Comprehensive interrogation of the cellular response to fluorescent, detonation and functionalized nanodiamonds.

PubMed

Moore, Laura; Grobárová, Valéria; Shen, Helen; Man, Han Bin; Míčová, Júlia; Ledvina, Miroslav; Štursa, Jan; Nesladek, Milos; Fišerová, Anna; Ho, Dean

2014-10-21

Nanodiamonds (NDs) are versatile nanoparticles that are currently being investigated for a variety of applications in drug delivery, biomedical imaging and nanoscale sensing. Although initial studies indicate that these small gems are biocompatible, there is a great deal of variability in synthesis methods and surface functionalization that has yet to be evaluated. Here we present a comprehensive analysis of the cellular compatibility of an array of nanodiamond subtypes and surface functionalization strategies. These results demonstrate that NDs are well tolerated by multiple cell types at both functional and gene expression levels. In addition, ND-mediated delivery of daunorubicin is less toxic to multiple cell types than treatment with daunorubicin alone, thus demonstrating the ability of the ND agent to improve drug tolerance and decrease therapeutic toxicity. Overall, the results here indicate that ND biocompatibility serves as a promising foundation for continued preclinical investigation.

Comprehensive interrogation of the cellular response to fluorescent, detonation and functionalized nanodiamonds

NASA Astrophysics Data System (ADS)

Moore, Laura; Grobárová, Valéria; Shen, Helen; Man, Han Bin; Míčová, Júlia; Ledvina, Miroslav; Štursa, Jan; Nesladek, Milos; Fišerová, Anna; Ho, Dean

2014-09-01

Nanodiamonds (NDs) are versatile nanoparticles that are currently being investigated for a variety of applications in drug delivery, biomedical imaging and nanoscale sensing. Although initial studies indicate that these small gems are biocompatible, there is a great deal of variability in synthesis methods and surface functionalization that has yet to be evaluated. Here we present a comprehensive analysis of the cellular compatibility of an array of nanodiamond subtypes and surface functionalization strategies. These results demonstrate that NDs are well tolerated by multiple cell types at both functional and gene expression levels. In addition, ND-mediated delivery of daunorubicin is less toxic to multiple cell types than treatment with daunorubicin alone, thus demonstrating the ability of the ND agent to improve drug tolerance and decrease therapeutic toxicity. Overall, the results here indicate that ND biocompatibility serves as a promising foundation for continued preclinical investigation.

Early classification of Alzheimer's disease using hippocampal texture from structural MRI

NASA Astrophysics Data System (ADS)

Zhao, Kun; Ding, Yanhui; Wang, Pan; Dou, Xuejiao; Zhou, Bo; Yao, Hongxiang; An, Ningyu; Zhang, Yongxin; Zhang, Xi; Liu, Yong

2017-03-01

Convergent evidence has been collected to support that Alzheimer's disease (AD) is associated with reduction in hippocampal volume based on anatomical magnetic resonance imaging (MRI) and impaired functional connectivity based on functional MRI. Radiomics texture analysis has been previously successfully used to identify MRI biomarkers of several diseases, including AD, mild cognitive impairment and multiple sclerosis. In this study, our goal was to determine if MRI hippocampal textures, including the intensity, shape, texture and wavelet features, could be served as an MRI biomarker of AD. For this purpose, the texture marker was trained and evaluated from MRI data of 48 AD and 39 normal samples. The result highlights the presence of hippocampal texture abnormalities in AD, and the possibility that texture may serve as a neuroimaging biomarker for AD.

GLABROUS (CmGL) encodes a HD-ZIP IV transcription factor playing roles in multicellular trichome initiation in melon

USDA-ARS?s Scientific Manuscript database

Trichomes are small hairs covering the above-ground parts of plants that serve multiple functions in plant life such as protection against insects and pathogens. Little is known about the genetic control and regulation of trichome development in melon. In this study, we identified a melon mutant, cm...

Two Sides of the Same Coin: Student-Faculty Perspectives of the Course Syllabus

ERIC Educational Resources Information Center

McDonald, Jeanette; Siddall, Gillian; Mandell, Deena; Hughes, Sandy

2010-01-01

Course syllabi play an important role in teaching, learning, and course design. They serve multiple functions and audiences and represent the end product of a scholarly process. In the following article, select findings from a mixed methods study examining how faculty and students conceptualize course syllabi are presented, specifically the design…

Conceptualizing the Functional Requirements for a Next-Generation E-Portfolio System

ERIC Educational Resources Information Center

Mu, Enrique; Wormer, Sallie; Foizey, Roberta; Barkon, Beverly; Vehec, Mark

2010-01-01

The use of e-portfolio systems in higher education has not grown as anticipated by early adopters when the potential benefits first became apparent, yet the promise remains. The vision of a flexible tool that meets multiple goals--serving as a showcase for student work, promoting self-reflection, supporting assessment and accreditation efforts,…

Caregiver-Teacher Concordance of Challenging Behaviors in Children with Autism Spectrum Disorder Served in Community Mental Health Settings

ERIC Educational Resources Information Center

Stadnick, Nicole; Chlebowski, Colby; Brookman-Frazee, Lauren

2017-01-01

Children with autism spectrum disorder (ASD) exhibit high rates of challenging behaviors that impair functioning and represent the primary presenting problem in mental health (MH) services. Obtaining symptom reports from multiple informants is critical for treatment planning. This study evaluated caregiver-teacher concordance of ratings of the…

The SLP-76 Src homology 2 domain is required for T cell development and activation.

PubMed

Burns, Jeremy C; Corbo, Evann; Degen, Janine; Gohil, Mercy; Anterasian, Christine; Schraven, Burkart; Koretzky, Gary A; Kliche, Stefanie; Jordan, Martha S

2011-11-01

The adapter protein Src homology 2 (SH2) domain-containing leukocyte protein of 76 kDa (SLP-76) is critical for multiple aspects of T cell development and function. Through its protein-binding domains, SLP-76 serves as a platform for the assembly of multiple enzymes and adapter proteins that function together to activate second messengers required for TCR signal propagation. The N terminus of SLP-76, which contains three tyrosines that serve as docking sites for SH2 domain-containing proteins, and the central proline-rich region of SLP-76 have been well studied and are known to be important for both thymocyte selection and activation of peripheral T cells. Less is known about the function of the C-terminal SH2 domain of SLP-76. This region inducibly associates with ADAP and HPK1. Combining regulated deletion of endogenous SLP-76 with transgenic expression of a SLP-76 SH2 domain mutant, we demonstrate that the SLP-76 SH2 domain is required for peripheral T cell activation and positive selection of thymocytes, a function not previously attributed to this region. This domain is also important for T cell proliferation, IL-2 production, and phosphorylation of protein kinase D and IκB. ADAP-deficient T cells display similar, but in some cases less severe, defects despite phosphorylation of a negative regulatory site on SLP-76 by HPK1, a function that is lost in SLP-76 SH2 domain mutant T cells.

Analyzing nature's protective design: The glyptodont body armor.

PubMed

du Plessis, Anton; Broeckhoven, Chris; Yadroitsev, Igor; Yadroitsava, Ina; le Roux, Stephan Gerhard

2018-06-01

Many animal species evolved some form of body armor, such as scales of fish and bony plates or osteoderms of reptiles. Although a protective function is often taken for granted, recent studies show that body armor might comprise multiple functionalities and is shaped by trade-offs among these functionalities. Hence, despite the fact that natural body armor might serve as bio-inspiration for the development of artificial protective materials, focussing on model systems in which body armor serves a solely protective function might be pivotal. In this study, we investigate the osteoderms of Glyptotherium arizonae, an extinct armadillo-like mammal in which body armor evolved as protection against predators and/or tail club blows of conspecifics. By using a combination of micro-computed tomography, reverse-engineering, stress simulations and mechanical testing of 3D printed models, we show that the combination of dense compact layers and porous lattice core might provide an optimized combination of strength and high energy absorption. Copyright © 2018 Elsevier Ltd. All rights reserved.

The Genetic-Algorithm-Based Normal Boundary Intersection (GANBI) Method; An Efficient Approach to Pareto Multiobjective Optimization for Engineering Design

DTIC Science & Technology

2006-05-15

alarm performance in a cost-effective manner is the use of track - before - detect strategies, in which multiple sensor detections must occur within the...corresponding to the traditional sensor coverage problem. Also, in the track - before - detect context, reference is made to the field-level functions of...detection and false alarm as successful search and false search, respectively, because the track - before - detect process serves as a searching function

Engaging Students in Constructive Youth-Adult Relationships: A Case Study of Urban School-Based Agriculture Students and Positive Adult Mentors

ERIC Educational Resources Information Center

Bird, William A.; Martin, Michael J.; Tummons, John D.; Ball, Anna L.

2013-01-01

The purpose of this bounded single case study was to explore the day-to-day functioning of a successful urban school-based agriculture veterinary program. Findings indicated student success was a product of multiple youth-adult relationships created through communal environments. Adults served as mentors with whom students felt constant, caring…

Quality of Bone Healing: Perspectives and Assessment Techniques

DTIC Science & Technology

2014-01-01

connective tissue specialized for load bearing . Embryologically, the formation of bone occurs via two routes: intramembranous and endochondral ossification.1...primarily suited to load bearing with two distinct configurations: an inner, porous, cancellous architecture and an outer, denser, cortical bone...delineate the multiple functions served by the human skeleton and then evaluate techniques for clinical assessment. Mechanical load bearing and transduction

Affective brain areas and sleep disordered breathing

PubMed Central

Harper, Ronald M.; Kumar, Rajesh; Macey, Paul M.; Woo, Mary A.; Ogren, Jennifer A.

2014-01-01

The neural damage accompanying the hypoxia, reduced perfusion, and other consequences of sleep-disordered breathing found in obstructive sleep apnea, heart failure (HF), and congenital central hypoventilation syndrome (CCHS), appears in areas that serve multiple functions, including emotional drives to breathe, and involve systems that serve affective, cardiovascular, and breathing roles. The damage, assessed with structural magnetic resonance imaging (MRI) procedures, shows tissue loss or water content and diffusion changes indicative of injury, and impaired axonal integrity between structures; damage is preferentially unilateral. Functional MRI responses in affected areas also are time- or amplitude- distorted to ventilatory or autonomic challenges. Among the structures injured are the insular, cingulate, and ventral medial prefrontal cortices, as well as cerebellar deep nuclei and cortex, anterior hypothalamus, raphé, ventrolateral medulla, basal ganglia and, in CCHS, the locus coeruleus. Raphé and locus coeruleus injury may modify serotonergic and adrenergic modulation of upper airway and arousal characteristics. Since both axons and gray matter show injury, the consequences to function, especially to autonomic, cognitive, and mood regulation, are major. Several affected rostral sites, including the insular and cingulate cortices and hippocampus, mediate aspects of dyspnea, especially in CCHS, while others, including the anterior cingulate and thalamus, participate in initiation of inspiration after central breathing pauses, and the medullary injury can impair baroreflex and breathing control. The ancillary injury associated with sleep-disordered breathing to central structures can elicit multiple other distortions in cardiovascular, cognitive, and emotional functions in addition to effects on breathing regulation. PMID:24746053

Attack risk for butterflies changes with eyespot number and size

PubMed Central

Ho, Sebastian; Schachat, Sandra R.; Piel, William H.; Monteiro, Antónia

2016-01-01

Butterfly eyespots are known to function in predator deflection and predator intimidation, but it is still unclear what factors cause eyespots to serve one function over the other. Both functions have been demonstrated in different species that varied in eyespot size, eyespot number and wing size, leaving the contribution of each of these factors to butterfly survival unclear. Here, we study how each of these factors contributes to eyespot function by using paper butterfly models, where each factor is varied in turn, and exposing these models to predation in the field. We find that the presence of multiple, small eyespots results in high predation, whereas single large eyespots (larger than 6 mm in diameter) results in low predation. These data indicate that single large eyespots intimidate predators, whereas multiple small eyespots produce a conspicuous, but non-intimidating signal to predators. We propose that eyespots may gain an intimidation function by increasing in size. Our measurements of eyespot size in 255 nymphalid butterfly species show that large eyespots are relatively rare and occur predominantly on ventral wing surfaces. By mapping eyespot size on the phylogeny of the family Nymphalidae, we show that these large eyespots, with a potential intimidation function, are dispersed throughout multiple nymphalid lineages, indicating that phylogeny is not a strong predictor of eyespot size. PMID:26909190

The SLP-76 SH2 domain is required for T cell development and activation

PubMed Central

Burns, Jeremy C.; Corbo, Evann; Degen, Janine; Gohil, Mercy; Anterasian, Christine; Schraven, Burkart; Koretzky, Gary A.; Kliche, Stefanie; Jordan, Martha S.

2011-01-01

The adaptor protein Src homology 2 (SH2) domain containing leukocyte protein of 76 kDa (SLP-76) is critical for multiple aspects of T cell development and function. Through its protein-binding domains, SLP-76 serves as a platform for the assembly of multiple enzymes and adaptor proteins that function together to activate second messengers required for TCR signal propagation. The N-terminus of SLP-76, which contains three tyrosines that serve as docking sites for SH2 domain-containing proteins, and the central proline-rich region of SLP-76 have been well studied and are known to be important for both thymocyte selection and activation of peripheral T cells. Less is known about the function of the C-terminal SH2 domain of SLP-76. This region inducibly associates with the adhesion- and degranulation-promoting adaptor protein (ADAP) and hematopoietic progenitor kinase 1 (HPK1). Combining regulated deletion of endogenous SLP-76 with transgenic expression of a SLP-76 SH2 domain mutant, we demonstrate that the SLP-76 SH2 domain is required for peripheral T cell activation and positive selection of thymocytes, a function not previously attributed to this region. This domain is also important for T cell proliferation, IL-2 production and phosphorylation of protein kinase D (PKD) and IκB. ADAP-deficient T cells display similar, but in some cases less severe, defects despite phosphorylation of a negative regulatory site on SLP-76 by HPK1, a function that is lost in SLP-76 SH2 domain mutant T cells. PMID:21949020

Perceived discrimination, family functioning, and depressive symptoms among immigrant women in Taiwan.

PubMed

Yang, Hao-Jan; Wu, Jyun-Yi; Huang, Sheng-Shiung; Lien, Mei-Huei; Lee, Tony Szu-Hsien

2014-10-01

This study examined the moderating effect of family functioning on the relationship between perceived discrimination and depressive symptoms in immigrant women. A total of 239 immigrant women were selected from four administrative regions in Central Taiwan. Questionnaires concerning perceived discrimination, family functioning (including family cohesion and family adaptability), depressive symptoms, and demographic characteristics were completed by either women themselves (N = 120) or their husbands (N = 119). The moderating effect of family functioning on the relationship between perceived discrimination and depression symptoms was analyzed using multiple regression analysis. Findings showed that a higher level of perceived discrimination among immigrant women is associated with more severe depressive symptoms. Family functioning serves as a moderator between the relationship of perceived discrimination and depressive symptoms, but the moderating effect of family adaptability was evident only in data reported by immigrant women. The results indicate that perceived discrimination has negative mental health implications, and also point to the importance of family functioning for depression. Findings suggest that providers should consider addressing immigrant women's mental health needs through declining their psychosocial distress at multiple ecological levels.

Nucleophosmin/B23 regulates ubiquitin dynamics in nucleoli by recruiting deubiquitylating enzyme USP36.

PubMed

Endo, Akinori; Kitamura, Naomi; Komada, Masayuki

2009-10-09

The nucleolus is a subnuclear compartment with multiple cellular functions, including ribosome biogenesis. USP36 is a deubiquitylating enzyme that localizes to nucleoli and plays an essential role in regulating the structure and function of the organelle. However, how the localization of USP36 is regulated remains unknown. Here, we identified a short stretch of basic amino acids (RGKEKKIKKFKREKRR) that resides in the C-terminal region of USP36 and serves as a nucleolar localization signal for the protein. We found that this motif interacts with a central acidic region of nucleophosmin/B23, a major nucleolar protein involved in various nucleolar functions. Knockdown of nucleophosmin/B23 resulted in a significant reduction in the amount of USP36 in nucleoli, without affecting the cellular USP36 level. This was associated with elevated ubiquitylation levels of fibrillarin, a USP36 substrate protein in nucleoli. We conclude that nucleophosmin/B23 recruits USP36 to nucleoli, thereby serving as a platform for the regulation of nucleolar protein functions through ubiquitylation/deubiquitylation.

Heat Load Sharing in a Capillary Pumped Loop with Multiple Evaporators and Multiple Condensers

NASA Technical Reports Server (NTRS)

Ku, Jentung

2005-01-01

This paper describes the heat load sharing function among multiple parallel evaporators in a capillary pumped loop (CPL). In the normal mode of operation, the evaporators cool the instruments by absorbing the waste heat. When an instruments is turned off, the attached evaporator can keep it warm by receiving heat from other evaporators serving the operating instruments. This is referred to as heat load sharing. A theoretical basis of heat load sharing is given first. The fact that the wicks in the powered evaporators will develop capillary pressure to force the generated vapor to flow to cold locations where the pressure is lower leads to the conclusion that heat load sharing is an inherent function of a CPL with multiple evaporators. Heat load sharing has been verified with many CPLs in ground tests. Experimental results of the Capillary Pumped Loop 3 (CAPL 3) Flight Experiment are presented in this paper. Factors that affect the amount of heat being shared are discussed. Some constraints of heat load sharing are also addressed.

Cytoskeleton-centric protein transportation by exosomes transforms tumor-favorable macrophages.

PubMed

Chen, Zhipeng; Yang, Lijuan; Cui, Yizhi; Zhou, Yanlong; Yin, Xingfeng; Guo, Jiahui; Zhang, Gong; Wang, Tong; He, Qing-Yu

2016-10-11

The exosome is a key initiator of pre-metastatic niche in numerous cancers, where macrophages serve as primary inducers of tumor microenvironment. However, the proteome that can be exosomally transported from cancer cells to macrophages has not been sufficiently characterized so far. Here, we used colorectal cancer (CRC) exosomes to educate tumor-favorable macrophages. With a SILAC-based mass spectrometry strategy, we successfully traced the proteome transported from CRC exosomes to macrophages. Such a proteome primarily focused on promoting cytoskeleton rearrangement, which was biologically validated with multiple cell lines. We reproduced the exosomal transportation of functional vimentin as a proof-of-concept example. In addition, we found that some CRC exosomes could be recognized by macrophages via Fc receptors. Therefore, we revealed the active and necessary role of exosomes secreted from CRC cells to transform cancer-favorable macrophages, with the cytoskeleton-centric proteins serving as the top functional unit.

Understanding large multiprotein complexes: applying a multiple allosteric networks model to explain the function of the Mediator transcription complex.

PubMed

Lewis, Brian A

2010-01-15

The regulation of transcription and of many other cellular processes involves large multi-subunit protein complexes. In the context of transcription, it is known that these complexes serve as regulatory platforms that connect activator DNA-binding proteins to a target promoter. However, there is still a lack of understanding regarding the function of these complexes. Why do multi-subunit complexes exist? What is the molecular basis of the function of their constituent subunits, and how are these subunits organized within a complex? What is the reason for physical connections between certain subunits and not others? In this article, I address these issues through a model of network allostery and its application to the eukaryotic RNA polymerase II Mediator transcription complex. The multiple allosteric networks model (MANM) suggests that protein complexes such as Mediator exist not only as physical but also as functional networks of interconnected proteins through which information is transferred from subunit to subunit by the propagation of an allosteric state known as conformational spread. Additionally, there are multiple distinct sub-networks within the Mediator complex that can be defined by their connections to different subunits; these sub-networks have discrete functions that are activated when specific subunits interact with other activator proteins.

Design of polystyrene latex particles covered with polyoxometalate clusters via multiple covalent bonding

DOE PAGES

Chen, Xinyue; Li, Hui; Yin, Panchao; ...

2015-02-27

In this study, polyoxometalates (POMs) covalently functionalized with methyl methacrylate groups were applied as surfactants in the emulsion polymerization reaction of styrene. Due to the copolymerization of the methyl methacrylate groups and the styrene monomers, the polyoxometalate clusters are covalently grafted onto the surface of polystyrene latex nanoparticles. Finally, such latex particles are fully covered with catalytic POM clusters and might serve as quasi-homogeneous catalysts.

The German Skills Machine: Sustaining Comparative Advantage in a Global Economy. Policies and Institutions: Germany, Europe, and Transatlantic Relations, Volume 3.

ERIC Educational Resources Information Center

Culpepper, Pepper D., Ed.; Finegold, David, Ed.

This book examines the effectiveness and distributive ramifications of the institutions of German skill provision as they functioned at home in the 1990s and as they served as a template for reform in other industrialized countries. The volume relies on multiple sources of data, including in-firm case studies, larger-scale surveys of companies,…

New Brunswick Laboratory progress report, October 1994--September 1995

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

NONE

The mission of the New Brunswick Laboratory (NBL) of the A. S. Department of Energy (DOE) is to serve as the National Certifying Authority for nuclear reference materials and to provide an independent Federal technical staff and laboratory resource performing nuclear material measurement, safeguards, and non-proliferation functions in support of multiple program sponsors. This annual report describes accomplishments achieved in carrying out NBL`s assigned missions.

Microglia in the developing brain: a potential target with lifetime effects

PubMed Central

Harry, G. Jean; Kraft, Andrew D.

2012-01-01

Microglia are a heterogeneous group of monocyte-derived cells serving multiple roles within the brain, many of which are associated with immune and macrophage like properties. These cells are known to serve a critical role during brain injury and to maintain homeostasis; yet, their defined roles during development have yet to be elucidated. Microglial actions appear to influence events associated with neuronal proliferation and differentiation during development, as well as, contribute to processes associated with the removal of dying neurons or cellular debris and management of synaptic connections. These long-lived cells display changes during injury and with aging that are critical to the maintenance of the neuronal environment over the lifespan of the organism. These processes may be altered by changes in the colonization of the brain or by inflammatory events during development. This review addresses the role of microglia during brain development, both structurally and functionally, as well as the inherent vulnerability of the developing nervous system. A framework is presented considering microglia as a critical nervous system-specific cell that can influence multiple aspects of brain development (e.g., vascularization, synaptogenesis, and myelination) and have a long term impact on the functional vulnerability of the nervous system to a subsequent insult, whether environmental, physical, age-related, or disease-related. PMID:22322212

Collaborative real-time scheduling of multiple PTZ cameras for multiple object tracking in video surveillance

NASA Astrophysics Data System (ADS)

Liu, Yu-Che; Huang, Chung-Lin

2013-03-01

This paper proposes a multi-PTZ-camera control mechanism to acquire close-up imagery of human objects in a surveillance system. The control algorithm is based on the output of multi-camera, multi-target tracking. Three main concerns of the algorithm are (1) the imagery of human object's face for biometric purposes, (2) the optimal video quality of the human objects, and (3) minimum hand-off time. Here, we define an objective function based on the expected capture conditions such as the camera-subject distance, pan tile angles of capture, face visibility and others. Such objective function serves to effectively balance the number of captures per subject and quality of captures. In the experiments, we demonstrate the performance of the system which operates in real-time under real world conditions on three PTZ cameras.

The role of recurrent disturbances for ecosystem multifunctionality.

PubMed

Villnäs, Anna; Norkko, Joanna; Hietanen, Susanna; Josefson, Alf B; Lukkari, Kaarina; Norkko, Alf

2013-10-01

Ecosystem functioning is threatened by an increasing number of anthropogenic stressors, creating a legacy of disturbance that undermines ecosystem resilience. However, few empirical studies have assessed to what extent an ecosystem can tolerate repeated disturbances and sustain its multiple functions. By inducing increasingly recurring hypoxic disturbances to a sedimentary ecosystem, we show that the majority of individual ecosystem functions experience gradual degradation patterns in response to repetitive pulse disturbances. The degradation in overall ecosystem functioning was, however, evident at an earlier stage than for single ecosystem functions and was induced after a short pulse of hypoxia (i.e., three days), which likely reduced ecosystem resistance to further hypoxic perturbations. The increasing number of repeated pulse disturbances gradually moved the system closer to a press response. In addition to the disturbance regime, the changes in benthic trait composition as well as habitat heterogeneity were important for explaining the variability in overall ecosystem functioning. Our results suggest that disturbance-induced responses across multiple ecosystem functions can serve as a warning signal for losses of the adaptive capacity of an ecosystem, and might at an early stage provide information to managers and policy makers when remediation efforts should be initiated.

Enhancement of emission of InGaN/GaN multiple-quantum-well nanorods by coupling to Au-nanoparticle plasmons

NASA Astrophysics Data System (ADS)

Xing, Jieying; Chen, Yinsong; Liu, Yuebo; Liang, Jiezhi; Chen, Jie; Ren, Yuan; Han, Xiaobiao; Zhong, Changming; Yang, Hang; Huang, Dejia; Hou, Yaqian; Wu, Zhisheng; Liu, Yang; Zhang, Baijun

2018-05-01

We demonstrate the enhancement of emission of InGaN/GaN multiple-quantum-well nanorods by nearly a factor of 2 by coupling them to localized surface plasmons of Au nano-particles (NPs). The Au NPs are fabricated in situ on the nanorods using a Ni/SiO2/Au/SiNx compound functional layer. This layer serves as a combination dry-etch mask for fabricating the nanorods and the Au NPs, as well as providing isolation necessary to prevent fluorescence quenching. Time-resolved photoluminescence measurements confirm that emission enhancement originates from the coupling.

Effects of Functional Groups in Redox-Active Organic Molecules: A High-Throughput Screening Approach

DOE PAGES

Pelzer, Kenley M.; Cheng, Lei; Curtiss, Larry A.

2016-12-08

Nonaqueous redox flow batteries have attracted recent attention with their potential for high electrochemical storage capacity, with organic electrolytes serving as solvents with a wide electrochemical stability window. Organic molecules can also serve as electroactive species, where molecules with low reduction potentials or high oxidation potentials can provide substantial chemical energy. To identify promising electrolytes in a vast chemical space, high-throughput screening (HTS) of candidate molecules plays an important role, where HTS is used to calculate properties of thousands of molecules and identify a few organic molecules worthy of further attention in battery research. Here, in this work, we presentmore » reduction and oxidation potentials obtained from HTS of 4178 molecules. The molecules are composed of base groups of five- or six-membered rings with one or two functional groups attached, with the set of possible functional groups including both electron-withdrawing and electron-donating groups. In addition to observing the trends in potentials that result from differences in organic base groups and functional groups, we analyze the effects of molecular characteristics such as multiple bonds, Hammett parameters, and functional group position. In conclusion, this work provides useful guidance in determining how the identities of the base groups and functional groups are correlated with desirable reduction and oxidation potentials.« less

Effects of Functional Groups in Redox-Active Organic Molecules: A High-Throughput Screening Approach

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

Pelzer, Kenley M.; Cheng, Lei; Curtiss, Larry A.

Nonaqueous redox flow batteries have attracted recent attention with their potential for high electrochemical storage capacity, with organic electrolytes serving as solvents with a wide electrochemical stability window. Organic molecules can also serve as electroactive species, where molecules with low reduction potentials or high oxidation potentials can provide substantial chemical energy. To identify promising electrolytes in a vast chemical space, high-throughput screening (HTS) of candidate molecules plays an important role, where HTS is used to calculate properties of thousands of molecules and identify a few organic molecules worthy of further attention in battery research. Here, in this work, we presentmore » reduction and oxidation potentials obtained from HTS of 4178 molecules. The molecules are composed of base groups of five- or six-membered rings with one or two functional groups attached, with the set of possible functional groups including both electron-withdrawing and electron-donating groups. In addition to observing the trends in potentials that result from differences in organic base groups and functional groups, we analyze the effects of molecular characteristics such as multiple bonds, Hammett parameters, and functional group position. In conclusion, this work provides useful guidance in determining how the identities of the base groups and functional groups are correlated with desirable reduction and oxidation potentials.« less

Extending multi-tenant architectures: a database model for a multi-target support in SaaS applications

NASA Astrophysics Data System (ADS)

Rico, Antonio; Noguera, Manuel; Garrido, José Luis; Benghazi, Kawtar; Barjis, Joseph

2016-05-01

Multi-tenant architectures (MTAs) are considered a cornerstone in the success of Software as a Service as a new application distribution formula. Multi-tenancy allows multiple customers (i.e. tenants) to be consolidated into the same operational system. This way, tenants run and share the same application instance as well as costs, which are significantly reduced. Functional needs vary from one tenant to another; either companies from different sectors run different types of applications or, although deploying the same functionality, they do differ in the extent of their complexity. In any case, MTA leaves one major concern regarding the companies' data, their privacy and security, which requires special attention to the data layer. In this article, we propose an extended data model that enhances traditional MTAs in respect of this concern. This extension - called multi-target - allows MT applications to host, manage and serve multiple functionalities within the same multi-tenant (MT) environment. The practical deployment of this approach will allow SaaS vendors to target multiple markets or address different levels of functional complexity and yet commercialise just one single MT application. The applicability of the approach is demonstrated via a case study of a real multi-tenancy multi-target (MT2) implementation, called Globalgest.

The HSP70 family and cancer

PubMed Central

Murphy, Maureen E.

2013-01-01

The HSP70 family of heat shock proteins consists of molecular chaperones of approximately 70kDa in size that serve critical roles in protein homeostasis. These adenosine triphosphatases unfold misfolded or denatured proteins and can keep these proteins in an unfolded, folding-competent state. They also protect nascently translating proteins, promote the cellular or organellar transport of proteins, reduce proteotoxic protein aggregates and serve general housekeeping roles in maintaining protein homeostasis. The HSP70 family is the most conserved in evolution, and all eukaryotes contain multiple members. Some members of this family serve specific organellar- or tissue-specific functions; however, in many cases, these members can function redundantly. Overall, the HSP70 family of proteins can be thought of as a potent buffering system for cellular stress, either from extrinsic (physiological, viral and environmental) or intrinsic (replicative or oncogenic) stimuli. As such, this family serves a critical survival function in the cell. Not surprisingly, cancer cells rely heavily on this buffering system for survival. The overwhelming majority of human tumors overexpress HSP70 family members, and expression of these proteins is typically a marker for poor prognosis. With the proof of principle that inhibitors of the HSP90 chaperone have emerged as important anticancer agents, intense focus has now been placed on the potential for HSP70 inhibitors to assume a role as a significant chemotherapeutic avenue. In this review, the history, regulation, mechanism of action and role in cancer of the HSP70 family are reviewed. Additionally, the promise of pharmacologically targeting this protein for cancer therapy is addressed. PMID:23563090

Protein kinase FgSch9 serves as a mediator of the target of rapamycin and high osmolarity glycerol pathways and regulates multiple stress responses and secondary metabolism in Fusarium graminearum.

PubMed

Gu, Qin; Zhang, Chengqi; Yu, Fangwei; Yin, Yanni; Shim, Won-Bo; Ma, Zhonghua

2015-08-01

Saccharomyces cerevisiae protein kinase Sch9 is one of the downstream effectors of the target of rapamycin (TOR) complex 1 and plays multiple roles in stress resistance, longevity and nutrient sensing. However, the functions of Sch9 orthologs in filamentous fungi, particularly in pathogenic species, have not been characterized to date. Here, we investigated biological and genetic functions of FgSch9 in Fusarium graminearum. The FgSCH9 deletion mutant (ΔFgSch9) was defective in aerial hyphal growth, hyphal branching and conidial germination. The mutant exhibited increased sensitivity to osmotic and oxidative stresses, cell wall-damaging agents, and to rapamycin, while showing increased thermal tolerance. We identified FgMaf1 as one of the FgSch9-interacting proteins that plays an important role in regulating mycotoxin biosynthesis and virulence of F. graminearum. Co-immunoprecipitation and affinity capture-mass spectrometry assays showed that FgSch9 also interacts with FgTor and FgHog1. More importantly, both ΔFgSch9 and FgHog1 null mutant (ΔFgHog1) exhibited increased sensitivity to osmotic and oxidative stresses. This defect was more severe in the FgSch9/FgHog1 double mutant. Taken together, we propose that FgSch9 serves as a mediator of the TOR and high osmolarity glycerol pathways, and regulates vegetative differentiation, multiple stress responses and secondary metabolism in F. graminearum. © 2014 Society for Applied Microbiology and John Wiley & Sons Ltd.

A Low Cost Micro-Computer Based Local Area Network for Medical Office and Medical Center Automation

PubMed Central

Epstein, Mel H.; Epstein, Lynn H.; Emerson, Ron G.

1984-01-01

A Low Cost Micro-computer based Local Area Network for medical office automation is described which makes use of an array of multiple and different personal computers interconnected by a local area network. Each computer on the network functions as fully potent workstations for data entry and report generation. The network allows each workstation complete access to the entire database. Additionally, designated computers may serve as access ports for remote terminals. Through “Gateways” the network may serve as a front end for a large mainframe, or may interface with another network. The system provides for the medical office environment the expandability and flexibility of a multi-terminal mainframe system at a far lower cost without sacrifice of performance.

Industrial Wasteland as Faced with Contemporary Landscape Architects’ Challenges

NASA Astrophysics Data System (ADS)

Tubielewicz-Michalczuk, Malwina

2017-10-01

The following article describes the problem of regeneration of industrial wasteland. It is illustrated with examples selected form various design projects created by outstanding contemporary landscape architects. It also shows how a correctly planned and performed project concerning regeneration of derelict industrial sites serves multiple functions, i. e. it serves as recreational zone as well as activates people. Moreover, it significantly enhances environmental value of a given area as well as stimulates emergence of innovative landscape investments. The paper presents innovative compositional arrangements used in creating projects concerning brownfields; balanced proportions of spatial elements, the possibility of approaching the area from different levels and perspectives and, also, the possibility of engaging fully with nature by physical contact with it.

Evaluating the Functionality of Conceptual Models

NASA Astrophysics Data System (ADS)

Mehmood, Kashif; Cherfi, Samira Si-Said

Conceptual models serve as the blueprints of information systems and their quality plays decisive role in the success of the end system. It has been witnessed that majority of the IS change-requests results due to deficient functionalities in the information systems. Therefore, a good analysis and design method should ensure that conceptual models are functionally correct and complete, as they are the communicating mediator between the users and the development team. Conceptual model is said to be functionally complete if it represents all the relevant features of the application domain and covers all the specified requirements. Our approach evaluates the functional aspects on multiple levels of granularity in addition to providing the corrective actions or transformation for improvement. This approach has been empirically validated by practitioners through a survey.

Trajectory of change in pain, depression, and physical functioning after physical activity adoption in fibromyalgia.

PubMed

Steiner, Jennifer L; Bigatti, Silvia M; Ang, Dennis C

2015-07-01

Fibromyalgia is associated with widespread pain, depression, and declines in physical functioning. The purpose of this study was to examine the trajectory of these symptoms over time related to physical activity adoption and maintenance via motivational interviewing versus education, to increase physical activity. There were no treatment group differences; we divided the sample (n = 184) based on changes in physical activity. Repeated measures analyses demonstrated differential patterns in depression, pain, and physical functioning at 24 and 36 weeks. Findings suggest increased physical activity may serve as a multiple-target intervention that provides moderate to large, long-lasting benefits for individuals with fibromyalgia. © The Author(s) 2013.

Drugs, Biogenic Amine Targets and the Developing Brain

PubMed Central

Frederick, Aliya L.; Stanwood, Gregg D.

2009-01-01

Defects in the development of the brain have profound impacts on mature brain functions and underlie psychopathology. Classical neurotransmitters and neuromodulators, such as dopamine, serotonin, norepinephrine, acetycholine, glutamate and GABA, have pleiotropic effects during brain development. In other words, these molecules produce multiple, diverse effects to serve as regulators of distinct cellular functions at different times in neurodevelopment. These systems are impacted upon by a variety of illicit drugs of abuse, neurotherapeutics, and environmental contaminants. In this review, we describe the impact of drugs and chemicals on brain formation and function in animal models and in human populations, highlighting sensitive periods and effects that may not emerge until later in life. PMID:19372683

Multiple components of surround modulation in primary visual cortex: multiple neural circuits with multiple functions?

PubMed Central

Nurminen, Lauri; Angelucci, Alessandra

2014-01-01

The responses of neurons in primary visual cortex (V1) to stimulation of their receptive field (RF) are modulated by stimuli in the RF surround. This modulation is suppressive when the stimuli in the RF and surround are of similar orientation, but less suppressive or facilitatory when they are cross-oriented. Similarly, in human vision surround stimuli selectively suppress the perceived contrast of a central stimulus. Although the properties of surround modulation have been thoroughly characterized in many species, cortical areas and sensory modalities, its role in perception remains unknown. Here we argue that surround modulation in V1 consists of multiple components having different spatio-temporal and tuning properties, generated by different neural circuits and serving different visual functions. One component arises from LGN afferents, is fast, untuned for orientation, and spatially restricted to the surround region nearest to the RF (the near-surround); its function is to normalize V1 cell responses to local contrast. Intra-V1 horizontal connections contribute a slower, narrowly orientation-tuned component to near-surround modulation, whose function is to increase the coding efficiency of natural images in manner that leads to the extraction of object boundaries. The third component is generated by topdown feedback connections to V1, is fast, broadly orientation-tuned, and extends into the far-surround; its function is to enhance the salience of behaviorally relevant visual features. Far- and near-surround modulation, thus, act as parallel mechanisms: the former quickly detects and guides saccades/attention to salient visual scene locations, the latter segments object boundaries in the scene. PMID:25204770

Erythrocyte membrane fatty acids in multiple myeloma patients.

PubMed

Jurczyszyn, Artur; Czepiel, Jacek; Gdula-Argasińska, Joanna; Czapkiewicz, Anna; Biesiada, Grażyna; Dróżdż, Mirosław; Perucki, William; Castillo, Jorge J

2014-10-01

Mounting data show that fatty acids (FA) and fatty acid synthase (FAS) function could be potential targets for multiple myeloma (MM) therapy. Our study aimed at comparing the FA composition of erythrocyte membranes of MM patients and healthy controls. MM patients had higher saturated FA and n-6 polyunsaturated FA (PUFA) and lower monounsaturated, n-3 PUFA and trans-FA indices than controls. The n-3/n-6 PUFA ratio was lower in MM patients and there was distinct clustering of variants of individual FA in MM patients. The FA content of erythrocyte membrane could serve as a diagnostic and/or predictive biomarker in MM. Copyright © 2014. Published by Elsevier Ltd.

Serving Bowl Selection Biases the Amount of Food Served

ERIC Educational Resources Information Center

van Kleef, Ellen; Shimizu, Mitsuru; Wansink, Brian

2012-01-01

Objective: To determine how common serving bowls containing food for multiple persons influence serving behavior and consumption and whether they do so independently of satiation and food evaluation. Methods: In this between-subjects experiment, 68 participants were randomly assigned to either a group serving pasta from a large-sized bowl (6.9-L…

Adaptable Transponder for Multiple Telemetry Systems

NASA Technical Reports Server (NTRS)

Sims, William Herbert, III (Inventor); Varnavas, Kosta A. (Inventor)

2014-01-01

The present invention is a stackable telemetry circuit board for use in telemetry systems for satellites and other purposes. The present invention incorporates previously-qualified interchangeable circuit boards, or "decks," that perform functions such as power, signal receiving and transmission, and processing. Each deck is adapted to serve a range of telemetry applications. This provides flexibility in the construction of the stackable telemetry circuit board and significantly reduces the cost and time necessary to develop a telemetry system.

The effects of moclobemide on autonomic and cognitive functions in healthy volunteers.

PubMed

Siepmann, M; Handel, J; Mueck-Weymann, M; Kirch, W

2004-03-01

Moclobemide, a reversible and selective inhibitor of the MAO-A isoenzyme, is marketed as an antidepressant that lacks autonomic and cognitive side effects. However, only few and inconclusive quantitative data on the effects of moclobemide on autonomic and cognitive functions have been reported in the literature. Therefore, a double-blind, randomized, placebo-controlled crossover trial was performed. Twelve healthy male volunteers (age 22-29 years) received orally 150 mg moclobemide b.i.d. and placebo for 14 days each. Heart rate variability (HRV) and skin conductance response (SCR) following sudden deep breath were employed as parameters for autonomic function. Quantitative EEG (qEEG) and psychometric tests served as parameters for cognitive function. Measurements were performed before the start of drug administration and repeatedly on the last treatment day. Parameters of HRV and SCR were not changed by multiple dosing with moclobemide (P > 0.05). Neither cognitive functions such as flicker fusion frequency, memory, choice reaction time, and psychomotor performance nor qEEG was significantly influenced, but subjective tiredness was decreased at all time points of measurement after multiple dosing with moclobemide (P < 0.05). In conclusion, moclobemide does not appear to influence autonomic functions or cognitive functions when given subchronically to healthy humans. In contrast, changes in subjective mood hint at a subtle activating effect.

Neuropsychological Functioning in Preterm-Born Twins and Singletons at Preschool Age.

