diastatic power, ß-Amylase Activity, and ß-Amylase Thermostability vs. Allelic Variation at the Bmy1 Locus in a Sample of North American Barley Germplasm

USDA-ARS?s Scientific Manuscript database

Malting quality data including diastatic power, ß-amylase activity, and ß-amylase thermostability, were collected on malts from three barley (Hordeum vulgare L.) breeding program trials containing two growth habits and 165 lines grown in multiple environments. We attempted to identify causal polymor...

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

PubMed

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.

7 CFR 613.2 - Policy and objectives.

Code of Federal Regulations, 2014 CFR

2014-01-01

... requiring vegetative multiplication in ways appropriate for particular States and particular species by...; (10) Improving wildlife food and cover, including threatened and endangered and pollinator species... other energy-related activities; and (15) Evaluating plants and techniques to combat invasive plant...

7 CFR 613.2 - Policy and objectives.

Code of Federal Regulations, 2013 CFR

2013-01-01

... requiring vegetative multiplication in ways appropriate for particular States and particular species by...; (10) Improving wildlife food and cover, including threatened and endangered and pollinator species... other energy-related activities; and (15) Evaluating plants and techniques to combat invasive plant...

7 CFR 613.2 - Policy and objectives.

Code of Federal Regulations, 2012 CFR

2012-01-01

... requiring vegetative multiplication in ways appropriate for particular States and particular species by...; (10) Improving wildlife food and cover, including threatened and endangered and pollinator species... other energy-related activities; and (15) Evaluating plants and techniques to combat invasive plant...

Genetics Home Reference: familial pityriasis rubra pilaris

MedlinePlus

... interacting proteins known as nuclear factor-kappa-B (NF-κB). NF-κB regulates the activity of multiple genes, including ... but it is particularly abundant in the skin. NF-κB signaling appears to play an important role ...

Review of Measures of Worksite Environmental and Policy Supports for Physical Activity and Healthy Eating

PubMed Central

Reeds, Dominic N.; van Bakergem, Margaret A.; Marx, Christine M.; Brownson, Ross C.; Pamulapati, Surya C.; Hoehner, Christine M.

2015-01-01

Introduction Obesity prevention strategies are needed that target multiple settings, including the worksite. The objective of this study was to assess the state of science concerning available measures of worksite environmental and policy supports for physical activity (PA) and healthy eating (HE). Methods We searched multiple databases for instruments used to assess worksite environments and policies. Two commonly cited instruments developed by state public health departments were also included. Studies that were published from 1991 through 2013 in peer-reviewed publications and gray literature that discussed the development or use of these instruments were analyzed. Instrument administration mode and measurement properties were documented. Items were classified by general health topic, 5 domains of general worksite strategy, and 19 subdomains of worksite strategy specific to PA or HE. Characteristics of worksite measures were described including measurement properties, length, and administration mode, as well as frequencies of items by domain and subdomain. Results Seventeen instruments met inclusion criteria (9 employee surveys, 5 manager surveys, 1 observational assessment, and 2 studies that used multiple administration modes). Fourteen instruments included reliability testing. More items were related to PA than HE. Most instruments (n = 10) lacked items in the internal social environment domain. The most common PA subdomains were exercise facilities and lockers/showers; the most common HE subdomain was healthy options/vending. Conclusion This review highlights gaps in measurement of the worksite social environment. The findings provide a useful resource for researchers and practitioners and should inform future instrument development. PMID:25950572

Review of measures of worksite environmental and policy supports for physical activity and healthy eating.

PubMed

Hipp, J Aaron; Reeds, Dominic N; van Bakergem, Margaret A; Marx, Christine M; Brownson, Ross C; Pamulapati, Surya C; Hoehner, Christine M

2015-05-07

Obesity prevention strategies are needed that target multiple settings, including the worksite. The objective of this study was to assess the state of science concerning available measures of worksite environmental and policy supports for physical activity (PA) and healthy eating (HE). We searched multiple databases for instruments used to assess worksite environments and policies. Two commonly cited instruments developed by state public health departments were also included. Studies that were published from 1991 through 2013 in peer-reviewed publications and gray literature that discussed the development or use of these instruments were analyzed. Instrument administration mode and measurement properties were documented. Items were classified by general health topic, 5 domains of general worksite strategy, and 19 subdomains of worksite strategy specific to PA or HE. Characteristics of worksite measures were described including measurement properties, length, and administration mode, as well as frequencies of items by domain and subdomain. Seventeen instruments met inclusion criteria (9 employee surveys, 5 manager surveys, 1 observational assessment, and 2 studies that used multiple administration modes). Fourteen instruments included reliability testing. More items were related to PA than HE. Most instruments (n = 10) lacked items in the internal social environment domain. The most common PA subdomains were exercise facilities and lockers/showers; the most common HE subdomain was healthy options/vending. This review highlights gaps in measurement of the worksite social environment. The findings provide a useful resource for researchers and practitioners and should inform future instrument development.

Multiple role adaptation among women who have children and re-enter nursing school in Taiwan.

PubMed

Lin, Li-Ling

2005-03-01

This study assessed multiple role adaptation within maternal and student roles among female RNs who had children and returned to school for baccalaureate degrees in Taiwan. Using Roy's Adaptation Model as the theoretical framework, relationships were explored among demographic (number of children, age of youngest child, employment status), physical (sleep quality, health perception, activity), and psychosocial factors (self-identity, role expectation, role involvement, social support) and multiple role adaptation (role accumulation). The sample included 118 mother-students who had at least one child younger than age 18 and who were studying in nursing programs in Taiwan. The highest correlation was found between activity and role accumulation followed by significant correlations between sleep quality, health perception, maternal role expectation, and age of youngest child and role accumulation. In regression analyses, the complete model explained 46% of the variance in role accumulation. Implications for education and future research are identified.

Exploring metabolic dysfunction in chronic kidney disease

PubMed Central

2012-01-01

Impaired kidney function and chronic kidney disease (CKD) leading to kidney failure and end-stage renal disease (ESRD) is a serious medical condition associated with increased morbidity, mortality, and in particular cardiovascular disease (CVD) risk. CKD is associated with multiple physiological and metabolic disturbances, including hypertension, dyslipidemia and the anorexia-cachexia syndrome which are linked to poor outcomes. Specific hormonal, inflammatory, and nutritional-metabolic factors may play key roles in CKD development and pathogenesis. These include raised proinflammatory cytokines, such as interleukin-1 and −6, tumor necrosis factor, altered hepatic acute phase proteins, including reduced albumin, increased C-reactive protein, and perturbations in normal anabolic hormone responses with reduced growth hormone-insulin-like growth factor-1 axis activity. Others include hyperactivation of the renin-angiotensin aldosterone system (RAAS), with angiotensin II and aldosterone implicated in hypertension and the promotion of insulin resistance, and subsequent pharmacological blockade shown to improve blood pressure, metabolic control and offer reno-protective effects. Abnormal adipocytokine levels including leptin and adiponectin may further promote the insulin resistant, and proinflammatory state in CKD. Ghrelin may be also implicated and controversial studies suggest activities may be reduced in human CKD, and may provide a rationale for administration of acyl-ghrelin. Poor vitamin D status has also been associated with patient outcome and CVD risk and may indicate a role for supplementation. Glucocorticoid activities traditionally known for their involvement in the pathogenesis of a number of disease states are increased and may be implicated in CKD-associated hypertension, insulin resistance, diabetes risk and cachexia, both directly and indirectly through effects on other systems including activation of the mineralcorticoid receptor. Insight into the multiple factors altered in CKD may provide useful information on disease pathogenesis, clinical assessment and treatment rationale such as potential pharmacological, nutritional and exercise therapies. PMID:22537670

Multiple oil pay revives interest

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stremel, K.

1984-03-01

Good, relatively shallow multiple pay oil potential is reviving interest in the flanks of the prolific Big Horn Basin. Operators say that although the areal extent of the basin's fields may not be that large, potential pay zones can exceed 250 feet. Several companies have stepped up geophysical work and activity. A discussion of trapping systems, test wells and stratigraphy studies are included from various petroleum companies. The interest was sparked by lower acreage costs and poor economic conditions elsewhere.

A Systematic Review and Meta-Analysis of Strength Training in Individuals With Multiple Sclerosis Or Parkinson Disease

PubMed Central

Cruickshank, Travis M.; Reyes, Alvaro R.; Ziman, Melanie R.

2015-01-01

Abstract Strength training has, in recent years, been shown to be beneficial for people with Parkinson disease and multiple sclerosis. Consensus regarding its utility for these disorders nevertheless remains contentious among healthcare professionals. Greater clarity is required, especially in regards to the type and magnitude of effects as well as the response differences to strength training between individuals with Parkinson disease or multiple sclerosis. This study examines the effects, magnitude of those effects, and response differences to strength training between patients with Parkinson disease or multiple sclerosis. A comprehensive search of electronic databases including Physiotherapy Evidence Database scale, PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and CINAHL was conducted from inception to July 2014. English articles investigating the effect of strength training for individuals with neurodegenerative disorders were selected. Strength training trials that met the inclusion criteria were found for individuals with Parkinson disease or multiple sclerosis. Individuals with Parkinson disease or multiple sclerosis were included in the study. Strength training interventions included traditional (free weights/machine exercises) and nontraditional programs (eccentric cycling). Included articles were critically appraised using the Physiotherapy Evidence Database scale. Of the 507 articles retrieved, only 20 articles met the inclusion criteria. Of these, 14 were randomized and 6 were nonrandomized controlled articles in Parkinson disease or multiple sclerosis. Six randomized and 2 nonrandomized controlled articles originated from 3 trials and were subsequently pooled for systematic analysis. Strength training was found to significantly improve muscle strength in people with Parkinson disease (15%–83.2%) and multiple sclerosis (4.5%–36%). Significant improvements in mobility (11.4%) and disease progression were also reported in people with Parkinson disease after strength training. Furthermore, significant improvements in fatigue (8.2%), functional capacity (21.5%), quality of life (8.3%), power (17.6%), and electromyography activity (24.4%) were found in individuals with multiple sclerosis after strength training. The limitations of the study were the heterogeneity of interventions and study outcomes in Parkinson disease and multiple sclerosis trials. Strength training is useful for increasing muscle strength in Parkinson disease and to a lesser extent multiple sclerosis. PMID:25634170

A systematic review and meta-analysis of strength training in individuals with multiple sclerosis or Parkinson disease.

PubMed

Cruickshank, Travis M; Reyes, Alvaro R; Ziman, Melanie R

2015-01-01

Strength training has, in recent years, been shown to be beneficial for people with Parkinson disease and multiple sclerosis. Consensus regarding its utility for these disorders nevertheless remains contentious among healthcare professionals. Greater clarity is required, especially in regards to the type and magnitude of effects as well as the response differences to strength training between individuals with Parkinson disease or multiple sclerosis. This study examines the effects, magnitude of those effects, and response differences to strength training between patients with Parkinson disease or multiple sclerosis. A comprehensive search of electronic databases including Physiotherapy Evidence Database scale, PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and CINAHL was conducted from inception to July 2014. English articles investigating the effect of strength training for individuals with neurodegenerative disorders were selected. Strength training trials that met the inclusion criteria were found for individuals with Parkinson disease or multiple sclerosis. Individuals with Parkinson disease or multiple sclerosis were included in the study. Strength training interventions included traditional (free weights/machine exercises) and nontraditional programs (eccentric cycling). Included articles were critically appraised using the Physiotherapy Evidence Database scale. Of the 507 articles retrieved, only 20 articles met the inclusion criteria. Of these, 14 were randomized and 6 were nonrandomized controlled articles in Parkinson disease or multiple sclerosis. Six randomized and 2 nonrandomized controlled articles originated from 3 trials and were subsequently pooled for systematic analysis. Strength training was found to significantly improve muscle strength in people with Parkinson disease (15%-83.2%) and multiple sclerosis (4.5%-36%). Significant improvements in mobility (11.4%) and disease progression were also reported in people with Parkinson disease after strength training. Furthermore, significant improvements in fatigue (8.2%), functional capacity (21.5%), quality of life (8.3%), power (17.6%), and electromyography activity (24.4%) were found in individuals with multiple sclerosis after strength training. The limitations of the study were the heterogeneity of interventions and study outcomes in Parkinson disease and multiple sclerosis trials. Strength training is useful for increasing muscle strength in Parkinson disease and to a lesser extent multiple sclerosis.

A delicate balance: role of MMP-9 in brain development and pathophysiology of neurodevelopmental disorders.

PubMed

Reinhard, Sarah M; Razak, Khaleel; Ethell, Iryna M

2015-01-01

The extracellular matrix (ECM) is a critical regulator of neural network development and plasticity. As neuronal circuits develop, the ECM stabilizes synaptic contacts, while its cleavage has both permissive and active roles in the regulation of plasticity. Matrix metalloproteinase 9 (MMP-9) is a member of a large family of zinc-dependent endopeptidases that can cleave ECM and several cell surface receptors allowing for synaptic and circuit level reorganization. It is becoming increasingly clear that the regulated activity of MMP-9 is critical for central nervous system (CNS) development. In particular, MMP-9 has a role in the development of sensory circuits during early postnatal periods, called 'critical periods.' MMP-9 can regulate sensory-mediated, local circuit reorganization through its ability to control synaptogenesis, axonal pathfinding and myelination. Although activity-dependent activation of MMP-9 at specific synapses plays an important role in multiple plasticity mechanisms throughout the CNS, misregulated activation of the enzyme is implicated in a number of neurodegenerative disorders, including traumatic brain injury, multiple sclerosis, and Alzheimer's disease. Growing evidence also suggests a role for MMP-9 in the pathophysiology of neurodevelopmental disorders including Fragile X Syndrome. This review outlines the various actions of MMP-9 during postnatal brain development, critical for future studies exploring novel therapeutic strategies for neurodevelopmental disorders.

Effect of lipoic acid consumption on oxidative stress among multiple sclerosis patients: a randomized controlled clinical trial.

PubMed

Khalili, Mohammad; Eghtesadi, Shahryar; Mirshafiey, Abbas; Eskandari, Ghazaleh; Sanoobar, Meisam; Sahraian, Mohamad Ali; Motevalian, Abbas; Norouzi, Abbas; Moftakhar, Shirin; Azimi, Amirreza

2014-01-01

Multiple sclerosis is a neurodegenerative and demyelinating disease of central nervous system. High levels of oxidative stress are associated with inflammation and play an important role in pathogenesis of multiple sclerosis. This double-blind, randomized controlled clinical study was carried out to determine the effect of daily consumption of lipoic acid on oxidative stress among multiple sclerosis patients. A total of 52 relapsing-remitting multiple sclerosis patients, aged 18-50 years with Expanded Disability Status Scale ≤5.5 were assigned to consume either lipoic acid (1200 mg/day) or placebo capsules for 12 weeks. Fasting blood samples were collected before the first dose taken and 12 hours after the last. Dietary intakes were obtained by using 3-day dietary records. Consumption of lipoic acid resulted in a significant improvement of total antioxidant capacity (TAC) in comparison to the placebo group (P = 0.004). Although a significant change of TAC (-1511 mmol/L, P = 0.001) was found within lipoic acid group, other markers of oxidative stress including superoxide dismutase activity, glutathione peroxidase activity, and malondialdehyde levels were not affected by lipoic acid consumption. These results suggest that 1200 mg of lipoic acid improves serum TAC among multiple sclerosis patients but does not affect other markers of oxidative stress.

Dual control of pcdh8l/PCNS expression and function in Xenopus laevis neural crest cells by adam13/33 via the transcription factors tfap2α and arid3a.

PubMed

Khedgikar, Vikram; Abbruzzese, Genevieve; Mathavan, Ketan; Szydlo, Hannah; Cousin, Helene; Alfandari, Dominique

2017-08-22

Adam13/33 is a cell surface metalloprotease critical for cranial neural crest (CNC) cell migration. It can cleave multiple substrates including itself, fibronectin, ephrinB, cadherin-11, pcdh8 and pcdh8l (this work). Cleavage of cadherin-11 produces an extracellular fragment that promotes CNC migration. In addition, the adam13 cytoplasmic domain is cleaved by gamma secretase, translocates into the nucleus and regulates multiple genes. Here, we show that adam13 interacts with the arid3a/dril1/Bright transcription factor. This interaction promotes a proteolytic cleavage of arid3a and its translocation to the nucleus where it regulates another transcription factor: tfap2α. Tfap2α in turn activates multiple genes including the protocadherin pcdh8l (PCNS). The proteolytic activity of adam13 is critical for the release of arid3a from the plasma membrane while the cytoplasmic domain appears critical for the cleavage of arid3a. In addition to this transcriptional control of pcdh8l, adam13 cleaves pcdh8l generating an extracellular fragment that also regulates cell migration.

Dual control of pcdh8l/PCNS expression and function in Xenopus laevis neural crest cells by adam13/33 via the transcription factors tfap2α and arid3a

PubMed Central

Khedgikar, Vikram; Abbruzzese, Genevieve; Mathavan, Ketan; Szydlo, Hannah; Cousin, Helene

2017-01-01

Adam13/33 is a cell surface metalloprotease critical for cranial neural crest (CNC) cell migration. It can cleave multiple substrates including itself, fibronectin, ephrinB, cadherin-11, pcdh8 and pcdh8l (this work). Cleavage of cadherin-11 produces an extracellular fragment that promotes CNC migration. In addition, the adam13 cytoplasmic domain is cleaved by gamma secretase, translocates into the nucleus and regulates multiple genes. Here, we show that adam13 interacts with the arid3a/dril1/Bright transcription factor. This interaction promotes a proteolytic cleavage of arid3a and its translocation to the nucleus where it regulates another transcription factor: tfap2α. Tfap2α in turn activates multiple genes including the protocadherin pcdh8l (PCNS). The proteolytic activity of adam13 is critical for the release of arid3a from the plasma membrane while the cytoplasmic domain appears critical for the cleavage of arid3a. In addition to this transcriptional control of pcdh8l, adam13 cleaves pcdh8l generating an extracellular fragment that also regulates cell migration. PMID:28829038

Localized epigenetic silencing of a damage-activated WNT enhancer limits regeneration in mature Drosophila imaginal discs

PubMed Central

Harris, Robin E; Setiawan, Linda; Saul, Josh; Hariharan, Iswar K

2016-01-01

Many organisms lose the capacity to regenerate damaged tissues as they mature. Damaged Drosophila imaginal discs regenerate efficiently early in the third larval instar (L3) but progressively lose this ability. This correlates with reduced damage-responsive expression of multiple genes, including the WNT genes wingless (wg) and Wnt6. We demonstrate that damage-responsive expression of both genes requires a bipartite enhancer whose activity declines during L3. Within this enhancer, a damage-responsive module stays active throughout L3, while an adjacent silencing element nucleates increasing levels of epigenetic silencing restricted to this enhancer. Cas9-mediated deletion of the silencing element alleviates WNT repression, but is, in itself, insufficient to promote regeneration. However, directing Myc expression to the blastema overcomes repression of multiple genes, including wg, and restores cellular responses necessary for regeneration. Localized epigenetic silencing of damage-responsive enhancers can therefore restrict regenerative capacity in maturing organisms without compromising gene functions regulated by developmental signals. DOI: http://dx.doi.org/10.7554/eLife.11588.001 PMID:26840050

Driving competences and neuropsychological factors associated to driving counseling in multiple sclerosis.

PubMed

Badenes, Dolors; Garolera, Maite; Casas, Laura; Cejudo-Bolivar, Juan Carlos; de Francisco, Jorge; Zaragoza, Silvia; Calzado, Noemi; Aguilar, Miquel

2014-05-01

Multiple Sclerosis (MS) significantly impacts daily living activities, including car driving. To investigate driving difficulties experienced with MS, we compared 50 MS patients with minor or moderate disability and 50 healthy controls (HC) using computerized driving tests (the ASDE driver test and the Useful Field of View (UFOV) test) and neuropsychological tests. Inclusion criteria included being active drivers. We evaluated whether cognitive deterioration in MS is associated with the results of driving tests by comparing MS patients without cognitive deterioration with HC. The results indicated that the MS patients performed worse than the HCs in attention, information processing, working memory and visuomotor coordination tasks. Furthermore, MS patients with cognitive impairments experienced more difficulties in the driving tests than did the non-impaired MS patients. Motor dysfunction associated with MS also played an important role in this activity. The results of this study suggest that MS should be assessed carefully and that special emphasis should be placed on visuomotor coordination and executive functions because patients with minor motor disability and subtle cognitive impairments can pass measures predictive of driving safety.

Dual mechanisms regulating glutamate decarboxylases and accumulation of gamma-aminobutyric acid in tea (Camellia sinensis) leaves exposed to multiple stresses

PubMed Central

Mei, Xin; Chen, Yiyong; Zhang, Lingyun; Fu, Xiumin; Wei, Qing; Grierson, Don; Zhou, Ying; Huang, Yahui; Dong, Fang; Yang, Ziyin

2016-01-01

γ-Aminobutyric acid (GABA) is one of the major inhibitory neurotransmitters in the central nervous system. It has multiple positive effects on mammalian physiology and is an important bioactive component of tea (Camellia sinensis). GABA generally occurs at a very low level in plants but GABA content increases substantially after exposure to a range of stresses, especially oxygen-deficiency. During processing of tea leaves, a combination of anoxic stress and mechanical damage are essential for the high accumulation of GABA. This is believed to be initiated by a change in glutamate decarboxylase activity, but the underlying mechanisms are unclear. In the present study we characterized factors regulating the expression and activity of three tea glutamate decarboxylase genes (CsGAD1, 2, and 3), and their encoded enzymes. The results suggests that, unlike the model plant Arabidopsis thaliana, there are dual mechanisms regulating the accumulation of GABA in tea leaves exposed to multiple stresses, including activation of CsGAD1 enzymatic activity by calmodulin upon the onset of the stress and accumulation of high levels of CsGAD2 mRNA induced by a combination of anoxic stress and mechanical damage. PMID:27021285

Dual mechanisms regulating glutamate decarboxylases and accumulation of gamma-aminobutyric acid in tea (Camellia sinensis) leaves exposed to multiple stresses.

PubMed

Mei, Xin; Chen, Yiyong; Zhang, Lingyun; Fu, Xiumin; Wei, Qing; Grierson, Don; Zhou, Ying; Huang, Yahui; Dong, Fang; Yang, Ziyin

2016-03-29

γ-Aminobutyric acid (GABA) is one of the major inhibitory neurotransmitters in the central nervous system. It has multiple positive effects on mammalian physiology and is an important bioactive component of tea (Camellia sinensis). GABA generally occurs at a very low level in plants but GABA content increases substantially after exposure to a range of stresses, especially oxygen-deficiency. During processing of tea leaves, a combination of anoxic stress and mechanical damage are essential for the high accumulation of GABA. This is believed to be initiated by a change in glutamate decarboxylase activity, but the underlying mechanisms are unclear. In the present study we characterized factors regulating the expression and activity of three tea glutamate decarboxylase genes (CsGAD1, 2, and 3), and their encoded enzymes. The results suggests that, unlike the model plant Arabidopsis thaliana, there are dual mechanisms regulating the accumulation of GABA in tea leaves exposed to multiple stresses, including activation of CsGAD1 enzymatic activity by calmodulin upon the onset of the stress and accumulation of high levels of CsGAD2 mRNA induced by a combination of anoxic stress and mechanical damage.

Loading, Release, Biodegradation, and Biocompatibility of a Nanovector Delivery System

NASA Technical Reports Server (NTRS)

Ferrai, Mauro; Tasciotti, Ennio

2012-01-01

A nanovector multistage system has been created to overcome or bypass sequential barriers within the human body, in order to deliver a therapeutic or imaging agent to a specific location. This innovation consists of a composition that includes two or more stages of particles, such that smaller, later-stage particles are contained in the larger, early-stage particles. An active agent, such as a therapeutic agent or imaging agent, is preferentially delivered and/or localized to a particular target site in the body of a subject. The multistage composition overcomes multiple biological barriers in the body. The multistage composition also allows for simultaneous delivery and localization at the same or different target sites of multiple active agents.

The study of chemical composition and pharmacological action of the alkaloid from plants of Lycoris Herb

NASA Astrophysics Data System (ADS)

Ji, Y. B.; Wei, C.; Xin, G. S.

2017-12-01

Recently, studies on Lycoris type alkaloids received the attention of scholars home and abroad. Lycoris type contains lots of alkaloids, it can be divided into seven types according to its molecular structure, including Lycorine, Crinine, Galanthamine, Tazettine, Narciclasine, Lycorenine, Homolycorine and Montanine. Researches have shown that Lycoris type possess multiple phamocology activity, such as strong anti-tumor activity of human breast cancer cell (MCF-7), human leukemia cell(HL-60); and strong inhibition effect of flu virus, measles virus, polio virus and SARS virus; Besides, Lycorine type has strong anti-Acetylcholinesterase effect. In a word, Lycorine type, Lycoris type alkaloids carries multiple pharmacology effect and is a promising substance.

Radiative transfer in multilayered random medium with laminar structure - Green's function approach

NASA Technical Reports Server (NTRS)

Karam, M. A.; Fung, A. K.

1986-01-01

For a multilayered random medium with a laminar structure a Green's function approach is introduced to obtain the emitted intensity due to an arbitrary point source. It is then shown that the approach is applicable to both active and passive remote sensing. In active remote sensing, the computed radar backscattering cross section for the multilayered medium includes the effects of both volume multiple scattering and surface multiple scattering at the layer boundaries. In passive remote sensing, the brightness temperature is obtained for arbitrary temperature profiles in the layers. As an illustration the brightness temperature and reflectivity are calculated for a bounded layer and compared with results in the literature.

A pictorial view of the physical activity socialization of young adolescents outside of school.

PubMed

Beets, Michael W; Banda, Jorge A; Erwin, Heather E; Beighle, Aaron

2011-12-01

Childhood obesity prevention has fallen short of anticipated impact. Therefore, intervention programs need to be redirected to other potential settings to increase youth physical activity. This qualitative study, using autodriven interview techniques, was conducted to identify out-of-school settings that youth perceive as important for physical activity. Sixty-six children took photographs involving their physical activity involvement. A subsample completed follow-up focus groups. Salient themes included types of physical activities related to free play, fitness, organized sports, and chores. Most photographs included multiple children of similar age and were taken outdoors. Data suggest children associate chores with physical activity and engage in fitness-related activities. In addition, friends and family, the outdoors, and importantly, the home emerged as natural intervention components that may prove useful towards decreasing the physical inactivity and obesity of youth.

Stress peptide PACAP engages multiple signaling pathways within the carotid body to initiate excitatory responses in respiratory and sympathetic chemosensory afferents.

PubMed

Roy, Arijit; Derakhshan, Fatemeh; Wilson, Richard J A

2013-06-15

Consistent with a critical role in respiratory and autonomic stress responses, the carotid bodies are strongly excited by pituitary adenylate cyclase-activating polypeptide (PACAP), a neuropeptide implicated in stress responses throughout the sympathetic nervous system. PACAP excites isolated carotid body glomus cells via activation of PAC1 receptors, with one study suggesting PAC1-induced excitation is due entirely to protein kinase A (PKA)-mediated inhibition of TASK channels. However, in other systems, PAC1 is known to be coupled to multiple intracellular signaling pathways, including PKA, phospholipase C (PLC), phospholipase D (PLD), and protein kinase C (PKC), that trigger multiple downstream effectors including increased Ca²⁺ mobilization, inhibition of various K⁺ channels, and activation of nonselective cation channels. This study tests if non-PKA/TASK channel signaling helps mediate the stimulatory effects of PACAP on the carotid body. Using an ex vivo arterially perfused rat carotid body preparation, we show that PACAP-38 stimulates carotid sinus nerve activity in a biphasic manner (peak response, falling to plateau). PKA blocker H-89 only reduced the plateau response (~41%), whereas the TASK-1-like K⁺ channel blocker/transient receptor potential vanilloid 1 channel agonist anandamide only inhibited the peak response (~48%), suggesting involvement of additional pathways. The PLD blocker CAY10594 significantly inhibited both peak and plateau responses. The PLC blocker U73122 decimated both peak and plateau responses. Brefeldin A, a blocker of Epac (cAMP-activated guanine exchange factor, reported to link Gs-coupled receptors with PLC/PLD), also reduced both phases of the response, as did blocking signaling downstream of PLC/PLD with the PKC inhibitors chelerythrine chloride and GF109203X. Suggesting the involvement of non-TASK ion channels in the effects of PACAP, the A-type K⁺ channel blocker 4-aminopyridine, and the putative transient receptor potential channel (TRPC)/T-type calcium channel blocker SKF96365 each significantly inhibited the peak and steady-state responses. These data suggest the stimulatory effect of PACAP-38 on carotid body sensory activity is mediated through multiple signaling pathways: the PLC-PKC pathways predominates, with TRPC and/or T-type channel activation and Kv channel inactivation; only partial involvement is attributable to PKA and PLD activation.

Strategies that facilitate participation in family activities of children and adolescents with profound intellectual and multiple disabilities: parents' and personal assistants' experiences.

PubMed

Axelsson, Anna Karin; Imms, Christine; Wilder, Jenny

2014-01-01

Participation throughout one's life plays a significant role for development and emotional well-being. For this reason, there is a need to identify ways to facilitate participation in family activities for children and adolescents with profound intellectual and multiple disabilities (PIMD). The study design was qualitative and explorative, based on semi structured interviews with 11 parents and 9 personal assistants of children with PIMD. The interviews revealed participation-facilitating strategies relating to the children's/adolescent's proximal environment, such as "Availability and acceptability of the activity", "Good knowledge about the child" and a "A positive attitude of people close to the child", as well as strategies related to the children/adolescents themselves: "Sense of belonging", "Possible for the child/adolescent to understand", "Opportunities to influence" and "Feeling of being needed". Children and adolescents with PIMD are dependent on support obtained through their environment. The identified strategies, individually adapted through awareness and knowledge by the parents and the personal assistants, provide important evidence to assist our understanding in gaining understanding about how to improve participation in family activities of children and adolescents with PIMD. Participation-facilitating strategies related to the child/adolescent and his or her proximal environments are identified to improve participation in children and adolescents with profound intellectual and multiple disabilities (PIMD). Examples of strategies for the child's/adolescents' proximal environment include "good knowledge about the child/adolescent", and, for the child/adolescent, include creating "sense of belonging" and "opportunities to influence". Identifying and making these strategies explicit may assist in enhancing the participation of children and adolescents with PIMD in family activities. People in the child's/adolescent's proximal environment need to set the scene for participation.

Integrating Multiple Space Ground Sensors to Track Volcanic Activity

NASA Technical Reports Server (NTRS)

Chien, Steve; Davies, Ashley; Doubleday, Joshua; Tran, Daniel; Jones, Samuel; Kjartansson, Einar; Thorsteinsson, Hrobjartur; Vogfjord, Kristin; Guomundsson, Magnus; Thordarson, Thor;

Human placenta-derived cells (PDA-001) for the treatment of adults with multiple sclerosis: a randomized, placebo-controlled, multiple-dose study.

PubMed

Lublin, Fred D; Bowen, James D; Huddlestone, John; Kremenchutzky, Marcelo; Carpenter, Adam; Corboy, John R; Freedman, Mark S; Krupp, Lauren; Paulo, Corri; Hariri, Robert J; Fischkoff, Steven A

2014-11-01

Infusion of PDA-001, a preparation of mesenchymal-like cells derived from full-term human placenta, is a new approach in the treatment of patients with multiple sclerosis. This safety study aimed to rule out the possibility of paradoxical exacerbation of disease activity by PDA-001 in patients with multiple sclerosis. This was a phase 1b, multicenter, randomized, double-blind, placebo-controlled, 2-dose ranging study including patients with relapsing-remitting multiple sclerosis or secondary progressive multiple sclerosis. The study was conducted at 6 sites in the United States and 2 sites in Canada. Patients were randomized 3:1 to receive 2 low-dose infusions of PDA-001 (150×10(6) cells) or placebo, given 1 week apart. After completing this cohort, subsequent patients received high-dose PDA-001 (600×10(6) cells) or placebo. Monthly brain magnetic resonance imaging scans were performed. The primary end point was ruling out the possibility of paradoxical worsening of MS disease activity. This was monitored using Cutter׳s rule (≥5 new gadolinium lesions on 2 consecutive scans) by brain magnetic resonance imaging on a monthly basis for six months and also the frequency of multiple sclerosis relapse. Ten patients with relapsing-remitting multiple sclerosis and 6 with secondary progressive multiple sclerosis were randomly assigned to treatment: 6 to low-dose PDA-001, 6 to high-dose PDA-001, and 4 to placebo. No patient met Cutter׳s rule. One patient receiving high-dose PDA-001 had an increase in T2 and gadolinium lesions and in Expanded Disability Status Scale score during a multiple sclerosis flare 5 months after receiving PDA-001. No other patient had an increase in Expanded Disability Status Scale score>0.5, and most had stable or decreasing Expanded Disability Status Scale scores. With high-dose PDA-001, 1 patient experienced a grade 1 anaphylactoid reaction and 1 had grade 2 superficial thrombophlebitis. Other adverse events were mild to moderate and included headache, fatigue, infusion site reactions, and urinary tract infection. PDA-001 infusions were safe and well tolerated in relapsing-remitting multiple sclerosis and secondary progressive multiple sclerosis patients. No paradoxical worsening of lesion counts was noted with either dose. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Measurements of gluconeogenesis and glycogenolysis: A methodological review

USDA-ARS?s Scientific Manuscript database

Gluconeogenesis is a complex metabolic process that involves multiple enzymatic steps regulated by myriad factors, including substrate concentrations, the redox state, activation and inhibition of specific enzyme steps, and hormonal modulation. At present, the most widely accepted technique to deter...

Postage Stamps as Pedagogical Instruments in the Italian Curriculum.

ERIC Educational Resources Information Center

Nuessel, Frank; Cicogna, Caterina

1992-01-01

Examination of several interrelated topics on postage stamps, including their multiple functions and significance as semiotic artifacts, precedes suggestions for incorporating them into the Italian language curriculum in such activities as reading, writing, speaking, listening, and cultural understanding. (CB)

Roundhouse Diagrams.

ERIC Educational Resources Information Center

Ward, Robin E.; Wandersee, James

2000-01-01

Students must understand key concepts through reasoning, searching out related concepts, and making connections within multiple systems to learn science. The Roundhouse diagram was developed to be a concise, holistic, graphic representation of a science topic, process, or activity. Includes sample Roundhouse diagrams, a diagram checklist, and…

Increasing Physical Activity and Participation in People With Multiple Sclerosis: A Review.

PubMed

Backus, Deborah

2016-09-01

Multiple sclerosis (MS) is a chronic progressive disease of the central nervous system (CNS) affecting >2.5 million people worldwide. Damage to neurons in the CNS causes various sensorimotor and cognitive symptoms, such as fatigue, pain, spasticity, memory deficits, and impairment of mobility. Until the late 1990s, it was believed that symptoms of MS would be worsened with physical exertion and people with MS were encouraged to limit physical activity and exertion. Not only has emerging evidence suggested that physical activity, including exercise, is safe for people with MS, there is also evidence that at least some of the disability that occurs after MS is due to secondary deconditioning from the sedentary lifestyle adopted because of the symptoms of MS, not just CNS damage alone. Therefore, not only is physical activity safe, it is also required for maintaining function and health in people with MS. The purpose of this article is to review the unique physical and social barriers to physical activity in people with MS, including those with moderate to severe disability who use a wheelchair or scooter for mobility. We will discuss how existing guidelines for physical activity may not meet the needs of people with MS and present evidence-based considerations for promoting physical activity in people with MS. Ultimately, the goal is to overcome the barriers to physical activity and improve health, participation, and quality of life in people with MS. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Integrated exhaust and electrically heated particulate filter regeneration systems

DOEpatents

Gonze, Eugene V.; Paratore, Jr., Michael J.

2013-01-08

A system includes a particulate matter (PM) filter that includes multiple zones. An electrical heater includes heater segments that are associated with respective ones of the zones. The electrical heater is arranged upstream from and proximate with the PM filter. A post-fuel injection system injects fuel into at least one of a cylinder of an engine and an exhaust system. A control module is configured to operate in a first mode that includes activating the electrical heater to heat exhaust of the engine. The control module is also configured to operate in a second mode that includes activating the post-injection system to heat the exhaust. The control module selectively operates in at least one of the first mode and the second mode.

Improving fatigue and depression in individuals with multiple sclerosis using telephone-administered physical activity counseling.

PubMed

Turner, Aaron P; Hartoonian, Narineh; Sloan, Alicia P; Benich, Marisa; Kivlahan, Daniel R; Hughes, Christina; Hughes, Abbey J; Haselkorn, Jodie K

2016-04-01

To evaluate the impact of a physical activity intervention consisting of telephone counseling with home-based monitoring to improve fatigue and depression in individuals with multiple sclerosis (MS). Single-blind randomized controlled trial. Sixty-four individuals with MS received either telephone counseling (N = 31), or self-directed physical activity education (N = 33). The education condition (EC) consisted of advice to increase physical activity and a DVD with examples of in-home exercises for multiple physical ability levels. The telephone counseling condition (TC) included EC as well as mailed graphic feedback, 6 telephone counseling sessions using principles of motivational interviewing, and telehealth home monitoring to track progress on physical activity goals. Booster sessions were provided when participants indicated they did not meet their goals. Assessment was conducted at baseline, 3-month, and 6-month follow-up. TC participants reported significantly reduced fatigue (d = -.70), reduced depression (d = -.72) and increased physical activity (d = .92) relative to EC participants. Of individuals receiving TC, 33.3% experienced clinically significant improvement in fatigue (vs. 18.2% in EC) and 53.3% experienced clinically significant improvement in depression (vs. 9.1% in EC). Improvements in physical activity mediated improvements in fatigue with a similar trend for depression. TC was highly feasible (participants completed 99.5% of schedule telephone sessions) and well tolerated (100% rated it highly successful). Telephone-based counseling with home monitoring is a promising modality to improve physical activity and treat fatigue and depression. (c) 2016 APA, all rights reserved).

Myosin II Activity Softens Cells in Suspension.

PubMed

Chan, Chii J; Ekpenyong, Andrew E; Golfier, Stefan; Li, Wenhong; Chalut, Kevin J; Otto, Oliver; Elgeti, Jens; Guck, Jochen; Lautenschläger, Franziska

2015-04-21

The cellular cytoskeleton is crucial for many cellular functions such as cell motility and wound healing, as well as other processes that require shape change or force generation. Actin is one cytoskeleton component that regulates cell mechanics. Important properties driving this regulation include the amount of actin, its level of cross-linking, and its coordination with the activity of specific molecular motors like myosin. While studies investigating the contribution of myosin activity to cell mechanics have been performed on cells attached to a substrate, we investigated mechanical properties of cells in suspension. To do this, we used multiple probes for cell mechanics including a microfluidic optical stretcher, a microfluidic microcirculation mimetic, and real-time deformability cytometry. We found that nonadherent blood cells, cells arrested in mitosis, and naturally adherent cells brought into suspension, stiffen and become more solidlike upon myosin inhibition across multiple timescales (milliseconds to minutes). Our results hold across several pharmacological and genetic perturbations targeting myosin. Our findings suggest that myosin II activity contributes to increased whole-cell compliance and fluidity. This finding is contrary to what has been reported for cells attached to a substrate, which stiffen via active myosin driven prestress. Our results establish the importance of myosin II as an active component in modulating suspended cell mechanics, with a functional role distinctly different from that for substrate-adhered cells. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Charge Transfer in Multiple Site Chemical Systems.

DTIC Science & Technology

1985-05-30

oxidation either chemically (using excess Ce+(IV)) or electrochemically (using a reticulated vitreous carbon electrode potentiostated at +1.20 V vs.. SCE...The resulting polymers form fairly stable, electrochemically active films on the cxidizing electrode, which can be Pt, SnO2 or vitreous carbon ...surface, including platinum and glassy carbon electrodes. The redox couples incorporated include polypyrydyl omplexes of iron, ruthenium and osmium

Overlapping Networks Engaged during Spoken Language Production and Its Cognitive Control

PubMed Central

Wise, Richard J.S.; Mehta, Amrish; Leech, Robert

2014-01-01

Spoken language production is a complex brain function that relies on large-scale networks. These include domain-specific networks that mediate language-specific processes, as well as domain-general networks mediating top-down and bottom-up attentional control. Language control is thought to involve a left-lateralized fronto-temporal-parietal (FTP) system. However, these regions do not always activate for language tasks and similar regions have been implicated in nonlinguistic cognitive processes. These inconsistent findings suggest that either the left FTP is involved in multidomain cognitive control or that there are multiple spatially overlapping FTP systems. We present evidence from an fMRI study using multivariate analysis to identify spatiotemporal networks involved in spoken language production in humans. We compared spoken language production (Speech) with multiple baselines, counting (Count), nonverbal decision (Decision), and “rest,” to pull apart the multiple partially overlapping networks that are involved in speech production. A left-lateralized FTP network was activated during Speech and deactivated during Count and nonverbal Decision trials, implicating it in cognitive control specific to sentential spoken language production. A mirror right-lateralized FTP network was activated in the Count and Decision trials, but not Speech. Importantly, a second overlapping left FTP network showed relative deactivation in Speech. These three networks, with distinct time courses, overlapped in the left parietal lobe. Contrary to the standard model of the left FTP as being dominant for speech, we revealed a more complex pattern within the left FTP, including at least two left FTP networks with competing functional roles, only one of which was activated in speech production. PMID:24966373

Overlapping networks engaged during spoken language production and its cognitive control.

PubMed

Geranmayeh, Fatemeh; Wise, Richard J S; Mehta, Amrish; Leech, Robert

2014-06-25

Spoken language production is a complex brain function that relies on large-scale networks. These include domain-specific networks that mediate language-specific processes, as well as domain-general networks mediating top-down and bottom-up attentional control. Language control is thought to involve a left-lateralized fronto-temporal-parietal (FTP) system. However, these regions do not always activate for language tasks and similar regions have been implicated in nonlinguistic cognitive processes. These inconsistent findings suggest that either the left FTP is involved in multidomain cognitive control or that there are multiple spatially overlapping FTP systems. We present evidence from an fMRI study using multivariate analysis to identify spatiotemporal networks involved in spoken language production in humans. We compared spoken language production (Speech) with multiple baselines, counting (Count), nonverbal decision (Decision), and "rest," to pull apart the multiple partially overlapping networks that are involved in speech production. A left-lateralized FTP network was activated during Speech and deactivated during Count and nonverbal Decision trials, implicating it in cognitive control specific to sentential spoken language production. A mirror right-lateralized FTP network was activated in the Count and Decision trials, but not Speech. Importantly, a second overlapping left FTP network showed relative deactivation in Speech. These three networks, with distinct time courses, overlapped in the left parietal lobe. Contrary to the standard model of the left FTP as being dominant for speech, we revealed a more complex pattern within the left FTP, including at least two left FTP networks with competing functional roles, only one of which was activated in speech production. Copyright © 2014 Geranmayeh et al.

The Role of Mammalian Sirtuins in the Regulation of Metabolism, Aging, and Longevity

PubMed Central

Satoh, Akiko; Stein, Liana

2013-01-01

Ever since the discovery of sirtuins a decade ago, interest in this family of NAD-dependent deacetylases has exploded, generating multiple lines of evidence implicating sirtuins as evolutionarily conserved regulators of lifespan. In mammals, it has been established that sirtuins regulate physiological responses to metabolism and stress, two key factors that affect the process of aging. Further investigation into the intimate connection among sirtuins, metabolism, and aging has implicated the activation of SIRT1 as both preventative and therapeutic measures against multiple age-associated disorders including type 2 diabetes and Alzheimer’s disease. SIRT1 activation has clear potential to not only prevent age-associated diseases but also to extend healthspan and perhaps lifespan. Sirtuin activating compounds and NAD intermediates are two promising ways to achieve these elusive goals. PMID:21879449

In vivo modification of tRNA with an artificial nucleobase leads to full disease remission in an animal model of multiple sclerosis.

PubMed

Varghese, Sreeja; Cotter, Michelle; Chevot, Franciane; Fergus, Claire; Cunningham, Colm; Mills, Kingston H; Connon, Stephen J; Southern, John M; Kelly, Vincent P

2017-02-28

Queuine is a modified pyrrolopyrimidine nucleobase derived exclusively from bacteria. It post-transcriptionally replaces guanine 34 in transfer RNA isoacceptors for Asp, Asn, His and Tyr, in almost all eukaryotic organisms, through the activity of the ancient tRNA guanine transglycosylase (TGT) enzyme. tRNA hypomodification with queuine is a characteristic of rapidly-proliferating, non-differentiated cells. Autoimmune diseases, including multiple sclerosis, are characterised by the rapid expansion of T cells directed to self-antigens. Here, we demonstrate the potential medicinal relevance of targeting the modification of tRNA in the treatment of a chronic multiple sclerosis model—murine experimental autoimmune encephalomyelitis. Administration of a de novo designed eukaryotic TGT substrate (NPPDAG) led to an unprecedented complete reversal of clinical symptoms and a dramatic reduction of markers associated with immune hyperactivation and neuronal damage after five daily doses. TGT is essential for the therapeutic effect, since animals deficient in TGT activity were refractory to therapy. The data suggest that exploitation of the eukaryotic TGT enzyme is a promising approach for the treatment of multiple sclerosis.

Compositional diversity of rehabilitated tropical lands supports multiple ecosystem services and buffers uncertainties

PubMed Central

Knoke, Thomas; Paul, Carola; Hildebrandt, Patrick; Calvas, Baltazar; Castro, Luz Maria; Härtl, Fabian; Döllerer, Martin; Hamer, Ute; Windhorst, David; Wiersma, Yolanda F.; Curatola Fernández, Giulia F.; Obermeier, Wolfgang A.; Adams, Julia; Breuer, Lutz; Mosandl, Reinhard; Beck, Erwin; Weber, Michael; Stimm, Bernd; Haber, Wolfgang; Fürst, Christine; Bendix, Jörg

2016-01-01

High landscape diversity is assumed to increase the number and level of ecosystem services. However, the interactions between ecosystem service provision, disturbance and landscape composition are poorly understood. Here we present a novel approach to include uncertainty in the optimization of land allocation for improving the provision of multiple ecosystem services. We refer to the rehabilitation of abandoned agricultural lands in Ecuador including two types of both afforestation and pasture rehabilitation, together with a succession option. Our results show that high compositional landscape diversity supports multiple ecosystem services (multifunction effect). This implicitly provides a buffer against uncertainty. Our work shows that active integration of uncertainty is only important when optimizing single or highly correlated ecosystem services and that the multifunction effect on landscape diversity is stronger than the uncertainty effect. This is an important insight to support a land-use planning based on ecosystem services. PMID:27292766

Compositional diversity of rehabilitated tropical lands supports multiple ecosystem services and buffers uncertainties.

PubMed

Knoke, Thomas; Paul, Carola; Hildebrandt, Patrick; Calvas, Baltazar; Castro, Luz Maria; Härtl, Fabian; Döllerer, Martin; Hamer, Ute; Windhorst, David; Wiersma, Yolanda F; Curatola Fernández, Giulia F; Obermeier, Wolfgang A; Adams, Julia; Breuer, Lutz; Mosandl, Reinhard; Beck, Erwin; Weber, Michael; Stimm, Bernd; Haber, Wolfgang; Fürst, Christine; Bendix, Jörg

2016-06-13

High landscape diversity is assumed to increase the number and level of ecosystem services. However, the interactions between ecosystem service provision, disturbance and landscape composition are poorly understood. Here we present a novel approach to include uncertainty in the optimization of land allocation for improving the provision of multiple ecosystem services. We refer to the rehabilitation of abandoned agricultural lands in Ecuador including two types of both afforestation and pasture rehabilitation, together with a succession option. Our results show that high compositional landscape diversity supports multiple ecosystem services (multifunction effect). This implicitly provides a buffer against uncertainty. Our work shows that active integration of uncertainty is only important when optimizing single or highly correlated ecosystem services and that the multifunction effect on landscape diversity is stronger than the uncertainty effect. This is an important insight to support a land-use planning based on ecosystem services.

Physical Activity and Its Correlates in Youth with Multiple Sclerosis.

PubMed

Grover, Stephanie A; Sawicki, Carolyn P; Kinnett-Hopkins, Dominique; Finlayson, Marcia; Schneiderman, Jane E; Banwell, Brenda; Till, Christine; Motl, Robert W; Yeh, E Ann

2016-12-01

To investigate physical activity levels in youth with multiple sclerosis and monophasic acquired demyelinating syndromes ([mono-ADS], ie, children without relapsing disease) compared with healthy controls and to determine factors that contribute to engagement in physical activity. We hypothesized that greater physical activity goal setting and physical activity self-efficacy would be associated with greater levels of vigorous physical activity in youth with multiple sclerosis. A total of 68 consecutive patients (27 multiple sclerosis, 41 mono-ADS) and 37 healthy controls completed fatigue, depression, Physical Activity Self-Efficacy Scale, perceived disability, Exercise Goal-Setting scale, and physical activity questionnaires, and wore an accelerometer for 7 days. All patients had no ambulatory limitations (Expanded Disability Status Scale, scores all <4). Youth with multiple sclerosis engaged in fewer minutes per day of vigorous (P = .009) and moderate and vigorous physical activity (P = .048) than did patients with mono-ADS and healthy controls. A lower proportion of the group with multiple sclerosis (63%) reported participating in any strenuous physical activity than the mono-ADS (85%) and healthy control (89%) groups (P = .020). When we adjusted for age and sex, the Physical Activity Self-Efficacy Scale and Exercise Goal-Setting scale were associated positively with vigorous physical activity in the group with multiple sclerosis. Fatigue and depression did not predict physical activity or accelerometry metrics. Youth with multiple sclerosis participate in less physical activity than their counterparts with mono-ADS and healthy controls. Physical activity self-efficacy and exercise goal setting serve as potentially modifiable correlates of physical activity, and are measures suited to future interventions aimed to increase physical activity in youth with multiple sclerosis. Copyright © 2016 Elsevier Inc. All rights reserved.

Characterizing climate change impacts on human exposures to air pollutants

EPA Science Inventory

Human exposures to air pollutants such as ozone (O3) have the potential to be altered by changes in climate through multiple factors that drive population exposures, including: ambient pollutant concentrations, human activity patterns, population sizes and distributions, and hous...

78 FR 42089 - Statement of Organization, Functions and Delegations of Authority

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-15

... related to external media relations and internal employee communications including those for the..., visual, and multimedia activities in support of communications efforts through multiple media formats... of Communications and the Office of Management. Specifically, this notice: (1) Transfers the Freedom...

The human cytoplasmic dynein interactome reveals novel activators of motility

PubMed Central

Redwine, William B; DeSantis, Morgan E; Hollyer, Ian; Htet, Zaw Min; Tran, Phuoc Tien; Swanson, Selene K; Florens, Laurence; Washburn, Michael P; Reck-Peterson, Samara L

2017-01-01

In human cells, cytoplasmic dynein-1 is essential for long-distance transport of many cargos, including organelles, RNAs, proteins, and viruses, towards microtubule minus ends. To understand how a single motor achieves cargo specificity, we identified the human dynein interactome by attaching a promiscuous biotin ligase (‘BioID’) to seven components of the dynein machinery, including a subunit of the essential cofactor dynactin. This method reported spatial information about the large cytosolic dynein/dynactin complex in living cells. To achieve maximal motile activity and to bind its cargos, human dynein/dynactin requires ‘activators’, of which only five have been described. We developed methods to identify new activators in our BioID data, and discovered that ninein and ninein-like are a new family of dynein activators. Analysis of the protein interactomes for six activators, including ninein and ninein-like, suggests that each dynein activator has multiple cargos. DOI: http://dx.doi.org/10.7554/eLife.28257.001 PMID:28718761

A Low Power, Parallel Wearable Multi-Sensor System for Human Activity Evaluation.