PubMed

Raz, Sarah; Piercy, Jamie C; Heitzer, Andrew M; Peters, Brittany N; Newman, Julie Bapp; DeBastos, Angela K; Ofen, Noa; Batton, Beau; Batton, Daniel G

2016-10-01

A limited body of research is available on the relationships between multiplicity of birth and neuropsychological functioning in preterm children who were conceived in the age of assisted reproductive technology and served by the modern neonatal intensive care unit. Our chief objective was to evaluate whether, after adjustment for sociodemographic factors and perinatal complications, twin birth accounted for a unique portion of developmental outcome variance in children born at-risk in the surfactant era. We compared the neuropsychological functioning of 77 twins and 144 singletons born preterm (<34 gestational weeks) and served by William Beaumont Hospital, Royal Oak, MI. Children were evaluated at preschool age, using standardized tests of memory, language, perceptual, and motor abilities. Multiple regression analyses, adjusting for sociodemographic and perinatal variables, revealed no differences on memory or motor indices between preterm twins and their singleton counterparts. In contrast, performance of language and visual processing tasks was significantly lower in twins despite reduced perinatal risk in comparison to singletons. Effect sizes ranged from .33 to .38 standard deviations for global language and visual processing ability indices, respectively. No significant group by sex interactions were observed, and comparison of first-, or second-born twins with singletons yielded medium effect sizes (Cohen's d=.56 and .40, respectively). The modest twin disadvantage on language and visual processing tasks at preschool-age could not be readily attributable to socioeconomic or perinatal variables. The possibility of biological or social twinning-related phenomena as mechanisms underlying the observed performance gaps are discussed. (JINS, 2016, 22, 865-877).

The Calibration Target for the Mars 2020 SHERLOC Instrument: Multiple Science Roles for Future Manned and Unmanned Mars Exploration

NASA Technical Reports Server (NTRS)

Fries, M.; Bhartia, R.; Beegle, L.; Burton, A.; Ross, A.; Shahar, A.

2014-01-01

The Scanning Habitable Environments with Raman & Luminescence for Organics & Chemicals (SHERLOC) instrument is a deep ultraviolet (UV) Raman/fluorescence instrument selected as part of the Mars 2020 rover instrument suite. SHERLOC will be mounted on the rover arm and its primary role is to identify carbonaceous species in martian samples, which may be selected for inclusion into a returnable sample cache. The SHERLOC instrument will require the use of a calibration target, and by design, multiple science roles will be addressed in the design of the target. Samples of materials used in NASA Extravehicular Mobility unit (EMU, or "space suit") manufacture have been included in the target to serve as both solid polymer calibration targets for SHERLOC instrument function, as well as for testing the resiliency of those materials under martian ambient conditions. A martian meteorite will also be included in the target to serve as a well-characterized example of a martian rock that contains trace carbonaceous material. This rock will be the first rock that we know of that has completed a round trip between planets and will therefore serve an EPO role to attract public attention to science and planetary exploration. The SHERLOC calibration target will address a wide range of NASA goals to include basic science of interest to both the Science Mission Directorate (SMD) and Human Exploration and Operations Mission Directorate (HEOMD).

Systems Level Analyses Reveal Multiple Regulatory Activities of CodY Controlling Metabolism, Motility and Virulence in Listeria monocytogenes

PubMed Central

Lobel, Lior; Herskovits, Anat A.

2016-01-01

Bacteria sense and respond to many environmental cues, rewiring their regulatory network to facilitate adaptation to new conditions/niches. Global transcription factors that co-regulate multiple pathways simultaneously are essential to this regulatory rewiring. CodY is one such global regulator, controlling expression of both metabolic and virulence genes in Gram-positive bacteria. Branch chained amino acids (BCAAs) serve as a ligand for CodY and modulate its activity. Classically, CodY was considered to function primarily as a repressor under rich growth conditions. However, our previous studies of the bacterial pathogen Listeria monocytogenes revealed that CodY is active also when the bacteria are starved for BCAAs. Under these conditions, CodY loses the ability to repress genes (e.g., metabolic genes) and functions as a direct activator of the master virulence regulator gene, prfA. This observation raised the possibility that CodY possesses multiple functions that allow it to coordinate gene expression across a wide spectrum of metabolic growth conditions, and thus better adapt bacteria to the mammalian niche. To gain a deeper understanding of CodY’s regulatory repertoire and identify direct target genes, we performed a genome wide analysis of the CodY regulon and DNA binding under both rich and minimal growth conditions, using RNA-Seq and ChIP-Seq techniques. We demonstrate here that CodY is indeed active (i.e., binds DNA) under both conditions, serving as a repressor and activator of different genes. Further, we identified new genes and pathways that are directly regulated by CodY (e.g., sigB, arg, his, actA, glpF, gadG, gdhA, poxB, glnR and fla genes), integrating metabolism, stress responses, motility and virulence in L. monocytogenes. This study establishes CodY as a multifaceted factor regulating L. monocytogenes physiology in a highly versatile manner. PMID:26895237

Randomized controlled pilot study of customized pamphlets to promote physical activity and symptom self-management in women with multiple sclerosis.

PubMed

Plow, Matthew; Bethoux, Francois; McDaniel, Corey; McGlynn, Mark; Marcus, Bess

2014-02-01

Investigate the feasibility and potential efficacy of a customized print-based intervention to promote physical activity and symptom self-management in women with multiple sclerosis. A randomly allocated two-group repeated measures design, with a delayed-treatment contact group serving as the control. Participants were randomized to receive the intervention immediately (n =14) or receive it at week 12 (n =16). Outcome measures were administered at weeks 1, 12, and 24. Community-based in metropolitan area. Thirty women with multiple sclerosis. Prescribing a home-exercise program and following up with customized pamphlets, which are matched to participants' stage of readiness to change physical activity behavior and physical activity barriers (e.g. encouraging self-management of symptoms). Physical Activity and Disability Survey-revised, Godin Leisure-Time Exercise Questionnaire, SF-12, Symptoms of Multiple Sclerosis Scale, and 6-minute walk test. Intent-to-treat analyses using mixed multivariate analysis of variance (MANOVA) were conducted on (1) physical activity levels and (2) health and function outcomes. The mixed MANOVAs for physical activity levels and health and function outcomes indicated significant improvements in the immediate group compared with the delayed group (i.e. condition by time interaction was significant, Wilks' λ = 0.59, F(2, 27) = 9.31, P = 0.001 and Wilks' λ = 0.70, F(4, 25) = 2.72, P = 0.052, respectively). The intervention had moderate to large effect sizes in improving physical activity levels (d = 0.63 to 0.89), perceptions of physical function (d = 0.63), and 6-minute walk test (d=0.86). This pilot study indicates that a customized print-based intervention shows promise in improving physical activity levels and health and function in women with multiple sclerosis.

Cognitive and academic functioning of juvenile detainees: implications for correctional populations and public health.

PubMed

Lansing, Amy E; Washburn, Jason J; Abram, Karen M; Thomas, Ursula C; Welty, Leah J; Teplin, Linda A

2014-01-01

Cognitive functioning affects health. This study assessed cognitive functioning among participants in the Northwestern Juvenile Project, a stratified random sample of 1,829 newly detained juveniles (10 to 18 years old) from Cook County, Illinois. The study examined receptive vocabulary, oral reading, arithmetic computation skills, and general intellectual abilities. The sample exhibited impaired overall intellectual functioning and deficits in all areas. Males performed more poorly than females. More than three quarters of males showed below average overall intellectual functioning, and 9 in 10 had below average receptive vocabulary skills. Hispanic and African American males performed more poorly than non-Hispanic White males. The multiple systems that serve delinquent youth--correctional, health, legal, and rehabilitative--must collaborate to tailor needed services to the cognitive level of youth in the juvenile justice system.

Cognitive and academic functioning of juvenile detainees: Implications for correctional populations and public health

PubMed Central

Lansing, Amy E.; Washburn, Jason J.; Abram, Karen M.; Thomas, Ursula C.; Welty, Leah J.; Teplin, Linda A.

2014-01-01

Cognitive functioning affects health. This study assessed cognitive functioning among participants in the Northwestern Juvenile Project, a stratified random sample of 1,829 newly detained juveniles (10-18 years old) from Cook County, Illinois. We examined receptive vocabulary, oral reading, arithmetic computation skills, and general intellectual abilities. Our sample exhibited impaired overall intellectual functioning and deficits in all areas. Males performed more poorly than females overall. More than three-quarters of males showed below average overall intellectual functioning, and nine in ten males had below average receptive vocabulary skills. Hispanic and African American males performed more poorly than non-Hispanic white males; The multiple systems that serve delinquent youth—correctional, health, legal, and rehabilitative—must collaborate to tailor needed services to the cognitive level of youth in the juvenile justice system. PMID:24352405

Reduced Abd-B Hox function during kidney development results in lineage infidelity.

PubMed

Magella, Bliss; Mahoney, Robert; Adam, Mike; Potter, S Steven

2018-06-15

Hox genes can function as key drivers of segment identity, with Hox mutations in Drosophila often resulting in dramatic homeotic transformations. In addition, however, they can serve other essential functions. In mammals, the study of Hox gene roles in development is complicated by the presence of four Hox clusters with a total of 39 genes showing extensive functional overlap. In this study, in order to better understand shared core Hox functions, we examined kidney development in mice with frameshift mutations of multiple Abd-B type Hox genes. The resulting phenotypes included dramatically reduced branching morphogenesis of the ureteric bud, premature depletion of nephron progenitors and abnormal development of the stromal compartment. Most unexpected, however, we also observed a cellular level lineage infidelity in nephron segments. Scattered cells within the proximal tubules, for example, expressed genes normally expressed only in collecting ducts. Multiple combinations of inappropriate nephron segment specific marker expression were found. In some cases, cells within a tubule showed incorrect identity, while in other cases cells showed ambiguous character, with simultaneous expression of genes associated with more than one nephron segment. These results give evidence that Hox genes have an overlapping core function at the cellular level in driving and/or maintaining correct differentiation decisions. Copyright © 2018 Elsevier Inc. All rights reserved.

GP96 is a GARP chaperone and controls regulatory T cell functions.

PubMed

Zhang, Yongliang; Wu, Bill X; Metelli, Alessandra; Thaxton, Jessica E; Hong, Feng; Rachidi, Saleh; Ansa-Addo, Ephraim; Sun, Shaoli; Vasu, Chenthamarakshan; Yang, Yi; Liu, Bei; Li, Zihai

2015-02-01

Molecular chaperones control a multitude of cellular functions via folding chaperone-specific client proteins. CD4+FOXP3+ Tregs play key roles in maintaining peripheral tolerance, which is subject to regulation by multiple molecular switches, including mTOR and hypoxia-inducible factor. It is not clear whether GP96 (also known as GRP94), which is a master TLR and integrin chaperone, controls Treg function. Using murine genetic models, we demonstrated that GP96 is required for Treg maintenance and function, as loss of GP96 resulted in instability of the Treg lineage and impairment of suppressive functions in vivo. In the absence of GP96, Tregs were unable to maintain FOXP3 expression levels, resulting in systemic accumulation of pathogenic IFN-γ-producing and IL-17-producing T cells. We determined that GP96 serves as an essential chaperone for the cell-surface protein glycoprotein A repetitions predominant (GARP), which is a docking receptor for latent membrane-associated TGF-β (mLTGF-β). The loss of both GARP and integrins on GP96-deficient Tregs prevented expression of mLTGF-β and resulted in inefficient production of active TGF-β. Our work demonstrates that GP96 regulates multiple facets of Treg biology, thereby placing Treg stability and immunosuppressive functions strategically under the control of a major stress chaperone.

The standardization of terminology of lower urinary tract function in children and adolescents: Update report from the standardization committee of the International Children's Continence Society.

PubMed

Austin, Paul F; Bauer, Stuart B; Bower, Wendy; Chase, Janet; Franco, Israel; Hoebeke, Piet; Rittig, Søren; Walle, Johan Vande; von Gontard, Alexander; Wright, Anne; Yang, Stephen S; Nevéus, Tryggve

2016-04-01

The impact of the original International Children's Continence Society (ICCS) terminology document on lower urinary tract (LUT) function resulted in the global establishment of uniformity and clarity in the characterization of LUT function and dysfunction in children across multiple healthcare disciplines. The present document serves as a stand-alone terminology update reflecting refinement and current advancement of knowledge on pediatric LUT function. A variety of worldwide experts from multiple disciplines within the ICCS leadership who care for children with LUT dysfunction were assembled as part of the standardization committee. A critical review of the previous ICCS terminology document and the current literature was performed. Additionally, contributions and feedback from the multidisciplinary ICCS membership were solicited. Following a review of the literature over the last 7 years, the ICCS experts assembled a new terminology document reflecting current understanding of bladder function and LUT dysfunction in children using the resources from the literature review, expert opinion and ICCS member feedback. The present ICCS terminology document provides a current and consensus update to the evolving terminology and understanding of LUT function in children. Neurourol. Urodynam. 35:471-481, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

The Mechanism of Restricting the Legal Status of Individuals Convicted of Multiple Offences

ERIC Educational Resources Information Center

Korotkikh, Natalya N.

2016-01-01

The subject of the article is the legal status of individuals serving custodial sentences. Special emphasis is laid on the legal status of individuals serving sentences for multiple offences. The soviet state directed substantial public resources to maintenance of basic human conditions in prisons. Now the Russian Federation, which embarked on a…

Neurocognitive accounts of developmental dyscalculia and its remediation.

PubMed

Iuculano, T

2016-01-01

Numbers are one of the most pervasive stimulus categories in our environment and an integral foundation of modern society. Yet, up to 20% of individuals fail to understand, represent, and manipulate numbers and form the basis of arithmetic, a condition termed developmental dyscalculia (DD). Multiple cognitive and neural systems including those that serve numerical, mnemonic, visuospatial, and cognitive control functions have independently been implicated in the etiology of DD, yet most studies have not taken a comprehensive or dynamic view of the disorder. This chapter supports the view of DD as a multifaceted neurodevelopmental disorder that is the result of multiple aberrancies at one or multiple levels of the information processing hierarchy, which supports successful arithmetic learning, and suggests that interventions should target all these systems to achieve successful outcomes, at the behavioral and neural levels. © 2016 Elsevier B.V. All rights reserved.

Low Dose Radiation Cancer Risks: Epidemiological and Toxicological Models

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

David G. Hoel, PhD

2012-04-19

The basic purpose of this one year research grant was to extend the two stage clonal expansion model (TSCE) of carcinogenesis to exposures other than the usual single acute exposure. The two-stage clonal expansion model of carcinogenesis incorporates the biological process of carcinogenesis, which involves two mutations and the clonal proliferation of the intermediate cells, in a stochastic, mathematical way. The current TSCE model serves a general purpose of acute exposure models but requires numerical computation of both the survival and hazard functions. The primary objective of this research project was to develop the analytical expressions for the survival functionmore » and the hazard function of the occurrence of the first cancer cell for acute, continuous and multiple exposure cases within the framework of the piece-wise constant parameter two-stage clonal expansion model of carcinogenesis. For acute exposure and multiple exposures of acute series, it is either only allowed to have the first mutation rate vary with the dose, or to have all the parameters be dose dependent; for multiple exposures of continuous exposures, all the parameters are allowed to vary with the dose. With these analytical functions, it becomes easy to evaluate the risks of cancer and allows one to deal with the various exposure patterns in cancer risk assessment. A second objective was to apply the TSCE model with varing continuous exposures from the cancer studies of inhaled plutonium in beagle dogs. Using step functions to estimate the retention functions of the pulmonary exposure of plutonium the multiple exposure versions of the TSCE model was to be used to estimate the beagle dog lung cancer risks. The mathematical equations of the multiple exposure versions of the TSCE model were developed. A draft manuscript which is attached provides the results of this mathematical work. The application work using the beagle dog data from plutonium exposure has not been completed due to the fact that the research project did not continue beyond its first year.« less

Sweet Taste Receptor Signaling Network: Possible Implication for Cognitive Functioning

PubMed Central

Welcome, Menizibeya O.; Mastorakis, Nikos E.; Pereverzev, Vladimir A.

2015-01-01

Sweet taste receptors are transmembrane protein network specialized in the transmission of information from special “sweet” molecules into the intracellular domain. These receptors can sense the taste of a range of molecules and transmit the information downstream to several acceptors, modulate cell specific functions and metabolism, and mediate cell-to-cell coupling through paracrine mechanism. Recent reports indicate that sweet taste receptors are widely distributed in the body and serves specific function relative to their localization. Due to their pleiotropic signaling properties and multisubstrate ligand affinity, sweet taste receptors are able to cooperatively bind multiple substances and mediate signaling by other receptors. Based on increasing evidence about the role of these receptors in the initiation and control of absorption and metabolism, and the pivotal role of metabolic (glucose) regulation in the central nervous system functioning, we propose a possible implication of sweet taste receptor signaling in modulating cognitive functioning. PMID:25653876

Functional Analysis of HIV/AIDS Stigma: Consensus or Divergence?

ERIC Educational Resources Information Center

Hosseinzadeh, Hassan; Hossain, Syeda Zakia

2011-01-01

Functional theory proposes that attitudes may serve a variety of purposes for individuals. This study aimed to determine whether stigmatized attitudes toward HIV/AIDS serve the same function for all (consensus function) or serve different functions for different individuals (divergence function) by assessing various aspects of HIV/AIDS stigma…

ArcGIS Framework for Scientific Data Analysis and Serving

NASA Astrophysics Data System (ADS)

Xu, H.; Ju, W.; Zhang, J.

2015-12-01

ArcGIS is a platform for managing, visualizing, analyzing, and serving geospatial data. Scientific data as part of the geospatial data features multiple dimensions (X, Y, time, and depth) and large volume. Multidimensional mosaic dataset (MDMD), a newly enhanced data model in ArcGIS, models the multidimensional gridded data (e.g. raster or image) as a hypercube and enables ArcGIS's capabilities to handle the large volume and near-real time scientific data. Built on top of geodatabase, the MDMD stores the dimension values and the variables (2D arrays) in a geodatabase table which allows accessing a slice or slices of the hypercube through a simple query and supports animating changes along time or vertical dimension using ArcGIS desktop or web clients. Through raster types, MDMD can manage not only netCDF, GRIB, and HDF formats but also many other formats or satellite data. It is scalable and can handle large data volume. The parallel geo-processing engine makes the data ingestion fast and easily. Raster function, definition of a raster processing algorithm, is a very important component in ArcGIS platform for on-demand raster processing and analysis. The scientific data analytics is achieved through the MDMD and raster function templates which perform on-demand scientific computation with variables ingested in the MDMD. For example, aggregating monthly average from daily data; computing total rainfall of a year; calculating heat index for forecasting data, and identifying fishing habitat zones etc. Addtionally, MDMD with the associated raster function templates can be served through ArcGIS server as image services which provide a framework for on-demand server side computation and analysis, and the published services can be accessed by multiple clients such as ArcMap, ArcGIS Online, JavaScript, REST, WCS, and WMS. This presentation will focus on the MDMD model and raster processing templates. In addtion, MODIS land cover, NDFD weather service, and HYCOM ocean model will be used to illustrate how ArcGIS platform and MDMD model can facilitate scientific data visualization and analytics and how the analysis results can be shared to more audience through ArcGIS Online and Portal.

Many-to-one form-to-function mapping weakens parallel morphological evolution.

PubMed

Thompson, Cole J; Ahmed, Newaz I; Veen, Thor; Peichel, Catherine L; Hendry, Andrew P; Bolnick, Daniel I; Stuart, Yoel E

2017-11-01

Evolutionary ecologists aim to explain and predict evolutionary change under different selective regimes. Theory suggests that such evolutionary prediction should be more difficult for biomechanical systems in which different trait combinations generate the same functional output: "many-to-one mapping." Many-to-one mapping of phenotype to function enables multiple morphological solutions to meet the same adaptive challenges. Therefore, many-to-one mapping should undermine parallel morphological evolution, and hence evolutionary predictability, even when selection pressures are shared among populations. Studying 16 replicate pairs of lake- and stream-adapted threespine stickleback (Gasterosteus aculeatus), we quantified three parts of the teleost feeding apparatus and used biomechanical models to calculate their expected functional outputs. The three feeding structures differed in their form-to-function relationship from one-to-one (lower jaw lever ratio) to increasingly many-to-one (buccal suction index, opercular 4-bar linkage). We tested for (1) weaker linear correlations between phenotype and calculated function, and (2) less parallel evolution across lake-stream pairs, in the many-to-one systems relative to the one-to-one system. We confirm both predictions, thus supporting the theoretical expectation that increasing many-to-one mapping undermines parallel evolution. Therefore, sole consideration of morphological variation within and among populations might not serve as a proxy for functional variation when multiple adaptive trait combinations exist. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

Genetic testing for hereditary cancer predisposition: BRCA1/2, Lynch syndrome, and beyond

PubMed Central

Hall, MJ; Obeid, EI; Schwartz, SC; Mantia-Smaldone, G; Forman, AD; Daly, MB

2016-01-01

Obstetrician/gynecologists and gynecologic oncologists serve an integral role in the care of women at increased hereditary risk of cancer. Their contribution includes initial identification of high risk patients, screening procedures like bimanual exam, trans-vaginal ultrasound and endometrial biopsy, prophylaxis via TAH and/or BSO, and chemoprevention. Further, gynecologists also serve a central role in the management of the secondary repercussions of efforts to mitigate increased cancer risks, including vasomotor symptoms, sexual function, bone health, cardiovascular disease, and mental health. The past several years has seen multiple new high and moderate penetrance genes introduced into the clinical care of women at increased risk of gynecologic malignancy. Awareness of these new genes and the availability of new multigene panel tests is critical for providers on the front-line of women’s health. PMID:26812021

Optimizing health system response to patient's needs: an argument for the importance of functioning information.

PubMed

Hopfe, Maren; Prodinger, Birgit; Bickenbach, Jerome E; Stucki, Gerold

2017-06-06

Current health systems are increasingly challenged to meet the needs of a growing number of patients living with chronic and often multiple health conditions. The primary outcome of care, it is argued, is not merely curing disease but also optimizing functioning over a person's life span. According to the World Health Organization, functioning can serve as foundation for a comprehensive picture of health and augment the biomedical perspective with a broader and more comprehensive picture of health as it plays out in people's lives. The crucial importance of information about patient's functioning for a well-performing health system, however, has yet to be sufficiently appreciated. This paper argues that functioning information is fundamental in all components of health systems and enhances the capacity of health systems to optimize patients' health and health-related needs. Beyond making sense of biomedical disease patterns, health systems can profit from using functioning information to improve interprofessional collaboration and achieve cross-cutting disease treatment outcomes. Implications for rehabilitation Functioning is a key health outcome for rehabilitation within health systems. Information on restoring, maintaining, and optimizing human functioning can strengthen health system response to patients' health and rehabilitative needs. Functioning information guides health systems to achieve cross-cutting health outcomes that respond to the needs of the growing number of individuals living with chronic and multiple health conditions. Accounting for individuals functioning helps to overcome fragmentation of care and to improve interprofessional collaboration across settings.

Establishing books as conditioned reinforcers for preschool children as a function of an observational intervention.

PubMed

Singer-Dudek, Jessica; Oblak, Mara; Greer, R Douglas

2011-01-01

We tested the effects of an observational intervention (Greer & Singer-Dudek, 2008) on establishing children's books as conditioned reinforcers using a delayed multiple baseline design. Three preschool students with mild language and developmental delays served as the participants. Prior to the intervention, books did not function as reinforcers for any of the participants. The observational intervention consisted of a situation in which the participant observed a confederate being presented with access to books contingent on correct responses and the participant received nothing for correct responses. After several sessions of this treatment, the previously neutral books acquired reinforcing properties for maintenance and acquisition responses for all three participants.

ESTABLISHING BOOKS AS CONDITIONED REINFORCERS FOR PRESCHOOL CHILDREN AS A FUNCTION OF AN OBSERVATIONAL INTERVENTION

PubMed Central

Singer-Dudek, Jessica; Oblak, Mara; Greer, R. Douglas

2011-01-01

We tested the effects of an observational intervention (Greer & Singer-Dudek, 2008) on establishing children's books as conditioned reinforcers using a delayed multiple baseline design. Three preschool students with mild language and developmental delays served as the participants. Prior to the intervention, books did not function as reinforcers for any of the participants. The observational intervention consisted of a situation in which the participant observed a confederate being presented with access to books contingent on correct responses and the participant received nothing for correct responses. After several sessions of this treatment, the previously neutral books acquired reinforcing properties for maintenance and acquisition responses for all three participants. PMID:21941376

The ‘when’ parietal pathway explored by lesion studies

PubMed Central

Battelli, Lorella; Walsh, Vincent; Pascual-Leone, Alvaro; Cavanagh, Patrick

2016-01-01

Summary The perception of events in space and time is at the root of our interactions with the environment. The precision with which we perceive visual events in time enables us to act upon objects with great accuracy and the loss of such functions, due to brain lesions can be catastrophic. We outline a visual timing mechanism that deals with the trajectory of an object’s existence across time, a critical function when keeping track of multiple objects that temporally overlap or occur sequentially. Recent evidence suggests these functions are served by an extended network of areas which we call the ‘when’ pathway. Here we show that the when pathway is distinct from and interacts with, the well established ‘where’ and ‘what’ pathways. PMID:18708141

The Popeye Domain Containing Genes and Their Function in Striated Muscle

PubMed Central

Schindler, Roland F. R.; Scotton, Chiara; French, Vanessa; Ferlini, Alessandra; Brand, Thomas

2016-01-01

The Popeye domain containing (POPDC) genes encode a novel class of cAMP effector proteins, which are abundantly expressed in heart and skeletal muscle. Here, we will review their role in striated muscle as deduced from work in cell and animal models and the recent analysis of patients carrying a missense mutation in POPDC1. Evidence suggests that POPDC proteins control membrane trafficking of interacting proteins. Furthermore, we will discuss the current catalogue of established protein-protein interactions. In recent years, the number of POPDC-interacting proteins has been rising and currently includes ion channels (TREK-1), sarcolemma-associated proteins serving functions in mechanical stability (dystrophin), compartmentalization (caveolin 3), scaffolding (ZO-1), trafficking (NDRG4, VAMP2/3) and repair (dysferlin) or acting as a guanine nucleotide exchange factor for Rho-family GTPases (GEFT). Recent evidence suggests that POPDC proteins might also control the cellular level of the nuclear proto-oncoprotein c-Myc. These data suggest that this family of cAMP-binding proteins probably serves multiple roles in striated muscle. PMID:27347491

Palladium-Catalyzed Asymmetric Allylic Alkylation of 3-Substituted 1 H-Indoles and Tryptophan Derivatives with Vinylcyclopropanes.

PubMed

Trost, Barry M; Bai, Wen-Ju; Hohn, Christoph; Bai, Yu; Cregg, James J

2018-05-30

Vinylcyclopropanes (VCPs) are known to generate 1,3-dipoles with a palladium catalyst that initially serve as nucleophiles to undergo [3 + 2] cycloadditions with electron-deficient olefins. In this report, we reverse this reactivity and drive the 1,3-dipoles to serve as electrophiles by employing 3-alkylated indoles as nucleophiles. This represents the first use of VCPs for the completely atom-economic functionalization of 3-substituted 1 H-indoles and tryptophan derivatives via a Pd-catalyzed asymmetric allylic alkylation (Pd-AAA). Excellent yields and high chemo-, regio-, and enantioselectivities have been realized, providing various indolenine and indoline products. The method is amenable to gram scale and works efficiently with tryptophan derivatives that contain a diketopiperazine or diketomorpholine ring, allowing us to synthesize mollenine A in a rapid and ligand-controlled fashion. The obtained indolenine products bear an imine, an internal olefin, and a malonate motif, giving multiple sites with diverse reactivities for product diversification. Complicated polycyclic skeletons can be conveniently constructed by leveraging this unique juxtaposition of functional groups.

The Function to Serve: A Social-Justice-Oriented Investigation of Community College Mission Statements

ERIC Educational Resources Information Center

Andrade, Luis M.; Lundberg, Carol A.

2018-01-01

This study investigated the ways that mission statements from 70 Hispanic-serving community colleges communicated their commitment to their Hispanic-serving function. Reference specifically to the Hispanic-serving function was absent, but references to culture and access were relatively common. Findings describe the ways culture and access were…

Architecture and Functionality of the Advanced Life Support On-Line Project Information System (OPIS)

NASA Technical Reports Server (NTRS)

Hogan, John A.; Levri, Julie A.; Morrow, Rich; Cavazzoni, Jim; Rodriquez, Luis F.; Riano, Rebecca; Whitaker, Dawn R.

2004-01-01

An ongoing effort is underway at NASA Amcs Research Center (ARC) tu develop an On-line Project Information System (OPIS) for the Advanced Life Support (ALS) Program. The objective of this three-year project is to develop, test, revise and deploy OPIS to enhance the quality of decision-making metrics and attainment of Program goals through improved knowledge sharing. OPIS will centrally locate detailed project information solicited from investigators on an annual basis and make it readily accessible by the ALS Community via a web-accessible interface. The data will be stored in an object-oriented relational database (created in MySQL(Trademark) located on a secure server at NASA ARC. OPE will simultaneously serve several functions, including being an R&TD status information hub that can potentially serve as the primary annual reporting mechanism. Using OPIS, ALS managers and element leads will be able to carry out informed research and technology development investment decisions, and allow analysts to perform accurate systems evaluations. Additionally, the range and specificity of information solicited will serve to educate technology developers of programmatic needs. OPIS will collect comprehensive information from all ALS projects as well as highly detailed information specific to technology development in each ALS area (Waste, Water, Air, Biomass, Food, Thermal, and Control). Because the scope of needed information can vary dramatically between areas, element-specific technology information is being compiled with the aid of multiple specialized working groups. This paper presents the current development status in terms of the architecture and functionality of OPIS. Possible implementation approaches for OPIS are also discussed.

The standardization of terminology of lower urinary tract function in children and adolescents: update report from the Standardization Committee of the International Children's Continence Society.

PubMed

Austin, Paul F; Bauer, Stuart B; Bower, Wendy; Chase, Janet; Franco, Israel; Hoebeke, Piet; Rittig, Søren; Vande Walle, Johan; von Gontard, Alexander; Wright, Anne; Yang, Stephen S; Nevéus, Tryggve

2014-06-01

The impact of the original International Children's Continence Society terminology document on lower urinary tract function resulted in the global establishment of uniformity and clarity in the characterization of lower urinary tract function and dysfunction in children across multiple health care disciplines. The present document serves as a stand-alone terminology update reflecting refinement and current advancement of knowledge on pediatric lower urinary tract function. A variety of worldwide experts from multiple disciplines in the ICCS leadership who care for children with lower urinary tract dysfunction were assembled as part of the standardization committee. A critical review of the previous ICCS terminology document and the current literature was performed. In addition, contributions and feedback from the multidisciplinary ICCS membership were solicited. Following a review of the literature during the last 7 years the ICCS experts assembled a new terminology document reflecting the current understanding of bladder function and lower urinary tract dysfunction in children using resources from the literature review, expert opinion and ICCS member feedback. The present ICCS terminology document provides a current and consensus update to the evolving terminology and understanding of lower urinary tract function in children. For the complete document visit http://jurology.com/. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Integration of functional myotubes with a Bio-MEMS device for non-invasive interrogation.

PubMed

Wilson, Kerry; Molnar, Peter; Hickman, James

2007-07-01

We have developed a biological micro-electromechanical system (Bio-MEMS) device consisting of surface-modified microfabricated silicon cantilevers and an AFM detection apparatus for the study of cultured myotubes. With this system we are able to selectively stimulate the myotubes as well as report on a variety of physiological properties of the myotubes in real time and in a high-throughput manner. This system will serve as the foundation for future work integrating multiple tissue types for the creation of Bio-MEMS analogues of complex tissues and biological circuits.

Like a slippery fish, a little slime is a good thing: the glycocalyx revealed.

PubMed

Biddle, Chuck

2013-12-01

The glycocalyx is a dynamic network of multiple membrane-bound complexes lining the vascular endothelium. Its role in maintaining vascular homeostasis includes regulating vascular permeability as well as a range of vital functions, such as mechanotransduction, hemostasis, modulation of inflammatory processes, and serving as an antiatherogenic. Revisionist thinking about the Starling principle is discussed in terms of the major influence of the glycocalyx on capillary and tissue fluid homeostasis. The clinical and pathophysiologic threats to the glycocalyx are reviewed as well as strategies to maintain its integrity.

Design and Implementation of the PALM-3000 Real-Time Control System

NASA Technical Reports Server (NTRS)

Truong, Tuan N.; Bouchez, Antonin H.; Burruss, Rick S.; Dekany, Richard G.; Guiwits, Stephen R.; Roberts, Jennifer E.; Shelton, Jean C.; Troy, Mitchell

2012-01-01

This paper reflects, from a computational perspective, on the experience gathered in designing and implementing realtime control of the PALM-3000 adaptive optics system currently in operation at the Palomar Observatory. We review the algorithms that serve as functional requirements driving the architecture developed, and describe key design issues and solutions that contributed to the system's low compute-latency. Additionally, we describe an implementation of dense matrix-vector-multiplication for wavefront reconstruction that exceeds 95% of the maximum sustained achievable bandwidth on NVIDIA Geforce 8800GTX GPU.

Metabolism and function of phenazines in bacteria: impacts on the behavior of bacteria in the environment and biotechnological processes

PubMed Central

Pierson, Elizabeth A.

2010-01-01

Phenazines constitute a large group of nitrogen-containing heterocyclic compounds produced by a diverse range of bacteria. Both natural and synthetic phenazine derivatives are studied due their impacts on bacterial interactions and biotechnological processes. Phenazines serve as electron shuttles to alternate terminal acceptors, modify cellular redox states, act as cell signals that regulate patterns of gene expression, contribute to biofilm formation and architecture, and enhance bacterial survival. Phenazines have diverse effects on eukaryotic hosts and host tissues, including the modification of multiple host cellular responses. In plants, phenazines also may influence growth and elicit induced systemic resistance. Here, we discuss emerging evidence that phenazines play multiple roles for the producing organism and contribute to their behavior and ecological fitness. PMID:20352425

Post Pareto optimization-A case

NASA Astrophysics Data System (ADS)

Popov, Stoyan; Baeva, Silvia; Marinova, Daniela

2017-12-01

Simulation performance may be evaluated according to multiple quality measures that are in competition and their simultaneous consideration poses a conflict. In the current study we propose a practical framework for investigating such simulation performance criteria, exploring the inherent conflicts amongst them and identifying the best available tradeoffs, based upon multi-objective Pareto optimization. This approach necessitates the rigorous derivation of performance criteria to serve as objective functions and undergo vector optimization. We demonstrate the effectiveness of our proposed approach by applying it with multiple stochastic quality measures. We formulate performance criteria of this use-case, pose an optimization problem, and solve it by means of a simulation-based Pareto approach. Upon attainment of the underlying Pareto Frontier, we analyze it and prescribe preference-dependent configurations for the optimal simulation training.

Optimal design of compact and connected nature reserves for multiple species.

PubMed

Wang, Yicheng; Önal, Hayri

2016-04-01

When designing a conservation reserve system for multiple species, spatial attributes of the reserves must be taken into account at species level. The existing optimal reserve design literature considers either one spatial attribute or when multiple attributes are considered the analysis is restricted only to one species. We built a linear integer programing model that incorporates compactness and connectivity of the landscape reserved for multiple species. The model identifies multiple reserves that each serve a subset of target species with a specified coverage probability threshold to ensure the species' long-term survival in the reserve, and each target species is covered (protected) with another probability threshold at the reserve system level. We modeled compactness by minimizing the total distance between selected sites and central sites, and we modeled connectivity of a selected site to its designated central site by selecting at least one of its adjacent sites that has a nearer distance to the central site. We considered structural distance and functional distances that incorporated site quality between sites. We tested the model using randomly generated data on 2 species, one ground species that required structural connectivity and the other an avian species that required functional connectivity. We applied the model to 10 bird species listed as endangered by the state of Illinois (U.S.A.). Spatial coherence and selection cost of the reserves differed substantially depending on the weights assigned to these 2 criteria. The model can be used to design a reserve system for multiple species, especially species whose habitats are far apart in which case multiple disjunct but compact and connected reserves are advantageous. The model can be modified to increase or decrease the distance between reserves to reduce or promote population connectivity. © 2015 Society for Conservation Biology.

Functional roles of flavonoids in photoprotection: new evidence, lessons from the past.

PubMed

Agati, Giovanni; Brunetti, Cecilia; Di Ferdinando, Martina; Ferrini, Francesco; Pollastri, Susanna; Tattini, Massimiliano

2013-11-01

We discuss on the relative significance of different functional roles potentially served by flavonoids in photoprotection, with special emphasis to their ability to scavenge reactive oxygen species (ROS) and control the development of individual organs and whole plant. We propose a model in which chloroplast-located flavonoids scavenge H2O2 and singlet oxygen generated under excess light-stress, thus avoiding programmed cell death. We also draw a picture in which vacuolar flavonoids in conjunction with peroxidases and ascorbic acid constitute a secondary antioxidant system aimed at detoxifying H2O2, which may diffuse out of the chloroplast at considerable rates and enter the vacuole following excess light stress-induced depletion of ascorbate peroxidase. We hypothesize for flavonols key roles as developmental regulators in early and current-day land-plants, based on their ability to modulate auxin movement and auxin catabolism. We show that antioxidant flavonoids display the greatest capacity to regulate key steps of cell growth and differentiation in eukaryotes. These regulatory functions of flavonoids, which are shared by plants and animals, are fully accomplished in the nM concentration range, as likely occurred in early land plants. We therefore conclude that functions of flavonoids as antioxidants and/or developmental regulators flavonoids are of great value in photoprotection. We also suggest that UV-B screening was just one of the multiple functions served by flavonoids when early land-plants faced an abrupt increase in sunlight irradiance. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Genetic testing for hereditary cancer predisposition: BRCA1/2, Lynch syndrome, and beyond.

PubMed

Hall, M J; Obeid, E I; Schwartz, S C; Mantia-Smaldone, G; Forman, A D; Daly, M B

2016-03-01

Obstetrician/gynecologists and gynecologic oncologists serve an integral role in the care of women at increased hereditary risk of cancer. Their contribution includes initial identification of high risk patients, screening procedures like bimanual exam, trans-vaginal ultrasound and endometrial biopsy, prophylaxis via TAH and/or BSO, and chemoprevention. Further, gynecologists also serve a central role in the management of the secondary repercussions of efforts to mitigate increased cancer risks, including vasomotor symptoms, sexual function, bone health, cardiovascular disease, and mental health. The past several years has seen multiple new high and moderate penetrance genes introduced into the clinical care of women at increased risk of gynecologic malignancy. Awareness of these new genes and the availability of new multi-gene panel tests is critical for providers on the front-line of women's health. Copyright © 2016 Elsevier Inc. All rights reserved.

CD22 serves as a receptor for soluble IgM.

PubMed

Adachi, Takahiro; Harumiya, Satoru; Takematsu, Hiromu; Kozutsumi, Yasunori; Wabl, Matthias; Fujimoto, Manabu; Tedder, Thomas F

2012-01-01

CD22 (Siglec-2) is a B-cell membrane-bound lectin that recognizes glycan ligands containing α2,6-linked sialic acid (α2,6Sia) and negatively regulates signaling through the B-cell Ag receptor (BCR). Although CD22 has been investigated extensively, its precise function remains unclear due to acting multiple phases. Here, we demonstrate that CD22 is efficiently activated in trans by complexes of Ag and soluble IgM (sIgM) due to the presence of glycan ligands on sIgM. This result strongly suggests sIgM as a natural trans ligand for CD22. Also, CD22 appears to serve as a receptor for sIgM, which induces a negative feedback loop for B-cell activation similar to the Fc receptor for IgG (FcγRIIB). Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Emergent properties of interacting populations of spiking neurons.

PubMed

Cardanobile, Stefano; Rotter, Stefan

2011-01-01

Dynamic neuronal networks are a key paradigm of increasing importance in brain research, concerned with the functional analysis of biological neuronal networks and, at the same time, with the synthesis of artificial brain-like systems. In this context, neuronal network models serve as mathematical tools to understand the function of brains, but they might as well develop into future tools for enhancing certain functions of our nervous system. Here, we present and discuss our recent achievements in developing multiplicative point processes into a viable mathematical framework for spiking network modeling. The perspective is that the dynamic behavior of these neuronal networks is faithfully reflected by a set of non-linear rate equations, describing all interactions on the population level. These equations are similar in structure to Lotka-Volterra equations, well known by their use in modeling predator-prey relations in population biology, but abundant applications to economic theory have also been described. We present a number of biologically relevant examples for spiking network function, which can be studied with the help of the aforementioned correspondence between spike trains and specific systems of non-linear coupled ordinary differential equations. We claim that, enabled by the use of multiplicative point processes, we can make essential contributions to a more thorough understanding of the dynamical properties of interacting neuronal populations.