PubMed

Li, Yuecheng; Jia, Wenyan; Yu, Tianjian; Luan, Bo; Mao, Zhi-Hong; Zhang, Hong; Sun, Mingui

2015-04-01

In this paper, the design of a low power heterogeneous wearable multi-sensor system, built with Zynq System-on-Chip (SoC), for human activity evaluation is presented. The powerful data processing capability and flexibility of this SoC represent significant improvements over our previous ARM based system designs. The new system captures and compresses multiple color images and sensor data simultaneously. Several strategies are adopted to minimize power consumption. Our wearable system provides a new tool for the evaluation of human activity, including diet, physical activity and lifestyle.

Immuno-therapy of Acute Radiation Syndromes : Extracorporeal Immuno-Lympho-Plasmo-Sorption.

NASA Astrophysics Data System (ADS)

Popov, Dmitri; Maliev, Slava

Methods Results Summary and conclusions Introduction: Existing Medical Management of the Acute Radiation Syndromes (ARS) does not include methods of specific immunotherapy and active detoxication. Though the Acute Radiation Syndromes were defined as an acute toxic poisonous with development of pathological processes: Systemic Inflammatory Response Syndrome (SIRS), Toxic Multiple Organ Injury (TMOI), Toxic Multiple Organ Dysfunction Syndrome(TMODS), Toxic Multiple Organ Failure (TMOF). Radiation Toxins of SRD Group play an important role as the trigger mechanisms in development of the ARS clinical symptoms. Methods: Immuno-Lympho-Plasmo-Sorption is a type of Immuno-therapy which includes prin-ciples of immunochromato-graphy, plasmopheresis, and hemodialysis. Specific Antiradiation Antitoxic Antibodies are the active pharmacological agents of immunotherapy . Antiradia-tion Antitoxic Antibodies bind selectively to Radiation Neurotoxins, Cytotoxins, Hematotox-ins and neutralize their toxic activity. We have developed the highly sensitive method and system for extracorporeal-immune-lypmh-plasmo-sorption with antigen-specific IgG which is clinically important for treatment of the toxic and immunologic phases of the ARS. The method of extracorporeal-immune-lypmh-plasmo-sorption includes Antiradiation Antitoxic Antibodies (AAA) immobilized on microporous polymeric membranes with a pore size that is capable to provide diffusion of blood-lymph plasma. Plasma of blood or lymph of irradiated mammals contains Radiation Toxins (RT) that have toxic and antigenic properties. Radiation Toxins are Antigen-specific to Antitoxic blocking antibodies (Immunoglobulin G). Plasma diffuses through membranes with immobilized AAA and AA-antibodies bind to the polysaccharide chain of tox-ins molecules and complexes of AAA-RT that are captured on membrane surfaces. RT were removed from plasma. Re-transfusion of plasma of blood and lymph had been provided. We show a statistical significant reduction in postradiation lethality.

Children with mathematical learning disability fail in recruiting verbal and numerical brain regions when solving simple multiplication problems.

PubMed

Berteletti, Ilaria; Prado, Jérôme; Booth, James R

2014-08-01

Greater skill in solving single-digit multiplication problems requires a progressive shift from a reliance on numerical to verbal mechanisms over development. Children with mathematical learning disability (MD), however, are thought to suffer from a specific impairment in numerical mechanisms. Here we tested the hypothesis that this impairment might prevent MD children from transitioning toward verbal mechanisms when solving single-digit multiplication problems. Brain activations during multiplication problems were compared in MD and typically developing (TD) children (3rd to 7th graders) in numerical and verbal regions which were individuated by independent localizer tasks. We used small (e.g., 2 × 3) and large (e.g., 7 × 9) problems as these problems likely differ in their reliance on verbal versus numerical mechanisms. Results indicate that MD children have reduced activations in both the verbal (i.e., left inferior frontal gyrus and left middle temporal to superior temporal gyri) and the numerical (i.e., right superior parietal lobule including intra-parietal sulcus) regions suggesting that both mechanisms are impaired. Moreover, the only reliable activation observed for MD children was in the numerical region when solving small problems. This suggests that MD children could effectively engage numerical mechanisms only for the easier problems. Conversely, TD children showed a modulation of activation with problem size in the verbal regions. This suggests that TD children were effectively engaging verbal mechanisms for the easier problems. Moreover, TD children with better language skills were more effective at engaging verbal mechanisms. In conclusion, results suggest that the numerical- and language-related processes involved in solving multiplication problems are impaired in MD children. Published by Elsevier Ltd.

Spatial organization of hominin activities at Gesher Benot Ya'aqov, Israel.

PubMed

Alperson-Afil, Nira; Sharon, Gonen; Kislev, Mordechai; Melamed, Yoel; Zohar, Irit; Ashkenazi, Shosh; Rabinovich, Rivka; Biton, Rebecca; Werker, Ella; Hartman, Gideon; Feibel, Craig; Goren-Inbar, Naama

2009-12-18

The spatial designation of discrete areas for different activities reflects formalized conceptualization of a living space. The results of spatial analyses of a Middle Pleistocene Acheulian archaeological horizon (about 750,000 years ago) at Gesher Benot Ya'aqov, Israel, indicate that hominins differentiated their activities (stone knapping, tool use, floral and faunal processing and consumption) across space. These were organized in two main areas, including multiple activities around a hearth. The diversity of human activities and the distinctive patterning with which they are organized implies advanced organizational skills of the Gesher Benot Ya'aqov hominins.

The active site structure of tetanus neurotoxin resolved by multiple scattering analysis in X-Ray absorption spectroscopy.

PubMed Central

Meneghini, C; Morante, S

1998-01-01

A detailed study of the x-ray absorption spectrum of tetanus neurotoxin in the K-edge EXAFS region of the zinc absorber is presented that allows the complete identification of the amino acid residues coordinated to the zinc active site. A very satisfactory interpretation of the experimental data can be given if multiple scattering contributions are included in the analysis. Comparing the absorption spectrum of tetanus neurotoxin to that of two other structurally similar zinc-endopeptidases, thermolysin and astacin, in which the zinc coordination mode is known from crystallographic data, we conclude that in tetanus neurotoxin, besides a water molecule, zinc is coordinated to two histidines and a tyrosine. PMID:9746536

Quality of Care for PTSD and Depression in the Military Health System

DTIC Science & Technology

evaluate the receipt of recommended assessments and treatments. These measures draw on multiple data sources including administrative encounter data...services are effective in reducing symptoms. When comparing performance between 20122013 and 20132014, most measures demonstrated slight improvement ...in 20132014 for over 38,000 active-component service members with PTSD or depression. The assessment includes performance on 30 quality measures to

Collaborative Planning of Robotic Exploration

NASA Technical Reports Server (NTRS)

Norris, Jeffrey; Backes, Paul; Powell, Mark; Vona, Marsette; Steinke, Robert

2004-01-01

The Science Activity Planner (SAP) software system includes an uplink-planning component, which enables collaborative planning of activities to be undertaken by an exploratory robot on a remote planet or on Earth. Included in the uplink-planning component is the SAP-Uplink Browser, which enables users to load multiple spacecraft activity plans into a single window, compare them, and merge them. The uplink-planning component includes a subcomponent that implements the Rover Markup Language Activity Planning format (RML-AP), based on the Extensible Markup Language (XML) format that enables the representation, within a single document, of planned spacecraft and robotic activities together with the scientific reasons for the activities. Each such document is highly parseable and can be validated easily. Another subcomponent of the uplink-planning component is the Activity Dictionary Markup Language (ADML), which eliminates the need for two mission activity dictionaries - one in a human-readable format and one in a machine-readable format. Style sheets that have been developed along with the ADML format enable users to edit one dictionary in a user-friendly environment without compromising

A Review of Non-Chemical Stressors and Their Importance in Cumulative Risk Assessment

EPA Science Inventory

Cumulative exposure/risk assessments need to include non-chemical stressors as well as human activities and chemical data. Multiple stressor research can offer information on the interactions between chemical and non-chemical stressors needed for cumulative risk assessment resea...

Empowering Infants through Responsive and Intentional Play Activities

ERIC Educational Resources Information Center

Shin, Minsun; Partyka, Thomas

2017-01-01

This qualitative case study explored how an infant teacher provided meaningful learning experiences for infants through play and the teacher's educational rationale behind these experiences. Findings were based on multiple sources of data, including classroom observations (natural observation and videotaped observation) for approximately 12 weeks…

Impact of cover crops on soil nitrate, crop yield and quality

USDA-ARS?s Scientific Manuscript database

There are multiple benefits of incorporating cover crops into current production systems including decreasing erosion, improving water infiltration, increasing soil organic matter and biological activity but in water limited areas caution should be utilized. A field study was established in the fal...

Experimenting with Temperature Probes.

ERIC Educational Resources Information Center

Roth, Wolff-Michael

1989-01-01

Presented are four activities which are designed to familiarize children with the multiple uses of computers and help them learn about heat and temperature using temperature probes. Included are the tempering effect of water, heat capacity, caloric content of foods, and weather. Hardware and software are discussed. (CW)

Dynamic changes in DNA demethylation in the tree shrew (Tupaia belangeri chinensis) brain during postnatal development and aging.

PubMed

Wei, Shu; Hua, Hai-Rong; Chen, Qian-Quan; Zhang, Ying; Chen, Fei; Li, Shu-Qing; Li, Fan; Li, Jia-Li

2017-03-18

Brain development and aging are associated with alterations in multiple epigenetic systems, including DNA methylation and demethylation patterns. Here, we observed that the levels of the 5-hydroxymethylcytosine (5hmC) ten-eleven translocation (TET) enzyme-mediated active DNA demethylation products were dynamically changed and involved in postnatal brain development and aging in tree shrews ( Tupaia belangeri chinensis ). The levels of 5hmC in multiple anatomic structures showed a gradual increase throughout postnatal development, whereas a significant decrease in 5hmC was found in several brain regions in aged tree shrews, including in the prefrontal cortex and hippocampus, but not the cerebellum. Active changes in Tet mRNA levels indicated that TET2 and TET3 predominantly contributed to the changes in 5hmC levels. Our findings provide new insight into the dynamic changes in 5hmC levels in tree shrew brains during postnatal development and aging processes.

Expression profiling of peroxisome proliferator-activated receptor-delta (PPAR-delta) in mouse tissues using tissue microarray.

PubMed

Higashiyama, Hiroyuki; Billin, Andrew N; Okamoto, Yuji; Kinoshita, Mine; Asano, Satoshi

2007-05-01

Peroxisome proliferator-activated receptor-delta (PPAR-delta) is known as a transcription factor involved in the regulation of fatty acid oxidation and mitochondrial biogenesis in several tissues, such as skeletal muscle, liver and adipose tissues. In this study, to elucidate systemic physiological functions of PPAR-delta, we examined the tissue distribution and localization of PPAR-delta in adult mouse tissues using tissue microarray (TMA)-based immunohistochemistry. PPAR-delta positive signals were observed on variety of tissues/cells in multiple systems including cardiovascular, urinary, respiratory, digestive, endocrine, nervous, hematopoietic, immune, musculoskeletal, sensory and reproductive organ systems. In these organs, PPAR-delta immunoreactivity was generally localized on the nucleus, although cytoplasmic localization was observed on several cell types including neurons in the nervous system and cells of the islet of Langerhans. These expression profiling data implicate various physiological roles of PPAR-delta in multiple organ systems. TMA-based immunohistochemistry enables to profile comprehensive protein localization and distribution in a high-throughput manner.

The Effect of High Versus Low Teacher Affect and Passive Versus Active Student Activity During Music Listening on Preschool Children's Attention, Piece Preference, Time Spent Listening, and Piece Recognition.

ERIC Educational Resources Information Center

Sims, Wendy L.

1986-01-01

Small-group listening lessons and subsequent individual posttests were used to judge 94 three- through five-year-old subjects' attention, paired-comparison piece preference, time spent listening, and piece recognition. Research procedures included a modified multiple baseline design and split-screen video taping of instructional sessions.…

Drones for aerodynamic and structural testing /DAST/ - A status report

NASA Technical Reports Server (NTRS)

Murrow, H. N.; Eckstrom, C. V.

1978-01-01

A program for providing research data on aerodynamic loads and active control systems on wings with supercritical airfoils in the transonic speed range is described. Analytical development, wind tunnel tests, and flight tests are included. A Firebee II target drone vehicle has been modified for use as a flight test facility. The program currently includes flight experiments on two aeroelastic research wings. The primary purpose of the first flight experiment is to demonstrate an active control system for flutter suppression on a transport-type wing. Design and fabrication of the wing are complete and after installing research instrumentation and the flutter suppression system, flight testing is expected to begin in early 1979. The experiment on the second research wing - a fuel-conservative transport type - is to demonstrate multiple active control systems including flutter suppression, maneuver load alleviation, gust load alleviation, and reduce static stability. Of special importance for this second experiment is the development and validation of integrated design methods which include the benefits of active controls in the structural design.

[Morphological signs of inflammatory activity in different clinical forms of drug-resistant pulmonary tuberculosis].

PubMed

Elipashev, A A; Nikolsky, V O; Shprykov, A S

to determine whether the activity of tuberculous inflammation is associated with different clinical forms of drug-resistant pulmonary tuberculosis. The material taken from 310 patients operated on in 2010-2015 were retrospectively examined. The patients underwent economical lung resections of limited extent (typical and atypical ones of up to 3 segments) for circumscribed forms of tuberculosis with bacterial excretion. A study group consisted of 161 (51.9%) patients with drug-resistant variants of pulmonary tuberculosis. A control group included 149 (48.1%) patients with preserved susceptibility of Mycobacterium tuberculosis to anti-TB drugs. The activity of specific changes in tuberculosis was morphologically evaluated in accordance with the classification proposed by B.M. Ariel in 1998. The highest activity of fourth-to-fifth degree specific inflammation, including that outside the primary involvement focus, was obtained in the drug-resistant pulmonary tuberculosis group due to the predominance of patients with cavernous and fibrous-cavernous tuberculosis versus those in whom the susceptibility to chemotherapeutic agents was preserved. A macroscopic study showed that the primary lesion focus had a median size in one-half of the all the examinees; but large tuberculomas, caverns, and fibrous caverns over 4 cm in diameter were multiple and detected in the drug-resistant pulmonary tuberculosis group. Multidrug resistance was observed in more than 60% of the patients with fibrous-cavernous pulmonary tuberculosis, extensive drug resistance was seen in those with cavernous tuberculosis, which is an aggravating factor. The data obtained from the morphological study of the intraoperative material can specify the clinical form of tuberculosis and evaluate the efficiency of preoperative specific therapy. The highest activity of specific inflammation was observed in patients with multiple drug-resistant pulmonary tuberculosis, the prevalence of third-to-fourth degree specific changes was seen in those with multiple and extensively drug-resistant tuberculosis. The findings suggest that the activity of tuberculous inflammation is associated with different clinical forms of drug-resistant tuberculosis and with a spectrum of drug resistance.

A delicate balance: role of MMP-9 in brain development and pathophysiology of neurodevelopmental disorders

PubMed Central

Reinhard, Sarah M.; Razak, Khaleel; Ethell, Iryna M.

2015-01-01

The extracellular matrix (ECM) is a critical regulator of neural network development and plasticity. As neuronal circuits develop, the ECM stabilizes synaptic contacts, while its cleavage has both permissive and active roles in the regulation of plasticity. Matrix metalloproteinase 9 (MMP-9) is a member of a large family of zinc-dependent endopeptidases that can cleave ECM and several cell surface receptors allowing for synaptic and circuit level reorganization. It is becoming increasingly clear that the regulated activity of MMP-9 is critical for central nervous system (CNS) development. In particular, MMP-9 has a role in the development of sensory circuits during early postnatal periods, called ‘critical periods.’ MMP-9 can regulate sensory-mediated, local circuit reorganization through its ability to control synaptogenesis, axonal pathfinding and myelination. Although activity-dependent activation of MMP-9 at specific synapses plays an important role in multiple plasticity mechanisms throughout the CNS, misregulated activation of the enzyme is implicated in a number of neurodegenerative disorders, including traumatic brain injury, multiple sclerosis, and Alzheimer’s disease. Growing evidence also suggests a role for MMP-9 in the pathophysiology of neurodevelopmental disorders including Fragile X Syndrome. This review outlines the various actions of MMP-9 during postnatal brain development, critical for future studies exploring novel therapeutic strategies for neurodevelopmental disorders. PMID:26283917

The Association Between Sexual Satisfaction and Body Image in Women

PubMed Central

Pujols, Yasisca; Meston, Cindy M.; Seal, Brooke N.

2010-01-01

Introduction Although sexual functioning has been linked to sexual satisfaction, it only partially explains the degree to which women report being sexually satisfied. Other factors include quality of life, relational variables, and individual factors such as body image. Of the few studies that have investigated the link between body image and sexual satisfaction, most have considered body image to be a single construct and have shown mixed results. Aim The present study assessed multiple body image variables in order to better understand which aspects of body image influence multiple domains of sexual satisfaction, including sexual communication, compatibility, contentment, personal concern, and relational concern in a community sample of women. Methods Women between the ages of 18 and 49 years in sexual relationships (N = 154) participated in an Internet survey that assessed sexual functioning, five domains of sexual satisfaction, and several body image variables. Main Outcome Measures Body image variables included the sexual attractiveness, weight concern, and physical condition subscales of the Body Esteem Scale, the appearance-based subscale of the Cognitive Distractions During Sexual Activity Scale, and body mass index. Total score of the Sexual Satisfaction Scale for Women was the main outcome measure. Sexual functioning was measured by a modified Female Sexual Function Index. Results Consistent with expectations, correlations indicated significant positive relationships between sexual functioning, sexual satisfaction, and all body image variables. A multiple regression analysis revealed that sexual satisfaction was predicted by high body esteem and low frequency of appearance-based distracting thoughts during sexual activity, even after controlling for sexual functioning status. Conclusion Several aspects of body image, including weight concern, physical condition, sexual attractiveness, and thoughts about the body during sexual activity predict sexual satisfaction in women. The findings suggest that women who experience low sexual satisfaction may benefit from treatments that target these specific aspects of body image. PMID:19968771

Gut-CNS-Axis as Possibility to Modulate Inflammatory Disease Activity-Implications for Multiple Sclerosis.

PubMed

Fleck, Ann-Katrin; Schuppan, Detlef; Wiendl, Heinz; Klotz, Luisa

2017-07-14

In the last decade the role of environmental factors as modulators of disease activity and progression has received increasing attention. In contrast to classical environmental modulators such as exposure to sun-light or fine dust pollution, nutrition is an ideal tool for a personalized human intervention. Various studies demonstrate a key role of dietary factors in autoimmune diseases including Inflammatory Bowel Disease (IBD), rheumatoid arthritis or inflammatory central nervous system (CNS) diseases such as Multiple Sclerosis (MS). In this review we discuss the connection between diet and inflammatory processes via the gut-CNS-axis. This axis describes a bi-directional communication system and comprises neuronal signaling, neuroendocrine pathways and modulation of immune responses. Therefore, the gut-CNS-axis represents an emerging target to modify CNS inflammatory activity ultimately opening new avenues for complementary and adjunctive treatment of autoimmune diseases such as MS.

AXARM: An Extensible Remote Assistance and Monitoring Tool for ND Telerehabilitation

NASA Astrophysics Data System (ADS)

Bueno, Antonio; Marzo, Jose L.; Vallejo, Xavier

AXARM is a multimedia tool for rehabilitation specialists that allow remote assistance and monitoring of patients activities. This tool is the evolution of the work done in 2005-06 between the BCDS research group of UdG and the Multiple Sclerosis Foundation (FEM in Spanish) in Girona under the TRiEM project. Multiple Sclerosis (MS) is a neurodegenerative disease (ND) that can provoke significant exhaustion in patients even just by going to the medical centre for rehabilitation or regular checking visits. The tool presented in this paper allows the medical staff to remotely carry on patient consults and activities from their home, minimizing the displacements to medical consulting. AXARM has a hybrid P2P architecture and consists essentially of a cross-platform videoconference system, with audio/video recording capabilities. The system can easily be extended to include new capabilities like, among others, asynchronous activities whose result can later be analyzed by the medical personnel.

Renal thrombotic microangiopathy caused by interferon beta-1a treatment for multiple sclerosis

PubMed Central

Mahe, Julien; Meurette, Aurélie; Moreau, Anne; Vercel, Caroline; Jolliet, Pascale

2013-01-01

Interferon beta-1a is available as an immunomodulating agent for relapsing forms of multiple sclerosis. Common side effects include flu-like symptoms, asthenia, anorexia, and administration site reaction. Kidney disorders are rarely reported. In this study we describe the case of a woman who has been undergoing treatment with interferon beta-1a for multiple sclerosis for 5 years. She developed a hemolytic-uremic syndrome with intravascular hemolysis in a context of severe hypertension. A kidney biopsy showed a thrombotic microangiopathy. This observation highlights an uncommon side effect of long-term interferon beta-1a therapy. Pathophysiological mechanisms leading to this complication might be explained by the antiangiogenic activity of interferon. PMID:23950639

Motion analysis report

NASA Technical Reports Server (NTRS)

Badler, N. I.

1985-01-01

Human motion analysis is the task of converting actual human movements into computer readable data. Such movement information may be obtained though active or passive sensing methods. Active methods include physical measuring devices such as goniometers on joints of the body, force plates, and manually operated sensors such as a Cybex dynamometer. Passive sensing de-couples the position measuring device from actual human contact. Passive sensors include Selspot scanning systems (since there is no mechanical connection between the subject's attached LEDs and the infrared sensing cameras), sonic (spark-based) three-dimensional digitizers, Polhemus six-dimensional tracking systems, and image processing systems based on multiple views and photogrammetric calculations.

Walking impairment in patients with multiple sclerosis: exercise training as a treatment option.

PubMed

Motl, Robert W; Goldman, Myla D; Benedict, Ralph H B

2010-11-16

Multiple sclerosis (MS) is a chronic disease of the central nervous system that culminates in the progression of physical and cognitive disability over time. Walking impairment is a ubiquitous feature of MS and a sentinel characteristic of the later or advanced stages of the disease. This paper presents a conceptual rationale along with empirical evidence for exercise training as a rehabilitation approach for managing walking impairment and improving walking function in persons with MS. Conceptually, MS is associated with a decrease in physical activity, which, in turn, can result in deconditioning across multiple domains of physiological functioning. The resulting deconditioning feeds back and further drives physical inactivity until a threshold is reached that likely initiates the progression of walking impairment in MS. Empirically, physical activity and exercise training have been associated with beneficial effects on walking function in persons with MS. This is based on cross-sectional, longitudinal, and experimental research that included diversity in the breadth of measures of walking, persons with MS, and exercise/physical activity characteristics. Of particular importance, future researchers might consider examining the combinatory effects of exercise training plus pharmacological agents on walking mobility in MS. Collectively, exercise training and physical activity might hold significant potential for the management of progressive mobility disability in MS.

Using health promotion guidelines for persons with disabilities to develop and evaluate a physical activity program for individuals with multiple sclerosis: A feasibility study.

PubMed

Dixon-Ibarra, Alicia; Nery-Hurwit, Mara; Driver, Simon; MacDonald, Megan

2017-04-01

The Health Education for Persons with Multiple Sclerosis (HEMS) program was developed in response to the need for interventions aimed at increasing physical activity for individuals with Multiple Sclerosis (MS). It was developed and evaluated using Drum and colleagues (2009) guidelines for implementing health promotion programs for individuals with disabilities. The purpose of this feasibility study is to describe the development, implementation, and evaluation of the HEMS program. Thirteen individuals with MS completed the 8-week health education program. A mixed method approach for evaluation was implemented (i.e., survey and focus groups). Process and resource feasibility demonstrated that over half of the participants attended at least 80% of the weekly sessions. Focus group data provided valuable feedback for future iterations of the program including critiques on the delivery, content, and group support provided. Outcome evaluation showed increases in self-efficacy (survey), improvements in theoretical constructs (focus groups), and increased physical activity (focus groups). Results show that health promotion programs for persons with MS can improve physical activity and related constructs. Next steps will be to revise, implement, and reevaluate the HEMS program in a larger randomized control trial. Published by Elsevier Ltd.

Effectiveness of and User Experience With Web-Based Interventions in Increasing Physical Activity Levels in People With Multiple Sclerosis: A Systematic Review.

PubMed

Dennett, Rachel; Gunn, Hilary; Freeman, Jennifer A

2018-05-15

Supporting people with multiple sclerosis (MS) to achieve and maintain recommended levels of physical activity is important but challenging. Web-based interventions are increasingly being used to deliver targeted exercise programs and promote physical activity. The purpose of this study was to systematically review current evidence regarding the effectiveness and user experience of web-based interventions in increasing physical activity in people with MS. MEDLINE, EMBASE, CINAHL, AMED, PEDro, PsychInfo, Web of Sciences, The Cochrane Library, and gray literature were searched from 1990 to September 2016. English language articles reporting the use of web-based interventions to increase physical activity in adults with MS were included. Eligible quantitative studies were of any design and reported a measure of physical activity. Qualitative studies exploring users' experiences in any context were included. Of the 881 articles identified, 9 met the inclusion criteria. Two reviewers independently assessed methodological quality and extracted data using standardized critical appraisal and data extraction tools from the Joanna Briggs Institute Meta Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI). Meta-analysis of self-reported physical activity questionnaire data from 4 studies demonstrated a standardized mean difference of 0.67 (95% CI = 0.43-0.92), indicating a positive effect in favor of the web-based interventions. Narrative review of accelerometry data from 3 studies indicated increases in objectively measured physical activity. No qualitative studies met the inclusion criteria. In the 9 included articles, only 2 different interventions (used with people who were ambulant) were reported. Web-based interventions had a short-term positive effect on self-reported physical activity in people who had MS and were ambulant. Evidence is not currently available to support or refute their use in the long-term or with people who are not ambulant.

Therapeutic and cosmetic applications of mangiferin: a patent review.

PubMed

Telang, Manasi; Dhulap, Sivakami; Mandhare, Anita; Hirwani, Rajkumar

2013-12-01

Mangiferin, a natural C-glucoside xanthone [2-C-β-D-glucopyranosyl-1, 3, 6, 7-tetrahydroxyxanthone], is abundantly present in young leaves and stem bark of the mango tree. The xanthonoid structure of mangiferin with C-glycosyl linkage and polyhydroxy components contributes to its free radical-scavenging ability, leading to a potent antioxidant effect as well as multiple biological activities. An extensive search was carried out to collect patent information on mangiferin and its derivatives using various patent databases spanning all priority years to date. The patents claiming therapeutic and cosmetic applications of mangiferin and its derivatives were analyzed in detail. The technology areas covered in this article include metabolic disorders, cosmeceuticals, multiple uses of the same compound, miscellaneous uses, infectious diseases, inflammation, cancer and autoimmune disorders, and neurological disorders. Mangiferin has the potential to modulate multiple molecular targets including nuclear factor-kappa B (NF-κB) signaling and cyclooxygenase-2 (COX-2) protein expression. Mangiferin exhibits antioxidant, antidiabetic, antihyperuricemic, antiviral, anticancer and antiinflammatory activities. The molecular structure of mangiferin fulfils the four Lipinski's requisites reported to favor high bioavailability by oral administration. There is no evidence of adverse side effects of mangiferin so far. Mangiferin could thus be a promising candidate for development of a multipotent drug.

Co-pyrolysis kinetics of sewage sludge and bagasse using multiple normal distributed activation energy model (M-DAEM).

PubMed

Lin, Yan; Chen, Zhihao; Dai, Minquan; Fang, Shiwen; Liao, Yanfen; Yu, Zhaosheng; Ma, Xiaoqian

2018-07-01

In this study, the kinetic models of bagasse, sewage sludge and their mixture were established by the multiple normal distributed activation energy model. Blending with sewage sludge, the initial temperature declined from 437 K to 418 K. The pyrolytic species could be divided into five categories, including analogous hemicelluloses I, hemicelluloses II, cellulose, lignin and bio-char. In these species, the average activation energies and the deviations situated at reasonable ranges of 166.4673-323.7261 kJ/mol and 0.1063-35.2973 kJ/mol, respectively, which were conformed to the references. The kinetic models were well matched to experimental data, and the R 2 were greater than 99.999%y. In the local sensitivity analysis, the distributed average activation energy had stronger effect on the robustness than other kinetic parameters. And the content of pyrolytic species determined which series of kinetic parameters were more important. Copyright © 2018 Elsevier Ltd. All rights reserved.

Potential use of multiple surveillance data in the forecast of hospital admissions

PubMed Central

Lau, Eric H.Y.; Ip, Dennis K.M.; Cowling, Benjamin J.

2013-01-01

Objective This paper describes the potential use of multiple influenza surveillance data to forecast hospital admissions for respiratory diseases. Introduction A sudden surge in hospital admissions in public hospital during influenza peak season has been a challenge to healthcare and manpower planning. In Hong Kong, the timing of influenza peak seasons are variable and early short-term indication of possible surge may facilitate preparedness which could be translated into strategies such as early discharge or reallocation of extra hospital beds. In this study we explore the potential use of multiple routinely collected syndromic data in the forecast of hospital admissions. Methods A multivariate dynamic linear time series model was fitted to multiple syndromic data including influenza-like illness (ILI) rates among networks of public and private general practitioners (GP), and school absenteeism rates, plus drop-in fever count data from designated flu clinics (DFC) that were created during the pandemic. The latent process derived from the model has been used as a measure of the influenza activity [1]. We compare the cross-correlations between estimated influenza level based on multiple surveillance data and GP ILI data, versus accident and emergency hospital admissions with principal diagnoses of respiratory diseases and pneumonia & influenza (P&I). Results The estimated influenza activity has higher cross-correlation with respiratory and P&I admissions (ρ=0.66 and 0.73 respectively) compared to that of GP ILI rates (Table 1). Cross correlations drop distinctly after lag 2 for both estimated influenza activity and GP ILI rates. Conclusions The use of a multivariate method to integrate information from multiple sources of influenza surveillance data may have the potential to improve forecasting of admission surge of respiratory diseases.

Reliability of Classifying Multiple Sclerosis Disease Activity Using Magnetic Resonance Imaging in a Multiple Sclerosis Clinic

PubMed Central

Altay, Ebru Erbayat; Fisher, Elizabeth; Jones, Stephen E.; Hara-Cleaver, Claire; Lee, Jar-Chi; Rudick, Richard A.

2013-01-01

Objective To assess the reliability of new magnetic resonance imaging (MRI) lesion counts by clinicians in a multiple sclerosis specialty clinic. Design An observational study. Setting A multiple sclerosis specialty clinic. Patients Eighty-five patients with multiple sclerosis participating in a National Institutes of Health–supported longitudinal study were included. Intervention Each patient had a brain MRI scan at entry and 6 months later using a standardized protocol. Main Outcome Measures The number of new T2 lesions, newly enlarging T2 lesions, and gadolinium-enhancing lesions were measured on the 6-month MRI using a computer-based image analysis program for the original study. For this study, images were reanalyzed by an expert neuroradiologist and 3 clinician raters. The neuroradiologist evaluated the original image pairs; the clinicians evaluated image pairs that were modified to simulate clinical practice. New lesion counts were compared across raters, as was classification of patients as MRI active or inactive. Results Agreement on lesion counts was highest for gadolinium-enhancing lesions, intermediate for new T2 lesions, and poor for enlarging T2 lesions. In 18% to 25% of the cases, MRI activity was classified differently by the clinician raters compared with the neuroradiologist or computer program. Variability among the clinical raters for estimates of new T2 lesions was affected most strongly by the image modifications that simulated low image quality and different head position. Conclusions Between-rater variability in new T2 lesion counts may be reduced by improved standardization of image acquisitions, but this approach may not be practical in most clinical environments. Ultimately, more reliable, robust, and accessible image analysis methods are needed for accurate multiple sclerosis disease-modifying drug monitoring and decision making in the routine clinic setting. PMID:23599930

Recent Developments in C-H Activation for Materials Science in the Center for Selective C-H Activation.

PubMed

Zhang, Junxiang; Kang, Lauren J; Parker, Timothy C; Blakey, Simon B; Luscombe, Christine K; Marder, Seth R

2018-04-16

Abstract : Organic electronics is a rapidly growing field driven in large part by the synthesis of ∏-conjugated molecules and polymers. Traditional aryl cross-coupling reactions such as the Stille and Suzuki have been used extensively in the synthesis of ∏-conjugated molecules and polymers, but the synthesis of intermediates necessary for traditional cross-couplings can include multiple steps with toxic and hazardous reagents. Direct arylation through C-H bond activation has the potential to reduce the number of steps and hazards while being more atom-economical. Within the Center for Selective C-H Functionalization (CCHF), we have been developing C-H activation methodology for the synthesis of ∏-conjugated materials of interest, including direct arylation of difficult-to-functionalize electron acceptor intermediates and living polymerization of ∏-conjugated polymers through C-H activation.

Managing temporal relations

NASA Technical Reports Server (NTRS)

Britt, Daniel L.; Geoffroy, Amy L.; Gohring, John R.

1990-01-01

Various temporal constraints on the execution of activities are described, and their representation in the scheduling system MAESTRO is discussed. Initial examples are presented using a sample activity described. Those examples are expanded to include a second activity, and the types of temporal constraints that can obtain between two activities are explored. Soft constraints, or preferences, in activity placement are discussed. Multiple performances of activities are considered, with respect to both hard and soft constraints. The primary methods used in MAESTRO to handle temporal constraints are described as are certain aspects of contingency handling with respect to temporal constraints. A discussion of the overall approach, with indications of future directions for this research, concludes the study.

Computer-Based Cognitive Training for Executive Functions after Stroke: A Systematic Review

PubMed Central

van de Ven, Renate M.; Murre, Jaap M. J.; Veltman, Dick J.; Schmand, Ben A.

2016-01-01

Background: Stroke commonly results in cognitive impairments in working memory, attention, and executive function, which may be restored with appropriate training programs. Our aim was to systematically review the evidence for computer-based cognitive training of executive dysfunctions. Methods: Studies were included if they concerned adults who had suffered stroke or other types of acquired brain injury, if the intervention was computer training of executive functions, and if the outcome was related to executive functioning. We searched in MEDLINE, PsycINFO, Web of Science, and The Cochrane Library. Study quality was evaluated based on the CONSORT Statement. Treatment effect was evaluated based on differences compared to pre-treatment and/or to a control group. Results: Twenty studies were included. Two were randomized controlled trials that used an active control group. The other studies included multiple baselines, a passive control group, or were uncontrolled. Improvements were observed in tasks similar to the training (near transfer) and in tasks dissimilar to the training (far transfer). However, these effects were not larger in trained than in active control groups. Two studies evaluated neural effects and found changes in both functional and structural connectivity. Most studies suffered from methodological limitations (e.g., lack of an active control group and no adjustment for multiple testing) hampering differentiation of training effects from spontaneous recovery, retest effects, and placebo effects. Conclusions: The positive findings of most studies, including neural changes, warrant continuation of research in this field, but only if its methodological limitations are addressed. PMID:27148007

Everyday memory strategies for medication adherence.

PubMed

Boron, Julie Blaskewicz; Rogers, Wendy A; Fisk, Arthur D

2013-01-01

The need to manage chronic diseases and multiple medications increases for many older adults. Older adults are aware of memory declines and incorporate compensatory techniques. Everyday memory strategies used to support medication adherence were investigated. A survey distributed to 2000 households in the Atlanta metropolitan area yielded a 19.9% response rate including 354 older adults, aged 60-80 years. Older adults reported forgetting to take their medications, more so as their activity deviated from normal routines, such as unexpected activities. The majority of older adults endorsed at least two compensatory strategies, which they perceived to be more helpful in normal routines. Compensatory strategies were associated with higher education, more medications, having concern, and self-efficacy to take medications. As memory changes, older adults rely on multiple cues, and perceive reliance on multiple cues to be helpful. These data have implications for the design and successful implementation of medication reminder systems and interventions. Copyright © 2013 Mosby, Inc. All rights reserved.

Joint Identification of Genetic Variants for Physical Activity in Korean Population

PubMed Central

Kim, Jayoun; Kim, Jaehee; Min, Haesook; Oh, Sohee; Kim, Yeonjung; Lee, Andy H.; Park, Taesung

2014-01-01

There has been limited research on genome-wide association with physical activity (PA). This study ascertained genetic associations between PA and 344,893 single nucleotide polymorphism (SNP) markers in 8842 Korean samples. PA data were obtained from a validated questionnaire that included information on PA intensity and duration. Metabolic equivalent of tasks were calculated to estimate the total daily PA level for each individual. In addition to single- and multiple-SNP association tests, a pathway enrichment analysis was performed to identify the biological significance of SNP markers. Although no significant SNP was found at genome-wide significance level via single-SNP association tests, 59 genetic variants mapped to 76 genes were identified via a multiple SNP approach using a bootstrap selection stability measure. Pathway analysis for these 59 variants showed that maturity onset diabetes of the young (MODY) was enriched. Joint identification of SNPs could enable the identification of multiple SNPs with good predictive power for PA and a pathway enriched for PA. PMID:25026172

Evaluation of effects of shellfish aquaculture and capture fishery on a semi-closed bay ecosystem

NASA Astrophysics Data System (ADS)

Han, Dongyan; Chen, Yong; Zhang, Chongliang; Ren, Yiping; Xu, Binduo; Xue, Ying

2018-07-01

Coastal waters in the world are suffering from multiple anthropogenic disturbances, including capture fisheries and aquaculture. Ignoring possible interactions between multiple disturbances may cause serious consequences in our understanding of ecosystem dynamics. This study simulates individual and combined effects of fishing activities and shellfish cultivation on a semi-closed bay ecosystem using Ecopath with Ecosim (EwE). The changes of biomass and ecosystem structure were examined for three scenarios of having fishing alone, shellfish cultivation alone and both fishing and aquaculture. We found considerable impacts of shellfish aquaculture but minor impacts from fishing, suggesting shellfish aquaculture had dominated impacts on the study ecosystem. In addition, the effects of fishing and shellfish aquaculture were not additive on species biomass, rather showing a combined effect with synergy. Given the same loss in fisheries yield, controlling fishing and shellfish aquaculture simultaneously was more efficient for increasing nekton biomass compared to the control of either activity. We highlight the necessity for integrating management of multiple human stressors for an ecosystem-based management.

The role of sustained observations in tracking impacts of environmental change on marine biodiversity and ecosystems

PubMed Central

Mieszkowska, N.; Sugden, H.; Firth, L. B.; Hawkins, S. J.

2014-01-01

Marine biodiversity currently faces unprecedented threats from multiple pressures arising from human activities. Global drivers such as climate change and ocean acidification interact with regional eutrophication, exploitation of commercial fish stocks and localized pressures including pollution, coastal development and the extraction of aggregates and fuel, causing alteration and degradation of habitats and communities. Segregating natural from anthropogenically induced change in marine ecosystems requires long-term, sustained observations of marine biota. In this review, we outline the history of biological recording in the coastal and shelf seas of the UK and Ireland and highlight where sustained observations have contributed new understanding of how anthropogenic activities have impacted on marine biodiversity. The contributions of sustained observations, from those collected at observatories, single station platforms and multiple-site programmes to the emergent field of multiple stressor impacts research, are discussed, along with implications for management and sustainable governance of marine resources in an era of unprecedented use of the marine environment. PMID:25157190

Markers of sympathetic nervous system activity associate with complex plasma lipids in metabolic syndrome subjects.

PubMed

Nestel, Paul J; Khan, Anmar A; Straznicky, Nora E; Mellett, Natalie A; Jayawardana, Kaushala; Mundra, Piyushkumar A; Lambert, Gavin W; Meikle, Peter J

2017-01-01

Plasma sphingolipids including ceramides, and gangliosides are associated with insulin resistance (IR) through effects on insulin signalling and glucose metabolism. Our studies of subjects with metabolic syndrome (MetS) showed close relationships between IR and sympathetic nervous system (SNS) activity including arterial norepinephrine (NE). We have therefore investigated possible associations of IR and SNS activity with complex lipids that are involved in both insulin sensitivity and neurotransmission. We performed a cross-sectional assessment of 23 lipid classes/subclasses (total 339 lipid species) by tandem mass spectrometry in 94 overweight untreated subjects with IR (quantified by HOMA-IR, Matsuda index and plasma insulin). Independently of IR parameters, several circulating complex lipids associated significantly with arterial NE and NEFA (non-esterified fatty acids) and marginally with heart rate (HR). After accounting for BMI, HOMA-IR, systolic BP, age, gender, and correction for multiple comparisons, these associations were significant (p < 0.05): NE with ceramide, phosphatidylcholine, alkyl- and alkenylphosphatidylcholine and free cholesterol; NEFA with mono- di- and trihexosylceramide, G M3 ganglioside, sphingomyelin, phosphatidylcholine, alkyl- and alkenylphosphatidylcholine, phosphatidylinositol and free cholesterol; HR marginally (p = or <0.1>0.05) with ceramide, G M3 ganglioside, sphingomyelin, lysophosphatidylcholine, phosphatidylinositol, lysophosphatidylinositol and free cholesterol. Multiple subspecies of these lipids significantly associated with NE and NEFA. None of the IR biomarkers associated significantly with lipid classes/subclasses after correction for multiple comparisons. This is the first demonstration that arterial norepinephrine and NEFA, that reflect both SNS activity and IR, associate significantly with circulating complex lipids independently of IR, suggesting a role for such lipids in neural mechanisms operating in MetS. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Consistent radiative transfer modeling of active and passive observations of precipitation

NASA Astrophysics Data System (ADS)

Adams, Ian

2016-04-01

Spaceborne platforms such as the Tropical Rainfall Measurement Mission (TRMM) and the Global Precipitation Measurement (GPM) mission exploit a combination of active and passive sensors to provide a greater understanding of the three-dimensional structure of precipitation. While "operationalized" retrieval algorithms require fast forward models, the ability to perform higher fidelity simulations is necessary in order to understand the physics of remote sensing problems by testing assumptions and developing parameterizations for the fast models. To ensure proper synergy between active and passive modeling, forward models must be consistent when modeling the responses of radars and radiometers. This work presents a self-consistent transfer model for simulating radar reflectivities and millimeter wave brightness temperatures for precipitating scenes. To accomplish this, we extended the Atmospheric Radiative Transfer Simulator (ARTS) version 2.3 to solve the radiative transfer equation for active sensors and multiple scattering conditions. Early versions of ARTS (1.1) included a passive Monte Carlo solver, and ARTS is capable of handling atmospheres of up to three dimensions with ellipsoidal planetary geometries. The modular nature of ARTS facilitates extensibility, and the well-developed ray-tracing tools are suited for implementation of Monte Carlo algorithms. Finally, since ARTS handles the full Stokes vector, co- and cross-polarized reflectivity products are possible for scenarios that include nonspherical particles, with or without preferential alignment. The accuracy of the forward model will be demonstrated with precipitation events observed by TRMM and GPM, and the effects of multiple scattering will be detailed. The three-dimensional nature of the radiative transfer model will be useful for understanding the effects of nonuniform beamfill and multiple scattering for spatially heterogeneous precipitation events. The targets of this forward model are GPM (the Dual-wavelength Precipitation Radar (DPR) and GPM Microwave Imager (GMI)).

Extracellular cyclophilin-A stimulates ERK1/2 phosphorylation in a cell-dependent manner but broadly stimulates nuclear factor kappa B

PubMed Central

2012-01-01

Background Although the peptidyl-prolyl isomerase, cyclophilin-A (peptidyl-prolyl isomerase, PPIA), has been studied for decades in the context of its intracellular functions, its extracellular roles as a major contributor to both inflammation and multiple cancers have more recently emerged. A wide range of activities have been ascribed to extracellular PPIA that include induction of cytokine and matrix metalloproteinase (MMP) secretion, which potentially underlie its roles in inflammation and tumorigenesis. However, there have been conflicting reports as to which particular signaling events are under extracellular PPIA regulation, which may be due to either cell-dependent responses and/or the use of commercial preparations recently shown to be highly impure. Methods We have produced and validated the purity of recombinant PPIA in order to subject it to a comparative analysis between different cell types. Specifically, we have used a combination of multiple methods such as luciferase reporter screens, translocation assays, phosphorylation assays, and nuclear magnetic resonance to compare extracellular PPIA activities in several different cell lines that included epithelial and monocytic cells. Results Our findings have revealed that extracellular PPIA activity is cell type-dependent and that PPIA signals via multiple cellular receptors beyond the single transmembrane receptor previously identified, Extracellular Matrix MetalloPRoteinase Inducer (EMMPRIN). Finally, while our studies provide important insight into the cell-specific responses, they also indicate that there are consistent responses such as nuclear factor kappa B (NFκB) signaling induced in all cell lines tested. Conclusions We conclude that although extracellular PPIA activates several common pathways, it also targets different receptors in different cell types, resulting in a complex, integrated signaling network that is cell type-specific. PMID:22631225

Combined exposure of Japanese quails to cyanotoxins, Newcastle virus and lead: oxidative stress responses.

PubMed

Paskova, Veronika; Veronika, Paskova; Paskerova, Hana; Hana, Paskerova; Pikula, Jiri; Jiri, Pikula; Bandouchova, Hana; Hana, Bandouchova; Sedlackova, Jana; Jana, Sedlackova; Hilscherova, Klara; Klara, Hilscherova

2011-10-01

Wild birds are continually exposed to many anthropogenic and natural stressors in their habitats. Over the last decades, mass mortalities of wild birds constitute a serious problem and may possibly have more causations such as natural toxins including cyanotoxins, parasitic diseases, industrial chemicals and other anthropogenic contaminants. This study brings new knowledge on the effects of controlled exposure to multiple stressors in birds. The aim was to test the hypothesis that influence of cyanobacterial biomass, lead and antigenic load may combine to enhance the effects on birds, including modulation of antioxidative and detoxification responses. Eight treatment groups of model species Japanese quail (Coturnix coturnix japonica) were exposed to various combinations of these stressors. The parameters of detoxification and oxidative stress were studied in liver and heart after 30 days of exposure. The antioxidative enzymatic defense in birds seems to be activated quite efficiently, which was documented by the elevated levels and activities of antioxidative and detoxification compounds and by the low incidence of damage to lipid membranes. The greatest modulations of glutathione level and activities of glutathione-S-transferase, glutathione peroxidase, glutathione reductase, superoxide dismutase, catalase and lipid peroxidation were shown mostly in the groups with combined multiple exposures. The results indicate that the antioxidative system plays an important role in the protective response of the tissues to applied stressors and that its greater induction helps to protect the birds from more serious damage. Most significant changes of these "defense" parameters in case of multiple stressors suggest activation of this universal mechanism in situation with complex exposure and its crucial role in protection of the bird health in the environment. Copyright © 2011 Elsevier Inc. All rights reserved.

Lead Adsorption into Activated Carbon: A Critical Review of the Literature

EPA Science Inventory

Lead has been widely used in many industries due to its desirable chemical and physical properties such as its malleability and resistance to corrosion. However, Lead poisoning is a serious health hazard that causes severe damage to multiple target organs including kidney, liver,...

Multiple imaging mode X-ray computed tomography for distinguishing active and inactive phases in lithium-ion battery cathodes

NASA Astrophysics Data System (ADS)

Komini Babu, Siddharth; Mohamed, Alexander I.; Whitacre, Jay F.; Litster, Shawn

2015-06-01

This paper presents the use of nanometer scale resolution X-ray computed tomography (nano-CT) in the three-dimensional (3D) imaging of a Li-ion battery cathode, including the separate volumes of active material, binder plus conductive additive, and pore. The different high and low atomic number (Z) materials are distinguished by sequentially imaging the lithium cobalt oxide electrode in absorption and then Zernike phase contrast modes. Morphological parameters of the active material and the additives are extracted from the 3D reconstructions, including the distribution of contact areas between the additives and the active material. This method could provide a better understanding of the electric current distribution and structural integrity of battery electrodes, as well as provide detailed geometries for computational models.

Violence and unsafe sexual practices in adolescents under 15 years of age.

PubMed

Teixeira, Sérgio Araujo Martins; Taquette, Stella Regina

2010-01-01

To identify factors associated with unprotected sexual activity in females under the age of 15 years. Cross-sectional observational study of sexually active adolescents under the age of 15 seen at a public outpatient gynecology clinic. Data were collected by means of semi-structured interviews (personal information and data on sexuality), clinical examination, and laboratory tests for diagnosis of sexually transmitted infections. Data were analyzed by frequency testing, association of variables (with p <0.05) and multiple correspondence analysis. One hundred sexually active adolescents between the ages of 11 and 14 were interviewed and examined. Of these, 71% declared themselves black; one-third were behind in school; 80% began sexual activity before the age of 13; 58% reported having been victims of violence within the family environment, and 13% had suffered sexual abuse; 77% did not use condoms regularly; and 22% had STIs. Unprotected sexual activity was more frequent with first sexual intercourse before the age of 13, commercial sexual exploitation, multiple sexual partners, intrafamily violence and school delay, as well as black race, unexpected pregnancy, and STIs. The multiple types of violence suffered by teenagers, including structural, intrafamily, and sexual violence, increase their vulnerability to early, unprotected sexual activity and to STIs and unexpected pregnancy. The synergistic effects of poverty, low educational achievement, and low self-esteem reduces the odds that adolescents will build the tools required for self-protection and exposes them to further victimization outside the family environment.

Discovery of cofactor-specific, bactericidal Mycobacterium tuberculosis InhA inhibitors using DNA-encoded library technology.

PubMed

Soutter, Holly H; Centrella, Paolo; Clark, Matthew A; Cuozzo, John W; Dumelin, Christoph E; Guie, Marie-Aude; Habeshian, Sevan; Keefe, Anthony D; Kennedy, Kaitlyn M; Sigel, Eric A; Troast, Dawn M; Zhang, Ying; Ferguson, Andrew D; Davies, Gareth; Stead, Eleanor R; Breed, Jason; Madhavapeddi, Prashanti; Read, Jon A

2016-12-06

Millions of individuals are infected with and die from tuberculosis (TB) each year, and multidrug-resistant (MDR) strains of TB are increasingly prevalent. As such, there is an urgent need to identify novel drugs to treat TB infections. Current frontline therapies include the drug isoniazid, which inhibits the essential NADH-dependent enoyl-acyl-carrier protein (ACP) reductase, InhA. To inhibit InhA, isoniazid must be activated by the catalase-peroxidase KatG. Isoniazid resistance is linked primarily to mutations in the katG gene. Discovery of InhA inhibitors that do not require KatG activation is crucial to combat MDR TB. Multiple discovery efforts have been made against InhA in recent years. Until recently, despite achieving high potency against the enzyme, these efforts have been thwarted by lack of cellular activity. We describe here the use of DNA-encoded X-Chem (DEX) screening, combined with selection of appropriate physical properties, to identify multiple classes of InhA inhibitors with cell-based activity. The utilization of DEX screening allowed the interrogation of very large compound libraries (10 11 unique small molecules) against multiple forms of the InhA enzyme in a multiplexed format. Comparison of the enriched library members across various screening conditions allowed the identification of cofactor-specific inhibitors of InhA that do not require activation by KatG, many of which had bactericidal activity in cell-based assays.