Performance characteristics of a batch service queueing system with functioning server failure and multiple vacations

NASA Astrophysics Data System (ADS)

Niranjan, S. P.; Chandrasekaran, V. M.; Indhira, K.

2018-04-01

This paper examines bulk arrival and batch service queueing system with functioning server failure and multiple vacations. Customers are arriving into the system in bulk according to Poisson process with rate λ. Arriving customers are served in batches with minimum of ‘a’ and maximum of ‘b’ number of customers according to general bulk service rule. In the service completion epoch if the queue length is less than ‘a’ then the server leaves for vacation (secondary job) of random length. After a vacation completion, if the queue length is still less than ‘a’ then the server leaves for another vacation. The server keeps on going vacation until the queue length reaches the value ‘a’. The server is not stable at all the times. Sometimes it may fails during functioning of customers. Though the server fails service process will not be interrupted.It will be continued for the current batch of customers with lower service rate than the regular service rate. The server will be repaired after the service completion with lower service rate. The probability generating function of the queue size at an arbitrary time epoch will be obtained for the modelled queueing system by using supplementary variable technique. Moreover various performance characteristics will also be derived with suitable numerical illustrations.

Emergent Properties of Interacting Populations of Spiking Neurons

PubMed Central

Cardanobile, Stefano; Rotter, Stefan

2011-01-01

Dynamic neuronal networks are a key paradigm of increasing importance in brain research, concerned with the functional analysis of biological neuronal networks and, at the same time, with the synthesis of artificial brain-like systems. In this context, neuronal network models serve as mathematical tools to understand the function of brains, but they might as well develop into future tools for enhancing certain functions of our nervous system. Here, we present and discuss our recent achievements in developing multiplicative point processes into a viable mathematical framework for spiking network modeling. The perspective is that the dynamic behavior of these neuronal networks is faithfully reflected by a set of non-linear rate equations, describing all interactions on the population level. These equations are similar in structure to Lotka-Volterra equations, well known by their use in modeling predator-prey relations in population biology, but abundant applications to economic theory have also been described. We present a number of biologically relevant examples for spiking network function, which can be studied with the help of the aforementioned correspondence between spike trains and specific systems of non-linear coupled ordinary differential equations. We claim that, enabled by the use of multiplicative point processes, we can make essential contributions to a more thorough understanding of the dynamical properties of interacting neuronal populations. PMID:22207844

Multiscale Mechanics of Articular Cartilage: Potentials and Challenges of Coupling Musculoskeletal, Joint, and Microscale Computational Models

PubMed Central

Halloran, J. P.; Sibole, S.; van Donkelaar, C. C.; van Turnhout, M. C.; Oomens, C. W. J.; Weiss, J. A.; Guilak, F.; Erdemir, A.

2012-01-01

Articular cartilage experiences significant mechanical loads during daily activities. Healthy cartilage provides the capacity for load bearing and regulates the mechanobiological processes for tissue development, maintenance, and repair. Experimental studies at multiple scales have provided a fundamental understanding of macroscopic mechanical function, evaluation of the micromechanical environment of chondrocytes, and the foundations for mechanobiological response. In addition, computational models of cartilage have offered a concise description of experimental data at many spatial levels under healthy and diseased conditions, and have served to generate hypotheses for the mechanical and biological function. Further, modeling and simulation provides a platform for predictive risk assessment, management of dysfunction, as well as a means to relate multiple spatial scales. Simulation-based investigation of cartilage comes with many challenges including both the computational burden and often insufficient availability of data for model development and validation. This review outlines recent modeling and simulation approaches to understand cartilage function from a mechanical systems perspective, and illustrates pathways to associate mechanics with biological function. Computational representations at single scales are provided from the body down to the microstructure, along with attempts to explore multiscale mechanisms of load sharing that dictate the mechanical environment of the cartilage and chondrocytes. PMID:22648577

Expression of CD44 3'-untranslated region regulates endogenous microRNA functions in tumorigenesis and angiogenesis.

PubMed

Jeyapalan, Zina; Deng, Zhaoqun; Shatseva, Tatiana; Fang, Ling; He, Chengyan; Yang, Burton B

2011-04-01

The non-coding 3'-untranslated region (UTR) plays an important role in the regulation of microRNA (miRNA) functions, since it can bind and inactivate multiple miRNAs. Here, we show the 3'-UTR of CD44 is able to antagonize cytoplasmic miRNAs, and result in the increased translation of CD44 and downstream target mRNA, CDC42. A series of cell function assays in the human breast cancer cell line, MT-1, have shown that the CD44 3'-UTR inhibits proliferation, colony formation and tumor growth. Furthermore, it modulated endothelial cell activities, favored angiogenesis, induced tumor cell apoptosis and increased sensitivity to Docetaxel. These results are due to the interaction of the CD44 3'-UTR with multiple miRNAs. Computational algorithms have predicted three miRNAs, miR-216a, miR-330 and miR-608, can bind to both the CD44 and CDC42 3'-UTRs. This was confirmed with luciferase assays, western blotting and immunohistochemical staining and correlated with a series of siRNA assays. Thus, the non-coding CD44 3'-UTR serves as a competitor for miRNA binding and subsequently inactivates miRNA functions, by freeing the target mRNAs from being repressed.

Expression of CD44 3′-untranslated region regulates endogenous microRNA functions in tumorigenesis and angiogenesis

PubMed Central

Jeyapalan, Zina; Deng, Zhaoqun; Shatseva, Tatiana; Fang, Ling; He, Chengyan; Yang, Burton B.

2011-01-01

The non-coding 3′-untranslated region (UTR) plays an important role in the regulation of microRNA (miRNA) functions, since it can bind and inactivate multiple miRNAs. Here, we show the 3′-UTR of CD44 is able to antagonize cytoplasmic miRNAs, and result in the increased translation of CD44 and downstream target mRNA, CDC42. A series of cell function assays in the human breast cancer cell line, MT-1, have shown that the CD44 3′-UTR inhibits proliferation, colony formation and tumor growth. Furthermore, it modulated endothelial cell activities, favored angiogenesis, induced tumor cell apoptosis and increased sensitivity to Docetaxel. These results are due to the interaction of the CD44 3′-UTR with multiple miRNAs. Computational algorithms have predicted three miRNAs, miR-216a, miR-330 and miR-608, can bind to both the CD44 and CDC42 3′-UTRs. This was confirmed with luciferase assays, western blotting and immunohistochemical staining and correlated with a series of siRNA assays. Thus, the non-coding CD44 3′-UTR serves as a competitor for miRNA binding and subsequently inactivates miRNA functions, by freeing the target mRNAs from being repressed. PMID:21149267

The study of non-fouling and non-specific cellular binding on functionalized surface for mammalian cell identification and manipulation

NASA Astrophysics Data System (ADS)

Zainudin, Nor Syuhada; Hambali, Nor Azura Malini Ahmad; Wahid, Mohamad Halim Abd; Retnasamy, Vithyacharan; Shahimin, Mukhzeer Mohamad

2017-04-01

Surface functionalization has emerged as a powerful tool for mapping limitless surface-cell membrane interaction in diverse biomolecular applications. Inhibition of non-specific biomolecular and cellular adhesion to solid surfaces is critical in improving the performance of some biomedical devices, particularly for in vitro bioassays. Some factors have to be paid particular attention in determining the right surface modification which are the types of surface, the methods and chemical solution that being used during the experimentation and also tools for analyzing the results. Improved surface functionalization technologies that provide better non-fouling performance in conjunction with specific attachment chemistries are sought for these applications. Hence, this paper serves as a review for multiple surface treatment methods including PEG grafting, adsorptive chemistries, self-assembled monolayers (SAMs) and plasma treatments.

Respiratory syncytial virus mechanisms to interfere with type 1 interferons.

PubMed

Barik, Sailen

2013-01-01

Respiratory syncytial virus (RSV) is a member of the Paramyxoviridae family that consists of viruses with nonsegmented negative-strand RNA genome. Infection by these viruses triggers the innate antiviral response of the host, mainly type I interferon (IFN). Essentially all other viruses of this family produce IFN suppressor functions by co-transcriptional RNA editing. In contrast, RSV has evolved two unique nonstructural proteins, NS1 and NS2, to effectively serve this purpose. Together, NS1 and NS2 degrade or sequester multiple signaling proteins that affect both IFN induction and IFN effector functions. While the mechanism of action of NS1 and NS2 is a subject of active research, their effect on adaptive immunity is also being recognized. In this review, we discuss various aspects of NS1 and NS2 function with implications for vaccine design.

Mediator complex dependent regulation of cardiac development and disease.

PubMed

Grueter, Chad E

2013-06-01

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality. The risk factors for CVD include environmental and genetic components. Human mutations in genes involved in most aspects of cardiovascular function have been identified, many of which are involved in transcriptional regulation. The Mediator complex serves as a pivotal transcriptional regulator that functions to integrate diverse cellular signals by multiple mechanisms including recruiting RNA polymerase II, chromatin modifying proteins and non-coding RNAs to promoters in a context dependent manner. This review discusses components of the Mediator complex and the contribution of the Mediator complex to normal and pathological cardiac development and function. Enhanced understanding of the role of this core transcriptional regulatory complex in the heart will help us gain further insights into CVD. Copyright © 2013. Production and hosting by Elsevier Ltd.

BLNK: molecular scaffolding through ‘cis’-mediated organization of signaling proteins

PubMed Central

Chiu, Christopher W.; Dalton, Mark; Ishiai, Masamichi; Kurosaki, Tomohiro; Chan, Andrew C.

2002-01-01

Assembly of intracellular macromolecular complexes is thought to provide an important mechanism to coordinate the generation of second messengers upon receptor activation. We have previously identified a B cell linker protein, termed BLNK, which serves such a scaffolding function in B cells. We demonstrate here that phosphorylation of five tyrosine residues within human BLNK nucleates distinct signaling effectors following B cell antigen receptor activation. The phosphorylation of multiple tyrosine residues not only amplifies PLCγ-mediated signaling but also supports ‘cis’-mediated interaction between distinct signaling effectors within a large molecular complex. These data demonstrate the importance of coordinate phosphorylation of molecular scaffolds, and provide insights into how assembly of macromolecular complexes is required for normal receptor function. PMID:12456653

An Inverse U-Shaped Curve of Resting-State Networks in Individuals at High Risk of Alzheimer's Disease.

PubMed

Ye, Qing; Chen, Haifeng; Su, Fan; Shu, Hao; Gong, Liang; Xie, Chunming; Zhou, Hong; Bai, Feng

Higher functional connectivity (FC) in resting-state networks has been shown in individuals at risk of Alzheimer's disease (AD) by many studies. However, the longitudinal trajectories of the FC remain unknown. The present 35-month follow-up study aimed to explore longitudinal changes in higher FC in multiple resting-state networks in subjects with the apolipoprotein E ε4 allele (ApoE4) and/or amnestic mild cognitive impairment (aMCI). Fifty-one subjects with aMCI and 64 cognitively normal (CN) subjects underwent neuropsychological tests and resting-state functional magnetic resonance imaging (fMRI) scans twice from April 2011 to June 2015. Subjects were divided into 4 groups according to diagnosis and ApoE4 status. The CN non-ApoE4 group served as a control group, and other groups served as AD risk groups. The cross-sectional and longitudinal patterns of multiple resting-state networks, including default mode network, hippocampus network, executive control network, and salience network, were explored by comparing FC data between groups and between time points, respectively. At baseline, compared with the control group, the AD risk groups showed higher FC with 8 regions in multiple networks. At follow-up, 6 of the regions displayed longitudinally decreased FC in AD risk groups. In contrast, the FC with all of these regions was maintained in the control group. Notably, among the 3 risk groups, most of the higher FC at baseline (5 of the 8 regions) and longitudinally decreased FC at follow-up (4 of the 6 regions) were shown in the aMCI ApoE4 group. Higher resting-state FC is followed by a decline in subjects at AD risk, and this inverse U-shaped trajectory is more notable in subjects with higher risk. © Copyright 2018 Physicians Postgraduate Press, Inc.

User's Guide and Download for IECCU- Indoor Environmental Concentrations in Buildings with Conditioned and Unconditioned Zones

EPA Pesticide Factsheets

This program serves two purposes: (1) as a general-purpose indoor exposure model in buildings with multiple zones, multiple chemicals and multiple sources and sinks, and (2) as a special-purpose concentration model

On-chip integration of suspended InGaN/GaN multiple-quantum-well devices with versatile functionalities.

PubMed

Cai, Wei; Yang, Yongchao; Gao, Xumin; Yuan, Jialei; Yuan, Wei; Zhu, Hongbo; Wang, Yongjin

2016-03-21

We propose, fabricate and demonstrate on-chip photonic integration of suspended InGaN/GaN multiple quantum wells (MQWs) devices on the GaN-on-silicon platform. Both silicon removal and back wafer etching are conducted to obtain membrane-type devices, and suspended waveguides are used for the connection between p-n junction InGaN/GaN MQWs devices. As an in-plane data transmission system, the middle p-n junction InGaN/GaN MQWs device is used as a light emitting diode (LED) to deliver signals by modulating the intensity of the emitted light, and the other two devices act as photodetectors (PDs) to sense the light guided by the suspended waveguide and convert the photons into electrons, achieving 1 × 2 in-plane information transmission via visible light. Correspondingly, the three devices can function as independent PDs to realize multiple receivers for free space visible light communication. Further, the on-chip photonic platform can be used as an active electro-optical sensing system when the middle device acts as a PD and the other two devices serve as LEDs. The experimental results show that the auxiliary LED sources can enhance the amplitude of the induced photocurrent.

Background music genre can modulate flavor pleasantness and overall impression of food stimuli.

PubMed

Fiegel, Alexandra; Meullenet, Jean-François; Harrington, Robert J; Humble, Rachel; Seo, Han-Seok

2014-05-01

This study aimed to determine whether background music genre can alter food perception and acceptance, but also to determine how the effect of background music can vary as a function of type of food (emotional versus non-emotional foods) and source of music performer (single versus multiple performers). The music piece was edited into four genres: classical, jazz, hip-hop, and rock, by either a single or multiple performers. Following consumption of emotional (milk chocolate) or non-emotional food (bell peppers) with the four musical stimuli, participants were asked to rate sensory perception and impression of food stimuli. Participants liked food stimuli significantly more while listening to the jazz stimulus than the hip-hop stimulus. Further, the influence of background music on overall impression was present in the emotional food, but not in the non-emotional food. In addition, flavor pleasantness and overall impression of food stimuli differed between music genres arranged by a single performer, but not between those by multiple performers. In conclusion, our findings demonstrate that music genre can alter flavor pleasantness and overall impression of food stimuli. Furthermore, the influence of music genre on food acceptance varies as a function of the type of served food and the source of music performer. Published by Elsevier Ltd.

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

PubMed Central

Roby, Justin A.; Pijlman, Gorben P.; Wilusz, Jeffrey; Khromykh, Alexander A.

2014-01-01

Flaviviruses are a large group of positive strand RNA viruses transmitted by arthropods that include many human pathogens such as West Nile virus (WNV), Japanese encephalitis virus (JEV), yellow fever virus, dengue virus, and tick-borne encephalitis virus. All members in this genus tested so far are shown to produce a unique subgenomic flavivirus RNA (sfRNA) derived from the 3' untranslated region (UTR). sfRNA is a product of incomplete degradation of genomic RNA by the cell 5'–3' exoribonuclease XRN1 which stalls at highly ordered secondary RNA structures at the beginning of the 3'UTR. Generation of sfRNA results in inhibition of XRN1 activity leading to an increase in stability of many cellular mRNAs. Mutant WNV deficient in sfRNA generation was highly attenuated displaying a marked decrease in cytopathicity in cells and pathogenicity in mice. sfRNA has also been shown to inhibit the antiviral activity of IFN-α/β by yet unknown mechanism and of the RNAi pathway by likely serving as a decoy substrate for Dicer. Thus, sfRNA is involved in modulating multiple cellular pathways to facilitate viral pathogenicity; however the overlying mechanism linking all these multiple functions of sfRNA remains to be elucidated. PMID:24473339

Ionizing Radiation Selectively Reduces Skin Regulatory T Cells and Alters Immune Function

PubMed Central

Zhou, Yu; Ni, Houping; Balint, Klara; Sanzari, Jenine K.; Dentchev, Tzvete; Diffenderfer, Eric S.; Wilson, Jolaine M.; Cengel, Keith A.; Weissman, Drew

2014-01-01

The skin serves multiple functions that are critical for life. The protection from pathogens is achieved by a complicated interaction between aggressive effectors and controlling functions that limit damage. Inhomogeneous radiation with limited penetration is used in certain types of therapeutics and is experienced with exposure to solar particle events outside the protection of the Earth’s magnetic field. This study explores the effect of ionizing radiation on skin immune function. We demonstrate that radiation, both homogeneous and inhomogeneous, induces inflammation with resultant specific loss of regulatory T cells from the skin. This results in a hyper-responsive state with increased delayed type hypersensitivity in vivo and CD4+ T cell proliferation in vitro. The effects of inhomogeneous radiation to the skin of astronauts or as part of a therapeutic approach could result in an unexpected enhancement in skin immune function. The effects of this need to be considered in the design of radiation therapy protocols and in the development of countermeasures for extended space travel. PMID:24959865

Unexpected high vulnerability of functions in wilderness areas: evidence from coral reef fishes.

PubMed

D'agata, Stéphanie; Vigliola, Laurent; Graham, Nicholas A J; Wantiez, Laurent; Parravicini, Valeriano; Villéger, Sébastien; Mou-Tham, Gerard; Frolla, Philippe; Friedlander, Alan M; Kulbicki, Michel; Mouillot, David

2016-12-14

High species richness is thought to support the delivery of multiple ecosystem functions and services under changing environments. Yet, some species might perform unique functional roles while others are redundant. Thus, the benefits of high species richness in maintaining ecosystem functioning are uncertain if functions have little redundancy, potentially leading to high vulnerability of functions. We studied the natural propensity of assemblages to be functionally buffered against loss prior to fishing activities, using functional trait combinations, in coral reef fish assemblages across unfished wilderness areas of the Indo-Pacific: Chagos Archipelago, New Caledonia and French Polynesia. Fish functional diversity in these wilderness areas is highly vulnerable to fishing, explained by species- and abundance-based redundancy packed into a small combination of traits, leaving most other trait combinations (60%) sensitive to fishing, with no redundancy. Functional vulnerability peaks for mobile and sedentary top predators, and large species in general. Functional vulnerability decreases for certain functional entities in New Caledonia, where overall functional redundancy was higher. Uncovering these baseline patterns of functional vulnerability can offer early warning signals of the damaging effects from fishing, and may serve as baselines to guide precautionary and even proactive conservation actions. © 2016 The Author(s).

Unexpected high vulnerability of functions in wilderness areas: evidence from coral reef fishes

PubMed Central

Vigliola, Laurent; Graham, Nicholas A. J.; Wantiez, Laurent; Parravicini, Valeriano; Villéger, Sébastien; Mou-Tham, Gerard; Frolla, Philippe; Friedlander, Alan M.; Kulbicki, Michel; Mouillot, David

2016-01-01

High species richness is thought to support the delivery of multiple ecosystem functions and services under changing environments. Yet, some species might perform unique functional roles while others are redundant. Thus, the benefits of high species richness in maintaining ecosystem functioning are uncertain if functions have little redundancy, potentially leading to high vulnerability of functions. We studied the natural propensity of assemblages to be functionally buffered against loss prior to fishing activities, using functional trait combinations, in coral reef fish assemblages across unfished wilderness areas of the Indo-Pacific: Chagos Archipelago, New Caledonia and French Polynesia. Fish functional diversity in these wilderness areas is highly vulnerable to fishing, explained by species- and abundance-based redundancy packed into a small combination of traits, leaving most other trait combinations (60%) sensitive to fishing, with no redundancy. Functional vulnerability peaks for mobile and sedentary top predators, and large species in general. Functional vulnerability decreases for certain functional entities in New Caledonia, where overall functional redundancy was higher. Uncovering these baseline patterns of functional vulnerability can offer early warning signals of the damaging effects from fishing, and may serve as baselines to guide precautionary and even proactive conservation actions. PMID:27928042

Architecture and Functionality of the Advanced Life Support On-Line Project Information System

NASA Technical Reports Server (NTRS)

Hogan, John A.; Levri, Julie A.; Morrow, Rich; Cavazzoni, Jim; Rodriguez, Luis F.; Riano, Rebecca; Whitaker, Dawn R.

2004-01-01

An ongoing effort is underway at NASA Ames Research Center (ARC) to develop an On-line Project Information System (OPIS) for the Advanced Life Support (ALS) Program. The objective of this three-year project is to develop, test, revise and deploy OPIS to enhance the quality of decision-making metrics and attainment of Program goals through improved knowledge sharing. OPIS will centrally locate detailed project information solicited from investigators on an annual basis and make it readily accessible by the ALS Community via a Web-accessible interface. The data will be stored in an object-oriented relational database (created in MySQL) located on a secure server at NASA ARC. OPE will simultaneously serve several functions, including being an research and technology development (R&TD) status information hub that can potentially serve as the primary annual reporting mechanism for ALS-funded projects. Using OPIS, ALS managers and element leads will be able to carry out informed R&TD investment decisions, and allow analysts to perform accurate systems evaluations. Additionally, the range and specificity of information solicited will serve to educate technology developers of programmatic needs. OPIS will collect comprehensive information from all ALS projects as well as highly detailed information specific to technology development in each ALS area (Waste, Water, Air, Biomass, Food, Thermal, Controls and Systems Analysis). Because the scope of needed information can vary dramatically between areas, element-specific technology information is being compiled with the aid of multiple specialized working groups. This paper presents the current development status in terms of the architecture and functionality of OPIS. Possible implementation approaches for OPIS are also discussed.

Topographic heterogeneity influences fish use of an experimentally restored tidal marsh.

PubMed

Larkin, Daniel J; Madon, Sharook P; West, Janelle M; Zedler, Joy B

2008-03-01

Ecological theory predicts that incorporating habitat heterogeneity into restoration sites should enhance diversity and key functions, yet research is limited on how topographic heterogeneity affects higher trophic levels. Our large (8-ha) southern California restoration experiment tested effects of tidal creek networks and pools on trophic structure of salt marsh habitat and high-tide use by two regionally dominant fish species, California killifish (Fundulus parvipinnis) and longjaw mudsucker (Gillichthys mirabilis). We expected tidal creeks to function as "conduits" that would enhance connectivity between subtidal and intertidal habitat and pools to serve as microhabitat "oases" for fishes. Pools did provide abundant invertebrate prey and were a preferred microhabitat for F. parvipinnis, even when the entire marsh was inundated (catch rates were 61% higher in pools). However, G. mirabilis showed no preference for pools. At a larger scale, effects of tidal creek networks were also mixed. Areas containing creeks had 12% higher catch rates of G. mirabilis, but lower catch rates and feeding rates of F. parvipinnis. Collectively, the results indicate that restoring multiple forms of heterogeneity is required to provide opportunities for multiple target consumers.

The MiRNA Journey from Theory to Practice as a CNS Biomarker.

PubMed

Stoicea, Nicoleta; Du, Amy; Lakis, D Christie; Tipton, Courtney; Arias-Morales, Carlos E; Bergese, Sergio D

2016-01-01

MicroRNAs (miRNAs), small nucleotide sequences that control gene transcription, have the potential to serve an expanded function as indicators in the diagnosis and progression of neurological disorders. Studies involving debilitating neurological diseases such as, Alzheimer's disease, multiple sclerosis, traumatic brain injuries, Parkinson's disease and CNS tumors, already provide validation for their clinical diagnostic use. These small nucleotide sequences have several features, making them favorable candidates as biomarkers, including function in multiple tissues, stability in bodily fluids, a role in pathogenesis, and the ability to be detected early in the disease course. Cerebrospinal fluid, with its cell-free environment, collection process that minimizes tissue damage, and direct contact with the brain and spinal cord, is a promising source of miRNA in the diagnosis of many neurological disorders. Despite the advantages of miRNA analysis, current analytic technology is not yet affordable as a clinically viable diagnostic tool and requires standardization. The goal of this review is to explore the prospective use of CSF miRNA as a reliable and affordable biomarker for different neurological disorders.

The MiRNA Journey from Theory to Practice as a CNS Biomarker

PubMed Central

Stoicea, Nicoleta; Du, Amy; Lakis, D. Christie; Tipton, Courtney; Arias-Morales, Carlos E.; Bergese, Sergio D.

2016-01-01

MicroRNAs (miRNAs), small nucleotide sequences that control gene transcription, have the potential to serve an expanded function as indicators in the diagnosis and progression of neurological disorders. Studies involving debilitating neurological diseases such as, Alzheimer's disease, multiple sclerosis, traumatic brain injuries, Parkinson's disease and CNS tumors, already provide validation for their clinical diagnostic use. These small nucleotide sequences have several features, making them favorable candidates as biomarkers, including function in multiple tissues, stability in bodily fluids, a role in pathogenesis, and the ability to be detected early in the disease course. Cerebrospinal fluid, with its cell-free environment, collection process that minimizes tissue damage, and direct contact with the brain and spinal cord, is a promising source of miRNA in the diagnosis of many neurological disorders. Despite the advantages of miRNA analysis, current analytic technology is not yet affordable as a clinically viable diagnostic tool and requires standardization. The goal of this review is to explore the prospective use of CSF miRNA as a reliable and affordable biomarker for different neurological disorders. PMID:26904099

Positive neuropsychology: The science and practice of promoting cognitive health.

PubMed

Randolph, John J

2018-01-01

Positive psychology has influenced multiple subfields within psychology and areas outside of psychology. While positive psychology's focus on positive mental health and character strengths did not appear to meaningfully impact neuropsychology in its earlier stages, more recent indications suggest that the neuropsychological literature, and perhaps the field as a whole, has begun to embrace related research and practice applications. In this context, positive neuropsychology has emerged as a neuropsychological orientation focused on the study and practice of promoting cognitive health. The present review discusses the origins of positive neuropsychology and elaborates on its six key evidence-based domains: compensatory strategy use, activity engagement, prevention of cognitive impairment, public education, exceptional cognition, and positive cognitive outcomes in neuropsychiatric populations. This broad perspective on cognitive wellness can easily be embraced by both clinicians and researchers and offers multiple directions for future growth. Ultimately, consideration of various methods to promote cognitive health can inform our understanding of optimal brain function, maximize functioning in individuals with cognitive limitations, and enhance quality of life among populations served by neuropsychologists.

MEMS applications in space exploration

NASA Astrophysics Data System (ADS)

Tang, William C.

1997-09-01

Space exploration in the coming century will emphasize cost effectiveness and highly focused mission objectives, which will result in frequent multiple missions that broaden the scope of space science and to validate new technologies on a timely basis. MEMS is one of the key enabling technology to create cost-effective, ultra-miniaturized, robust, and functionally focused spacecraft for both robotic and human exploration programs. Examples of MEMS devices at various stages of development include microgyroscope, microseismometer, microhygrometer, quadrupole mass spectrometer, and micropropulsion engine. These devices, when proven successful, will serve as models for developing components and systems for new-millennium spacecraft.

Applications of MEMS for Space Exploration

NASA Astrophysics Data System (ADS)

Tang, William C.

1998-03-01

Space exploration in the coming century will emphasize cost effectiveness and highly focused mission objectives, which will result in frequent multiple missions that broaden the scope of space science and to validate new technologies on a timely basis. Micro Electro Mechanical Systems (MEMS) is one of the key enabling technologies to create cost-effective, ultra-miniaturized, robust, and functionally focused spacecraft for both robotic and human exploration programs. Examples of MEMS devices at various stages of development include microgyroscope, microseismometer, microhygrometer, quadrupole mass spectrometer, and micropropulsion engine. These devices, when proven successful, will serve as models for developing components and systems for new-millennium spacecraft.

Functional properties of behaviour problems depending on level of intellectual disability.

PubMed

Medeiros, K; Rojahn, J; Moore, L L; van Ingen, D J

2014-02-01

Behaviour problems are common among individuals with intellectual disabilities (ID) especially in those with more severe forms. The determination of the functional profile of a targeted behaviour has important implications for the design of customised behavioural interventions. We investigated the relationship between the level of ID and the functional profile of aggression, stereotypy and self-injurious behaviour (SIB) using the Questions about Behavioural Function (QABF). Two staff members at two time points completed the QABF for each of 115 adults with varying levels of ID participating in a day training and habilitation programme. Our results suggest that there is a differential relationship between the functions of behaviour problems and level of ID. While SIB is more often seen by raters to be maintained by escape of social demands and by attaining access to tangible items with the decline of the intellectual level, aggressive and stereotypic behaviours were identified more often as serving multiple functions equally across functioning level. © 2013 The Authors. Journal of Intellectual Disability Research © 2013 John Wiley & Sons Ltd, MENCAP & IASSIDD.

Predicting the cumulative effect of multiple disturbances on seagrass connectivity.

PubMed

Grech, Alana; Hanert, Emmanuel; McKenzie, Len; Rasheed, Michael; Thomas, Christopher; Tol, Samantha; Wang, Mingzhu; Waycott, Michelle; Wolter, Jolan; Coles, Rob

2018-03-15

The rate of exchange, or connectivity, among populations effects their ability to recover after disturbance events. However, there is limited information on the extent to which populations are connected or how multiple disturbances affect connectivity, especially in coastal and marine ecosystems. We used network analysis and the outputs of a biophysical model to measure potential functional connectivity and predict the impact of multiple disturbances on seagrasses in the central Great Barrier Reef World Heritage Area (GBRWHA), Australia. The seagrass networks were densely connected, indicating that seagrasses are resilient to the random loss of meadows. Our analysis identified discrete meadows that are important sources of seagrass propagules and that serve as stepping stones connecting various different parts of the network. Several of these meadows were close to urban areas or ports and likely to be at risk from coastal development. Deep water meadows were highly connected to coastal meadows and may function as a refuge, but only for non-foundation species. We evaluated changes to the structure and functioning of the seagrass networks when one or more discrete meadows were removed due to multiple disturbance events. The scale of disturbance required to disconnect the seagrass networks into two or more components was on average >245 km, about half the length of the metapopulation. The densely connected seagrass meadows of the central GBRWHA are not limited by the supply of propagules; therefore, management should focus on improving environmental conditions that support natural seagrass recruitment and recovery processes. Our study provides a new framework for assessing the impact of global change on the connectivity and persistence of coastal and marine ecosystems. Without this knowledge, management actions, including coastal restoration, may prove unnecessary and be unsuccessful. © 2018 John Wiley & Sons Ltd.

The Cerefy Neuroradiology Atlas: a Talairach-Tournoux atlas-based tool for analysis of neuroimages available over the internet.

PubMed

Nowinski, Wieslaw L; Belov, Dmitry

2003-09-01

The article introduces an atlas-assisted method and a tool called the Cerefy Neuroradiology Atlas (CNA), available over the Internet for neuroradiology and human brain mapping. The CNA contains an enhanced, extended, and fully segmented and labeled electronic version of the Talairach-Tournoux brain atlas, including parcelated gyri and Brodmann's areas. To our best knowledge, this is the first online, publicly available application with the Talairach-Tournoux atlas. The process of atlas-assisted neuroimage analysis is done in five steps: image data loading, Talairach landmark setting, atlas normalization, image data exploration and analysis, and result saving. Neuroimage analysis is supported by a near-real-time, atlas-to-data warping based on the Talairach transformation. The CNA runs on multiple platforms; is able to process simultaneously multiple anatomical and functional data sets; and provides functions for a rapid atlas-to-data registration, interactive structure labeling and annotating, and mensuration. It is also empowered with several unique features, including interactive atlas warping facilitating fine tuning of atlas-to-data fit, navigation on the triplanar formed by the image data and the atlas, multiple-images-in-one display with interactive atlas-anatomy-function blending, multiple label display, and saving of labeled and annotated image data. The CNA is useful for fast atlas-assisted analysis of neuroimage data sets. It increases accuracy and reduces time in localization analysis of activation regions; facilitates to communicate the information on the interpreted scans from the neuroradiologist to other clinicians and medical students; increases the neuroradiologist's confidence in terms of anatomy and spatial relationships; and serves as a user-friendly, public domain tool for neuroeducation. At present, more than 700 users from five continents have subscribed to the CNA.

Structural and functional analysis of 5S rRNA in Saccharomyces cerevisiae

PubMed Central

Kiparisov, S.; Sergiev, P. V.; Dontsova, O. A.; Petrov, A.; Meskauskas, A.; Dinman, J. D.

2005-01-01

5S rRNA extends from the central protuberance of the large ribosomal subunit, through the A-site finger, and down to the GTPase-associated center. Here, we present a structure-function analysis of seven 5S rRNA alleles which are sufficient for viability in the yeast Saccharomyces cerevisiae when expressed in the absence of wild-type 5S rRNAs, and extend this analysis using a large bank of mutant alleles that show semidominant phenotypes in the presence of wild-type 5S rRNA. This analysis supports the hypothesis that 5S rRNA serves to link together several different functional centers of the ribosome. Data are also presented which suggest that in eukaryotic genomes selection has favored the maintenance of multiple alleles of 5S rRNA, and that these may provide cells with a mechanism to post-transcriptionally regulate gene expression. PMID:16047201

Neuronal Lipid Metabolism: Multiple Pathways Driving Functional Outcomes in Health and Disease

PubMed Central

Tracey, Timothy J.; Steyn, Frederik J.; Wolvetang, Ernst J.; Ngo, Shyuan T.

2018-01-01

Lipids are a fundamental class of organic molecules implicated in a wide range of biological processes related to their structural diversity, and based on this can be broadly classified into five categories; fatty acids, triacylglycerols (TAGs), phospholipids, sterol lipids and sphingolipids. Different lipid classes play major roles in neuronal cell populations; they can be used as energy substrates, act as building blocks for cellular structural machinery, serve as bioactive molecules, or a combination of each. In amyotrophic lateral sclerosis (ALS), dysfunctions in lipid metabolism and function have been identified as potential drivers of pathogenesis. In particular, aberrant lipid metabolism is proposed to underlie denervation of neuromuscular junctions, mitochondrial dysfunction, excitotoxicity, impaired neuronal transport, cytoskeletal defects, inflammation and reduced neurotransmitter release. Here we review current knowledge of the roles of lipid metabolism and function in the CNS and discuss how modulating these pathways may offer novel therapeutic options for treating ALS. PMID:29410613

Basic science for the clinician 53: mast cells.

PubMed

Sigal, Leonard H

2011-10-01

Mast cells stand at the interface between the innate immune system and the acquired (adaptive) immune response, serving as sentinels detecting invaders and directing a concerted and coordinated response. Mast cells reside immediately under body surfaces and within lymph nodes, near blood vessels and nerves, perfectly situated to for early detection and defense. They secrete a wide array of prostanoids, cytokines, chemokines, and other proteins mediators and modifiers of a variety of immune and inflammatory functions and bear surface markers suggesting broad functions, including as antigen-presenting cells. Although usually not given their due in medical school lectures, there is great likelihood that mast cells will be implicated in the pathogenesis of rheumatoid arthritis, scleroderma, multiple sclerosis, and perhaps cancer. Thus, better insights into mast cell functions and mast cell-derived effector molecules should command our attention as we move forward in better understanding disease immunopathogenesis and directed intelligent therapeutics development.

Thyroid C-Cell Biology and Oncogenic Transformation

PubMed Central

Cote, Gilbert J.; Grubbs, Elizabeth G.; Hofmann, Marie-Claude

2017-01-01

The thyroid parafollicular cell, or commonly named “C-cell,” functions in serum calcium homeostasis. Elevations in serum calcium trigger release of calcitonin from the C-cell, which in turn functions to inhibit absorption of calcium by the intestine, resorption of bone by the osteoclast, and reabsorption of calcium by renal tubular cells. Oncogenic transformation of the thyroid C-cell is thought to progress through a hyperplastic process prior to malignancy with increasing levels of serum calcitonin serving as a biomarker for tumor burden. The discovery that Multiple Endocrine Neoplasia, type 2 is caused by activating mutations of the RET gene serves to highlight the RET-RAS-MAPK signaling pathway in both initiation and progression of medullary thyroid carcinoma. Thyroid C-cells are known to express RET at high levels relative to most cell types, therefore aberrant activation of this receptor is targeted primarily to the C-cell, providing one possible cause of tissue-specific oncogenesis. The role of RET signaling in normal C-cell function is unknown though calcitonin gene transcription appears to be sensitive to RET activation. Beyond RET the modeling of oncogenesis in animals and screening of human tumors for candidate gene mutations has uncovered mutation of RAS family members and inactivation of Rb1 regulatory pathway as potential mediators of C-cell transformation. A growing understanding of how RET interacts with these pathways, both in normal C-cell function and during oncogenic transformation will help in the development of novel molecular targeted therapies. PMID:26494382

A Cellular Neural Networks Based DiffServ Switch for Satellite Communication Systems

NASA Astrophysics Data System (ADS)

Tarchi, Daniele; Fantacci, Romano; Gubellini, Roberto; Pecorella, Tommaso

2003-07-01

Recent developments of Internet services and advanced compression methods has revived interest on IP based multimedia satellite communication systems. However a main problem arising here is to guarantee specific Quality of Service (QoS) constraints in order to have good performance for each traffic class.Among various QoS approach used in Internet, recently the DiffServ technique has became the most promising so- lution, mainly for its simplicity with respect to different alternatives. Moreover, in satellite communication systems, DiffServ policy computational capabilities are placed at the edge points (end-to-end philosophy); this is very important for a network constituted by one satellite link because it allows to reduce the implementation complexity of the satellite on-board equipments.The satellite switch under consideration makes use of the Multiple Input Queuing approach. Packets arrived at a switch input are stored in a shared buffer but they are logically ordered in individual queues, one for each possible output link. According to the DiffServ policy, within a same logical queue, packets are reordered in individual sub-queues according to the priority. A suitable implementation of the DiffServ policy based on a Cellular Neural Network (CNN) is proposed in the paper in order to achieve QoS requirements.The CNNs are a set of linear and nonlinear circuits connected among them that allow parallel and asynchronous computation. CNNs are a class of neural networks similar to Hopfield Neural Networks (HNN), but more flexible and suitable for solving the output contention problem, inherent of switching systems, for VLSI implementation.In this paper a CNN has been designed in order to maximize a cost functional, related to the on-board switch through- put and QoS constraints. The initial state for each neural cell is obtained looking at the presence of at least one packet from a certain input logical queue to a specific output line. The input value for each neural cell is a function of priority and length of each input logical queue. The versatility of neural network make feasible to take the best decision for the packet to be delivered to each output satellite beam, in order to meet specific QoS constraints. Numerical results for CNN approach highlights that Neural network convergence within a time slot is guaranteed, and an optimal, or at least near-optimal, solution in terms of cost function is achieved.The proposed system is based on the IETF (Internet Engineering Task Force) recommendations; this means that traffic entering the switching fabric could be marked as Expedited Forward (EF) or Assured Forward (AF), otherwise handled as Best Effort (BE). Two Assured Forward classes with different emission priority have been implemented, taking into account time spent inside the logical queue and its length. Expedited Forward traffic is typical of services to be delivered with the maximum priority, as streaming or interactive services. The packets, belonging to services that need a certain level of priority with low packet loss, are marked as Assured Forward. Best Effort traffic is related to e-mail or file transfer, or other that have not particular QoS requirements. The CNN used to solve conflict situations act as an arbiter for all the output links. Differently from other Multiple Input Queuing approach, where one arbiter for each output line is present, in proposed approach there exist only one arbiter that make the best decision. The selected rule has been defined in order to give priority to packets, according to opportunely defined functionals characteristic of each traffic class, under the constraint that no more than one packet can be delivered to the same output line. The functionals depend on queue length and time spent inside the queue by front packet.The performance of the proposed DiffServ switch has been derived in terms of delay and jitter; buffer occupancy has been analyzed for different configuration, such as a unique common buffer, one buffer for each input line, one buffer for each input line and each priority class.The obtained results highlight an high flexibility of satellite switch with CNN, taking into account that functional used to calculate priority of each queue could be easily changed, without any complexity gain nor change in CNN structure, in order to consider different traffic characteristic. Numerical results show that proposed algorithm outperform the switches based on Multiple Input Queuing, that use strictly priority methods, in terms of delay and jitter. Different buffer size have been also considered in order to analyze packet loss for CNN switch algorithm, comparing different configuration described above.The good behavior of the proposed DiffServ switch has been verified in the case of traffic with pareto distribution for packet length and a geometrical distribution for packet interarrival time, highlighting good performance in terms of delay and jitter. Numerical results also demonstrate the stability of this method for heavy load traffic; in particular maximum permitted load is higher for higher priority classes.

Evaluation of the gastrointestinal tolerability of corn starch fiber, a novel dietary fiber, in two independent randomized, double-blind, crossover studies in healthy men and women.

PubMed

Crincoli, Christine M; Garcia-Campayo, Vicenta; Rihner, Marisa O; Nikiforov, Andrey I; Liska, DeAnn; van de Ligt, Jennifer L G

2016-11-01

Two independent clinical studies were conducted to compare the gastrointestinal (GI) tolerability of corn starch fiber, a novel dietary fiber, at up to 50 g/day (single-dose study) or 90 g/day (multiple-serving study) with a negative control (no fiber) and a positive control (50 or 90 g polydextrose, for single- and multiple-serving studies, respectively) in generally healthy study volunteers. Flatulence and borborygmus were the primary symptoms reported at the higher doses of corn starch fiber and for the positive control interventions. Bowel movements were increased over 48 h with corn starch fiber at 90 g. Thresholds for mild GI effects were established at 30 g as a single dose and 60 g as multiple servings spread over the day. Other than moderate abdominal pain and mild increased appetite in one subject at 90-g corn starch fiber, no test article-related adverse events were reported.

A Generic Multiple Reaction Monitoring Based Approach for Plant Flavonoids Profiling Using a Triple Quadrupole Linear Ion Trap Mass Spectrometry

NASA Astrophysics Data System (ADS)

Yan, Zhixiang; Lin, Ge; Ye, Yang; Wang, Yitao; Yan, Ru

2014-06-01

Flavonoids are one of the largest classes of plant secondary metabolites serving a variety of functions in plants and associating with a number of health benefits for humans. Typically, they are co-identified with many other secondary metabolites using untargeted metabolomics. The limited data quality of untargeted workflow calls for a shift from the breadth-first to the depth-first screening strategy when a specific biosynthetic pathway is focused on. Here we introduce a generic multiple reaction monitoring (MRM)-based approach for flavonoids profiling in plants using a hybrid triple quadrupole linear ion trap (QTrap) mass spectrometer. The approach includes four steps: (1) preliminary profiling of major aglycones by multiple ion monitoring triggered enhanced product ion scan (MIM-EPI); (2) glycones profiling by precursor ion triggered EPI scan (PI-EPI) of major aglycones; (3) comprehensive aglycones profiling by combining MIM-EPI and neutral loss triggered EPI scan (NL-EPI) of major glycone; (4) in-depth flavonoids profiling by MRM-EPI with elaborated MRM transitions. Particularly, incorporation of the NH3 loss and sugar elimination proved to be very informative and confirmative for flavonoids screening. This approach was applied for profiling flavonoids in Astragali radix ( Huangqi), a famous herb widely used for medicinal and nutritional purposes in China. In total, 421 flavonoids were tentatively characterized, among which less than 40 have been previously reported in this medicinal plant. This MRM-based approach provides versatility and sensitivity that required for flavonoids profiling in plants and serves as a useful tool for plant metabolomics.

Genetic architecture of the circadian clock and flowering time in Brassica rapa.

PubMed

Lou, P; Xie, Q; Xu, X; Edwards, C E; Brock, M T; Weinig, C; McClung, C R

2011-08-01

The circadian clock serves to coordinate physiology and behavior with the diurnal cycles derived from the daily rotation of the earth. In plants, circadian rhythms contribute to growth and yield and, hence, to both agricultural productivity and evolutionary fitness. Arabidopsis thaliana has served as a tractable model species in which to dissect clock mechanism and function, but it now becomes important to define the extent to which the Arabidopsis model can be extrapolated to other species, including crops. Accordingly, we have extended our studies to the close Arabidopsis relative and crop species, Brassica rapa. We have investigated natural variation in circadian function and flowering time among multiple B. rapa collections. There is wide variation in clock function, based on a robust rhythm in cotyledon movement, within a collection of B. rapa accessions, wild populations and recombinant inbred lines (RILs) derived from a cross between parents from two distinct subspecies, a rapid cycling Chinese cabbage (ssp. pekinensis) and a Yellow Sarson oilseed (ssp. trilocularis). We further analyzed the RILs to identify the quantitative trait loci (QTL) responsible for this natural variation in clock period and temperature compensation, as well as for flowering time under different temperature and day length settings. Most clock and flowering-time QTL mapped to overlapping chromosomal loci. We have exploited micro-synteny between the Arabidopsis and B. rapa genomes to identify candidate genes for these QTL.

Long non-coding RNA H19 regulates viability and metastasis, and is upregulated in retinoblastoma.

PubMed

Li, Li; Chen, Wei; Wang, Yuchuan; Tang, Luosheng; Han, Mei

2018-06-01

Retinoblastoma is the most common type of intraocular pediatric malignant tumor, which typically affects children <6 years of age. However, the underlying molecular mechanisms of retinoblastoma progression remain unclear. The aim of the present study was to investigate the function of long non-coding RNA (lncRNA) H19 in retinoblastoma clinical samples and cell lines, using reverse transcription-quantitative polymerase chain reaction, western blotting, colony formation, MTT, fluorescence activated cell sorting, cell invasion and migration, and in vivo growth assays. The results demonstrated that H19 may serve a critical oncogenic function in the progression of retinoblastoma, as lncRNA H19 levels were markedly increased in retinoblastoma cells and tissues compared with corresponding controls. In addition, patients with retinoblastoma with increased lncRNA H19 expression experienced poorer survival time compared with those with decreased lncRNA H19 levels. Knockdown of lncRNA H19 significantly suppressed retinoblastoma cell proliferation, migration and invasion in vitro and in vivo . Furthermore, lncRNA H19 expression was also associated with multiple proteins, including cyclin-dependent kinase 1, B-cell lymphoma-associated X protein, apoptosis regulator, tumor protein p53, vimentin, cadherin 13 and matrix metallopeptidase 9. In conclusion, lncRNA H19 may serve an important function in tumorigenesis and may be a potential target for therapy and prognosis in retinoblastoma.

Examining the use of HIT functions among physicians serving minority populations.

PubMed

Tarver, Will; Menachemi, Nir

2014-02-01

The Institute of Medicine highlighted the fact that the U.S. health care system does not provide consistent, high quality medical care to all people. The routine use of health information technology (HIT) that includes certain key functions may be critical in reducing such disparities. We used logistic regression analyses to examine differences when it comes to the routine use of key HIT functions that are linked to improvements in clinical care. Physicians predominantly serving Black patients were more likely than physicians predominantly serving White patients to routinely use HIT to generate reminders for clinicians and patients about preventive services. Similarly, physicians predominantly serving Hispanic patients were more likely than physicians predominantly serving White patients to routinely use HIT to access patients' preferred language. Importantly, although minority-serving institutions have lower adoption rates overall, differences exist in the routine use of key HIT functions that have the potential to reduce health disparities.

The evolutionary landscape of intergenic trans-splicing events in insects

PubMed Central

Kong, Yimeng; Zhou, Hongxia; Yu, Yao; Chen, Longxian; Hao, Pei; Li, Xuan

2015-01-01

To explore the landscape of intergenic trans-splicing events and characterize their functions and evolutionary dynamics, we conduct a mega-data study of a phylogeny containing eight species across five orders of class Insecta, a model system spanning 400 million years of evolution. A total of 1,627 trans-splicing events involving 2,199 genes are identified, accounting for 1.58% of the total genes. Homology analysis reveals that mod(mdg4)-like trans-splicing is the only conserved event that is consistently observed in multiple species across two orders, which represents a unique case of functional diversification involving trans-splicing. Thus, evolutionarily its potential for generating proteins with novel function is not broadly utilized by insects. Furthermore, 146 non-mod trans-spliced transcripts are found to resemble canonical genes from different species. Trans-splicing preserving the function of ‘breakup' genes may serve as a general mechanism for relaxing the constraints on gene structure, with profound implications for the evolution of genes and genomes. PMID:26521696

Fermionic Approach to Weighted Hurwitz Numbers and Topological Recursion

NASA Astrophysics Data System (ADS)

Alexandrov, A.; Chapuy, G.; Eynard, B.; Harnad, J.

2017-12-01

A fermionic representation is given for all the quantities entering in the generating function approach to weighted Hurwitz numbers and topological recursion. This includes: KP and 2D Toda {τ} -functions of hypergeometric type, which serve as generating functions for weighted single and double Hurwitz numbers; the Baker function, which is expanded in an adapted basis obtained by applying the same dressing transformation to all vacuum basis elements; the multipair correlators and the multicurrent correlators. Multiplicative recursion relations and a linear differential system are deduced for the adapted bases and their duals, and a Christoffel-Darboux type formula is derived for the pair correlator. The quantum and classical spectral curves linking this theory with the topological recursion program are derived, as well as the generalized cut-and-join equations. The results are detailed for four special cases: the simple single and double Hurwitz numbers, the weakly monotone case, corresponding to signed enumeration of coverings, the strongly monotone case, corresponding to Belyi curves and the simplest version of quantum weighted Hurwitz numbers.

Fermionic Approach to Weighted Hurwitz Numbers and Topological Recursion

NASA Astrophysics Data System (ADS)

Alexandrov, A.; Chapuy, G.; Eynard, B.; Harnad, J.

2018-06-01

A fermionic representation is given for all the quantities entering in the generating function approach to weighted Hurwitz numbers and topological recursion. This includes: KP and 2 D Toda {τ} -functions of hypergeometric type, which serve as generating functions for weighted single and double Hurwitz numbers; the Baker function, which is expanded in an adapted basis obtained by applying the same dressing transformation to all vacuum basis elements; the multipair correlators and the multicurrent correlators. Multiplicative recursion relations and a linear differential system are deduced for the adapted bases and their duals, and a Christoffel-Darboux type formula is derived for the pair correlator. The quantum and classical spectral curves linking this theory with the topological recursion program are derived, as well as the generalized cut-and-join equations. The results are detailed for four special cases: the simple single and double Hurwitz numbers, the weakly monotone case, corresponding to signed enumeration of coverings, the strongly monotone case, corresponding to Belyi curves and the simplest version of quantum weighted Hurwitz numbers.

Multiple Disabilities: Is Rural Inclusion Possible?

ERIC Educational Resources Information Center

Cates, Dennis L.; Smiley, Frederick M.

This paper focuses on the difficulties faced by rural school districts in their efforts to serve children with severe multiple disabilities. Both historic and contemporary views on mainstreaming and inclusion of students with multiple disabilities are presented. Concerns of educators about the inclusion of such students center around the amount of…

Cortical travelling waves: mechanisms and computational principles

PubMed Central

Muller, Lyle; Chavane, Frédéric; Reynolds, John

2018-01-01

Multichannel recording technologies have revealed travelling waves of neural activity in multiple sensory, motor and cognitive systems. These waves can be spontaneously generated by recurrent circuits or evoked by external stimuli. They travel along brain networks at multiple scales, transiently modulating spiking and excitability as they pass. Here, we review recent experimental findings that have found evidence for travelling waves at single-area (mesoscopic) and whole-brain (macroscopic) scales. We place these findings in the context of the current theoretical understanding of wave generation and propagation in recurrent networks. During the large low-frequency rhythms of sleep or the relatively desynchronized state of the awake cortex, travelling waves may serve a variety of functions, from long-term memory consolidation to processing of dynamic visual stimuli. We explore new avenues for experimental and computational understanding of the role of spatiotemporal activity patterns in the cortex. PMID:29563572

Skin Rejuvenation with Non-Invasive Pulsed Electric Fields

NASA Astrophysics Data System (ADS)

Golberg, Alexander; Khan, Saiqa; Belov, Vasily; Quinn, Kyle P.; Albadawi, Hassan; Felix Broelsch, G.; Watkins, Michael T.; Georgakoudi, Irene; Papisov, Mikhail; Mihm, Martin C., Jr.; Austen, William G., Jr.; Yarmush, Martin L.

2015-05-01

Degenerative skin diseases affect one third of individuals over the age of sixty. Current therapies use various physical and chemical methods to rejuvenate skin; but since the therapies affect many tissue components including cells and extracellular matrix, they may also induce significant side effects, such as scarring. Here we report on a new, non-invasive, non-thermal technique to rejuvenate skin with pulsed electric fields. The fields destroy cells while simultaneously completely preserving the extracellular matrix architecture and releasing multiple growth factors locally that induce new cells and tissue growth. We have identified the specific pulsed electric field parameters in rats that lead to prominent proliferation of the epidermis, formation of microvasculature, and secretion of new collagen at treated areas without scarring. Our results suggest that pulsed electric fields can improve skin function and thus can potentially serve as a novel non-invasive skin therapy for multiple degenerative skin diseases.

Cascading Effects of BPT for Child Internalizing Problems and Caregiver Depression

PubMed Central

Gonzalez, Michelle A.; Jones, Deborah J.

2016-01-01

Behavioral Parent Training (BPT) is the standard of care for early onset (3 to 8 years old) disruptive behavior disorders (DBDs). Preliminary evidence suggests that BPT may also produce cascading treatment effects for comorbid and interrelated symptomatology in children, primarily internalizing problems, as well as symptomatology in multiple systems of the family, including caregiver depressive symptomatology. What is less well understood, however, is why and how BPT functions to impact these multiple symptom clusters within and between family members. Accordingly, this manuscript aims to serve as a conceptual and theoretical consideration of the mechanisms through which BPT may produce generalized treatment effects among children with early onset DBDs and internalizing problems, as well as the psychosocial difficulties among their caregivers. It is our intention that the hypothesized mechanisms highlighted in this review may guide advances in clinical research, as well as assessment and practice. PMID:27676702

Control of proliferation and cancer growth by the Hippo signaling pathway

PubMed Central

Ehmer, Ursula; Sage, Julien

2015-01-01

The control of cell division is essential for normal development and the maintenance of cellular homeostasis. Abnormal cell proliferation is associated with multiple pathological states, including cancer. While the Hippo/YAP signaling pathway was initially thought to control organ size and growth, increasing evidence indicates that this pathway also plays a major role in the control of proliferation independent of organ size control. In particular, accumulating evidence indicates that the Hippo/YAP signaling pathway functionally interacts with multiple other cellular pathways and serves as a central node in the regulation of cell division, especially in cancer cells. Here recent observations are highlighted that connect Hippo/YAP signaling to transcription, the basic cell cycle machinery, and the control of cell division. Furthermore, the oncogenic and tumor suppressive attributes of YAP/TAZ are reviewed which emphasizes the relevance of the Hippo pathway in cancer. PMID:26432795

Muc4/MUC4 functions and regulation in cancer.

PubMed

Carraway, Kermit L; Theodoropoulos, George; Kozloski, Goldi A; Carothers Carraway, Coralie A

2009-12-01

The membrane mucin MUC4 (human) is abundantly expressed in many epithelia, where it is proposed to play a protective role, and is overexpressed in some epithelial tumors. Studies on the rat homologue, Muc4, indicate that it acts through anti-adhesive or signaling mechanisms. In particular, Muc4/MUC4 can serve as a ligand/modulator of the receptor tyrosine kinase ErbB2, regulating its phosphorylation and the phosphorylation of its partner ErbB3, with or without the involvement of the ErbB3 ligand neuregulin. Muc4/MUC4 can also modulate cell apoptosis via multiple mechanisms, both ErbB2 dependent and independent. Muc4/MUC4 expression is regulated by multiple mechanisms, ranging from transcriptional to post-translational. The roles of MUC4 in tumors suggest that it may be valuable as a tumor marker or target for therapy.

Enterprise-wide worklist management.

PubMed

Locko, Roberta C; Blume, Hartwig; Goble, John C

2002-01-01

Radiologists in multi-facility health care delivery networks must serve not only their own departments but also departments of associated clinical facilities. We describe our experience with a picture archiving and communication system (PACS) implementation that provides a dynamic view of relevant radiological workload across multiple facilities. We implemented a distributed query system that permits management of enterprise worklists based on modality, body part, exam status, and other criteria that span multiple compatible PACSs. Dynamic worklists, with lesser flexibility, can be constructed if the incompatible PACSs support specific DICOM functionality. Enterprise-wide worklists were implemented across Generations Plus/Northern Manhattan Health Network, linking radiology departments of three hospitals (Harlem, Lincoln, and Metropolitan) with 1465 beds and 4260 ambulatory patients per day. Enterprise-wide, dynamic worklist management improves utilization of radiologists and enhances the quality of care across large multi-facility health care delivery organizations. Integration of other workflow-related components remain a significant challenge.

Monolithic photonic integrated circuit with a GaN-based bent waveguide

NASA Astrophysics Data System (ADS)

Cai, Wei; Qin, Chuan; Zhang, Shuai; Yuan, Jialei; Zhang, Fenghua; Wang, Yongjin

2018-06-01

Integration of a transmitter, waveguide and receiver into a single chip can generate a multicomponent system with multiple functionalities. Here, we fabricate and characterize a GaN-based photonic integrated circuit (PIC) on a GaN-on-silicon platform. With removal of the silicon and back wafer thinning of the epitaxial film, ultrathin membrane-type devices and highly confined suspended GaN waveguides were formed. Two suspended-membrane InGaN/GaN multiple-quantum-well diodes (MQW-diodes) served as an MQW light-emitting diode (MQW-LED) to emit light and an MQW photodiode (MQW-PD) to sense light. The optical interconnects between the MQW-LED and MQW-PD were achieved using the GaN bent waveguide. The GaN-based PIC consisting of an MQW-LED, waveguides and an MQW-PD forms an in-plane light communication system with a data transmission rate of 70 Mbps.

SMAD Signaling Is Required for Structural Integrity of the Female Reproductive Tract and Uterine Function During Early Pregnancy in Mice1

PubMed Central

Rodriguez, Amanda; Tripurani, Swamy K.; Burton, Jason C.; Clementi, Caterina; Larina, Irina; Pangas, Stephanie A.

2016-01-01

Pregnancy is a complex physiological process tightly controlled by the interplay among hormones, morphogens, transcription factors, and signaling pathways. Although recent studies using genetically engineered mouse models have revealed that ligands and receptors of transforming growth factor beta (TGFbeta) and bone morphogenetic protein (BMP) signaling pathways are essential for multiple reproductive events during pregnancy, the functional role of SMAD transcription factors, which serve as the canonical signaling platform for the TGFbeta/BMP pathways, in the oviduct and uterus is undefined. Here, we used a mouse model containing triple conditional deletion of the BMP receptor signaling Smads (Smad1 and Smad5) and Smad4, the central mediator of both TGFbeta and BMP signaling, to investigate the role of the SMADs in reproductive tract structure and function in cells from the Amhr2 lineage. Unlike the respective single- or double-knockouts, female Smad1flox/flox Smad5flox/flox Smad4flox/flox Amhr2cre/+conditional knockout (i.e., Smad1/5/4-Amhr2-cre KO) mice are sterile. We discovered that Smad1/5/4-Amhr2-cre KO females have malformed oviducts that subsequently develop oviductal diverticuli. These oviducts showed dysregulation of multiple genes essential for oviduct and smooth muscle development. In addition, uteri from Smad1/5/4-Amhr2-cre KO females exhibit multiple defects in stroma, epithelium, and smooth muscle layers and fail to assemble a closed uterine lumen upon embryo implantation, with defective uterine decidualization that led to pregnancy loss at early to mid-gestation. Taken together, our study uncovers a new role for the SMAD transcription factors in maintaining the structural and functional integrity of oviduct and uterus, required for establishment and maintenance of pregnancy. PMID:27335065

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

A Modular Laser Apparatus for Polarimetry, Nephelometry, and Fluorimetry in General Chemistry

ERIC Educational Resources Information Center

Jurzenski, Jessica; Darveau, Scott A.; Gindt, Yvonne; Mueller, Jessica; Vaverka, April; Barta, Cheri; Fitch, Anthony

2004-01-01

A novel apparatus that strengthens the connection between research and teaching laboratories and serves multiple purposes is described. A versatile laser apparatus suitable for the undergraduate teaching laboratory that may serve as polarimeter, nephelometer or fluorimeter is designed.

76 FR 36135 - Agency Information Collection Activities; Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-21

... serves multiple practical purposes: (1) To collect and analyze descriptive, outcome, and service... on access to high-quality, trauma-informed care; (3) to evaluate NCTSN centers' training and... below. Descriptive and Clinical Outcomes In order to describe the children served, their trauma...

New approach to CT pixel-based photon dose calculations in heterogeneous media

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

Wong, J.W.; Henkelman, R.M.

The effects of small cavities on dose in water and the dose in a homogeneous nonunit density medium illustrate that inhomogeneities do not act independently in photon dose perturbation, and serve as two constraints which should be satisfied by approximate methods of computed tomography (CT) pixel-based dose calculations. Current methods at best satisfy only one of the two constraints and show inadequacies in some intermediate geometries. We have developed an approximate method that satisfies both these constraints and treats much of the synergistic effect of multiple inhomogeneities correctly. The method calculates primary and first-scatter doses by first-order ray tracing withmore » the first-scatter contribution augmented by a component of second scatter that behaves like first scatter. Multiple-scatter dose perturbation values extracted from small cavity experiments are used in a function which approximates the small residual multiple-scatter dose. For a wide range of geometries tested, our method agrees very well with measurements. The average deviation is less than 2% with a maximum of 3%. In comparison, calculations based on existing methods can have errors larger than 10%.« less

MODIS polarization performance and anomalous four-cycle polarization phenomenon

NASA Astrophysics Data System (ADS)

Young, James B.; Knight, Ed; Merrow, Cindy

1998-10-01

The Moderate Resolution Imaging Spectroradiometer (MODIS) will be one of the primary instruments observing the earth on the Earth Observing System (EOS) scheduled for launch in 1999. MODIS polarization performance characterization was required for the 0.4 to 0.6 micrometers (VIS), 0.6 micrometers to 1.0 micrometers (NIR), and 1.0 micrometers to 2.3 micrometers (SWIR) regions. A polarized source assembly (PSA) consisting of a collimator with a rotatable Ahrens polarizer was used to illuminate MODIS with a linearly polarized beam. MODIS signal function having two-cycles per 360 degrees prism rotation signal function was expected. However, some spectral bands had a distinct four-cycle anomalous signal. The expected two-cycle function was present in all regions with the four-cycle anomaly being limited to the NIR region. Fourier analysis was very useful tooling determining the cause of the anomaly. A simplified polarization model of the PSA and MODIS was generated using Mueller matrices-Stokes vector formalism. Parametric modeling illustrated that this anomaly could be produced by energy having multiple passes between PSA Ahrens prism and the MODIS focal plane filters. Furthermore, the model gave NIR four-cycle magnitudes that were consistent with observations. The IVS and SWIR optical trans had birefringent elements that served to scramble the multiple pass anomaly. The model validity was demonstrated with an experimental setup that had partial aperture illumination which eliminated the possibility of multiple passes. The four-cycle response was eliminated while producing the same two-cycle polarization response. Data will be shown to illustrate the four-cycle phenomenon.

Guilt: an interpersonal approach.

PubMed

Baumeister, R F; Stillwell, A M; Heatherton, T F

1994-03-01

Multiple sets of empirical research findings on guilt are reviewed to evaluate the view that guilt should be understood as an essentially social phenomenon that happens between people as much as it happens inside them. Guilt appears to arise from interpersonal transactions (including transgressions and positive inequities) and to vary significantly with the interpersonal context. In particular, guilt patterns appear to be strongest, most common, and most consistent in the context of communal relationships, which are characterized by expectations of mutual concern. Guilt serves various relationship-enhancing functions, including motivating people to treat partners well and avoid transgressions, minimizing inequities and enabling less powerful partners to get their way, and redistributing emotional distress.

The Challenge of Ecophysiological Biodiversity for Biotechnological Applications of Marine Microalgae

PubMed Central

Barra, Lucia; Chandrasekaran, Raghu; Corato, Federico; Brunet, Christophe

2014-01-01

In this review, we aim to explore the potential of microalgal biodiversity and ecology for biotechnological use. A deeper exploration of the biodiversity richness and ecophysiological properties of microalgae is crucial for enhancing their use for applicative purposes. After describing the actual biotechnological use of microalgae, we consider the multiple faces of taxonomical, morphological, functional and ecophysiological biodiversity of these organisms, and investigate how these properties could better serve the biotechnological field. Lastly, we propose new approaches to enhancing microalgal growth, photosynthesis, and synthesis of valuable products used in biotechnological fields, mainly focusing on culture conditions, especially light manipulations and genetic modifications. PMID:24663117

Endocannabinoid signalling and the deteriorating brain

PubMed Central

Di Marzo, Vincenzo; Stella, Nephi; Zimmer, Andreas

2015-01-01

Ageing is characterized by the progressive impairment of physiological functions and increased risk of developing debilitating disorders, including chronic inflammation and neurodegenerative diseases. These disorders have common molecular mechanisms that can be targeted therapeutically. In the wake of the approval of the first cannabinoid-based drug for the symptomatic treatment of multiple sclerosis, we examine how endocannabinoid (eCB) signalling controls — and is affected by — normal ageing and neuroinflammatory and neurodegenerative disorders. We propose a conceptual framework linking eCB signalling to the control of the cellular and molecular hallmarks of these processes, and categorize the key components of endocannabinoid signalling that may serve as targets for novel therapeutics. PMID:25524120

Bridges or Barriers? Conceptualization of the Role of Multiple Identity Gateway Groups in Intergroup Relations.

PubMed

Levy, Aharon; Saguy, Tamar; Halperin, Eran; van Zomeren, Martijn

2017-01-01

The modern era of globalization has been accompanied by a massive growth in interconnections between groups, and has led to the sharing of multiple identities by individuals and groups. Following these developments, research has focused on the issue of multiple identities, and has shed important light on how individuals who hold these complex forms of identity feel and behave, and on the reactions they elicit from members of other groups. However, the potential of groups with such multiple identities (e.g., biracials, immigrants, etc.) to affect the intergroup relations between the groups that represent the respective sources of the different identities (e.g., Blacks and Whites, country of origin and country of residence, etc.) has not been examined to date. Accordingly, in this paper, we first systematically explore the potential of groups in which people identify with multiple social categories, or groups that are perceived as such by others, to play a role in intergroup dynamics. Next, we offer a theoretical framework outlining what functions groups of people with shared multiple identities may serve (as bridges or barriers ) by proposing how their presence may facilitate or deteriorate intergroup relations. Finally, we present recent empirical research examining how groups of people with shared multiple identities can act as gateways and bridge the cleft between two separate groups that represent the respective sources of their different identities, and discuss the theoretical and practical implications for the field of intergroup relations.

Bridges or Barriers? Conceptualization of the Role of Multiple Identity Gateway Groups in Intergroup Relations

PubMed Central

Levy, Aharon; Saguy, Tamar; Halperin, Eran; van Zomeren, Martijn

2017-01-01

The modern era of globalization has been accompanied by a massive growth in interconnections between groups, and has led to the sharing of multiple identities by individuals and groups. Following these developments, research has focused on the issue of multiple identities, and has shed important light on how individuals who hold these complex forms of identity feel and behave, and on the reactions they elicit from members of other groups. However, the potential of groups with such multiple identities (e.g., biracials, immigrants, etc.) to affect the intergroup relations between the groups that represent the respective sources of the different identities (e.g., Blacks and Whites, country of origin and country of residence, etc.) has not been examined to date. Accordingly, in this paper, we first systematically explore the potential of groups in which people identify with multiple social categories, or groups that are perceived as such by others, to play a role in intergroup dynamics. Next, we offer a theoretical framework outlining what functions groups of people with shared multiple identities may serve (as bridges or barriers) by proposing how their presence may facilitate or deteriorate intergroup relations. Finally, we present recent empirical research examining how groups of people with shared multiple identities can act as gateways and bridge the cleft between two separate groups that represent the respective sources of their different identities, and discuss the theoretical and practical implications for the field of intergroup relations. PMID:28706501

Multi-functionality Redefined with Colloidal Carotene Carbon Nanoparticles for Synchronized Chemical Imaging, Enriched Cellular Uptake and Therapy.

PubMed

Misra, Santosh K; Mukherjee, Prabuddha; Chang, Huei-Huei; Tiwari, Saumya; Gryka, Mark; Bhargava, Rohit; Pan, Dipanjan

2016-07-11

Typically, multiplexing high nanoparticle uptake, imaging, and therapy requires careful integration of three different functions of a multiscale molecular-particle assembly. Here, we present a simpler approach to multiplexing by utilizing one component of the system for multiple functions. Specifically, we successfully synthesized and characterized colloidal carotene carbon nanoparticle (C(3)-NP), in which a single functional molecule served a threefold purpose. First, the presence of carotene moieties promoted the passage of the particle through the cell membrane and into the cells. Second, the ligand acted as a potent detrimental moiety for cancer cells and, finally, the ligands produced optical contrast for robust microscopic detection in complex cellular environments. In comparative tests, C(3)-NP were found to provide effective intracellular delivery that enables both robust detection at cellular and tissue level and presents significant therapeutic potential without altering the mechanism of intracellular action of β-carotene. Surface coating of C(3) with phospholipid was used to generate C(3)-Lipocoat nanoparticles with further improved function and biocompatibility, paving the path to eventual in vivo studies.

Multi-functionality Redefined with Colloidal Carotene Carbon Nanoparticles for Synchronized Chemical Imaging, Enriched Cellular Uptake and Therapy

PubMed Central

Misra, Santosh K.; Mukherjee, Prabuddha; Chang, Huei-Huei; Tiwari, Saumya; Gryka, Mark; Bhargava, Rohit; Pan, Dipanjan

2016-01-01

Typically, multiplexing high nanoparticle uptake, imaging, and therapy requires careful integration of three different functions of a multiscale molecular-particle assembly. Here, we present a simpler approach to multiplexing by utilizing one component of the system for multiple functions. Specifically, we successfully synthesized and characterized colloidal carotene carbon nanoparticle (C3-NP), in which a single functional molecule served a threefold purpose. First, the presence of carotene moieties promoted the passage of the particle through the cell membrane and into the cells. Second, the ligand acted as a potent detrimental moiety for cancer cells and, finally, the ligands produced optical contrast for robust microscopic detection in complex cellular environments. In comparative tests, C3-NP were found to provide effective intracellular delivery that enables both robust detection at cellular and tissue level and presents significant therapeutic potential without altering the mechanism of intracellular action of β-carotene. Surface coating of C3 with phospholipid was used to generate C3-Lipocoat nanoparticles with further improved function and biocompatibility, paving the path to eventual in vivo studies. PMID:27405011

Multi-functionality Redefined with Colloidal Carotene Carbon Nanoparticles for Synchronized Chemical Imaging, Enriched Cellular Uptake and Therapy

NASA Astrophysics Data System (ADS)

Misra, Santosh K.; Mukherjee, Prabuddha; Chang, Huei-Huei; Tiwari, Saumya; Gryka, Mark; Bhargava, Rohit; Pan, Dipanjan

2016-07-01

Typically, multiplexing high nanoparticle uptake, imaging, and therapy requires careful integration of three different functions of a multiscale molecular-particle assembly. Here, we present a simpler approach to multiplexing by utilizing one component of the system for multiple functions. Specifically, we successfully synthesized and characterized colloidal carotene carbon nanoparticle (C3-NP), in which a single functional molecule served a threefold purpose. First, the presence of carotene moieties promoted the passage of the particle through the cell membrane and into the cells. Second, the ligand acted as a potent detrimental moiety for cancer cells and, finally, the ligands produced optical contrast for robust microscopic detection in complex cellular environments. In comparative tests, C3-NP were found to provide effective intracellular delivery that enables both robust detection at cellular and tissue level and presents significant therapeutic potential without altering the mechanism of intracellular action of β-carotene. Surface coating of C3 with phospholipid was used to generate C3-Lipocoat nanoparticles with further improved function and biocompatibility, paving the path to eventual in vivo studies.

Orangutan pantomime: elaborating the message

PubMed Central

Russon, Anne; Andrews, Kristin

2011-01-01

We present an exploratory study of forest-living orangutan pantomiming, i.e. gesturing in which they act out their meaning, focusing on its occurrence, communicative functions, and complexities. Studies show that captive great apes may elaborate messages if communication fails, and isolated reports suggest that great apes occasionally pantomime. We predicted forest-living orangutans would pantomime spontaneously to communicate, especially to elaborate after communication failures. Mining existing databases on free-ranging rehabilitant orangutans' behaviour identified 18 salient pantomimes. These pantomimes most often functioned as elaborations of failed requests, but also as deceptions and declaratives. Complexities identified include multimodality, re-enactments of past events and several features of language (productivity, compositionality, systematicity). These findings confirm that free-ranging rehabilitant orangutans pantomime and use pantomime to elaborate on their messages. Further, they use pantomime for multiple functions and create complex pantomimes that can express propositionally structured content. Thus, orangutan pantomime serves as a medium for communication, not a particular function. Mining cases of complex great ape communication originally reported in functional terms may then yield more evidence of pantomime. PMID:20702451

Assessment of stage of change, decisional balance, self-efficacy, and use of processes of change of low-income parents for increasing servings of fruits and vegetables to preschool-aged children.

PubMed

Hildebrand, Deana A; Betts, Nancy M

2009-01-01

Use the Transtheoretical Model of Behavior Change (TTM) to determine the proportionate stage of change of low-income parents and primary caregivers (PPC) for increasing accessibility, measured as servings served, of fruits and vegetables (FV) to their preschool-aged children and evaluate response differences for theoretical constructs. Cross-sectional, quantitative survey design consisting of staging algorithm, construct scales, and food frequency questionnaire. Rural and urban communities in a southwestern state of the United States. 238 low-income PPC enrolled in federal nutrition education programs were recruited from group nutrition education sessions. Stage of change using a staging algorithm, TTM constructs of processes of change, decisional balance, and self-efficacy measured by multiple-item scales using Likert response, and fruit and vegetable servings served using a food frequency questionnaire. Descriptive analysis, Pearson's chi-square, analyses of variance with Tukey's Honestly Significant Difference post hoc test, and principal component function analysis. Of the surveyed PPC, 43% were in precontemplation/contemplation stages, and 29% were in the preparation stage for increasing FV accessibility (measured by servings served) to their preschool-aged children. PPC in the action/maintenance stages evidenced greater use of behavioral processes and had higher self-efficacy scores compared to PPC in precontemplation/contemplation and preparation stages. Interventions aimed at increasing FV accessibility for preschool-aged children should be tailored to meet PPCs' stage of change. Interventions targeting PPC in precontemplation/contemplation stages should use methods to share ideas for planning meals and snacks to include FV. Interventions for PPC in the preparation stage should aim to build skills in quick preparation of economical FV, address parental role modeling of FV consumption, and encourage goal setting. Learning formats providing social support may prove effective in prevention of behavior relapse for PPC in action/maintenance stages.

Infectious Disease Stigmas: Maladaptive in Modern Society

PubMed Central

Smith, Rachel A.; Hughes, David

2014-01-01

At multiple times in human history people have asked if there are good stigmas. Is there some useful function stigmas serve in the context of our evolutionary history; is stigma adaptive? This essay discusses stigmas as a group-selection strategy and the human context in which stigmas likely appeared. The next section explores how human patterns have changed in modern society and the consequences for infectious disease (ID) stigmas in the modern age. The concluding section suggests that while social-living species may be particularly apt to create and communicate ID stigmas and enact ID-related stigmatization, such stigma-related processes no longer function to protect human communities. Stigmas do not increase the ability of modern societies to survive infectious diseases, but in fact may be important drivers of problematic disease dynamics and act as catalysts for failures in protecting public health. PMID:25477728

The role of sleep in human declarative memory consolidation.

PubMed

Alger, Sara E; Chambers, Alexis M; Cunningham, Tony; Payne, Jessica D

2015-01-01

Through a variety of methods, researchers have begun unraveling the mystery of why humans spend one-third of their lives asleep. Though sleep likely serves multiple functions, it has become clear that the sleeping brain offers an ideal environment for solidifying newly learned information in the brain. Sleep , which comprises a complex collection of brain states, supports the consolidation of many different types of information. It not only promotes learning and memory stabilization, but also memory reorganization that can lead to various forms of insightful behavior. As this chapter will describe, research provides ample support for these crucial cognitive functions of sleep . Focusing on the declarative memory system in humans, we review the literature regarding the benefits of sleep for both neutral and emotionally salient declarative memory. Finally, we discuss the literature regarding the impact of sleep on emotion regulation.

General base-general acid catalysis by terpenoid cyclases.

PubMed

Pemberton, Travis A; Christianson, David W

2016-07-01

Terpenoid cyclases catalyze the most complex reactions in biology, in that more than half of the substrate carbon atoms often undergo changes in bonding during the course of a multistep cyclization cascade that proceeds through multiple carbocation intermediates. Many cyclization mechanisms require stereospecific deprotonation and reprotonation steps, and most cyclization cascades are terminated by deprotonation to yield an olefin product. The first bacterial terpenoid cyclase to yield a crystal structure was pentalenene synthase from Streptomyces exfoliatus UC5319. This cyclase generates the hydrocarbon precursor of the pentalenolactone family of antibiotics. The structures of pentalenene synthase and other terpenoid cyclases reveal predominantly nonpolar active sites typically lacking amino acid side chains capable of serving general base-general acid functions. What chemical species, then, enables the Brønsted acid-base chemistry required in the catalytic mechanisms of these enzymes? The most likely candidate for such general base-general acid chemistry is the co-product inorganic pyrophosphate. Here, we briefly review biological and nonbiological systems in which phosphate and its derivatives serve general base and general acid functions in catalysis. These examples highlight the fact that the Brønsted acid-base activities of phosphate derivatives are comparable to the Brønsted acid-base activities of amino acid side chains.

General Base-General Acid Catalysis by Terpenoid Cyclases§

PubMed Central

Pemberton, Travis A.; Christianson, David W.

2016-01-01

Terpenoid cyclases catalyze the most complex reactions in biology, in that more than half of the substrate carbon atoms often undergo changes in bonding during the course of a multistep cyclization cascade that proceeds through multiple carbocation intermediates. Many cyclization mechanisms require stereospecific deprotonation and reprotonation steps, and most cyclization cascades are terminated by deprotonation to yield an olefin product. The first bacterial terpenoid cyclase to yield a crystal structure was pentalenene synthase from Streptomyces exfoliatus UC5319. This cyclase generates the hydrocarbon precursor of the pentalenolactone family of antibiotics. The structures of pentalenene synthase and other terpenoid cyclases reveal predominantly nonpolar active sites typically lacking amino acid side chains capable of serving general base-general acid functions. What chemical species, then, enables the Brønsted acid-base chemistry required in the catalytic mechanisms of these enzymes? The most likely candidate for such general base-general acid chemistry is the co-product inorganic pyrophosphate. Here, we briefly review biological and nonbiological systems in which phosphate and its derivatives serve general base and general acid functions in catalysis. These examples highlight the fact that the Brønsted acid-base activities of phosphate derivatives are comparable to the Brønsted acid-base activities of amino acid side chains. PMID:27072285

Oscillatory dynamics in the dorsal and ventral attention networks during the reorienting of attention.

PubMed

Proskovec, Amy L; Heinrichs-Graham, Elizabeth; Wiesman, Alex I; McDermott, Timothy J; Wilson, Tony W

2018-05-01

The ability to reorient attention within the visual field is central to daily functioning, and numerous fMRI studies have shown that the dorsal and ventral attention networks (DAN, VAN) are critical to such processes. However, despite the instantaneous nature of attentional shifts, the dynamics of oscillatory activity serving attentional reorientation remain poorly characterized. In this study, we utilized magnetoencephalography (MEG) and a Posner task to probe the dynamics of attentional reorienting in 29 healthy adults. MEG data were transformed into the time-frequency domain and significant oscillatory responses were imaged using a beamformer. Voxel time series were then extracted from peak voxels in the functional beamformer images. These time series were used to quantify the dynamics of attentional reorienting, and to compute dynamic functional connectivity. Our results indicated strong increases in theta and decreases in alpha and beta activity across many nodes in the DAN and VAN. Interestingly, theta responses were generally stronger during trials that required attentional reorienting relative to those that did not, while alpha and beta oscillations were more dynamic, with many regions exhibiting significantly stronger responses during non-reorienting trials initially, and the opposite pattern during later processing. Finally, stronger functional connectivity was found following target presentation (575-700 ms) between bilateral superior parietal lobules during attentional reorienting. In sum, these data show that visual attention is served by multiple cortical regions within the DAN and VAN, and that attentional reorienting processes are often associated with spectrally-specific oscillations that have largely distinct spatiotemporal dynamics. © 2018 Wiley Periodicals, Inc.

Similarity in form and function of the hippocampus in rodents, monkeys, and humans.