Protein disulfide isomerase a multifunctional protein with multiple physiological roles

NASA Astrophysics Data System (ADS)

Ali Khan, Hyder; Mutus, Bulent

2014-08-01

Protein disulfide isomerase (PDI), is a member of the thioredoxin superfamily of redox proteins. PDI has three catalytic activities including, thiol-disulfide oxireductase, disulfide isomerase and redox-dependent chaperone. Originally, PDI was identified in the lumen of the endoplasmic reticulum and subsequently detected at additional locations, such as cell surfaces and the cytosol. This review will provide an overview of the recent advances in relating the structural features of PDI to its multiple catalytic roles as well as its physiological and pathophysiological functions related to redox regulation and protein folding.

Immunology and Oxidative Stress in Multiple Sclerosis: Clinical and Basic Approach

PubMed Central

Ortiz, Genaro G.; Pacheco-Moisés, Fermín P.; Bitzer-Quintero, Oscar K.; Ramírez-Anguiano, Ana C.; Flores-Alvarado, Luis J.; Ramírez-Ramírez, Viridiana; Macias-Islas, Miguel A.; Torres-Sánchez, Erandis D.

2013-01-01

Multiple sclerosis (MS) exhibits many of the hallmarks of an inflammatory autoimmune disorder including breakdown of the blood-brain barrier (BBB), the recruitment of lymphocytes, microglia, and macrophages to lesion sites, the presence of multiple lesions, generally being more pronounced in the brain stem and spinal cord, the predominantly perivascular location of lesions, the temporal maturation of lesions from inflammation through demyelination, to gliosis and partial remyelination, and the presence of immunoglobulin in the central nervous system and cerebrospinal fluid. Lymphocytes activated in the periphery infiltrate the central nervous system to trigger a local immune response that ultimately damages myelin and axons. Pro-inflammatory cytokines amplify the inflammatory cascade by compromising the BBB, recruiting immune cells from the periphery, and activating resident microglia. inflammation-associated oxidative burst in activated microglia and macrophages plays an important role in the demyelination and free radical-mediated tissue injury in the pathogenesis of MS. The inflammatory environment in demyelinating lesions leads to the generation of oxygen- and nitrogen-free radicals as well as proinflammatory cytokines which contribute to the development and progression of the disease. Inflammation can lead to oxidative stress and vice versa. Thus, oxidative stress and inflammation are involved in a self-perpetuating cycle. PMID:24174971

Software forecasting as it is really done: A study of JPL software engineers

NASA Technical Reports Server (NTRS)

Griesel, Martha Ann; Hihn, Jairus M.; Bruno, Kristin J.; Fouser, Thomas J.; Tausworthe, Robert C.

1993-01-01

This paper presents a summary of the results to date of a Jet Propulsion Laboratory internally funded research task to study the costing process and parameters used by internally recognized software cost estimating experts. Protocol Analysis and Markov process modeling were used to capture software engineer's forecasting mental models. While there is significant variation between the mental models that were studied, it was nevertheless possible to identify a core set of cost forecasting activities, and it was also found that the mental models cluster around three forecasting techniques. Further partitioning of the mental models revealed clustering of activities, that is very suggestive of a forecasting lifecycle. The different forecasting methods identified were based on the use of multiple-decomposition steps or multiple forecasting steps. The multiple forecasting steps involved either forecasting software size or an additional effort forecast. Virtually no subject used risk reduction steps in combination. The results of the analysis include: the identification of a core set of well defined costing activities, a proposed software forecasting life cycle, and the identification of several basic software forecasting mental models. The paper concludes with a discussion of the implications of the results for current individual and institutional practices.

A novel peptide with potent and broad-spectrum antiviral activities against multiple respiratory viruses

PubMed Central

Zhao, Hanjun; Zhou, Jie; Zhang, Ke; Chu, Hin; Liu, Dabin; Poon, Vincent Kwok-Man; Chan, Chris Chung-Sing; Leung, Ho-Chuen; Fai, Ng; Lin, Yong-Ping; Zhang, Anna Jin-Xia; Jin, Dong-Yan; Yuen, Kwok-Yung; Zheng, Bo-Jian

2016-01-01

A safe, potent and broad-spectrum antiviral is urgently needed to combat emerging respiratory viruses. In light of the broad antiviral activity of β-defensins, we tested the antiviral activity of 11 peptides derived from mouse β-defensin-4 and found that a short peptide, P9, exhibited potent and broad-spectrum antiviral effects against multiple respiratory viruses in vitro and in vivo, including influenza A virus H1N1, H3N2, H5N1, H7N7, H7N9, SARS-CoV and MERS-CoV. The antiviral activity of P9 was attributed to its high-affinity binding to viral glycoproteins, as well as the abundance of basic amino acids in its composition. After binding viral particles through viral surface glycoproteins, P9 entered into cells together with the viruses via endocytosis and prevented endosomal acidification, which blocked membrane fusion and subsequent viral RNA release. This study has paved the avenue for developing new prophylactic and therapeutic agents with broad-spectrum antiviral activities. PMID:26911565

Secreted CLCA1 modulates TMEM16A to activate Ca(2+)-dependent chloride currents in human cells.

PubMed

Sala-Rabanal, Monica; Yurtsever, Zeynep; Nichols, Colin G; Brett, Tom J

2015-03-17

Calcium-activated chloride channel regulator 1 (CLCA1) activates calcium-dependent chloride currents; neither the target, nor mechanism, is known. We demonstrate that secreted CLCA1 activates calcium-dependent chloride currents in HEK293T cells in a paracrine fashion, and endogenous TMEM16A/Anoctamin1 conducts the currents. Exposure to exogenous CLCA1 increases cell surface levels of TMEM16A and cellular binding experiments indicate CLCA1 engages TMEM16A on the surface of these cells. Altogether, our data suggest that CLCA1 stabilizes TMEM16A on the cell surface, thus increasing surface expression, which results in increased calcium-dependent chloride currents. Our results identify the first Cl(-) channel target of the CLCA family of proteins and establish CLCA1 as the first secreted direct modifier of TMEM16A activity, delineating a unique mechanism to increase currents. These results suggest cooperative roles for CLCA and TMEM16 proteins in influencing the physiology of multiple tissues, and the pathology of multiple diseases, including asthma, COPD, cystic fibrosis, and certain cancers.

The compartmentalized inflammatory response in the multiple sclerosis brain is composed of tissue-resident CD8+ T lymphocytes and B cells.

PubMed

Machado-Santos, Joana; Saji, Etsuji; Tröscher, Anna R; Paunovic, Manuela; Liblau, Roland; Gabriely, Galina; Bien, Christian G; Bauer, Jan; Lassmann, Hans

2018-06-04

Multiple sclerosis is an inflammatory demyelinating disease in which active demyelination and neurodegeneration are associated with lymphocyte infiltrates in the brain. However, so far little is known regarding the phenotype and function of these infiltrating lymphocyte populations. In this study, we performed an in-depth phenotypic characterization of T and B cell infiltrates in a large set of multiple sclerosis cases with different disease and lesion stages and compared the findings with those seen in inflammatory, non-inflammatory and normal human controls. In multiple sclerosis lesions, we found a dominance of CD8+ T cells and a prominent contribution of CD20+ B cells in all disease courses and lesion stages, including acute multiple sclerosis cases with very short disease duration, while CD4+ T cells were sparse. A dominance of CD8+ T cells was also seen in other inflammatory controls, such as Rasmussen's encephalitis and viral encephalitis, but the contribution of B cells in these diseases was modest. Phenotypic analysis of the CD8+ T cells suggested that part of the infiltrating cells in active lesions proliferate, show an activated cytotoxic phenotype and are in part destroyed by apoptosis. Further characterization of the remaining cells suggest that CD8+ T cells acquire features of tissue-resident memory cells, which may be focally reactivated in active lesions of acute, relapsing and progressive multiple sclerosis, while B cells, at least in part, gradually transform into plasma cells. The loss of surface molecules involved in the egress of leucocytes from inflamed tissue, such as S1P1 or CCR7, and the upregulation of CD103 expression may be responsible for the compartmentalization of the inflammatory response in established lesions. Similar phenotypic changes of tissue-infiltrating CD8+ T cells were also seen in Rasmussen's encephalitis. Our data underline the potential importance of CD8+ T lymphocytes and B cells in the inflammatory response in established multiple sclerosis lesions. Tissue-resident T and B cells may represent guardians of previous inflammatory brain disease, which can be reactivated and sustain the inflammatory response, when they are re-exposed to their specific antigen.

Everolimus improves neuropsychiatric symptoms in a patient with tuberous sclerosis carrying a novel TSC2 mutation.

PubMed

Hwang, Su-Kyeong; Lee, Jae-Hyung; Yang, Jung-Eun; Lim, Chae-Seok; Lee, Jin-A; Lee, Yong-Seok; Lee, Kyungmin; Kaang, Bong-Kiun

2016-05-23

Tuberous sclerosis complex (TSC) is a neurocutaneous disorder characterized by multiple symptoms including neuropsychological deficits such as seizures, intellectual disability, and autism. TSC is inherited in an autosomal dominant pattern and is caused by mutations in either the TSC1 or TSC2 genes, which enhance activation of the mammalian target of rapamycin (mTOR) signaling pathway. Recent studies have suggested that mTOR inhibitors such as rapamycin can reverse TSC-associated deficits in rodent models of TSC. In addition, clinical trials are ongoing to test the efficacy of mTOR inhibitors toward the psychiatric symptoms associated with TSC. Here, we report a case study of a Korean patient with TSC, who exhibited multiple symptoms including frequent seizures, intellectual disability, language delays, and social problems. We performed whole exome sequencing and identified a novel small deletion mutation in TSC2. Expressing the novel deletion mutant in HEK293T cells significantly increased mTOR pathway activation. Furthermore, everolimus treatment showed not only reduction in SEGA size, but dramatically improved behavioral deficits including autism related behaviors in the patient. In summary, we identified a novel small deletion mutation in TSC2 associated with severe TSC in a Korean family that enhances the activation of mTOR signaling in vitro. Everolimus treatment improved behavioral deficits in the patient.

Assessment of capacity-building activities for forest measurement, reporting, and verification, 2011–15

USGS Publications Warehouse

Peneva-Reed, Elitsa I.; Romijn, J. Erika

2018-05-31

This report was written as a collaborative effort between the U.S. Geological Survey, SilvaCarbon, and Wageningen University with funding provided by the U.S. Agency for International Development and the European Space Agency, respectively, to address a pressing need for enhanced result-based monitoring and evaluation of delivered capacity-building activities. For this report, the capacity-building activities delivered by capacity-building providers (referred to as “providers” hereafter) during 2011–15 (the study period) to support countries in building measurement, reporting, and verification (MRV) systems for reducing emissions from deforestation and forest degradation (REDD+) were assessed and evaluated.Summarizing capacity-building activities and outcomes across multiple providers was challenging. Many of the providers did not have information readily available, which precluded them from participating in this study despite the usefulness of their information. This issue led to a key proposed future action: Capacity-building providers could establish a central repository within the Global Forestry Observation Initiative (GFOI; http://www.gfoi.org/) where data from past, current, and future activities of all capacity-building providers could be stored. The repository could be maintained in a manner to continually learn from previous lessons.Although various providers monitored and evaluated the success of their capacity-building activities, such evaluations only assessed the success of immediate outcomes and not the overarching outcomes and impacts of activities implemented by multiple providers. Good monitoring and evaluation should continuously monitor and periodically evaluate all factors affecting the outcomes of a provided capacity-building activity.The absence of a methodology to produce quantitative evidence of a causal link between multiple capacity-building activities delivered and successful outcomes left only a plausible association. A previous publication argued that plausible association, although not a precise measurement of cause and effect, was a realistic tool. Our review of the available literature on this subject did not find another similar assessment to assess capacity-building activities for supporting the countries in building MRV system for REDD+.Four countries from the main forested regions of Africa, the Americas, and Asia were chosen as subjects for this report based on the length of time SilvaCarbon and other providers have provided capacity-building activities toward MRV system for REDD+: Colombia (the Americas), the Democratic Republic of the Congo (DRC; Africa), Peru (the Americas), and the Republic of the Philippines (referred to as “the Philippines” hereafter; Asia).Several providers were contacted for information to include in this report, but, because of various constraints, only SilvaCarbon, the Food and Agriculture Organization of the United Nations (FAO), and the World Wildlife Fund (WWF) participated in this study. These three providers supported various targeted capacity-building activities through-out Africa, the Americas, and Asia, including the following: technical workshops at national and regional levels (referred to as “workshops” hereafter), hands on training, study tours, technical details by experts, technical consultation between providers and recipients, sponsorship for travel, organizing network meetings, developing sampling protocols, assessing deforestation and degradation drivers, estimating carbon stock and flow, designing monitoring systems for multiple uses, promoting public-private partnerships to scale up investments on MRV system for REDD+, and assisting with the design of national forest monitoring systems.Their activities were planned in coordination with key partners in each country and region and with the support and assistance of other providers. Note that several other organizations and institutions assisted the providers to deliver capacity-building activities, including Boston University, Conservation International, Stanford University, University of Maryland, and Wageningen University & Research.

AgMIP Training in Multiple Crop Models and Tools

NASA Technical Reports Server (NTRS)

Boote, Kenneth J.; Porter, Cheryl H.; Hargreaves, John; Hoogenboom, Gerrit; Thornburn, Peter; Mutter, Carolyn

2015-01-01

The Agricultural Model Intercomparison and Improvement Project (AgMIP) has the goal of using multiple crop models to evaluate climate impacts on agricultural production and food security in developed and developing countries. There are several major limitations that must be overcome to achieve this goal, including the need to train AgMIP regional research team (RRT) crop modelers to use models other than the ones they are currently familiar with, plus the need to harmonize and interconvert the disparate input file formats used for the various models. Two activities were followed to address these shortcomings among AgMIP RRTs to enable them to use multiple models to evaluate climate impacts on crop production and food security. We designed and conducted courses in which participants trained on two different sets of crop models, with emphasis on the model of least experience. In a second activity, the AgMIP IT group created templates for inputting data on soils, management, weather, and crops into AgMIP harmonized databases, and developed translation tools for converting the harmonized data into files that are ready for multiple crop model simulations. The strategies for creating and conducting the multi-model course and developing entry and translation tools are reviewed in this chapter.

40 CFR 63.10010 - What are my monitoring, installation, operation, and maintenance requirements?

Code of Federal Regulations, 2013 CFR

2013-07-01

... that emissions are controlled with a common control device or series of control devices, are discharged... parallel control devices or multiple series of control devices are discharged to the atmosphere through... quality control activities (including, as applicable, calibration checks and required zero and span...

40 CFR 63.10010 - What are my monitoring, installation, operation, and maintenance requirements?

Code of Federal Regulations, 2014 CFR

2014-07-01

... that emissions are controlled with a common control device or series of control devices, are discharged... parallel control devices or multiple series of control devices are discharged to the atmosphere through... quality control activities (including, as applicable, calibration checks and required zero and span...

Investigation of Macrophage Differentiation and Cytokine Production in an Undergraduate Immunology Laboratory

ERIC Educational Resources Information Center

Berkes, Charlotte; Chan, Leo Li-Ying

2015-01-01

We have developed a semester-long laboratory project for an undergraduate immunology course in which students study multiple aspects of macrophage biology including differentiation from progenitors in the bone marrow, activation upon stimulation with microbial ligands, expression of cell surface markers, and modulation of cytokine production. In…

Changes in channel morphology over human time scales [Chapter 32

Treesearch

John M. Buffington

2012-01-01

Rivers are exposed to changing environmental conditions over multiple spatial and temporal scales, with the imposed environmental conditions and response potential of the river modulated to varying degrees by human activity and our exploitation of natural resources. Watershed features that control river morphology include topography (valley slope and channel...

Enhancing Communication by Means of a Virtual Learning Community.

ERIC Educational Resources Information Center

Verkler, Karen; Hutchinson, Cynthia J.

1999-01-01

Explains how faculty at a college of education are creating a virtual learning community among faculty, adjuncts, and graduate assistants teaching multiple sections of the same course. Discusses goals of the Web site that include consistency in course material and content delivery; incorporating resources and activities; and improving…

Cultural and Social Factors Affecting Women's Physical Activity Participation in Taiwan

ERIC Educational Resources Information Center

Yu, Chia-Chen; Liaw, Yin-Hua; Barnd, Susan

2004-01-01

The world is becoming a global village and within many professions, including physical education and sport, individuals have multiple opportunities to work and socialize with people from different ethnic backgrounds, cultures, lifestyles, religions, etc. Due to the increasing cultural diversity, it is important for physical education and sport…

"Woman Hollering Creek" a Traves de la Musica: Articulating Mexicanidad to Pochismo

ERIC Educational Resources Information Center

French, Lydia A.

2011-01-01

This essay intervenes in contemporary scholarship on Sandra Cisneros's "Woman Hollering Creek" (1991) by examining the canciones she uses as epigraphs and their relationship to the multiple nationalisms that Chicana/os actively negotiate. I argue that Cisneros's decision to include powerfully nationalist Mexican cancion traditions…

Graduate Student Perceptions and Experiences of Professional Development Activities

ERIC Educational Resources Information Center

Rizzolo, Sonja; DeForest, Aubreena R.; DeCino, Daniel A.; Strear, Molly; Landram, Suzanne

2016-01-01

Graduate higher education has done little to assess and understand graduate students' needs and experiences beyond the classroom. Therefore, we conducted a phenomenological study using multiple data collection tools, including survey and focus groups from two different time periods to implement a multiphase needs assessment. The goal of the…

Rainbows of Intelligence. Exploring How Students Learn.

ERIC Educational Resources Information Center

Teele, Sue

This book offers practical applications for exploring multiple intelligences in the classroom to help each student express his or her own personal learning rainbow. Special features of the book include seven complete lesson plans ready to be adapted to any grade level; objectives, activities, and applications that meet U.S. and California…

Middle School Physical Education Teachers' Perspectives on Overweight Students

ERIC Educational Resources Information Center

Doolittle, Sarah A.; Rukavina, Paul B.; Li, Weidong; Manson, Mara; Beale, Angela

2016-01-01

Using the Social Ecological Constraints model, a qualitative multiple case study design was used to explore experienced and committed middle school physical education teachers' perspectives on overweight and obese students (OWS), and how and why they acted to include OWS in physical education and physical activity opportunities in their school…

Effect of new auxin herbicide formulations on control of herbicide resistant weeds and on microbial activities in the rhizosphere

USDA-ARS?s Scientific Manuscript database

Widespread distribution of glyphosate-resistant weeds in soybean-growing areas across Mississippi has economically affected soybean planting and follow-up crop management operations. New multiple herbicide-resistant crop (including soybean) technologies with associated formulations will soon be comm...

Multiple species inventory and monitoring technical guide

Treesearch

P.N. Manley; B. Van Horne; J.K. Roth; W.J. Zielinski; M.M. McKenzie; T.J. Weller; F.W. Weckerly; C. Vojta

2006-01-01

The National Forest Management Act (1976) recognizes the importance of maintaining species and community diversity on National Forest System (NFS) lands as a critical component of our ecological and cultural heritage. Monitoring is required of land management to assess the success of management activities in meeting legal, regulatory, and policy objectives, including...

Elevating the Importance of Teaching. National Project III. Final Report.

ERIC Educational Resources Information Center

Owens, Richard E.

An in-depth study was conducted of instructional improvement activities at Kansas State University, including a student evaluation instrument of teacher performance, called Instructional Development and Effectiveness Assessment (IDEA). Faculty reactions to the total evaluation system, the use of results for multiple purposes, and the current…

Web-Based Inquiry Learning: Facilitating Thoughtful Literacy with WebQuests

ERIC Educational Resources Information Center

Ikpeze, Chinwe H.; Boyd, Fenice B.

2007-01-01

An action research study investigated how the multiple tasks found in WebQuests facilitate fifth-grade students' literacy skills and higher order thinking. Findings indicate that WebQuests are most successful when activities are carefully selected and systematically delivered. Implications for teaching include the necessity for adequate planning,…

Discovering Nature: The Benefits of Teaching Outside of the Classroom

ERIC Educational Resources Information Center

Jacobi-Vessels, Jill L.

2013-01-01

Nature play can be an effective teaching strategy across the curriculum and may provide children and teachers with lasting memories. Research shows that experiences in natural settings provide multiple benefits to young children, including increased physical activity, reduced obesity, improved concentration, and enhanced social skills. Early…

PARTIAL LEAST SQUARE ANALYSES FOR ASSOCIATION OF LANDSCAPE METRICS WITH WATER BIOLOGICAL AND CHEMICAL PROPERTIES IN THE SAVANNAH RIVER BASIN

EPA Science Inventory

Surface water quality is related to conditions in the surrounding geophysical environment, including soils, landcover, and anthropogenic activities. A number of statistical methods may be used to analyze and explore relationships among variables. Single-, multiple- and multivaria...

The Application of Learning Theories in Community College Classrooms. UCLA Community College Bibliography

ERIC Educational Resources Information Center

Carducci, Rozana

2006-01-01

The references in this document provide an overview of empirical and conceptual scholarship on the application of learning theories in community college classrooms. Specific theories discussed in the citations include: active learning, cooperative learning, multiple intelligences, problem-based learning, and self-regulated learning. In addition to…

Contextualised Skill Acquisition Research: A New Framework to Study the Development of Sport Expertise

ERIC Educational Resources Information Center

Uehara, Luiz; Button, Chris; Falcous, Mark; Davids, Keith

2016-01-01

Background: Under the view of dynamical system theory, expertise in sports emerges from the interaction of multiple constraints. At an individual level, important interactions amongst constraints could include the relationships that evolve between one's family, playmates/coaches, and specific training activities. Or more broadly, other…

Active Games: An Approach to Teaching Mathematical Skills to the Educable Mentally Retarded

ERIC Educational Resources Information Center

Taylor, George R.; Watkins, Susan T.

1974-01-01

Several games involving both motor behavior and practice with mathematical skills are described. These include adaptations of musical chairs (subtraction), call ball (multiplication), and ring toss (linear measurement); other games are designed to provide practice on identifying numerals, telling time, using money, and naming fractions. (SD)

Cleavage/alteration of interleukin-8 by matrix metalloproteinase-9 in the female lower genital tract.

PubMed

Zariffard, M Reza; Anastos, Kathryn; French, Audrey L; Munyazesa, Elisaphane; Cohen, Mardge; Landay, Alan L; Spear, Gregory T

2015-01-01

Interleukin-8 (IL-8, CXCL8) plays important roles in immune responses at mucosal sites including in the lower genital tract. Since several types of bacteria produce proteases that cleave IL-8 and many types of bacteria can be present in lower genital tract microbiota, we assessed genital fluids for IL-8 cleavage/alteration. Genital fluids collected by lavage from 200 women (23 HIV-seronegative and 177 HIV-seropositive) were tested for IL-8 cleavage/alteration by ELISA. IL-8 cleaving/altering activity was observed in fluids from both HIV-positive (28%) and HIV-negative women (35%). There was no clear relationship between the activity and the types of bacteria present in the lower genital tract as determined by high-throughput sequencing of the 16S rRNA gene. Protease inhibitors specific for matrix metalloproteinases (MMPs) reduced the activity and a multiplex assay that detects both inactive and active MMPs showed the presence of multiple MMPs, including MMP-1, -3, -7, -8, -9, -10 and -12 in genital secretions from many of the women. The IL-8-cleaving/altering activity significantly correlated with active MMP-9 as well as with cleavage of a substrate that is acted on by several active MMPs. These studies show that multiple MMPs are present in the genital tract of women and strongly suggest that MMP-9 in genital secretions can cleave IL-8 at this mucosal site. These studies suggest that MMP-mediated cleavage of IL-8 can modulate inflammatory responses in the lower genital tract.

Investigation of Marine-Derived Fungal Diversity and Their Exploitable Biological Activities

PubMed Central

Hong, Joo-Hyun; Jang, Seokyoon; Heo, Young Mok; Min, Mihee; Lee, Hwanhwi; Lee, Young Min; Lee, Hanbyul; Kim, Jae-Jin

2015-01-01

Marine fungi are potential producers of bioactive compounds that may have pharmacological and medicinal applications. Fungi were cultured from marine brown algae and identified using multiple target genes to confirm phylogenetic placement. These target genes included the internal transcribed spacer (ITS), the nuclear large subunit (LSU), and the β-tubulin region. Various biological activities of marine-derived fungi were evaluated, including their antifungal, antioxidant and cellulolytic enzyme activities. As a result, a total of 50 fungi was isolated from the brown algae Sargassum sp. Among the 50 isolated fungi, Corollospora angusta was the dominant species in this study. The genus Arthrinium showed a relatively strong antifungal activity to all of the target plant pathogenic fungi. In particular, Arthrinium saccharicola KUC21221 showed high radical scavenging activity and the highest activities in terms of filter paper units (0.39 U/mL), endoglucanase activity (0.38 U/mL), and β-glucosidase activity (1.04 U/mL). PMID:26133554

Cell- and virus-mediated regulation of the barrier-to-autointegration factor's phosphorylation state controls its DNA binding, dimerization, subcellular localization, and antipoxviral activity.

PubMed

Jamin, Augusta; Wicklund, April; Wiebe, Matthew S

2014-05-01

Barrier-to-autointegration factor (BAF) is a DNA binding protein with multiple cellular functions, including the ability to act as a potent defense against vaccinia virus infection. This antiviral function involves BAF's ability to condense double-stranded DNA and subsequently prevent viral DNA replication. In recent years, it has become increasingly evident that dynamic phosphorylation involving the vaccinia virus B1 kinase and cellular enzymes is likely a key regulator of multiple BAF functions; however, the precise mechanisms are poorly understood. Here we analyzed how phosphorylation impacts BAF's DNA binding, subcellular localization, dimerization, and antipoxviral activity through the characterization of BAF phosphomimetic and unphosphorylatable mutants. Our studies demonstrate that increased phosphorylation enhances BAF's mobilization from the nucleus to the cytosol, while dephosphorylation restricts BAF to the nucleus. Phosphorylation also impairs both BAF's dimerization and its DNA binding activity. Furthermore, our studies of BAF's antiviral activity revealed that hyperphosphorylated BAF is unable to suppress viral DNA replication or virus production. Interestingly, the unphosphorylatable BAF mutant, which is capable of binding DNA but localizes predominantly to the nucleus, was also incapable of suppressing viral replication. Thus, both DNA binding and localization are important determinants of BAF's antiviral function. Finally, our examination of how phosphatases are involved in regulating BAF revealed that PP2A dephosphorylates BAF during vaccinia infection, thus counterbalancing the activity of the B1 kinase. Altogether, these data demonstrate that phosphoregulation of BAF by viral and cellular enzymes modulates this protein at multiple molecular levels, thus determining its effectiveness as an antiviral factor and likely other functions as well. The barrier-to-autointegration factor (BAF) contributes to cellular genomic integrity in multiple ways, the best characterized of which are as a host defense against cytoplasmic DNA and as a regulator of mitotic nuclear reassembly. Although dynamic phosphorylation involving both viral and cellular enzymes is likely a key regulator of multiple BAF functions, the precise mechanisms involved are poorly understood. Here we demonstrate that phosphorylation coordinately regulates BAF's DNA binding, subcellular localization, dimerization, and antipoxviral activity. Overall, our findings provide new insights into how phosphoregulation of BAF modulates this protein at multiple levels and governs its effectiveness as an antiviral factor against foreign DNA.

Characteristics and correlates of coping with multiple sclerosis: a systematic review.

PubMed

Keramat Kar, Maryam; Whitehead, Lisa; Smith, Catherine M

2017-10-10

The purpose of this systematic review was to examine coping strategies that people with multiple sclerosis use, and to identify factors that influence their coping pattern. This systematic review followed the Joanna Briggs Institute guidelines for synthesizing descriptive quantitative research. The following databases were searched from the inception of databases until December 2016: Ovid (Medline, Embase, CINAHL, and PsycINFO), Science Direct, Web of Science, and Scopus. Manual search was also conducted from the reference lists of retrieved articles. Findings related to the patterns of coping with multiple sclerosis and factors influencing coping with multiple sclerosis were extracted and synthesized. The search of the database yielded 455 articles. After excluding duplicates (n = 341) and studies that did not meet the inclusion criteria (n = 27), 71 studies were included in the full-text review. Following the full-text, a further 21 studies were excluded. Quality appraisal of 50 studies was completed, and 38 studies were included in the review. Synthesis of findings indicated that people with multiple sclerosis use emotional and avoidance coping strategies more than other types of coping, particularly in the early stages of the disease. In comparison to the general population, people with multiple sclerosis were less likely to use active coping strategies and used more avoidance and emotional coping strategies. The pattern of coping with multiple sclerosis was associated with individual, clinical and psychological factors including gender, educational level, clinical course, mood and mental status, attitude, personality traits, and religious beliefs. The findings of this review suggest that considering individual or disease-related factors could help healthcare professionals in identifying those less likely to adapt to multiple sclerosis. This information could also be used to provide client-centered rehabilitation for people living with multiple sclerosis based on their individual responses and perceptions for coping. Implications for rehabilitation Engagement in coping with multiple sclerosis has been associated with individual factors and neuropsychological functions. Considering individual and disease-related factors would allow healthcare professionals to provide more tailored interventions to maintain and master coping with multiple sclerosis. People living with multiple sclerosis should be empowered to appraise and manage ability to cope based on the contextual evidence (individual and clinical condition). Rehabilitation services should move beyond physical management incorporating behavioral aspects for better functioning in living with multiple sclerosis.

Short-Range Temporal Interactions in Sleep; Hippocampal Spike Avalanches Support a Large Milieu of Sequential Activity Including Replay

PubMed Central

Mahoney, J. Matthew; Titiz, Ali S.; Hernan, Amanda E.; Scott, Rod C.

2016-01-01

Hippocampal neural systems consolidate multiple complex behaviors into memory. However, the temporal structure of neural firing supporting complex memory consolidation is unknown. Replay of hippocampal place cells during sleep supports the view that a simple repetitive behavior modifies sleep firing dynamics, but does not explain how multiple episodes could be integrated into associative networks for recollection during future cognition. Here we decode sequential firing structure within spike avalanches of all pyramidal cells recorded in sleeping rats after running in a circular track. We find that short sequences that combine into multiple long sequences capture the majority of the sequential structure during sleep, including replay of hippocampal place cells. The ensemble, however, is not optimized for maximally producing the behavior-enriched episode. Thus behavioral programming of sequential correlations occurs at the level of short-range interactions, not whole behavioral sequences and these short sequences are assembled into a large and complex milieu that could support complex memory consolidation. PMID:26866597

Multiple access techniques and spectrum utilization of the GLOBALSTAR mobile satellite system

NASA Astrophysics Data System (ADS)

Louie, Ming; Cohen, Michel; Rouffet, Denis; Gilhousen, Klein S.

The GLOBALSTAR System is a Low Earth Orbit (LEO) satellite-based mobile communications system that is interoperable with the current and future Public Land Mobile Network (PLMN). The GLOBALSTAR System concept is based upon technological advancement in two key areas: (1) the advancement in LEO satellite technology; (2) the advancement in cellular telephone technology, including the commercial applications of Code Division Multiple Access (CDMA) technologies, and of the most recent progress in Time Division Multiple Access technologies. The GLOBALSTAR System uses elements of CDMA, Frequency Division Multiple Access (FDMA), and Time Division Multiple Access (TDMA) technology, combining with satellite Multiple Beam Antenna (MBA) technology, to arrive at one of the most efficient modulation and multiple access system ever proposed for a satellite communications system. The technology used in GLOBALSTAR exploits the following techniques in obtaining high spectral efficiency and affordable cost per channel, with minimum coordination among different systems: power control, in open and closed loops, voice activation, spot beam satellite antenna for frequency reuse, weighted satellite antenna gain, multiple satellite coverage, and handoff between satellites. The GLOBALSTAR system design will use the following frequency bands: 1610-1626.5 MHz for up-link and 2483.5-2500 MHz for down-link.

Acyl-CoA:cholesterol acyltransferases (ACATs/SOATs): Enzymes with multiple sterols as substrates and as activators.

PubMed

Rogers, Maximillian A; Liu, Jay; Song, Bao-Liang; Li, Bo-Liang; Chang, Catherine C Y; Chang, Ta-Yuan

2015-07-01

Cholesterol is essential to the growth and viability of cells. The metabolites of cholesterol include: steroids, oxysterols, and bile acids, all of which play important physiological functions. Cholesterol and its metabolites have been implicated in the pathogenesis of multiple human diseases, including: atherosclerosis, cancer, neurodegenerative diseases, and diabetes. Thus, understanding how cells maintain the homeostasis of cholesterol and its metabolites is an important area of study. Acyl-coenzyme A:cholesterol acyltransferases (ACATs, also abbreviated as SOATs) converts cholesterol to cholesteryl esters and play key roles in the regulation of cellular cholesterol homeostasis. ACATs are most unusual enzymes because (i) they metabolize diverse substrates including both sterols and certain steroids; (ii) they contain two different binding sites for steroidal molecules. In mammals, there are two ACAT genes that encode two different enzymes, ACAT1 and ACAT2. Both are allosteric enzymes that can be activated by a variety of sterols. In addition to cholesterol, other sterols that possess the 3-beta OH at C-3, including PREG, oxysterols (such as 24(S)-hydroxycholesterol and 27-hydroxycholesterol, etc.), and various plant sterols, could all be ACAT substrates. All sterols that possess the iso-octyl side chain including cholesterol, oxysterols, various plant sterols could all be activators of ACAT. PREG can only be an ACAT substrate because it lacks the iso-octyl side chain required to be an ACAT activator. The unnatural cholesterol analogs epi-cholesterol (with 3-alpha OH in steroid ring B) and ent-cholesterol (the mirror image of cholesterol) contain the iso-octyl side chain but do not have the 3-beta OH at C-3. Thus, they can only serve as activators and cannot serve as substrates. Thus, within the ACAT holoenzyme, there are site(s) that bind sterol as substrate and site(s) that bind sterol as activator; these sites are distinct from each other. These features form the basis to further pursue ACAT structure-function analysis, and can be explored to develop novel allosteric ACAT inhibitors for therapeutic purposes. This article is part of a Special Issue entitled 'Steroid/Sterol signaling'. Copyright © 2014. Published by Elsevier Ltd.

Extracurricular Activities in Multiethnic Middle Schools: Ideal Context for Positive Intergroup Attitudes?

PubMed

Knifsend, Casey A; Juvonen, Jaana

2017-06-01

This study examined processes by which extracurricular participation is linked with positive ethnic intergroup attitudes in multiethnic middle schools in California. Specifically, the mediating roles of activity-related cross-ethnic friendships and social identities including alliances with multiple groups were examined in a sample including African American or Black, East or South-East Asian, White, and Latino youth (N = 1,446; M age  = 11.60 in sixth grade). Results of multilevel modeling suggested that in addition to activity-related cross-ethnic friendships, complex social identities mediated the association between availability of cross-ethnic peers in activities and ethnic intergroup attitudes. Results are discussed in terms of how activities can be structured to promote cross-ethnic relationships and complex social identities, as well as positive ethnic intergroup attitudes. © 2016 The Authors. Journal of Research on Adolescence © 2016 Society for Research on Adolescence.

Coordination of receptor signaling in multiple hematopoietic cell lineages by the adaptor protein SLP-76.

PubMed

Jordan, Martha S; Koretzky, Gary A

2010-04-01

The adaptor protein SLP-76 is expressed in multiple hematopoietic lineages including T cells, platelets, and neutrophils. SLP-76 mediated signaling is dependent on its multiple protein interaction domains, as it creates a scaffold on which key signaling complexes are built. SLP-76 is critical for supporting signaling downstream of both immunoreceptors and integrins. The signaling molecules used both upstream and downstream of SLP-76 are similar among these receptors and across cell types; however, important differences exist. Appreciating how SLP-76 coordinates signal transduction across different cell and receptor types provides insights into the complex interplay of pathways critical for activation of cells of the immune system that are essential for host defense.

Advancements in Nanomedicine for Multiple Myeloma.

PubMed

Detappe, Alexandre; Bustoros, Mark; Mouhieddine, Tarek H; Ghoroghchian, P Peter

2018-06-01

In the past decades, considerable progress has been made in our understanding and treatment of multiple myeloma. Several challenges remain including our abilities to longitudinally image tumor responses to treatment, to combine various therapeutic agents with different mechanisms of action but with overlapping toxicities, and to efficiently harness the power of the immune system to augment remission and/or to induce permanent cures. Nanomedicine may help to address many of these outstanding issues, affording novel diagnostic capabilities and offering disruptive technologies that promise to revolutionize treatment. Here, we review recent developments and the future of nanomedicine for multiple myeloma, highlighting new considerations in nanoparticle designs that may help to augment active targeting, to facilitate longitudinal imaging, and to improve drug delivery. Copyright © 2018 Elsevier Ltd. All rights reserved.

Children's organized physical activity patterns from childhood into adolescence.

PubMed

Findlay, Leanne C; Garner, Rochelle E; Kohen, Dafna E

2009-11-01

Few longitudinal studies of physical activity have included young children or used nationally representative datasets. The purpose of the current study was to explore patterns of organized physical activity for Canadian children aged 4 through 17 years. Data from 5 cycles of the National Longitudinal Survey of Children and Youth were analyzed separately for boys (n = 4463) and girls (n = 4354) using multiple trajectory modeling. Boys' and girls' organized physical activity was best represented by 3 trajectory groups. For boys, these groups were labeled: high stable, high decreasing, and low decreasing participation. For girls, these groups were labeled: high decreasing, moderate stable, and low decreasing participation. Risk factors (parental education, household income, urban/rural dwelling, and single/dual parent) were explored. For boys and girls, having a parent with postsecondary education and living in a higher income household were associated with a greater likelihood of weekly participation in organized physical activity. Living in an urban area was also significantly associated with a greater likelihood of weekly participation for girls. Results suggest that Canadian children's organized physical activity is best represented by multiple patterns of participation that tend to peak in middle childhood and decline into adolescence.

Broad-spectrum agents for flaviviral infections: dengue, Zika and beyond.

PubMed

Boldescu, Veaceslav; Behnam, Mira A M; Vasilakis, Nikos; Klein, Christian D

2017-08-01

Infections with flaviviruses, such as dengue, West Nile virus and the recently re-emerging Zika virus, are an increasing and probably lasting global risk. This Review summarizes and comments on the opportunities for broad-spectrum agents that are active against multiple flaviviruses. Broad-spectrum activity is particularly desirable to prepare for the next flaviviral epidemic, which could emerge from as-yet unknown or neglected viruses. Potential molecular targets for broad-spectrum antiflaviviral compounds include viral proteins, such as the viral protease or polymerase, and host targets that are exploited by these viruses during entry and replication, including α-glucosidase and proteins involved in nucleoside biosynthesis. Numerous compounds with broad-spectrum antiviral activity have already been identified by target-specific or phenotypic assays. For other compounds, broad-spectrum activity can be anticipated because of their mode of action and molecular targets.

Individual Differences in Diabetes Risk: Role of Sleep Disturbances

DTIC Science & Technology

2010-08-01

and have been shown by multiple groups, including us, to be affected by sleep deprivation. So far, we have indeed measured levels of leptin and ghrelin ...for leptin and ghrelin . The new procedure described below will cut these cost by 75%. This technology will also increase the scientific output of the...the manufacturer a custom supplied panel of assays that includes insulin, pancreatic polypeptide (PP), leptin, active ghrelin , as well as the two

[Bone structure in rheumatoid arthritis].

PubMed

Ono, Kumiko; Ohashi, Satoru; Tanaka, Sakae; Matsumoto, Takuya

2013-07-01

In rheumatoid arthritis (RA) , the osteoclast pathway is activated by abnormal immune conditions accompanied by chronic inflammation, resulting in periarticular osteoporosis and local bone destruction around joints. In addition, multiple factors, including reduced physical activity and pharmacotherapies such as steroids, lead to systemic osteoporosis. These conditions cause decreasing bone mineral density and deterioration of bone quality, and expose patients to increased risk of fracture. Understanding the bone structures of RA and evaluating fracture risk are central to the treatment of RA.

Activity matters: a web-based resource to enable people with multiple sclerosis to become more active.

PubMed

Casey, Blathin; Coote, Susan; Byrne, Molly

2018-03-27

Increasing physical activity (PA) through exercise is associated with improvements in many of the symptoms associated with multiple sclerosis (MS) such as fatigue, strength, balance, and mobility. Despite this, people with MS remain largely inactive. Interventions that are grounded in theory and that aim to change PA behavior need to be developed. The purpose of this study was to describe the development process of a web-based resource, namely, "Activity Matters," to enable people with MS to become more active. Development of the "Activity Matters" online intervention was guided by the UK's Medical Research Council (MRC) framework for the development and evaluation of complex interventions and the behavior change wheel (BCW). Seven sources of data were used to inform the process and were mapped on to both the MRC and BCW frameworks. The intervention is theoretically based, and constructs including knowledge, memory, attention and decision processes, skills, social influences, environmental context and resources, beliefs about capabilities, beliefs about consequences, goals, and emotions were recognized as important. "Activity Matters" is the first MS PA intervention to be developed using the theoretical approach outlined by the BCW and MRC complex interventions frameworks. The next phase of this work is to test the usability, acceptability, and preliminary effectiveness of "Activity Matters" among people with MS.

Accelerometry in persons with multiple sclerosis: measurement of physical activity or walking mobility?

PubMed

Weikert, Madeline; Motl, Robert W; Suh, Yoojin; McAuley, Edward; Wynn, Daniel

2010-03-15

Motion sensors such as accelerometers have been recognized as an ideal measure of physical activity in persons with MS. This study examined the hypothesis that accelerometer movement counts represent a measure of both physical activity and walking mobility in individuals with MS. The sample included 269 individuals with a definite diagnosis of relapsing-remitting MS who completed the Godin Leisure-Time Exercise Questionnaire (GLTEQ), International Physical Activity Questionnaire (IPAQ), Multiple Sclerosis Walking Scale-12 (MSWS-12), Patient Determined Disease Steps (PDDS), and then wore an ActiGraph accelerometer for 7days. The data were analyzed using bivariate correlation and confirmatory factor analysis. The results indicated that (a) the GLTEQ and IPAQ scores were strongly correlated and loaded significantly on a physical activity latent variable, (b) the MSWS-12 and PDDS scores strongly correlated and loaded significantly on a walking mobility latent variable, and (c) the accelerometer movement counts correlated similarly with the scores from the four self-report questionnaires and cross-loaded on both physical activity and walking mobility latent variables. Our data suggest that accelerometers are measuring both physical activity and walking mobility in persons with MS, whereas self-report instruments are measuring either physical activity or walking mobility in this population.

Molecular control of brain size: Regulators of neural stem cell life, death and beyond

DOE Office of Scientific and Technical Information (OSTI.GOV)

Joseph, Bertrand; Hermanson, Ola, E-mail: ola.hermanson@ki.se

2010-05-01

The proper development of the brain and other organs depends on multiple parameters, including strictly controlled expansion of specific progenitor pools. The regulation of such expansion events includes enzymatic activities that govern the correct number of specific cells to be generated via an orchestrated control of cell proliferation, cell cycle exit, differentiation, cell death etc. Certain proteins in turn exert direct control of these enzymatic activities and thus progenitor pool expansion and organ size. The members of the Cip/Kip family (p21Cip1/p27Kip1/p57Kip2) are well-known regulators of cell cycle exit that interact with and inhibit the activity of cyclin-CDK complexes, whereas membersmore » of the p53/p63/p73 family are traditionally associated with regulation of cell death. It has however become clear that the roles for these proteins are not as clear-cut as initially thought. In this review, we discuss the roles for proteins of the Cip/Kip and p53/p63/p73 families in the regulation of cell cycle control, differentiation, and death of neural stem cells. We suggest that these proteins act as molecular interfaces, or 'pilots', to assure the correct assembly of protein complexes with enzymatic activities at the right place at the right time, thereby regulating essential decisions in multiple cellular events.« less

RITA inhibits multiple myeloma cell growth through induction of p53-mediated caspase-dependent apoptosis and synergistically enhances nutlin-induced cytotoxic responses.

PubMed

Saha, Manujendra N; Jiang, Hua; Mukai, Asuka; Chang, Hong

2010-11-01

Mutations or deletions of p53 are relatively rare in multiple myeloma (MM), at least in newly diagnosed patients. Thus, restoration of p53 tumor suppressor function in MM by blocking the inhibitory role of murine double minute 2 (MDM2) is a promising and applicable therapeutic strategy. RITA and nutlin are two new classes of small molecule MDM2 inhibitors that prevent the p53-MDM2 interaction. Earlier reports showed p53-dependent activity of RITA in solid tumors as well as in leukemias. We and others recently described nutlin-induced apoptosis in MM cells, but it remains unclear whether RITA exerts antimyeloma activity. Here, we found that RITA activates the p53 pathway and induces apoptosis in MM cell lines and primary MM samples, preferentially killing myeloma cells. The activation of p53 induced by RITA was mediated through modulation of multiple apoptotic regulatory proteins, including upregulation of a proapoptotic protein (NOXA), downregulation of an antiapoptotic protein, Mcl-1, and activation of caspases through extrinsic pathways. Moreover, a number of key p53-mediated apoptotic target genes were identified by gene expression profiling and further validated by quantitative real-time PCR. Importantly, the combination of RITA with nutlin displayed a strong synergism on growth inhibition with the combination index ranging from 0.56 to 0.82 in MM cells. Our data support further clinical evaluation of RITA as a potential novel therapeutic intervention in MM. ©2010 AACR.

The interpretation of physical activity, exercise, and sedentary behaviours by persons with multiple sclerosis.

PubMed

Kinnett-Hopkins, Dominique; Learmonth, Yvonne; Hubbard, Elizabeth; Pilutti, Lara; Roberts, Sarah; Fanning, Jason; Wójcicki, Thomas; McAuley, Edward; Motl, Robert

2017-11-07

This study adopted a qualitative research design with directed content analysis and examined the interpretations of physical activity, exercise, and sedentary behaviour by persons with multiple sclerosis. Fifty three persons with multiple sclerosis who were enrolled in an exercise trial took part in semi-structured interviews regarding personal interpretations of physical activity, exercise, and sedentary behaviours. Forty three percent of participants indicated a consistent understanding of physical activity, 42% of participants indicated a consistent understanding of exercise, and 83% of participants indicated a consistent understanding of sedentary behaviour with the standard definitions. There was evidence of definitional ambiguity (i.e., 57, 58, and 11% of the sample for physical activity, exercise, and sedentary behaviour, respectively); 6% of the sample inconsistently defined sedentary behaviour with standard definitions. Some participants described physical activity in a manner that more closely aligned with exercise and confused sedentary behaviour with exercise or sleeping/napping. Results highlight the need to provide and utilise consistent definitions for accurate understanding, proper evaluation and communication of physical activity, exercise, and sedentary behaviours among persons with multiple sclerosis. The application of consistent definitions may minimise ambiguity, alleviate the equivocality of findings in the literature, and translate into improved communication about these behaviours in multiple sclerosis. Implications for Rehabilitation The symptoms of multiple sclerosis can be managed through participation in physical activity and exercise. Persons with multiple sclerosis are not engaging in sufficient levels of physical activity and exercise for health benefits. Rehabilitation professionals should use established definitions of physical activity, exercise, and sedentary behaviours when communicating about these behaviours among persons with multiple sclerosis.

Reassessment of Non-Monosynaptic Excitation from the Motor Cortex to Motoneurons in Single Motor Units of the Human Biceps Brachii

PubMed Central

Nakajima, Tsuyoshi; Tazoe, Toshiki; Sakamoto, Masanori; Endoh, Takashi; Shibuya, Satoshi; Elias, Leonardo A.; Mezzarane, Rinaldo A.; Komiyama, Tomoyoshi; Ohki, Yukari

2017-01-01

Corticospinal excitation is mediated by polysynaptic pathways in several vertebrates, including dexterous monkeys. However, indirect non-monosynaptic excitation has not been clearly observed following transcranial electrical stimulation (TES) or cervicomedullary stimulation (CMS) in humans. The present study evaluated indirect motor pathways in normal human subjects by recording the activities of single motor units (MUs) in the biceps brachii (BB) muscle. The pyramidal tract was stimulated with weak TES, CMS, and transcranial magnetic stimulation (TMS) contralateral to the recording side. During tasks involving weak co-contraction of the BB and hand muscles, all stimulation methods activated MUs with short latencies. Peristimulus time histograms (PSTHs) showed that responses with similar durations were induced by TES (1.9 ± 1.4 ms) and CMS (2.0 ± 1.4 ms), and these responses often showed multiple peaks with the PSTH peak having a long duration (65.3% and 44.9%, respectively). Such long-duration excitatory responses with multiple peaks were rarely observed in the finger muscles following TES or in the BB following stimulation of the Ia fibers. The responses obtained with TES were compared in the same 14 BB MUs during the co-contraction and isolated BB contraction tasks. Eleven and three units, respectively, exhibited activation with multiple peaks during the two tasks. In order to determine the dispersion effects on the axon conduction velocities (CVs) and synaptic noise, a simulation study that was comparable to the TES experiments was performed with a biologically plausible neuromuscular model. When the model included the monosynaptic-pyramidal tract, multiple peaks were obtained in about 34.5% of the motoneurons (MNs). The experimental and simulation results indicated the existence of task-dependent disparate inputs from the pyramidal tract to the MNs of the upper limb. These results suggested that intercalated interneurons are present in the spinal cord and that these interneurons might be equivalent to those identified in animal experiments. PMID:28194103

The Role of Airborne Proteins in Atopic Dermatitis

PubMed Central

Hostetler, Sarah Grim; Kaffenberger, Benjamin; Hostetler, Todd

2010-01-01

Atopic dermatitis is a common, chronic skin condition. A subpopulation of patients may have cutaneous exposure to common airborne proteins exacerbating their disease through direct proteolytic activity, direct activation of proteinase-activated receptor-2 itch receptors, and immunoglobulin E binding. The most common airborne proteins significant in atopic dermatitis include house dust mites, cockroach, pet dander, and multiple pollens. The literature on atopy patch testing, skin-prick testing, and specific IgE is mixed, with greater support for the use of atopy patch test. Patients with airborne proteins contributing to their disease typically have lesions predominately on air-exposed skin surfaces including the face, neck, and arms; a history of exacerbations after exposure to airborne proteins; severe disease resistant to conventional therapies; and concurrent asthma. Treatment strategies include airborne protein avoidance, removal of airborne proteins from the skin, and barrier repair. Further research is needed to establish the benefit of allergen-specific immunotherapy. PMID:20725535

Effect of Spin Multiplicity in O2 Adsorption and Dissociation on Small Bimetallic AuAg Clusters.

PubMed

García-Cruz, Raúl; Poulain, Enrique; Hernández-Pérez, Isaías; Reyes-Nava, Juan A; González-Torres, Julio C; Rubio-Ponce, A; Olvera-Neria, Oscar

2017-08-17

To dispose of atomic oxygen, it is necessary the O 2 activation; however, an energy barrier must be overcome to break the O-O bond. This work presents theoretical calculations of the O 2 adsorption and dissociation on small pure Au n and Ag m and bimetallic Au n Ag m (n + m ≤ 6) clusters using the density functional theory (DFT) and the zeroth-order regular approximation (ZORA) to explicitly include scalar relativistic effects. The most stable Au n Ag m clusters contain a higher concentration of Au with Ag atoms located in the center of the cluster. The O 2 adsorption energy on pure and bimetallic clusters and the ensuing geometries depend on the spin multiplicity of the system. For a doublet multiplicity, O 2 is adsorbed in a bridge configuration, whereas for a triplet only one O-metal bond is formed. The charge transfer from metal toward O 2 occupies the σ* O-O antibonding natural bond orbital, which weakens the oxygen bond. The Au 3 ( 2 A) cluster presents the lowest activation energy to dissociate O 2 , whereas the opposite applies to the AuAg ( 3 A) system. In the O 2 activation, bimetallic clusters are not as active as pure Au n clusters due to the charge donated by Ag atoms being shared between O 2 and Au atoms.