PubMed

Clark, Robert E; Squire, Larry R

2013-06-18

We begin by describing an historical scientific debate in which the fundamental idea that species are related by evolutionary descent was challenged. The challenge was based on supposed neuroanatomical differences between humans and other primates with respect to a structure known then as the hippocampus minor. The debate took place in the early 1860 s, just after the publication of Darwin's famous book. We then recount the difficult road that was traveled to develop an animal model of human memory impairment, a matter that also turned on questions about similarities and differences between humans and other primates. We then describe how the insight that there are multiple memory systems helped to secure the animal model and how the animal model was ultimately used to identify the neuroanatomy of long-term declarative memory (sometimes termed explicit memory). Finally, we describe a challenge to the animal model and to cross-species comparisons by considering the case of the concurrent discrimination task, drawing on findings from humans and monkeys. We suggest that analysis of such cases, based on the understanding that there are multiple memory systems with different properties, has served to emphasize the similarities in memory function across mammalian species.

Fischer–Tropsch Synthesis: XANES Spectra of Potassium in Promoted Precipitated Iron Catalysts as a Function of Time On-stream

DOE PAGES

Jacobs, Gary; Pendyala, Venkat Ramana Rao; Martinelli, Michela; ...

2017-06-06

XANES K-edge spectra of potassium promoter in precipitated Fe catalysts were acquired following activation by carburization in CO and as a function of time on-stream during the course of a Fischer–Tropsch synthesis run for a 100Fe:2K catalyst by withdrawing catalysts, sealed in wax product, for analysis. CO-activated and end-of-run spectra of the catalyst were also obtained for a 100Fe:5K catalyst. Peaks representing electronic transitions and multiple scattering were observed and resembled reference spectra for potassium carbonate or potassium formate. The shift in the multiple scattering peak to higher energy was consistent with sintering of potassium promoter during the course ofmore » the reaction test. The catalyst, however, retained its carbidic state, as demonstrated by XANES and EXAFS spectra at the iron K-edge, suggesting that sintering of potassium did not adversely affect the carburization rate, which is important for preventing iron carbides from oxidizing. This method serves as a starting point for developing better understanding of the chemical state and changes in structure occurring with alkali promoter.« less

Balancing exploration, uncertainty and computational demands in many objective reservoir optimization

NASA Astrophysics Data System (ADS)

Zatarain Salazar, Jazmin; Reed, Patrick M.; Quinn, Julianne D.; Giuliani, Matteo; Castelletti, Andrea

2017-11-01

Reservoir operations are central to our ability to manage river basin systems serving conflicting multi-sectoral demands under increasingly uncertain futures. These challenges motivate the need for new solution strategies capable of effectively and efficiently discovering the multi-sectoral tradeoffs that are inherent to alternative reservoir operation policies. Evolutionary many-objective direct policy search (EMODPS) is gaining importance in this context due to its capability of addressing multiple objectives and its flexibility in incorporating multiple sources of uncertainties. This simulation-optimization framework has high potential for addressing the complexities of water resources management, and it can benefit from current advances in parallel computing and meta-heuristics. This study contributes a diagnostic assessment of state-of-the-art parallel strategies for the auto-adaptive Borg Multi Objective Evolutionary Algorithm (MOEA) to support EMODPS. Our analysis focuses on the Lower Susquehanna River Basin (LSRB) system where multiple sectoral demands from hydropower production, urban water supply, recreation and environmental flows need to be balanced. Using EMODPS with different parallel configurations of the Borg MOEA, we optimize operating policies over different size ensembles of synthetic streamflows and evaporation rates. As we increase the ensemble size, we increase the statistical fidelity of our objective function evaluations at the cost of higher computational demands. This study demonstrates how to overcome the mathematical and computational barriers associated with capturing uncertainties in stochastic multiobjective reservoir control optimization, where parallel algorithmic search serves to reduce the wall-clock time in discovering high quality representations of key operational tradeoffs. Our results show that emerging self-adaptive parallelization schemes exploiting cooperative search populations are crucial. Such strategies provide a promising new set of tools for effectively balancing exploration, uncertainty, and computational demands when using EMODPS.

Climate Science's Globally Distributed Infrastructure

NASA Astrophysics Data System (ADS)

Williams, D. N.

2016-12-01

The Earth System Grid Federation (ESGF) is primarily funded by the Department of Energy's (DOE's) Office of Science (the Office of Biological and Environmental Research [BER] Climate Data Informatics Program and the Office of Advanced Scientific Computing Research Next Generation Network for Science Program), the National Oceanic and Atmospheric Administration (NOAA), the National Aeronautics and Space Administration (NASA), and the National Science Foundation (NSF), the European Infrastructure for the European Network for Earth System Modeling (IS-ENES), and the Australian National University (ANU). Support also comes from other U.S. federal and international agencies. The federation works across multiple worldwide data centers and spans seven international network organizations to provide users with the ability to access, analyze, and visualize data using a globally federated collection of networks, computers, and software. Its architecture employs a series of geographically distributed peer nodes that are independently administered and united by common federation protocols and application programming interfaces (APIs). The full ESGF infrastructure has now been adopted by multiple Earth science projects and allows access to petabytes of geophysical data, including the Coupled Model Intercomparison Project (CMIP; output used by the Intergovernmental Panel on Climate Change assessment reports), multiple model intercomparison projects (MIPs; endorsed by the World Climate Research Programme [WCRP]), and the Accelerated Climate Modeling for Energy (ACME; ESGF is included in the overarching ACME workflow process to store model output). ESGF is a successful example of integration of disparate open-source technologies into a cohesive functional system that serves the needs the global climate science community. Data served by ESGF includes not only model output but also observational data from satellites and instruments, reanalysis, and generated images.

Recovery High Schools

ERIC Educational Resources Information Center

Vogel, Carl

2009-01-01

This article discusses recovery high schools which are designed specifically to serve students who have been through a professional substance abuse treatment program and are working to stay away from drugs and alcohol. The schools typically serve multiple districts and are funded from both the per-pupil state funds that follow a student and what…

76 FR 53138 - Agency Information Collection Activities: Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-25

... serves multiple practical purposes: (1) To collect and analyze descriptive, outcome, and service... impact on access to high-quality, trauma-informed care; (3) to evaluate NCTSI centers' training and... below. Descriptive and Clinical Outcomes In order to describe the children served, their trauma...

AutoFACT: An Automatic Functional Annotation and Classification Tool

PubMed Central

Koski, Liisa B; Gray, Michael W; Lang, B Franz; Burger, Gertraud

2005-01-01

Background Assignment of function to new molecular sequence data is an essential step in genomics projects. The usual process involves similarity searches of a given sequence against one or more databases, an arduous process for large datasets. Results We present AutoFACT, a fully automated and customizable annotation tool that assigns biologically informative functions to a sequence. Key features of this tool are that it (1) analyzes nucleotide and protein sequence data; (2) determines the most informative functional description by combining multiple BLAST reports from several user-selected databases; (3) assigns putative metabolic pathways, functional classes, enzyme classes, GeneOntology terms and locus names; and (4) generates output in HTML, text and GFF formats for the user's convenience. We have compared AutoFACT to four well-established annotation pipelines. The error rate of functional annotation is estimated to be only between 1–2%. Comparison of AutoFACT to the traditional top-BLAST-hit annotation method shows that our procedure increases the number of functionally informative annotations by approximately 50%. Conclusion AutoFACT will serve as a useful annotation tool for smaller sequencing groups lacking dedicated bioinformatics staff. It is implemented in PERL and runs on LINUX/UNIX platforms. AutoFACT is available at . PMID:15960857

DL-sQUAL: A Multiple-Item Scale for Measuring Service Quality of Online Distance Learning Programs

ERIC Educational Resources Information Center

Shaik, Naj; Lowe, Sue; Pinegar, Kem

2006-01-01

Education is a service with multiplicity of student interactions over time and across multiple touch points. Quality teaching needs to be supplemented by consistent quality supporting services for programs to succeed under the competitive distance learning landscape. ServQual and e-SQ scales have been proposed for measuring quality of traditional…

Application of Item Analysis to Assess Multiple-Choice Examinations in the Mississippi Master Cattle Producer Program

ERIC Educational Resources Information Center

Parish, Jane A.; Karisch, Brandi B.

2013-01-01

Item analysis can serve as a useful tool in improving multiple-choice questions used in Extension programming. It can identify gaps between instruction and assessment. An item analysis of Mississippi Master Cattle Producer program multiple-choice examination responses was performed to determine the difficulty of individual examinations, assess the…

Blends of Pheromones, With and Without Host Plant Volatiles, Can Attract Multiple Species of Cerambycid Beetles Simultaneously

Treesearch

L.M. Hanks; J.A. Mongold-Diers; T.H. Atkinson; M.K. Fierke; M.D. Ginzel; E.E. Graham; T.M. Poland; A.B. Richards; M.L. Richardson; J.G. Millar

2018-01-01

Pheromone components of cerambycid beetles are often conserved, with a given compound serving as a pheromone component for multiple related species, including species native to different continents. Consequently, a single synthesized compound may attract multiple species to a trap simultaneously. Furthermore, our previous research in east-central Illinois had...

Biomechanical analysis of three tennis serve types using a markerless system.

PubMed

Abrams, Geoffrey D; Harris, Alex H S; Andriacchi, Thomas P; Safran, Marc R

2014-02-01

The tennis serve is commonly associated with musculoskeletal injury. Advanced players are able to hit multiple serve types with different types of spin. No investigation has characterised the kinematics of all three serve types for the upper extremity and back. Seven NCAA Division I male tennis players performed three successful flat, kick and slice serves. Serves were recorded using an eight camera markerless motion capture system. Laser scanning was utilised to accurately collect body dimensions and data were computed using inverse kinematic methods. There was no significant difference in maximum back extension angle for the flat, kick or slice serves. The kick serve had a higher force magnitude at the back than the flat and slice as well as larger posteriorly directed shoulder forces. The flat serve had significantly greater maximum shoulder internal rotation velocity versus the slice serve. Force and torque magnitudes at the elbow and wrist were not significantly different between the serves. The kick serve places higher physical demands on the back and shoulder while the slice serve demonstrated lower overall kinetic forces. This information may have injury prevention and rehabilitation implications.

Synthesis and functionalization of gold nanorods for probing plasmonic enhancement mechanisms in organic photovoltaic active layers

NASA Astrophysics Data System (ADS)

Wadams, Robert Christopher

DNA nanotechnology is one of the most flourishing interdisciplinary research fields. Through the features of programmability and predictability, DNA nanostructures can be designed to self-assemble into a variety of periodic or aperiodic patterns of different shapes and length scales, and more importantly, they can be used as scaffolds for organizing other nanoparticles, proteins and chemical groups. By leveraging these molecules, DNA nanostructures can be used to direct the organization of complex bio-inspired materials that may serve as smart drug delivery systems and in vitro or in vivo bio-molecular computing and diagnostic devices. In this dissertation I describe a systematic study of the thermodynamic properties of complex DNA nanostructures, including 2D and 3D DNA origami, in order to understand their assembly, stability and functionality and inform future design endeavors. It is conceivable that a more thorough understanding of DNA self-assembly can be used to guide the structural design process and optimize the conditions for assembly, manipulation, and functionalization, thus benefiting both upstream design and downstream applications. As a biocompatible nanoscale motif, the successful integration, stabilization and separation of DNA nanostructures from cells/cell lysate suggests its potential to serve as a diagnostic platform at the cellular level. Here, DNA origami was used to capture and identify multiple T cell receptor mRNA species from single cells within a mixed cell population. This demonstrates the potential of DNA nanostructure as an ideal nano scale tool for biological applications.

Preclinical studies in support of defibrotide for the treatment of multiple myeloma and other neoplasias.

PubMed

Mitsiades, Constantine S; Rouleau, Cecile; Echart, Cinara; Menon, Krishna; Teicher, Beverly; Distaso, Maria; Palumbo, Antonio; Boccadoro, Mario; Anderson, Kenneth C; Iacobelli, Massimo; Richardson, Paul G

2009-02-15

Defibrotide, an orally bioavailable polydisperse oligonucleotide, has promising activity in hepatic veno-occlusive disease, a stem cell transplantation-related toxicity characterized by microangiopathy. The antithrombotic properties of defibrotide and its minimal hemorrhagic risk could serve for treatment of cancer-associated thrombotic complications. Given its cytoprotective effect on endothelium, we investigated whether defibrotide protects tumor cells from cytotoxic antitumor agents. Further, given its antiadhesive properties, we evaluated whether defibrotide modulates the protection conferred to multiple myeloma cells by bone marrow stromal cells. Defibrotide lacks significant single-agent in vitro cytotoxicity on multiple myeloma or solid tumor cells and does not attenuate their in vitro response to dexamethasone, bortezomib, immunomodulatory thalidomide derivatives, and conventional chemotherapeutics, including melphalan and cyclophosphamide. Importantly, defibrotide enhances in vivo chemosensitivity of multiple myeloma and mammary carcinoma xenografts in animal models. In cocultures of multiple myeloma cells with bone marrow stromal cells in vitro, defibrotide enhances the multiple myeloma cell sensitivity to melphalan and dexamethasone, and decreases multiple myeloma-bone marrow stromal cell adhesion and its sequelae, including nuclear factor-kappaB activation in multiple myeloma and bone marrow stromal cells, and associated cytokine production. Moreover, defibrotide inhibits expression and/or function of key mediators of multiple myeloma interaction with bone marrow stromal cell and endothelium, including heparanase, angiogenic cytokines, and adhesion molecules. Defibrotide's in vivo chemosensitizing properties and lack of direct in vitro activity against tumor cells suggest that it favorably modulates antitumor interactions between bone marrow stromal cells and endothelia in the tumor microenvironment. These data support clinical studies of defibrotide in combination with conventional and novel therapies to potentially improve patient outcome in multiple myeloma and other malignancies.

[Collagens: why such a structural complexity?].

PubMed

Borel, J P; Monboisse, J C

1993-01-01

The collagens are a family of extracellular fibrillar proteins, characterized by the presence of one or several domains termed "triple helix", that are made of three polypeptide chains folded around each other. They elicit a huge worldwide research activity, marked every year by the publishing of dozens of books and thousands of papers. This family is presently represented by more than 16 individualized types, all differing by their molecular structure and by the way helical and globular domains are arranged. In any case, however, at least one triple helical domain exists. It is formed by the association of three polypeptide chains, each of them containing a glycine every three residues and many proline or hydroxyproline residues, and attests for the belonging of the protein to the collagen group. These multiple molecular forms and their specific architecture raise questions that remain unsolved. Why is this triple helix structure adopted in the case of collagens? Is it because the simple alpha helix of protein cannot extend over more than a few nanometers and is not solid enough? Why not a double helix like that of DNA? It would probably not be rigid enough. Why are there many globular domains interspersed between fibrillar ones? Probably these domains are useful for the association of peptide chains in register prior to their folding, then they participate in the transport of the elementary molecules from the synthesizing cells to their final place in the connective tissue and, finally, they insert the molecules into their specific place inside the growing fibrils. Collagen fibres as they are evidenced by histological methods, for instance in tendons, are of complex structure. Most of their constituting sub-units are type I tropocollagen molecules but they also contain in their center a filament of type V collagen that seems to serve as a guide during their edification. On the surface of the fibres are molecules of type III collagen that limit the growth in diameter and also type XII molecules that serve to bind the fibres to the surrounding substances. The collagen type multiplicity is explained by their various functions (mechanical role for tendons and ligaments, functions of wrapping around muscle cells, basement membrane role as a support for endothelial cells, function of glomerular filter, etc.). The fact that every collagen type contains several different polypeptide chains remains poorly explained. It may serve for the orientation of every elementary molecule inside the complex array of the polymer.(ABSTRACT TRUNCATED AT 400 WORDS)

A test of multiple hypotheses for the function of call sharing in female budgerigars, Melopsittacus undulatus

PubMed Central

Young, Anna M.; Cordier, Breanne; Mundry, Roger; Wright, Timothy F.

2014-01-01

In many social species group, members share acoustically similar calls. Functional hypotheses have been proposed for call sharing, but previous studies have been limited by an inability to distinguish among these hypotheses. We examined the function of vocal sharing in female budgerigars with a two-part experimental design that allowed us to distinguish between two functional hypotheses. The social association hypothesis proposes that shared calls help animals mediate affiliative and aggressive interactions, while the password hypothesis proposes that shared calls allow animals to distinguish group identity and exclude nonmembers. We also tested the labeling hypothesis, a mechanistic explanation which proposes that shared calls are used to address specific individuals within the sender–receiver relationship. We tested the social association hypothesis by creating four–member flocks of unfamiliar female budgerigars (Melopsittacus undulatus) and then monitoring the birds’ calls, social behaviors, and stress levels via fecal glucocorticoid metabolites. We tested the password hypothesis by moving immigrants into established social groups. To test the labeling hypothesis, we conducted additional recording sessions in which individuals were paired with different group members. The social association hypothesis was supported by the development of multiple shared call types in each cage and a correlation between the number of shared call types and the number of aggressive interactions between pairs of birds. We also found support for calls serving as a labeling mechanism using discriminant function analysis with a permutation procedure. Our results did not support the password hypothesis, as there was no difference in stress or directed behaviors between immigrant and control birds. PMID:24860236

A Hitchhiker's Guide to Functional Magnetic Resonance Imaging

PubMed Central

Soares, José M.; Magalhães, Ricardo; Moreira, Pedro S.; Sousa, Alexandre; Ganz, Edward; Sampaio, Adriana; Alves, Victor; Marques, Paulo; Sousa, Nuno

2016-01-01

Functional Magnetic Resonance Imaging (fMRI) studies have become increasingly popular both with clinicians and researchers as they are capable of providing unique insights into brain functions. However, multiple technical considerations (ranging from specifics of paradigm design to imaging artifacts, complex protocol definition, and multitude of processing and methods of analysis, as well as intrinsic methodological limitations) must be considered and addressed in order to optimize fMRI analysis and to arrive at the most accurate and grounded interpretation of the data. In practice, the researcher/clinician must choose, from many available options, the most suitable software tool for each stage of the fMRI analysis pipeline. Herein we provide a straightforward guide designed to address, for each of the major stages, the techniques, and tools involved in the process. We have developed this guide both to help those new to the technique to overcome the most critical difficulties in its use, as well as to serve as a resource for the neuroimaging community. PMID:27891073

Metal-free Synthesis of Ynones from Acyl Chlorides and Potassium Alkynyltrifluoroborate Salts

PubMed Central

Taylor, Cassandra L.; Bolshan, Yuri

2015-01-01

Ynones are a valuable functional group and building block in organic synthesis. Ynones serve as a precursor to many important organic functional groups and scaffolds. Traditional methods for the preparation of ynones are associated with drawbacks including harsh conditions, multiple purification steps, and the presence of unwanted byproducts. An alternative method for the straightforward preparation of ynones from acyl chlorides and potassium alkynyltrifluoroborate salts is described herein. The adoption of organotrifluoroborate salts as an alternative to organometallic reagents for the formation of new carbon-carbon bonds has a number of advantages. Potassium organotrifluoroborate salts are shelf stable, have good functional group tolerance, low toxicity, and a wide variety are straightforward to prepare. The title reaction proceeds rapidly at ambient temperature in the presence of a Lewis acid without the exclusion of air and moisture. Fair to excellent yields may be obtained via reaction of various aryl and alkyl acid chlorides with alkynyltrifluoroborate salts in the presence of boron trichloride. PMID:25742169

A continuous function model for path prediction of entities

NASA Astrophysics Data System (ADS)

Nanda, S.; Pray, R.

2007-04-01

As militaries across the world continue to evolve, the roles of humans in various theatres of operation are being increasingly targeted by military planners for substitution with automation. Forward observation and direction of supporting arms to neutralize threats from dynamic adversaries is one such example. However, contemporary tracking and targeting systems are incapable of serving autonomously for they do not embody the sophisticated algorithms necessary to predict the future positions of adversaries with the accuracy offered by the cognitive and analytical abilities of human operators. The need for these systems to incorporate methods characterizing such intelligence is therefore compelling. In this paper, we present a novel technique to achieve this goal by modeling the path of an entity as a continuous polynomial function of multiple variables expressed as a Taylor series with a finite number of terms. We demonstrate the method for evaluating the coefficient of each term to define this function unambiguously for any given entity, and illustrate its use to determine the entity's position at any point in time in the future.

CORUM: the comprehensive resource of mammalian protein complexes

PubMed Central

Ruepp, Andreas; Brauner, Barbara; Dunger-Kaltenbach, Irmtraud; Frishman, Goar; Montrone, Corinna; Stransky, Michael; Waegele, Brigitte; Schmidt, Thorsten; Doudieu, Octave Noubibou; Stümpflen, Volker; Mewes, H. Werner

2008-01-01

Protein complexes are key molecular entities that integrate multiple gene products to perform cellular functions. The CORUM (http://mips.gsf.de/genre/proj/corum/index.html) database is a collection of experimentally verified mammalian protein complexes. Information is manually derived by critical reading of the scientific literature from expert annotators. Information about protein complexes includes protein complex names, subunits, literature references as well as the function of the complexes. For functional annotation, we use the FunCat catalogue that enables to organize the protein complex space into biologically meaningful subsets. The database contains more than 1750 protein complexes that are built from 2400 different genes, thus representing 12% of the protein-coding genes in human. A web-based system is available to query, view and download the data. CORUM provides a comprehensive dataset of protein complexes for discoveries in systems biology, analyses of protein networks and protein complex-associated diseases. Comparable to the MIPS reference dataset of protein complexes from yeast, CORUM intends to serve as a reference for mammalian protein complexes. PMID:17965090

The molecular functions of hepatocyte nuclear factors - In and beyond the liver.

PubMed

Lau, Hwee Hui; Ng, Natasha Hui Jin; Loo, Larry Sai Weng; Jasmen, Joanita Binte; Teo, Adrian Kee Keong

2018-05-01

The hepatocyte nuclear factors (HNFs) namely HNF1α/β, FOXA1/2/3, HNF4α/γ and ONECUT1/2 are expressed in a variety of tissues and organs, including the liver, pancreas and kidney. The spatial and temporal manner of HNF expression regulates embryonic development and subsequently the development of multiple tissues during adulthood. Though the HNFs were initially identified individually based on their roles in the liver, numerous studies have now revealed that the HNFs cross-regulate one another and exhibit synergistic relationships in the regulation of tissue development and function. The complex HNF transcriptional regulatory networks have largely been elucidated in rodent models, but less so in human biological systems. Several heterozygous mutations in these HNFs were found to cause diseases in humans but not in rodents, suggesting clear species-specific differences in mutational mechanisms that remain to be uncovered. In this review, we compare and contrast the expression patterns of the HNFs, the HNF cross-regulatory networks and how these liver-enriched transcription factors serve multiple functions in the liver and beyond, extending our focus to the pancreas and kidney. We also summarise the insights gained from both human and rodent studies of mutations in several HNFs that are known to lead to different disease conditions. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Climate change mitigation and adaptation in the land use sector: from complementarity to synergy.

PubMed

Duguma, Lalisa A; Minang, Peter A; van Noordwijk, Meine

2014-09-01

Currently, mitigation and adaptation measures are handled separately, due to differences in priorities for the measures and segregated planning and implementation policies at international and national levels. There is a growing argument that synergistic approaches to adaptation and mitigation could bring substantial benefits at multiple scales in the land use sector. Nonetheless, efforts to implement synergies between adaptation and mitigation measures are rare due to the weak conceptual framing of the approach and constraining policy issues. In this paper, we explore the attributes of synergy and the necessary enabling conditions and discuss, as an example, experience with the Ngitili system in Tanzania that serves both adaptation and mitigation functions. An in-depth look into the current practices suggests that more emphasis is laid on complementarity-i.e., mitigation projects providing adaptation co-benefits and vice versa rather than on synergy. Unlike complementarity, synergy should emphasize functionally sustainable landscape systems in which adaptation and mitigation are optimized as part of multiple functions. We argue that the current practice of seeking co-benefits (complementarity) is a necessary but insufficient step toward addressing synergy. Moving forward from complementarity will require a paradigm shift from current compartmentalization between mitigation and adaptation to systems thinking at landscape scale. However, enabling policy, institutional, and investment conditions need to be developed at global, national, and local levels to achieve synergistic goals.

Inhibition of the B7-H3 immune checkpoint limits tumor growth by enhancing cytotoxic lymphocyte function.

PubMed

Lee, Young-Hee; Martin-Orozco, Natalia; Zheng, Peilin; Li, Jing; Zhang, Peng; Tan, Haidong; Park, Hyun Jung; Jeong, Mira; Chang, Seon Hee; Kim, Byung-Seok; Xiong, Wei; Zang, Wenjuan; Guo, Li; Liu, Yang; Dong, Zhong-Jun; Overwijk, Willem W; Hwu, Patrick; Yi, Qing; Kwak, Larry; Yang, Zhiying; Mak, Tak W; Li, Wei; Radvanyi, Laszlo G; Ni, Ling; Liu, Dongfang; Dong, Chen

2017-08-01

The interaction between tumor and the immune system is still poorly understood. Significant clinical responses have been achieved in cancer patients treated with antibodies against the CTLA4 and PD-1/PD-L1 checkpoints; however, only a small portion of patients responded to the therapies, indicating a need to explore additional co-inhibitory molecules for cancer treatment. B7-H3, a member of the B7 superfamily, was previously shown by us to inhibit T-cell activation and autoimmunity. In this study, we have analyzed the function of B7-H3 in tumor immunity. Expression of B7-H3 was found in multiple tumor lines, tumor-infiltrating dendritic cells, and macrophages. B7-H3-deficient mice or mice treated with an antagonistic antibody to B7-H3 showed reduced growth of multiple tumors, which depended on NK and CD8 + T cells. With a putative receptor expressed by cytotoxic lymphocytes, B7-H3 inhibited their activation, and its deficiency resulted in increased cytotoxic lymphocyte function in tumor-bearing mice. Combining blockades of B7-H3 and PD-1 resulted in further enhanced therapeutic control of late-stage tumors. Taken together, our results indicate that the B7-H3 checkpoint may serve as a novel target for immunotherapy against cancer.

Generalizing the Arden Syntax to a Common Clinical Application Language.

PubMed

Kraus, Stefan

2018-01-01

The Arden Syntax for Medical Logic Systems is a standard for encoding and sharing knowledge in the form of Medical Logic Modules (MLMs). Although the Arden Syntax has been designed to meet the requirements of data-driven clinical event monitoring, multiple studies suggest that its language constructs may be suitable for use outside the intended application area and even as a common clinical application language. Such a broader context, however, requires to reconsider some language features. The purpose of this paper is to outline the related modifications on the basis of a generalized Arden Syntax version. The implemented prototype provides multiple adjustments to the standard, such as an option to use programming language constructs without the frame-like MLM structure, a JSON compliant data type system, a means to use MLMs as user-defined functions, and native support of restful web services with integrated data mapping. This study does not aim to promote an actually new language, but a more generic version of the proven Arden Syntax standard. Such an easy-to-understand domain-specific language for common clinical applications might cover multiple additional medical subdomains and serve as a lingua franca for arbitrary clinical algorithms, therefore avoiding a patchwork of multiple all-purpose languages between, and even within, institutions.

Exploring What Leads High School Students to Enroll in Hispanic-Serving Institutions: A Multilevel Analysis

ERIC Educational Resources Information Center

Nunez, Anne-Marie; Bowers, Alex J.

2011-01-01

This study examined the student and high school contextual factors associated with high school students' enrollment in Hispanic-Serving Institutions (HSIs). The authors drew on a conceptual framework of college choice involving the concepts of multiple capitals and individual and organizational habitus to examine the postsecondary trajectories of…

Serving Special Needs Students in the School Library Media Center. Greenwood Professional Guides in School Librarianship.

ERIC Educational Resources Information Center

Wesson, Caren L., Ed.; Keefe, Margaret J., Ed.

This collection of papers considers how the school library media specialist serves special needs students and classroom teachers in multiple roles as teacher, information specialist, and instructional consultant or collaborator. Included are the following papers: "Teaching Library and Information Skills to Special Needs Students" (Caren…

Portable Power And Digital-Communication Units

NASA Technical Reports Server (NTRS)

Levin, Richard R.; Henry, Paul K.; Rosenberg, Leigh S.

1992-01-01

Conceptual network of electronic-equipment modules provides electrical power and digital radio communications at multiple sites not served by cables. System includes central communication unit and portable units powered by solar photovoltaic arrays. Useful to serve equipment that must be set up quickly at remote sites or buildings that cannot be modified to provide cable connections.

NovelFam3000 – Uncharacterized human protein domains conserved across model organisms

PubMed Central

Kemmer, Danielle; Podowski, Raf M; Arenillas, David; Lim, Jonathan; Hodges, Emily; Roth, Peggy; Sonnhammer, Erik LL; Höög, Christer; Wasserman, Wyeth W

2006-01-01

Background Despite significant efforts from the research community, an extensive portion of the proteins encoded by human genes lack an assigned cellular function. Most metazoan proteins are composed of structural and/or functional domains, of which many appear in multiple proteins. Once a domain is characterized in one protein, the presence of a similar sequence in an uncharacterized protein serves as a basis for inference of function. Thus knowledge of a domain's function, or the protein within which it arises, can facilitate the analysis of an entire set of proteins. Description From the Pfam domain database, we extracted uncharacterized protein domains represented in proteins from humans, worms, and flies. A data centre was created to facilitate the analysis of the uncharacterized domain-containing proteins. The centre both provides researchers with links to dispersed internet resources containing gene-specific experimental data and enables them to post relevant experimental results or comments. For each human gene in the system, a characterization score is posted, allowing users to track the progress of characterization over time or to identify for study uncharacterized domains in well-characterized genes. As a test of the system, a subset of 39 domains was selected for analysis and the experimental results posted to the NovelFam3000 system. For 25 human protein members of these 39 domain families, detailed sub-cellular localizations were determined. Specific observations are presented based on the analysis of the integrated information provided through the online NovelFam3000 system. Conclusion Consistent experimental results between multiple members of a domain family allow for inferences of the domain's functional role. We unite bioinformatics resources and experimental data in order to accelerate the functional characterization of scarcely annotated domain families. PMID:16533400

Dimensions of functional social support and psychological symptoms.

PubMed

Schonfeld, I S

1991-11-01

In the summer following graduation a sample of 125 female college graduates (mean age = 28) completed Cohen & Wills' ISEL (1985) which includes scales measuring four social support functions: belonging (social companionship), appraisal (availability of confidants), tangible (instrumental), and self-esteem support. In the summer and fall subject status on two outcome scales was ascertained: the Psychophysiologic Symptom Scale and the Center for Epidemiologic Studies Depression Scale (CES-D). Reliability of the difference scores suggested that the ISEL scales do not measure entirely different constructs and the ISEL Self-esteem Scale is operationally redundant with the Rosenberg Self-esteem scale and the CES-D. Cross-sectional analyses indicated that the ISEL scales were related to symptoms. By contrast, standard longitudinal and prospective MLR analyses indicated that only the Belonging Scale was significantly related to future symptoms. The issues of confounding support with symptoms and the dimensionality of the subscales were discussed. The study suggests that specific functions of support take on greater importance during major life transitions and that any one supportive behaviour often serves multiple functions.

Safety and driver behavior studies at multiple lane approaches to stop-controlled intersections.

DOT National Transportation Integrated Search

2010-05-01

Multiple-lane approaches (MLAs) controlled by stop signs are becoming increasingly common in Nebraska. Installation of MLAs occurs when a single approach lane can no longer adequately serve the minor road traffic volume, and a signal is unwarranted b...

An Efficient Scheduling Scheme on Charging Stations for Smart Transportation

NASA Astrophysics Data System (ADS)

Kim, Hye-Jin; Lee, Junghoon; Park, Gyung-Leen; Kang, Min-Jae; Kang, Mikyung

This paper proposes a reservation-based scheduling scheme for the charging station to decide the service order of multiple requests, aiming at improving the satisfiability of electric vehicles. The proposed scheme makes it possible for a customer to reduce the charge cost and waiting time, while a station can extend the number of clients it can serve. A linear rank function is defined based on estimated arrival time, waiting time bound, and the amount of needed power, reducing the scheduling complexity. Receiving the requests from the clients, the power station decides the charge order by the rank function and then replies to the requesters with the waiting time and cost it can guarantee. Each requester can decide whether to charge at that station or try another station. This scheduler can evolve to integrate a new pricing policy and services, enriching the electric vehicle transport system.

Listening to Another Sense: Somatosensory Integration in the Auditory System

PubMed Central

Wu, Calvin; Stefanescu, Roxana A.; Martel, David T.

2014-01-01

Conventionally, sensory systems are viewed as separate entities, each with its own physiological process serving a different purpose. However, many functions require integrative inputs from multiple sensory systems, and sensory intersection and convergence occur throughout the central nervous system. The neural processes for hearing perception undergo significant modulation by the two other major sensory systems, vision and somatosensation. This synthesis occurs at every level of the ascending auditory pathway: the cochlear nucleus, inferior colliculus, medial geniculate body, and the auditory cortex. In this review, we explore the process of multisensory integration from 1) anatomical (inputs and connections), 2) physiological (cellular responses), 3) functional, and 4) pathological aspects. We focus on the convergence between auditory and somatosensory inputs in each ascending auditory station. This review highlights the intricacy of sensory processing, and offers a multisensory perspective regarding the understanding of sensory disorders. PMID:25526698

New Brunswick Laboratory: Progress report, October 1993 through September 1994

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

NONE

The mission of the New Brunswick Laboratory of the US Department of Energy (DOE) is to serve as the National Certifying Authority for nuclear reference materials and to provide an independent Federal technical staff and laboratory resource performing nuclear material measurement, safeguards and non-proliferation functions in support of multiple program sponsors. During FY 94 New Brunswick Laboratory (NBL) completed development of a Strategic Plan which will aid in better defining performance oriented laboratory goals and objectives in each functional area consistent with the changing needs of the global nuclear community. This annual report describes accomplishments achieved in carrying out NBL`smore » assigned missions. Details of completed projects are reported in separate topical reports or as open-literature publications. Programs discussed here are: (1) safeguards assistance; (2) reference materials program; (3) measurement evaluation; (4) measurement services; and (5) measurement development.« less

ABCB5 maintains melanoma-initiating cells through a pro-inflammatory cytokine signaling circuit

PubMed Central

Wilson, Brian J.; Saab, Karim R.; Ma, Jie; Schatton, Tobias; Pütz, Pablo; Zhan, Qian; Murphy, George F.; Gasser, Martin; Waaga-Gasser, Ana Maria; Frank, Natasha Y.; Frank, Markus H.

2014-01-01

The drug efflux transporter ABCB5 identifies cancer stem-like cells (CSC) in diverse human malignancies, where its expression is associated with clinical disease progression and tumor recurrence. ABCB5 confers therapeutic resistance but other functions in tumorigenesis independent of drug efflux have not been described that might help explain why it is so broadly overexpressed in human cancer. Here we show that in melanoma-initiating cells ABCB5 controls IL-1β secretion which serves to maintain slow-cycling, chemoresistant cells through an IL-1β/IL8/CXCR1 cytokine signaling circuit. This CSC maintenance circuit involved reciprocal paracrine interactions with ABCB5-negative cancer cell populations. ABCB5 blockade induced cellular differentiation, reversed resistance to multiple chemotherapeutic agents, and impaired tumor growth in vivo. Together, our results defined a novel function for ABCB5 in CSC maintenance and tumor growth. PMID:24934811

An epigenetic view of developmental diseases: new targets, new therapies.

PubMed

Xie, Pei; Zang, Li-Qun; Li, Xue-Kun; Shu, Qiang

2016-08-01

Function of epigenetic modifications is one of the most competitive fields in life science. Over the past several decades, it has been revealed that epigenetic modifications play essential roles in development and diseases including developmental diseases. In the present review, we summarize the recent progress about the function of epigenetic regulation, especially DNA and RNA modifications in developmental diseases. Original research articles and literature reviews published in PubMed-indexed journals. DNA modifications including methylation and demethylation can regulate gene expression, and are involved in development and multiple diseases including Rett syndrome, Autism spectrum disorders, congenital heart disease and cancer, etc. RNA methylation and demethylation play important roles in RNA processing, reprogramming, circadian, and neuronal activity, and then modulate development. DNA and RNA modifications play important roles in development and diseases through regulating gene expression. Epigenetic components could serve as novel targets for the treatment of developmental diseases.

Education and training in the MEDICOM system.

PubMed

Marinos, G; Palamas, S; Vlachos, I; Panou-Diamandi, O; Kalivas, D; Koutsouris, D

2000-01-01

MEDICOM system is a world wide telematics application for electronic commerce of medical devices. It has been designed so as to provide the health care professionals with a central Internet access to up-to-date information about medical equipment from multiple manufacturers, in a particular easy and friendly way. Moreover, the Medicom system will serve the health care professionals' requirements for high-quality information about specific products in a form of multimedia presentations and that of a secure communication channel with the community of manufacturers, especially for post marketing surveillance. The system will provide the medical staff (physicians and technicians) with demonstrations of the operation procedures and the functioning of high-tech equipment in a form of virtual models. Moreover, through the medicom system the end users of medical devices can have access to on line libraries and participate in special newsgroups. This paper discusses the architectural structure of the MEDICOM system with emphasis to its educational and training functionality.

Infrared spectroscopy and density functional calculations on titanium-dinitrogen complexes

NASA Astrophysics Data System (ADS)

Yoo, Hae-Wook; Choi, Changhyeok; Cho, Soo Gyeong; Jung, Yousung; Choi, Myong Yong

2018-04-01

Titanium-nitrogen complexes were generated by laser ablated titanium (Ti) atoms and N2 gas molecules in this study. These complexes were isolated on the pre-deposited solid Ar matrix on the pre-cooled KBr window (T ∼ 5.4 K), allowing infrared spectra to be measured. Laser ablation experiments with 15N2 isotope provided distinct isotopic shifts in the infrared spectra that strongly implicated the formation of titanium-nitrogen complexes, Ti(NN)x. Density functional theory (DFT) calculations were employed to investigate the molecular structures, electronic ground state, relative energies, and IR frequencies of the anticipated Ti(NN)x complexes. Based on laser ablation experiments and DFT calculations, we were able to assign multiple Ti(NN)x (x = 1-6) species. Particularly, Ti(NN)5 and Ti(NN)6, which have high nitrogen content, may serve as good precursors in preparing polynitrogens.

Maturation of the infant microbiome community structure and function across multiple body sites and in relation to mode of delivery.

PubMed

Chu, Derrick M; Ma, Jun; Prince, Amanda L; Antony, Kathleen M; Seferovic, Maxim D; Aagaard, Kjersti M

2017-03-01

Human microbial communities are characterized by their taxonomic, metagenomic and metabolic diversity, which varies by distinct body sites and influences human physiology. However, when and how microbial communities within each body niche acquire unique taxonomical and functional signatures in early life remains underexplored. We thus sought to determine the taxonomic composition and potential metabolic function of the neonatal and early infant microbiota across multiple body sites and assess the effect of the mode of delivery and its potential confounders or modifiers. A cohort of pregnant women in their early third trimester (n = 81) were prospectively enrolled for longitudinal sampling through 6 weeks after delivery, and a second matched cross-sectional cohort (n = 81) was additionally recruited for sampling once at the time of delivery. Samples across multiple body sites, including stool, oral gingiva, nares, skin and vagina were collected for each maternal-infant dyad. Whole-genome shotgun sequencing and sequencing analysis of the gene encoding the 16S rRNA were performed to interrogate the composition and function of the neonatal and maternal microbiota. We found that the neonatal microbiota and its associated functional pathways were relatively homogeneous across all body sites at delivery, with the notable exception of the neonatal meconium. However, by 6 weeks after delivery, the infant microbiota structure and function had substantially expanded and diversified, with the body site serving as the primary determinant of the composition of the bacterial community and its functional capacity. Although minor variations in the neonatal (immediately at birth) microbiota community structure were associated with the cesarean mode of delivery in some body sites (oral gingiva, nares and skin; R 2 = 0.038), this was not true for neonatal stool (meconium; Mann-Whitney P > 0.05), and there was no observable difference in community function regardless of delivery mode. For infants at 6 weeks of age, the microbiota structure and function had expanded and diversified with demonstrable body site specificity (P < 0.001, R 2 = 0.189) but without discernable differences in community structure or function between infants delivered vaginally or by cesarean surgery (P = 0.057, R 2 = 0.007). We conclude that within the first 6 weeks of life, the infant microbiota undergoes substantial reorganization, which is primarily driven by body site and not by mode of delivery.

Maturation of the Infant Microbiome Community Structure and Function Across Multiple Body Sites and in Relation to Mode of Delivery

PubMed Central

Chu, Derrick M.; Ma, Jun; Prince, Amanda L.; Antony, Kathleen M.; Seferovic, Maxim D.; Aagaard, Kjersti M.

2017-01-01

Human microbial communities are characterized by their taxonomic, metagenomic, and metabolic diversity, which varies by distinct body sites and influences human physiology. However, when and how microbial communities within each body niche acquire unique taxonomical and functional signatures in early life remains underexplored. We thus sought to assess the taxonomic composition and potential metabolic function of the neonatal and early infant microbiota across multiple body sites, and assess the impact of mode of delivery and its potential confounders or modifiers. A cohort of pregnant women in their early 3rd trimester (n=81) were prospectively enrolled for longitudinal sampling through 6 weeks post-delivery, and a second matched cross-sectional cohort (n=81) was additionally recruited for sampling once at delivery. Samples were collected for each maternal-infant dyad across multiple body sites, including stool, oral gingiva, nares, skin and vagina. 16S rRNA gene sequencing analysis and whole genome shotgun sequencing was performed to interrogate the composition and function of the neonatal and maternal microbiota. We found that the neonatal microbiota and its associated functional pathways were relatively homogenous across all body sites at delivery, with the notable exception of neonatal meconium. However, by 6 weeks, the infant microbiota structure and function had significantly expanded and diversified, with body site serving as the primary determinant of the bacterial community composition and its functional capacity. Although minor variations in the neonatal (immediately at birth) microbiota community structure were associated with Cesarean delivery in some body sites (oral, nares, and skin; R2 = 0.038), this was not true in neonatal stool (meconium, Mann-Whitney p>0.05) and there was no observable difference in community function regardless of delivery mode. By 6 weeks of age, the infant microbiota structure and function had expanded and diversified with demonstrable body site specificity (p<0.001, R2 = 0.189), and no discernable differences in neither community structure nor function by Cesarean delivery were identifiable (p=0.057, R2 = 0.007). We conclude that within the first 6 weeks of life, the infant microbiota undergoes significant reorganization that is primarily driven by body site and not by mode of delivery. PMID:28112736

Compartmentalization and Functionality of Nuclear Disorder: Intrinsic Disorder and Protein-Protein Interactions in Intra-Nuclear Compartments

PubMed Central

Meng, Fanchi; Na, Insung; Kurgan, Lukasz; Uversky, Vladimir N.

2015-01-01

The cell nucleus contains a number of membrane-less organelles or intra-nuclear compartments. These compartments are dynamic structures representing liquid-droplet phases which are only slightly denser than the bulk intra-nuclear fluid. They possess different functions, have diverse morphologies, and are typically composed of RNA (or, in some cases, DNA) and proteins. We analyzed 3005 mouse proteins localized in specific intra-nuclear organelles, such as nucleolus, chromatin, Cajal bodies, nuclear speckles, promyelocytic leukemia (PML) nuclear bodies, nuclear lamina, nuclear pores, and perinuclear compartment and compared them with ~29,863 non-nuclear proteins from mouse proteome. Our analysis revealed that intrinsic disorder is enriched in the majority of intra-nuclear compartments, except for the nuclear pore and lamina. These compartments are depleted in proteins that lack disordered domains and enriched in proteins that have multiple disordered domains. Moonlighting proteins found in multiple intra-nuclear compartments are more likely to have multiple disordered domains. Protein-protein interaction networks in the intra-nuclear compartments are denser and include more hubs compared to the non-nuclear proteins. Hubs in the intra-nuclear compartments (except for the nuclear pore) are enriched in disorder compared with non-nuclear hubs and non-nuclear proteins. Therefore, our work provides support to the idea of the functional importance of intrinsic disorder in the cell nucleus and shows that many proteins associated with sub-nuclear organelles in nuclei of mouse cells are enriched in disorder. This high level of disorder in the mouse nuclear proteins defines their ability to serve as very promiscuous binders, possessing both large quantities of potential disorder-based interaction sites and the ability of a single such site to be involved in a large number of interactions. PMID:26712748

Theory of particle detection and multiplicity counting with dead time effects

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

Pal, L.; Pazsit, I.

The subject of this paper is the investigation of the effect of the dead time on the statistics of the particle detection process. A theoretical treatment is provided with the application of the methods of renewal theory. The detector efficiency and various types of the dead time are accounted for. Exact analytical results are derived for the probability distribution functions, the expectations and the variances of the number of detected particles. Explicit solutions are given for a few representative cases. The results should serve for the evaluation of the measurements in view of the dead time correction effects for themore » higher moments of the detector counts. (authors)« less

Integrated Multi-process Microfluidic Systems for Automating Analysis

PubMed Central

Yang, Weichun; Woolley, Adam T.

2010-01-01

Microfluidic technologies have been applied extensively in rapid sample analysis. Some current challenges for standard microfluidic systems are relatively high detection limits, and reduced resolving power and peak capacity compared to conventional approaches. The integration of multiple functions and components onto a single platform can overcome these separation and detection limitations of microfluidics. Multiplexed systems can greatly increase peak capacity in multidimensional separations and can increase sample throughput by analyzing many samples simultaneously. On-chip sample preparation, including labeling, preconcentration, cleanup and amplification, can all serve to speed up and automate processes in integrated microfluidic systems. This paper summarizes advances in integrated multi-process microfluidic systems for automated analysis, their benefits and areas for needed improvement. PMID:20514343

PubMed

Espiard, S; Vantyghem, M-C; Desailloud, R

2017-10-01

Parathormone (PTH), produced by parathyroid glands, is the main regulator of calcium homeostasis. Hypoparathyroidism (hypoPT), due to decrease of PTH production, is a rare disease. Symptoms are multiple, altering function of several organs and leading to a decrease of quality of life. Acquired etiologies, including thyroïdectomy, the main cause of hypoPT, can be distinguished from congenital etiologies, including genetic defects. HypoPT, which is classically treated by supplementation by calcium and active vitamin D, can now be treated by recombinant injection in certain indications as a poor control under classical therapy. Here are summarized current knowledge on etiologies, epidemiology, clinical manifestations and management of hypoPT. © 2017 Elsevier Masson SAS. Tous droits réservés.

Using the Natural Language Paradigm (NLP) to increase vocalizations of older adults with cognitive impairments.

PubMed

Leblanc, Linda A; Geiger, Kaneen B; Sautter, Rachael A; Sidener, Tina M

2007-01-01

The Natural Language Paradigm (NLP) has proven effective in increasing spontaneous verbalizations for children with autism. This study investigated the use of NLP with older adults with cognitive impairments served at a leisure-based adult day program for seniors. Three individuals with limited spontaneous use of functional language participated in a multiple baseline design across participants. Data were collected on appropriate and inappropriate vocalizations with appropriate vocalizations coded as prompted or unprompted during baseline and treatment sessions. All participants experienced increases in appropriate speech during NLP with variable response patterns. Additionally, the two participants with substantial inappropriate vocalizations showed decreases in inappropriate speech. Implications for intervention in day programs are discussed.

Polymeric scaffolds for three-dimensional culture of nerve cells: a model of peripheral nerve regeneration

PubMed Central

Ayala-Caminero, Radamés; Pinzón-Herrera, Luis; Martinez, Carol A. Rivera; Almodovar, Jorge

2018-01-01

Understanding peripheral nerve repair requires the evaluation of 3D structures that serve as platforms for 3D cell culture. Multiple platforms for 3D cell culture have been developed, mimicking peripheral nerve growth and function, in order to study tissue repair or diseases. To recreate an appropriate 3D environment for peripheral nerve cells, key factors are to be considered including: selection of cells, polymeric biomaterials to be used, and fabrication techniques to shape and form the 3D scaffolds for cellular culture. This review focuses on polymeric 3D platforms used for the development of 3D peripheral nerve cell cultures. PMID:29515936

Soft currencies, cash economies, new monies: Past and present

PubMed Central

Guyer, Jane I.

2012-01-01

Current variation in the forms of money challenges economic anthropologists and historians to review theory and comparative findings on multiple currency systems. There are four main sections to the paper devoted to (i) the present continuum of hard to soft currencies as an instance of multiplicity, including discussion of different combinations of the classic four functions of money, especially the relationship between store of value and medium of exchange; (ii) the logic of anthropological inquiry into multiple currency economies; (iii) the case of the monies of Atlantic Africa, applying the analytics of exchange rates as conversions to African transactions; and (iv) the return to economic life in a present day Nigerian economy lived in soft currency and cash. The paper identifies five findings that suggest foci for future research. (i) The widespread occurrence of conversions, which bring together ranking principles within transactions. (ii) Several types of positional ranking ranging from simple stepwise ordinal scales to iconic ordinality that creates a parabolic curve of value. (iii) Fictional units of account that serve to mediate both the memorization of nonreductive transactions and their nature as conversions. (iv) The importance of the temporal reach of what constitutes wealth: over the short run, the life span, intergenerational succession, and in (legal) perpetuity (as for corporate and sovereign debts and specified assets). (v) The social niches in which these qualities are brought together in transactional regimes. In conclusion, the paper returns to the exchange function of cash, soft currencies, and new money forms. PMID:22308423

Tactical resource allocation and elective patient admission planning in care processes.

PubMed

Hulshof, Peter J H; Boucherie, Richard J; Hans, Erwin W; Hurink, Johann L

2013-06-01

Tactical planning of resources in hospitals concerns elective patient admission planning and the intermediate term allocation of resource capacities. Its main objectives are to achieve equitable access for patients, to meet production targets/to serve the strategically agreed number of patients, and to use resources efficiently. This paper proposes a method to develop a tactical resource allocation and elective patient admission plan. These tactical plans allocate available resources to various care processes and determine the selection of patients to be served that are at a particular stage of their care process. Our method is developed in a Mixed Integer Linear Programming (MILP) framework and copes with multiple resources, multiple time periods and multiple patient groups with various uncertain treatment paths through the hospital, thereby integrating decision making for a chain of hospital resources. Computational results indicate that our method leads to a more equitable distribution of resources and provides control of patient access times, the number of patients served and the fraction of allocated resource capacity. Our approach is generic, as the base MILP and the solution approach allow for including various extensions to both the objective criteria and the constraints. Consequently, the proposed method is applicable in various settings of tactical hospital management.

Estimating Herd Immunity to Amphibian Chytridiomycosis in Madagascar Based on the Defensive Function of Amphibian Skin Bacteria

PubMed Central

Bletz, Molly C.; Myers, Jillian; Woodhams, Douglas C.; Rabemananjara, Falitiana C. E.; Rakotonirina, Angela; Weldon, Che; Edmonds, Devin; Vences, Miguel; Harris, Reid N.

2017-01-01

For decades, Amphibians have been globally threatened by the still expanding infectious disease, chytridiomycosis. Madagascar is an amphibian biodiversity hotspot where Batrachochytrium dendrobatidis (Bd) has only recently been detected. While no Bd-associated population declines have been reported, the risk of declines is high when invasive virulent lineages become involved. Cutaneous bacteria contribute to host innate immunity by providing defense against pathogens for numerous animals, including amphibians. Little is known, however, about the cutaneous bacterial residents of Malagasy amphibians and the functional capacity they have against Bd. We cultured 3179 skin bacterial isolates from over 90 frog species across Madagascar, identified them via Sanger sequencing of approximately 700 bp of the 16S rRNA gene, and characterized their functional capacity against Bd. A subset of isolates was also tested against multiple Bd genotypes. In addition, we applied the concept of herd immunity to estimate Bd-associated risk for amphibian communities across Madagascar based on bacterial antifungal activity. We found that multiple bacterial isolates (39% of all isolates) cultured from the skin of Malagasy frogs were able to inhibit Bd. Mean inhibition was weakly correlated with bacterial phylogeny, and certain taxonomic groups appear to have a high proportion of inhibitory isolates, such as the Enterobacteriaceae, Pseudomonadaceae, and Xanthamonadaceae (84, 80, and 75% respectively). Functional capacity of bacteria against Bd varied among Bd genotypes; however, there were some bacteria that showed broad spectrum inhibition against all tested Bd genotypes, suggesting that these bacteria would be good candidates for probiotic therapies. We estimated Bd-associated risk for sampled amphibian communities based on the concept of herd immunity. Multiple amphibian communities, including those in the amphibian diversity hotspots, Andasibe and Ranomafana, were estimated to be below the 80% herd immunity threshold, suggesting they may be at higher risk to chytridiomycosis if a lethal Bd genotype emerges in Madagascar. While this predictive approach rests on multiple assumptions, and incorporates only one component of hosts' defense against Bd, their culturable cutaneous bacterial defense, it can serve as a foundation for continued research on Bd-associated risk for the endemic frogs of Madagascar. PMID:28959244

Substance Use and Self-Harm: Case Studies From Patients Admitted to an Urban Hospital Following Medically Serious Self-Harm.

PubMed

Breet, Elsie; Bantjes, Jason

2017-12-01

Few qualitative studies have explored the relationship between substance use and self-harm. We employed a multiple-case study research design to analyze data from 80 patients who were admitted to a hospital in South Africa following self-harm. Our analysis revealed, from the perspective of patients, a number of distinct ways in which substance use is implicated in self-harm. Some patients reported that substance intoxication resulted in poor decision making and impulsivity, which led to self-harm. Others said substance use facilitated their self-harm. Some participants detailed how in the past their chronic substance use had served an adaptive function helping them to cope with distress, but more recently, this coping mechanism had failed which precipitated their self-harm. Some participants reported that substance use by someone else triggered their self-harm. Findings suggest that there are multiple pathways and a host of variables which mediate the relationship between substance use and self-harm.

The guanylyl cyclase family at Y2K.

PubMed

Wedel, B; Garbers, D

2001-01-01

During the 1980s the purification, cloning, and expression of various forms of guanylyl cyclase (GC) revealed that they served as receptors for extracellular signals. Seven membrane forms, which presumably exist as homodimers, and four subunits of apparent heterodimers (commonly referred to as the soluble forms) are known, but in animals such as nematodes, much larger numbers of GCs are expressed. The number of transmembrane segments (none, one, or multiple) divide the GC family into three groups. Those with no or one transmembrane segment bind nitric oxide/carbon monoxide (NO/CO) or peptides. There are no known ligands for the multiple transmembrane segment class of GCs. Mutational and structural analyses support a model where catalysis requires a shared substrate binding site between the subunits, whether homomeric or heteromeric in nature. Because some cyclases or cyclase ligand genes lack specific GC inhibitors, disruption of either has been used to define the functions of individual cyclases, as well as to define human genetic disease counterparts.

Multiple layers of temporal and spatial control regulate accumulation of the fruiting body-specific protein APP in Sordaria macrospora and Neurospora crassa.

PubMed

Nowrousian, Minou; Piotrowski, Markus; Kück, Ulrich

2007-07-01

During fungal fruiting body development, specialized cell types differentiate from vegetative mycelium. We have isolated a protein from the ascomycete Sordaria macrospora that is not present during vegetative growth but accumulates in perithecia. The protein was sequenced by mass spectrometry and the corresponding gene was termed app (abundant perithecial protein). app transcript occurs only after the onset of sexual development; however, the formation of ascospores is not a prerequisite for APP accumulation. The transcript of the Neurospora crassa ortholog is present prior to fertilization, but the protein accumulates only after fertilization. In crosses of N. crassa Deltaapp strains with the wild type, APP accumulates when the wild type serves as female parent, but not in the reciprocal cross; thus, the presence of a functional female app allele is necessary and sufficient for APP accumulation. These findings highlight multiple layers of temporal and spatial control of gene expression during fungal development.

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

Jacobs, Gary; Pendyala, Venkat Ramana Rao; Martinelli, Michela

XANES K-edge spectra of potassium promoter in precipitated Fe catalysts were acquired following activation by carburization in CO and as a function of time on-stream during the course of a Fischer–Tropsch synthesis run for a 100Fe:2K catalyst by withdrawing catalysts, sealed in wax product, for analysis. CO-activated and end-of-run spectra of the catalyst were also obtained for a 100Fe:5K catalyst. Peaks representing electronic transitions and multiple scattering were observed and resembled reference spectra for potassium carbonate or potassium formate. The shift in the multiple scattering peak to higher energy was consistent with sintering of potassium promoter during the course ofmore » the reaction test. The catalyst, however, retained its carbidic state, as demonstrated by XANES and EXAFS spectra at the iron K-edge, suggesting that sintering of potassium did not adversely affect the carburization rate, which is important for preventing iron carbides from oxidizing. This method serves as a starting point for developing better understanding of the chemical state and changes in structure occurring with alkali promoter.« less

The impact of attachment and depression symptoms on multiple risk behaviors in post-war adolescents in northern Uganda.

PubMed

Okello, J; Nakimuli-Mpungu, E; Klasen, F; Voss, C; Musisi, S; Broekaert, E; Derluyn, I

2015-07-15

We have previously shown that depression symptoms are associated with multiple risk behaviors and that parental attachments are protective against depression symptoms in post-war adolescents. Accumulating literature indicates that low levels of attachment may sensitize individuals to increased multiple risk behaviors when depression symptoms exist. This investigation examined the interactive effects of attachment and depression symptoms on multiple risk behavior. We conducted hierarchical logistic regression analyses to examine the impact of attachment and depression symptoms on multiple risk behavior in our post-war sample of 551 adolescents in Gulu district. Analyses revealed interactive effects for only maternal attachment-by-depression interaction. Interestingly, high levels of maternal attachment exacerbated the relationship between depression symptoms and multiple risk behaviors while low levels of maternal attachment attenuated this relationship. It is possible that this analysis could be biased by a common underlying factor that influences self-reporting and therefore is correlated with each of self-reported attachment security, depressive symptoms, and multiple risk behaviors. These findings suggest that maternal attachment serves as a protective factor at low levels while serving as an additional risk factor at high levels. Findings support and expand current knowledge about the roles that attachment and depression symptoms play in the development of multiple risk behaviors and suggest a more complex etiology for post-war adolescents. Copyright © 2015 Elsevier B.V. All rights reserved.

Ncam1a and Ncam1b: two carriers of polysialic acid with different functions in the developing zebrafish nervous system.

PubMed

Langhauser, Melanie; Ustinova, Jana; Rivera-Milla, Eric; Ivannikov, Darja; Seidl, Carmen; Slomka, Christin; Finne, Jukka; Yoshihara, Yoshihiro; Bastmeyer, Martin; Bentrop, Joachim

2012-02-01

Polysialic acid (polySia) is mainly described as a glycan modification of the neural cell adhesion molecule NCAM1. PolySia-NCAM1 has multiple functions during the development of vertebrate nervous systems including axon extension and fasciculation. Phylogenetic analyses reveal the presence of two related gene clusters, NCAM1 and NCAM2, in tetrapods and fishes. Within the ncam1 cluster, teleost fishes express ncam1a (ncam) and ncam1b (pcam) as duplicated paralogs which arose from a second round of ray-finned fish-specific genome duplication. Tetrapods, in contrast, express a single NCAM1 gene. Using the zebrafish model, we identify Ncam1b as a novel major carrier of polySia in the nervous system. PolySia-Ncam1a is expressed predominantly in rostral regions of the developing nervous system, whereas polySia-Ncam1b prevails caudally. We show that ncam1a and ncam1b have different expression domains which only partially overlap. Furthermore, Ncam1a and Ncam1b and their polySia modifications serve different functions in axon guidance. Formation of the posterior commissure at the forebrain/midbrain junction requires polySia-Ncam1a on the axons for proper fasciculation, whereas Ncam1b, expressed by midbrain cell bodies, serves as an instructive guidance cue for the dorso-medially directed growth of axons. Spinal motor axons, on the other hand, depend on axonally expressed Ncam1b for correct growth toward their target region. Collectively, these findings suggest that the genome duplication in the teleost lineage has provided the basis for a functional diversification of polySia carriers in the nervous system.

Complex expression and localization of inactivating Kv channels in cultured hippocampal astrocytes.

PubMed

Bekar, Lane K; Loewen, Matthew E; Cao, Kun; Sun, Xianfeng; Leis, Jerome; Wang, Rui; Forsyth, George W; Walz, Wolfgang

2005-03-01

Voltage-gated potassium channels are well established as critical for setting action potential frequency, membrane potential, and neurotransmitter release in neurons. However, their role in the "nonexcitable" glial cell type is yet to be fully understood. We used whole cell current kinetics, pharmacology, immunocytochemistry, and RT-PCR to characterize A-type current in hippocampal astrocyte cultures to better understand its function. Pharmacological analysis suggests that approximately 70, 10, and <5% of total A current is associated with Kv4, Kv3, and Kv1 channels, respectively. In addition, pharmacology and kinetics provide evidence for a significant contribution of KChIP accessory proteins to astrocytic A-channel composition. Localization of the Shaw Kv3.4 channel to astrocytic processes and the Shal Kv4.3 channel to soma suggest that these channels serve a specific function. Given this complex A-type channel expression pattern, we assessed the role of A currents in membrane voltage oscillations in response to current injections. Although TEA-sensitive delayed-rectifying currents are involved in the extent of repolarization, 4-AP-sensitive A currents serve to increase the rate. As in neurons, this effect may enable astrocytes to respond rapidly to high-frequency synaptic events. Our results indicate that hippocampal astrocytes in vitro express multiple A-type Kv channel alpha-subunits with accessory, possibly Ca(2+)-sensitive, cytoplasmic subunits that appear to be specifically localized to subcellular membrane compartments. Function of these channels remains to be determined in a physiological setting. However, this study suggests that they enable astrocytes to respond rapidly with membrane voltage oscillations to high-frequency incoming signals, possibly synchronizing astrocyte function to neuronal activity.

Institutional Identity and Organizational Structure in Multi-Campus Universities.

ERIC Educational Resources Information Center

Dengerink, Harold A.

2001-01-01

Explores the structure of universities with multiple campuses but no independent central administrative system. Discusses the hybrid missions of branch campuses, which are asked to serve both the overall university and local constituent communities. Explains that these multiple missions may conflict and thus require intentional organizational…

For All Intents and Purposes: Twitter as a Foundational Technology for Teachers

ERIC Educational Resources Information Center

Greenhalgh, Spencer P.; Rosenberg, Joshua M.; Wolf, Leigh Graves

2016-01-01

Twitter is increasingly accepted as an important educational technology and has been shown to serve a range of purposes. In fact, this variety suggests that Twitter has the potential to serve as a foundational technology: one capable of supporting teachers' learning across multiple formal and informal contexts. To explore this possibility, we…

20 CFR 663.430 - Under what circumstances may mechanisms other than ITA's be used to provide training services?

Code of Federal Regulations, 2011 CFR

2011-04-01

... are an insufficient number of eligible providers in the local area to accomplish the purpose of a... organization to serve special participant populations that face multiple barriers to employment, as described... demonstrated effectiveness, particularly as it applies to the special participant population to be served. The...

Telephone-Administered Cognitive Behavioral Therapy for Veterans Served by Community-Based Outpatient Clinics

ERIC Educational Resources Information Center

Mohr, David C.; Carmody, Timothy; Erickson, Lauren; Jin, Ling; Leader, Julie

2011-01-01

Objective: Multiple trials have found telephone-administered cognitive behavioral therapy (T-CBT) to be effective for the treatment of depression. The aim of this study was to evaluate T-CBT for the treatment of depression among veterans served by community-based outpatient clinics (CBOCs) outside of major urban areas. Method: Eighty-five veterans…

At Risk on the Border: Assessment of Student Learning at an Hispanic Serving Institution

ERIC Educational Resources Information Center

Davila, Mario A.; Lovett, Steve; Hartley, Deborah J.

2018-01-01

Hispanics face multiple barriers to academic achievement. This study measured learning in an undergraduate criminal justice program at an Hispanic Serving Institution bordering Mexico. We estimated the average gains students achieved across core content areas using a technique that can be used by other faculty as part of program assessment. The…

Leveraging Innovation in Science Education: Using Writing and Assessment to Decode the Class Size Conundrum

ERIC Educational Resources Information Center

Camfield, Eileen Kogl; McFall, Eileen Eckert; Land, Kirkwood M.

2016-01-01

Introductory biology courses are supposed to serve as gateways for many majors, but too often they serve instead as gatekeepers. Reliance on lectures, large classes, and multiple-choice tests results in high drop and failure rates. Critiques of undergraduate science education are clear about the problems with conventional introductory science…

APL: An Alternative to the Multi-Language Environment for Education. Systems Research Memo Number Four.

ERIC Educational Resources Information Center

Lippert, Henry T.; Harris, Edward V.

The diverse requirements for computing facilities in education place heavy demands upon available resources. Although multiple or very large computers can supply such diverse needs, their cost makes them impractical for many institutions. Small computers which serve a few specific needs may be an economical answer. However, to serve operationally…

Humin as an electron donor for enhancement of multiple microbial reduction reactions with different redox potentials in a consortium.

PubMed

Zhang, Dongdong; Zhang, Chunfang; Xiao, Zhixing; Suzuki, Daisuke; Katayama, Arata

2015-02-01

A solid-phase humin, acting as an electron donor, was able to enhance multiple reductive biotransformations, including dechlorination of pentachlorophenol (PCP), dissimilatory reduction of amorphous Fe (III) oxide (FeOOH), and reduction of nitrate, in a consortium. Humin that was chemically reduced by NaBH4 served as an electron donor for these microbial reducing reactions, with electron donating capacities of 0.013 mmol e(-)/g for PCP dechlorination, 0.15 mmol e(-)/g for iron reduction, and 0.30 mmol e(-)/g for nitrate reduction. Two pairs of oxidation and reduction peaks within the humin were detected by cyclic voltammetry analysis. 16S rRNA gene sequencing-based microbial community analysis of the consortium incubated with different terminal electron acceptors, suggested that Dehalobacter sp., Bacteroides sp., and Sulfurospirillum sp. were involved in the PCP dechlorination, dissimilatory iron reduction, and nitrate reduction, respectively. These findings suggested that humin functioned as a versatile redox mediator, donating electrons for multiple respiration reactions with different redox potentials. Copyright © 2014 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Ultrasensitive response motifs: basic amplifiers in molecular signalling networks

PubMed Central

Zhang, Qiang; Bhattacharya, Sudin; Andersen, Melvin E.

2013-01-01

Multi-component signal transduction pathways and gene regulatory circuits underpin integrated cellular responses to perturbations. A recurring set of network motifs serve as the basic building blocks of these molecular signalling networks. This review focuses on ultrasensitive response motifs (URMs) that amplify small percentage changes in the input signal into larger percentage changes in the output response. URMs generally possess a sigmoid input–output relationship that is steeper than the Michaelis–Menten type of response and is often approximated by the Hill function. Six types of URMs can be commonly found in intracellular molecular networks and each has a distinct kinetic mechanism for signal amplification. These URMs are: (i) positive cooperative binding, (ii) homo-multimerization, (iii) multistep signalling, (iv) molecular titration, (v) zero-order covalent modification cycle and (vi) positive feedback. Multiple URMs can be combined to generate highly switch-like responses. Serving as basic signal amplifiers, these URMs are essential for molecular circuits to produce complex nonlinear dynamics, including multistability, robust adaptation and oscillation. These dynamic properties are in turn responsible for higher-level cellular behaviours, such as cell fate determination, homeostasis and biological rhythm. PMID:23615029

Situating the default-mode network along a principal gradient of macroscale cortical organization

PubMed Central

Margulies, Daniel S.; Goulas, Alexandros; Falkiewicz, Marcel; Huntenburg, Julia M.; Langs, Georg; Bezgin, Gleb; Eickhoff, Simon B.; Castellanos, F. Xavier; Petrides, Michael; Jefferies, Elizabeth; Smallwood, Jonathan

2016-01-01

Understanding how the structure of cognition arises from the topographical organization of the cortex is a primary goal in neuroscience. Previous work has described local functional gradients extending from perceptual and motor regions to cortical areas representing more abstract functions, but an overarching framework for the association between structure and function is still lacking. Here, we show that the principal gradient revealed by the decomposition of connectivity data in humans and the macaque monkey is anchored by, at one end, regions serving primary sensory/motor functions and at the other end, transmodal regions that, in humans, are known as the default-mode network (DMN). These DMN regions exhibit the greatest geodesic distance along the cortical surface—and are precisely equidistant—from primary sensory/motor morphological landmarks. The principal gradient also provides an organizing spatial framework for multiple large-scale networks and characterizes a spectrum from unimodal to heteromodal activity in a functional metaanalysis. Together, these observations provide a characterization of the topographical organization of cortex and indicate that the role of the DMN in cognition might arise from its position at one extreme of a hierarchy, allowing it to process transmodal information that is unrelated to immediate sensory input. PMID:27791099

Conceptual Understanding of Multiplicative Properties through Endogenous Digital Game Play

ERIC Educational Resources Information Center

Denham, Andre

2012-01-01

This study purposed to determine the effect of an endogenously designed instructional game on conceptual understanding of the associative and distributive properties of multiplication. Additional this study sought to investigate if performance on measures of conceptual understanding taken prior to and after game play could serve as predictors of…

Cyber infrastructure for Fusarium: three integrated platforms supporting strain identification, phylogenetics, comparative genomics and knowledge sharing.

PubMed

Park, Bongsoo; Park, Jongsun; Cheong, Kyeong-Chae; Choi, Jaeyoung; Jung, Kyongyong; Kim, Donghan; Lee, Yong-Hwan; Ward, Todd J; O'Donnell, Kerry; Geiser, David M; Kang, Seogchan

2011-01-01

The fungal genus Fusarium includes many plant and/or animal pathogenic species and produces diverse toxins. Although accurate species identification is critical for managing such threats, it is difficult to identify Fusarium morphologically. Fortunately, extensive molecular phylogenetic studies, founded on well-preserved culture collections, have established a robust foundation for Fusarium classification. Genomes of four Fusarium species have been published with more being currently sequenced. The Cyber infrastructure for Fusarium (CiF; http://www.fusariumdb.org/) was built to support archiving and utilization of rapidly increasing data and knowledge and consists of Fusarium-ID, Fusarium Comparative Genomics Platform (FCGP) and Fusarium Community Platform (FCP). The Fusarium-ID archives phylogenetic marker sequences from most known species along with information associated with characterized isolates and supports strain identification and phylogenetic analyses. The FCGP currently archives five genomes from four species. Besides supporting genome browsing and analysis, the FCGP presents computed characteristics of multiple gene families and functional groups. The Cart/Favorite function allows users to collect sequences from Fusarium-ID and the FCGP and analyze them later using multiple tools without requiring repeated copying-and-pasting of sequences. The FCP is designed to serve as an online community forum for sharing and preserving accumulated experience and knowledge to support future research and education.

Common carp disrupt ecosystem structure and function through middle-out effects

USGS Publications Warehouse

Kaemingk, Mark A.; Jolley, Jeffrey C.; Paukert, Craig P.; Willis, David W.; Henderson, Kjetil R.; Holland, Richard S.; Wanner, Greg A.; Lindvall, Mark L.

2016-01-01

Middle-out effects or a combination of top-down and bottom-up processes create many theoretical and empirical challenges in the realm of trophic ecology. We propose using specific autecology or species trait (i.e. behavioural) information to help explain and understand trophic dynamics that may involve complicated and non-unidirectional trophic interactions. The common carp (Cyprinus carpio) served as our model species for whole-lake observational and experimental studies; four trophic levels were measured to assess common carp-mediated middle-out effects across multiple lakes. We hypothesised that common carp could influence aquatic ecosystems through multiple pathways (i.e. abiotic and biotic foraging, early life feeding, nutrient). Both studies revealed most trophic levels were affected by common carp, highlighting strong middle-out effects likely caused by common carp foraging activities and abiotic influence (i.e. sediment resuspension). The loss of water transparency, submersed vegetation and a shift in zooplankton dynamics were the strongest effects. Trophic levels furthest from direct pathway effects were also affected (fish life history traits). The present study demonstrates that common carp can exert substantial effects on ecosystem structure and function. Species capable of middle-out effects can greatly modify communities through a variety of available pathways and are not confined to traditional top-down or bottom-up processes.

Multiple channel coincidence detector and controller for microseismic data analysis

DOEpatents

Fasching, George E.

1976-11-16

A multiple channel coincidence detector circuit is provided for analyzing data either in real time or recorded data on a magnetic tape during an experiment for determining location and progression of fractures in an oil field or the like while water is being injected at high pressure in wells located in the field. The circuit is based upon the utilization of a set of parity generator trees combined with monostable multivibrators to detect the occurrence of two events at any pair of channel input terminals that are within a preselected time frame and have an amplitude above a preselected magnitude. The parity generators perform an exclusive OR function in a timing circuit composed of monostable multivibrators that serve to yield an output when two events are present in the preselected time frame. Any coincidences falling outside this time frame are considered either noise or not otherwise useful in the analysis of the recorded data. Input pulses of absolute magnitude below the low-level threshold setting of a bipolar low-level threshold detector are unwanted and therefore rejected. A control output is provided for a utilization device from a coincidence hold circuit that may be used to halt a tape search unit at the time of coincidence or perform other useful control functions.

Evaluation of high-density, multi-contact nerve cuffs for activation of grasp muscles in monkeys

NASA Astrophysics Data System (ADS)

Brill, N. A.; Naufel, S. N.; Polasek, K.; Ethier, C.; Cheesborough, J.; Agnew, S.; Miller, L. E.; Tyler, D. J.

2018-06-01

Objective. The objective of this work was to evaluate whether nerve cuffs can selectively activate hand muscles for functional electrical stimulation (FES). FES typically involves identifying and implanting electrodes in many individual muscles, but nerve cuffs only require implantation at a single site around the nerve. This method is surgically more attractive. Nerve cuffs may also more effectively stimulate intrinsic hand muscles, which are difficult to implant and stimulate without spillover to adjacent muscles. Approach. To evaluate its ability to selectively activate muscles, we implanted and tested the flat interface nerve electrode (FINE), which is designed to selectively stimulate peripheral nerves that innervate multiple muscles (Tyler and Durand 2002 IEEE Trans. Neural Syst. Rehabil. Eng. 10 294-303). We implanted FINEs on the nerves and bipolar intramuscular wires for recording compound muscle action potentials (CMAPs) from up to 20 muscles in each arm of six monkeys. We then collected recruitment curves while the animals were anesthetized. Main result. A single FINE implanted on an upper extremity nerve in the monkey can selectively activate muscles or small groups of muscles to produce multiple, independent hand functions. Significance. FINE cuffs can serve as a viable supplement to intramuscular electrodes in FES systems, where they can better activate intrinsic and extrinsic muscles with lower currents and less extensive surgery.

Prediction processes during multiple object tracking (MOT): involvement of dorsal and ventral premotor cortices

PubMed Central

Atmaca, Silke; Stadler, Waltraud; Keitel, Anne; Ott, Derek V M; Lepsien, Jöran; Prinz, Wolfgang

2013-01-01

Background The multiple object tracking (MOT) paradigm is a cognitive task that requires parallel tracking of several identical, moving objects following nongoal-directed, arbitrary motion trajectories. Aims The current study aimed to investigate the employment of prediction processes during MOT. As an indicator for the involvement of prediction processes, we targeted the human premotor cortex (PM). The PM has been repeatedly implicated to serve the internal modeling of future actions and action effects, as well as purely perceptual events, by means of predictive feedforward functions. Materials and methods Using functional magnetic resonance imaging (fMRI), BOLD activations recorded during MOT were contrasted with those recorded during the execution of a cognitive control task that used an identical stimulus display and demanded similar attentional load. A particular effort was made to identify and exclude previously found activation in the PM-adjacent frontal eye fields (FEF). Results We replicated prior results, revealing occipitotemporal, parietal, and frontal areas to be engaged in MOT. Discussion The activation in frontal areas is interpreted to originate from dorsal and ventral premotor cortices. The results are discussed in light of our assumption that MOT engages prediction processes. Conclusion We propose that our results provide first clues that MOT does not only involve visuospatial perception and attention processes, but prediction processes as well. PMID:24363971

Acute carbon dioxide avoidance in Caenorhabditis elegans

PubMed Central

Hallem, Elissa A.; Sternberg, Paul W.

2008-01-01

Carbon dioxide is produced as a by-product of cellular respiration by all aerobic organisms and thus serves for many animals as an important indicator of food, mates, and predators. However, whether free-living terrestrial nematodes such as Caenorhabditis elegans respond to CO2 was unclear. We have demonstrated that adult C. elegans display an acute avoidance response upon exposure to CO2 that is characterized by the cessation of forward movement and the rapid initiation of backward movement. This response is mediated by a cGMP signaling pathway that includes the cGMP-gated heteromeric channel TAX-2/TAX-4. CO2 avoidance is modulated by multiple signaling molecules, including the neuropeptide Y receptor NPR-1 and the calcineurin subunits TAX-6 and CNB-1. Nutritional status also modulates CO2 responsiveness via the insulin and TGFβ signaling pathways. CO2 response is mediated by a neural circuit that includes the BAG neurons, a pair of sensory neurons of previously unknown function. TAX-2/TAX-4 function in the BAG neurons to mediate acute CO2 avoidance. Our results demonstrate that C. elegans senses and responds to CO2 using multiple signaling pathways and a neural network that includes the BAG neurons and that this response is modulated by the physiological state of the worm. PMID:18524955

Acute carbon dioxide avoidance in Caenorhabditis elegans.

PubMed

Hallem, Elissa A; Sternberg, Paul W

2008-06-10

Carbon dioxide is produced as a by-product of cellular respiration by all aerobic organisms and thus serves for many animals as an important indicator of food, mates, and predators. However, whether free-living terrestrial nematodes such as Caenorhabditis elegans respond to CO2 was unclear. We have demonstrated that adult C. elegans display an acute avoidance response upon exposure to CO2 that is characterized by the cessation of forward movement and the rapid initiation of backward movement. This response is mediated by a cGMP signaling pathway that includes the cGMP-gated heteromeric channel TAX-2/TAX-4. CO2 avoidance is modulated by multiple signaling molecules, including the neuropeptide Y receptor NPR-1 and the calcineurin subunits TAX-6 and CNB-1. Nutritional status also modulates CO2 responsiveness via the insulin and TGFbeta signaling pathways. CO2 response is mediated by a neural circuit that includes the BAG neurons, a pair of sensory neurons of previously unknown function. TAX-2/TAX-4 function in the BAG neurons to mediate acute CO2 avoidance. Our results demonstrate that C. elegans senses and responds to CO2 using multiple signaling pathways and a neural network that includes the BAG neurons and that this response is modulated by the physiological state of the worm.

Cyber infrastructure for Fusarium: three integrated platforms supporting strain identification, phylogenetics, comparative genomics and knowledge sharing

PubMed Central

Park, Bongsoo; Park, Jongsun; Cheong, Kyeong-Chae; Choi, Jaeyoung; Jung, Kyongyong; Kim, Donghan; Lee, Yong-Hwan; Ward, Todd J.; O'Donnell, Kerry; Geiser, David M.; Kang, Seogchan

2011-01-01

The fungal genus Fusarium includes many plant and/or animal pathogenic species and produces diverse toxins. Although accurate species identification is critical for managing such threats, it is difficult to identify Fusarium morphologically. Fortunately, extensive molecular phylogenetic studies, founded on well-preserved culture collections, have established a robust foundation for Fusarium classification. Genomes of four Fusarium species have been published with more being currently sequenced. The Cyber infrastructure for Fusarium (CiF; http://www.fusariumdb.org/) was built to support archiving and utilization of rapidly increasing data and knowledge and consists of Fusarium-ID, Fusarium Comparative Genomics Platform (FCGP) and Fusarium Community Platform (FCP). The Fusarium-ID archives phylogenetic marker sequences from most known species along with information associated with characterized isolates and supports strain identification and phylogenetic analyses. The FCGP currently archives five genomes from four species. Besides supporting genome browsing and analysis, the FCGP presents computed characteristics of multiple gene families and functional groups. The Cart/Favorite function allows users to collect sequences from Fusarium-ID and the FCGP and analyze them later using multiple tools without requiring repeated copying-and-pasting of sequences. The FCP is designed to serve as an online community forum for sharing and preserving accumulated experience and knowledge to support future research and education. PMID:21087991

Phenotype–genotype correlation in Hirschsprung disease is illuminated by comparative analysis of the RET protein sequence

PubMed Central

Kashuk, Carl S.; Stone, Eric A.; Grice, Elizabeth A.; Portnoy, Matthew E.; Green, Eric D.; Sidow, Arend; Chakravarti, Aravinda; McCallion, Andrew S.

2005-01-01

The ability to discriminate between deleterious and neutral amino acid substitutions in the genes of patients remains a significant challenge in human genetics. The increasing availability of genomic sequence data from multiple vertebrate species allows inclusion of sequence conservation and physicochemical properties of residues to be used for functional prediction. In this study, the RET receptor tyrosine kinase serves as a model disease gene in which a broad spectrum (≥116) of disease-associated mutations has been identified among patients with Hirschsprung disease and multiple endocrine neoplasia type 2. We report the alignment of the human RET protein sequence with the orthologous sequences of 12 non-human vertebrates (eight mammalian, one avian, and three teleost species), their comparative analysis, the evolutionary topology of the RET protein, and predicted tolerance for all published missense mutations. We show that, although evolutionary conservation alone provides significant information to predict the effect of a RET mutation, a model that combines comparative sequence data with analysis of physiochemical properties in a quantitative framework provides far greater accuracy. Although the ability to discern the impact of a mutation is imperfect, our analyses permit substantial discrimination between predicted functional classes of RET mutations and disease severity even for a multigenic disease such as Hirschsprung disease. PMID:15956201

Associations between parenting, media use, cumulative risk, and children's executive functioning.