In vivo contributions of BH3-only proteins to neuronal death following seizures, ischemia, and traumatic brain injury

PubMed Central

Engel, Tobias; Plesnila, Nikolaus; Prehn, Jochen H M; Henshall, David C

2011-01-01

The Bcl-2 homology (BH) domain 3-only proteins are a proapoptotic subgroup of the Bcl-2 gene family, which regulate cell death via effects on mitochondria. The BH3-only proteins react to various cell stressors and promote cell death by binding and inactivating antiapoptotic Bcl-2 family members and direct activation of proapoptotic multi-BH domain proteins such as Bax. Here, we review the in vivo evidence for their involvement in the pathophysiology of status epilepticus and contrast it to ischemia and traumatic brain injury. Seizures in rodents activate three potent proapoptotic BH3-only proteins: Bid, Bim, and Puma. Analysis of damage after seizures in mice singly deficient for each BH3-only protein supports a causal role for Puma and to a lesser extent Bim but, surprisingly, not Bid. In ischemia and trauma, where core aspects of the pathophysiology of cell death overlap, multiple BH3-only proteins are also activated and Bid has been shown to be required for neuronal death. The findings suggest that while each neurologic insult activates multiple BH3-only proteins, there may be specificity in their functional contribution. Future challenges include evaluating the remaining BH3-only proteins, explaining different causal contributions, and, if possible, exploring neurologic outcomes in mouse models deficient for multiple BH3-only proteins. PMID:21364604

AMP-activated protein kinase-mediated feedback phosphorylation controls the Ca2+/calmodulin (CaM) dependence of Ca2+/CaM-dependent protein kinase kinase β.

PubMed

Nakanishi, Akihiro; Hatano, Naoya; Fujiwara, Yuya; Sha'ri, Arian; Takabatake, Shota; Akano, Hiroki; Kanayama, Naoki; Magari, Masaki; Nozaki, Naohito; Tokumitsu, Hiroshi

2017-12-01

The Ca 2+ /calmodulin-dependent protein kinase kinase β (CaMKKβ)/5'-AMP-activated protein kinase (AMPK) phosphorylation cascade affects various Ca 2+ -dependent metabolic pathways and cancer growth. Unlike recombinant CaMKKβ that exhibits higher basal activity (autonomous activity), activation of the CaMKKβ/AMPK signaling pathway requires increased intracellular Ca 2+ concentrations. Moreover, the Ca 2+ /CaM dependence of CaMKKβ appears to arise from multiple phosphorylation events, including autophosphorylation and activities furnished by other protein kinases. However, the effects of proximal downstream kinases on CaMKKβ activity have not yet been evaluated. Here, we demonstrate feedback phosphorylation of CaMKKβ at multiple residues by CaMKKβ-activated AMPK in addition to autophosphorylation in vitro , leading to reduced autonomous, but not Ca 2+ /CaM-activated, CaMKKβ activity. MS analysis and site-directed mutagenesis of AMPK phosphorylation sites in CaMKKβ indicated that Thr 144 phosphorylation by activated AMPK converts CaMKKβ into a Ca 2+ /CaM-dependent enzyme as shown by completely Ca 2+ /CaM-dependent CaMKK activity of a phosphomimetic T144E CaMKKβ mutant. CaMKKβ mutant analysis indicated that the C-terminal domain (residues 471-587), including the autoinhibitory region, plays an important role in stabilizing an inactive conformation in a Thr 144 phosphorylation-dependent manner. Furthermore, immunoblot analysis with anti-phospho-Thr 144 antibody revealed phosphorylation of Thr 144 in CaMKKβ in transfected COS-7 cells that was further enhanced by exogenous expression of AMPKα. These results indicate that AMPK-mediated feedback phosphorylation of CaMKKβ regulates the CaMKKβ/AMPK signaling cascade and may be physiologically important for intracellular maintenance of Ca 2+ -dependent AMPK activation by CaMKKβ. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Detection of Mycobacterium tuberculosis peptides in the exosomes of patients with active and latent M. tuberculosis infection using MRM-MS.

PubMed

Kruh-Garcia, Nicole A; Wolfe, Lisa M; Chaisson, Lelia H; Worodria, William O; Nahid, Payam; Schorey, Jeff S; Davis, J Lucian; Dobos, Karen M

2014-01-01

The identification of easily measured, accurate diagnostic biomarkers for active tuberculosis (TB) will have a significant impact on global TB control efforts. Because of the host and pathogen complexities involved in TB pathogenesis, identifying a single biomarker that is adequately sensitive and specific continues to be a major hurdle. Our previous studies in models of TB demonstrated that exosomes, such as those released from infected macrophages, contain mycobacterial products, including many Mtb proteins. In this report, we describe the development of targeted proteomics assays employing multiplexed multiple reaction monitoring mass spectrometry (MRM-MS) in order to allow us to follow those proteins previously identified by western blot or shotgun mass spectrometry, and enhance biomarker discovery to include detection of Mtb proteins in human serum exosomes. Targeted MRM-MS assays were applied to exosomes isolated from human serum samples obtained from culture-confirmed active TB patients to detect 76 peptides representing 33 unique Mtb proteins. Our studies revealed the first identification of bacteria-derived biomarker candidates of active TB in exosomes from human serum. Twenty of the 33 proteins targeted for detection were found in the exosomes of TB patients, and included multiple peptides from 8 proteins (Antigen 85B, Antigen 85C, Apa, BfrB, GlcB, HspX, KatG, and Mpt64). Interestingly, all of these proteins are known mycobacterial adhesins and/or proteins that contribute to the intracellular survival of Mtb. These proteins will be included as target analytes in future validation studies as they may serve as markers for persistent active and latent Mtb infection. In summary, this work is the first step in identifying a unique and specific panel of Mtb peptide biomarkers encapsulated in exosomes and reveals complex biomarker patterns across a spectrum of TB disease states.

Detection of Mycobacterium tuberculosis Peptides in the Exosomes of Patients with Active and Latent M. tuberculosis Infection Using MRM-MS

PubMed Central

Kruh-Garcia, Nicole A.; Wolfe, Lisa M.; Chaisson, Lelia H.; Worodria, William O.; Nahid, Payam; Schorey, Jeff S.; Davis, J. Lucian; Dobos, Karen M.

2014-01-01

The identification of easily measured, accurate diagnostic biomarkers for active tuberculosis (TB) will have a significant impact on global TB control efforts. Because of the host and pathogen complexities involved in TB pathogenesis, identifying a single biomarker that is adequately sensitive and specific continues to be a major hurdle. Our previous studies in models of TB demonstrated that exosomes, such as those released from infected macrophages, contain mycobacterial products, including many Mtb proteins. In this report, we describe the development of targeted proteomics assays employing multiplexed multiple reaction monitoring mass spectrometry (MRM-MS) in order to allow us to follow those proteins previously identified by western blot or shotgun mass spectrometry, and enhance biomarker discovery to include detection of Mtb proteins in human serum exosomes. Targeted MRM-MS assays were applied to exosomes isolated from human serum samples obtained from culture-confirmed active TB patients to detect 76 peptides representing 33 unique Mtb proteins. Our studies revealed the first identification of bacteria-derived biomarker candidates of active TB in exosomes from human serum. Twenty of the 33 proteins targeted for detection were found in the exosomes of TB patients, and included multiple peptides from 8 proteins (Antigen 85B, Antigen 85C, Apa, BfrB, GlcB, HspX, KatG, and Mpt64). Interestingly, all of these proteins are known mycobacterial adhesins and/or proteins that contribute to the intracellular survival of Mtb. These proteins will be included as target analytes in future validation studies as they may serve as markers for persistent active and latent Mtb infection. In summary, this work is the first step in identifying a unique and specific panel of Mtb peptide biomarkers encapsulated in exosomes and reveals complex biomarker patterns across a spectrum of TB disease states. PMID:25080351

The Gab1 protein is a docking site for multiple proteins involved in signaling by the B cell antigen receptor.

PubMed

Ingham, R J; Holgado-Madruga, M; Siu, C; Wong, A J; Gold, M R

1998-11-13

Gab1 is a member of the docking/scaffolding protein family which includes IRS-1, IRS-2, c-Cbl, p130(cas), and p62(dok). These proteins contain a variety of protein-protein interaction motifs including multiple tyrosine residues that when phosphorylated can act as binding sites for Src homology 2 (SH2) domain-containing signaling proteins. We show in the RAMOS human B cell line that Gab1 is tyrosine-phosphorylated in response to B cell antigen receptor (BCR) engagement. Moreover, tyrosine phosphorylation of Gab1 correlated with the binding of several SH2-containing signaling proteins to Gab1 including Shc, Grb2, phosphatidylinositol 3-kinase, and the SHP-2 tyrosine phosphatase. Far Western analysis showed that the SH2 domains of Shc, SHP-2, and the p85 subunit of phosphatidylinositol 3-kinase could bind directly to tyrosine-phosphorylated Gab1 isolated from activated RAMOS cells. In contrast, the Grb2 SH2 domain did not bind directly to Gab1 but instead to the Shc and SHP-2 associated with Gab1. We also show that Gab1 is present in the membrane-enriched particulate fraction of RAMOS cells and that Gab1/signaling protein complexes are found in this fraction after BCR engagement. Thus, tyrosine-phosphorylated Gab1 may recruit cytosolic signaling proteins to cellular membranes where they can act on membrane-bound targets. This may be a critical step in the activation of multiple BCR signaling pathways.

Rehabilitation in multiple sclerosis.

PubMed

Kubsik-Gidlewska, Anna M; Klimkiewicz, Paulina; Klimkiewicz, Robert; Janczewska, Katarzyna; Woldańska-Okońska, Marta

2017-07-01

The aim of the study is to present a strategy of rehabilitation in multiple sclerosis on the basis of the latest developments in the field of physiotherapy. The publications on the problem discuss a wide range of methods of physiotherapy that can be used in order to reduce the degree of disability and alleviate the symptoms associated with the disease. The complexity of the disease, the difficulty in determining the appropriate treatment and a wide range of symptoms require a comprehensive approach to the patient, which would include both pharmacology and neurorehabilitation. Rehabilitation, which includes psychotherapy and symptomatic therapy, is regarded nowadays as the best form of treatment for multiple sclerosis. An indepth diagnostic assessment of functional status and prognosis should be carried out before the start of the rehabilitation process. The prognosis should take into account the mental state, the neurological status and the awareness of the patient. The kinesiotherapy program in multiple sclerosis is based on a gradation of physiotherapy which assumes a gradual transition from basic movements to more complex ones till global functions are obtained. The most appropriate form of treatment is functional rehabilitation combined with physical procedures. Recent reports indicate the need for aerobic training to be included in the rehabilitation program. The introduction of physical activities, regardless of the severity of the disease, will reduce the negative effects of akinesia, and thus increase the functional capabilities of all body systems.

Tumor-targeted nanomedicines for cancer theranostics

PubMed Central

Lammers, Twan; Shi, Yang

2017-01-01

Chemotherapeutic drugs have multiple drawbacks, including severe side effects and suboptimal therapeutic efficacy. Nanomedicines assist in improving the biodistribution and the target accumulation of chemotherapeutic drugs, and are therefore able to enhance the balance between efficacy and toxicity. Multiple different types of nanomedicines have been evaluated over the years, including liposomes, polymer-drug conjugates and polymeric micelles, which rely on strategies such as passive targeting, active targeting and triggered release for improved tumor-directed drug delivery. Based on the notion that tumors and metastases are highly heterogeneous, it is important to integrate imaging properties in nanomedicine formulations in order to enable non-invasive and quantitative assessment of targeting efficiency. By allowing for patient pre-selection, such next generation nanotheranostics are useful for facilitating clinical translation and personalizing nanomedicine treatments. PMID:27865762

Sarmentine, a natural herbicide from Piper species with multiple herbicide mechanisms of action

USDA-ARS?s Scientific Manuscript database

Sarmentine, 1-(1-pyrrolidinyl)-(2E,4E)-2,4-decadien-1-one, is a natural amide isolated from the fruits of Piper species. The compound has a number of interesting biological properties, including its broad-spectrum activity on weeds as a contact herbicide. Initial studies highlighted a similarity in ...

40 CFR 63.10010 - What are my monitoring, installation, operation, and maintenance requirements?

Code of Federal Regulations, 2012 CFR

2012-07-01

... emissions are controlled with a common control device or series of control devices, are discharged to the... devices or multiple series of control devices are discharged to the atmosphere through more than one stack... control activities (including, as applicable, calibration checks and required zero and span adjustments...

Temporality of Emotion: Antecedent and Successive Variants of Frustration When Learning Chemistry

ERIC Educational Resources Information Center

King, Donna; Ritchie, Stephen M.; Sandhu, Maryam; Henderson, Senka; Boland, Ben

2017-01-01

Learning science in the middle years can be an emotional experience. In this study, we explored ninth-grade students' discrete emotions expressed during science activities in a 9-week unit on chemistry. Individual student's emotions were analyzed through multiple data sources including classroom videos, interviews, and emotions diaries completed…

An Empirical Investigation of a Theoretically Based Measure of Perceived Wellness

ERIC Educational Resources Information Center

Harari, Marc J.; Waehler, Charles A.; Rogers, James R.

2005-01-01

The Perceived Wellness Survey (PWS; T. Adams, 1995; T. Adams, J. Bezner, & M. Steinhardt, 1997) is a recently developed instrument intended to operationalize the comprehensive Perceived Wellness Model (T. Adams, J. Bezner, & M. Steinhardt, 1997), an innovative model that attempts to include the balance of multiple life activities in its evaluation…

Global climate change and fragmentation of native brook trout distribution in the southern Appalachian Mountains

Treesearch

Patricia A. Flebbe

1997-01-01

Current distributions of native brook trout (Salvelinus fontinalis) in the Southern Appalachians are restricted to upper elevations by multiple factors, including habitat requirements, introduced rainbow (Oncorhynchus mykiss) and brown (Salmo trutta) trout, and other human activities. Present-day distribution of brook trout habitat is already fragmented. Increased...

Active and passive forest management for multiple values.

Treesearch

Andrew B. Carey

2006-01-01

Comparisons of natural and managed forests suggest that single-focus management of 2nd growth is unlikely to achieve broad conservation goals because biocomplexity is important to ecosystem capacity to produce useful goods and services. Biocomplexity includes species composition, the absolute and relative abundances of those species, and their arrangement in space (for...

Screening the ToxCast Phase I, II, and e1K Chemical Libraries for Inhibition of Deiodinase Type 1,2 and 3 Enzyme Activity

EPA Science Inventory

Thyroid hormone (TH) signaling and homeostasis is dependent upon coordination of multiple key events including thyroidal iodide uptake and hormone synthesis, and peripheral metabolism and elimination. Deiodinase enzymes play an essential role in converting the pro-hormone thyroxi...

A Strategy for Embedding Functional Motor and Early Numeracy Skill Instruction into Physical Education Activities

ERIC Educational Resources Information Center

Whinnery, Stacie B.; Whinnery, Keith W.; Eddins, Daisy

2016-01-01

This article addresses the challenges educators face when attempting to find a balance between both functional and academic skill instruction for students with severe, multiple disabilities including motor impairments. The authors describe a strategy that employs embedded instruction of early numeracy and functional motor skills during physical…

Biostable multi-Aib analogs of tachykinin-related peptides demonstrate potent oral aphicidal activity in the pea aphid Acyrthosiphon pisum (Hemiptera: Aphidae)

USDA-ARS?s Scientific Manuscript database

The tachykinin-related peptides (TRPs) are multifunctional neuropeptides found in a variety of arthropod species, including the pea aphid Acyrthosiphon pisum (Hemiptera: Aphidae). Two novel biostable TRP analogs containing multiple, sterically-hindered Aib residues were synthesized and found to exhi...

78 FR 37546 - Agency Information Collection Activities; Proposed Collection; Comment Request; Evaluation of the...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-21

... collection of information is necessary for the proper performance of FDA's functions, including whether the... multiple, discrete waves of media advertising planned for the campaigns. Outcome Evaluation Study The..., 8,281 completes at the second followup, and 6,625 completes at the third followup survey waves. The...

82 FR 58411 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2017-12-12

... be in the form of a web page for a fictitious drug targeted toward consumers who have chronic pain or... prescription drug information in multiple formats--including print, television, web, and other modes--would be... framed items. Moreover, the slider questions referenced by the commenter are semantic differentials...

Developing Computer-Interactive Tape Exercises for Intermediate-Level Business French.

ERIC Educational Resources Information Center

Garnett, Mary Anne

One college language teacher developed computer-interactive audiotape exercises for an intermediate-level class in business French. The project was undertaken because of a need for appropriate materials at that level. The use of authoring software permitted development of a variety of activity types, including multiple-choice, fill-in-the-blank,…

Activities for Differentiated Instruction Addressing All Levels of Bloom's Taxonomy and Eight Multiple Intelligences.

ERIC Educational Resources Information Center

Rule, Audrey C., Ed.; Lord, Linda Hurley, Ed.

This manuscript contains 13 curriculum units designed to enhance differentiated instruction for learners with special needs from grades 1-12, including gifted students. It integrates Benjamin S. Bloom's levels of cognitive understanding with Howard Gardner's eight domains of intelligence to provide a framework for individualized instruction. Each…

12 CFR 584.2-1 - Prescribed services and activities of savings and loan holding companies.

Code of Federal Regulations, 2013 CFR

2013-01-01

... warehousing of such real estate loans, except that such a company or subsidiary shall not invest in a loan... installed therein), including brokerage and warehousing of such chattel paper; (iii) Loans, with or without... other multiple holding companies and affiliates thereof: (i) Data processing; (ii) Credit information...

12 CFR 584.2-1 - Prescribed services and activities of savings and loan holding companies.

Code of Federal Regulations, 2012 CFR

2012-01-01

... warehousing of such real estate loans, except that such a company or subsidiary shall not invest in a loan... installed therein), including brokerage and warehousing of such chattel paper; (iii) Loans, with or without... other multiple holding companies and affiliates thereof: (i) Data processing; (ii) Credit information...

12 CFR 584.2-1 - Prescribed services and activities of savings and loan holding companies.

Code of Federal Regulations, 2014 CFR

2014-01-01

... warehousing of such real estate loans, except that such a company or subsidiary shall not invest in a loan... installed therein), including brokerage and warehousing of such chattel paper; (iii) Loans, with or without... other multiple holding companies and affiliates thereof: (i) Data processing; (ii) Credit information...

Distinct encoding of risk and value in economic choice between multiple risky options☆

PubMed Central

Wright, Nicholas D.; Symmonds, Mkael; Dolan, Raymond J.

2013-01-01

Neural encoding of value-based stimuli is suggested to involve representations of summary statistics, including risk and expected value (EV). A more complex, but ecologically more common, context is when multiple risky options are evaluated together. However, it is unknown whether encoding related to option evaluation in these situations involves similar principles. Here we employed fMRI during a task that parametrically manipulated EV and risk in two simultaneously presented lotteries, both of which contained either gains or losses. We found representations of EV in medial prefrontal cortex and anterior insula, an encoding that was dependent on which option was chosen (i.e. chosen and unchosen EV) and whether the choice was over gains or losses. Parietal activity reflected whether the riskier or surer option was selected, whilst activity in a network of regions that also included parietal cortex reflected both combined risk and difference in risk for the two options. Our findings provide support for the idea that summary statistics underpin a representation of value-based stimuli, and further that these summary statistics undergo distinct forms of encoding. PMID:23684860

Status of and candidates for cell therapy in liver cirrhosis: overcoming the "point of no return" in advanced liver cirrhosis.

PubMed

Terai, Shuji; Tsuchiya, Atsunori

2017-02-01

The treatment of liver cirrhosis is currently being standardized and developed specifically to reduce activation of hepatic stellate cells (HSCs), inhibit fibrosis, increase degradation of matrix components, and reduce activated myofibroblasts. Cell therapy can be applied in the treatment of liver cirrhosis; however, the characteristic features of this therapy differ from those of other treatments because of the involvement of a living body origin and production of multiple cytokines, chemokines, matrix metalloproteinases (MMPs), and growth factors. Thus, cell therapies can potentially have multiple effects on the damaged liver, including alleviating liver cirrhosis and stimulating liver regeneration with affecting the host cells. Cell therapies initially involved autologous bone marrow cell infusion, and have recently developed to include the use of specific cells such as mesenchymal stem cells and macrophages. The associated molecular mechanisms, routes of administration, possibility of allogeneic cell therapy, and host conditions appropriate for cell therapies are now being extensively analyzed. In this review, we summarize the status and future prospects of cell therapy for liver cirrhosis.

Multiagent Work Practice Simulation: Progress and Challenges

NASA Technical Reports Server (NTRS)

Clancey, William J.; Sierhuis, Maarten; Shaffe, Michael G. (Technical Monitor)

2001-01-01

Modeling and simulating complex human-system interactions requires going beyond formal procedures and information flows to analyze how people interact with each other. Such work practices include conversations, modes of communication, informal assistance, impromptu meetings, workarounds, and so on. To make these social processes visible, we have developed a multiagent simulation tool, called Brahms, for modeling the activities of people belonging to multiple groups, situated in a physical environment (geographic regions, buildings, transport vehicles, etc.) consisting of tools, documents, and a computer system. We are finding many useful applications of Brahms for system requirements analysis, instruction, implementing software agents, and as a workbench for relating cognitive and social theories of human behavior. Many challenges remain for representing work practices, including modeling: memory over multiple days, scheduled activities combining physical objects, groups, and locations on a timeline (such as a Space Shuttle mission), habitat vehicles with trajectories (such as the Shuttle), agent movement in 3D space (e.g., inside the International Space Station), agent posture and line of sight, coupled movements (such as carrying objects), and learning (mimicry, forming habits, detecting repetition, etc.).

Multiagent Work Practice Simulation: Progress and Challenges

NASA Technical Reports Server (NTRS)

Clancey, William J.; Sierhuis, Maarten

2002-01-01

Modeling and simulating complex human-system interactions requires going beyond formal procedures and information flows to analyze how people interact with each other. Such work practices include conversations, modes of communication, informal assistance, impromptu meetings, workarounds, and so on. To make these social processes visible, we have developed a multiagent simulation tool, called Brahms, for modeling the activities of people belonging to multiple groups, situated in a physical environment (geographic regions, buildings, transport vehicles, etc.) consisting of tools, documents, and computer systems. We are finding many useful applications of Brahms for system requirements analysis, instruction, implementing software agents, and as a workbench for relating cognitive and social theories of human behavior. Many challenges remain for representing work practices, including modeling: memory over multiple days, scheduled activities combining physical objects, groups, and locations on a timeline (such as a Space Shuttle mission), habitat vehicles with trajectories (such as the Shuttle), agent movement in 3d space (e.g., inside the International Space Station), agent posture and line of sight, coupled movements (such as carrying objects), and learning (mimicry, forming habits, detecting repetition, etc.).

Physical activity motivation and benefits in people with multiple sclerosis.

PubMed

Fasczewski, Kimberly S; Gill, Diane L; Rothberger, Sara M

2018-06-01

Multiple sclerosis is a degenerative neurological disease that affects 2.1 million people worldwide. There is no cure, but an expanding body of research supports the positive impact of physical activity and suggests physical activity has benefits for the individual's psychological and physical well-being. Using Self-Determination Theory as a framework, mixed methods with a focus on qualitative interviews were used to explore physical activity motivation and benefits with a sample of highly active people with multiple sclerosis (n = 15). Disability level ranged from not disabled to wheelchair bound with the majority of participants reporting minimal impact from multiple sclerosis. Survey data were collected using a number of open-ended questions along with measures of self-efficacy, self-determined motivation, physical activity, and quality of life. Additionally, eight individuals participated in semistructured telephone interviews focused on (a) motivation and strategies used to maintain physical activity and (b) the benefits and impact of physical activity in their lives. The main findings were consistent with Self-Determination Theory; participants described feelings of accomplishment and competence in both their physical activity and daily life, as well as a sense of independence and autonomy. Similarly, all participants cited benefits, and the main themes were enhanced satisfaction with life and an overall positive outlook on life. Results provide insight into the role of physical activity in a highly active sample and have implications for professionals working in physical activity settings with the multiple sclerosis population. Interventions aimed at increasing long-term physical activity adherence should focus on increasing autonomy and competence for physical activity in the individual and promoting potential increased quality of life outcomes from physical activity participation. Implications for Rehabilitation Multiple sclerosis is a chronic degenerative neurological disease that the individual lives with for a majority of the lifespan. Physical activity is one means that has been shown to aid is the control of multiple sclerosis symptoms. Increasing patient understanding of the benefits of using physical activity as a means to control multiple sclerosis symptoms may result in long-term physical activity adherence. Physical activity interventions that develop feelings of competence and independent choice in the patient may be more successful for long-term participation.

Features in visual search combine linearly

PubMed Central

Pramod, R. T.; Arun, S. P.

2014-01-01

Single features such as line orientation and length are known to guide visual search, but relatively little is known about how multiple features combine in search. To address this question, we investigated how search for targets differing in multiple features (intensity, length, orientation) from the distracters is related to searches for targets differing in each of the individual features. We tested race models (based on reaction times) and co-activation models (based on reciprocal of reaction times) for their ability to predict multiple feature searches. Multiple feature searches were best accounted for by a co-activation model in which feature information combined linearly (r = 0.95). This result agrees with the classic finding that these features are separable i.e., subjective dissimilarity ratings sum linearly. We then replicated the classical finding that the length and width of a rectangle are integral features—in other words, they combine nonlinearly in visual search. However, to our surprise, upon including aspect ratio as an additional feature, length and width combined linearly and this model outperformed all other models. Thus, length and width of a rectangle became separable when considered together with aspect ratio. This finding predicts that searches involving shapes with identical aspect ratio should be more difficult than searches where shapes differ in aspect ratio. We confirmed this prediction on a variety of shapes. We conclude that features in visual search co-activate linearly and demonstrate for the first time that aspect ratio is a novel feature that guides visual search. PMID:24715328

Heat pump system with selective space cooling

DOEpatents

Pendergrass, J.C.

1997-05-13

A reversible heat pump provides multiple heating and cooling modes and includes a compressor, an evaporator and heat exchanger all interconnected and charged with refrigerant fluid. The heat exchanger includes tanks connected in series to the water supply and a condenser feed line with heat transfer sections connected in counterflow relationship. The heat pump has an accumulator and suction line for the refrigerant fluid upstream of the compressor. Sub-cool transfer tubes associated with the accumulator/suction line reclaim a portion of the heat from the heat exchanger. A reversing valve switches between heating/cooling modes. A first bypass is operative to direct the refrigerant fluid around the sub-cool transfer tubes in the space cooling only mode and during which an expansion valve is utilized upstream of the evaporator/indoor coil. A second bypass is provided around the expansion valve. A programmable microprocessor activates the first bypass in the cooling only mode and deactivates the second bypass, and vice-versa in the multiple heating modes for said heat exchanger. In the heating modes, the evaporator may include an auxiliary outdoor coil for direct supplemental heat dissipation into ambient air. In the multiple heating modes, the condensed refrigerant fluid is regulated by a flow control valve. 4 figs.

Heat pump system with selective space cooling

DOEpatents

Pendergrass, Joseph C.

1997-01-01

A reversible heat pump provides multiple heating and cooling modes and includes a compressor, an evaporator and heat exchanger all interconnected and charged with refrigerant fluid. The heat exchanger includes tanks connected in series to the water supply and a condenser feed line with heat transfer sections connected in counterflow relationship. The heat pump has an accumulator and suction line for the refrigerant fluid upstream of the compressor. Sub-cool transfer tubes associated with the accumulator/suction line reclaim a portion of the heat from the heat exchanger. A reversing valve switches between heating/cooling modes. A first bypass is operative to direct the refrigerant fluid around the sub-cool transfer tubes in the space cooling only mode and during which an expansion valve is utilized upstream of the evaporator/indoor coil. A second bypass is provided around the expansion valve. A programmable microprocessor activates the first bypass in the cooling only mode and deactivates the second bypass, and vice-versa in the multiple heating modes for said heat exchanger. In the heating modes, the evaporator may include an auxiliary outdoor coil for direct supplemental heat dissipation into ambient air. In the multiple heating modes, the condensed refrigerant fluid is regulated by a flow control valve.

Multiple Endocrine Neoplasia Type 2B Unmasked by 18 F-FDG PET/CT and 131 I-MIBG SPECT/CT.

PubMed

Sun, Xun; Arnous, Maher Mohamad Rajab; Lan, Xiaoli

2017-04-01

F-FDG PET/CT was performed to detect an occult malignancy in a 26-year-old woman with complicated medical history which included paroxysmal hypertension and significantly elevated tumor marker. The images revealed lesions in the thyroid, lymph nodes, and bilateral adrenal glands. Further I-MIBG SPECT/CT revealed intense activity in the lesion in the left adrenal gland, which was consistent with pheochromocytoma. The pathology examination after subsequent neck biopsy demonstrated medullary thyroid carcinoma. A diagnosis of multiple endocrine neoplasia type 2B was eventually made.

Disposition, Metabolism and Histone Deacetylase and Acetyltransferase Inhibition Activity of Tetrahydrocurcumin and Other Curcuminoids

PubMed Central

Novaes, Júlia T.; Sayre, Casey L.; Majeed, Muhammed; Ho, Emmanuel A.; Oliveira, Ana Luísa de P.; Martinez, Stephanie E.; Davies, Neal M.; Lakowski, Ted M.

2017-01-01

Tetrahydrocurcumin (THC), curcumin and calebin-A are curcuminoids found in turmeric (Curcuma longa). Curcuminoids have been established to have a variety of pharmacological activities and are used as natural health supplements. The purpose of this study was to identify the metabolism, excretion, antioxidant, anti-inflammatory and anticancer properties of these curcuminoids and to determine disposition of THC in rats after oral administration. We developed a UHPLC–MS/MS assay for THC in rat serum and urine. THC shows multiple redistribution phases with corresponding increases in urinary excretion rate. In-vitro antioxidant activity, histone deacetylase (HDAC) activity, histone acetyltransferase (HAT) activity and anti-inflammatory inhibitory activity were examined using commercial assay kits. Anticancer activity was determined in Sup-T1 lymphoma cells. Our results indicate THC was poorly absorbed after oral administration and primarily excreted via non-renal routes. All curcuminoids exhibited multiple pharmacological effects in vitro, including potent antioxidant activity as well as inhibition of CYP2C9, CYP3A4 and lipoxygenase activity without affecting the release of TNF-α. Unlike curcumin and calebin-A, THC did not inhibit HDAC1 and PCAF and displayed a weaker growth inhibition activity against Sup-T1 cells. We show evidence for the first time that curcumin and calebin-A inhibit HAT and PCAF, possibly through a Michael-addition mechanism. PMID:29023392

Wightianines A-E, dihydro-β-agarofuran sesquiterpenes from Parnassia wightiana, and their antifungal and insecticidal activities.

PubMed

Wang, Dong-Mei; Zhang, Cheng-Chen; Zhang, Qiang; Shafiq, Nusrat; Pescitelli, Gennaro; Li, Deng-Wu; Gao, Jin-Ming

2014-07-16

Five new sesquiterpene polyol esters with a dihydro-β-agarofuran skeleton, designated as wightianines A-E (1-5), besides two known compounds, were isolated from the methanolic extract of the whole plant of the traditional herbal medicine Parnassia wightiana Wall. The structures of the isolated compounds were elucidated on the basis of spectroscopic analyses, including two-dimensional nuclear magnetic resonance techniques (correlation spectroscopy, heteronuclear multiple-quantum coherence, nuclear Overhauser effect spectrometry, and heteronuclear multiple-bond correlation) and electronic circular dichroism studies. The antifungal and insecticidal activities of five compounds were evaluated against several plant pathogenic fungi and armyworm larvae (Mythimna separata Walker). Among the test metabolites, compounds 2 and 7 both exhibited potent antifungal activity against the phytopathogenic fungus Cytospora sp. with minimum inhibitory concentration values of 0.78 μg/mL, which are equal to the two positive controls, hymexazol and carbendazim. However, no insecticidal activity of the test compounds was observed in the present study. Compounds 2 and 7 could be promising leads for developing new fungicides against agriculturally important fungus Cytospora sp.

The vigorous immune microenvironment of microsatellite instable colon cancer is balanced by multiple counter-inhibitory checkpoints

PubMed Central

Llosa, Nicolas J.; Cruise, Michael; Tam, Ada; Wick, Elizabeth C.; Hechenbleikner, Elizabeth M.; Taube, Janis M.; Blosser, Lee; Fan, Hongni; Wang, Hao; Luber, Brandon; Zhang, Ming; Papadopoulos, Nickolas; Kinzler, Kenneth W.; Vogelstein, Bert; Sears, Cynthia L.; Anders, Robert A.; Pardoll, Drew M.; Housseau, Franck

2014-01-01

We examined the immune microenvironment of primary colorectal cancer (CRC) using immunohistochemistry, laser capture microdissection/qRT-PCR, flow cytometry and functional analysis of tumor infiltrating lymphocytes. A subset of CRC displayed high infiltration with activated CD8+ CTL as well as activated Th1 cells characterized by IFN-γ production and the Th1 transcription factor Tbet. Parallel analysis of tumor genotypes revealed that virtually all of the tumors with this active Th1/CTL microenvironment had defects in mismatch repair, as evidenced by microsatellite instability (MSI). Counterbalancing this active Th1/CTL microenvironment, MSI tumors selectively demonstrated highly up-regulated expression of multiple immune checkpoints, including five – PD-1, PD-L1, CTLA-4, LAG-3 and IDO – currently being targeted clinically with inhibitors. These findings link tumor genotype with the immune microenvironment, and explain why MSI tumors are not naturally eliminated despite a hostile Th1/CTL microenvironment. They further suggest that blockade of specific checkpoints may be selectively efficacious in the MSI subset of CRC. PMID:25358689

Disability relating to basic and instrumental activities of daily living: a zopulation-based study with elderly in Pelotas, Rio Grande do Sul, Brazil, 2014.

PubMed

Farías-Antúnez, Simone; Lima, Natália Peixoto; Bierhals, Isabel Oliveira; Gomes, Ana Paula; Vieira, Luna Strieder; Tomasi, Elaine

2018-06-11

to estimate the prevalence of disability related to basic and instrumental activities of daily living and its association with socioeconomic, demographic, behavioral and health characteristics in the elderly. population-based cross-sectional study in Pelotas, Brazil, in 2014; Katz and Lawton scales were used to assess the outcomes using Poisson regression. the study included 1.451 elderly individuals; the prevalence of disability for basic and instrumental activities was 36.1% and 34.0%, respectively, and 18.1% in both; higher prevalence of functional disability were observed individuals ≥80 years (PR=3.01; 95%CI 2.17;4.18), not working (PR=2.02; 95%CI 1.13;3.60) and those with multiple morbidities (PR=3.28; 95%CI 1.38;7.79); and lower in individuals with ≥12 years of schooling (PR=0.40; 95%CI 0.24;0.66), and that were physically active (PR=0.42; 95%CI 0.21;0.82). functional disability was associated to individuals older than 80, with less schooling years and affected by multiple morbidities.

A small molecule inhibitior of the NLRP3 inflammasome is a potential therapeutic for inflammatory diseases

PubMed Central

Coll, Rebecca C.; Robertson, Avril A. B.; Chae, Jae Jin; Higgins, Sarah C.; Muñoz-Planillo, Raúl; Inserra, Marco C.; Vetter, Irina; Dungan, Lara S.; Monks, Brian G.; Stutz, Andrea; Croker, Daniel E.; Butler, Mark S.; Haneklaus, Moritz; Sutton, Caroline E.; Núñez, Gabriel; Latz, Eicke; Kastner, Daniel L.; Mills, Kingston H. G.; Masters, Seth L.; Schroder, Kate; Cooper, Matthew A.; O’Neill, Luke A. J.

2015-01-01

The NLRP3 inflammasome is a component of the inflammatory process and its aberrant activation is pathogenic in inherited disorders such as the cryopyrin associated periodic syndromes (CAPS) and complex diseases such as multiple sclerosis, type 2 diabetes and atherosclerosis. We describe the development of MCC950, a potent, selective, small molecule inhibitor of NLRP3. MCC950 blocks canonical and non-canonical NLRP3 activation at nanomolar concentrations. MCC950 specifically inhibits NLRP3 but not AIM2, NLRC4 or NLRP1 activation. MCC950 reduces Interleukin-1p (IL-1β) production in vivo and attenuates the severity of experimental autoimmune encephalomyelitis (EAE), a disease model of multiple sclerosis. Furthermore, MCC950 treatment rescues neonatal lethality in a mouse model of CAPS and is active in ex vivo samples from individuals with Muckle-Wells syndrome. MCC950 is thus a potential therapeutic for NLRP3-associated syndromes, including autoinflammatory and autoimmune diseases, and a tool for the further study of the NLRP3 inflammasome in human health and disease. PMID:25686105

A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases.

PubMed

Coll, Rebecca C; Robertson, Avril A B; Chae, Jae Jin; Higgins, Sarah C; Muñoz-Planillo, Raúl; Inserra, Marco C; Vetter, Irina; Dungan, Lara S; Monks, Brian G; Stutz, Andrea; Croker, Daniel E; Butler, Mark S; Haneklaus, Moritz; Sutton, Caroline E; Núñez, Gabriel; Latz, Eicke; Kastner, Daniel L; Mills, Kingston H G; Masters, Seth L; Schroder, Kate; Cooper, Matthew A; O'Neill, Luke A J

2015-03-01

The NOD-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3) inflammasome is a component of the inflammatory process, and its aberrant activation is pathogenic in inherited disorders such as cryopyrin-associated periodic syndrome (CAPS) and complex diseases such as multiple sclerosis, type 2 diabetes, Alzheimer's disease and atherosclerosis. We describe the development of MCC950, a potent, selective, small-molecule inhibitor of NLRP3. MCC950 blocked canonical and noncanonical NLRP3 activation at nanomolar concentrations. MCC950 specifically inhibited activation of NLRP3 but not the AIM2, NLRC4 or NLRP1 inflammasomes. MCC950 reduced interleukin-1β (IL-1β) production in vivo and attenuated the severity of experimental autoimmune encephalomyelitis (EAE), a disease model of multiple sclerosis. Furthermore, MCC950 treatment rescued neonatal lethality in a mouse model of CAPS and was active in ex vivo samples from individuals with Muckle-Wells syndrome. MCC950 is thus a potential therapeutic for NLRP3-associated syndromes, including autoinflammatory and autoimmune diseases, and a tool for further study of the NLRP3 inflammasome in human health and disease.

Identification of Program Signatures from Cloud Computing System Telemetry Data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nichols, Nicole M.; Greaves, Mark T.; Smith, William P.

Malicious cloud computing activity can take many forms, including running unauthorized programs in a virtual environment. Detection of these malicious activities while preserving the privacy of the user is an important research challenge. Prior work has shown the potential viability of using cloud service billing metrics as a mechanism for proxy identification of malicious programs. Previously this novel detection method has been evaluated in a synthetic and isolated computational environment. In this paper we demonstrate the ability of billing metrics to identify programs, in an active cloud computing environment, including multiple virtual machines running on the same hypervisor. The openmore » source cloud computing platform OpenStack, is used for private cloud management at Pacific Northwest National Laboratory. OpenStack provides a billing tool (Ceilometer) to collect system telemetry measurements. We identify four different programs running on four virtual machines under the same cloud user account. Programs were identified with up to 95% accuracy. This accuracy is dependent on the distinctiveness of telemetry measurements for the specific programs we tested. Future work will examine the scalability of this approach for a larger selection of programs to better understand the uniqueness needed to identify a program. Additionally, future work should address the separation of signatures when multiple programs are running on the same virtual machine.« less

Education and Public Outreach at The Pavilion Lake Research Project: Fusion of Science and Education using Web 2.0

NASA Astrophysics Data System (ADS)

Cowie, B. R.; Lim, D. S.; Pendery, R.; Laval, B.; Slater, G. F.; Brady, A. L.; Dearing, W. L.; Downs, M.; Forrest, A.; Lees, D. S.; Lind, R. A.; Marinova, M.; Reid, D.; Seibert, M. A.; Shepard, R.; Williams, D.

2009-12-01

The Pavilion Lake Research Project (PLRP) is an international multi-disciplinary science and exploration effort to explain the origin and preservation potential of freshwater microbialites in Pavilion Lake, British Columbia, Canada. Using multiple exploration platforms including one person DeepWorker submersibles, Autonomous Underwater Vehicles, and SCUBA divers, the PLRP acts as an analogue research site for conducting science in extreme environments, such as the Moon or Mars. In 2009, the PLRP integrated several Web 2.0 technologies to provide a pilot-scale Education and Public Outreach (EPO) program targeting the internet savvy generation. The seamless integration of multiple technologies including Google Earth, Wordpress, Youtube, Twitter and Facebook, facilitated the rapid distribution of exciting and accessible science and exploration information over multiple channels. Field updates, science reports, and multimedia including videos, interactive maps, and immersive visualization were rapidly available through multiple social media channels, partly due to the ease of integration of these multiple technologies. Additionally, the successful application of videoconferencing via a readily available technology (Skype) has greatly increased the capacity of our team to conduct real-time education and public outreach from remote locations. The improved communication afforded by Web 2.0 has increased the quality of EPO provided by the PLRP, and has enabled a higher level of interaction between the science team and the community at large. Feedback from these online interactions suggest that remote communication via Web 2.0 technologies were effective tools for increasing public discourse and awareness of the science and exploration activity at Pavilion Lake.

Multi-stage complex contagions.

PubMed

Melnik, Sergey; Ward, Jonathan A; Gleeson, James P; Porter, Mason A

2013-03-01

The spread of ideas across a social network can be studied using complex contagion models, in which agents are activated by contact with multiple activated neighbors. The investigation of complex contagions can provide crucial insights into social influence and behavior-adoption cascades on networks. In this paper, we introduce a model of a multi-stage complex contagion on networks. Agents at different stages-which could, for example, represent differing levels of support for a social movement or differing levels of commitment to a certain product or idea-exert different amounts of influence on their neighbors. We demonstrate that the presence of even one additional stage introduces novel dynamical behavior, including interplay between multiple cascades, which cannot occur in single-stage contagion models. We find that cascades-and hence collective action-can be driven not only by high-stage influencers but also by low-stage influencers.

Multi-stage complex contagions

NASA Astrophysics Data System (ADS)

Melnik, Sergey; Ward, Jonathan A.; Gleeson, James P.; Porter, Mason A.

2013-03-01

The spread of ideas across a social network can be studied using complex contagion models, in which agents are activated by contact with multiple activated neighbors. The investigation of complex contagions can provide crucial insights into social influence and behavior-adoption cascades on networks. In this paper, we introduce a model of a multi-stage complex contagion on networks. Agents at different stages—which could, for example, represent differing levels of support for a social movement or differing levels of commitment to a certain product or idea—exert different amounts of influence on their neighbors. We demonstrate that the presence of even one additional stage introduces novel dynamical behavior, including interplay between multiple cascades, which cannot occur in single-stage contagion models. We find that cascades—and hence collective action—can be driven not only by high-stage influencers but also by low-stage influencers.

Roles of mTOR Signaling in Brain Development.

PubMed

Lee, Da Yong

2015-09-01

mTOR is a serine/threonine kinase composed of multiple protein components. Intracellular signaling of mTOR complexes is involved in many of physiological functions including cell survival, proliferation and differentiation through the regulation of protein synthesis in multiple cell types. During brain development, mTOR-mediated signaling pathway plays a crucial role in the process of neuronal and glial differentiation and the maintenance of the stemness of neural stem cells. The abnormalities in the activity of mTOR and its downstream signaling molecules in neural stem cells result in severe defects of brain developmental processes causing a significant number of brain disorders, such as pediatric brain tumors, autism, seizure, learning disability and mental retardation. Understanding the implication of mTOR activity in neural stem cells would be able to provide an important clue in the development of future brain developmental disorder therapies.

The value of partnerships in state obesity prevention and control programs.

PubMed

Hersey, James; Kelly, Bridget; Roussel, Amy; Curtis, LaShawn; Horne, Joseph; Williams-Piehota, Pamela; Kuester, Sarah; Farris, Rosanne

2012-03-01

State health departments funded by the Centers for Disease Control and Prevention's Nutrition, Physical Activity, and Obesity Program collaborate with multiple partners to develop and implement comprehensive obesity prevention and control programs. A mixed-methods evaluation of 28 state programs over a 5-year period assessed states' progress on program requirements, including developing statewide partnerships and coordinating with partners to support obesity prevention and control efforts. States with greater partnership involvement leveraged more funding support for their programs, passed more obesity-related policies, and were more likely to implement obesity interventions in multiple settings. Case studies provided guidance for establishing and maintaining strong partnerships. Findings from this study offer emerging evidence to support assumptions about the centrality of partnerships to states' success in obesity program development and implementation and related health promotion activities.

Immune complex-mediated autoimmunity in a patient With Smith-Magenis syndrome (del 17p11.2).

PubMed

Yang, Jianying; Chandrasekharappa, Settara C; Vilboux, Thierry; Smith, Ann C M; Peterson, Erik J

2014-08-01

Smith-Magenis syndrome (SMS) is a sporadic congenital disorder involving multiple organ systems caused by chromosome 17p11.2 deletions. Smith-Magenis syndrome features craniofacial and skeletal anomalies, cognitive impairment, and neurobehavioral abnormalities. In addition, some SMS patients may exhibit hypogammaglobulinemia. We report the first case of SMS-associated autoimmunity in a woman who presented with adult onset of multiple autoimmune disorders, including systemic lupus erythematosus, antiphospholipid antibody syndrome, and autoimmune hepatitis. Molecular analysis using single-nucleotide polymorphism array confirmed a de novo 3.8-Mb deletion (breakpoints, chr17: 16,660,721-20,417,975), resulting in haploinsufficiency for TACI (transmembrane activator and CAML interactor). Our data are consistent with potential loss of function for the BAFF (B cell-activating factor) receptor TACI as a contributing factor to human autoimmune phenomena.

Loss of Pancreas upon Activated Wnt Signaling Is Concomitant with Emergence of Gastrointestinal Identity

PubMed Central

Herrero-Martin, Griselda; Puri, Sapna; Taketo, Makoto Mark; Rojas, Anabel; Hebrok, Matthias; Cano, David A.

2016-01-01

Organ formation is achieved through the complex interplay between signaling pathways and transcriptional cascades. The canonical Wnt signaling pathway plays multiple roles during embryonic development including patterning, proliferation and differentiation in distinct tissues. Previous studies have established the importance of this pathway at multiple stages of pancreas formation as well as in postnatal organ function and homeostasis. In mice, gain-of-function experiments have demonstrated that activation of the canonical Wnt pathway results in pancreatic hypoplasia, a phenomenon whose underlying mechanisms remains to be elucidated. Here, we show that ectopic activation of epithelial canonical Wnt signaling causes aberrant induction of gastric and intestinal markers both in the pancreatic epithelium and mesenchyme, leading to the development of gut-like features. Furthermore, we provide evidence that β -catenin-induced impairment of pancreas formation depends on Hedgehog signaling. Together, our data emphasize the developmental plasticity of pancreatic progenitors and further underscore the key role of precise regulation of signaling pathways to maintain appropriate organ boundaries. PMID:27736991

I’ll Be Back: On the Multiple Lives of Users of a Mobile Activity Tracking Application

PubMed Central

Lin, Zhiyuan; Althoff, Tim; Leskovec, Jure

2018-01-01

Mobile health applications that track activities, such as exercise, sleep, and diet, are becoming widely used. While these activity tracking applications have the potential to improve our health, user engagement and retention are critical factors for their success. However, long-term user engagement patterns in real-world activity tracking applications are not yet well understood. Here we study user engagement patterns within a mobile physical activity tracking application consisting of 115 million logged activities taken by over a million users over 31 months. Specifically, we show that over 75% of users return and re-engage with the application after prolonged periods of inactivity, no matter the duration of the inactivity. We find a surprising result that the re-engagement usage patterns resemble those of the start of the initial engagement period, rather than being a simple continuation of the end of the initial engagement period. This evidence points to a conceptual model of multiple lives of user engagement, extending the prevalent single life view of user activity. We demonstrate that these multiple lives occur because the users have a variety of different primary intents or goals for using the app. These primary intents are associated with how long each life lasts and how likely the user is to re-engage for a new life. We find evidence for users being more likely to stop using the app once they achieved their primary intent or goal (e.g., weight loss). However, these users might return once their original intent resurfaces (e.g., wanting to lose newly gained weight). We discuss implications of the multiple life paradigm and propose a novel prediction task of predicting the number of lives of a user. Based on insights developed in this work, including a marker of improved primary intent performance, our prediction models achieve 71% ROC AUC. Overall, our research has implications for modeling user re-engagement in health activity tracking applications and has consequences for how notifications, recommendations as well as gamification can be used to increase engagement. PMID:29780978

Plasma Endothelial Microparticles in Multiple Sclerosis: A Novel Metric Assay of Disease Activity and Response to Treatment

DTIC Science & Technology

2011-09-01

direct link to a source of increased tissue iron deposition which is characteristic for multiple sclerosis . The results of these data and their... Multiple Sclerosis : A Novel Metric Assay of Disease Activity and Response to Treatment PRINCIPAL INVESTIGATOR: Jonathan Steven...SUBTITLE 5a. CONTRACT NUMBER Plasma Endothelial Microparticles in Multiple Sclerosis : A Novel Metric Assay of Disease Activity and Response to

Use of Magnetic Resonance Imaging as Well as Clinical Disease Activity in the Clinical Classification of Multiple Sclerosis and Assessment of Its Course

PubMed Central

Dhib-Jalbut, Suhayl; Dowling, Peter; Durelli, Luca; Ford, Corey; Giovannoni, Gavin; Halper, June; Harris, Colleen; Herbert, Joseph; Li, David; Lincoln, John A.; Lisak, Robert; Lublin, Fred D.; Lucchinetti, Claudia F.; Moore, Wayne; Naismith, Robert T.; Oehninger, Carlos; Simon, Jack; Sormani, Maria Pia

2012-01-01

It has recently been suggested that the Lublin-Reingold clinical classification of multiple sclerosis (MS) be modified to include the use of magnetic resonance imaging (MRI). An international consensus conference sponsored by the Consortium of Multiple Sclerosis Centers (CMSC) was held from March 5 to 7, 2010, to review the available evidence on the need for such modification of the Lublin-Reingold criteria and whether the addition of MRI or other biomarkers might lead to a better understanding of MS pathophysiology and disease course over time. The conference participants concluded that evidence of new MRI gadolinium-enhancing (Gd+) T1-weighted lesions and unequivocally new or enlarging T2-weighted lesions (subclinical activity, subclinical relapses) should be added to the clinical classification of MS in distinguishing relapsing inflammatory from progressive forms of the disease. The consensus was that these changes to the classification system would provide more rigorous definitions and categorization of MS course, leading to better insights as to the evolution and treatment of MS. PMID:24453741

The role of sustained observations in tracking impacts of environmental change on marine biodiversity and ecosystems.

PubMed

Mieszkowska, N; Sugden, H; Firth, L B; Hawkins, S J

2014-09-28

Marine biodiversity currently faces unprecedented threats from multiple pressures arising from human activities. Global drivers such as climate change and ocean acidification interact with regional eutrophication, exploitation of commercial fish stocks and localized pressures including pollution, coastal development and the extraction of aggregates and fuel, causing alteration and degradation of habitats and communities. Segregating natural from anthropogenically induced change in marine ecosystems requires long-term, sustained observations of marine biota. In this review, we outline the history of biological recording in the coastal and shelf seas of the UK and Ireland and highlight where sustained observations have contributed new understanding of how anthropogenic activities have impacted on marine biodiversity. The contributions of sustained observations, from those collected at observatories, single station platforms and multiple-site programmes to the emergent field of multiple stressor impacts research, are discussed, along with implications for management and sustainable governance of marine resources in an era of unprecedented use of the marine environment. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Pavlovian conditioning of multiple opioid-like responses in mice.

PubMed

Bryant, Camron D; Roberts, Kristofer W; Culbertson, Christopher S; Le, Alan; Evans, Christopher J; Fanselow, Michael S

2009-07-01

Conditional responses in rodents such as locomotion have been reported for drugs of abuse and similar to the placebo response in humans, may be associated with the expectation of reward. We examined several conditional opioid-like responses and the influence of drug expectation on conditioned place preference and concomitant conditional locomotion. Male C57BL/6J mice were conditioned with the selective mu opioid receptor agonist fentanyl (0.2mg/kg, i.p.) in a novel context and subsequently given a vehicle injection. In separate experiments, locomotor activity, Straub tail, hot plate sensitivity, and conditioned place preference (CPP) were measured. Mice exhibited multiple conditional opioid-like responses including conditional hyperlocomotion, a conditional pattern of opioid-like locomotion, Straub tail, analgesia, and place preference. Modulating drug expectation via administration of fentanyl to "demonstrator" mice in the home cage did not affect the expression of conditioned place preference or the concomitant locomotor activity in "observer" mice. In summary, Pavlovian conditioning of an opioid in a novel context induced multiple conditional opioid-like behaviors and provides a model for studying the neurobiological mechanisms of the placebo response in mice.

Seasonally asymmetric enhancement of northern vegetation productivity

NASA Astrophysics Data System (ADS)

Park, T.; Myneni, R.

2017-12-01

Multiple evidences of widespread greening and increasing terrestrial carbon uptake have been documented. In particular, enhanced gross productivity of northern vegetation has been a critical role leading to observed carbon uptake trend. However, seasonal photosynthetic activity and its contribution to observed annual carbon uptake trend and interannual variability are not well understood. Here, we introduce a multiple-source of datasets including ground, atmospheric and satellite observations, and multiple process-based global vegetation models to understand how seasonal variation of land surface vegetation controls a large-scale carbon exchange. Our analysis clearly shows a seasonally asymmetric enhancement of northern vegetation productivity in growing season during last decades. Particularly, increasing gross productivity in late spring and early summer is obvious and dominant driver explaining observed trend and variability. We observe more asymmetric productivity enhancement in warmer region and this spatially varying asymmetricity in northern vegetation are likely explained by canopy development rate, thermal and light availability. These results imply that continued warming may facilitate amplifying asymmetric vegetation activity and cause these trends to become more pervasive, in turn warming induced regime shift in northern land.

Secondary science teachers' use of laboratory activities: Linking epistemological beliefs, goals, and practices

NASA Astrophysics Data System (ADS)

Kang, Nam-Hwa; Wallace, Carolyn S.

2005-01-01

The purpose of this study was to explore how science teachers' epistemological beliefs and teaching goals are related to their use of lab activities. Research questions include (a) What are the teachers' epistemological beliefs pertaining to lab activities? (b) Why do the science teachers use lab activities? (c) How are the teachers' epistemological beliefs and instructional goals related to teaching actions? Two major aspects of epistemologies guided this study: ontological aspect (certainty/diversity of truth) and relational aspect (relationship between the knower and the known). The ontological aspect addresses whether one views knowledge as one certain truth or as tentative multiple truths. The relational aspect addresses whether one views him/herself as a receiver of prescribed knowledge separating self from knowledge construction or as an active meaning maker connecting self to the knowledge construction processes. More sophisticated epistemological beliefs include the acknowledgement of multiple interpretations of the same phenomena and active role of the knower in knowledge construction. Three experienced secondary science teachers were interviewed and observed throughout an academic course. The findings illustrate that a teacher's naïve epistemological beliefs are clearly reflected in the teacher's teaching practices. However, a teacher's sophisticated epistemological beliefs are not always clearly connected to the practice. This seems to be related to the necessary negotiation among their epistemological beliefs, teaching contexts, and instructional goals. Ontological and relational beliefs seem to be connected to different facets of teaching practices. Findings indicate that various syntheses of different aspects of epistemological beliefs and instructional goals are linked to teachers' diverse ways of using lab activities. Implications for research and teacher education are discussed.

Disparity between Physical Capacity and Participation in Seniors with Chronic Disease

PubMed Central

Ashe, Maureen C.; Eng, Janice J.; Miller, William C.; Soon, Judith A.

2011-01-01

Consistently low rates of physical activity are reported for older adults and there is even lower participation if a chronic disease is present. Purpose To explore the predictors of physical capacity and participation in older community-dwelling individuals living with multiple chronic diseases. Methods This was a descriptive cross-sectional investigation of physical capacity (physiological potential) and physical activity participation (recorded engagement in physical activity). Multiple regression and odds ratios were used to investigate determinants of physical capacity (6 Minute Walk Test) and physical activity participation (Physical Activity Scale for Individuals with Physical Disabilities Questionnaire; pedometer steps/day). Results 200 community dwelling ambulatory participants living with 2 or more chronic disease were assessed. Sixty-five percent (65%) were women and the mean age was 74 ± 6 years (range 65–90 years). Mobility (Timed Up and Go) was a consistent determinant across all 3 primary outcomes. For the Six Minute Walk Test, determinants included mobility, BMI, grip strength, number of medications, leg strength, balance and Chronic Disease Management Self Efficacy Scale (r2=0.58; P=.000). The determinants for the self-reported participation measure (Physical Activity Scale for Individuals with Physical Disabilities Questionnaire) was mobility (r2=0.04; P=.007). For the mean daily pedometer steps, the determinants included mobility, body mass index (BMI), age and Chronic Disease Management Self-Efficacy Scale (r2=0.27; P=.000). There were higher risks for inactivity associated with impairments compared with the presence of a chronic disease. In addition, over 1/3 of participants had sufficient physical capacity, but did not meet minimal recommendations of physical activity. Conclusion This study suggests that it is easier to predict an individual’s physical capacity than their actual physical participation. PMID:17596782

Recruitment of activated IRF-3 and CBP/p300 to herpes simplex virus ICP0 nuclear foci: Potential role in blocking IFN-{beta} induction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Melroe, Gregory T.; Silva, Lindsey; Schaffer, Priscilla A.

2007-04-10

The host innate response to viral infection includes the production of interferons, which is dependent on the coordinated activity of multiple transcription factors. Herpes simplex virus 1 (HSV-1) has been shown to block efficient interferon expression by multiple mechanisms. We and others have demonstrated that HSV-1 can inhibit the transcription of genes promoted by interferon regulatory factor-3 (IRF-3), including interferon beta (IFN-{beta}), and that the immediate-early ICP0 protein is sufficient for this function. However, the exact mechanism by which ICP0 blocks IRF-3 activity has yet to be determined. Unlike some other viral proteins that inhibit IRF-3 activity, ICP0 does notmore » appear to affect phosphorylation and dimerization of IRF-3. Here, we show that a portion of activated IRF-3 co-localizes with nuclear foci containing ICP0 at early times after virus infection. Co-localization to ICP0-containing foci is also seen with the IRF-3-binding partners and transcriptional co-activators, CBP and p300. In addition, using immunoprecipitation of infected cell lysates, we can immunoprecipitate a complex containing ICP0, IRF-3, and CBP. Thus we hypothesize that ICP0 recruits activated IRF-3 and CBP/p300 to nuclear structures, away from the host chromatin. This leads to the inactivation and accelerated degradation of IRF-3, resulting in reduced transcription of IFN-{beta} and an inhibition of the host response. Therefore, ICP0 provides an example of how viruses can block IFN-{beta} induction by sequestration of important transcription factors essential for the host response.« less

p21-Activated kinase 5: a pleiotropic kinase.

PubMed

Wen, Yi-Yang; Wang, Xiao-Xia; Pei, Dong-Sheng; Zheng, Jun-Nian

2013-12-15

The PAKs (p21-activated kinases) are highly conserved serine/threonine protein kinases which comprise six mammalian PAKs. PAK5 (p21-activated kinase 5) is the least understood member of PAKs that regulate many intracellular processes when they are stimulated by activated forms of the small GTPases Cdc42 and Rac. PAK5 takes an important part in multiple signal pathways in mammalian cells and controls a variety of cellular functions including cytoskeleton organization, cell motility and apoptosis. The main goal of this review is to describe the structure, mechanisms underlying its activity regulation, its role in apoptosis and the likely directions of further research. Copyright © 2013 Elsevier Ltd. All rights reserved.

Minocycline: far beyond an antibiotic

PubMed Central

Garrido-Mesa, N; Zarzuelo, A; Gálvez, J

2013-01-01

Minocycline is a second-generation, semi-synthetic tetracycline that has been in therapeutic use for over 30 years because of its antibiotic properties against both gram-positive and gram-negative bacteria. It is mainly used in the treatment of acne vulgaris and some sexually transmitted diseases. Recently, it has been reported that tetracyclines can exert a variety of biological actions that are independent of their anti-microbial activity, including anti-inflammatory and anti-apoptotic activities, and inhibition of proteolysis, angiogenesis and tumour metastasis. These findings specifically concern to minocycline as it has recently been found to have multiple non-antibiotic biological effects that are beneficial in experimental models of various diseases with an inflammatory basis, including dermatitis, periodontitis, atherosclerosis and autoimmune disorders such as rheumatoid arthritis and inflammatory bowel disease. Of note, minocycline has also emerged as the most effective tetracycline derivative at providing neuroprotection. This effect has been confirmed in experimental models of ischaemia, traumatic brain injury and neuropathic pain, and of several neurodegenerative conditions including Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, Alzheimer's disease, multiple sclerosis and spinal cord injury. Moreover, other pre-clinical studies have shown its ability to inhibit malignant cell growth and activation and replication of human immunodeficiency virus, and to prevent bone resorption. Considering the above-mentioned findings, this review will cover the most important topics in the pharmacology of minocycline to date, supporting its evaluation as a new therapeutic approach for many of the diseases described herein. PMID:23441623

Barriers to physical activity and restorative care for residents in long-term care: a review of the literature.

PubMed

Benjamin, Kathleen; Edwards, Nancy; Ploeg, Jenny; Legault, Frances

2014-01-01

Despite the benefits of physical activity, residents living in long-term care (LTC) are relatively sedentary. Designing successful physical activity and restorative care programs requires a good understanding of implementation barriers. A database search (2002-2013) yielded seven studies (nine articles) that met our inclusion criteria. We also reviewed 31 randomized controlled trials (RCTs) to determine if the authors explicitly discussed the barriers encountered while implementing their interventions. Eleven RCTs (13 articles) included a discussion of the barriers. Hence, a total of 18 studies (22 articles) were included in this review. Barriers occurred at resident (e.g., health status), environmental (e.g., lack of space for physical activity), and organizational (e.g., staffing and funding constraints) levels. These barriers intersect to adversely affect the physical activity of older people living in LTC. Future studies targeting physical activity interventions for residents living in LTC are needed to address these multiple levels of influence.

Is the canonical RAF-MEK-ERK signaling pathway a therapeutic target in SCLC?

PubMed Central

Cristea, Sandra; Sage, Julien

2017-01-01

The activity of the RAF-MEK-ERK signaling pathway is critical for the proliferation of normal and cancerous cells. Oncogenic mutations driving the development of lung adenocarcinoma often activate this signaling pathway. In contrast, pathway activity levels and their biological roles are not well established in small cell lung cancer (SCLC), a fast-growing neuroendocrine lung cancer subtype. Here we discuss the function of the RAF-MEK-ERK kinase pathway and the mechanisms leading to its activation in SCLC cells. In particular, we argue that activation of this pathway may be beneficial to the survival, proliferation and spread of SCLC cells in response to multiple stimuli. We also consider evidence that high levels of RAF-MEK-ERK pathway activity may be detrimental to SCLC tumors, including in part by interfering with their neuroendocrine fate. Based on these observations, we examine when small molecules targeting kinases in the RAF-MEK-ERK pathway may be useful therapeutically in SCLC patients, including in combination with other therapeutic agents. PMID:27133774

Development of an ESL curriculum to educate Chinese immigrants about physical activity.

PubMed

Taylor, Victoria M; Cripe, Swee May; Acorda, Elizabeth; Teh, Chong; Coronado, Gloria; Do, Hoai; Woodall, Erica; Hislop, T Gregory

2008-08-01

Regular physical activity reduces the risk of many chronic conditions. Multiple studies have shown that Asians in North America engage in less physical activity than the general population. One area for strategic development in the area of health education is the design and evaluation of English as a second language (ESL) curricula. The PRECEDE model and findings from focus groups were used to develop a physical activity ESL curriculum for Chinese immigrants. In general, focus group participants recognized that physical activity contributes to physical and mental wellbeing. However, the benefits of physical activity were most commonly described in terms of improved blood circulation, immune responses, digestion, and reflexes. The importance of peer pressure and the encouragement of friends in adhering to regular physical activity regimens were mentioned frequently. Reported barriers to regular physical activity included lack of time, weather conditions, and financial costs. The ESL curriculum aims to both promote physical activity and improve knowledge, and includes seven different ESL exercises. Our curriculum development methods could be replicated for other health education topics and in other limited English-speaking populations.

DEVELOPMENT OF AN ESL CURRICULUM TO EDUCATE CHINESE IMMIGRANTS ABOUT PHYSICAL ACTIVITY

PubMed Central

Taylor, Victoria M.; Cripe, Swee May; Acorda, Elizabeth; Teh, Chong; Coronado, Gloria; Do, Hoai; Woodall, Erica; Hislop, T. Gregory

2009-01-01

Regular physical activity reduces the risk of many chronic conditions. Multiple studies have shown that Asians in North America engage in less physical activity than the general population. One area for strategic development in the area of health education is the design and evaluation of English as a second language (ESL) curricula. The PRECEDE model and findings from focus groups were used to develop a physical activity ESL curriculum for Chinese immigrants. In general, focus group participants recognized that physical activity contributes to physical and mental wellbeing. However, the benefits of physical activity were most commonly described in terms of improved blood circulation, immune responses, digestion, and reflexes. The importance of peer pressure and the encouragement of friends in adhering to regular physical activity regimens were mentioned frequently. Reported barriers to regular physical activity included lack of time, weather conditions, and financial costs. The ESL curriculum aims to both promote physical activity and improve knowledge, and includes seven different ESL exercises. Our curriculum development methods could be replicated for other health education topics and in other limited English-speaking populations. PMID:17943444

Multimodal Wireless Sensor Network-Based Ambient Assisted Living in Real Homes with Multiple Residents

PubMed Central

Tunca, Can; Alemdar, Hande; Ertan, Halil; Incel, Ozlem Durmaz; Ersoy, Cem

2014-01-01

Human activity recognition and behavior monitoring in a home setting using wireless sensor networks (WSNs) provide a great potential for ambient assisted living (AAL) applications, ranging from health and wellbeing monitoring to resource consumption monitoring. However, due to the limitations of the sensor devices, challenges in wireless communication and the challenges in processing large amounts of sensor data in order to recognize complex human activities, WSN-based AAL systems are not effectively integrated in the home environment. Additionally, given the variety of sensor types and activities, selecting the most suitable set of sensors in the deployment is an important task. In order to investigate and propose solutions to such challenges, we introduce a WSN-based multimodal AAL system compatible for homes with multiple residents. Particularly, we focus on the details of the system architecture, including the challenges of sensor selection, deployment, networking and data collection and provide guidelines for the design and deployment of an effective AAL system. We also present the details of the field study we conducted, using the systems deployed in two different real home environments with multiple residents. With these systems, we are able to collect ambient sensor data from multiple homes. This data can be used to assess the wellbeing of the residents and identify deviations from everyday routines, which may be indicators of health problems. Finally, in order to elaborate on the possible applications of the proposed AAL system and to exemplify directions for processing the collected data, we provide the results of several human activity inference experiments, along with examples on how such results could be interpreted. We believe that the experiences shared in this work will contribute towards accelerating the acceptance of WSN-based AAL systems in the home setting. PMID:24887044

Multimodal wireless sensor network-based ambient assisted living in real homes with multiple residents.

PubMed

Tunca, Can; Alemdar, Hande; Ertan, Halil; Incel, Ozlem Durmaz; Ersoy, Cem

2014-05-30

Human activity recognition and behavior monitoring in a home setting using wireless sensor networks (WSNs) provide a great potential for ambient assisted living (AAL) applications, ranging from health and wellbeing monitoring to resource consumption monitoring. However, due to the limitations of the sensor devices, challenges in wireless communication and the challenges in processing large amounts of sensor data in order to recognize complex human activities, WSN-based AAL systems are not effectively integrated in the home environment. Additionally, given the variety of sensor types and activities, selecting the most suitable set of sensors in the deployment is an important task. In order to investigate and propose solutions to such challenges, we introduce a WSN-based multimodal AAL system compatible for homes with multiple residents. Particularly, we focus on the details of the system architecture, including the challenges of sensor selection, deployment, networking and data collection and provide guidelines for the design and deployment of an effective AAL system. We also present the details of the field study we conducted, using the systems deployed in two different real home environments with multiple residents. With these systems, we are able to collect ambient sensor data from multiple homes. This data can be used to assess the wellbeing of the residents and identify deviations from everyday routines, which may be indicators of health problems. Finally, in order to elaborate on the possible applications of the proposed AAL system and to exemplify directions for processing the collected data, we provide the results of several human activity inference experiments, along with examples on how such results could be interpreted. We believe that the experiences shared in this work will contribute towards accelerating the acceptance of WSN-based AAL systems in the home setting.

Bringing functions together with fusion enzymes--from nature's inventions to biotechnological applications.

PubMed

Elleuche, Skander

2015-02-01

It is a mammoth task to develop a modular protein toolbox enabling the production of posttranslational organized multifunctional enzymes that catalyze reactions in complex pathways. However, nature has always guided scientists to mimic evolutionary inventions in the laboratory and, nowadays, versatile methods have been established to experimentally connect enzymatic activities with multiple advantages. Among the oldest known natural examples is the linkage of two or more juxtaposed proteins catalyzing consecutive, non-consecutive, or opposing reactions by a native peptide bond. There are multiple reasons for the artificial construction of such fusion enzymes including improved catalytic activities, enabled substrate channelling by proximity of biocatalysts, higher stabilities, and cheaper production processes. To produce fused proteins, it is either possible to genetically fuse coding open reading frames or to connect proteins in a posttranslational process. Molecular biology techniques that have been established for the production of end-to-end or insertional fusions include overlap extension polymerase chain reaction, cloning, and recombination approaches. Depending on their flexibility and applicability, these methods offer various advantages to produce fusion genes in high throughput, different orientations, and including linker sequences to maximize the flexibility and performance of fusion partners. In this review, practical techniques to fuse genes are highlighted, enzymatic parameters to choose adequate enzymes for fusion approaches are summarized, and examples with biotechnological relevance are presented including a focus on plant biomass-degrading glycosyl hydrolases.

Deployment Area Selection and Land Withdrawal/Acquisition. Chapter 4. M-X/MPS (M-X/Multiple Protective Shelter). Volume 1. Environmental Consequences to the Study Regions and Operating Base Vicinities.

DTIC Science & Technology

1981-10-02

to the point of energy imbalance and declining reproductive rates. Increased human population would also increase poaching of pronghorn in areas...reduced. Such effects, however, could be mitigated as discussed below and in ETR-38. Increased human activity, including poaching , harassment, habitat...when intense activity would be widespread in their habitat. Mortality resulting from habitat loss and poaching would decrease herd size during 4-205 4

A Cognitive System Model for Human/Automation Dynamics in Airspace Management

NASA Technical Reports Server (NTRS)

Corker, Kevin M.; Pisanich, Gregory; Lebacqz, J. Victor (Technical Monitor)

1997-01-01

NASA has initiated a significant thrust of research and development focused on providing the flight crew and air traffic managers automation aids to increase capacity in en route and terminal area operations through the use of flexible, more fuel-efficient routing, while improving the level of safety in commercial carrier operations. In that system development, definition of cognitive requirements for integrated multi-operator dynamic aiding systems is fundamental. In order to support that cognitive function definition, we have extended the Man Machine Integrated Design and Analysis System (MIDAS) to include representation of multiple cognitive agents (both human operators and intelligent aiding systems) operating aircraft, airline operations centers and air traffic control centers in the evolving airspace. The demands of this application require representation of many intelligent agents sharing world-models, and coordinating action/intention with cooperative scheduling of goals and actions in a potentially unpredictable world of operations. The MIDAS operator models have undergone significant development in order to understand the requirements for operator aiding and the impact of that aiding in the complex nondeterminate system of national airspace operations. The operator model's structure has been modified to include attention functions, action priority, and situation assessment. The cognitive function model has been expanded to include working memory operations including retrieval from long-term store, interference, visual-motor and verbal articulatory loop functions, and time-based losses. The operator's activity structures have been developed to include prioritization and interruption of multiple parallel activities among multiple operators, to provide for anticipation (knowledge of the intention and action of remote operators), and to respond to failures of the system and other operators in the system in situation-specific paradigms. The model's internal representation has been be modified so that multiple, autonomous sets of equipment will function in a scenario as the single equipment sets do now. In order to support the analysis requirements with multiple items of equipment, it is necessary for equipment to access the state of other equipment objects at initialization time (a radar object may need to access the position and speed of aircraft in its area, for example), and as a function of perception and sensor system interaction. The model has been improved to include multiple world-states as a function of equipment am operator interaction. The model has been used -1o predict the impact of warning and alert zones in aircraft operation, and, more critic-ally, the interaction of flight-deck based warning mechanisms and air traffic controller action in response to ground-based conflict prediction and alerting systems. In this operation, two operating systems provide alerting to two autonomous, but linked sets of operators, whose view of the system and whose dynamics in response are radically different. System stability and operator action was predicted using the MIDAS model.

CHANDRA OBSERVATIONS OF GALAXY ZOO MERGERS: FREQUENCY OF BINARY ACTIVE NUCLEI IN MASSIVE MERGERS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Teng, Stacy H.; Schawinski, Kevin; Urry, C. Megan

We present the results from a Chandra pilot study of 12 massive galaxy mergers selected from Galaxy Zoo. The sample includes major mergers down to a host galaxy mass of 10{sup 11} M{sub Sun} that already have optical active galactic nucleus (AGN) signatures in at least one of the progenitors. We find that the coincidences of optically selected active nuclei with mildly obscured (N{sub H} {approx}< 1.1 Multiplication-Sign 10{sup 22} cm{sup -2}) X-ray nuclei are relatively common (8/12), but the detections are too faint (<40 counts per nucleus; f{sub 2-10keV} {approx}< 1.2 Multiplication-Sign 10{sup -13} erg s{sup -1} cm{sup -2})more » to reliably separate starburst and nuclear activity as the origin of the X-ray emission. Only one merger is found to have confirmed binary X-ray nuclei, though the X-ray emission from its southern nucleus could be due solely to star formation. Thus, the occurrences of binary AGNs in these mergers are rare (0%-8%), unless most merger-induced active nuclei are very heavily obscured or Compton thick.« less

Determinants of physical activity in America: a first characterization of physical activity profile using the National Health and Nutrition Examination Survey (NHANES).

PubMed

Kao, Ming-Chih Jeffrey; Jarosz, Renata; Goldin, Michael; Patel, Amy; Smuck, Matthew

2014-10-01

To develop and implement methodologies for characterizing accelerometry-derived patterns of physical activity (PA) in the United States in relation to demographics, anthropometrics, behaviors, and comorbidities using the National Health and Nutrition Examination Survey (NHANES) dataset. Retrospective analysis of nationally representative database. Computer-generated modeling in silico. A total of 6329 adults in the United States from the NHANES 2003-2004 database. To discover subtle multivariate signal in the dynamic and noisy accelerometry data, we developed a novel approach, termed discretized multiple adaptive regression and implemented the algorithm in SAS 9.2 (SAS Institute, Cary, NC). Demographic, anthropometric, comorbidity, and behavioral variables. The intensity of PA decreased with both increased age and increased body mass index. Both greater education and greater income correlate with increased activity over short durations and reduced activity intensity over long durations. Numerous predictors demonstrated effects within activity ranges that may be masked by use of the standard activity intensity intervals. These include age, one of the most robust variables, where we discovered decreasing activities inside the moderate activity range. It also includes gender, where women compared with men have increased proportions of active times up to the center of light activity range, and income greater than $45,000, where a complex effect is seen with little correspondence to existing cut-points. The results presented in this study suggest that the method of multiple regression and heat map visualization can generate insights otherwise hidden in large datasets such as NHANES. A review of the provided heat maps reveals the trends discussed previously involving demographic, anthropometric, comorbidity, and behavioral variables. It also demonstrates the power of accelerometry to expose alterations in PA. Ultimately, this study provides a US population-based norm to use in future studies of PA. Copyright © 2014 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2017-06-01

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

Return to Sports After Multiple Trauma: Which Factors Are Responsible?-Results From a 17-Year Follow-up.

PubMed

Weber, Christian D; Horst, Klemens; Nguyen, Anthony R; Bader, Magdalena J; Probst, Christian; Zelle, Boris; Pape, Hans-Christoph; Dienstknecht, Thomas

2017-09-01

We hypothesize that the majority of polytraumatised patients are unable to maintain their preinjury level of sporting activity, and that musculoskeletal injuries are a major contributing factor. We assessed the impact of such injuries on sporting prowess, with a focus on isolating, particularly debilitating musculoskeletal trauma. We conducted a cohort study of 637 patients at a level 1 trauma centre, to assess the long-term outcome of severe trauma on return to sporting activities (RTS). Data collated on the multiply injured patient included preinjury physical activity, standardized outcome scores (SF-12, GOS, HASPOC), and clinical follow-up of at least 10 years duration. The return to preinjury sports participation was defined as a primary outcome parameter. Regression analyses were performed to identify specific injuries interfering with the RTS. Prognostic study; Level of evidence, II. Mean follow-up was 17 ± 5 years. We included 465 patients, including 207 athletic and 258 nonathletic individuals. Mean age at the time of injury was 26 ± 11.5 years and injury severity was comparable between the 2 cohorts. The deleterious effects on quality of life and the total duration of the rehabilitation process were also similar in athletes and nonathletes. Athletes were more likely to be unable to return to preinjury activities, or to return to a lower level of sporting prowess posttrauma. We identified knee injuries as the type of musculoskeletal trauma most likely to be career ending for the athlete (odds ratio 3.4, 95% confidence interval, 1.4-8.3; P = 0.008). Our results demonstrate an enforced shift from high-impact and team sports to low-impact activities after multiple trauma. Injuries of the lower extremities, especially around the knee joint, seem to have the highest lifechanging potential, preventing individuals from returning to their previous sporting activities.

Teaching children with autism to use photographic activity schedules: maintenance and generalization of complex response chains.

PubMed Central

MacDuff, G S; Krantz, P J; McClannahan, L E

1993-01-01

We used a graduated guidance procedure to teach 4 boys with autism to follow photographic activity schedules to increase on-task and on-schedule behavior. The multiple baseline across participants design included baseline, teaching, maintenance, resequencing of photographs, and generalization to novel photographs phases. The results indicated that photographic activity schedules (albums depicting after-school activities) produced sustained engagement, and skills generalized to a new sequence of photographs and to new photographs. The acquisition of schedule-following skills enabled these children with severe developmental disabilities to display lengthy response chains, independently change activities, and change activities in different group home settings in the absence of immediate supervision and prompts from others. PMID:8473261

The Moon Village Concept

NASA Astrophysics Data System (ADS)

Messina, Piero; Foing, Bernard H.; Hufenbach, Bernhard; Haignere, Claudie; Schrogl, Kai-Uwe

2016-07-01

The "Moon Village" concept Space exploration is anchored in the International Space Station and in the current and future automatic and planetary automatic and robotic missions that pave the way for future long-term exploration objectives. The Moon represents a prime choice for scientific, operational and programmatic reasons and could be the enterprise that federates all interested Nations. On these considerations ESA is currently elaborating the concept of a Moon Village as an ensemble where multiple users can carry out multiple activities. The Moon Village has the ambition to serve a number of objectives that have proven to be of interest (including astronomy, fundamental research, resources management, moon science, etc. ) to the space community and should be the catalyst of new alliances between public and private entities including non-space industries. Additionally the Moon Village should provide a strong inspirational and education tool for the younger generations . The Moon Village will rely both on automatic, robotic and human-tendered structures to achieve sustainable moon surface operations serving multiple purposes on an open-architecture basis. This Europe-inspired initiative should rally all communities (across scientific disciplines, nations, industries) and make it to the top of the political agendas as a the scientific and technological undertaking but also political and inspirational endeavour of the XXI century. The current reflections are of course based on the current activities and plans on board the ISS and the discussion held in international fora such as the ISECG. The paper will present the status of these reflections, also in view of the ESA Council at Ministerial Level 2016, and will give an overview of the on-going activities being carried out to enable the vision of a Moon Village.

Enhanced multisensory integration and motor reactivation after active motor learning of audiovisual associations.

PubMed

Butler, Andrew J; James, Thomas W; James, Karin Harman

2011-11-01

Everyday experience affords us many opportunities to learn about objects through multiple senses using physical interaction. Previous work has shown that active motor learning of unisensory items enhances memory and leads to the involvement of motor systems during subsequent perception. However, the impact of active motor learning on subsequent perception and recognition of associations among multiple senses has not been investigated. Twenty participants were included in an fMRI study that explored the impact of active motor learning on subsequent processing of unisensory and multisensory stimuli. Participants were exposed to visuo-motor associations between novel objects and novel sounds either through self-generated actions on the objects or by observing an experimenter produce the actions. Immediately after exposure, accuracy, RT, and BOLD fMRI measures were collected with unisensory and multisensory stimuli in associative perception and recognition tasks. Response times during audiovisual associative and unisensory recognition were enhanced by active learning, as was accuracy during audiovisual associative recognition. The difference in motor cortex activation between old and new associations was greater for the active than the passive group. Furthermore, functional connectivity between visual and motor cortices was stronger after active learning than passive learning. Active learning also led to greater activation of the fusiform gyrus during subsequent unisensory visual perception. Finally, brain regions implicated in audiovisual integration (e.g., STS) showed greater multisensory gain after active learning than after passive learning. Overall, the results show that active motor learning modulates the processing of multisensory associations.

Getting Australia more active: challenges and opportunities for health promotion.

PubMed

Hills, A P; Street, S J; Harris, N

2014-04-01

A growing body of evidence demonstrates that regular physical activity promotes health and assists in the prevention of non-communicable diseases but this is presently curtailed by low and unhealthy participation rates in Australia and comparable industrialised countries. Compounding the problem is knowledge that physical inactivity is independently associated with poor health outcomes. Despite physical activity being described as public health's 'best bet' or 'best buy', motivating individuals and groups to adopt and maintain physical activity continues to be a major challenge for health professionals. Global advocacy for prevention efforts must be operationalised through national to local strategies to promote and support physical activity in multiple settings including the home, schools and workplace. The Australian health promotion community has and continues to play a leadership role in physical activity promotion. However, there is an urgent need to continue to promote the importance of physical activity, along with its pivotal role in the prevention of non-communicable diseases, alongside related agendas including healthy diets, tobacco control and environmental sustainability. This commentary overviews the contemporary status of physical activity promotion in Australia and identifies key challenges and opportunities moving forward.

Secondary treatment of films of colloidal quantum dots for optoelectronics and devices produced thereby

DOEpatents

Semonin, Octavi Escala; Luther, Joseph M; Beard, Matthew C; Chen, Hsiang-Yu

2014-04-01

A method of forming an optoelectronic device. The method includes providing a deposition surface and contacting the deposition surface with a ligand exchange chemical and contacting the deposition surface with a quantum dot (QD) colloid. This initial process is repeated over one or more cycles to form an initial QD film on the deposition surface. The method further includes subsequently contacting the QD film with a secondary treatment chemical and optionally contacting the surface with additional QDs to form an enhanced QD layer exhibiting multiple exciton generation (MEG) upon absorption of high energy photons by the QD active layer. Devices having an enhanced QD active layer as described above are also disclosed.

Write Now! Using Reflective Writing beyond the Humanities and Social Sciences

ERIC Educational Resources Information Center

Cannady, Rachel E.; Gallo, Kasia Z.

2016-01-01

Writing is an important teaching and learning tool that fosters active and critical thinking. There are multiple pressures for disciplines outside the humanities and social sciences to integrate writing in their courses. The shift from teaching solely discipline-specific skills to including writing in a meaningful way can be a daunting process. An…

Multiple DC, single AC converter with a switched DC transformer

DOEpatents

Donnelly, M.K.; Hammerstrom, D.J.

1997-05-20

The invention is an improvement of the PASC inverter, wherein the improvements include the reduction from two shorting gates per transformer to one shorting gate per transformer and replacement of active control of the shorting gate with passive control of the shorting gate. Further advantages are obtained through the use of anti-parallel gate sets. 14 figs.

Multiple DC, single AC converter with a switched DC transformer

DOEpatents

Donnelly, Matthew K.; Hammerstrom, Donald J.

1997-01-01

The invention is an improvement of the PASC inverter, wherein the improvements include the reduction from two shorting gates per transformer to one shorting gate per transformer and replacement of active control of the shorting gate with passive control of the shorting gate. Further advantages are obtained through the use of anti-parallel gate sets.

Fisheries indicators, freshwater

USGS Publications Warehouse

Kwak, Thomas J.

2010-01-01

Freshwater fisheries exist among diverse ecosystems and fauna, provide societal benefits, and are influenced by human activities. Fisheries scientists assess the status and sustainability of fisheries by multiple approaches, including abundance and condition indices, population parameters, community indices, modeling, and surveys of habitat and human dimensions. The future sustainability of freshwater fisheries is limited not by available methods but by society’s will.

GEARS a 3D Virtual Learning Environment and Virtual Social and Educational World Used in Online Secondary Schools

ERIC Educational Resources Information Center

Barkand, Jonathan; Kush, Joseph

2009-01-01

Virtual Learning Environments (VLEs) are becoming increasingly popular in online education environments and have multiple pedagogical advantages over more traditional approaches to education. VLEs include 3D worlds where students can engage in simulated learning activities such as Second Life. According to Claudia L'Amoreaux at Linden Lab, "at…

A Manual for Planning a Secondary School Building, Pamphlet C-6, Home Economics.

ERIC Educational Resources Information Center

Wohlers, A. E.

The home economics suite should be planned in relation to the number of teaching stations required and the types of activities that will be carried on in the various rooms. Rooms and spaces under consideration include clothing laboratories, combination or multiple use teaching stations, and auxiliary rooms. Maximum flexibility of use is possible…

Sold to Dominic for 1 Troy and 3 (24) Fin: An Economic Money System.

ERIC Educational Resources Information Center

Williams, Sandra L.

Arranged in two sections, this paper details a project for incorporating ongoing economics study into a sixth-grade curriculum by creating an imaginary economic system. Section 1 highlights the main activities of the project, which include the following. A money system, based on units of 12 to enhance multiplication skills, was instituted, with…

High-mobility group box 1 is an important mediator of microglial activation induced by cortical spreading depression.

PubMed

Takizawa, Tsubasa; Shibata, Mamoru; Kayama, Yohei; Shimizu, Toshihiko; Toriumi, Haruki; Ebine, Taeko; Unekawa, Miyuki; Koh, Anri; Yoshimura, Akihiko; Suzuki, Norihiro

2017-03-01

Single episodes of cortical spreading depression (CSD) are believed to cause typical migraine aura, whereas clusters of spreading depolarizations have been observed in cerebral ischemia and subarachnoid hemorrhage. We recently demonstrated that the release of high-mobility group box 1 (HMGB1) from cortical neurons after CSD in a rodent model is dependent on the number of CSD episodes, such that only multiple CSD episodes can induce significant HMGB1 release. Here, we report that only multiple CSD inductions caused microglial hypertrophy (activation) accompanied by a greater impact on the transcription activity of the HMGB1 receptor genes, TLR2 and TLR4, while the total number of cortical microglia was not affected. Both an HMGB1-neurtalizing antibody and the HMGB1 inhibitor glycyrrhizin abrogated multiple CSD-induced microglial hypertrophy. Moreover, multiple CSD inductions failed to induce microglial hypertrophy in TLR2/4 double knockout mice. These results strongly implicate the HMGB1-TLR2/4 axis in the activation of microglia following multiple CSD inductions. Increased expression of the lysosomal acid hydrolase cathepsin D was detected in activated microglia by immunostaining, suggesting that lysosomal phagocytic activity may be enhanced in multiple CSD-activated microglia.

Spontaneous mutations in CYC8 and MIG1 suppress the short chronological lifespan of budding yeast lacking SNF1/AMPK

PubMed Central

Maqani, Nazif; Fine, Ryan D.; Shahid, Mehreen; Li, Mingguang; Enriquez-Hesles, Elisa; Smith, Jeffrey S.

2018-01-01

Chronologically aging yeast cells are prone to adaptive regrowth, whereby mutants with a survival advantage spontaneously appear and re-enter the cell cycle in stationary phase cultures. Adaptive regrowth is especially noticeable with short-lived strains, including those defective for SNF1, the homolog of mammalian AMP-activated protein kinase (AMPK). SNF1 becomes active in response to multiple environmental stresses that occur in chronologically aging cells, including glucose depletion and oxidative stress. SNF1 is also required for the extension of chronological lifespan (CLS) by caloric restriction (CR) as defined as limiting glucose at the time of culture inoculation. To identify specific downstream SNF1 targets responsible for CLS extension during CR, we screened for adaptive regrowth mutants that restore chronological longevity to a short-lived snf1∆ parental strain. Whole genome sequencing of the adapted mutants revealed missense mutations in TPR motifs 9 and 10 of the transcriptional co-repressor Cyc8 that specifically mediate repression through the transcriptional repressor Mig1. Another mutation occurred in MIG1 itself, thus implicating the activation of Mig1-repressed genes as a key function of SNF1 in maintaining CLS. Consistent with this conclusion, the cyc8 TPR mutations partially restored growth on alternative carbon sources and significantly extended CLS compared to the snf1∆ parent. Furthermore, cyc8 TPR mutations reactivated multiple Mig1-repressed genes, including the transcription factor gene CAT8, which is responsible for activating genes of the glyoxylate and gluconeogenesis pathways. Deleting CAT8 completely blocked CLS extension by the cyc8 TPR mutations on CLS, identifying these pathways as key Snf1-regulated CLS determinants.

Overweight dogs exercise less frequently and for shorter periods: results of a large online survey of dog owners from the UK.

PubMed

German, Alexander J; Blackwell, Emily; Evans, Mark; Westgarth, Carri

2017-01-01

Canine obesity is now the number one health concern in dogs worldwide. Regular physical activity can improve health, and owners are advised to exercise their dogs on a regular basis. However, limited information exists about associations between overweight status of dogs and walking activity. An online survey was conducted between June and August in 2014, coinciding with the broadcast of a national UK television programme, exploring dog behaviour. Information gathered included signalment, overweight status, and owner-reported information on duration and frequency of dog walking. The University of Liverpool Ethics Committee approved the project, and owners consented to data use. Simple and multiple logistic regression analyses were used to determine associations between overweight status and dog walking activity. Data were available from 11 154 adult dogs, and 1801 (16·1 %) of these were reported as overweight by their owners. Dogs reported to be overweight dogs were more likely to be neutered ( P  < 0·0001) and older ( P  < 0·0001). Various breeds were over-represented including beagle, Cavalier King Charles spaniel, golden retriever, Labrador retriever and pug ( P  < 0·0001 for all). Both frequency and duration of walking were negatively associated with overweight status ( P  < 0·0001 for both). On multiple regression analysis, duration and frequency were independently and negatively associated with the odds of being overweight, along with a range of other factors including age, neuter status and breed. This study has identified associations between overweight status and exercise. In the future, studies should determine the reason for this association, and whether changes in walking activity can influence weight status.

FMRI activity during associative encoding is correlated with cardiorespiratory fitness and source memory performance in older adults

PubMed Central

Hayes, Scott M.; Hayes, Jasmeet P.; Williams, Victoria J.; Liu, Huiting; Verfaellie, Mieke

2017-01-01

Older adults (OA), relative to young adults (YA), exhibit age-related alterations in functional Magnetic Resonance Imaging (fMRI) activity during associative encoding, which contributes to deficits in source memory. Yet, there are remarkable individual differences in brain health and memory performance among OA. Cardiorespiratory fitness (CRF) is one individual difference factor that may attenuate brain aging, and thereby contribute to enhanced source memory in OA. To examine this possibility, 26 OA and 31 YA completed a treadmill-based exercise test to evaluate CRF (peak VO2) and fMRI to examine brain activation during a face-name associative encoding task. Our results indicated that in OA, peak VO2 was positively associated with fMRI activity during associative encoding in multiple regions including bilateral prefrontal cortex, medial frontal cortex, bilateral thalamus and left hippocampus. Next, a conjunction analysis was conducted to assess whether CRF influenced age-related differences in fMRI activation. We classified OA as high or low CRF and compared their activation to YA. High fit OA (HFOA) showed fMRI activation more similar to YA than low fit OA (LFOA) (i.e., reduced age-related differences) in multiple regions including thalamus, posterior and prefrontal cortex. Conversely, in other regions, primarily in prefrontal cortex, HFOA, but not LFOA, demonstrated greater activation than YA (i.e., increased age-related differences). Further, fMRI activity in these brain regions was positively associated with source memory among OA, with a mediation model demonstrating that associative encoding activation in medial frontal cortex indirectly influenced the relationship between peak VO2 and subsequent source memory performance. These results indicate that CRF may contribute to neuroplasticity among OA, reducing age-related differences in some brain regions, consistent with the brain maintenance hypothesis, but accentuating age-differences in other regions, consistent with the brain compensation hypothesis. PMID:28161031

Predictive Physiological Anticipation Preceding Seemingly Unpredictable Stimuli: A Meta-Analysis

PubMed Central

Mossbridge, Julia; Tressoldi, Patrizio; Utts, Jessica

2012-01-01

This meta-analysis of 26 reports published between 1978 and 2010 tests an unusual hypothesis: for stimuli of two or more types that are presented in an order designed to be unpredictable and that produce different post-stimulus physiological activity, the direction of pre-stimulus physiological activity reflects the direction of post-stimulus physiological activity, resulting in an unexplained anticipatory effect. The reports we examined used one of two paradigms: (1) randomly ordered presentations of arousing vs. neutral stimuli, or (2) guessing tasks with feedback (correct vs. incorrect). Dependent variables included: electrodermal activity, heart rate, blood volume, pupil dilation, electroencephalographic activity, and blood oxygenation level dependent (BOLD) activity. To avoid including data hand-picked from multiple different analyses, no post hoc experiments were considered. The results reveal a significant overall effect with a small effect size [fixed effect: overall ES = 0.21, 95% CI = 0.15–0.27, z = 6.9, p < 2.7 × 10−12; random effects: overall (weighted) ES = 0.21, 95% CI = 0.13–0.29, z = 5.3, p < 5.7 × 10−8]. Higher quality experiments produced a quantitatively larger effect size and a greater level of significance than lower quality studies. The number of contrary unpublished reports that would be necessary to reduce the level of significance to chance (p > 0.05) was conservatively calculated to be 87 reports. We explore alternative explanations and examine the potential linkage between this unexplained anticipatory activity and other results demonstrating meaningful pre-stimulus activity preceding behaviorally relevant events. We conclude that to further examine this currently unexplained anticipatory activity, multiple replications arising from different laboratories using the same methods are necessary. The cause of this anticipatory activity, which undoubtedly lies within the realm of natural physical processes (as opposed to supernatural or paranormal ones), remains to be determined. PMID:23109927

FMRI activity during associative encoding is correlated with cardiorespiratory fitness and source memory performance in older adults.

PubMed

Hayes, Scott M; Hayes, Jasmeet P; Williams, Victoria J; Liu, Huiting; Verfaellie, Mieke

2017-06-01

Older adults (OA), relative to young adults (YA), exhibit age-related alterations in functional Magnetic Resonance Imaging (fMRI) activity during associative encoding, which contributes to deficits in source memory. Yet, there are remarkable individual differences in brain health and memory performance among OA. Cardiorespiratory fitness (CRF) is one individual difference factor that may attenuate brain aging, and thereby contribute to enhanced source memory in OA. To examine this possibility, 26 OA and 31 YA completed a treadmill-based exercise test to evaluate CRF (peak VO 2 ) and fMRI to examine brain activation during a face-name associative encoding task. Our results indicated that in OA, peak VO 2 was positively associated with fMRI activity during associative encoding in multiple regions including bilateral prefrontal cortex, medial frontal cortex, bilateral thalamus and left hippocampus. Next, a conjunction analysis was conducted to assess whether CRF influenced age-related differences in fMRI activation. We classified OA as high or low CRF and compared their activation to YA. High fit OA (HFOA) showed fMRI activation more similar to YA than low fit OA (LFOA) (i.e., reduced age-related differences) in multiple regions including thalamus, posterior and prefrontal cortex. Conversely, in other regions, primarily in prefrontal cortex, HFOA, but not LFOA, demonstrated greater activation than YA (i.e., increased age-related differences). Further, fMRI activity in these brain regions was positively associated with source memory among OA, with a mediation model demonstrating that associative encoding activation in medial frontal cortex indirectly influenced the relationship between peak VO 2 and subsequent source memory performance. These results indicate that CRF may contribute to neuroplasticity among OA, reducing age-related differences in some brain regions, consistent with the brain maintenance hypothesis, but accentuating age-differences in other regions, consistent with the brain compensation hypothesis. Published by Elsevier Ltd.

Antimicrobial Activities of Methanol, Ethanol and Supercritical CO2 Extracts of Philippine Piper betle L. on Clinical Isolates of Gram Positive and Gram Negative Bacteria with Transferable Multiple Drug Resistance

PubMed Central

Valle, Demetrio L.; Cabrera, Esperanza C.; Puzon, Juliana Janet M.; Rivera, Windell L.

2016-01-01

Piper betle L. has traditionally been used in alternative medicine in different countries for various therapeutic purposes, including as an anti-infective agent. However, studies reported in the literature are mainly on its activities on drug susceptible bacterial strains. This study determined the antimicrobial activities of its ethanol, methanol, and supercritical CO2 extracts on clinical isolates of multiple drug resistant bacteria which have been identified by the Infectious Disease Society of America as among the currently more challenging strains in clinical management. Assay methods included the standard disc diffusion method and the broth microdilution method for the determination of the minimum inhibitory concentration (MIC) and the minimum bactericidal concentrations (MBC) of the extracts for the test microorganisms. This study revealed the bactericidal activities of all the P. betle leaf crude extracts on methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), extended spectrum β-lactamase-producing Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae, and metallo-β-lactamase-producing Pseudomonas aeruginosa and Acinetobacter baumannii, with minimum bactericidal concentrations that ranged from 19μg/ml to 1250 μg/ml. The extracts proved to be more potent against the Gram positive MRSA and VRE than for the Gram negative test bacteria. VRE isolates were more susceptible to all the extracts than the MRSA isolates. Generally, the ethanol extracts proved to be more potent than the methanol extracts and supercritical CO2 extracts as shown by their lower MICs for both the Gram positive and Gram negative MDRs. MTT cytotoxicity assay showed that the highest concentration (100 μg/ml) of P. betle ethanol extract tested was not toxic to normal human dermal fibroblasts (HDFn). Data from the study firmly established P. betle as an alternative source of anti-infectives against multiple drug resistant bacteria. PMID:26741962

Antimicrobial Activities of Methanol, Ethanol and Supercritical CO2 Extracts of Philippine Piper betle L. on Clinical Isolates of Gram Positive and Gram Negative Bacteria with Transferable Multiple Drug Resistance.

PubMed

Valle, Demetrio L; Cabrera, Esperanza C; Puzon, Juliana Janet M; Rivera, Windell L

2016-01-01

Piper betle L. has traditionally been used in alternative medicine in different countries for various therapeutic purposes, including as an anti-infective agent. However, studies reported in the literature are mainly on its activities on drug susceptible bacterial strains. This study determined the antimicrobial activities of its ethanol, methanol, and supercritical CO2 extracts on clinical isolates of multiple drug resistant bacteria which have been identified by the Infectious Disease Society of America as among the currently more challenging strains in clinical management. Assay methods included the standard disc diffusion method and the broth microdilution method for the determination of the minimum inhibitory concentration (MIC) and the minimum bactericidal concentrations (MBC) of the extracts for the test microorganisms. This study revealed the bactericidal activities of all the P. betle leaf crude extracts on methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), extended spectrum β-lactamase-producing Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae, and metallo-β-lactamase-producing Pseudomonas aeruginosa and Acinetobacter baumannii, with minimum bactericidal concentrations that ranged from 19μg/ml to 1250 μg/ml. The extracts proved to be more potent against the Gram positive MRSA and VRE than for the Gram negative test bacteria. VRE isolates were more susceptible to all the extracts than the MRSA isolates. Generally, the ethanol extracts proved to be more potent than the methanol extracts and supercritical CO2 extracts as shown by their lower MICs for both the Gram positive and Gram negative MDRs. MTT cytotoxicity assay showed that the highest concentration (100 μg/ml) of P. betle ethanol extract tested was not toxic to normal human dermal fibroblasts (HDFn). Data from the study firmly established P. betle as an alternative source of anti-infectives against multiple drug resistant bacteria.

Classroom sound can be used to classify teaching practices in college science courses.

PubMed

Owens, Melinda T; Seidel, Shannon B; Wong, Mike; Bejines, Travis E; Lietz, Susanne; Perez, Joseph R; Sit, Shangheng; Subedar, Zahur-Saleh; Acker, Gigi N; Akana, Susan F; Balukjian, Brad; Benton, Hilary P; Blair, J R; Boaz, Segal M; Boyer, Katharyn E; Bram, Jason B; Burrus, Laura W; Byrd, Dana T; Caporale, Natalia; Carpenter, Edward J; Chan, Yee-Hung Mark; Chen, Lily; Chovnick, Amy; Chu, Diana S; Clarkson, Bryan K; Cooper, Sara E; Creech, Catherine; Crow, Karen D; de la Torre, José R; Denetclaw, Wilfred F; Duncan, Kathleen E; Edwards, Amy S; Erickson, Karen L; Fuse, Megumi; Gorga, Joseph J; Govindan, Brinda; Green, L Jeanette; Hankamp, Paul Z; Harris, Holly E; He, Zheng-Hui; Ingalls, Stephen; Ingmire, Peter D; Jacobs, J Rebecca; Kamakea, Mark; Kimpo, Rhea R; Knight, Jonathan D; Krause, Sara K; Krueger, Lori E; Light, Terrye L; Lund, Lance; Márquez-Magaña, Leticia M; McCarthy, Briana K; McPheron, Linda J; Miller-Sims, Vanessa C; Moffatt, Christopher A; Muick, Pamela C; Nagami, Paul H; Nusse, Gloria L; Okimura, Kristine M; Pasion, Sally G; Patterson, Robert; Pennings, Pleuni S; Riggs, Blake; Romeo, Joseph; Roy, Scott W; Russo-Tait, Tatiane; Schultheis, Lisa M; Sengupta, Lakshmikanta; Small, Rachel; Spicer, Greg S; Stillman, Jonathon H; Swei, Andrea; Wade, Jennifer M; Waters, Steven B; Weinstein, Steven L; Willsie, Julia K; Wright, Diana W; Harrison, Colin D; Kelley, Loretta A; Trujillo, Gloriana; Domingo, Carmen R; Schinske, Jeffrey N; Tanner, Kimberly D

2017-03-21

Active-learning pedagogies have been repeatedly demonstrated to produce superior learning gains with large effect sizes compared with lecture-based pedagogies. Shifting large numbers of college science, technology, engineering, and mathematics (STEM) faculty to include any active learning in their teaching may retain and more effectively educate far more students than having a few faculty completely transform their teaching, but the extent to which STEM faculty are changing their teaching methods is unclear. Here, we describe the development and application of the machine-learning-derived algorithm Decibel Analysis for Research in Teaching (DART), which can analyze thousands of hours of STEM course audio recordings quickly, with minimal costs, and without need for human observers. DART analyzes the volume and variance of classroom recordings to predict the quantity of time spent on single voice (e.g., lecture), multiple voice (e.g., pair discussion), and no voice (e.g., clicker question thinking) activities. Applying DART to 1,486 recordings of class sessions from 67 courses, a total of 1,720 h of audio, revealed varied patterns of lecture (single voice) and nonlecture activity (multiple and no voice) use. We also found that there was significantly more use of multiple and no voice strategies in courses for STEM majors compared with courses for non-STEM majors, indicating that DART can be used to compare teaching strategies in different types of courses. Therefore, DART has the potential to systematically inventory the presence of active learning with ∼90% accuracy across thousands of courses in diverse settings with minimal effort.