PubMed

Linebarger, Deborah L; Barr, Rachel; Lapierre, Matthew A; Piotrowski, Jessica T

2014-01-01

This study was designed to examine how parenting style, media exposure, and cumulative risk were associated with executive functioning (EF) during early childhood. A nationally representative group of US parents/caregivers (N = 1156) with 1 child between 2 and 8 years participated in a telephone survey. Parents were asked to report on their child's exposure to television, music, and book reading through a 24-hour time diary. Parents also reported a host of demographic and parenting variables as well as questions on their child's EF. Separate multiple regressions for preschool (2-5 years) and school-aged (6-8 years) children grouped by cumulative risk were conducted. Parenting style moderated the risks of exposure to background television on EF for high-risk preschool-age children. Educational TV exposure served as a buffer for high-risk school-aged children. Cumulative risk, age, and parenting quality interacted with a number of the exposure effects. The study showed a complex pattern of associations between cumulative risk, parenting, and media exposure with EF during early childhood. Consistent with the American Academy of Pediatrics, these findings support the recommendation that background television should be turned off when a child is in the room and suggest that exposure to high-quality content across multiple media platforms may be beneficial.

Prolactin-dependent modulation of organogenesis in the vertebrate: Recent discoveries in zebrafish.

PubMed

Nguyen, Nhu; Stellwag, Edmund J; Zhu, Yong

2008-11-01

The scientific literature is replete with evidence of the multifarious functions of the prolactin (PRL)/growth hormone (GH) superfamily in adult vertebrates. However, little information is available on the roles of PRL and related hormones prior to the adult stage of development. A limited number of studies suggest that GH functions to stimulate glucose transport and protein synthesis in mouse blastocytes and may be involved during mammalian embryogenesis. In contrast, the evidence for a role of PRL during vertebrate embryogenesis is limited and controversial. Genes encoding GH/PRL hormones and their respective receptors are actively transcribed and translated in various animal models at different time points, particularly during tissue remodeling. We have addressed the potential function of GH/PRL hormones during embryonic development in zebrafish by the temporary inhibition of in vivo PRL translation. This treatment caused multiple morphological defects consistent with a role of PRL in embryonic-stage organogenesis. The affected organs and tissues are known targets of PRL activity in fish and homologous structures in mammalian species. Traditionally, the GH/PRL hormones are viewed as classical endocrine hormones, mediating functions through the circulatory system. More recent evidence points to cytokine-like actions of these hormones through either an autocrine or a paracrine mechanism. In some situations they could mimic actions of developmentally regulated genes as suggested by experiments in multiple organisms. In this review, we present similarities and disparities between zebrafish and mammalian models in relation to PRL and PRLR activity. We conclude that the zebrafish could serve as a suitable alternative to the rodent model to study PRL functions in development, especially in relation to organogenesis.

Functional significance of O-GlcNAc modification in regulating neuronal properties.

PubMed

Hwang, Hongik; Rhim, Hyewhon

2018-03-01

Post-translational modifications (PTMs) covalently modify proteins and diversify protein functions. Along with protein phosphorylation, another common PTM is the addition of O-linked β-N-acetylglucosamine (O-GlcNAc) to serine and/or threonine residues. O-GlcNAc modification is similar to phosphorylation in that it occurs to serine and threonine residues and cycles on and off with a similar time scale. However, a striking difference is that the addition and removal of the O-GlcNAc moiety on all substrates are mediated by the two enzymes regardless of proteins, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), respectively. O-GlcNAcylation can interact or potentially compete with phosphorylation on serine and threonine residues, and thus serves as an important molecular mechanism to modulate protein functions and activation. However, it has been challenging to address the role of O-GlcNAc modification in regulating protein functions at the molecular level due to the lack of convenient tools to determine the sites and degrees of O-GlcNAcylation. Studies in this field have only begun to expand significantly thanks to the recent advances in detection and manipulation methods such as quantitative proteomics and highly selective small-molecule inhibitors for OGT and OGA. Interestingly, multiple brain regions, especially hippocampus, express high levels of both OGT and OGA, and a number of neuron-specific proteins have been reported to undergo O-GlcNAcylation. This review aims to discuss the recent updates concerning the impacts of O-GlcNAc modification on neuronal functions at multiple levels ranging from intrinsic neuronal properties to synaptic plasticity and animal behaviors. Copyright © 2017 Elsevier Ltd. All rights reserved.

Building a New Generation of Learning: Conversations to Catalyze Our Construction

ERIC Educational Resources Information Center

Milliron, Mark David; Plinske, Kathleen; Noonan-Terry, Coral

2008-01-01

Rather than focus primarily on the next generation of learners, the authors argue we are best served to focus on building out our on-ground and online infrastructures for a new generation of learning--blending multiple learning modes, technologies, and techniques over the course of the next 15-20 years to serve the diverse array of students from…

Fulfilling Multiple Missions Concurrently: An Ethnographic Study of a Campus Children's Center's Trials and Triumphs in Serving Six Populations

ERIC Educational Resources Information Center

Calica, Corinna Dy-Liacco

2017-01-01

The study is a comprehensive ethnographic investigation into how a campus children's center and laboratory school site can simultaneously serve six major population groups (i.e., parents, college students, teachers, faculty, administrators, and researchers) while maintaining program operations. The study carefully examines the converging and…

The functional cancer map: a systems-level synopsis of genetic deregulation in cancer.

PubMed

Krupp, Markus; Maass, Thorsten; Marquardt, Jens U; Staib, Frank; Bauer, Tobias; König, Rainer; Biesterfeld, Stefan; Galle, Peter R; Tresch, Achim; Teufel, Andreas

2011-06-30

Cancer cells are characterized by massive dysegulation of physiological cell functions with considerable disruption of transcriptional regulation. Genome-wide transcriptome profiling can be utilized for early detection and molecular classification of cancers. Accurate discrimination of functionally different tumor types may help to guide selection of targeted therapy in translational research. Concise grouping of tumor types in cancer maps according to their molecular profile may further be helpful for the development of new therapeutic modalities or open new avenues for already established therapies. Complete available human tumor data of the Stanford Microarray Database was downloaded and filtered for relevance, adequacy and reliability. A total of 649 tumor samples from more than 1400 experiments and 58 different tissues were analyzed. Next, a method to score deregulation of KEGG pathway maps in different tumor entities was established, which was then used to convert hundreds of gene expression profiles into corresponding tumor-specific pathway activity profiles. Based on the latter, we defined a measure for functional similarity between tumor entities, which yielded to phylogeny of tumors. We provide a comprehensive, easy-to-interpret functional cancer map that characterizes tumor types with respect to their biological and functional behavior. Consistently, multiple pathways commonly associated with tumor progression were revealed as common features in the majority of the tumors. However, several pathways previously not linked to carcinogenesis were identified in multiple cancers suggesting an essential role of these pathways in cancer biology. Among these pathways were 'ECM-receptor interaction', 'Complement and Coagulation cascades', and 'PPAR signaling pathway'. The functional cancer map provides a systematic view on molecular similarities across different cancers by comparing tumors on the level of pathway activity. This work resulted in identification of novel superimposed functional pathways potentially linked to cancer biology. Therefore, our work may serve as a starting point for rationalizing combination of tumor therapeutics as well as for expanding the application of well-established targeted tumor therapies.

Evidence of poorer life-course mental health outcomes among veterans of the Korean War cohort.

PubMed

Brooks, Matthew Stephen; Fulton, Lawrence

2010-03-01

Comparing the outcomes of veterans who served in Korea and those who served elsewhere, we examined the treatment of post-traumatic stress disorder (PTSD), other mental health conditions, psychiatric treatment locations, and six mental health well-being measures. The analytic sample consisted of nationally representative data from the 2001 National Survey of Veterans (NSV). Analyses included multiple logistic regressions that controlled for sociodemographic characteristics. Korean era veterans in the NSV (n = 4030): 1498 served in Korea; 2532 elsewhere during the era. Veterans who served in Korea have notably poorer mental health than those who served elsewhere. These results suggest higher resource needs among aging Korean era veterans. Clinicians, policy makers and the Department of Veterans Affairs should focus on mental health services to older veterans.

Comparing Matchplay Characteristics and Physical Demands of Junior and Professional Tennis Athletes in the Era of Big Data.

PubMed

Kovalchik, Stephanie A; Reid, Machar

2017-12-01

Differences in the competitive performance characteristics of junior and professional tennis players are not well understood. The present study provides a comprehensive comparative analysis of junior and professional matchplay. The study utilized multiple large-scale datasets covering match, point, and shot outcomes over multiple years of competition. Regression analysis was used to identify differences between junior and professional matchplay. Top professional men and women were found to play significantly more matches, sets, and games compared to junior players of an equivalent ranking. Professional players had a greater serve advantage, men winning 4 and women winning 2 additional percentage points on serve compared to juniors. Clutch ability in break point conversion was 6 to 8 percentage points greater for junior players. In general, shots were more powerful and more accurate at the professional level with the largest differences observed for male players on serve. Serving to the center of the court was more than two times more common for junior players on first serve. While male professionals performed 50% more total work in a Grand Slam match than juniors, junior girls performed 50% more work than professional women. Understanding how competitiveness, play demands, and the physical characteristics of shots differ between junior and professional tennis players can help set realistic expectations and developmentally appropriate training for transitioning players.

Multiple Targets of Salicylic Acid and Its Derivatives in Plants and Animals

PubMed Central

Klessig, Daniel F.; Tian, Miaoying; Choi, Hyong Woo

2016-01-01

Salicylic acid (SA) is a critical plant hormone that is involved in many processes, including seed germination, root initiation, stomatal closure, floral induction, thermogenesis, and response to abiotic and biotic stresses. Its central role in plant immunity, although extensively studied, is still only partially understood. Classical biochemical approaches and, more recently, genome-wide high-throughput screens have identified more than two dozen plant SA-binding proteins (SABPs), as well as multiple candidates that have yet to be characterized. Some of these proteins bind SA with high affinity, while the affinity of others exhibit is low. Given that SA levels vary greatly even within a particular plant species depending on subcellular location, tissue type, developmental stage, and with respect to both time and location after an environmental stimulus such as infection, the presence of SABPs exhibiting a wide range of affinities for SA may provide great flexibility and multiple mechanisms through which SA can act. SA and its derivatives, both natural and synthetic, also have multiple targets in animals/humans. Interestingly, many of these proteins, like their plant counterparts, are associated with immunity or disease development. Two recently identified SABPs, high mobility group box protein and glyceraldehyde 3-phosphate dehydrogenase, are critical proteins that not only serve key structural or metabolic functions but also play prominent roles in disease responses in both kingdoms. PMID:27303403

Multiple Grammars and Second Language Representation

ERIC Educational Resources Information Center

Amaral, Luiz; Roeper, Tom

2014-01-01

This paper presents an extension of the Multiple Grammars Theory (Roeper, 1999) to provide a formal mechanism that can serve as a generative-based alternative to current descriptive models of interlanguage. The theory extends historical work by Kroch and Taylor (1997), and has been taken into a computational direction by Yang (2003). The proposal…

The Multiple Roles that Youth Development Program Leaders Adopt with Youth

ERIC Educational Resources Information Center

Walker, Kathrin C.

2011-01-01

The roles that program leaders establish in their relationships with youth structure how leaders are able to foster youth development. This article examines the complex roles program leaders create in youth programs and investigates how they balanced multiple roles to most effectively respond to the youth they serve. Analyses of qualitative data…

Effect of Rehabilitation Technology Services on Vocational Rehabilitation Outcomes of Individuals with Multiple Sclerosis

ERIC Educational Resources Information Center

Chiu, Chung-Yi; Tansey, Timothy N.; Chan, Fong; Strauser, David; Frain, Michael P.; Arora, Simran

2015-01-01

Objectives: To examine the effect of rehabilitation technology interventions on the employment or job retention outcomes of individuals with multiple sclerosis (MS) served by the state-federal vocational rehabilitation program using a case-control study design. Participants: Data for this study were extracted from the Rehabilitation Services…

Optimizing Multiple-Choice Tests as Learning Events

ERIC Educational Resources Information Center

Little, Jeri Lynn

2011-01-01

Although generally used for assessment, tests can also serve as tools for learning--but different test formats may not be equally beneficial. Specifically, research has shown multiple-choice tests to be less effective than cued-recall tests in improving the later retention of the tested information (e.g., see meta-analysis by Hamaker, 1986),…

Synthesis of monolithic graphene – graphite integrated electronics

PubMed Central

Park, Jang-Ung; Nam, SungWoo; Lee, Mi-Sun; Lieber, Charles M.

2013-01-01

Encoding electronic functionality into nanoscale elements during chemical synthesis has been extensively explored over the past decade as the key to developing integrated nanosystems1 with functions defined by synthesis2-6. Graphene7-12 has been recently explored as a two-dimensional nanoscale material, and has demonstrated simple device functions based on conventional top-down fabrication13-20. However, the synthetic approach to encoding electronic functionality and thus enabling an entire integrated graphene electronics in a chemical synthesis had not previously been demonstrated. Here we report an unconventional approach for the synthesis of monolithically-integrated electronic devices based on graphene and graphite. Spatial patterning of heterogeneous catalyst metals permits the selective growth of graphene and graphite, with controlled number of graphene layers. Graphene transistor arrays with graphitic electrodes and interconnects were formed from synthesis. These functional, all-carbon structures were transferrable onto a variety of substrates. The integrated transistor arrays were used to demonstrate real-time, multiplexed chemical sensing, and more significantly, multiple carbon layers of the graphene-graphite device components were vertically assembled to form a three-dimensional flexible structure which served as a top-gate transistor array. These results represent a substantial progress towards encoding electronic functionality via chemical synthesis and suggest future promise for one-step integration of graphene-graphite based electronics. PMID:22101813

Synthesis of monolithic graphene-graphite integrated electronics.

PubMed

Park, Jang-Ung; Nam, SungWoo; Lee, Mi-Sun; Lieber, Charles M

2011-11-20

Encoding electronic functionality into nanoscale elements during chemical synthesis has been extensively explored over the past decade as the key to developing integrated nanosystems with functions defined by synthesis. Graphene has been recently explored as a two-dimensional nanoscale material, and has demonstrated simple device functions based on conventional top-down fabrication. However, the synthetic approach to encoding electronic functionality and thus enabling an entire integrated graphene electronics in a chemical synthesis had not previously been demonstrated. Here we report an unconventional approach for the synthesis of monolithically integrated electronic devices based on graphene and graphite. Spatial patterning of heterogeneous metal catalysts permits the selective growth of graphene and graphite, with a controlled number of graphene layers. Graphene transistor arrays with graphitic electrodes and interconnects were formed from the synthesis. These functional, all-carbon structures were transferable onto a variety of substrates. The integrated transistor arrays were used to demonstrate real-time, multiplexed chemical sensing and more significantly, multiple carbon layers of the graphene-graphite device components were vertically assembled to form a three-dimensional flexible structure which served as a top-gate transistor array. These results represent substantial progress towards encoding electronic functionality through chemical synthesis and suggest the future promise of one-step integration of graphene-graphite based electronics.

The hierarchical brain network for face recognition.

PubMed

Zhen, Zonglei; Fang, Huizhen; Liu, Jia

2013-01-01

Numerous functional magnetic resonance imaging (fMRI) studies have identified multiple cortical regions that are involved in face processing in the human brain. However, few studies have characterized the face-processing network as a functioning whole. In this study, we used fMRI to identify face-selective regions in the entire brain and then explore the hierarchical structure of the face-processing network by analyzing functional connectivity among these regions. We identified twenty-five regions mainly in the occipital, temporal and frontal cortex that showed a reliable response selective to faces (versus objects) across participants and across scan sessions. Furthermore, these regions were clustered into three relatively independent sub-networks in a face-recognition task on the basis of the strength of functional connectivity among them. The functionality of the sub-networks likely corresponds to the recognition of individual identity, retrieval of semantic knowledge and representation of emotional information. Interestingly, when the task was switched to object recognition from face recognition, the functional connectivity between the inferior occipital gyrus and the rest of the face-selective regions were significantly reduced, suggesting that this region may serve as an entry node in the face-processing network. In sum, our study provides empirical evidence for cognitive and neural models of face recognition and helps elucidate the neural mechanisms underlying face recognition at the network level.

An anatomical and functional topography of human auditory cortical areas

PubMed Central

Moerel, Michelle; De Martino, Federico; Formisano, Elia

2014-01-01

While advances in magnetic resonance imaging (MRI) throughout the last decades have enabled the detailed anatomical and functional inspection of the human brain non-invasively, to date there is no consensus regarding the precise subdivision and topography of the areas forming the human auditory cortex. Here, we propose a topography of the human auditory areas based on insights on the anatomical and functional properties of human auditory areas as revealed by studies of cyto- and myelo-architecture and fMRI investigations at ultra-high magnetic field (7 Tesla). Importantly, we illustrate that—whereas a group-based approach to analyze functional (tonotopic) maps is appropriate to highlight the main tonotopic axis—the examination of tonotopic maps at single subject level is required to detail the topography of primary and non-primary areas that may be more variable across subjects. Furthermore, we show that considering multiple maps indicative of anatomical (i.e., myelination) as well as of functional properties (e.g., broadness of frequency tuning) is helpful in identifying auditory cortical areas in individual human brains. We propose and discuss a topography of areas that is consistent with old and recent anatomical post-mortem characterizations of the human auditory cortex and that may serve as a working model for neuroscience studies of auditory functions. PMID:25120426

A Global Protein Kinase and Phosphatase Interaction Network in Yeast

PubMed Central

Breitkreutz, Ashton; Choi, Hyungwon; Sharom, Jeffrey R.; Boucher, Lorrie; Neduva, Victor; Larsen, Brett; Lin, Zhen-Yuan; Breitkreutz, Bobby-Joe; Stark, Chris; Liu, Guomin; Ahn, Jessica; Dewar-Darch, Danielle; Reguly, Teresa; Tang, Xiaojing; Almeida, Ricardo; Qin, Zhaohui Steve; Pawson, Tony; Gingras, Anne-Claude; Nesvizhskii, Alexey I.; Tyers, Mike

2011-01-01

The interactions of protein kinases and phosphatases with their regulatory subunits and substrates underpin cellular regulation. We identified a kinase and phosphatase interaction (KPI) network of 1844 interactions in budding yeast by mass spectrometric analysis of protein complexes. The KPI network contained many dense local regions of interactions that suggested new functions. Notably, the cell cycle phosphatase Cdc14 associated with multiple kinases that revealed roles for Cdc14 in mitogen-activated protein kinase signaling, the DNA damage response, and metabolism, whereas interactions of the target of rapamycin complex 1 (TORC1) uncovered new effector kinases in nitrogen and carbon metabolism. An extensive backbone of kinase-kinase interactions cross-connects the proteome and may serve to coordinate diverse cellular responses. PMID:20489023

Membrane Assembly and Ion Transport Ability of a Fluorinated Nanopore

PubMed Central

Godbout, Raphaël; Légaré, Sébastien; Auger, Maud; Carpentier, Claudia; Otis, François; Auger, Michèle; Lagüe, Patrick; Voyer, Normand

2016-01-01

A novel 21-residue peptide incorporating six fluorinated amino acids was prepared. It was designed to fold into an amphiphilic alpha helical structure of nanoscale length with one hydrophobic face and one fluorinated face. The formation of a fluorous interface serves as the main vector for the formation of a superstructure in a bilayer membrane. Fluorescence assays showed this ion channel's ability to facilitate the translocation of alkali metal ions through a phospholipid membrane, with selectivity for sodium ions. Computational studies showed that a tetramer structure is the most probable and stable supramolecular assembly for the active ion channel structure. The results illustrate the possibility of exploiting multiple Fδ-:M+ interactions for ion transport and using fluorous interfaces to create functional nanostructures. PMID:27835700

Membrane Assembly and Ion Transport Ability of a Fluorinated Nanopore.

PubMed

Godbout, Raphaël; Légaré, Sébastien; Auger, Maud; Carpentier, Claudia; Otis, François; Auger, Michèle; Lagüe, Patrick; Voyer, Normand

2016-01-01

A novel 21-residue peptide incorporating six fluorinated amino acids was prepared. It was designed to fold into an amphiphilic alpha helical structure of nanoscale length with one hydrophobic face and one fluorinated face. The formation of a fluorous interface serves as the main vector for the formation of a superstructure in a bilayer membrane. Fluorescence assays showed this ion channel's ability to facilitate the translocation of alkali metal ions through a phospholipid membrane, with selectivity for sodium ions. Computational studies showed that a tetramer structure is the most probable and stable supramolecular assembly for the active ion channel structure. The results illustrate the possibility of exploiting multiple Fδ-:M+ interactions for ion transport and using fluorous interfaces to create functional nanostructures.

An Underground Revolution: Biodiversity and Soil Ecological Engineering for Agricultural Sustainability.

PubMed

Bender, S Franz; Wagg, Cameron; van der Heijden, Marcel G A

2016-06-01

Soil organisms are an integral component of ecosystems, but their activities receive little recognition in agricultural management strategies. Here we synthesize the potential of soil organisms to enhance ecosystem service delivery and demonstrate that soil biodiversity promotes multiple ecosystem functions simultaneously (i.e., ecosystem multifunctionality). We apply the concept of ecological intensification to soils and we develop strategies for targeted exploitation of soil biological traits. We compile promising approaches to enhance agricultural sustainability through the promotion of soil biodiversity and targeted management of soil community composition. We present soil ecological engineering as a concept to generate human land-use systems, which can serve immediate human needs while minimizing environmental impacts. Copyright © 2016 Elsevier Ltd. All rights reserved.

Building intelligent communication systems for handicapped aphasiacs.

PubMed

Fu, Yu-Fen; Ho, Cheng-Seen

2010-01-01

This paper presents an intelligent system allowing handicapped aphasiacs to perform basic communication tasks. It has the following three key features: (1) A 6-sensor data glove measures the finger gestures of a patient in terms of the bending degrees of his fingers. (2) A finger language recognition subsystem recognizes language components from the finger gestures. It employs multiple regression analysis to automatically extract proper finger features so that the recognition model can be fast and correctly constructed by a radial basis function neural network. (3) A coordinate-indexed virtual keyboard allows the users to directly access the letters on the keyboard at a practical speed. The system serves as a viable tool for natural and affordable communication for handicapped aphasiacs through continuous finger language input.

Crossing the Virtual World Barrier with OpenAvatar

NASA Technical Reports Server (NTRS)

Joy, Bruce; Kavle, Lori; Tan, Ian

2012-01-01

There are multiple standards and formats for 3D models in virtual environments. The problem is that there is no open source platform for generating models out of discrete parts; this results in the process of having to "reinvent the wheel" when new games, virtual worlds and simulations want to enable their users to create their own avatars or easily customize in-world objects. OpenAvatar is designed to provide a framework to allow artists and programmers to create reusable assets which can be used by end users to generate vast numbers of complete models that are unique and functional. OpenAvatar serves as a framework which facilitates the modularization of 3D models allowing parts to be interchanged within a set of logical constraints.

Video Modeling and Observational Learning to Teach Gaming Access to Students with ASD.

PubMed

Spriggs, Amy D; Gast, David L; Knight, Victoria F

2016-09-01

The purpose of this study was to evaluate both video modeling and observational learning to teach age-appropriate recreation and leisure skills (i.e., accessing video games) to students with autism spectrum disorder. Effects of video modeling were evaluated via a multiple probe design across participants and criteria for mastery were based on these results. Secondary measures were collected on observational learning across participants and behaviors. Participants included 4 children with autism, ages 8-11, who were served in self-contained special education classrooms. Results indicated a functional relation between video modeling and increased independence in gaming; observational learning occurred for at least some steps across students. Results, implications for practitioners, limitations, and ideas for future research are discussed.

Extracellular Vesicles as Biomarkers and Therapeutics in Dermatology: A Focus on Exosomes.

PubMed

McBride, Jeffrey D; Rodriguez-Menocal, Luis; Badiavas, Evangelos V

2017-08-01

Extracellular vesicles (exosomes, microvesicles, and apoptotic bodies) are ubiquitous in human tissues, circulation, and body fluids. Of these vesicles, exosomes are of growing interest among investigators across multiple fields, including dermatology. The characteristics of exosomes, their associated cargo (nucleic acids, proteins, and lipids), and downstream functions are vastly different, depending on the cell origin. Here, we review concepts in extracellular vesicle biology, with a focus on exosomes, highlighting recent studies in the field of dermatology. Furthermore, we highlight emerging technical issues associated with isolating and measuring exosomes. Extracellular vesicles, including exosomes, have immediate potential for serving as biomarkers and therapeutics in dermatology over the next decade. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Liver fatty-acid-binding protein in heart and kidney allograft recipients in relation to kidney function.

PubMed

Przybylowski, P; Koc-Zorawska, E; Malyszko, J S; Kozlowska, S; Mysliwiec, M; Malyszko, J

2011-10-01

Mammalian intracellular fatty-acid-binding proteins (FABPs), a large multigene family, encode 14-kD proteins that are members of a superfamily of lipid-binding proteins. FABPs are tissue specific. Liver-type FABP (L-FABP) can be filtered through the glomerulus owing to its small molecular size, similar to cystatin C, but it is reabsorbed by proximal tubule epithelial cells like other small proteins. In the human kidney, L-FABP is expressed predominantly in proximal tubules. It had been suggested that the presence of L-FABP in urine reflects hypoxic conditions resulting from decreased peritubular capillary flow, serving as a marker of acute kidney injury. The aim of this study was to assess urinary L-FABP in 111 heart and 76 kidney transplant recipients in relation to kidney function. Complete blood count, urea, fasting glucose, creatinine, and the N-terminal fragment of brain natriuretic protein were studied by standard laboratory methods; L-FABP and cystatin C, by ELISA using commercially available kits. Kidney transplant recipients displayed significantly higher L-FABP than heart recipients. Upon univariate analysis, urinary L-FABP correlated, with serum creatinine, cystatin C and estimated glomerular filtration ratio (eGFR) in kidney allograft recipients. However, in heart transplant recipients it was not related to kidney function, as reflected by creatinine or eGFR; was strongly related to cystatin C (r=0.34; P<.001) and urinary creatinine (r=-0.29; P<.01), and NGAL (r=0.29; P<.01). Upon multiple regression analysis, the best predictor of urinary L-FABP in kidney allograft recipients, was eGFR whereas in heart recipients, no parameter independently predicted L-FABP. Successful heart transplantation is associated with kidney injury as reflected by a reduced eGFR; however, in this population, L-FABP did not serve as a marker of kidney function. In contrast, in kidney allograft recipients, L-FABP may be a potential early marker for impaired kidney function/injury. Copyright © 2011 Elsevier Inc. All rights reserved.

Clustering multilayer omics data using MuNCut.

PubMed

Teran Hidalgo, Sebastian J; Ma, Shuangge

2018-03-14

Omics profiling is now a routine component of biomedical studies. In the analysis of omics data, clustering is an essential step and serves multiple purposes including for example revealing the unknown functionalities of omics units, assisting dimension reduction in outcome model building, and others. In the most recent omics studies, a prominent trend is to conduct multilayer profiling, which collects multiple types of genetic, genomic, epigenetic and other measurements on the same subjects. In the literature, clustering methods tailored to multilayer omics data are still limited. Directly applying the existing clustering methods to multilayer omics data and clustering each layer first and then combing across layers are both "suboptimal" in that they do not accommodate the interconnections within layers and across layers in an informative way. In this study, we develop the MuNCut (Multilayer NCut) clustering approach. It is tailored to multilayer omics data and sufficiently accounts for both across- and within-layer connections. It is based on the novel NCut technique and also takes advantages of regularized sparse estimation. It has an intuitive formulation and is computationally very feasible. To facilitate implementation, we develop the function muncut in the R package NcutYX. Under a wide spectrum of simulation settings, it outperforms competitors. The analysis of TCGA (The Cancer Genome Atlas) data on breast cancer and cervical cancer shows that MuNCut generates biologically meaningful results which differ from those using the alternatives. We propose a more effective clustering analysis of multiple omics data. It provides a new venue for jointly analyzing genetic, genomic, epigenetic and other measurements.

Circuit to Construct Mapping: A Mathematical Tool for Assisting the Diagnosis and Treatment in Major Depressive Disorder

PubMed Central

Bielczyk, Natalia Z.; Buitelaar, Jan K.; Glennon, Jeffrey C.; Tiesinga, Paul H. E.

2015-01-01

Major depressive disorder (MDD) is a serious condition with a lifetime prevalence exceeding 16% worldwide. MDD is a heterogeneous disorder that involves multiple behavioral symptoms on the one hand and multiple neuronal circuits on the other hand. In this review, we integrate the literature on cognitive and physiological biomarkers of MDD with the insights derived from mathematical models of brain networks, especially models that can be used for fMRI datasets. We refer to the recent NIH research domain criteria initiative, in which a concept of “constructs” as functional units of mental disorders is introduced. Constructs are biomarkers present at multiple levels of brain functioning – cognition, genetics, brain anatomy, and neurophysiology. In this review, we propose a new approach which we called circuit to construct mapping (CCM), which aims to characterize causal relations between the underlying network dynamics (as the cause) and the constructs referring to the clinical symptoms of MDD (as the effect). CCM involves extracting diagnostic categories from behavioral data, linking circuits that are causal to these categories with use of clinical neuroimaging data, and modeling the dynamics of the emerging circuits with attractor dynamics in order to provide new, neuroimaging-related biomarkers for MDD. The CCM approach optimizes the clinical diagnosis and patient stratification. It also addresses the recent demand for linking circuits to behavior, and provides a new insight into clinical treatment by investigating the dynamics of neuronal circuits underneath cognitive dimensions of MDD. CCM can serve as a new regime toward personalized medicine, assisting the diagnosis and treatment of MDD. PMID:25767450

Flexible, phase-matched, linear receive arrays for high-field MRI in monkeys.

PubMed

Goense, Jozien; Logothetis, Nikos K; Merkle, Hellmut

2010-10-01

High signal-to-noise ratios (SNR) are essential for high-resolution anatomical and functional MRI. Phased arrays are advantageous for this but have the drawback that they often have inflexible and bulky configurations. Particularly in experiments where functional MRI is combined with simultaneous electrophysiology, space constraints can be prohibitive. To this end we developed a highly flexible multiple receive element phased array for use on anesthetized monkeys. The elements are interchangeable and different sizes and combinations of coil elements can be used, for instance, combinations of single and overlapped elements. The preamplifiers including control electronics are detachable and can serve a variety of prefabricated and phase matched arrays of different configurations, allowing the elements to always be placed in close proximity to the area of interest. Optimizing performance of the individual elements ensured high SNR at the cortical surface as well as in deeper laying structures. Performance of a variety of arrangements of gapped linear arrays was evaluated at 4.7 and 7T in high-resolution anatomical and functional MRI. Copyright © 2010 Elsevier Inc. All rights reserved.

Regulation of cerebrospinal fluid (CSF) flow in neurodegenerative, neurovascular and neuroinflammatory disease

PubMed Central

Simon, Matthew J.; Iliff, Jeffrey J.

2015-01-01

Cerebrospinal fluid (CSF) circulation and turnover provides a sink for the elimination of solutes from the brain interstitium, serving an important homeostatic role for the function of the central nervous system. Disruption of normal CSF circulation and turnover is believed to contribute to the development of many diseases, including neurodegenerative conditions such as Alzheimer’s disease, ischemic and traumatic brain injury, and neuroinflammatory conditions such as multiple sclerosis. Recent insights into CSF biology suggesting that CSF and interstitial fluid exchange along a brain-wide network of perivascular spaces termed the ‘glymphatic’ system suggest that CSF circulation may interact intimately with glial and vascular function to regulate basic aspects of brain function. Dysfunction within this glial vascular network, which is a feature of the aging and injured brain, is a potentially critical link between brain injury, neuroinflammation and the development of chronic neurodegeneration. Ongoing research within this field may provide a powerful new framework for understanding the common links between neurodegenerative, neurovascular and neuroinflammatory disease, in addition to providing potentially novel therapeutic targets for these conditions. PMID:26499397

Crystal Structures of Phd-Doc, HigA, and YeeU Establish Multiple Evolutionary Links between Microbial Growth-Regulating Toxin-Antitoxin Systems

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

Arbing, Mark A.; Handelman, Samuel K.; Kuzin, Alexandre P.

2010-09-27

Bacterial toxin-antitoxin (TA) systems serve a variety of physiological functions including regulation of cell growth and maintenance of foreign genetic elements. Sequence analyses suggest that TA families are linked by complex evolutionary relationships reflecting likely swapping of functional domains between different TA families. Our crystal structures of Phd-Doc from bacteriophage P1, the HigA antitoxin from Escherichia coli CFT073, and YeeU of the YeeUWV systems from E. coli K12 and Shigella flexneri confirm this inference and reveal additional, unanticipated structural relationships. The growth-regulating Doc toxin exhibits structural similarity to secreted virulence factors that are toxic for eukaryotic target cells. The Phdmore » antitoxin possesses the same fold as both the YefM and NE2111 antitoxins that inhibit structurally unrelated toxins. YeeU, which has an antitoxin-like activity that represses toxin expression, is structurally similar to the ribosome-interacting toxins YoeB and RelE. These observations suggest extensive functional exchanges have occurred between TA systems during bacterial evolution.« less

Factors Influencing Functional Outcomes and Return-to-Work After Amputation: A Review of the Literature.

PubMed

Darter, Benjamin J; Hawley, Carolyn E; Armstrong, Amy J; Avellone, Lauren; Wehman, Paul

2018-02-03

Purpose Amputation is a life changing event that can significantly impact an individual's physical and mental well-being. Our objective was to review literature exploring the impact of amputation upon a person's functioning and inclusion in the workplace. Methods Medline, CINAHL, and PsycINFO were searched using keywords related to amputation, employment and community reintegration. Eligible studies were published since 2000 and one of the following study designs: randomized controlled trial, non-randomized controlled trial, retrospective study, prospective study, concurrent cohort study, or cross sectional study. Studies for civilians with amputation as well as service members and Veterans with amputation were considered for inclusion. Results The search identified 995 articles, 25 of which met inclusion/exclusion criteria and were included in the review. While strong evidence for correlations and predictors of outcomes after amputation were limited, multiple factors were identified as contributing to physical functioning and employment after amputation. Conclusions Outcomes after amputation can vary widely with many potentially inter-related factors contributing. The factors identified may also serve to inform the development of interventions aiming to improve functional performance and reintegration after amputation. Furthermore, the review highlights the need for more high quality prospective studies.

The roles of melanin-concentrating hormone in energy balance and reproductive function: Are they connected?

PubMed

Naufahu, Jane; Cunliffe, Adam D; Murray, Joanne F

2013-01-01

Melanin-concentrating hormone (MCH) is an anabolic neuropeptide with multiple and diverse physiological functions including a key role in energy homoeostasis. Rodent studies have shown that the ablation of functional MCH results in a lean phenotype, increased energy expenditure and resistance to diet-induced obesity. These findings have generated interest among pharmaceutical companies vigilant for potential anti-obesity agents. Nutritional status affects reproductive physiology and behaviours, thereby optimising reproductive success and the ability to meet energetic demands. This complex control system entails the integration of direct or indirect peripheral stimuli with central effector systems and involves numerous mediators. A role for MCH in the reproductive axis has emerged, giving rise to the premise that MCH may serve as an integratory mediator between those discrete systems that regulate energy balance and reproductive function. Hence, this review focuses on published evidence concerning i) the role of MCH in energy homoeostasis and ii) the regulatory role of MCH in the reproductive axis. The question as to whether the MCH system mediates the integration of energy homoeostasis with the neuroendocrine reproductive axis and, if so, by what means has received limited coverage in the literature; evidence to date and current theories are summarised herein.

Why are you telling me that? A conceptual model of the social function of autobiographical memory.

PubMed

Alea, Nicole; Bluck, Susan

2003-03-01

In an effort to stimulate and guide empirical work within a functional framework, this paper provides a conceptual model of the social functions of autobiographical memory (AM) across the lifespan. The model delineates the processes and variables involved when AMs are shared to serve social functions. Components of the model include: lifespan contextual influences, the qualitative characteristics of memory (emotionality and level of detail recalled), the speaker's characteristics (age, gender, and personality), the familiarity and similarity of the listener to the speaker, the level of responsiveness during the memory-sharing process, and the nature of the social relationship in which the memory sharing occurs (valence and length of the relationship). These components are shown to influence the type of social function served and/or, the extent to which social functions are served. Directions for future empirical work to substantiate the model and hypotheses derived from the model are provided.

Feasibility of neuro-morphic computing to emulate error-conflict based decision making.

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

Branch, Darren W.

2009-09-01

A key aspect of decision making is determining when errors or conflicts exist in information and knowing whether to continue or terminate an action. Understanding the error-conflict processing is crucial in order to emulate higher brain functions in hardware and software systems. Specific brain regions, most notably the anterior cingulate cortex (ACC) are known to respond to the presence of conflicts in information by assigning a value to an action. Essentially, this conflict signal triggers strategic adjustments in cognitive control, which serve to prevent further conflict. The most probable mechanism is the ACC reports and discriminates different types of feedback,more » both positive and negative, that relate to different adaptations. Unique cells called spindle neurons that are primarily found in the ACC (layer Vb) are known to be responsible for cognitive dissonance (disambiguation between alternatives). Thus, the ACC through a specific set of cells likely plays a central role in the ability of humans to make difficult decisions and solve challenging problems in the midst of conflicting information. In addition to dealing with cognitive dissonance, decision making in high consequence scenarios also relies on the integration of multiple sets of information (sensory, reward, emotion, etc.). Thus, a second area of interest for this proposal lies in the corticostriatal networks that serve as an integration region for multiple cognitive inputs. In order to engineer neurological decision making processes in silicon devices, we will determine the key cells, inputs, and outputs of conflict/error detection in the ACC region. The second goal is understand in vitro models of corticostriatal networks and the impact of physical deficits on decision making, specifically in stressful scenarios with conflicting streams of data from multiple inputs. We will elucidate the mechanisms of cognitive data integration in order to implement a future corticostriatal-like network in silicon devices for improved decision processing.« less

A Multiple Case Study Analysis Exploring Autism Spectrum Disorder as a Culture

ERIC Educational Resources Information Center

Hutto, Lori Lynn

2017-01-01

This qualitative multiple case study analysis included the exploration of the phenomenon of Autism Spectrum Disorder (ASD) from a cultural standpoint, rather than the traditional view of deficits caused by disability. This effort was undertaken to determine if those within this population would be better served by the educational system and more…

A Collaboratively Designed Child Mental Health Service Model: Multiple Family Groups for Urban Children with Conduct Difficulties

ERIC Educational Resources Information Center

McKay, Mary M.; Gopalan, Geetha; Franco, Lydia; Dean-Assael, Kara; Chacko, Anil; Jackson, Jerrold M.; Fuss, Ashley

2011-01-01

This article presents preliminary outcomes associated with an experimental, longitudinal study of a Multiple Family Group (MFG) service delivery approach set within 13 urban outpatient clinics serving children and their families living in inner-city, primarily African American and Latino communities. Specifically, this article focuses on parent…

DServO: A Peer-to-Peer-based Approach to Biomedical Ontology Repositories.

PubMed

Mambone, Zakaria; Savadogo, Mahamadi; Some, Borlli Michel Jonas; Diallo, Gayo

2015-01-01

We present in this poster an extension of the ServO ontology server system, which adopts a decentralized Peer-To-Peer approach for managing multiple heterogeneous knowledge organization systems. It relies on the use of the JXTA protocol coupled with information retrieval techniques to provide a decentralized infrastructure for managing multiples instances of Ontology Repositories.

An Analysis of Statements of the Multiplication Principle in Combinatorics, Discrete, and Finite Mathematics Textbooks

ERIC Educational Resources Information Center

Lockwood, Elise; Reed, Zackery; Caughman, John S.

2017-01-01

The multiplication principle serves as a cornerstone in enumerative combinatorics. The principle underpins many basic counting formulas and provides students with a critical element of combinatorial justification. Given its importance, the way in which it is presented in textbooks is surprisingly varied. In this paper, we analyze a number of…

Jigsaw Research Communities: Coordinating Research and Service across Multiple Courses to Serve a Single Community Partner

ERIC Educational Resources Information Center

Cross, Anne; Eckberg, Deborah A.

2015-01-01

This article describes a public scholarship project in which two faculty members worked together to integrate service-learning and research into multiple courses to benefit a single community partner. The project linked undergraduate students, graduate students, and faculty in a broad-based research endeavor that contributed to the survival and…

Note: Toward multiple addressable optical trapping

PubMed Central

Faustov, Alexei R.; Webb, Michael R.; Walt, David R.