Classroom sound can be used to classify teaching practices in college science courses

PubMed Central

Seidel, Shannon B.; Wong, Mike; Bejines, Travis E.; Lietz, Susanne; Perez, Joseph R.; Sit, Shangheng; Subedar, Zahur-Saleh; Acker, Gigi N.; Akana, Susan F.; Balukjian, Brad; Benton, Hilary P.; Blair, J. R.; Boaz, Segal M.; Boyer, Katharyn E.; Bram, Jason B.; Burrus, Laura W.; Byrd, Dana T.; Caporale, Natalia; Carpenter, Edward J.; Chan, Yee-Hung Mark; Chen, Lily; Chovnick, Amy; Chu, Diana S.; Clarkson, Bryan K.; Cooper, Sara E.; Creech, Catherine; Crow, Karen D.; de la Torre, José R.; Denetclaw, Wilfred F.; Duncan, Kathleen E.; Edwards, Amy S.; Erickson, Karen L.; Fuse, Megumi; Gorga, Joseph J.; Govindan, Brinda; Green, L. Jeanette; Hankamp, Paul Z.; Harris, Holly E.; He, Zheng-Hui; Ingalls, Stephen; Ingmire, Peter D.; Jacobs, J. Rebecca; Kamakea, Mark; Kimpo, Rhea R.; Knight, Jonathan D.; Krause, Sara K.; Krueger, Lori E.; Light, Terrye L.; Lund, Lance; Márquez-Magaña, Leticia M.; McCarthy, Briana K.; McPheron, Linda J.; Miller-Sims, Vanessa C.; Moffatt, Christopher A.; Muick, Pamela C.; Nagami, Paul H.; Nusse, Gloria L.; Okimura, Kristine M.; Pasion, Sally G.; Patterson, Robert; Riggs, Blake; Romeo, Joseph; Roy, Scott W.; Russo-Tait, Tatiane; Schultheis, Lisa M.; Sengupta, Lakshmikanta; Small, Rachel; Spicer, Greg S.; Stillman, Jonathon H.; Swei, Andrea; Wade, Jennifer M.; Waters, Steven B.; Weinstein, Steven L.; Willsie, Julia K.; Wright, Diana W.; Harrison, Colin D.; Kelley, Loretta A.; Trujillo, Gloriana; Domingo, Carmen R.; Schinske, Jeffrey N.; Tanner, Kimberly D.

2017-01-01

Active-learning pedagogies have been repeatedly demonstrated to produce superior learning gains with large effect sizes compared with lecture-based pedagogies. Shifting large numbers of college science, technology, engineering, and mathematics (STEM) faculty to include any active learning in their teaching may retain and more effectively educate far more students than having a few faculty completely transform their teaching, but the extent to which STEM faculty are changing their teaching methods is unclear. Here, we describe the development and application of the machine-learning–derived algorithm Decibel Analysis for Research in Teaching (DART), which can analyze thousands of hours of STEM course audio recordings quickly, with minimal costs, and without need for human observers. DART analyzes the volume and variance of classroom recordings to predict the quantity of time spent on single voice (e.g., lecture), multiple voice (e.g., pair discussion), and no voice (e.g., clicker question thinking) activities. Applying DART to 1,486 recordings of class sessions from 67 courses, a total of 1,720 h of audio, revealed varied patterns of lecture (single voice) and nonlecture activity (multiple and no voice) use. We also found that there was significantly more use of multiple and no voice strategies in courses for STEM majors compared with courses for non-STEM majors, indicating that DART can be used to compare teaching strategies in different types of courses. Therefore, DART has the potential to systematically inventory the presence of active learning with ∼90% accuracy across thousands of courses in diverse settings with minimal effort. PMID:28265087

Neural bases of human mate choice: multiple value dimensions, sex difference, and self-assessment system.

PubMed

Funayama, Risa; Sugiura, Motoaki; Sassa, Yuko; Jeong, Hyeonjeong; Wakusawa, Keisuke; Horie, Kaoru; Sato, Shigeru; Kawashima, Ryuta

2012-01-01

Mate choice is an example of sophisticated daily decision making supported by multiple componential processes. In mate-choice literature, different characteristics of the value dimensions, including the sex difference in the value dimensions, and the involvement of self-assessment due to the mutual nature of the choice, have been suggested. We examined whether the brain-activation pattern during virtual mate choice would be congruent with these characteristics in terms of stimulus selectivity and activated brain regions. In measuring brain activity, young men and women were shown two pictures of either faces or behaviors, and they indicated which person they would choose either as a spouse or as a friend. Activation selective to spouse choice was observed face-selectively in men's amygdala and behavior-selectively in women's motor system. During both partner-choice conditions, behavior-selective activation was observed in the temporoparietal regions. Taking the available knowledge of these regions into account, these results are congruent with the suggested characteristics of value dimensions for physical attractiveness, parenting resources, and beneficial personality traits for a long-lasting relationship, respectively. The medial prefrontal and posterior cingulate cortices were nonselectively activated during the partner choices, suggesting the involvement of a self-assessment process. The results thus provide neuroscientific support for the multi-component mate-choice mechanism.

Productive engagement among older Americans: prevalence, patterns, and implications for public policy.

PubMed

Hinterlong, James E

2008-01-01

This study estimates the prevalence of productive engagement among adults aged 60 and over residing in the United States over a nine-year period. We analyze three waves of data from the Americans' Changing Lives Study, which allows the findings to describe the non-institutionalized older American population. Focusing upon five activities--formal paid employment, irregular paid work, unpaid volunteerism, caregiving, and informal assistance to others--we identify changes in the engagement rates, examine the extent to which engagement occurs through single or multiple concurrent activities, and document intra-individual patterns of engagement within and across forms of productive activity, including the continuity, initiation, and cessation of involvement. The findings reveal that late-life productive engagement is widespread, with the majority of older individuals involved in multiple forms of activity concurrently. Non-market-based activities such as caregiving, informal assistance, and volunteering are most prevalent. Initiation and cessation of activities are common and yield more complex patterns and lower rates of non-participation than are revealed in cross-sectional analyses. Time spent in productive engagement is highly variable and exhibits an overall decline across time. We conclude by highlighting policy strategies to increase the availability and quality of opportunities for productive engagement and promote planning for engagement in late life.

The neural coding of creative idea generation across adolescence and early adulthood

PubMed Central

Kleibeuker, Sietske W.; Koolschijn, P. Cédric M. P.; Jolles, Dietsje D.; De Dreu, Carsten K. W.; Crone, Eveline A.

2013-01-01

Creativity is considered key to human prosperity, yet the neurocognitive principles underlying creative performance, and their development, are still poorly understood. To fill this void, we examined the neural correlates of divergent thinking in adults (25–30 years) and adolescents (15–17 years). Participants generated alternative uses (AU) or ordinary characteristics (OC) for common objects while brain activity was assessed using fMRI. Adults outperformed adolescents on the number of solutions for AU and OC trials. Contrasting neural activity for AU with OC trials revealed increased recruitment of left angular gyrus, left supramarginal gyrus, and bilateral middle temporal gyrus in both adults and adolescents. When only trials with multiple AU were included in the analysis, participants showed additional left inferior frontal gyrus (IFG)/middle frontal gyrus (MFG) activation for AU compared to OC trials. Correspondingly, individual difference analyses showed a positive correlation between activations for AU relative to OC trials in left IFG/MFG and divergent thinking performance and activations were more pronounced in adults than in adolescents. Taken together, the results of this study demonstrated that creative idea generation involves recruitment of mainly left lateralized parietal and temporal brain regions. Generating multiple creative ideas, a hallmark of divergent thinking, shows additional lateral PFC activation that is not yet optimized in adolescence. PMID:24416008

Dead Pericarps of Dry Fruits Function as Long-Term Storage for Active Hydrolytic Enzymes and Other Substances That Affect Germination and Microbial Growth

PubMed Central

Godwin, James; Raviv, Buzi; Grafi, Gideon

2017-01-01

It is commonly assumed that dead pericarps of dry indehiscent fruits have evolved to provide an additional physical layer for embryo protection and as a means for long distance dispersal. The pericarps of dry fruits undergo programmed cell death (PCD) during maturation whereby most macromolecules such DNA, RNA, and proteins are thought to be degraded and their constituents remobilized to filial tissues such as embryo and endosperm. We wanted to test the hypothesis that the dead pericarp represents an elaborated layer that is capable of storing active proteins and other substances for increasing survival rate of germinating seeds. Using in gel assays we found that dead pericarps of both dehiscent and indehiscent dry fruits of various plant species including Arabidopsis thaliana and Sinapis alba release upon hydration multiple active hydrolytic enzymes that can persist in an active form for decades, including nucleases, proteases, and chitinases. Proteomic analysis of indehiscent pericarp of S. alba revealed multiple proteins released upon hydration, among them proteases and chitinases, as well as proteins involved in reactive oxygen species (ROS) detoxification and cell wall modification. Pericarps appear to function also as a nutritional element-rich storage for nitrate, potassium, phosphorus, sulfur, and others. Sinapis alba dehiscent and indehiscent pericarps possess germination inhibitory substances as well as substances that promote microbial growth. Collectively, our study explored previously unknown features of the dead pericarp acting also as a reservoir of biological active proteins, and other substances capable of “engineering” the microenvironment for the benefit of the embryo. PMID:29257090

Everyday science & science every day: Science-related talk & activities across settings

NASA Astrophysics Data System (ADS)

Zimmerman, Heather

To understand the development of science-related thinking, acting, and learning in middle childhood, I studied youth in schools, homes, and other neighborhood settings over a three-year period. The research goal was to analyze how multiple everyday experiences influence children's participation in science-related practices and their thinking about science and scientists. Ethnographic and interaction analysis methodologies were to study the cognition and social interactions of the children as they participated in activities with peers, family, and teachers (n=128). Interviews and participant self-documentation protocols elucidated the participants' understandings of science. An Everyday Expertise (Bell et al., 2006) theoretical framework was employed to study the development of science understandings on three analytical planes: individual learner, social groups, and societal/community resources. Findings came from a cross-case analysis of urban science learners and from two within-case analyses of girls' science-related practices as they transitioned from elementary to middle school. Results included: (1) children participated actively in science across settings---including in their homes as well as in schools, (2) children's interests in science were not always aligned to the school science content, pedagogy, or school structures for participation, yet children found ways to engage with science despite these differences through crafting multiple pathways into science, (3) urban parents were active supporters of STEM-related learning environments through brokering access to social and material resources, (4) the youth often found science in their daily activities that formal education did not make use of, and (5) children's involvement with science-related practices can be developed into design principles to reach youth in culturally relevant ways.

Environmental perceptions and objective walking trail audits inform a community-based participatory research walking intervention

PubMed Central

2012-01-01

Background Given the documented physical activity disparities that exist among low-income minority communities and the increased focused on socio-ecological approaches to address physical inactivity, efforts aimed at understanding the built environment to support physical activity are needed. This community-based participatory research (CBPR) project investigates walking trails perceptions in a high minority southern community and objectively examines walking trails. The primary aim is to explore if perceived and objective audit variables predict meeting recommendations for walking and physical activity, MET/minutes/week of physical activity, and frequency of trail use. Methods A proportional sampling plan was used to survey community residents in this cross-sectional study. Previously validated instruments were pilot tested and appropriately adapted and included the short version of the validated International Physical Activity Questionnaire, trail use, and perceptions of walking trails. Walking trails were assessed using the valid and reliable Path Environmental Audit Tool which assesses four content areas including: design features, amenities, maintenance, and pedestrian safety from traffic. Analyses included Chi-square, one-way ANOVA's, multiple linear regression, and multiple logistic models. Results Numerous (n = 21) high quality walking trails were available. Across trails, there were very few indicators of incivilities and safety features rated relatively high. Among the 372 respondents, trail use significantly predicted meeting recommendations for walking and physical activity, and MET/minutes/week. While controlling for other variables, significant predictors of trail use included proximity to trails, as well as perceptions of walking trail safety, trail amenities, and neighborhood pedestrian safety. Furthermore, while controlling for education, gender, and income; for every one time per week increase in using walking trails, the odds for meeting walking recommendations increased 1.27 times, and the odds for meeting PA recommendation increased 3.54 times. Perceived and objective audit variables did not predict meeting physical activity recommendations. Conclusions To improve physical activity levels, intervention efforts are needed to maximize the use of existing trails, as well as improve residents' perceptions related to incivilities, safety, conditions of trail, and amenities of the walking trails. This study provides important insights for informing development of the CBPR walking intervention and informing local recreational and environmental policies in this southern community. PMID:22289653

EBF proteins participate in transcriptional regulation of Xenopus muscle development.

PubMed

Green, Yangsook Song; Vetter, Monica L

2011-10-01

EBF proteins have diverse functions in the development of multiple lineages, including neurons, B cells and adipocytes. During Drosophila muscle development EBF proteins are expressed in muscle progenitors and are required for muscle cell differentiation, but there is no known function of EBF proteins in vertebrate muscle development. In this study, we examine the expression of ebf genes in Xenopus muscle tissue and show that EBF activity is necessary for aspects of Xenopus skeletal muscle development, including somite organization, migration of hypaxial muscle anlagen toward the ventral abdomen, and development of jaw muscle. From a microarray screen, we have identified multiple candidate targets of EBF activity with known roles in muscle development. The candidate targets we have verified are MYOD, MYF5, M-Cadherin and SEB-4. In vivo overexpression of the ebf2 and ebf3 genes leads to ectopic expression of these candidate targets, and knockdown of EBF activity causes downregulation of the endogenous expression of the candidate targets. Furthermore, we found that MYOD and MYF5 are likely to be direct targets. Finally we show that MYOD can upregulate the expression of ebf genes, indicating the presence of a positive feedback loop between EBF and MYOD that we find to be important for maintenance of MYOD expression in Xenopus. These results suggest that EBF activity is important for both stabilizing commitment and driving aspects of differentiation in Xenopus muscle cells. Copyright © 2010 Elsevier Inc. All rights reserved.

Diffusion fMRI detects white-matter dysfunction in mice with acute optic neuritis

PubMed Central

Lin, Tsen-Hsuan; Spees, William M.; Chiang, Chia-Wen; Trinkaus, Kathryn; Cross, Anne H.; Song, Sheng-Kwei

2014-01-01

Optic neuritis is a frequent and early symptom of multiple sclerosis (MS). Conventional magnetic resonance (MR) techniques provide means to assess multiple MS-related pathologies, including axonal injury, demyelination, and inflammation. A method to directly and non-invasively probe white-matter function could further elucidate the interplay of underlying pathologies and functional impairments. Previously, we demonstrated a significant 27% activation-associated decrease in the apparent diffusion coefficient of water perpendicular to the axonal fibers (ADC⊥) in normal C57BL/6 mouse optic nerve with visual stimulation using diffusion fMRI. Here we apply this approach to explore the relationship between visual acuity, optic nerve pathology, and diffusion fMRI in the experimental autoimmune encephalomyelitis (EAE) mouse model of optic neuritis. Visual stimulation produced a significant 25% (vs. baseline) ADC⊥ decrease in sham EAE optic nerves, while only a 7% (vs. baseline) ADC⊥ decrease was seen in EAE mice with acute optic neuritis. The reduced activation-associated ADC⊥ response correlated with post-MRI immunohistochemistry determined pathologies (including inflammation, demyelination, and axonal injury). The negative correlation between activation-associated ADC⊥ response and visual acuity was also found when pooling EAE-affected and sham groups under our experimental criteria. Results suggest that reduction in diffusion fMRI directly reflects impaired axonal-activation in EAE mice with optic neuritis. Diffusion fMRI holds promise for directly gauging in vivo white-matter dysfunction or therapeutic responses in MS patients. PMID:24632420

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

PubMed

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.

A Bayesian Model of Category-Specific Emotional Brain Responses

PubMed Central

Wager, Tor D.; Kang, Jian; Johnson, Timothy D.; Nichols, Thomas E.; Satpute, Ajay B.; Barrett, Lisa Feldman

2015-01-01

Understanding emotion is critical for a science of healthy and disordered brain function, but the neurophysiological basis of emotional experience is still poorly understood. We analyzed human brain activity patterns from 148 studies of emotion categories (2159 total participants) using a novel hierarchical Bayesian model. The model allowed us to classify which of five categories—fear, anger, disgust, sadness, or happiness—is engaged by a study with 66% accuracy (43-86% across categories). Analyses of the activity patterns encoded in the model revealed that each emotion category is associated with unique, prototypical patterns of activity across multiple brain systems including the cortex, thalamus, amygdala, and other structures. The results indicate that emotion categories are not contained within any one region or system, but are represented as configurations across multiple brain networks. The model provides a precise summary of the prototypical patterns for each emotion category, and demonstrates that a sufficient characterization of emotion categories relies on (a) differential patterns of involvement in neocortical systems that differ between humans and other species, and (b) distinctive patterns of cortical-subcortical interactions. Thus, these findings are incompatible with several contemporary theories of emotion, including those that emphasize emotion-dedicated brain systems and those that propose emotion is localized primarily in subcortical activity. They are consistent with componential and constructionist views, which propose that emotions are differentiated by a combination of perceptual, mnemonic, prospective, and motivational elements. Such brain-based models of emotion provide a foundation for new translational and clinical approaches. PMID:25853490

Visual processing of multiple elements in the dyslexic brain: evidence for a superior parietal dysfunction

PubMed Central

Lobier, Muriel A.; Peyrin, Carole; Pichat, Cédric; Le Bas, Jean-François; Valdois, Sylviane

2014-01-01

The visual attention (VA) span deficit hypothesis of developmental dyslexia posits that impaired multiple element processing can be responsible for poor reading outcomes. In VA span impaired dyslexic children, poor performance on letter report tasks is associated with reduced parietal activations for multiple letter processing. While this hints towards a non-specific, attention-based dysfunction, it is still unclear whether reduced parietal activity generalizes to other types of stimuli. Furthermore, putative links between reduced parietal activity and reduced ventral occipito-temporal (vOT) in dyslexia have yet to be explored. Using functional magnetic resonance imaging, we measured brain activity in 12 VA span impaired dyslexic adults and 12 adult skilled readers while they carried out a categorization task on single or multiple alphanumeric or non-alphanumeric characters. While healthy readers activated parietal areas more strongly for multiple than single element processing (right-sided for alphanumeric and bilateral for non-alphanumeric), similar stronger multiple element right parietal activations were absent for dyslexic participants. Contrasts between skilled and dyslexic readers revealed significantly reduced right superior parietal lobule (SPL) activity for dyslexic readers regardless of stimuli type. Using a priori anatomically defined regions of interest, we showed that neural activity was reduced for dyslexic participants in both SPL and vOT bilaterally. Finally, we used multiple regressions to test whether SPL activity was related to vOT activity in each group. In the left hemisphere, SPL activity covaried with vOT activity for both normal and dyslexic readers. In contrast, in the right hemisphere, SPL activity covaried with vOT activity only for dyslexic readers. These results bring critical support to the VA interpretation of the VA Span deficit. In addition, they offer a new insight on how deficits in automatic vOT based word recognition could arise in developmental dyslexia. PMID:25071509

Multiple Immune-Inflammatory and Oxidative and Nitrosative Stress Pathways Explain the Frequent Presence of Depression in Multiple Sclerosis.

PubMed

Morris, Gerwyn; Reiche, Edna Maria Vissoci; Murru, Andrea; Carvalho, André F; Maes, Michael; Berk, Michael; Puri, Basant K

2018-01-02

Patients with a diagnosis of multiple sclerosis (MS) or major depressive disorder (MDD) share a wide array of biological abnormalities which are increasingly considered to play a contributory role in the pathogenesis and pathophysiology of both illnesses. Shared abnormalities include peripheral inflammation, neuroinflammation, chronic oxidative and nitrosative stress, mitochondrial dysfunction, gut dysbiosis, increased intestinal barrier permeability with bacterial translocation into the systemic circulation, neuroendocrine abnormalities and microglial pathology. Patients with MS and MDD also display a wide range of neuroimaging abnormalities and patients with MS who display symptoms of depression present with different neuroimaging profiles compared with MS patients who are depression-free. The precise details of such pathology are markedly different however. The recruitment of activated encephalitogenic Th17 T cells and subsequent bidirectional interaction leading to classically activated microglia is now considered to lie at the core of MS-specific pathology. The presence of activated microglia is common to both illnesses although the pattern of such action throughout the brain appears to be different. Upregulation of miRNAs also appears to be involved in microglial neurotoxicity and indeed T cell pathology in MS but does not appear to play a major role in MDD. It is suggested that the antidepressant lofepramine, and in particular its active metabolite desipramine, may be beneficial not only for depressive symptomatology but also for the neurological symptoms of MS. One clinical trial has been carried out thus far with, in particular, promising MRI findings.

A time-driven, activity-based costing methodology for determining the costs of red blood cell transfusion in patients with beta thalassaemia major.

PubMed

Burns, K E; Haysom, H E; Higgins, A M; Waters, N; Tahiri, R; Rushford, K; Dunstan, T; Saxby, K; Kaplan, Z; Chunilal, S; McQuilten, Z K; Wood, E M

2018-04-10

To describe the methodology to estimate the total cost of administration of a single unit of red blood cells (RBC) in adults with beta thalassaemia major in an Australian specialist haemoglobinopathy centre. Beta thalassaemia major is a genetic disorder of haemoglobin associated with multiple end-organ complications and typically requiring lifelong RBC transfusion therapy. New therapeutic agents are becoming available based on advances in understanding of the disorder and its consequences. Assessment of the true total cost of transfusion, incorporating both product and activity costs, is required in order to evaluate the benefits and costs of these new therapies. We describe the bottom-up, time-driven, activity-based costing methodology used to develop process maps to provide a step-by-step outline of the entire transfusion pathway. Detailed flowcharts for each process are described. Direct observations and timing of the process maps document all activities, resources, staff, equipment and consumables in detail. The analysis will include costs associated with performing these processes, including resources and consumables. Sensitivity analyses will be performed to determine the impact of different staffing levels, timings and probabilities associated with performing different tasks. Thirty-one process maps have been developed, with over 600 individual activities requiring multiple timings. These will be used for future detailed cost analyses. Detailed process maps using bottom-up, time-driven, activity-based costing for determining the cost of RBC transfusion in thalassaemia major have been developed. These could be adapted for wider use to understand and compare the costs and complexities of transfusion in other settings. © 2018 British Blood Transfusion Society.

Recent advances in occupational and environmental health hazards of workers exposed to gasoline compounds.

PubMed

Ekpenyong, Christopher E; Asuquo, Asuquo E

2017-02-21

The impact of health and environmental hazards, associated with the constituents of gasoline, on occupationally exposed workers has been recorded over the past few decades. However, the scientific literature on their pathogenic potential remains incomplete, which could affect the current understanding of the associated health risks. This review provides current information based on recently improved research techniques to evaluate gasoline toxicity profiles for humans. Our current knowledge provides insight into the intricate mechanism of gasoline-induced adverse effects, including the formation of reactive metabolites via bio-activation and subsequent generation of reactive oxygen species (ROS) and oxidative stress, which are involved in multiple mechanisms that are central to the aetiology of gasoline-induced toxicity. These mechanisms include covalent binding to deoxyribonucleic acid (DNA), leading to oxidative damage, tumor-suppression gene activity, and activation of pro-oncogenes. Furthermore, it results in induction of autoimmunity and local inflammatory responses, disruption of multiple neurotransmitters and immune cell function, derangement of various enzyme activities (e.g., sodiumpotassium adenosine triphosphate (Na+/K+/ATPase) activity, cytochrome P450 (CYP450), nitric oxide synthase (NOS), antioxidant enzyme activities, etc.), conjugation of bile, and non-specific cell membrane interaction, leading to damage of the membrane lipid bilayer and proteins. Available data suggests that exposure to gasoline or gasoline constituents have the potential to cause different types of illnesses. The data highlights the need to maintain safety measures via suitable research, medical surveillance, regulatory control, life style modification, early detection, and intervention to minimize exposure and manage suspected cases. They also present novel opportunities to design and develop effective therapeutic strategies against gasoline-induced detrimental effects. Int J Occup Med Environ Health 2017;30(1):1-26. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

Multiple cytoskeletal pathways and PI3K signaling mediate CDC-42-induced neuronal protrusion in C. elegans.

PubMed

Alan, Jamie K; Struckhoff, Eric C; Lundquist, Erik A

2013-01-01

Rho GTPases are key regulators of cellular protrusion and are involved in many developmental events including axon guidance during nervous system development. Rho GTPase pathways display functional redundancy in developmental events, including axon guidance. Therefore, their roles can often be masked when using simple loss-of-function genetic approaches. As a complement to loss-of-function genetics, we constructed a constitutively activated CDC-42(G12V) expressed in C. elegans neurons. CDC-42(G12V) drove the formation of ectopic lamellipodial and filopodial protrusions in the PDE neurons, which resembled protrusions normally found on migrating growth cones of axons. We then used a candidate gene approach to identify molecules that mediate CDC-42(G12V)-induced ectopic protrusions by determining if loss of function of the genes could suppress CDC-42(G12V). Using this approach, we identified 3 cytoskeletal pathways previously implicated in axon guidance, the Arp2/3 complex, UNC-115/abLIM, and UNC-43/Ena. We also identified the Nck-interacting kinase MIG-15/NIK and p21-activated kinases (PAKs), also implicated in axon guidance. Finally, PI3K signaling was required, specifically the Rictor/mTORC2 branch but not the mTORC1 branch that has been implicated in other aspects of PI3K signaling including stress and aging. Our results indicate that multiple pathways can mediate CDC-42-induced neuronal protrusions that might be relevant to growth cone protrusions during axon pathfinding. Each of these pathways involves Rac GTPases, which might serve to integrate the pathways and coordinate the multiple CDC-42 pathways. These pathways might be relevant to developmental events such as axon pathfinding as well as disease states such as metastatic melanoma.

Multiple cytoskeletal pathways and PI3K signaling mediate CDC-42-induced neuronal protrusion in C. elegans

PubMed Central

Alan, Jamie K; Struckhoff, Eric C; Lundquist, Erik A

2013-01-01

Rho GTPases are key regulators of cellular protrusion and are involved in many developmental events including axon guidance during nervous system development. Rho GTPase pathways display functional redundancy in developmental events, including axon guidance. Therefore, their roles can often be masked when using simple loss-of-function genetic approaches. As a complement to loss-of-function genetics, we constructed a constitutively activated CDC-42(G12V) expressed in C. elegans neurons. CDC-42(G12V) drove the formation of ectopic lamellipodial and filopodial protrusions in the PDE neurons, which resembled protrusions normally found on migrating growth cones of axons. We then used a candidate gene approach to identify molecules that mediate CDC-42(G12V)-induced ectopic protrusions by determining if loss of function of the genes could suppress CDC-42(G12V). Using this approach, we identified 3 cytoskeletal pathways previously implicated in axon guidance, the Arp2/3 complex, UNC-115/abLIM, and UNC-43/Ena. We also identified the Nck-interacting kinase MIG-15/NIK and p21-activated kinases (PAKs), also implicated in axon guidance. Finally, PI3K signaling was required, specifically the Rictor/mTORC2 branch but not the mTORC1 branch that has been implicated in other aspects of PI3K signaling including stress and aging. Our results indicate that multiple pathways can mediate CDC-42-induced neuronal protrusions that might be relevant to growth cone protrusions during axon pathfinding. Each of these pathways involves Rac GTPases, which might serve to integrate the pathways and coordinate the multiple CDC-42 pathways. These pathways might be relevant to developmental events such as axon pathfinding as well as disease states such as metastatic melanoma. PMID:24149939

Development of the Oxford Hills Healthy Moms Project using a social marketing process: a community-based physical activity and nutrition intervention for low-socioeconomic-status mothers in a rural area in Maine.

PubMed

Dharod, Jigna M; Drewette-Card, Rebecca; Crawford, David

2011-03-01

A physical activity and nutrition community intervention called the Oxford Hills Healthy Moms (OHHM) Project was developed using a multifaceted social marketing process, including review of state surveillance results, key informant interviews, and a survey and focus group discussions with low-socioeconomic-status (low-SES) mothers. This formative work was used to make key decisions on the selection of the intervention region, segmentation of the audience, and design of intervention strategies addressing multiple levels of the socioecological model. The OHHM Project aims to increase fruit and vegetable consumption and physical activity levels among low-SES mothers in the Oxford Hills region of Maine. The OHHM Project includes five components: (a) physical activity buddy program, (b) cooking club with education, (c) fruit and vegetable discount buying club with education, (d) increased access to produce vendors, and (e) increased access to places for physical activity.

Osthole: A Review on Its Bioactivities, Pharmacological Properties, and Potential as Alternative Medicine

PubMed Central

Zhang, Zhong-Rong; Leung, Wing Nang; Cheung, Ho Yee; Chan, Chun Wai

2015-01-01

This paper reviews the latest understanding of biological and pharmacological properties of osthole (7-methoxy-8-(3-methyl-2-butenyl)-2H-1-benzopyran-2-one), a natural product found in several medicinal plants such as Cnidium monnieri and Angelica pubescens. In vitro and in vivo experimental results have revealed that osthole demonstrates multiple pharmacological actions including neuroprotective, osteogenic, immunomodulatory, anticancer, hepatoprotective, cardiovascular protective, and antimicrobial activities. In addition, pharmacokinetic studies showed osthole uptake and utilization are fast and efficient in body. Moreover, the mechanisms of multiple pharmacological activities of osthole are very likely related to the modulatory effect on cyclic adenosine monophosphate (cAMP) and cyclic adenosine monophosphate (cGMP) level, though some mechanisms remain unclear. This review aims to summarize the pharmacological properties of osthole and give an overview of the underlying mechanisms, which showcase its potential as a multitarget alternative medicine. PMID:26246843

Characterization and production of multifunctional cationic peptides derived from rice proteins.

PubMed

Taniguchi, Masayuki; Ochiai, Akihito

2017-04-01

Food proteins have been identified as a source of bioactive peptides. These peptides are inactive within the sequence of the parent protein and must be released during gastrointestinal digestion, fermentation, or food processing. Of bioactive peptides, multifunctional cationic peptides are more useful than other peptides that have specific activity in promotion of health and/or the treatment of diseases. We have identified and characterized cationic peptides from rice enzymes and proteins that possess multiple functions, including antimicrobial, endotoxin-neutralizing, arginine gingipain-inhibitory, and/or angiogenic activities. In particular, we have elucidated the contribution of cationic amino acids (arginine and lysine) in the peptides to their bioactivities. Further, we have discussed the critical parameters, particularly proteinase preparations and fractionation or purification, in the enzymatic hydrolysis process for producing bioactive peptides from food proteins. Using an ampholyte-free isoelectric focusing (autofocusing) technique as a tool for fractionation, we successfully prepared fractions containing cationic peptides with multiple functions.

Regulation of Ubiquitination-Mediated Protein Degradation by Survival Kinases in Cancer

PubMed Central

Yamaguchi, Hirohito; Hsu, Jennifer L.; Hung, Mien-Chie

2011-01-01

The ubiquitin–proteasome system is essential for multiple physiological processes via selective degradation of target proteins and has been shown to plays a critical role in human cancer. Activation of oncogenic factors and inhibition of tumor suppressors have been shown to be essential for cancer development, and protein ubiquitination has been linked to the regulation of oncogenic factors and tumor suppressors. Three kinases, AKT, extracellular signal-regulated kinase, and IκB kinase, we refer to as oncokinases, are activated in multiple human cancers. We and others have identified several key downstream targets that are commonly regulated by these oncokinases, some of which are regulated directly or indirectly via ubiquitin-mediated proteasome degradation, including FOXO3, β-catenin, myeloid cell leukemia-1, and Snail. In this review, we summarize these findings from our and other groups and discuss potential future studies and applications in the clinic. PMID:22649777

Projects for increasing job satisfaction and creating a healthy work environment.

PubMed

Brunges, Michele; Foley-Brinza, Christine

2014-12-01

Workplace culture is one of the biggest factors driving employee commitment and engagement. Multiple studies have shown that hospitals will perform better over time if employees are committed to their jobs and engaged in what they do. By creating and implementing multiple projects during a three-year period, a team at the University of Florida Health Shands Hospital, Gainesville, increased job satisfaction. Projects included ensuring meal breaks were offered, creating a serenity area, developing the patient ambassador role, actively addressing bullying and unprofessional behavior, assigning a student mentee to work with staff members on culture change, offering regular fun activities, redesigning the unit, reorganizing schedules to reduce stress, implementing education and training initiatives, establishing a Unit Practice Council, and implementing reward and recognition programs. Survey results and anecdotal evidence suggest that these projects combined to increase employee satisfaction and employee retention rates. Copyright © 2014 AORN, Inc. Published by Elsevier Inc. All rights reserved.

Physical activity and exercise training in multiple sclerosis: a review and content analysis of qualitative research identifying perceived determinants and consequences.

PubMed

Learmonth, Yvonne C; Motl, Robert W

2016-01-01

This systematic review was conducted to provide rich and deep evidence of the perceived determinants and consequences of physical activity and exercise based on qualitative research in multiple sclerosis (MS). Electronic databases and article reference lists were searched to identify qualitative studies of physical activity and exercise in MS. Studies were included if they were written in English and examined consequences/determinants of physical activity in persons with MS. Content analysis of perceived determinants and consequences of physical activity and exercise was undertaken using an inductive analysis guided by the Physical Activity for people with Disabilities framework and Social Cognitive Theory, respectively. Nineteen articles were reviewed. The most commonly identified perceived barriers of physical activity and exercise were related to the environmental (i.e. minimal or no disabled facilities, and minimal or conflicting advice from healthcare professionals) and related to personal barriers (i.e. fatigue, and fear and apprehension). The most commonly identified perceived facilitators of physical activity were related to the environment (i.e. the type of exercise modality and peer support) and related to personal facilitators (i.e. appropriate exercise and feelings of accomplishment). The most commonly identified perceived beneficial consequences of physical activity and exercise were maintaining physical functions, increased social participation and feelings of self-management and control. The most commonly identified perceived adverse consequences were increased fatigue and feelings of frustration and lost control. Results will inform future research on the perceived determinants and consequences of physical activity and exercise in those with MS and can be adopted for developing professional education and interventions for physical activity and exercise in MS. Physical activity and exercise behaviour in people with multiple sclerosis (MS) is subject to a number of modifiable determinants. Healthcare professionals working to promote physical activity and exercise in those with MS should choose to endorse the positive benefits of participation. Future physical activity interventions for those with MS may be improved by incorporating behavioural management strategies.

Concept and implementation of the Globalstar mobile satellite system

NASA Technical Reports Server (NTRS)

Schindall, Joel

1995-01-01

Globalstar is a satellite-based mobile communications system which provides quality wireless communications (voice and/or data) anywhere in the world except the polar regions. The Globalstar system concept is based upon technological advancements in Low Earth Orbit (LEO) satellite technology and in cellular telephone technology, including the commercial application of Code Division Multiple Access (CDMA) technologies. The Globalstar system uses elements of CDMA and Frequency Division Multiple Access (FDMA), combined with satellite Multiple Beam Antenna (MBA) technology and advanced variable-rate vocoder technology to arrive at one of the most efficient modulation and multiple access systems ever proposed for a satellite communications system. The technology used in Globalstar includes the following techniques in obtaining high spectral efficiency and affordable cost per channel: (1) CDMA modulation with efficient power control; (2) high efficiency vocoder with voice activity factor; (3) spot beam antenna for increased gain and frequency reuse; (4) weighted satellite antenna gain for broad geographic coverage; (5) multisatellite user links (diversity) to enhance communications reliability; and (6) soft hand-off between beams and satellites. Initial launch is scheduled in 1997 and the system is scheduled to be operational in 1998. The Globalstar system utilizes frequencies in L-, S- and C-bands which have the potential to offer worldwide availability with authorization by the appropriate regulatory agencies.

Meeting the challenge of interacting threats in freshwater ecosystems: A call to scientists and managers

USGS Publications Warehouse

Craig, Laura S.; Olden, Julian D.; Arthington, Angela; Entrekin, Sally; Hawkins, Charles P.; Kelly, John J.; Kennedy, Theodore A.; Maitland, Bryan M.; Rosi, Emma J.; Roy, Allison; Strayer, David L.; Tank, Jennifer L.; West, Amie O.; Wooten, Matthew S.

2017-01-01

Human activities create threats that have consequences for freshwater ecosystems and, in most watersheds, observed ecological responses are the result of complex interactions among multiple threats and their associated ecological alterations. Here we discuss the value of considering multiple threats in research and management, offer suggestions for filling knowledge gaps, and provide guidance for addressing the urgent management challenges posed by multiple threats in freshwater ecosystems. There is a growing literature assessing responses to multiple alterations, and we build off this background to identify three areas that require greater attention: linking observed alterations to threats, understanding when and where threats overlap, and choosing metrics that best quantify the effects of multiple threats. Advancing science in these areas will help us understand existing ecosystem conditions and predict future risk from multiple threats. Because addressing the complex issues and novel ecosystems that arise from the interaction of multiple threats in freshwater ecosystems represents a significant management challenge, and the risks of management failure include loss of biodiversity, ecological goods, and ecosystem services, we also identify actions that could improve decision-making and management outcomes. These actions include drawing insights from management of individual threats, using threat attributes (e.g., causes and spatio-temporal dynamics) to identify suitable management approaches, testing management strategies that are likely to be successful despite uncertainties about the nature of interactions among threats, avoiding unintended consequences, and maximizing conservation benefits. We also acknowledge the broadly applicable challenges of decision-making within a socio-political and economic framework, and suggest that multidisciplinary teams will be needed to innovate solutions to meet the current and future challenge of interacting threats in freshwater ecosystems. 

The Rho Kinases: Critical Mediators of Multiple Profibrotic Processes and Rational Targets for New Therapies for Pulmonary Fibrosis

PubMed Central

Knipe, Rachel S.; Tager, Andrew M.

2015-01-01

Idiopathic pulmonary fibrosis (IPF) is characterized by progressive lung scarring, short median survival, and limited therapeutic options, creating great need for new pharmacologic therapies. IPF is thought to result from repetitive environmental injury to the lung epithelium, in the context of aberrant host wound healing responses. Tissue responses to injury fundamentally involve reorganization of the actin cytoskeleton of participating cells, including epithelial cells, fibroblasts, endothelial cells, and macrophages. Actin filament assembly and actomyosin contraction are directed by the Rho-associated coiled-coil forming protein kinase (ROCK) family of serine/threonine kinases (ROCK1 and ROCK2). As would therefore be expected, lung ROCK activation has been demonstrated in humans with IPF and in animal models of this disease. ROCK inhibitors can prevent fibrosis in these models, and more importantly, induce the regression of already established fibrosis. Here we review ROCK structure and function, upstream activators and downstream targets of ROCKs in pulmonary fibrosis, contributions of ROCKs to profibrotic cellular responses to lung injury, ROCK inhibitors and their efficacy in animal models of pulmonary fibrosis, and potential toxicities of ROCK inhibitors in humans, as well as involvement of ROCKs in fibrosis in other organs. As we discuss, ROCK activation is required for multiple profibrotic responses, in the lung and multiple other organs, suggesting ROCK participation in fundamental pathways that contribute to the pathogenesis of a broad array of fibrotic diseases. Multiple lines of evidence therefore indicate that ROCK inhibition has great potential to be a powerful therapeutic tool in the treatment of fibrosis, both in the lung and beyond. PMID:25395505

Multiphase flow microfluidics for the production of single or multiple emulsions for drug delivery.

PubMed

Zhao, Chun-Xia

2013-11-01

Considerable effort has been directed towards developing novel drug delivery systems. Microfluidics, capable of generating monodisperse single and multiple emulsion droplets, executing precise control and operations on these droplets, is a powerful tool for fabricating complex systems (microparticles, microcapsules, microgels) with uniform size, narrow size distribution and desired properties, which have great potential in drug delivery applications. This review presents an overview of the state-of-the-art multiphase flow microfluidics for the production of single emulsions or multiple emulsions for drug delivery. The review starts with a brief introduction of the approaches for making single and multiple emulsions, followed by presentation of some potential drug delivery systems (microparticles, microcapsules and microgels) fabricated in microfluidic devices using single or multiple emulsions as templates. The design principles, manufacturing processes and properties of these drug delivery systems are also discussed and compared. Furthermore, drug encapsulation and drug release (including passive and active controlled release) are provided and compared highlighting some key findings and insights. Finally, site-targeting delivery using multiphase flow microfluidics is also briefly introduced. Copyright © 2013 Elsevier B.V. All rights reserved.

Functional Magnetic Resonance Imaging with Concurrent Urodynamic Testing Identifies Brain Structures Involved in Micturition Cycle in Patients with Multiple Sclerosis.

PubMed

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 of interest for future intervention. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Monoterpene and sesquiterpene synthases and the origin of terpene skeletal diversity in plants.

PubMed

Degenhardt, Jörg; Köllner, Tobias G; Gershenzon, Jonathan

2009-01-01

The multitude of terpene carbon skeletons in plants is formed by enzymes known as terpene synthases. This review covers the monoterpene and sesquiterpene synthases presenting an up-to-date list of enzymes reported and evidence for their ability to form multiple products. The reaction mechanisms of these enzyme classes are described, and information on how terpene synthase proteins mediate catalysis is summarized. Correlations between specific amino acid motifs and terpene synthase function are described, including an analysis of the relationships between active site sequence and cyclization type and a discussion of whether specific protein features might facilitate multiple product formation.

Simvastatin Potently Induces Calcium-dependent Apoptosis of Human Leiomyoma Cells*

PubMed Central

Borahay, Mostafa A.; Kilic, Gokhan S.; Yallampalli, Chandrasekha; Snyder, Russell R.; Hankins, Gary D. V.; Al-Hendy, Ayman; Boehning, Darren

2014-01-01

Statins are drugs commonly used for the treatment of high plasma cholesterol levels. Beyond these well known lipid-lowering properties, they possess broad-reaching effects in vivo, including antitumor effects. Statins inhibit the growth of multiple tumors. However, the mechanisms remain incompletely understood. Here we show that simvastatin inhibits the proliferation of human leiomyoma cells. This was associated with decreased mitogen-activated protein kinase signaling and multiple changes in cell cycle progression. Simvastatin potently stimulated leiomyoma cell apoptosis in a manner mechanistically dependent upon apoptotic calcium release from voltage-gated calcium channels. Therefore, simvastatin possesses antitumor effects that are dependent upon the apoptotic calcium release machinery. PMID:25359773

New Approaches to the Diagnosis, Clinical Course, and Goals of Therapy in Multiple Sclerosis and Related Disorders.

PubMed

Krieger, Stephen C

2016-06-01

The diagnosis, categorization, and treatment of multiple sclerosis (MS) and other demyelinating diseases have shifted over the past decade, and many of the fundamental principles of MS pathogenesis and clinical course are being rewritten. Fundamental issues include selecting the right disease-modifying therapy for someone with active disease and how, or even if, patients with purely progressive MS should be treated. This article provides an overview and introduction to the current thinking in MS diagnosis and therapy with an emphasis on the data-driven and proactive approach that has come to define the current state of the art.

Severe disease exacerbations in patients with multiple sclerosis after discontinuing fingolimod.

PubMed

Członkowska, Anna; Smoliński, Łukasz; Litwin, Tomasz

Discontinuation of fingolimod in patients with multiple sclerosis (MS) can lead to disease reactivation. In this review, we describe cases of severe exacerbations in patients with MS following discontinuation of fingolimod, including three cases from our center. We consider potential mechanisms of disease reactivation after cessation of fingolimod, and the evidence supporting this rebound effect. We conclude that discontinuation of fingolimod results in the return of disease activity, which then leads to severe exacerbations (i.e., rebounds) in a clinically significant proportion of patients. Lastly, we consider disease-modifying treatment options for patients who discontinue fingolimod. Copyright © 2017. Published by Elsevier Urban & Partner Sp. z o.o.

High-Performance, Radiation-Hardened Electronics for Space and Lunar Environments

NASA Technical Reports Server (NTRS)

Keys, Andrew S.; Adams, James H.; Cressler, John D.; Darty, Ronald C.; Johnson, Michael A.; Patrick, Marshall C.

2008-01-01

The Radiation Hardened Electronics for Space Environments (RHESE) project develops advanced technologies needed for high performance electronic devices that will be capable of operating within the demanding radiation and thermal extremes of the space, lunar, and Martian environment. The technologies developed under this project enhance and enable avionics within multiple mission elements of NASA's Vision for Space Exploration. including the Constellation program's Orion Crew Exploration Vehicle. the Lunar Lander project, Lunar Outpost elements, and Extra Vehicular Activity (EVA) elements. This paper provides an overview of the RHESE project and its multiple task tasks, their technical approaches, and their targeted benefits as applied to NASA missions.

NLR-Dependent Regulation of Inflammation in Multiple Sclerosis

PubMed Central

Gharagozloo, Marjan; Gris, Katsiaryna V.; Mahvelati, Tara; Amrani, Abdelaziz; Lukens, John R.; Gris, Denis

2018-01-01

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) associated with inappropriate activation of lymphocytes, hyperinflammatory responses, demyelination, and neuronal damage. In the past decade, a number of biological immunomodulators have been developed that suppress the peripheral immune responses and slow down the progression of the disease. However, once the inflammation of the CNS has commenced, it can cause serious permanent neuronal damage. Therefore, there is a need for developing novel therapeutic approaches that control and regulate inflammatory responses within the CNS. Nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) are intracellular regulators of inflammation expressed by many cell types within the CNS. They redirect multiple signaling pathways initiated by pathogens and molecules released by injured tissues. NLR family members include positive regulators of inflammation, such as NLRP3 and NLRC4 and anti-inflammatory NLRs, such as NLRX1 and NLRP12. They exert immunomodulatory effect at the level of peripheral immune responses, including antigen recognition and lymphocyte activation and differentiation. Also, NLRs regulate tissue inflammatory responses. Understanding the molecular mechanisms that are placed at the crossroad of innate and adaptive immune responses, such as NLR-dependent pathways, could lead to the discovery of new therapeutic targets. In this review, we provide a summary of the role of NLRs in the pathogenesis of MS. We also summarize how anti-inflammatory NLRs regulate the immune response within the CNS. Finally, we speculate the therapeutic potential of targeting NLRs in MS. PMID:29403486

EG-1 interacts with c-Src and activates its signaling pathway.

PubMed

Lu, Ming; Zhang, Liping; Sartippour, Maryam R; Norris, Andrew J; Brooks, Mai N

2006-10-01

EG-1 is significantly elevated in breast, colorectal, and prostate cancers. Overexpression of EG-1 stimulates cellular proliferation, and targeted inhibition blocks mouse xenograft tumor growth. To further clarify the function of EG-1, we investigated its role in c-Src activation. We observed that EG-1 overexpression results in activation of c-Src, but found no evidence that EG-1 is a direct Src substrate. EG-1 also binds to other members of the Src family. Furthermore, EG-1 shows interaction with multiple other SH3- and WW-containing molecules involved in various signaling pathways. These observations suggest that EG-1 may be involved in signaling pathways including c-Src activation.

Greater neural pattern similarity across repetitions is associated with better memory.

PubMed

Xue, Gui; Dong, Qi; Chen, Chuansheng; Lu, Zhonglin; Mumford, Jeanette A; Poldrack, Russell A

2010-10-01

Repeated study improves memory, but the underlying neural mechanisms of this improvement are not well understood. Using functional magnetic resonance imaging and representational similarity analysis of brain activity, we found that, compared with forgotten items, subsequently remembered faces and words showed greater similarity in neural activation across multiple study in many brain regions, including (but not limited to) the regions whose mean activities were correlated with subsequent memory. This result addresses a longstanding debate in the study of memory by showing that successful episodic memory encoding occurs when the same neural representations are more precisely reactivated across study episodes, rather than when patterns of activation are more variable across time.

Mesoscopic Modeling of Blood Clotting: Coagulation Cascade and Platelets Adhesion

NASA Astrophysics Data System (ADS)

Yazdani, Alireza; Li, Zhen; Karniadakis, George

2015-11-01

The process of clot formation and growth at a site on a blood vessel wall involve a number of multi-scale simultaneous processes including: multiple chemical reactions in the coagulation cascade, species transport and flow. To model these processes we have incorporated advection-diffusion-reaction (ADR) of multiple species into an extended version of Dissipative Particle Dynamics (DPD) method which is considered as a coarse-grained Molecular Dynamics method. At the continuum level this is equivalent to the Navier-Stokes equation plus one advection-diffusion equation for each specie. The chemistry of clot formation is now understood to be determined by mechanisms involving reactions among many species in dilute solution, where reaction rate constants and species diffusion coefficients in plasma are known. The role of blood particulates, i.e. red cells and platelets, in the clotting process is studied by including them separately and together in the simulations. An agonist-induced platelet activation mechanism is presented, while platelets adhesive dynamics based on a stochastic bond formation/dissociation process is included in the model.

"We're going through a lot of struggles that people don't even know about": the need to understand African American males' help-seeking for mental health on multiple levels.

PubMed

Lindsey, Michael A; Marcell, Arik V

2012-09-01

Young adult Black males face challenges related to addressing their mental health needs, yet there is much more to know about their help-seeking experiences. Twenty-seven Black males, recruited from four community-based organizations, participated in four focus groups to explore perceptions of help-seeking for mental health. Identified themes, which function at individual, social network, community, and health care system levels, may facilitate or hinder Black males' mental health help-seeking. Themes included (a) "taking care of it oneself" as opposed to seeking help from someone; (b) issues engaging sources of help, including the ability to trust providers or the relationship closeness with social network members; and (c) "tipping points" that activate help-seeking to avert crises. Study findings provide initial evidence about the importance of addressing mental health interventions for Black males on multiple levels beyond the individual including engaging men's social supports, community, and the health care system.

Modified Advanced Crew Escape Suit Intravehicular Activity Suit for Extravehicular Activity Mobility Evaluations

NASA Technical Reports Server (NTRS)

Watson, Richard D.

2014-01-01

The use of an intravehicular activity (IVA) suit for a spacewalk or extravehicular activity (EVA) was evaluated for mobility and usability in the Neutral Buoyancy Laboratory (NBL) environment at the Sonny Carter Training Facility near NASA Johnson Space Center in Houston, Texas. The Space Shuttle Advanced Crew Escape Suit was modified to integrate with the Orion spacecraft. The first several missions of the Orion Multi-Purpose Crew Vehicle will not have mass available to carry an EVA-specific suit; therefore, any EVA required will have to be performed by the Modified Advanced Crew Escape Suit (MACES). Since the MACES was not designed with EVA in mind, it was unknown what mobility the suit would be able to provide for an EVA or whether a person could perform useful tasks for an extended time inside the pressurized suit. The suit was evaluated in multiple NBL runs by a variety of subjects, including crewmembers with significant EVA experience. Various functional mobility tasks performed included: translation, body positioning, tool carrying, body stabilization, equipment handling, and tool usage. Hardware configurations included with and without Thermal Micrometeoroid Garment, suit with IVA gloves and suit with EVA gloves. Most tasks were completed on International Space Station mock-ups with existing EVA tools. Some limited tasks were completed with prototype tools on a simulated rocky surface. Major findings include: demonstrating the ability to weigh-out the suit, understanding the need to have subjects perform multiple runs prior to getting feedback, determining critical sizing factors, and need for adjusting suit work envelope. Early testing demonstrated the feasibility of EVA's limited duration and limited scope. Further testing is required with more flight-like tasking and constraints to validate these early results. If the suit is used for EVA, it will require mission-specific modifications for umbilical management or Primary Life Support System integration, safety tether attachment, and tool interfaces. These evaluations are continuing through calendar year 2014.

Learning Setting-Generalized Activity Models for Smart Spaces

PubMed Central

Cook, Diane J.

2011-01-01

The data mining and pervasive computing technologies found in smart homes offer unprecedented opportunities for providing context-aware services, including health monitoring and assistance to individuals experiencing difficulties living independently at home. In order to provide these services, smart environment algorithms need to recognize and track activities that people normally perform as part of their daily routines. However, activity recognition has typically involved gathering and labeling large amounts of data in each setting to learn a model for activities in that setting. We hypothesize that generalized models can be learned for common activities that span multiple environment settings and resident types. We describe our approach to learning these models and demonstrate the approach using eleven CASAS datasets collected in seven environments. PMID:21461133

"I'd rather watch TV": an examination of physical activity in adults with mental retardation.

PubMed

Frey, Georgia C; Buchanan, Alice M; Rosser Sandt, Dawn D

2005-08-01

Interpretive ethnography was used as a framework to examine perceptions of physical activity behavior of 12 adults with mild mental retardation. Four parents and two job supervisors also agreed to participate. Multiple data sources included in-depth interviews, diaries, accelerometry, and informal observations. Participants reported many physical activity barriers, benefits, and leisure choices similar to the general population; however, two particularly salient themes related to negative influences and lack of guidance from support systems were apparently unique to this group. Results suggest that (a) adults with mental retardation need specially designed physical activity education and training programs and (b) supports system providers should be educated regarding the importance of physical activity to health for these individuals.

Performance improvement of organic thin film transistors by using active layer with sandwich structure

NASA Astrophysics Data System (ADS)

Ni, Yao; Zhou, Jianlin; Kuang, Peng; Lin, Hui; Gan, Ping; Hu, Shengdong; Lin, Zhi

2017-08-01

We report organic thin film transistors (OTFTs) with pentacene/fluorinated copper phthalo-cyanine (F16CuPc)/pentacene (PFP) sandwich configuration as active layers. The sandwich devices not only show hole mobility enhancement but also present a well control about threshold voltage and off-state current. By investigating various characteristics, including current-voltage hysteresis, organic film morphology, capacitance-voltage curve and resistance variation of active layers carefully, it has been found the performance improvement is mainly attributed to the low carrier traps and the higher conductivity of the sandwich active layer due to the additional induced carriers in F16CuPc/pentacene. Therefore, using proper multiple active layer is an effective way to gain high performance OTFTs.

Community-based group aquatic programme for individuals with multiple sclerosis: a pilot study.

PubMed

Salem, Yasser; Scott, Anne Hiller; Karpatkin, Herbert; Concert, George; Haller, Leah; Kaminsky, Eva; Weisbrot, Rivky; Spatz, Eugene

2011-01-01

The purpose of this study was to determine the feasibility of providing a community-based aquatic exercise programme and to examine the effects of a group aquatic exercise programme in individuals with multiple sclerosis. This study illustrates the implementation of a multidisciplinary community-based programme in a university community wellness centre coordinated with a local advocacy group. Eleven subjects with multiple sclerosis participated in a 5-week community-based aquatic exercise programme. Aquatic exercises were held twice weekly for 60 minutes and included aerobic exercises, strength training, flexibility exercises, balance training and walking activities. The 10-Metre Walk test, the Berg Balance Scale (BBS), the 'Timed Up and Go' (TUG) test, grip strength and the Modified Fatigue Impact Scale were used to assess motor function. Analysis of the scores demonstrated improved gait speed, BBS, TUG test and grip strength. The average attendance of the training sessions was good (88%), and no incidence of injuries, no incidence of falls and no adverse effects related to the exercise programme were reported. All participants reported that they enjoyed the programme, and they had improved after the training. A community-based aquatic exercise programme is feasible and resulted in improvement in motor functions of individuals with multiple sclerosis. These findings indicate that an aquatic training programme is appropriate and beneficial for individuals with multiple sclerosis and should be considered to augment the rehabilitation of those individuals. This programme may provide a viable model for a community-based wellness programme for people with disability including individuals with multiple sclerosis.

Diverse ways of perturbing the human arachidonic acid metabolic network to control inflammation.

PubMed

Meng, Hu; Liu, Ying; Lai, Luhua

2015-08-18

Inflammation and other common disorders including diabetes, cardiovascular disease, and cancer are often the result of several molecular abnormalities and are not likely to be resolved by a traditional single-target drug discovery approach. Though inflammation is a normal bodily reaction, uncontrolled and misdirected inflammation can cause inflammatory diseases such as rheumatoid arthritis and asthma. Nonsteroidal anti-inflammatory drugs including aspirin, ibuprofen, naproxen, or celecoxib are commonly used to relieve aches and pains, but often these drugs have undesirable and sometimes even fatal side effects. To facilitate safer and more effective anti-inflammatory drug discovery, a balanced treatment strategy should be developed at the biological network level. In this Account, we focus on our recent progress in modeling the inflammation-related arachidonic acid (AA) metabolic network and subsequent multiple drug design. We first constructed a mathematical model of inflammation based on experimental data and then applied the model to simulate the effects of commonly used anti-inflammatory drugs. Our results indicated that the model correctly reproduced the established bleeding and cardiovascular side effects. Multitarget optimal intervention (MTOI), a Monte Carlo simulated annealing based computational scheme, was then developed to identify key targets and optimal solutions for controlling inflammation. A number of optimal multitarget strategies were discovered that were both effective and safe and had minimal associated side effects. Experimental studies were performed to evaluate these multitarget control solutions further using different combinations of inhibitors to perturb the network. Consequently, simultaneous control of cyclooxygenase-1 and -2 and leukotriene A4 hydrolase, as well as 5-lipoxygenase and prostaglandin E2 synthase were found to be among the best solutions. A single compound that can bind multiple targets presents advantages including low risk of drug-drug interactions and robustness regarding concentration fluctuations. Thus, we developed strategies for multiple-target drug design and successfully discovered several series of multiple-target inhibitors. Optimal solutions for a disease network often involve mild but simultaneous interventions of multiple targets, which is in accord with the philosophy of traditional Chinese medicine (TCM). To this end, our AA network model can aptly explain TCM anti-inflammatory herbs and formulas at the molecular level. We also aimed to identify activators for several enzymes that appeared to have increased activity based on MTOI outcomes. Strategies were then developed to predict potential allosteric sites and to discover enzyme activators based on our hypothesis that combined treatment with the projected activators and inhibitors could balance different AA network pathways, control inflammation, and reduce associated adverse effects. Our work demonstrates that the integration of network modeling and drug discovery can provide novel solutions for disease control, which also calls for new developments in drug design concepts and methodologies. With the rapid accumulation of quantitative data and knowledge of the molecular networks of disease, we can expect an increase in the development and use of quantitative disease models to facilitate efficient and safe drug discovery.

Activational and effort-related aspects of motivation: neural mechanisms and implications for psychopathology

PubMed Central

Yohn, Samantha E.; López-Cruz, Laura; San Miguel, Noemí; Correa, Mercè

2016-01-01

Abstract Motivation has been defined as the process that allows organisms to regulate their internal and external environment, and control the probability, proximity and availability of stimuli. As such, motivation is a complex process that is critical for survival, which involves multiple behavioural functions mediated by a number of interacting neural circuits. Classical theories of motivation suggest that there are both directional and activational aspects of motivation, and activational aspects (i.e. speed and vigour of both the instigation and persistence of behaviour) are critical for enabling organisms to overcome work-related obstacles or constraints that separate them from significant stimuli. The present review discusses the role of brain dopamine and related circuits in behavioural activation, exertion of effort in instrumental behaviour, and effort-related decision-making, based upon both animal and human studies. Impairments in behavioural activation and effort-related aspects of motivation are associated with psychiatric symptoms such as anergia, fatigue, lassitude and psychomotor retardation, which cross multiple pathologies, including depression, schizophrenia, and Parkinson’s disease. Therefore, this review also attempts to provide an interdisciplinary approach that integrates findings from basic behavioural neuroscience, behavioural economics, clinical neuropsychology, psychiatry, and neurology, to provide a coherent framework for future research and theory in this critical field. Although dopamine systems are a critical part of the brain circuitry regulating behavioural activation, exertion of effort, and effort-related decision-making, mesolimbic dopamine is only one part of a distributed circuitry that includes multiple neurotransmitters and brain areas. Overall, there is a striking similarity between the brain areas involved in behavioural activation and effort-related processes in rodents and in humans. Animal models of effort-related decision-making are highly translatable to humans, and an emerging body of evidence indicates that alterations in effort-based decision-making are evident in several psychiatric and neurological disorders. People with major depression, schizophrenia, and Parkinson’s disease show evidence of decision-making biases towards a lower exertion of effort. Translational studies linking research with animal models, human volunteers, and clinical populations are greatly expanding our knowledge about the neural basis of effort-related motivational dysfunction, and it is hoped that this research will ultimately lead to improved treatment for motivational and psychomotor symptoms in psychiatry and neurology. PMID:27189581

Mechanism of amido-thiourea catalyzed enantioselective imine hydrocyanation: transition state stabilization via multiple non-covalent interactions.

PubMed

Zuend, Stephan J; Jacobsen, Eric N

2009-10-28

An experimental and computational investigation of amido-thiourea promoted imine hydrocyanation has revealed a new and unexpected mechanism of catalysis. Rather than direct activation of the imine by the thiourea, as had been proposed previously in related systems, the data are consistent with a mechanism involving catalyst-promoted proton transfer from hydrogen isocyanide to imine to generate diastereomeric iminium/cyanide ion pairs that are bound to catalyst through multiple noncovalent interactions; these ion pairs collapse to form the enantiomeric alpha-aminonitrile products. This mechanistic proposal is supported by the observation of a statistically significant correlation between experimental and calculated enantioselectivities induced by eight different catalysts (P < 0.01). The computed models reveal a basis for enantioselectivity that involves multiple stabilizing and destabilizing interactions between substrate and catalyst, including thiourea-cyanide and amide-iminium interactions.

Adaptive sensor-fault tolerant control for a class of multivariable uncertain nonlinear systems.

PubMed

Khebbache, Hicham; Tadjine, Mohamed; Labiod, Salim; Boulkroune, Abdesselem

2015-03-01

This paper deals with the active fault tolerant control (AFTC) problem for a class of multiple-input multiple-output (MIMO) uncertain nonlinear systems subject to sensor faults and external disturbances. The proposed AFTC method can tolerate three additive (bias, drift and loss of accuracy) and one multiplicative (loss of effectiveness) sensor faults. By employing backstepping technique, a novel adaptive backstepping-based AFTC scheme is developed using the fact that sensor faults and system uncertainties (including external disturbances and unexpected nonlinear functions caused by sensor faults) can be on-line estimated and compensated via robust adaptive schemes. The stability analysis of the closed-loop system is rigorously proven using a Lyapunov approach. The effectiveness of the proposed controller is illustrated by two simulation examples. Copyright © 2014 ISA. Published by Elsevier Ltd. All rights reserved.

"Intelligences That Plants Can Pass On": Play Dough, Fun and Teaching Strategies with Insights to Multiple Intelligences

ERIC Educational Resources Information Center

Laughlin, Kevin; Foley, Andi

2012-01-01

The "Intelligences That Plants Can Pass On" is an activity that involves several of Gardner's Multiple Intelligences and was designed for demonstrating the practical use of Multiple Intelligences in delivering education programs to all ages of learners. Instructions are provided for how to implement this activity, and the activity is linked to…

Passive colloids work together to become Active

NASA Astrophysics Data System (ADS)

Kandula, Hima Nagamanasa; Wang, Wei; Zhang, Jie; Wu, Huanxin; Han, Ming; Luijten, Erik; Granick, Steve

In recent years there is growing body of research to design self-propelled colloids to gain insights into non-equilibrium systems including living matter. While most active colloids developed hitherto entail prefabrication of Janus colloids and possess single fixed active site, we present one simple system where active colloids are formed in-situ naturally with multiple active sites and are reversible as well as reconfigurable. A binary mixture of Brownian colloids which have opposite polarizations when subjected to an AC electric field spontaneously assemble into clusters which are propelled by asymmetric induced charge electro osmosis. We find that tuning the relative sizes of the two species allows for the control over the number of active sites. More interestingly, the patches are dynamic enabling reconfiguration of the active cluster. Consequently, the clusters are active not only in motion but also in their structure.

Satisfaction with communicative participation as defined by adults with multiple sclerosis: a qualitative study.

PubMed

Yorkston, Kathryn M; Baylor, Carolyn R; Klasner, Estelle R; Deitz, Jean; Dudgeon, Brian J; Eadie, Tanya; Miller, Robert M; Amtmann, Dagmar

2007-01-01

This study examined satisfaction with communicative participation as reported by adults with multiple sclerosis (MS). Eight community-dwelling adults with MS participated in semi-structured interviews. They were asked to discuss their satisfaction with their communication in a variety of situations. Interviews were analyzed using a constant comparative method of qualitative description. Themes derived included: Comfort, consisting of Ease and Confidence; Success of the Outcome, including Function is Achieved and A Connection is Made; and Personal Meaning of Participation, including Personal Preferences, Comparison with the Past, and Thinking about One's Own Communication. Participants described multiple facets of satisfaction with communicative participation. Some of the dimensions were similar to those in existing assessment instruments such as levels of ease or difficulty with performance. Participants did not talk about frequency of activities as a key part of their satisfaction. Implications for identifying intervention targets and treatment outcome measurements are provided. The reader should be able to: 1) define communicative participation and identify key elements of this construct; 2) identify the issues that were most relevant to satisfaction with communicative participation with participants with MS; and 3) identify reasons for greater emphasis on the subjective viewpoint of people with communication disorders in measurement of treatment outcomes.

Transmedia Storytelling in Science Communication: One Subject, Multiple Media, Multiple Stories

NASA Astrophysics Data System (ADS)

Unger, M.; Moloney, K.

2012-12-01

Each communication medium has particular storytelling strengths. For example, video is particularly good at illustrating a progression of events, text at background and context, and games at describing systems. In what USC's Prof. Henry Jenkins described as "transmedia storytelling," multiple media are used simultaneously, in an expansive rather than repetitive way, to better tell a single, complex story. The audience is given multiple entry points to the story, and the story is exposed to diverse and dispersed audiences, ultimately engaging a broader public. We will examine the effectiveness of a transmedia approach to communicating scientific and other complex concepts to a broad and diverse audience. Using the recently developed Educational Visitor Center at the NCAR-Wyoming Supercomputing Center as a case study, we will evaluate the reach of various means of presenting information about the geosciences, climate change and computational science. These will include an assessment of video, mechanical and digital interactive elements, animated movie segments, web-based content, photography, scientific visualizations, printed material and docent-led activities.

Consensus statement on the treatment of multiple sclerosis by the Spanish Society of Neurology in 2016.

PubMed

García Merino, A; Ramón Ara Callizo, J; Fernández Fernández, O; Landete Pascual, L; Moral Torres, E; Rodríguez-Antigüedad Zarrantz, A

2017-03-01

With the advent of new disease-modifying drugs, the treatment of multiple sclerosis is becoming increasingly complex. Using consensus statements is therefore advisable. The present consensus statement, which was drawn up by the Spanish Society of Neurology's study group for demyelinating diseases, updates previous consensus statements on the disease. The present study lists the medications currently approved for multiple sclerosis and their official indications, and analyses such treatment-related aspects as activity, early treatment, maintenance, follow-up, treatment failure, changes in medication, and special therapeutic situations. This consensus statement includes treatment recommendations for a wide range of demyelinating diseases, from isolated demyelinating syndromes to the different forms of multiple sclerosis, as well as recommendations for initial therapy and changes in drug medication, and additional comments on induction and combined therapy and practical aspects of the use of these drugs. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Dovetail spoke internal permanent magnet machine

DOEpatents

Alexander, James Pellegrino [Ballston Lake, NY; EL-Refaie, Ayman Mohamed Fawzi [Niskayuna, NY; Lokhandwalla, Murtuza [Clifton Park, NY; Shah, Manoj Ramprasad [Latham, NY; VanDam, Jeremy Daniel [West Coxsackie, NY

2011-08-23

An internal permanent magnet (IPM) machine is provided. The IPM machine includes a stator assembly and a stator core. The stator core also includes multiple stator teeth. The stator assembly is further configured with stator windings to generate a stator magnetic field when excited with alternating currents and extends along a longitudinal axis with an inner surface defining a cavity. The IPM machine also includes a rotor assembly and a rotor core. The rotor core is disposed inside the cavity and configured to rotate about the longitudinal axis. The rotor assembly further includes a shaft. The shaft further includes multiple protrusions alternately arranged relative to multiple bottom structures provided on the shaft. The rotor assembly also includes multiple stacks of laminations disposed on the protrusions and dovetailed circumferentially around the shaft. The rotor assembly further includes multiple pair of permanent magnets for generating a magnetic field, which magnetic field interacts with the stator magnetic field to produce a torque. The multiple pair of permanent magnets are disposed between the stacks. The rotor assembly also includes multiple middle wedges mounted between each pair of the multiple permanent magnets.

In vivo imaging of zebrafish digestive organ function using multiple quenched fluorescent reporters.

PubMed

Hama, Kotaro; Provost, Elayne; Baranowski, Timothy C; Rubinstein, Amy L; Anderson, Jennifer L; Leach, Steven D; Farber, Steven A

2009-02-01

Optical clarity of larvae makes the zebrafish ideal for real-time analyses of vertebrate organ function through the use of fluorescent reporters of enzymatic activities. A key function of digestive organs is to couple the generation of enzymes with mechanical processes that enable nutrient availability and absorption. However, it has been extremely difficult, and in many cases not possible, to directly observe digestive processes in a live vertebrate. Here we describe a new method to visualize intestinal protein and lipid processing simultaneously in live zebrafish larvae using a quenched fluorescent protein (EnzChek) and phospholipid (PED6). By employing these reagents, we found that wild-type larvae exhibit significant variation in intestinal phospholipase and protease activities within a group but display a strong correlation between the activities within individuals. Furthermore, we found that pancreas function is essential for larval digestive protease activity but not for larval intestinal phospholipase activity. Although fat-free (ffr) mutant larvae were previously described to exhibit impaired lipid processes, we found they also had significantly reduced protease activity. Finally, we selected and evaluated compounds that were previously suggested to have altered phospholipase activity and are known or suspected to have inflammatory effects in the intestinal tract including nonsteroidal anti-inflammatory drugs, and identified a compound that significantly increases intestinal phospholipid processing. Thus the multiple fluorescent reporter-based methodology facilitates the rapid analysis of digestive organ function in live zebrafish larvae.

Performance evaluation of a semi-active cladding connection for multi-hazard mitigation

NASA Astrophysics Data System (ADS)

Gong, Yongqiang; Cao, Liang; Micheli, Laura; Laflamme, Simon; Quiel, Spencer; Ricles, James

2018-03-01

A novel semi-active damping device termed Variable Friction Cladding Connection (VFCC) has been previously proposed to leverage cladding systems for the mitigation of natural and man-made hazards. The VFCC is a semi-active friction damper that connects cladding elements to the structural system. The friction force is generated by sliding plates and varied using an actuator through a system of adjustable toggles. The dynamics of the device has been previously characterized in a laboratory environment. In this paper, the performance of the VFCC at mitigating non-simultaneous multi-hazard excitations that includes wind and seismic loads is investigated on a simulated benchmark building. Simulations consider the robustness with respect to some uncertainties, including the wear of the friction surfaces and sensor failure. The performance of the VFCC is compared against other connection strategies including traditional stiffness, passive viscous, and passive friction elements. Results show that the VFCC is robust and capable of outperforming passive systems for the mitigation of multiple hazards.

Young People's Perceptions of Relationships and Sexual Practices in the Abstinence-Only Context of Uganda

ERIC Educational Resources Information Center

de Haas, Billie; Hutter, Inge; Timmerman, Greetje

2017-01-01

The Ugandan government has been criticised on several grounds for its abstinence-only policies on sexuality education directed towards young people. These grounds include the failure to recognise the multiple realities faced by young people, some of whom may already be sexually active. In the study reported on this paper, students' perceptions of…

Unexpected visitor on FDG PET/CT--brown adipose tissue (BAT) in mesentery in a case of retroperitoneal extra-adrenal pheochromocytoma: is the BAT activation secondary to catecholamine-secreting pheochromocytoma?

PubMed

Joshi, Prathamesh Vijay; Lele, Vikram Ramchandra

2012-05-01

Fused positron emission tomography-computed tomography (PET/CT) technology has enabled the determination that nonmalignant fluorodeoxyglucose (FDG) uptake is observed in brown adipose tissue (BAT). FDG uptake in BAT is a known potential source of false-positive interpretations for PET. The typical locations of BAT include neck, supraclavicular area, mediastinum, and paravertebral intercostal spaces. Examples of atypical locations for BAT include posterior neck, left paratracheal area, axillae, perirenal area, and retrocrural area. We report PET/CT findings in a young male patient with malignant retroperitoneal extra-adrenal pheochromocytoma, who demonstrated FDG uptake in BAT at multiple locations including mesenteric BAT. We also propose catecholamine-secreting pheochromocytoma as a possible cause of BAT activation in our case.

Unifying mechanism for different fibrotic diseases

PubMed Central

Wernig, Gerlinde; Chen, Shih-Yu; Cui, Lu; Van Neste, Camille; Tsai, Jonathan M.; Kambham, Neeraja; Vogel, Hannes; Natkunam, Yaso; Gilliland, D. Gary; Nolan, Garry; Weissman, Irving L.

2017-01-01

Fibrotic diseases are not well-understood. They represent a number of different diseases that are characterized by the development of severe organ fibrosis without any obvious cause, such as the devastating diseases idiopathic pulmonary fibrosis (IPF) and scleroderma. These diseases have a poor prognosis comparable with endstage cancer and are uncurable. Given the phenotypic differences, it was assumed that the different fibrotic diseases also have different pathomechanisms. Here, we demonstrate that many endstage fibrotic diseases, including IPF; scleroderma; myelofibrosis; kidney-, pancreas-, and heart-fibrosis; and nonalcoholic steatohepatosis converge in the activation of the AP1 transcription factor c-JUN in the pathologic fibroblasts. Expression of the related AP1 transcription factor FRA2 was restricted to pulmonary artery hypertension. Induction of c-Jun in mice was sufficient to induce severe fibrosis in multiple organs and steatohepatosis, which was dependent on sustained c-Jun expression. Single cell mass cytometry revealed that c-Jun activates multiple signaling pathways in mice, including pAkt and CD47, which were also induced in human disease. αCD47 antibody treatment and VEGF or PI3K inhibition reversed various organ c-Jun–mediated fibroses in vivo. These data suggest that c-JUN is a central molecular mediator of most fibrotic conditions. PMID:28424250

Role of the blood-brain barrier in multiple sclerosis.

PubMed

Ortiz, Genaro Gabriel; Pacheco-Moisés, Fermín Paul; Macías-Islas, Miguel Ángel; Flores-Alvarado, Luis Javier; Mireles-Ramírez, Mario A; González-Renovato, Erika Daniela; Hernández-Navarro, Vanessa Elizabeth; Sánchez-López, Angélica Lizeth; Alatorre-Jiménez, Moisés Alejandro

2014-11-01

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system associated with demyelination and axonal loss eventually leading to neurodegeneration. MS exhibits many of the hallmarks of an inflammatory autoimmune disorder including breakdown of the blood-brain barrier (BBB). The BBB is a complex organization of cerebral endothelial cells, pericytes and their basal lamina, which are surrounded and supported by astrocytes and perivascular macrophages. In pathological conditions, lymphocytes activated in the periphery infiltrate the central nervous system to trigger a local immune response that ultimately damages myelin and axons. Cytotoxic factors including pro-inflammatory cytokines, proteases, and reactive oxygen and nitrogen species accumulate and may contribute to myelin destruction. Dysregulation of the BBB and transendothelial migration of activated leukocytes are among the earliest cerebrovascular abnormalities seen in MS brains and parallel the release of inflammatory cytokines. In this review we establish the importance of the role of the BBB in MS. Improvements in our understanding of molecular mechanism of BBB functioning in physiological and pathological conditions could lead to improvement in the quality of life of MS patients. Copyright © 2015 IMSS. Published by Elsevier Inc. All rights reserved.

An old drug with a new future: bendamustine in multiple myeloma.

PubMed

Gentile, Massimo; Recchia, Anna Grazia; Mazzone, Carla; Vigna, Ernesto; Martino, Massimo; Morabito, Lucio; Lucia, Eugenio; Bossio, Sabrina; De Stefano, Laura; Granata, Teresa; Palummo, Angela; Morabito, Fortunato

2013-11-01

Bendamustine is a unique bifunctional alkylating agent with promising activity in multiple myeloma (MM). It is currently licensed in Europe for use as frontline treatment with prednisolone for patients with MM who are unsuitable for transplantation and who are contraindicated for thalidomide and bortezomib therapy. Studies evaluating the safety and efficacy of bendamustine administered alone or in combination in both the upfront and relapse settings of MM patients, including those with renal insufficiency, were reviewed. The use of bendamustine as conditioning for autologous stem-cell transplantation and the possibility of stem-cell mobilization after bendamustine therapy are discussed. Bendamustine seems to be efficacious either in monotherapy or in combination with other drugs in previously treated or untreated patients. This is due to its unique mechanism of action including its ability to activate apoptosis and inhibit mitotic checkpoints, making it potentially more effective than other alkylating agents. Moreover, it has an acceptable toxicity profile and is suitable for patients with renal impairment. Finally, this drug does not seem to compromise the possibility of achieving a stem-cell mobilization. Nonetheless, data from Phase III studies demonstrating its effectiveness in terms of overall survival are not yet available.

p205, a potential tumor suppressor, inhibits cell proliferation via multiple pathways of cell cycle regulation.

PubMed

Asefa, Benyam; Dermott, Jonathan M; Kaldis, Philipp; Stefanisko, Karen; Garfinkel, David J; Keller, Jonathan R

2006-02-20

p205 is a member of the interferon-inducible p200 family of proteins that regulate cell proliferation. Over-expression of p205 inhibits cell growth, although its mechanism of action is currently unknown. Therefore, we evaluated the effect of p205 on the p53 and Rb-dependent pathways of cell cycle regulation. p205 expression results in elevated levels of p21, and activates the p21 promoter in vitro in a p53-dependent manner. In addition, p205 induces increased expression of Rb, and binds directly to Rb and p53. Interestingly, p205 also induces growth inhibition independent of p53 and Rb by delaying G2/M progression in proliferating cells, and is a substrate for Cdk2 kinase activity. Finally, we have identified other binding partners of p205 by a yeast two-hybrid screen, including the paired homeodomain protein HoxB2. Taken together, our results indicate that p205 induces growth arrest by interaction with multiple transcription factors that regulate the cell cycle, including but not entirely dependent on the Rb- and p53-mediated pathways of growth inhibition.

Allergen source materials: state-of-the-art.

PubMed

Esch, Robert E

2009-01-01

A variety of positive outcomes can be realized from validation and risk management activities (see Table 4). They are dependent on the participation of multiple functional groups including the quality unit, regulatory and legal affairs, engineering and production operations, research and development, and sales and marketing. Quality risk management is receiving increased attention in the area of public health, pharmacovigilance, and pharmaceutical manufacturing. Recent examples of its regulatory use in our industry include the assessment of the potential risks of transmissible spongiform encephalopathies (TSE) agents through contaminated products], the risks of precipitates in allergenic extracts, and the revision of the potency limits for standardized dust mite and grass allergen vaccines. Its application to allergen source material process validation activities allowed for a practical strategy, especially in a complex manufacturing environment involving hundreds of products with multiple intended uses. In addition, the use of tools such as FMEA was useful in evaluating proposed changes made to manufacturing procedures and product specifications, new regulatory actions, and customer feedback or complaints. The success of such a quality assurance programs will ultimately be reflected in the elimination or reduction of product failures, improvement in the detection and prediction of potential product failures, and increased confidence in product quality.

Challenges of Implementing a Communication-and-Resolution Program Where Multiple Organizations Must Cooperate.

PubMed

Mello, Michelle M; Armstrong, Sarah J; Greenberg, Yelena; McCotter, Patricia I; Gallagher, Thomas H

2016-12-01

To implement a communication-and-resolution program (CRP) in a setting in which liability insurers and health care facilities must collaborate to resolve incidents involving a facility and separately insured clinicians. Six hospitals and clinics and a liability insurer in Washington State. Sites designed and implemented CRPs and contributed information about cases and operational challenges over 20 months. Data were qualitatively analyzed. Data from interviews with personnel responsible for CRP implementation were triangulated with data on program cases collected by sites and notes recorded during meetings with sites and among project team members. Sites experienced small victories in resolving particular cases and streamlining some working relationships, but they were unable to successfully implement a collaborative CRP. Barriers included the insurer's distance from the point of care, passive rather than active support from top leaders, coordinating across departments and organizations, workload, nonparticipation by some physicians, and overcoming distrust. Operating CRPs where multiple organizations must collaborate can be highly challenging. Success likely requires several preconditions, including preexisting trust among organizations, active leadership engagement, physicians' commitment to participate, mechanisms for quickly transmitting information to insurers, tolerance for missteps, and clear protocols for joint investigations and resolutions. © Health Research and Educational Trust.

Film excerpts shown to specifically elicit various affects lead to overlapping activation foci in a large set of symmetrical brain regions in males.

PubMed

Karama, Sherif; Armony, Jorge; Beauregard, Mario

2011-01-01

While the limbic system theory continues to be part of common scientific parlance, its validity has been questioned on multiple grounds. Nonetheless, the issue of whether or not there exists a set of brain areas preferentially dedicated to emotional processing remains central within affective neuroscience. Recently, a widespread neural reference space for emotion which includes limbic as well as other regions was characterized in a large meta-analysis. As methodologically heterogeneous studies go into such meta-analyses, showing in an individual study in which all parameters are kept constant, the involvement of overlapping areas for various emotion conditions in keeping with the neural reference space for emotion, would serve as valuable confirmatory evidence. Here, using fMRI, 20 young adult men were scanned while viewing validated neutral and effective emotion-eliciting short film excerpts shown to quickly and specifically elicit disgust, amusement, or sexual arousal. Each emotion-specific run included, in random order, multiple neutral and emotion condition blocks. A stringent conjunction analysis revealed a large overlap across emotion conditions that fit remarkably well with the neural reference space for emotion. This overlap included symmetrical bilateral activation of the medial prefrontal cortex, the anterior cingulate, the temporo-occipital junction, the basal ganglia, the brainstem, the amygdala, the hippocampus, the thalamus, the subthalamic nucleus, the posterior hypothalamus, the cerebellum, as well as the frontal operculum extending towards the anterior insula. This study clearly confirms for the visual modality, that processing emotional stimuli leads to widespread increases in activation that cluster within relatively confined areas, regardless of valence.

Evaluation of the Activity of Lamivudine and Zidovudine against Ebola Virus.

PubMed

Cong, Yu; Dyall, Julie; Hart, Brit J; DeWald, Lisa Evans; Johnson, Joshua C; Postnikova, Elena; Zhou, Huanying; Gross, Robin; Rojas, Oscar; Alexander, Isis; Josleyn, Nicole; Zhang, Tengfei; Michelotti, Julia; Janosko, Krisztina; Glass, Pamela J; Flint, Mike; McMullan, Laura K; Spiropoulou, Christina F; Mierzwa, Tim; Guha, Rajarshi; Shinn, Paul; Michael, Sam; Klumpp-Thomas, Carleen; McKnight, Crystal; Thomas, Craig; Eakin, Ann E; O'Loughlin, Kathleen G; Green, Carol E; Catz, Paul; Mirsalis, Jon C; Honko, Anna N; Olinger, Gene G; Bennett, Richard S; Holbrook, Michael R; Hensley, Lisa E; Jahrling, Peter B

2016-01-01

In the fall of 2014, an international news agency reported that patients suffering from Ebola virus disease (EVD) in Liberia were treated successfully with lamivudine, an antiviral drug used to treat human immunodeficiency virus-1 and hepatitis B virus infections. According to the report, 13 out of 15 patients treated with lamivudine survived and were declared free from Ebola virus disease. In this study, the anti-Ebola virus (EBOV) activity of lamivudine and another antiretroviral, zidovudine, were evaluated in a diverse set of cell lines against two variants of wild-type EBOV. Variable assay parameters were assessed to include different multiplicities of infection, lengths of inoculation times, and durations of dosing. At a multiplicity of infection of 1, lamivudine and zidovudine had no effect on EBOV propagation in Vero E6, Hep G2, or HeLa cells, or in primary human monocyte-derived macrophages. At a multiplicity of infection of 0.1, zidovudine demonstrated limited anti-EBOV activity in Huh 7 cells. Under certain conditions, lamivudine had low anti-EBOV activity at the maximum concentration tested (320 μM). However, lamivudine never achieved greater than 30% viral inhibition, and the activity was not consistently reproducible. Combination of lamivudine and zidovudine showed no synergistic antiviral activity. Independently, a set of in vitro experiments testing lamivudine and zidovudine for antiviral activity against an Ebola-enhanced green fluorescent protein reporter virus was performed at the Centers for Disease Control and Prevention. No antiviral activity was observed for either compound. A study evaluating the efficacy of lamivudine in a guinea pig model of EVD found no survival benefit. This lack of benefit was observed despite plasma lamivudine concentrations in guinea pig of about 4 μg/ml obtained in a separately conducted pharmacokinetics study. These studies found no evidence to support the therapeutic use of lamivudine for the treatment of EVD.

Drugs and Diseases Interacting with Cigarette Smoking in US Prescription Drug Labelling.

PubMed

Li, Haibo; Shi, Qiang

2015-05-01

The US Food and Drug Administration (FDA) draft guidance for industry on drug interaction studies recommends, but does not mandate, that both cigarette smokers and non-smokers can be used to study drug metabolism in clinical trials, and that important results related to smoking should be included in drug labelling to guide medication usage. This study aimed to provide a comprehensive review of drugs or diseases interacting with smoking, as presented in all US drug labelling. The 62,857 drug labels deposited in the FDA Online Label Repository were searched using the keywords 'smoke', 'smoker(s)', 'smoking', 'tobacco' and 'cigarette(s)' on 19 June 2014. The resultant records were refined to include only human prescription drug labelling, for manual examination. For 188 single-active-ingredient drugs and 36 multiple-active-ingredient drugs, the labelling was found to contain smoking-related information. The pharmacokinetics of 29 and 21 single-active-ingredient drugs were affected and unaffected, respectively, by smoking. For the remaining drugs, the provided information related to smoking affecting efficacy, safety or diseases but not pharmacokinetics. Depending on the nature of specific drugs, the perturbation in pharmacokinetic parameters in smokers ranged from 13 to 500%, in comparison with non-smokers. Dosage modifications in smokers are necessary for four drugs and may be necessary for six drugs, but are unnecessary for seven drugs although the pharmacokinetic parameters of four of them are affected by smoking. Cigarette smoking is a risk factor for 16 types of diseases or adverse drug reactions. For one single-active-ingredient contraceptive drug and 10 multiple-active-ingredient contraceptive drugs, a black box warning (the FDA's strongest safety warning) is included in the labelling for increased risks of heart attacks and strokes in female smokers, and "women are strongly advised not to smoke" when using these drugs. This study presents the first comprehensive overview of cigarette smoking interacting with drugs and/or diseases, as presented in US drug labelling.

Three Hypothetical Inflammation Pathobiology Phenotypes and Pediatric Sepsis-Induced Multiple Organ Failure Outcome.

PubMed

Carcillo, Joseph A; Halstead, E Scott; Hall, Mark W; Nguyen, Trung C; Reeder, Ron; Aneja, Rajesh; Shakoory, Bita; Simon, Dennis

2017-06-01

We hypothesize that three inflammation pathobiology phenotypes are associated with increased inflammation, proclivity to develop features of macrophage activation syndrome, and multiple organ failure-related death in pediatric severe sepsis. Prospective cohort study comparing children with severe sepsis and any of three phenotypes: 1) immunoparalysis-associated multiple organ failure (whole blood ex vivo tumor necrosis factor response to endotoxin < 200 pg/mL), 2) thrombocytopenia-associated multiple organ failure (new onset thrombocytopenia with acute kidney injury and a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 activity < 57%), and/or 3) sequential multiple organ failure with hepatobiliary dysfunction (respiratory distress followed by liver dysfunction with soluble Fas ligand > 200 pg/mL), to those without any of these phenotypes. Tertiary children's hospital PICU. One hundred consecutive severe sepsis admissions. Clinical data were recorded daily, and blood was collected twice weekly. Multiple organ failure developed in 75 cases and eight died. Multiple organ failure cases with any of the three inflammation phenotypes (n = 37) had higher inflammation (C-reactive protein, p = 0.009 and ferritin, p < 0.001) than multiple organ failure cases without any of these phenotypes (n = 38) or cases with only single organ failure (n = 25). Development of features of macrophage activation syndrome and death were more common among multiple organ failure cases with any of the phenotypes (macrophage activation syndrome: 10/37, 27%; death: 8/37, 22%) compared to multiple organ failure cases without any phenotype (macrophage activation syndrome: 1/38, 3%; p = 0.003 and death: 0/38, 0%; p = 0.002). Our approach to phenotype categorization remains hypothetical, and the phenotypes identified need to be confirmed in multicenter studies of pediatric multiple organ dysfunction syndrome.

Microgap flat panel display

DOEpatents

Wuest, C.R.

1998-12-08

A microgap flat panel display is disclosed which includes a thin gas-filled display tube that utilizes switched X-Y ``pixel`` strips to trigger electron avalanches and activate a phosphor at a given location on a display screen. The panel utilizes the principal of electron multiplication in a gas subjected to a high electric field to provide sufficient electron current to activate standard luminescent phosphors located on an anode. The X-Y conductive strips of a few micron widths may for example, be deposited on opposite sides of a thin insulating substrate, or on one side of the adjacent substrates and function as a cathode. The X-Y strips are separated from the anode by a gap filled with a suitable gas. Electrical bias is selectively switched onto X and Y strips to activate a ``pixel`` in the region where these strips overlap. A small amount of a long-lived radioisotope is used to initiate an electron avalanche in the overlap region when bias is applied. The avalanche travels through the gas filled gap and activates a luminescent phosphor of a selected color. The bias is adjusted to give a proportional electron multiplication to control brightness for given pixel. 6 figs.

Semantic-based surveillance video retrieval.

PubMed

Hu, Weiming; Xie, Dan; Fu, Zhouyu; Zeng, Wenrong; Maybank, Steve

2007-04-01

Visual surveillance produces large amounts of video data. Effective indexing and retrieval from surveillance video databases are very important. Although there are many ways to represent the content of video clips in current video retrieval algorithms, there still exists a semantic gap between users and retrieval systems. Visual surveillance systems supply a platform for investigating semantic-based video retrieval. In this paper, a semantic-based video retrieval framework for visual surveillance is proposed. A cluster-based tracking algorithm is developed to acquire motion trajectories. The trajectories are then clustered hierarchically using the spatial and temporal information, to learn activity models. A hierarchical structure of semantic indexing and retrieval of object activities, where each individual activity automatically inherits all the semantic descriptions of the activity model to which it belongs, is proposed for accessing video clips and individual objects at the semantic level. The proposed retrieval framework supports various queries including queries by keywords, multiple object queries, and queries by sketch. For multiple object queries, succession and simultaneity restrictions, together with depth and breadth first orders, are considered. For sketch-based queries, a method for matching trajectories drawn by users to spatial trajectories is proposed. The effectiveness and efficiency of our framework are tested in a crowded traffic scene.

Oxidative Addition and Reductive Elimination at Main-Group Element Centers.

PubMed

Chu, Terry; Nikonov, Georgii I

2018-04-11

Oxidative addition and reductive elimination are key steps in a wide variety of catalytic reactions mediated by transition-metal complexes. Historically, this reactivity has been considered to be the exclusive domain of d-block elements. However, this paradigm has changed in recent years with the demonstration of transition-metal-like reactivity by main-group compounds. This Review highlights the substantial progress achieved in the past decade for the activation of robust single bonds by main-group compounds and the more recently realized activation of multiple bonds by these elements. We also discuss the significant discovery of reversible activation of single bonds and distinct examples of reductive elimination at main-group element centers. The review consists of three major parts, starting with oxidative addition of single bonds, proceeding to cleavage of multiple bonds, and culminated by the discussion of reversible bond activation and reductive elimination. Within each subsection, the discussion is arranged according to the type of bond being cleaved or formed and considers elements from the left to the right of each period and down each group of the periodic table. The majority of results discussed in this Review come from the past decade; however, earlier reports are also included to ensure completeness.

Control coil arrangement for a rotating machine rotor

DOEpatents

Shah, Manoj R.; Lewandowsk, Chad R.

2001-07-31

A rotating machine (e.g., a turbine, motor or generator) is provided wherein a fixed solenoid or other coil configuration is disposed adjacent to one or both ends of the active portion of the machine rotor for producing an axially directed flux in the active portion so as to provide planar axial control at single or multiple locations for rotor balance, levitation, centering, torque and thrust action. Permanent magnets can be used to produce an axial bias magnetic field. The rotor can include magnetic disks disposed in opposed, facing relation to the coil configuration.

Multi-carrier mobile TDMA system with active array antenna

NASA Technical Reports Server (NTRS)

Suzuki, Ryutaro; Matsumoto, Yasushi; Hamamoto, Naokazu

1990-01-01

A multi-carrier time division multiple access (TDMA) is proposed for the future mobile satellite communications systems that include a multi-satellite system. This TDMA system employs the active array antenna in which the digital beam forming technique is adopted to control the antenna beam direction. The antenna beam forming is carried out at the base band frequency by using the digital signal processing technique. The time division duplex technique is applied for the TDM/TDMA burst format, in order not to overlap transmit and receive timing.

Electrophysiological correlates of cocktail-party listening.

PubMed

Lewald, Jörg; Getzmann, Stephan

2015-10-01

Detecting, localizing, and selectively attending to a particular sound source of interest in complex auditory scenes composed of multiple competing sources is a remarkable capacity of the human auditory system. The neural basis of this so-called "cocktail-party effect" has remained largely unknown. Here, we studied the cortical network engaged in solving the "cocktail-party" problem, using event-related potentials (ERPs) in combination with two tasks demanding horizontal localization of a naturalistic target sound presented either in silence or in the presence of multiple competing sound sources. Presentation of multiple sound sources, as compared to single sources, induced an increased P1 amplitude, a reduction in N1, and a strong N2 component, resulting in a pronounced negativity in the ERP difference waveform (N2d) around 260 ms after stimulus onset. About 100 ms later, the anterior contralateral N2 subcomponent (N2ac) occurred in the multiple-sources condition, as computed from the amplitude difference for targets in the left minus right hemispaces. Cortical source analyses of the ERP modulation, resulting from the contrast of multiple vs. single sources, generally revealed an initial enhancement of electrical activity in right temporo-parietal areas, including auditory cortex, by multiple sources (at P1) that is followed by a reduction, with the primary sources shifting from right inferior parietal lobule (at N1) to left dorso-frontal cortex (at N2d). Thus, cocktail-party listening, as compared to single-source localization, appears to be based on a complex chronology of successive electrical activities within a specific cortical network involved in spatial hearing in complex situations. Copyright © 2015 Elsevier B.V. All rights reserved.

Systematic Review: The Effectiveness of Interventions to Reduce Falls and Improve Balance in Adults With Multiple Sclerosis.

PubMed

Gunn, Hilary; Markevics, Sophie; Haas, Bernhard; Marsden, Jonathan; Freeman, Jennifer

2015-10-01

To evaluate the effectiveness of interventions in reducing falls and/or improving balance as a falls risk in multiple sclerosis (MS). Computer-based and manual searches included the following medical subject heading keywords: "Multiple Sclerosis AND accidental falls" OR "Multiple Sclerosis AND postural balance" OR "Multiple Sclerosis AND exercise" OR "Multiple Sclerosis AND physical/physio therapy" NOT animals. All literature published to November 2014 with available full-text details were included. Studies were reviewed against the PICO (participants, interventions, comparisons, outcomes) selection criteria: P, adults with MS; I, falls management/balance rehabilitation interventions; C, randomized/quasi-randomized studies comparing intervention with usual care or placebo control; O, falls outcomes and measures of balance. Fifteen articles of the original 529 search results were included. Two reviewers independently extracted data and assessed methodological quality using the Cochrane Risk of Bias tool. Random-effects meta-analysis indicated a small decrease in falls risk (risk ratio, .74), although the 95% confidence interval (CI) crossed 1 (95% CI, .12-4.38). The pooled standardized mean difference (SMD) for balance outcomes was .55 (95% CI, .35-.74). SMD varied significantly between exercise subgroupings; gait, balance, and functional training interventions yielded the greatest pooled effect size (ES) (SMD=.82; 95% CI, 0.55-1.10). There was a moderate positive correlation between program volume (min/wk) and ES (Cohen's d) (r=.70, P=.009), and a moderate negative correlation between program duration in weeks and ES (r=-.62, P=.03). Variations in interventions and outcomes and methodological limitations mean that results must be viewed with caution. This review suggests that balance may improve through exercise interventions, but that the magnitude of the improvements achieved in existing programs may not be sufficient to impact falls outcomes. Supporting participants to achieve an appropriate intensity of practice of highly challenging balance activities appears to be critical to maximizing effectiveness. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Overexpression of the Arabidopsis CBF3 Transcriptional Activator Mimics Multiple Biochemical Changes Associated with Cold Acclimation1

PubMed Central

Gilmour, Sarah J.; Sebolt, Audrey M.; Salazar, Maite P.; Everard, John D.; Thomashow, Michael F.

2000-01-01

We further investigated the role of the Arabidopsis CBF regulatory genes in cold acclimation, the process whereby certain plants increase in freezing tolerance upon exposure to low temperature. The CBF genes, which are rapidly induced in response to low temperature, encode transcriptional activators that control the expression of genes containing the C-repeat/dehydration responsive element DNA regulatory element in their promoters. Constitutive expression of either CBF1 or CBF3 (also known as DREB1b and DREB1a, respectively) in transgenic Arabidopsis plants has been shown to induce the expression of target COR (cold-regulated) genes and to enhance freezing tolerance in nonacclimated plants. Here we demonstrate that overexpression of CBF3 in Arabidopsis also increases the freezing tolerance of cold-acclimated plants. Moreover, we show that it results in multiple biochemical changes associated with cold acclimation: CBF3-expressing plants had elevated levels of proline (Pro) and total soluble sugars, including sucrose, raffinose, glucose, and fructose. Plants overexpressing CBF3 also had elevated P5CS transcript levels suggesting that the increase in Pro levels resulted, at least in part, from increased expression of the key Pro biosynthetic enzyme Δ1-pyrroline-5-carboxylate synthase. These results lead us to propose that CBF3 integrates the activation of multiple components of the cold acclimation response. PMID:11115899

Multiple Activities of Punica granatum Linne against Acne Vulgaris.

PubMed

Lee, Chia-Jung; Chen, Lih-Geeng; Liang, Wen-Li; Wang, Ching-Chiung

2017-01-12

Acne is a common skin condition with sebum overproduction, hyperkeratosis, Propionibacterium acnes ( P . acnes ) and Staphylococcus aureus , and inflammation. Punica granatum (pomegranate) is well-known for its anti-inflammatory effects; however, few studies have discussed the anti-acne effects of pomegranate. In this study, we found that pomegranate extract (PG-E) significantly reduced P . acnes -induced edema in Wistar rat ears. Therefore, an evaluation platform using multiple pathogenic mechanisms of acne was established to explore the anti-acne effects of pomegranate. Results showed that PG-E inhibited bacterial growth and lipase activity. Through a bioguided-fractionation-isolation system, four hydrolysable tannins, punicalagin ( 1 ), punicalin ( 2 ), strictinin A ( 3 ), and granatin B ( 4 ), were isolated. Compounds 1 and 2 had greater anti-bacterial activities and anti-testosterone-induced HaCaT proliferative effects than the others. Compounds 1 , 3 , and 4 displayed lipase inhibitory effects. Compound 4 decreased cyclooxygenase-2 expression and downregulated prostaglandin E₂ production in heat-killed P . acnes -treated RAW 246.7 cells. In conclusion, PG-E is abundant in hydrolysable tannins that display multiple anti-acne capacities, including anti-bacterial, anti-lipase, anti-keratinocyte proliferation, and anti-inflammatory actions. Hence, PG-E has great potential in the application of anti-acne and skin-care products, and punicalagin ( 1 ), the most effective component in PG-E, can be employed as a quality control marker.

Sparse representation of whole-brain fMRI signals for identification of functional networks.

PubMed

Lv, Jinglei; Jiang, Xi; Li, Xiang; Zhu, Dajiang; Chen, Hanbo; Zhang, Tuo; Zhang, Shu; Hu, Xintao; Han, Junwei; Huang, Heng; Zhang, Jing; Guo, Lei; Liu, Tianming

2015-02-01

There have been several recent studies that used sparse representation for fMRI signal analysis and activation detection based on the assumption that each voxel's fMRI signal is linearly composed of sparse components. Previous studies have employed sparse coding to model functional networks in various modalities and scales. These prior contributions inspired the exploration of whether/how sparse representation can be used to identify functional networks in a voxel-wise way and on the whole brain scale. This paper presents a novel, alternative methodology of identifying multiple functional networks via sparse representation of whole-brain task-based fMRI signals. Our basic idea is that all fMRI signals within the whole brain of one subject are aggregated into a big data matrix, which is then factorized into an over-complete dictionary basis matrix and a reference weight matrix via an effective online dictionary learning algorithm. Our extensive experimental results have shown that this novel methodology can uncover multiple functional networks that can be well characterized and interpreted in spatial, temporal and frequency domains based on current brain science knowledge. Importantly, these well-characterized functional network components are quite reproducible in different brains. In general, our methods offer a novel, effective and unified solution to multiple fMRI data analysis tasks including activation detection, de-activation detection, and functional network identification. Copyright © 2014 Elsevier B.V. All rights reserved.

Omega-3 fatty acids, EPA and DHA induce apoptosis and enhance drug sensitivity in multiple myeloma cells but not in normal peripheral mononuclear cells.

PubMed

Abdi, J; Garssen, J; Faber, J; Redegeld, F A

2014-12-01

The n-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been shown to enhance the effect of chemotherapeutic drugs in clinical studies in cancer patients and to induce apoptotic tumor cell death in vitro. Until now, EPA and DHA have never been investigated in multiple myeloma (MM). Human myeloma cells (L363, OPM-1, OPM-2 and U266) and normal peripheral blood mononuclear cells were exposed to EPA and DHA, and effects on mitochondrial function and apoptosis, caspase-3 activation, gene expression and drug toxicity were measured. Exposure to EPA and DHA induced apoptosis and increased sensitivity to bortezomib in MM cells. Importantly, they did not affect viability of normal human peripheral mononuclear cells. Messenger RNA expression arrays showed that EPA and DHA modulated genes involved in multiple signaling pathways including nuclear factor (NF) κB, Notch, Hedgehog, oxidative stress and Wnt. EPA and DHA inhibited NFκB activity and induced apoptosis through mitochondrial perturbation and caspase-3 activation. Our study suggests that EPA and DHA induce selective cytotoxic effects in MM and increase sensitivity to bortezomib and calls for further exploration into a potential application of these n-3 polyunsaturated fatty acids in the therapy of MM. Copyright © 2014 Elsevier Inc. All rights reserved.

An APC/C-Cdh1 Biosensor Reveals the Dynamics of Cdh1 Inactivation at the G1/S Transition.

PubMed

Ondracka, Andrej; Robbins, Jonathan A; Cross, Frederick R

2016-01-01

B-type cyclin-dependent kinase activity must be turned off for mitotic exit and G1 stabilization. B-type cyclin degradation is mediated by the anaphase-promoting complex/cyclosome (APC/C); during and after mitotic exit, APC/C is dependent on Cdh1. Cdh1 is in turn phosphorylated and inactivated by cyclin-CDK at the Start transition of the new cell cycle. We developed a biosensor to assess the cell cycle dynamics of APC/C-Cdh1. Nuclear exit of the G1 transcriptional repressor Whi5 is a known marker of Start; APC/C-Cdh1 is inactivated 12 min after Whi5 nuclear exit with little measurable cell-to-cell timing variability. Multiple phosphorylation sites on Cdh1 act in a redundant manner to repress its activity. Reducing the number of phosphorylation sites on Cdh1 can to some extent be tolerated for cell viability, but it increases variability in timing of APC/C-Cdh1 inactivation. Mutants with minimal subsets of phosphorylation sites required for viability exhibit striking stochasticity in multiple responses including budding, nuclear division, and APC/C-Cdh1 activity itself. Multiple cyclin-CDK complexes, as well as the stoichiometric inhibitor Acm1, contribute to APC/C-Cdh1 inactivation; this redundant control is likely to promote rapid and reliable APC/C-Cdh1 inactivation immediately following the Start transition.

An Examination of Four Traditional School Physical Activity Models on Children's Step Counts and MVPA.

PubMed

Brusseau, Timothy A; Kulinna, Pamela H

2015-03-01

Schools have been identified as primary societal institutions for promoting children's physical activity (PA); however, limited evidence exists demonstrating which traditional school-based PA models maximize children's PA. The purpose of this study was to compare step counts and moderate-to-vigorous physical activity (MVPA) across 4 traditional school PA modules. Step count and MVPA data were collected on 5 consecutive school days from 298 children (Mage = 10.0 ± 0.6 years; 55% female) in Grade 5. PA was measured using the NL-1000 piezoelectric pedometer. The 4 models included (a) recess only, (b) multiple recesses, (c) recess and physical education (PE), and (d) multiple recesses and PE. Children accumulated the greatest PA on days that they had PE and multiple recess opportunities (5,242 ± 1,690 steps; 15.3 ± 8.8 min of MVPA). Children accumulated the least amount of PA on days with only 1 recess opportunity (3,312 ± 445 steps; 7.1 ± 2.3 min of MVPA). Across all models, children accumulated an additional 1,140 steps and 4.1 min of MVPA on PE days. It appears that PE is the most important school PA opportunity for maximizing children's PA. However, on days without PE, a 2nd recess can increase school PA by 20% (Δ = 850 steps; 3.8 min of MVPA).

Dandelion root extract affects colorectal cancer proliferation and survival through the activation of multiple death signalling pathways

PubMed Central

Ovadje, Pamela; Ammar, Saleem; Guerrero, Jose-Antonio; Arnason, John Thor; Pandey, Siyaram

2016-01-01

Dandelion extracts have been studied extensively in recent years for its anti-depressant and anti-inflammatory activity. Recent work from our lab, with in-vitro systems, shows the anti-cancer potential of an aqueous dandelion root extract (DRE) in several cancer cell models, with no toxicity to non-cancer cells. In this study, we examined the cancer cell-killing effectiveness of an aqueous DRE in colon cancer cell models. Aqueous DRE induced programmed cell death (PCD) selectively in > 95% of colon cancer cells, irrespective of their p53 status, by 48 hours of treatment. The anti-cancer efficacy of this extract was confirmed in in-vivo studies, as the oral administration of DRE retarded the growth of human colon xenograft models by more than 90%. We found the activation of multiple death pathways in cancer cells by DRE treatment, as revealed by gene expression analyses showing the expression of genes implicated in programmed cell death. Phytochemical analyses of the extract showed complex multi-component composition of the DRE, including some known bioactive phytochemicals such as α-amyrin, β-amyrin, lupeol and taraxasterol. This suggested that this natural extract could engage and effectively target multiple vulnerabilities of cancer cells. Therefore, DRE could be a non-toxic and effective anti-cancer alternative, instrumental for reducing the occurrence of cancer cells drug-resistance. PMID:27564258

Multiple Activities of Punica granatum Linne against Acne Vulgaris

PubMed Central

Lee, Chia-Jung; Chen, Lih-Geeng; Liang, Wen-Li; Wang, Ching-Chiung

2017-01-01

Acne is a common skin condition with sebum overproduction, hyperkeratosis, Propionibacterium acnes (P. acnes) and Staphylococcus aureus, and inflammation. Punica granatum (pomegranate) is well-known for its anti-inflammatory effects; however, few studies have discussed the anti-acne effects of pomegranate. In this study, we found that pomegranate extract (PG-E) significantly reduced P. acnes-induced edema in Wistar rat ears. Therefore, an evaluation platform using multiple pathogenic mechanisms of acne was established to explore the anti-acne effects of pomegranate. Results showed that PG-E inhibited bacterial growth and lipase activity. Through a bioguided-fractionation-isolation system, four hydrolysable tannins, punicalagin (1), punicalin (2), strictinin A (3), and granatin B (4), were isolated. Compounds 1 and 2 had greater anti-bacterial activities and anti-testosterone-induced HaCaT proliferative effects than the others. Compounds 1, 3, and 4 displayed lipase inhibitory effects. Compound 4 decreased cyclooxygenase-2 expression and downregulated prostaglandin E2 production in heat-killed P. acnes-treated RAW 246.7 cells. In conclusion, PG-E is abundant in hydrolysable tannins that display multiple anti-acne capacities, including anti-bacterial, anti-lipase, anti-keratinocyte proliferation, and anti-inflammatory actions. Hence, PG-E has great potential in the application of anti-acne and skin-care products, and punicalagin (1), the most effective component in PG-E, can be employed as a quality control marker. PMID:28085116

Multiple active myofascial trigger points and pressure pain sensitivity maps in the temporalis muscle are related in women with chronic tension type headache.

PubMed

Fernández-de-las-Peñas, César; Caminero, Ana B; Madeleine, Pascal; Guillem-Mesado, Amparo; Ge, Hong-You; Arendt-Nielsen, Lars; Pareja, Juan A

2009-01-01

To describe the common locations of active trigger points (TrPs) in the temporalis muscle and their referred pain patterns in chronic tension type headache (CTTH), and to determine if pressure sensitivity maps of this muscle can be used to describe the spatial distribution of active TrPs. Forty women with CTTH were included. An electronic pressure algometer was used to assess pressure pain thresholds (PPT) from 9 points over each temporalis muscle: 3 points in the anterior, medial and posterior part, respectively. Both muscles were examined for the presence of active TrPs over each of the 9 points. The referred pain pattern of each active TrP was assessed. Two-way analysis of variance detected significant differences in mean PPT levels between the measurement points (F=30.3; P<0.001), but not between sides (F=2.1; P=0.2). PPT scores decreased from the posterior to the anterior column (P<0.001). No differences were found in the number of active TrPs (F=0.3; P=0.9) between the dominant side the nondominant side. Significant differences were found in the distribution of the active TrPs (chi2=12.2; P<0.001): active TrPs were mostly found in the anterior column and in the middle of the muscle belly. The analysis of variance did not detect significant differences in the referred pain pattern between active TrPs (F=1.1, P=0.4). The topographical pressure pain sensitivity maps showed the distinct distribution of the TrPs indicated by locations with low PPTs. Multiple active TrPs in the temporalis muscle were found, particularly in the anterior column and in the middle of the muscle belly. Bilateral posterior to anterior decreased distribution of PPTs in the temporalis muscle in women with CTTH was found. The locations of active TrPs in the temporalis muscle corresponded well to the muscle areas with lower PPT, supporting the relationship between multiple active muscle TrPs and topographical pressure sensitivity maps in the temporalis muscle in women with CTTH.

DNA wrapping and distortion by an oligomeric homeodomain protein.

PubMed

Williams, Hannah; Jayaraman, Padma-Sheela; Gaston, Kevin

2008-10-31

Many transcription factors alter DNA or chromatin structure. Changes in chromatin structure are often brought about by the recruitment of chromatin-binding proteins, chromatin-modifying proteins, or other transcription co-activator or co-repressor proteins. However, some transcription factors form oligomeric assemblies that may themselves induce changes in DNA conformation and chromatin structure. The proline-rich homeodomain (PRH/Hex) protein is a transcription factor that regulates cell differentiation and cell proliferation, and has multiple roles in embryonic development. Earlier, we showed that PRH can repress transcription by multiple mechanisms, including the recruitment of co-repressor proteins belonging to the TLE family of chromatin-binding proteins. Our in vivo crosslinking studies have shown that PRH forms oligomeric complexes in cells and a variety of biophysical techniques suggest that the protein forms octamers. However, as yet we have little knowledge of the role played by PRH oligomerisation in the regulation of promoter activity or of the architecture of promoters that are regulated directly by PRH in cells. Here, we compare the binding of PRH and the isolated PRH homeodomain to DNA fragments with single and multiple PRH sites, using gel retardation assays and DNase I and chemical footprinting. We show that the PRH oligomer binds to multiple sites within the human Goosecoid promoter with high affinity and that the binding of PRH brings about DNA distortion. We suggest that PRH octamers wrap DNA in order to bring about transcriptional repression.

[Effects of nutritional status on the multiple sclerosis disease: systematic review].

PubMed

Ródenas Esteve, Irene; Wanden-Berghe, Carmina; Sanz-Valero, Javier

2018-01-19

To review the available scientific literature about the effects of nutritional status on the multiple sclerosis disease. A systematic review of the scientific literature in the Medline (PubMed), Scopus, Cochrane Library and Web of Science databases through November 2016. Search equation: ("Multiple Sclerosis"[Mesh] OR "Multiple Sclerosis"[Title/Abstract] OR "Disseminated Sclerosis"[Title/Abstract] OR "Multiple Sclerosis Acute Fulminating"[Title/Abstract]) AND ("Nutritional Status"[Mesh] OR "Nutritional Status"[Title/Abstract] OR "Nutrition Status"[Title/Abstract]). The quality of the selected articles was discussed using the STROBE questionnaire. The search was completed through experts inquiry and additional review of the bibliographic references included in the selected papers. The concordance between authors (Kappa index) had to be higher than 80% for inclusion in this review. Of the 160 references recovered, after applying inclusion and exclusion criteria, 29 articles were selected for review. Concordance between evaluators was 100.00%. The most studies established vitamin D levels. Others focused their research on finding out which nutrient deficits might be related to the multiple sclerosis development. Vitamin D may influence multiple sclerosis improvement. Sunlight and physical activity would be important factors, with nutritional status, in the course of this disease. It is necessary to produce new specific works that will delve into the subject to find out more about the relationship between nutritional status and multiple sclerosis.

Accelerometry is associated with walking mobility, not physical activity, in persons with multiple sclerosis.

PubMed

Weikert, Madeline; Suh, Yoojin; Lane, Abbi; Sandroff, Brian; Dlugonski, Deirdre; Fernhall, Bo; Motl, Robert W

2012-06-01

Accelerometers are seemingly a criterion standard of real-life walking mobility and this is supported by assumptions and empirical data. This application would be strengthened by including objective measures of walking mobility along with a matched control sample for verifying specificity versus generality in accelerometer output. We compared associations among accelerometer output, walking mobility, and physical activity between persons with multiple sclerosis (MS) and controls without a neurological disorder. Sixty-six persons (33 MS, 33 matched controls) completed a battery of questionnaires, performed the six-minute walk (6MW) and timed-up-and-go (TUG), and wore an accelerometer for a 7-day period. After this period, participants completed the Godin Leisure-Time Exercise Questionnaire (GLTEQ) and International Physical Activity Questionnaire (IPAQ). Accelerometer output was significantly correlated with only mobility measures (6MW, ρ=.78; TUG, ρ=-.68) in MS, whereas it correlated with both mobility (6MW, ρ=.58; TUG, ρ=-.49) and physical activity (GLTEQ, ρ=.56; IPAQ, ρ=.53) measures in controls. Regression analysis indicated that only 6MW explained variance in accelerometer output in MS (β=.65, R(2)=.43). These findings support the possibility that accelerometers primarily and specifically measure real-life walking mobility, not physical activity, in persons with MS. Copyright © 2011 IPEM. Published by Elsevier Ltd. All rights reserved.

Autonomous motivation and quality of life as predictors of physical activity in patients with schizophrenia.

PubMed

Costa, Raquel; Bastos, Tânia; Probst, Michel; Seabra, André; Vilhena, Estela; Corredeira, Rui

2018-02-08

Being physically active is a complex behaviour in patients with schizophrenia. Several factors were identified as barriers to achieving active behaviours in this population. Therefore, the purpose of this study was to investigate among a number of barriers what predicts the most on physical activity (PA) in patients with schizophrenia. A total of 114 patients (28♀) with schizophrenia were included. Body mass index (BMI) was calculated. Autonomous and controlled motivation (Behavioural Regulation in Exercise Questionnaire - 3), self-esteem (Rosenberg Self-esteem scale), quality of life (World Health Organization Quality of Life Scale - Brief version) and functional exercise capacity (6-minute walk test - 6MWT) were evaluated. Multiple Regression Analysis was applied to assess the effect of these variables on Total PA per week (International Physical Activity Questionnaire - short version). Autonomous motivation and domains of quality of life were positively correlated with Total PA per week. Stepwise multiple regression analyses showed that of all the candidate factors to predict PA, autonomous motivation and global domain of quality of life were found as significant predictors. Our findings help to understand the importance of autonomous motivation and quality of life for PA in patients with schizophrenia. Knowledge about these predictors may provide guidance to improve PA behaviour in this population.

Functional inactivation of hypocretin 1 receptors in the medial prefrontal cortex affects the pyramidal neuron activity and gamma oscillations: An in vivo multiple-channel single-unit recording study.

PubMed

He, C; Chen, Q-H; Ye, J-N; Li, C; Yang, L; Zhang, J; Xia, J-X; Hu, Z-A

2015-06-25

The hypocretin signaling is thought to play a critical role in maintaining wakefulness via stimulating the subcortical arousal pathways. Although the cortical areas, including the medial prefrontal cortex (mPFC), receive dense hypocretinergic fibers and express its receptors, it remains unclear whether the hypocretins can directly regulate the neural activity of the mPFC in vivo. In the present study, using multiple-channel single-unit recording study, we found that infusion of the SB-334867, a blocker for the Hcrtr1, beside the recording sites within the mPFC substantially exerted an inhibitory effect on the putative pyramidal neuron (PPN) activity in naturally behaving rats. In addition, functional blockade of the Hcrtr1 also selectively reduced the power of the gamma oscillations. The PPN activity and the power of the neural oscillations were not affected after microinjection of the TCS-OX2-29, a blocker for the Hcrtr2, within the mPFC. Together, these data indicate that endogenous hypocretins acting on the Hcrtr1 are required for the normal neural activity in the mPFC in vivo, and thus might directly contribute cortical arousal and mPFC-dependent cognitive processes. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Caffeic Acid Phenethyl Ester: A Review of Its Antioxidant Activity, Protective Effects against Ischemia-reperfusion Injury and Drug Adverse Reactions.

PubMed

Tolba, Mai F; Omar, Hany A; Azab, Samar S; Khalifa, Amani E; Abdel-Naim, Ashraf B; Abdel-Rahman, Sherif Z

2016-10-02

Propolis, a honey bee product, has been used in folk medicine for centuries for the treatment of abscesses, canker sores and for wound healing. Caffeic acid phenethyl ester (CAPE) is one of the most extensively investigated active components of propolis which possess many biological activities, including antibacterial, antiviral, antioxidant, anti-inflammatory, and anti-cancer effects. CAPE is a polyphenolic compound characterized by potent antioxidant and cytoprotective activities and protective effects against ischemia-reperfusion (I/R)-induced injury in multiple tissues such as brain, retina, heart, skeletal muscles, testis, ovaries, intestine, colon, and liver. Furthermore, several studies indicated the protective effects of CAPE against chemotherapy-induced adverse drug reactions (ADRs) including several antibiotics (streptomycin, vancomycin, isoniazid, ethambutol) and chemotherapeutic agents (mitomycin, doxorubicin, cisplatin, methotrexate). Due to the broad spectrum of pharmacological activities of CAPE, this review makes a special focus on the recently published data about CAPE antioxidant activity as well as its protective effects against I/R-induced injury and many adverse drug reactions.

The World Hypertension League: where now and where to in salt reduction

PubMed Central

Lackland, Daniel T.; Lisheng, Liu; Zhang, Xin-Hua; Nilsson, Peter M.; Niebylski, Mark L.

2015-01-01

High dietary salt is a leading risk for death and disability largely by causing increased blood pressure. Other associated health risks include gastric and renal cell cancers, osteoporosis, renal stones, and increased disease activity in multiple sclerosis, headache, increased body fat and Meniere’s disease. The World Hypertension League (WHL) has prioritized advocacy for salt reduction. WHL resources and actions include a non-governmental organization policy statement, dietary salt fact sheet, development of standardized nomenclature, call for quality research, collaboration in a weekly salt science update, development of a process to set recommended dietary salt research standards and regular literature reviews, development of adoptable power point slide sets to support WHL positions and resources, and critic of weak research studies on dietary salt. The WHL plans to continue to work with multiple governmental and non-governmental organizations to promote dietary salt reduction towards the World Health Organization (WHO) recommendations. PMID:26090335

Molecular screening strategies for NF1-like syndromes with café-au-lait macules

PubMed Central

Zhang, Jia; Li, Ming; Yao, Zhirong

2016-01-01

Multiple café-au-lait macules (CALM) are usually associated with neurofibromatosis type 1 (NF1), one of the most common hereditary disorders. However, a group of genetic disorders presenting with CALM have mutations that are involved in human skin pigmentation regulation signaling pathways, including KIT ligand/KIT proto-oncogene receptor tyrosine kinase and Ras/mitogen-activated protein kinase. These disorders, which include Legius syndrome, Noonan syndrome with multiple lentigines or LEOPARD syndrome, and familial progressive hyperpigmentation) are difficult to distinguish from NF1 at early stages, using skin appearance alone. Furthermore, certain syndromes are clinically overlapping and molecular testing is a vital diagnostic method. The present review aims to provide an overview of these ‘NF1-like’ inherited diseases and recommend a cost-effective strategy for making a clear diagnosis among these diseases with an ambiguous borderline. PMID:27666661

Molecular screening strategies for NF1-like syndromes with café-au-lait macules (Review).

PubMed

Zhang, Jia; Li, Ming; Yao, Zhirong

2016-11-01

Multiple café-au-lait macules (CALM) are usually associated with neurofibromatosis type 1 (NF1), one of the most common hereditary disorders. However, a group of genetic disorders presenting with CALM have mutations that are involved in human skin pigmentation regulation signaling pathways, including KIT ligand/KIT proto‑oncogene receptor tyrosine kinase and Ras/mitogen‑activated protein kinase. These disorders, which include Legius syndrome, Noonan syndrome with multiple lentigines or LEOPARD syndrome, and familial progressive hyperpigmentation) are difficult to distinguish from NF1 at early stages, using skin appearance alone. Furthermore, certain syndromes are clinically overlapping and molecular testing is a vital diagnostic method. The present review aims to provide an overview of these 'NF1‑like' inherited diseases and recommend a cost‑effective strategy for making a clear diagnosis among these diseases with an ambiguous borderline.

The antimicrobial activity of nanoparticles: present situation and prospects for the future

PubMed Central

Wang, Linlin; Hu, Chen; Shao, Longquan

2017-01-01

Nanoparticles (NPs) are increasingly used to target bacteria as an alternative to antibiotics. Nanotechnology may be particularly advantageous in treating bacterial infections. Examples include the utilization of NPs in antibacterial coatings for implantable devices and medicinal materials to prevent infection and promote wound healing, in antibiotic delivery systems to treat disease, in bacterial detection systems to generate microbial diagnostics, and in antibacterial vaccines to control bacterial infections. The antibacterial mechanisms of NPs are poorly understood, but the currently accepted mechanisms include oxidative stress induction, metal ion release, and non-oxidative mechanisms. The multiple simultaneous mechanisms of action against microbes would require multiple simultaneous gene mutations in the same bacterial cell for antibacterial resistance to develop; therefore, it is difficult for bacterial cells to become resistant to NPs. In this review, we discuss the antibacterial mechanisms of NPs against bacteria and the factors that are involved. The limitations of current research are also discussed. PMID:28243086

Experimental evaluation of candidate graphical microburst alert displays

NASA Technical Reports Server (NTRS)

Wanke, Craig R.; Hansman, R. John

1992-01-01

A piloted flight simulator experiment was conducted to evaluate issues related to the display of microburst alerts on electronic cockpit instrumentation. Issues addressed include display clarity, usefulness of multilevel microburst intensity information, and whether information from multiple sensors should be presented separately or 'fused' into combined alerts. Nine active airline pilots of 'glass cockpit' aircraft participated in the study. Microburst alerts presented on a moving map display were found to be visually clear and useful to pilots. Also, multilevel intensity information coded by colors or patterns was found to be important for decision making purposes. Pilot opinion was mixed on whether to 'fuse' data from multiple sensors, and some resulting design tradeoffs were identified. The positional information included in the graphical alert presentation was found useful by the pilots for planning lateral missed approach maneuvers, but may result in deviations which could interfere with normal airport operations. A number of flight crew training issues were also identified.

Inclusion complex of novel curcumin analogue CDF and β-cyclodextrin (1:2) and its enhanced in vivo anticancer activity against pancreatic cancer.

PubMed

Dandawate, Prasad R; Vyas, Alok; Ahmad, Aamir; Banerjee, Sanjeev; Deshpande, Jyoti; Swamy, K Venkateswara; Jamadar, Abeda; Dumhe-Klaire, Anne Catherine; Padhye, Subhash; Sarkar, Fazlul H

2012-07-01

Several formulations have been proposed to improve the systemic delivery of novel cancer therapeutic compounds, including cyclodextrin derivatives. We aimed to synthesize and characterize of CDF-β-cyclodextrin inclusion complex (1:2) (CDFCD). The compound was characterized by Fourier transform infrared, differential scanning calorimetry, powder X-ray diffraction studies, H1 & C13 NMR studies and scanning electron microscopic analysis. Its activity was tested against multiple cancer cell lines, and in vivo bioavailability was checked. CDF-β-cyclodextrin was found to lower IC(50) value by half when tested against multiple cancer cell lines. It preferentially accumulated in the pancreas, where levels of CDF-β-cyclodextrin in mice were 10 times higher than in serum, following intravenous administration of an aqueous CDF-β-cyclodextrin preparation. Novel curcumin analog CDF preferentially accumulates in the pancreas, leading to its potent anticancer activity against pancreatic cancer cells. Synthesis of such CDF-β-cyclodextrin self-assembly is an effective strategy to enhance its bioavailability and tissue distribution, warranting further evaluation for CDF delivery in clinical settings for treatment of human malignancies.

BRAF inhibitors suppress apoptosis through off-target inhibition of JNK signaling

PubMed Central

Vin, Harina; Ojeda, Sandra S; Ching, Grace; Leung, Marco L; Chitsazzadeh, Vida; Dwyer, David W; Adelmann, Charles H; Restrepo, Monica; Richards, Kristen N; Stewart, Larissa R; Du, Lili; Ferguson, Scarlett B; Chakravarti, Deepavali; Ehrenreiter, Karin; Baccarini, Manuela; Ruggieri, Rosamaria; Curry, Jonathan L; Kim, Kevin B; Ciurea, Ana M; Duvic, Madeleine; Prieto, Victor G; Ullrich, Stephen E; Dalby, Kevin N; Flores, Elsa R; Tsai, Kenneth Y

2013-01-01

Vemurafenib and dabrafenib selectively inhibit the v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) kinase, resulting in high response rates and increased survival in melanoma. Approximately 22% of individuals treated with vemurafenib develop cutaneous squamous cell carcinoma (cSCC) during therapy. The prevailing explanation for this is drug-induced paradoxical ERK activation, resulting in hyperproliferation. Here we show an unexpected and novel effect of vemurafenib/PLX4720 in suppressing apoptosis through the inhibition of multiple off-target kinases upstream of c-Jun N-terminal kinase (JNK), principally ZAK. JNK signaling is suppressed in multiple contexts, including in cSCC of vemurafenib-treated patients, as well as in mice. Expression of a mutant ZAK that cannot be inhibited reverses the suppression of JNK activation and apoptosis. Our results implicate suppression of JNK-dependent apoptosis as a significant, independent mechanism that cooperates with paradoxical ERK activation to induce cSCC, suggesting broad implications for understanding toxicities associated with BRAF inhibitors and for their use in combination therapies. DOI: http://dx.doi.org/10.7554/eLife.00969.001 PMID:24192036

Lhx6-positive GABA-releasing neurons of the zona incerta promote sleep

PubMed Central

Liu, Kai; Kim, Juhyun; Kim, Dong Won; Zhang, Yi Stephanie; Bao, Hechen; Denaxa, Myrto; Lim, Szu-Aun; Kim, Eileen; Liu, Chang; Wickersham, Ian R.; Pachnis, Vassilis; Hattar, Samer; Song, Juan; Brown, Solange P.; Blackshaw, Seth

2017-01-01

Multiple populations of wake-promoting neurons have been characterized in mammals, but few sleep-promoting neurons have been identified1. Wake-promoting cell types include hypocretin and GABA (γ-aminobutyric-acid)-releasing neurons of the lateral hypothalamus, which promote the transition to wakefulness from non-rapid eye movement (NREM) and rapid eye movement (REM) sleep2,3. Here we show that a subset of GABAergic neurons in the mouse ventral zona incerta, which express the LIM homeodomain factor Lhx6 and are activated by sleep pressure, both directly inhibit wake-active hypocretin and GABAergic cells in the lateral hypothalamus and receive inputs from multiple sleep–wake-regulating neurons. Conditional deletion of Lhx6 from the developing diencephalon leads to decreases in both NREM and REM sleep. Furthermore, selective activation and inhibition of Lhx6-positive neurons in the ventral zona incerta bidirectionally regulate sleep time in adult mice, in part through hypocretin-dependent mechanisms. These studies identify a GABAergic subpopulation of neurons in the ventral zona incerta that promote sleep. PMID:28847002

Differential expression and activation of a family of murine peroxisome proliferator-activated receptors.

PubMed Central

Kliewer, S A; Forman, B M; Blumberg, B; Ong, E S; Borgmeyer, U; Mangelsdorf, D J; Umesono, K; Evans, R M

1994-01-01

To gain insight into the function of peroxisome proliferator-activated receptor (PPAR) isoforms in mammals, we have cloned and characterized two PPAR alpha-related cDNAs (designated PPAR gamma and -delta, respectively) from mouse. The three PPAR isoforms display widely divergent patterns of expression during embryogenesis and in the adult. Surprisingly, PPAR gamma and -delta are not activated by pirinixic acid (Wy 14,643), a potent peroxisome proliferator and activator of PPAR alpha. However, PPAR gamma and -delta are activated by the structurally distinct peroxisome proliferator LY-171883 and linoleic acid, respectively, indicating that each of the isoforms can act as a regulated activator of transcription. These data suggest that tissue-specific responsiveness to peroxisome proliferators, including certain fatty acids, is in part a consequence of differential expression of multiple, pharmacologically distinct PPAR isoforms. Images PMID:8041794

Systematic, Evidence-Based Review of Exercise, Physical Activity, and Physical Fitness Effects on Cognition in Persons with Multiple Sclerosis.

PubMed

Sandroff, Brian M; Motl, Robert W; Scudder, Mark R; DeLuca, John

2016-09-01

Cognitive dysfunction is highly prevalent, disabling, and poorly-managed in persons with multiple sclerosis (MS). Recent evidence suggests that exercise might have beneficial effects on cognition in this population. The current systematic, evidence-based review examined the existing literature on exercise, physical activity, and physical fitness effects on cognition in MS to accurately describe the current status of the field, offer recommendations for clinicians, and identify study-specific and participant-specific characteristics for providing future direction for ongoing MS research. We performed an open-dated search of Medline, PsychInfo, and CINAHL in December 2015. The search strategy involved using the terms 'exercise' OR 'physical activity' OR 'physical fitness' OR 'aerobic' OR 'resistance' OR 'balance' OR 'walking' OR 'yoga' OR 'training' OR 'rehabilitation' AND 'multiple sclerosis'. Articles were eliminated from the systematic review if it was a review article, theoretical paper, or textbook chapter; did not involve persons with MS; involved only persons with pediatric-onset MS; did not involve neuropsychological outcomes; did not include empirical data to evaluate outcomes; involved pharmacological interventions; or was not available in English. The selected articles were first classified as examining exercise, physical activity, or physical fitness, and were then randomly assigned to 2 independent reviewers who rated each article for level of evidence based on American Academy of Neurology criteria. Reviewers further completed a table to characterize important elements of each study (i.e., intervention characteristics), the cognitive domain(s) that were targeted, participant-specific characteristics, outcome measures, and study results. The present review resulted in 26 studies on the effects of exercise, physical activity, and physical fitness on cognition in persons with MS. This included 1 Class I study, 3 Class II studies, 8 Class III studies, and 14 Class IV studies. Of the 26 total studies, 6 were randomized controlled trials. Overall, there is conflicting evidence for the effects of exercise on cognition in MS, and overall positive, but not definitive evidence for the effects of physical activity and physical fitness, respectively, on cognition in this population. Collectively, there is insufficient well-designed research to definitively conclude that exercise, physical activity, and physical fitness are effective for improving cognition in MS. This is based, in part, on methodological issues of Class I and II studies, such as inclusion of cognition as a secondary outcome (35 % of reviewed studies), poorly-developed exercise interventions, and paucity of research that included cognitively-impaired MS samples. However, promising evidence from Class III and Class IV studies may be useful for informing the development of better intervention research.

Coexistence and local μ-stability of multiple equilibrium points for memristive neural networks with nonmonotonic piecewise linear activation functions and unbounded time-varying delays.

PubMed

Nie, Xiaobing; Zheng, Wei Xing; Cao, Jinde

2016-12-01

In this paper, the coexistence and dynamical behaviors of multiple equilibrium points are discussed for a class of memristive neural networks (MNNs) with unbounded time-varying delays and nonmonotonic piecewise linear activation functions. By means of the fixed point theorem, nonsmooth analysis theory and rigorous mathematical analysis, it is proven that under some conditions, such n-neuron MNNs can have 5 n equilibrium points located in ℜ n , and 3 n of them are locally μ-stable. As a direct application, some criteria are also obtained on the multiple exponential stability, multiple power stability, multiple log-stability and multiple log-log-stability. All these results reveal that the addressed neural networks with activation functions introduced in this paper can generate greater storage capacity than the ones with Mexican-hat-type activation function. Numerical simulations are presented to substantiate the theoretical results. Copyright © 2016 Elsevier Ltd. All rights reserved.

Probabilistic tsunami hazard analysis: Multiple sources and global applications

USGS Publications Warehouse

Grezio, Anita; Babeyko, Andrey; Baptista, Maria Ana; Behrens, Jörn; Costa, Antonio; Davies, Gareth; Geist, Eric L.; Glimsdal, Sylfest; González, Frank I.; Griffin, Jonathan; Harbitz, Carl B.; LeVeque, Randall J.; Lorito, Stefano; Løvholt, Finn; Omira, Rachid; Mueller, Christof; Paris, Raphaël; Parsons, Thomas E.; Polet, Jascha; Power, William; Selva, Jacopo; Sørensen, Mathilde B.; Thio, Hong Kie

2017-01-01

Applying probabilistic methods to infrequent but devastating natural events is intrinsically challenging. For tsunami analyses, a suite of geophysical assessments should be in principle evaluated because of the different causes generating tsunamis (earthquakes, landslides, volcanic activity, meteorological events, and asteroid impacts) with varying mean recurrence rates. Probabilistic Tsunami Hazard Analyses (PTHAs) are conducted in different areas of the world at global, regional, and local scales with the aim of understanding tsunami hazard to inform tsunami risk reduction activities. PTHAs enhance knowledge of the potential tsunamigenic threat by estimating the probability of exceeding specific levels of tsunami intensity metrics (e.g., run-up or maximum inundation heights) within a certain period of time (exposure time) at given locations (target sites); these estimates can be summarized in hazard maps or hazard curves. This discussion presents a broad overview of PTHA, including (i) sources and mechanisms of tsunami generation, emphasizing the variety and complexity of the tsunami sources and their generation mechanisms, (ii) developments in modeling the propagation and impact of tsunami waves, and (iii) statistical procedures for tsunami hazard estimates that include the associated epistemic and aleatoric uncertainties. Key elements in understanding the potential tsunami hazard are discussed, in light of the rapid development of PTHA methods during the last decade and the globally distributed applications, including the importance of considering multiple sources, their relative intensities, probabilities of occurrence, and uncertainties in an integrated and consistent probabilistic framework.

Probabilistic Tsunami Hazard Analysis: Multiple Sources and Global Applications

NASA Astrophysics Data System (ADS)

Grezio, Anita; Babeyko, Andrey; Baptista, Maria Ana; Behrens, Jörn; Costa, Antonio; Davies, Gareth; Geist, Eric L.; Glimsdal, Sylfest; González, Frank I.; Griffin, Jonathan; Harbitz, Carl B.; LeVeque, Randall J.; Lorito, Stefano; Løvholt, Finn; Omira, Rachid; Mueller, Christof; Paris, Raphaël.; Parsons, Tom; Polet, Jascha; Power, William; Selva, Jacopo; Sørensen, Mathilde B.; Thio, Hong Kie

2017-12-01

Applying probabilistic methods to infrequent but devastating natural events is intrinsically challenging. For tsunami analyses, a suite of geophysical assessments should be in principle evaluated because of the different causes generating tsunamis (earthquakes, landslides, volcanic activity, meteorological events, and asteroid impacts) with varying mean recurrence rates. Probabilistic Tsunami Hazard Analyses (PTHAs) are conducted in different areas of the world at global, regional, and local scales with the aim of understanding tsunami hazard to inform tsunami risk reduction activities. PTHAs enhance knowledge of the potential tsunamigenic threat by estimating the probability of exceeding specific levels of tsunami intensity metrics (e.g., run-up or maximum inundation heights) within a certain period of time (exposure time) at given locations (target sites); these estimates can be summarized in hazard maps or hazard curves. This discussion presents a broad overview of PTHA, including (i) sources and mechanisms of tsunami generation, emphasizing the variety and complexity of the tsunami sources and their generation mechanisms, (ii) developments in modeling the propagation and impact of tsunami waves, and (iii) statistical procedures for tsunami hazard estimates that include the associated epistemic and aleatoric uncertainties. Key elements in understanding the potential tsunami hazard are discussed, in light of the rapid development of PTHA methods during the last decade and the globally distributed applications, including the importance of considering multiple sources, their relative intensities, probabilities of occurrence, and uncertainties in an integrated and consistent probabilistic framework.

Dietary proanthocyanidins prevent ultraviolet radiation-induced non-melanoma skin cancer through enhanced repair of damaged DNA-dependent activation of immune sensitivity.

PubMed

Katiyar, Santosh K; Pal, Harish C; Prasad, Ram

2017-10-01

Numerous plant products have been used to prevent and manage a wide variety of diseases for centuries. These products are now considered as promising options for the development of more effective and less toxic alternatives to the systems of medicine developed primarily in developed countries in the modern era. Grape seed proanthocyanidins (GSPs) are of great interest due to their anti-carcinogenic effects that have been demonstrated using various tumor models including ultraviolet (UV) radiation-induced non-melanoma skin cancer. In a pre-clinical mouse model supplementation of a control diet (AIN76A) with GSPs at concentrations of 0.2% and 0.5% (w/w) significantly inhibits the growth and multiplicity of UVB radiation-induced skin tumors. In this review, we summarize the evidence that this inhibition of UVB-induced skin tumor development by dietary GSPs is mediated by a multiplicity of coordinated effects including: (i) Promotion of the repair of damaged DNA by nuclear excision repair mechanisms, and (ii) DNA repair-dependent stimulation of the immune system following the functional activation of dendritic cells and effector T cells. Dietary GSPs hold promise for the development of an effective alternative strategy for the prevention of excessive solar UVB radiation exposure-induced skin diseases including the risk of non-melanoma skin cancer in humans. Copyright © 2017 Elsevier Ltd. All rights reserved.

A cost-effectiveness analysis of online, radio and print tobacco control advertisements targeting 25-39 year-old males.

PubMed

Clayforth, Cassandra; Pettigrew, Simone; Mooney, Katie; Lansdorp-Vogelaar, Iris; Rosenberg, Michael; Slevin, Terry

2014-06-01

To assess the relative cost-effectiveness of various non-television advertising media in encouraging 25-39 year-old male smokers to respond to a cessation-related call to action. Information about how new electronic media compare in effectiveness is important to inform the implementation of future tobacco control media campaigns. Two testimonial advertisements featuring members of the target group were developed for radio, press and online media. Multiple waves of media activity were scheduled over a period of seven weeks, including an initial integrated period that included all three media and subsequent single media phases that were interspersed with a week of no media activity. The resulting Quit website hits, Quitline telephone calls, and registrations to online and telephone counselling services were compared to advertising costs to determine the relative cost-effectiveness of each media in isolation and the integrated approach. The online-only campaign phase was substantially more cost-effective than the other phases, including the integrated approach. This finding is contrary to the current assumption that the use of a consistent message across multiple media simultaneously is the most cost-effective way of reaching and affecting target audiences. Online advertising may be a highly cost-effective channel for low-budget tobacco control media campaigns. © 2014 The Authors. ANZJPH © 2014 Public Health Association of Australia.

High speed internal permanent magnet machine and method of manufacturing the same

DOEpatents

Alexander, James Pellegrino [Ballston Lake, NY; EL-Refaie, Ayman Mohamed Fawzi [Niskayuna, NY; Lokhandwalla, Murtuza [Clifton Park, NY; Shah, Manoj Ramprasad [Latham, NY; VanDam, Jeremy Daniel [West Coxsackie, NY

2011-09-13

An internal permanent magnet (IPM) machine is provided. The IPM machine includes a stator assembly and a stator core. The stator core also includes multiple stator teeth. The stator assembly is further configured with stator windings to generate a magnetic field when excited with alternating currents and extends along a longitudinal axis with an inner surface defining a cavity. The IPM machine also includes a rotor assembly and a rotor core. The rotor core is disposed inside the cavity and configured to rotate about the longitudinal axis. The rotor assembly further includes a shaft. The shaft further includes multiple protrusions alternately arranged relative to multiple bottom structures provided on the shaft. The rotor assembly also includes multiple stacks of laminations disposed on the protrusions and dovetailed circumferentially around the shaft. The rotor assembly further includes multiple permanent magnets for generating a magnetic field, which interacts with the stator magnetic field to produce torque. The permanent magnets are disposed between the stacks. The rotor assembly also includes multiple bottom wedges disposed on the bottom structures of the shaft and configured to hold the multiple stacks and the multiple permanent magnets.

Underlying risk factors for prescribing errors in long-term aged care: a qualitative study.

PubMed

Tariq, Amina; Georgiou, Andrew; Raban, Magdalena; Baysari, Melissa Therese; Westbrook, Johanna

2016-09-01

To identify system-related risk factors perceived to contribute to prescribing errors in Australian long-term care settings, that is, residential aged care facilities (RACFs). The study used qualitative methods to explore factors that contribute to unsafe prescribing in RACFs. Data were collected at three RACFs in metropolitan Sydney, Australia between May and November 2011. Participants included RACF managers, doctors, pharmacists and RACF staff actively involved in prescribing-related processes. Methods included non-participant observations (74 h), in-depth semistructured interviews (n=25) and artefact analysis. Detailed process activity models were developed for observed prescribing episodes supplemented by triangulated analysis using content analysis methods. System-related factors perceived to increase the risk of prescribing errors in RACFs were classified into three overarching themes: communication systems, team coordination and staff management. Factors associated with communication systems included limited point-of-care access to information, inadequate handovers, information storage across different media (paper, electronic and memory), poor legibility of charts, information double handling, multiple faxing of medication charts and reliance on manual chart reviews. Team factors included lack of established lines of responsibility, inadequate team communication and limited participation of doctors in multidisciplinary initiatives like medication advisory committee meetings. Factors related to staff management and workload included doctors' time constraints and their accessibility, lack of trained RACF staff and high RACF staff turnover. The study highlights several system-related factors including laborious methods for exchanging medication information, which often act together to contribute to prescribing errors. Multiple interventions (eg, technology systems, team communication protocols) are required to support the collaborative nature of RACF prescribing. 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/

PATTERNS OF PHYSICAL ACTIVITY AMONG AMERICAN INDIAN CHILDREN: AN ASSESSMENT OF BARRIERS AND SUPPORT

PubMed Central

Thompson, Janice L.; Davis, Sally M.; Gittelsohn, Joel; Going, Scott; Becenti, Alberta; Metcalfe, Lauve; Stone, Elaine; Harnack, Lisa; Ring, Kim

2016-01-01

Estimates indicate that 10% to 50% of American Indian and non-Indian children in the U.S. are obese, defined as a body mass index ≥ 95th percentile of the NHANES II reference data. Pathways is a two-phase, multi-site study to develop and test a school-based obesity prevention program in American Indian schoolchildren in grades three through five. During Phase I feasibility prior to initiation of the Pathways trial, data were collected related to physical activity patterns, and the supports of, and barriers to, physical activity. Nine schools from communities representing six different tribal groups participated in this study. Multiple measures were used for data collection including direct observation, paired child interviews, and in-depth interviews and focus groups with adults. Students completed the self-administered Knowledge, Attitudes, and Behaviors (KAB) survey, and a Physical Activity Questionnaire (PAQ). Barriers to physical activity at schools included a lack of facilities, equipment, and trained staff persons for PE. Adults were not consistently active with their children, but they were highly supportive of their children’s activity level. Children reported a strong enjoyment of physical activity and strong peer support to be physically active. Weather conditions, safety concerns, and homework/chores were common barriers to physical activity reported by children and adult caregivers. The information was used to design culturally and age-appropriate, practical interventions including the five physical activity programs for schoolchildren in the Pathways study. PMID:11759094

Implementing multiple intervention strategies in Dutch public health-related policy networks.

PubMed

Harting, Janneke; Peters, Dorothee; Grêaux, Kimberly; van Assema, Patricia; Verweij, Stefan; Stronks, Karien; Klijn, Erik-Hans

2017-10-13

Improving public health requires multiple intervention strategies. Implementing such an intervention mix is supposed to require a multisectoral policy network. As evidence to support this assumption is scarce, we examined under which conditions public health-related policy networks were able to implement an intervention mix. Data were collected (2009-14) from 29 Dutch public health policy networks. Surveys were used to identify the number of policy sectors, participation of actors, level of trust, networking by the project leader, and intervention strategies implemented. Conditions sufficient for an intervention mix (≥3 of 4 non-educational strategies present) were determined in a fuzzy-set qualitative comparative analysis. A multisectoral policy network (≥7 of 14 sectors present) was neither a necessary nor a sufficient condition. In multisectoral networks, additionally required was either the active participation of network actors (≥50% actively involved) or active networking by the project leader (≥monthly contacts with network actors). In policy networks that included few sectors, a high level of trust (positive perceptions of each other's intentions) was needed-in the absence though of any of the other conditions. If the network actors were also actively involved, an extra requirement was active networking by the project leader. We conclude that the multisectoral composition of policy networks can contribute to the implementation of a variety of intervention strategies, but not without additional efforts. However, policy networks that include only few sectors are also able to implement an intervention mix. Here, trust seems to be the most important condition. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Multiplicative and additive modulation of neuronal tuning with population activity affects encoded information

PubMed Central

Arandia-Romero, Iñigo; Tanabe, Seiji; Drugowitsch, Jan; Kohn, Adam; Moreno-Bote, Rubén

2016-01-01

Numerous studies have shown that neuronal responses are modulated by stimulus properties, and also by the state of the local network. However, little is known about how activity fluctuations of neuronal populations modulate the sensory tuning of cells and affect their encoded information. We found that fluctuations in ongoing and stimulus-evoked population activity in primate visual cortex modulate the tuning of neurons in a multiplicative and additive manner. While distributed on a continuum, neurons with stronger multiplicative effects tended to have less additive modulation, and vice versa. The information encoded by multiplicatively-modulated neurons increased with greater population activity, while that of additively-modulated neurons decreased. These effects offset each other, so that population activity had little effect on total information. Our results thus suggest that intrinsic activity fluctuations may act as a `traffic light' that determines which subset of neurons are most informative. PMID:26924437

Innate immune recognition and inflammation in Neisseria meningitidis infection.

PubMed

Johswich, Kay

2017-03-01

Neisseria meningitidis (Nme) can cause meningitis and sepsis, diseases which are characterised by an overwhelming inflammatory response. Inflammation is triggered by host pattern recognition receptors (PRRs) which are activated by pathogen-associated molecular patterns (PAMPs). Nme contains multiple PAMPs including lipooligosaccharide, peptidoglycan, proteins and metabolites. Various classes of PRRs including Toll-like receptors, NOD-like receptors, C-type lectins, scavenger receptors, pentraxins and others are expressed by the host to respond to any given microbe. While Toll-like receptors and NOD-like receptors are pivotal in triggering inflammation, other PRRs act as modulators of inflammation or aid in functional antimicrobial responses such as phagocytosis or complement activation. This review aims to give an overview of the various Nme PAMPs reported to date, the PRRs they activate and their implications during the inflammatory response to infection. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Innate immune activity conditions the effect of regulatory variants upon monocyte gene expression.

PubMed

Fairfax, Benjamin P; Humburg, Peter; Makino, Seiko; Naranbhai, Vivek; Wong, Daniel; Lau, Evelyn; Jostins, Luke; Plant, Katharine; Andrews, Robert; McGee, Chris; Knight, Julian C

2014-03-07

To systematically investigate the impact of immune stimulation upon regulatory variant activity, we exposed primary monocytes from 432 healthy Europeans to interferon-γ (IFN-γ) or differing durations of lipopolysaccharide and mapped expression quantitative trait loci (eQTLs). More than half of cis-eQTLs identified, involving hundreds of genes and associated pathways, are detected specifically in stimulated monocytes. Induced innate immune activity reveals multiple master regulatory trans-eQTLs including the major histocompatibility complex (MHC), coding variants altering enzyme and receptor function, an IFN-β cytokine network showing temporal specificity, and an interferon regulatory factor 2 (IRF2) transcription factor-modulated network. Induced eQTL are significantly enriched for genome-wide association study loci, identifying context-specific associations to putative causal genes including CARD9, ATM, and IRF8. Thus, applying pathophysiologically relevant immune stimuli assists resolution of functional genetic variants.

New insights into IGF-1 signaling in the heart.

PubMed

Troncoso, Rodrigo; Ibarra, Cristián; Vicencio, Jose Miguel; Jaimovich, Enrique; Lavandero, Sergio

2014-03-01

Insulin-like growth factor 1 (IGF-1) signaling regulates contractility, metabolism, hypertrophy, autophagy, senescence, and apoptosis in the heart. IGF-1 deficiency is associated with an increased risk of cardiovascular disease, whereas cardiac activation of IGF-1 receptor (IGF-1R) protects from the detrimental effects of a high-fat diet and myocardial infarction. IGF-1R activates multiple pathways through its intrinsic tyrosine kinase activity and through coupling to heterotrimeric G protein. These pathways involve classic second messengers, phosphorylation cascades, lipid signaling, Ca(2+) transients, and gene expression. In addition, IGF-1R triggers signaling in different subcellular locations including the plasma membrane, perinuclear T tubules, and also in internalized vesicles. In this review, we provide a fresh and updated view of the complex IGF-1 scenario in the heart, including a critical focus on therapeutic strategies. Copyright © 2013 Elsevier Ltd. All rights reserved.

Supporting Simple Activity Engagement in Persons With Moderate to Severe Alzheimer's Disease Through a Technology-Aided Program.

PubMed

Lancioni, Giulio E; Singh, Nirbhay N; O'Reilly, Mark F; Sigafoos, Jeff; D'Amico, Fiora; Pinto, Katia; Chiapparino, Claudia

2017-05-01

These 2 studies assessed a technology-aided program to support mild physical exercise or simple occupational activity in participants with moderate to severe Alzheimer's disease. Study 1 included 11 participants who were to perform a leg-raising response. Study 2 included 10 participants who were to sort objects into different containers. The program ensured that they received positive stimulation contingent on the responses and reminders/prompts after periods of nonresponding. Each study was carried out according to a nonconcurrent multiple baseline design across participants. The program was successful in supporting mild physical exercise and activity with objects in the 2 groups of participants, respectively. The participants also showed signs of positive involvement (eg, smiles and verbalizations) during the sessions. Moreover, staff personnel rated the program and its impact positively. The program may be considered a practical resource for supporting positive engagement in persons with moderate to severe Alzheimer's disease.

Trichuris suis ova therapy in relapsing multiple sclerosis is safe but without signals of beneficial effect.

PubMed

Voldsgaard, A; Bager, P; Garde, E; Åkeson, P; Leffers, A M; Madsen, C G; Kapel, C; Roepstorff, A; Thamsborg, S M; Melbye, M; Siebner, H; Søndergaard, H B; Sellebjerg, F; Sørensen, P Soelberg

2015-11-01

An observational study has suggested that relapsing-remitting multiple sclerosis patients with helminth infections have lower disease activity and progression than uninfected multiple sclerosis patients. To evaluate the safety and efficacy on MRI activity of treatment with TSO in relapsing MS. The study was an open-label, magnetic resonance imaging assessor-blinded, baseline-to-treatment study including ten patients with relapsing forms of multiple sclerosis. Median (range) age was 41 (24-55) years, disease duration 9 (4-34) years, Expanded Disability Status Scale score 2.5 (1-5.0), and number of relapses within the last two years 3 (2-5). Four patients received no disease modifying therapy, while six patients received IFN-β. After an observational period of 8 weeks, patients received 2500 ova from the helminth Trichuris suis orally every second week for 12 weeks. Patients were followed with serial magnetic resonance imaging, neurological examinations, laboratory safety tests and expression of immunological biomarker genes. Treatment with Trichuris suis orally was well-tolerated apart from some gastrointestinal symptoms. Magnetic resonance imaging revealed 6 new or enlarged T2 lesions in the run-in period, 7 lesions in the early period and 21 lesions in the late treatment period. Two patients suffered a relapse before treatment and two during treatment. Eight patients developed eosinophilia. The expression of cytokines and transcription factors did not change. In a small group of relapsing multiple sclerosis patients, Trichuris suis oral therapy was well tolerated but without beneficial effect. © The Author(s), 2015.