2010-01-01

We describe a setup for addressable optical trapping in which a laser source is focused on a digital micromirror device and generates an optical trap in a microfluidic cell. In this paper, we report a proof-of-principle single beam∕single micromirror∕single three-dimensional trap arrangement that should serve as the basis for a multiple-trap instrument. PMID:20192526

Validation of a Cognitive Diagnostic Model across Multiple Forms of a Reading Comprehension Assessment

ERIC Educational Resources Information Center

Clark, Amy K.

2013-01-01

The present study sought to fit a cognitive diagnostic model (CDM) across multiple forms of a passage-based reading comprehension assessment using the attribute hierarchy method. Previous research on CDMs for reading comprehension assessments served as a basis for the attributes in the hierarchy. The two attribute hierarchies were fit to data from…

Motivation to serve in the military influences vulnerability to future posttraumatic stress disorder.

PubMed

Kaplan, Zeev; Weiser, Mark; Reichenberg, Abraham; Rabinowitz, Jonathan; Caspi, Asaf; Bodner, Ehud; Zohar, Joseph

2002-01-31

High motivation and belief in a cause have been reported to be protective against posttraumatic stress disorder (PTSD), while below-average intellectual functioning and poor educational achievements have been reported to increase vulnerability to PTSD. The main goal of this study was to assess the effect of education, and intellectual and behavioral functioning on the risk for future PTSD. Data collected before exposure to trauma, on intellectual and behavioral functioning, and educational achievements of 901 male Israeli adolescents who had performed pre-induction screening tests by the Israeli Draft Board, and were later diagnosed with PTSD, were compared with a control group of adolescents who were not later diagnosed with PTSD. Future PTSD patients had significantly lower intelligence, fewer years of formal education and lower scores on a scale assessing motivation to serve in the military, in comparison with the control group, with effect sizes (ES) ranging from 0.14-0.34. In contrast, future PTSD patients scored significantly higher on a scale assessing social functioning, ES=0.13. However, when controlling for the differences in motivation to serve, all of these differences disappeared. In this cohort, although slightly below average intellectual functioning and formal education, and better social functioning, independently increased vulnerability to suffer from PTSD, these associations disappeared when the future PTSD patients' lower motivation to serve in the military was included in the analysis. This suggests that low motivation to serve in the military might increase vulnerability for PTSD.

Limited Bandwidth Recognition of Collective Behaviors in Bio-Inspired Swarms

DTIC Science & Technology

2014-05-09

collective? Some swarm models exhibit multiple emergent behaviors from the same parameters. This provides increased expressivity at the cost of...swarms, namely, how do you know what the swarm is doing if you can’t ob- serve every agent in the collective? Some swarm models exhibit multiple ...flocking [15, 21, 12] or cyclic behavior [8, 7], and in some cases can exhibit multiple group behaviors depending on the model parameters used [6, 3, 17

Measuring Geographic Inequalities: Dealing with Multiple Health Resources by Data Envelopment Analysis.

PubMed

Dlouhý, Martin

2018-01-01

The existence of geographic differences in health resources, health expenditures, the utilization of health services, and health outcomes have been documented by a lot of studies from various countries of the world. In a publicly financed health system, equal access is one of the main objectives of the national health policy. That is why inequalities in the geographic allocation of health resources are an important health policy issue. Measures of inequality express the complexity of variation in the observed variable by a single number, and there is a variety of inequality measures available. The objective of this study is to develop a measure of the geographic inequality in the case of multiple health resources. The measure uses data envelopment analysis (DEA), which is a non-parametric method of production function estimation, to transform multiple resources into a single virtual health resource. The study shows that the DEA originally developed for measuring efficiency can be used successfully to measure inequality. For the illustrative purpose, the inequality measure is calculated for the Czech Republic. The values of separate Robin Hood Indexes (RHIs) are 6.64% for physicians and 3.96% for nurses. In the next step, we use combined RHI for both health resources. Its value 5.06% takes into account that the combinations of two health resources serve regional populations.

Gel-like double-emulsion droplets

NASA Astrophysics Data System (ADS)

Guzowski, Jan; Korczyk, Piotr; Garstecki, Piotr; Stone, Howard

2015-11-01

We experimentally study the problem of packing of micro-droplets inside a droplet of another immiscible liquid phase. We use microfluidics to encapsulate multiple monodisperse aqueous segments inside a drop of oil. For small numbers N (N<10) of the aqueous droplets and at their volume fraction in oil exceeding the close-packing threshold we observe multiple metastable structures with well-defined point-group symmetries. We attribute the observed metastability to the deformability of the droplets which leads to effective many-body interactions and energy barriers for rearrangement. By changing the composition of the oil phase we find that when the surface tensions of the droplets and of the encapsulating phase are comparable, the energy barriers are high enough to trap elongated structures or even linear chains, independently of N. However, when the surface tension of the encapsulating phase is much larger than that of the droplets, non-spherical morphologies are stable only at sufficiently high N. In such a case multiple internal interfaces can hold stresses and prevent relaxation of the global deformations which leads to a plastic, gel-like behavior. Our findings can serve as guidelines for synthesis of functional particles as well as for designing biomimetic materials, e.g. for tissue engineering. J.G. acknowledges financial support from Polish Ministry of Science provided within the framework Mobility Plus.

Multiple-choice tests stabilize access to marginal knowledge.

PubMed

Cantor, Allison D; Eslick, Andrea N; Marsh, Elizabeth J; Bjork, Robert A; Bjork, Elizabeth Ligon

2015-02-01

Marginal knowledge refers to knowledge that is stored in memory, but is not accessible at a given moment. For example, one might struggle to remember who wrote The Call of the Wild, even if that knowledge is stored in memory. Knowing how best to stabilize access to marginal knowledge is important, given that new learning often requires accessing and building on prior knowledge. While even a single opportunity to restudy marginal knowledge boosts its later accessibility (Berger, Hall, & Bahrick, 1999), in many situations explicit relearning opportunities are not available. Our question is whether multiple-choice tests (which by definition expose the learner to the correct answers) can also serve this function and, if so, how testing compares to restudying given that tests can be particularly powerful learning devices (Roediger & Karpicke, 2006). In four experiments, we found that multiple-choice testing had the power to stabilize access to marginal knowledge, and to do so for at least up to a week. Importantly, such tests did not need to be paired with feedback, although testing was no more powerful than studying. Overall, the results support the idea that one's knowledge base is unstable, with individual pieces of information coming in and out of reach. The present findings have implications for a key educational challenge: ensuring that students have continuing access to information they have learned.

Multicomponent self-assembly as a tool to harness new properties from peptides and proteins in material design.

PubMed

Okesola, Babatunde O; Mata, Alvaro

2018-05-21

Nature is enriched with a wide variety of complex, synergistic, and highly functional protein-based multicomponent assemblies. As such, nature has served as a source of inspiration for using multicomponent self-assembly as a platform to create highly ordered, complex, and dynamic protein and peptide-based nanostructures. Such an assembly system relies on the initial interaction of distinct individual building blocks leading to the formation of a complex that subsequently assembles into supramolecular architectures. This approach not only serves as a powerful platform for gaining insight into how proteins co-assemble in nature but also offers huge opportunities to harness new properties not inherent in the individual building blocks. In the past decades, various multicomponent self-assembly strategies have been used to extract synergistic properties from proteins and peptides. This review highlights the updates in the field of multicomponent self-assembly of proteins and peptides and summarizes various strategies, including covalent conjugation, ligand-receptor interactions, templated/directed assembly and non-specific co-assembly, for driving the self-assembly of multiple proteins and peptide-based building blocks into functional materials. In particular, we focus on peptide- or protein-containing multicomponent systems that, upon self-assembly, enable the emergence of new properties or phenomena. The ultimate goal of this review is to highlight the importance of multicomponent self-assembly in protein and peptide engineering, and to advocate its growth in the fields of materials science and nanotechnology.

Predicting Speech Intelligibility Decline in Amyotrophic Lateral Sclerosis Based on the Deterioration of Individual Speech Subsystems

PubMed Central

Yunusova, Yana; Wang, Jun; Zinman, Lorne; Pattee, Gary L.; Berry, James D.; Perry, Bridget; Green, Jordan R.

2016-01-01

Purpose To determine the mechanisms of speech intelligibility impairment due to neurologic impairments, intelligibility decline was modeled as a function of co-occurring changes in the articulatory, resonatory, phonatory, and respiratory subsystems. Method Sixty-six individuals diagnosed with amyotrophic lateral sclerosis (ALS) were studied longitudinally. The disease-related changes in articulatory, resonatory, phonatory, and respiratory subsystems were quantified using multiple instrumental measures, which were subjected to a principal component analysis and mixed effects models to derive a set of speech subsystem predictors. A stepwise approach was used to select the best set of subsystem predictors to model the overall decline in intelligibility. Results Intelligibility was modeled as a function of five predictors that corresponded to velocities of lip and jaw movements (articulatory), number of syllable repetitions in the alternating motion rate task (articulatory), nasal airflow (resonatory), maximum fundamental frequency (phonatory), and speech pauses (respiratory). The model accounted for 95.6% of the variance in intelligibility, among which the articulatory predictors showed the most substantial independent contribution (57.7%). Conclusion Articulatory impairments characterized by reduced velocities of lip and jaw movements and resonatory impairments characterized by increased nasal airflow served as the subsystem predictors of the longitudinal decline of speech intelligibility in ALS. Declines in maximum performance tasks such as the alternating motion rate preceded declines in intelligibility, thus serving as early predictors of bulbar dysfunction. Following the rapid decline in speech intelligibility, a precipitous decline in maximum performance tasks subsequently occurred. PMID:27148967

Predicting Speech Intelligibility Decline in Amyotrophic Lateral Sclerosis Based on the Deterioration of Individual Speech Subsystems.

PubMed

Rong, Panying; Yunusova, Yana; Wang, Jun; Zinman, Lorne; Pattee, Gary L; Berry, James D; Perry, Bridget; Green, Jordan R

2016-01-01

To determine the mechanisms of speech intelligibility impairment due to neurologic impairments, intelligibility decline was modeled as a function of co-occurring changes in the articulatory, resonatory, phonatory, and respiratory subsystems. Sixty-six individuals diagnosed with amyotrophic lateral sclerosis (ALS) were studied longitudinally. The disease-related changes in articulatory, resonatory, phonatory, and respiratory subsystems were quantified using multiple instrumental measures, which were subjected to a principal component analysis and mixed effects models to derive a set of speech subsystem predictors. A stepwise approach was used to select the best set of subsystem predictors to model the overall decline in intelligibility. Intelligibility was modeled as a function of five predictors that corresponded to velocities of lip and jaw movements (articulatory), number of syllable repetitions in the alternating motion rate task (articulatory), nasal airflow (resonatory), maximum fundamental frequency (phonatory), and speech pauses (respiratory). The model accounted for 95.6% of the variance in intelligibility, among which the articulatory predictors showed the most substantial independent contribution (57.7%). Articulatory impairments characterized by reduced velocities of lip and jaw movements and resonatory impairments characterized by increased nasal airflow served as the subsystem predictors of the longitudinal decline of speech intelligibility in ALS. Declines in maximum performance tasks such as the alternating motion rate preceded declines in intelligibility, thus serving as early predictors of bulbar dysfunction. Following the rapid decline in speech intelligibility, a precipitous decline in maximum performance tasks subsequently occurred.

Proceedings of the Mobile Satellite System Architectures and Multiple Access Techniques Workshop

NASA Technical Reports Server (NTRS)

Dessouky, Khaled

1989-01-01

The Mobile Satellite System Architectures and Multiple Access Techniques Workshop served as a forum for the debate of system and network architecture issues. Particular emphasis was on those issues relating to the choice of multiple access technique(s) for the Mobile Satellite Service (MSS). These proceedings contain articles that expand upon the 12 presentations given in the workshop. Contrasting views on Frequency Division Multiple Access (FDMA), Code Division Multiple Access (CDMA), and Time Division Multiple Access (TDMA)-based architectures are presented, and system issues relating to signaling, spacecraft design, and network management constraints are addressed. An overview article that summarizes the issues raised in the numerous discussion periods of the workshop is also included.

The crystal structure of augmenter of liver regeneration: A mammalian FAD-dependent sulfhydryl oxidase

PubMed Central

Wu, Chia-Kuei; Dailey, Tamara A.; Dailey, Harry A.; Wang, Bi-Cheng; Rose, John P.

2003-01-01

The crystal structure of recombinant rat augmenter of liver regeneration (ALRp) has been determined to 1.8 Å. The protein is a homodimer, stabilized by extensive noncovalent interactions and a network of hydrogen bonds, and possesses a noncovalently bound FAD in a motif previously found only in the related protein ERV2p. ALRp functions in vitro as a disulfide oxidase using dithiothreitol as reductant. Reduction of the flavin by DTT occurs under aerobic conditions resulting in a spectrum characteristic of a neutral semiquinone. This semiquinone is stable and is only fully reduced by addition of dithionite. Mutation of either of two cysteine residues that are located adjacent to the FAD results in inactivation of the oxidase activity. A comparison of ALRp with ERV2p is made that reveals a number of significant structural differences, which are related to the in vivo functions of these two proteins. Possible physiological roles of ALR are examined and a hypothesis that it may serve multiple roles is proposed. PMID:12717032

3D printing for soft robotics – a review

PubMed Central

Gul, Jahan Zeb; Sajid, Memoon; Rehman, Muhammad Muqeet; Siddiqui, Ghayas Uddin; Shah, Imran; Kim, Kyung-Hwan; Lee, Jae-Wook; Choi, Kyung Hyun

2018-01-01

Abstract Soft robots have received an increasing attention due to their advantages of high flexibility and safety for human operators but the fabrication is a challenge. Recently, 3D printing has been used as a key technology to fabricate soft robots because of high quality and printing multiple materials at the same time. Functional soft materials are particularly well suited for soft robotics due to a wide range of stimulants and sensitive demonstration of large deformations, high motion complexities and varied multi-functionalities. This review comprises a detailed survey of 3D printing in soft robotics. The development of key 3D printing technologies and new materials along with composites for soft robotic applications is investigated. A brief summary of 3D-printed soft devices suitable for medical to industrial applications is also included. The growing research on both 3D printing and soft robotics needs a summary of the major reported studies and the authors believe that this review article serves the purpose. PMID:29707065

3D printing for soft robotics - a review.

PubMed

Gul, Jahan Zeb; Sajid, Memoon; Rehman, Muhammad Muqeet; Siddiqui, Ghayas Uddin; Shah, Imran; Kim, Kyung-Hwan; Lee, Jae-Wook; Choi, Kyung Hyun

2018-01-01

Soft robots have received an increasing attention due to their advantages of high flexibility and safety for human operators but the fabrication is a challenge. Recently, 3D printing has been used as a key technology to fabricate soft robots because of high quality and printing multiple materials at the same time. Functional soft materials are particularly well suited for soft robotics due to a wide range of stimulants and sensitive demonstration of large deformations, high motion complexities and varied multi-functionalities. This review comprises a detailed survey of 3D printing in soft robotics. The development of key 3D printing technologies and new materials along with composites for soft robotic applications is investigated. A brief summary of 3D-printed soft devices suitable for medical to industrial applications is also included. The growing research on both 3D printing and soft robotics needs a summary of the major reported studies and the authors believe that this review article serves the purpose.

Biochemistry and Biology of GDF11 and Myostatin: Similarities, Differences, and Questions for Future Investigation.

PubMed

Walker, Ryan G; Poggioli, Tommaso; Katsimpardi, Lida; Buchanan, Sean M; Oh, Juhyun; Wattrus, Sam; Heidecker, Bettina; Fong, Yick W; Rubin, Lee L; Ganz, Peter; Thompson, Thomas B; Wagers, Amy J; Lee, Richard T

2016-04-01

Growth differentiation factor 11 (GDF11) and myostatin (or GDF8) are closely related members of the transforming growth factor β superfamily and are often perceived to serve similar or overlapping roles. Yet, despite commonalities in protein sequence, receptor utilization and signaling, accumulating evidence suggests that these 2 ligands can have distinct functions in many situations. GDF11 is essential for mammalian development and has been suggested to regulate aging of multiple tissues, whereas myostatin is a well-described negative regulator of postnatal skeletal and cardiac muscle mass and modulates metabolic processes. In this review, we discuss the biochemical regulation of GDF11 and myostatin and their functions in the heart, skeletal muscle, and brain. We also highlight recent clinical findings with respect to a potential role for GDF11 and/or myostatin in humans with heart disease. Finally, we address key outstanding questions related to GDF11 and myostatin dynamics and signaling during development, growth, and aging. © 2016 American Heart Association, Inc.

Drug-Eluting Fibers for HIV-1 Inhibition and Contraception

PubMed Central

Ball, Cameron; Krogstad, Emily; Chaowanachan, Thanyanan; Woodrow, Kim A.

2012-01-01

Multipurpose prevention technologies (MPTs) that simultaneously prevent sexually transmitted infections (STIs) and unintended pregnancy are a global health priority. Combining chemical and physical barriers offers the greatest potential to design effective MPTs, but integrating both functional modalities into a single device has been challenging. Here we show that drug-eluting fiber meshes designed for topical drug delivery can function as a combination chemical and physical barrier MPT. Using FDA-approved polymers, we fabricated nanofiber meshes with tunable fiber size and controlled degradation kinetics that facilitate simultaneous release of multiple agents against HIV-1, HSV-2, and sperm. We observed that drug-loaded meshes inhibited HIV-1 infection in vitro and physically obstructed sperm penetration. Furthermore, we report on a previously unknown activity of glycerol monolaurate (GML) to potently inhibit sperm motility and viability. The application of drug-eluting nanofibers for HIV-1 prevention and sperm inhibition may serve as an innovative platform technology for drug delivery to the lower female reproductive tract. PMID:23209601

Chemiresistive and Gravimetric Dual-Mode Gas Sensor toward Target Recognition and Differentiation.

PubMed

Chen, Yan; Zhang, Hao; Feng, Zhihong; Zhang, Hongxiang; Zhang, Rui; Yu, Yuanyuan; Tao, Jin; Zhao, Hongyuan; Guo, Wenlan; Pang, Wei; Duan, Xuexin; Liu, Jing; Zhang, Daihua

2016-08-24

We demonstrate a dual-mode gas sensor for simultaneous and independent acquisition of electrical and mechanical signals from the same gas adsorption event. The device integrates a graphene field-effect transistor (FET) with a piezoelectric resonator in a seamless manner by leveraging multiple structural and functional synergies. Dual signals resulting from independent physical processes, i.e., mass attachment and charge transfer can reflect intrinsic properties of gas molecules and potentially enable target recognition and quantification at the same time. Fabrication of the device is based on standard Integrated Circuit (IC) foundry processes and fully compatible with system-on-a-chip (SoC) integration to achieve extremely small form factors. In addition, the ability of simultaneous measurements of mass adsorption and charge transfer guides us to a more precise understanding of the interactions between graphene and various gas molecules. Besides its practical functions, the device serves as an effective tool to quantitatively investigate the physical processes and sensing mechanisms for a large library of sensing materials and target analytes.

Eating disorders and the serotonin connection: state, trait and developmental effects

PubMed Central

Steiger, Howard

2004-01-01

Alterations in brain serotonin (5-hydroxytryptamine [5-HT]) function are thought to contribute to diverse aspects of eating disorders, including binge eating, perfectionism, impulsivity and mood-regulation problems. In addition, 5-HT anomalies in individuals with eating disorders are believed to have multiple determinants associated with secondary (state-related) effects of their nutritional status, hereditary effects (related to such trait variations as impulsivity or perfectionism) and, possibly, long-term neurobiologic sequelae of developmental stressors (such as childhood abuse). On the strength of the available neurobiologic and genetic data, this paper presents the idea that 5-HT variations in those with eating disorders represent (1) a structured coaggregation of biologic, psychologic and social influences and (2) converging state, trait and developmental effects. Data are taken to support a multidimensional model of 5-HT function in eating disorders that, it is argued, can serve as a prototype for etiologic modelling, diagnostic classification and clinical decision-making bearing not only upon eating disorders but also upon other psychiatric disturbances. PMID:14719047

Atomically flat single-crystalline gold nanostructures for plasmonic nanocircuitry.

PubMed

Huang, Jer-Shing; Callegari, Victor; Geisler, Peter; Brüning, Christoph; Kern, Johannes; Prangsma, Jord C; Wu, Xiaofei; Feichtner, Thorsten; Ziegler, Johannes; Weinmann, Pia; Kamp, Martin; Forchel, Alfred; Biagioni, Paolo; Sennhauser, Urs; Hecht, Bert

2010-01-01

Deep subwavelength integration of high-definition plasmonic nanostructures is of key importance in the development of future optical nanocircuitry for high-speed communication, quantum computation and lab-on-a-chip applications. To date, the experimental realization of proposed extended plasmonic networks consisting of multiple functional elements remains challenging, mainly because of the multi-crystallinity of commonly used thermally evaporated gold layers. This can produce structural imperfections in individual circuit elements that drastically reduce the yield of functional integrated nanocircuits. In this paper we demonstrate the use of large (>100 μm(2)) but thin (<80 nm) chemically grown single-crystalline gold flakes that, after immobilization, serve as an ideal basis for focused ion beam milling and other top-down nanofabrication techniques on any desired substrate. Using this methodology we obtain high-definition ultrasmooth gold nanostructures with superior optical properties and reproducible nano-sized features over micrometre-length scales. Our approach provides a possible solution to overcome the current fabrication bottleneck and realize high-definition plasmonic nanocircuitry.

Transduction of Redox Signaling by Electrophile-Protein Reactions

PubMed Central

Rudolph, Tanja K.; Freeman, Bruce A.

2014-01-01

Over the last 50 years, the posttranslational modification (PTM) of proteins has emerged as a central mechanism for cells to regulate metabolism, growth, differentiation, cell-cell interactions, and immune responses. By influencing protein structure and function, PTM leads to a multiplication of proteome diversity. Redox-dependent PTMs, mediated by environmental and endogenously generated reactive species, induce cell signaling responses and can have toxic effects in organisms. PTMs induced by the electrophilic by-products of redox reactions most frequently occur at protein thiols; other nucleophilic amino acids serve as less favorable targets. Advances in mass spectrometry and affinity-chemistry strategies have improved the detection of electrophile-induced protein modifications both in vitro and in vivo and have revealed a high degree of amino acid and protein selectivity of electrophilic PTM. The identification of biological targets of electrophiles has motivated further study of the functional impact of various PTM reactions on specific signaling pathways and how this might affect organisms. PMID:19797270

Perception of the plant immune signal salicylic acid

PubMed Central

Yan, Shunping; Dong, Xinnian

2014-01-01

Salicylic acid (SA) plays a central role in plant innate immunity. The diverse functions of this simple phenolic compound suggest that plants may have multiple SA receptors. Several SA-binding proteins have been identified using biochemical approaches. However, genetic evidence supporting that they are the bona fide SA receptors has not been forthcoming. Mutant screens revealed that NPR1 is a master regulator of SA-mediated responses. Although NPR1 cannot bind SA in a conventional ligand-binding assay, its homologs NPR3 and NPR4 bind SA and function as SA receptors. During pathogen challenge, the SA gradient generated at the infection site is sensed by NPR3 and NPR4, which serve as the adaptors for the Cullin 3-based E3 ubiquitin ligase to regulate NPR1 degradation. Consequently, NPR1 is degraded at the infection site to remove its inhibition on effector-triggered cell death and defense, whereas NPR1 accumulates in neighboring cells to promote cell survival and SA-mediated resistance. PMID:24840293

Diversity of sharp-wave-ripple LFP signatures reveals differentiated brain-wide dynamical events.

PubMed

Ramirez-Villegas, Juan F; Logothetis, Nikos K; Besserve, Michel

2015-11-17

Sharp-wave-ripple (SPW-R) complexes are believed to mediate memory reactivation, transfer, and consolidation. However, their underlying neuronal dynamics at multiple scales remains poorly understood. Using concurrent hippocampal local field potential (LFP) recordings and functional MRI (fMRI), we study local changes in neuronal activity during SPW-R episodes and their brain-wide correlates. Analysis of the temporal alignment between SPW and ripple components reveals well-differentiated SPW-R subtypes in the CA1 LFP. SPW-R-triggered fMRI maps show that ripples aligned to the positive peak of their SPWs have enhanced neocortical metabolic up-regulation. In contrast, ripples occurring at the trough of their SPWs relate to weaker neocortical up-regulation and absent subcortical down-regulation, indicating differentiated involvement of neuromodulatory pathways in the ripple phenomenon mediated by long-range interactions. To our knowledge, this study provides the first evidence for the existence of SPW-R subtypes with differentiated CA1 activity and metabolic correlates in related brain areas, possibly serving different memory functions.

Diversity of sharp-wave–ripple LFP signatures reveals differentiated brain-wide dynamical events

PubMed Central

Ramirez-Villegas, Juan F.; Logothetis, Nikos K.; Besserve, Michel

2015-01-01

Sharp-wave–ripple (SPW-R) complexes are believed to mediate memory reactivation, transfer, and consolidation. However, their underlying neuronal dynamics at multiple scales remains poorly understood. Using concurrent hippocampal local field potential (LFP) recordings and functional MRI (fMRI), we study local changes in neuronal activity during SPW-R episodes and their brain-wide correlates. Analysis of the temporal alignment between SPW and ripple components reveals well-differentiated SPW-R subtypes in the CA1 LFP. SPW-R–triggered fMRI maps show that ripples aligned to the positive peak of their SPWs have enhanced neocortical metabolic up-regulation. In contrast, ripples occurring at the trough of their SPWs relate to weaker neocortical up-regulation and absent subcortical down-regulation, indicating differentiated involvement of neuromodulatory pathways in the ripple phenomenon mediated by long-range interactions. To our knowledge, this study provides the first evidence for the existence of SPW-R subtypes with differentiated CA1 activity and metabolic correlates in related brain areas, possibly serving different memory functions. PMID:26540729

GAMES identifies and annotates mutations in next-generation sequencing projects.

PubMed

Sana, Maria Elena; Iascone, Maria; Marchetti, Daniela; Palatini, Jeff; Galasso, Marco; Volinia, Stefano

2011-01-01

Next-generation sequencing (NGS) methods have the potential for changing the landscape of biomedical science, but at the same time pose several problems in analysis and interpretation. Currently, there are many commercial and public software packages that analyze NGS data. However, the limitations of these applications include output which is insufficiently annotated and of difficult functional comprehension to end users. We developed GAMES (Genomic Analysis of Mutations Extracted by Sequencing), a pipeline aiming to serve as an efficient middleman between data deluge and investigators. GAMES attains multiple levels of filtering and annotation, such as aligning the reads to a reference genome, performing quality control and mutational analysis, integrating results with genome annotations and sorting each mismatch/deletion according to a range of parameters. Variations are matched to known polymorphisms. The prediction of functional mutations is achieved by using different approaches. Overall GAMES enables an effective complexity reduction in large-scale DNA-sequencing projects. GAMES is available free of charge to academic users and may be obtained from http://aqua.unife.it/GAMES.

The Biochemistry of O-GlcNAc Transferase: Which Functions Make It Essential in Mammalian Cells?

PubMed

Levine, Zebulon G; Walker, Suzanne

2016-06-02

O-linked N-acetylglucosamine transferase (OGT) is found in all metazoans and plays an important role in development but at the single-cell level is only essential in dividing mammalian cells. Postmitotic mammalian cells and cells of invertebrates such as Caenorhabditis elegans and Drosophila can survive without copies of OGT. Why OGT is required in dividing mammalian cells but not in other cells remains unknown. OGT has multiple biochemical activities. Beyond its well-known role in adding β-O-GlcNAc to serine and threonine residues of nuclear and cytoplasmic proteins, OGT also acts as a protease in the maturation of the cell cycle regulator host cell factor 1 (HCF-1) and serves as an integral member of several protein complexes, many of them linked to gene expression. In this review, we summarize current understanding of the mechanisms underlying OGT's biochemical activities and address whether known functions of OGT could be related to its essential role in dividing mammalian cells.

Protein Glycosylation in Aspergillus fumigatus Is Essential for Cell Wall Synthesis and Serves as a Promising Model of Multicellular Eukaryotic Development

PubMed Central

Jin, Cheng

2012-01-01

Glycosylation is a conserved posttranslational modification that is found in all eukaryotes, which helps generate proteins with multiple functions. Our knowledge of glycosylation mainly comes from the investigation of the yeast Saccharomyces cerevisiae and mammalian cells. However, during the last decade, glycosylation in the human pathogenic mold Aspergillus fumigatus has drawn significant attention. It has been revealed that glycosylation in A. fumigatus is crucial for its growth, cell wall synthesis, and development and that the process is more complicated than that found in the budding yeast S. cerevisiae. The present paper implies that the investigation of glycosylation in A. fumigatus is not only vital for elucidating the mechanism of fungal cell wall synthesis, which will benefit the design of new antifungal therapies, but also helps to understand the role of protein glycosylation in the development of multicellular eukaryotes. This paper describes the advances in functional analysis of protein glycosylation in A. fumigatus. PMID:21977037

Are Some Attitudes More Self-Defining Than Others? Assessing Self-Related Attitude Functions and Their Consequences.

PubMed

Zunick, Peter V; Teeny, Jacob D; Fazio, Russell H

2017-08-01

Attitudes serve multiple functions, some related to the self-concept. We call attitudes that help people define who they are "self-defining." Across four studies, we tested a brief self-report measure of the extent to which an attitude is self-defining. Studies 1 and 2 showed that self-defining attitudes tend to be extreme, positive, and unambivalent. Studies 3 and 4 produced two main findings. First, self-definition was related to, but not redundant with, a number of other characteristics of the attitude (e.g., attitude certainty). Second, self-definition predicted participants' intentions to spontaneously advocate and, in Study 4, their reactions to an opportunity to advocate behaviorally (i.e., writing about their attitude in an optional response box) following a self-threat. Overall, the results highlight the utility of this approach and, more broadly, demonstrate the value of considering the role of the self in attitudinal processes, and vice versa.

Facile fabrication of mesoporous silica micro-jets with multi-functionalities† †Electronic supplementary information (ESI) available: Detailed BET experiments, videos and supplementary data. See DOI: 10.1039/c7nr04527a

PubMed Central

Vilela, D.; Hortelao, A. C.; Balderas-Xicohténcatl, R.; Hirscher, M.; Hahn, K.

2017-01-01

Self-propelled micro/nano-devices have been proved as powerful tools in various applications given their capability of both autonomous motion and on-demand task fulfilment. Tubular micro-jets stand out as an important member in the family of self-propelled micro/nano-devices and are widely explored with respect to their fabrication and functionalization. A few methods are currently available for the fabrication of tubular micro-jets, nevertheless there is still a demand to explore the fabrication of tubular micro-jets made of versatile materials and with the capability of multi-functionalization. Here, we present a facile strategy for the fabrication of mesoporous silica micro-jets (MSMJs) for tubular micromotors which can carry out multiple tasks depending on their functionalities. The synthesis of MSMJs does not require the use of any equipment, making it facile and cost-effective for future practical use. The MSMJs can be modified inside, outside or both with different kinds of metal nanoparticles, which provide these micromotors with a possibility of additional properties, such as the anti-bacterial effect by silver nanoparticles, or biochemical sensing based on surface enhanced Raman scattering (SERS) by gold nanoparticles. Because of the high porosity, high surface area and also the easy surface chemistry process, the MSMJs can be employed for the efficient removal of heavy metals in contaminated water, as well as for the controlled and active drug delivery, as two proof-of-concept examples of environmental and biomedical applications, respectively. Therefore, taking into account the new, simple and cheap method of fabrication, highly porous structure, and multiple functionalities, the mesoporous silica based micro-jets can serve as efficient tools for desired applications. PMID:28891580

Bone-derived mesenchymal stromal cells from HIV transgenic mice exhibit altered proliferation, differentiation capacity and paracrine functions along with impaired therapeutic potential in kidney injury

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

Cheng, Kang; Rai, Partab; Lan, Xiqian

Mesenchymal stem cells (MSCs) secrete paracrine factors that could be cytoprotective and serve roles in immunoregulation during tissue injury. Although MSCs express HIV receptors, and co-receptors, and are susceptible to HIV infection, whether HIV-1 may affect biological properties of MSCs needs more study. We evaluated cellular proliferation, differentiation and paracrine functions of MSCs isolated from compact bones of healthy control mice and Tg26 HIV-1 transgenic mice. The ability of MSCs to protect against cisplatin toxicity was studied in cultured renal tubular cells as well as in intact mice. We successfully isolated MSCs from healthy mice and Tg26 HIV-1 transgenic micemore » and found the latter expressed viral Nef, Vpu, NL4-3 and Vif genes. The proliferation and differentiation of Tg26 HIV-1 MSCs was inferior to MSCs from healthy mice. Moreover, transplantation of Tg26 HIV-1 MSCs less effectively improved outcomes compared with healthy MSCs in mice with acute kidney injury. Also, Tg26 HIV-1 MSCs secreted multiple cytokines, but at significantly lower levels than healthy MSCs, which resulted in failure of conditioned medium from these MSCs to protect cultured renal tubular cells from cisplatin toxicity. Therefore, HIV-1 had adverse biological effects on MSCs extending to their proliferation, differentiation, function, and therapeutic potential. These findings will help in advancing mechanistical insight in renal injury and repair in the setting of HIV-1 infection. -- Highlights: •MSCs isolated from HIV mice displayed HIV genes. •MSCs isolated from HIV mice exhibited attenuated growth and paracrine functions. •AKI mice with transplanted HIV-MSC displayed poor outcome. •HIV-1 MSC secreted multiple cytokines but at a lower level.« less

A functional analysis of the spacer of V(D)J recombination signal sequences.

PubMed

Lee, Alfred Ian; Fugmann, Sebastian D; Cowell, Lindsay G; Ptaszek, Leon M; Kelsoe, Garnett; Schatz, David G

2003-10-01

During lymphocyte development, V(D)J recombination assembles antigen receptor genes from component V, D, and J gene segments. These gene segments are flanked by a recombination signal sequence (RSS), which serves as the binding site for the recombination machinery. The murine Jbeta2.6 gene segment is a recombinationally inactive pseudogene, but examination of its RSS reveals no obvious reason for its failure to recombine. Mutagenesis of the Jbeta2.6 RSS demonstrates that the sequences of the heptamer, nonamer, and spacer are all important. Strikingly, changes solely in the spacer sequence can result in dramatic differences in the level of recombination. The subsequent analysis of a library of more than 4,000 spacer variants revealed that spacer residues of particular functional importance are correlated with their degree of conservation. Biochemical assays indicate distinct cooperation between the spacer and heptamer/nonamer along each step of the reaction pathway. The results suggest that the spacer serves not only to ensure the appropriate distance between the heptamer and nonamer but also regulates RSS activity by providing additional RAG:RSS interaction surfaces. We conclude that while RSSs are defined by a "digital" requirement for absolutely conserved nucleotides, the quality of RSS function is determined in an "analog" manner by numerous complex interactions between the RAG proteins and the less-well conserved nucleotides in the heptamer, the nonamer, and, importantly, the spacer. Those modulatory effects are accurately predicted by a new computational algorithm for "RSS information content." The interplay between such binary and multiplicative modes of interactions provides a general model for analyzing protein-DNA interactions in various biological systems.

The Scientific Filesystem.

PubMed

Sochat, Vanessa

2018-05-01

Here, we present the Scientific Filesystem (SCIF), an organizational format that supports exposure of executables and metadata for discoverability of scientific applications. The format includes a known filesystem structure, a definition for a set of environment variables describing it, and functions for generation of the variables and interaction with the libraries, metadata, and executables located within. SCIF makes it easy to expose metadata, multiple environments, installation steps, files, and entry points to render scientific applications consistent, modular, and discoverable. A SCIF can be installed on a traditional host or in a container technology such as Docker or Singularity. We start by reviewing the background and rationale for the SCIF, followed by an overview of the specification and the different levels of internal modules ("apps") that the organizational format affords. Finally, we demonstrate that SCIF is useful by implementing and discussing several use cases that improve user interaction and understanding of scientific applications. SCIF is released along with a client and integration in the Singularity 2.4 software to quickly install and interact with SCIF. When used inside of a reproducible container, a SCIF is a recipe for reproducibility and introspection of the functions and users that it serves. We use SCIF to evaluate container software, provide metrics, serve scientific workflows, and execute a primary function under different contexts. To encourage collaboration and sharing of applications, we developed tools along with an open source, version-controlled, tested, and programmatically accessible web infrastructure. SCIF and associated resources are available at https://sci-f.github.io. The ease of using SCIF, especially in the context of containers, offers promise for scientists' work to be self-documenting and programatically parseable for maximum reproducibility. SCIF opens up an abstraction from underlying programming languages and packaging logic to work with scientific applications, opening up new opportunities for scientific software development.

Facial expressivity during the clinical interview as a predictor functional disability in schizophrenia. a pilot study.

PubMed

Troisi, Alfonso; Pompili, Enrico; Binello, Luigi; Sterpone, Alessandro

2007-03-30

Despite the central role of nonverbal behavior in regulating social interactions, its relationship to functional disability in schizophrenia has received little empirical attention. This study aimed at assessing the relationship of patients' spontaneous facial expressivity during the clinical interview to clinician-rated and self-reported measures of functional disability. The nonverbal behavior of 28 stabilized patients with schizophrenia was analyzed by using the Ethological Coding System for Interviews (ECSI). Functional disability was assessed using the Global Assessment of Functioning (GAF) scale and the Sheehan Disability Scale (DISS). Partial correlation analysis controlling for the confounding effects of neuroleptic treatment showed that facial expressivity was correlated with the GAF score (r=0.42, P=0.03) and the scores on the subscales of the DISS measuring work (r=-0.52, P=0.005) and social (r=-0.50, P=0.007) disability. In a multiple regression model, nonverbal behavior explained variation in patients' work and social disability better than negative symptoms. The results of this pilot study suggest that deficits in encoding affiliative signals may play a role in determining or aggravating functional disability in schizophrenia. One clinical implication of this finding is that remediation training programs designed to improve nonverbal communication could also serve as a useful adjunct for improving work and social functioning in patients with schizophrenia.

Safe driving and executive functions in healthy middle-aged drivers.

PubMed

León-Domínguez, Umberto; Solís-Marcos, Ignacio; Barrio-Álvarez, Elena; Barroso Y Martín, Juan Manuel; León-Carrión, José

2017-01-01

The introduction of the point system driver's license in several European countries could offer a valid framework for evaluating driving skills. This is the first study to use this framework to assess the functional integrity of executive functions in middle-aged drivers with full points, partial points or no points on their driver's license (N = 270). The purpose of this study is to find differences in executive functions that could be determinants in safe driving. Cognitive tests were used to assess attention processes, processing speed, planning, cognitive flexibility, and inhibitory control. Analyses for covariance (ANCOVAS) were used for group comparisons while adjusting for education level. The Bonferroni method was used for correcting for multiple comparisons. Overall, drivers with the full points on their license showed better scores than the other two groups. In particular, significant differences were found in reaction times on Simple and Conditioned Attention tasks (both p-values < 0.001) and in number of type-III errors on the Tower of Hanoi task (p = 0.026). Differences in reaction time on attention tasks could serve as neuropsychological markers for safe driving. Further analysis should be conducted in order to determine the behavioral impact of impaired executive functioning on driving ability.

Vestibulo-ocular reflex function in children with high-functioning autism spectrum disorders.

PubMed

Carson, Tana B; Wilkes, Bradley J; Patel, Kunal; Pineda, Jill L; Ko, Ji H; Newell, Karl M; Bodfish, James W; Schubert, Michael C; Radonovich, Krestin; White, Keith D; Lewis, Mark H

2017-02-01

Sensorimotor processing alterations are a growing focus in the assessment and treatment of Autism Spectrum Disorders (ASD). The rotational vestibulo-ocular reflex (rVOR), which functions to maintain stable vision during head movements, is a sensorimotor system that may be useful in understanding such alterations and their underlying neurobiology. In this study, we assessed post-rotary nystagmus elicited by continuous whole body rotation among children with high-functioning ASD and typically developing children. Children with ASD exhibited increased rVOR gain, the ratio of eye velocity to head velocity, indicating a possible lack of cerebellar inhibitory input to brainstem vestibular nuclei in this population. The ASD group also showed less regular or periodic horizontal eye movements as indexed by greater variance accounted for by multiple higher frequency bandwidths as well as greater entropy scores compared to typically developing children. The decreased regularity or dysrhythmia in the temporal structure of nystagmus beats in children with ASD may be due to alterations in cerebellum and brainstem circuitry. These findings could potentially serve as a model to better understand the functional effects of differences in these brain structures in ASD. Autism Res 2017, 10: 251-266. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

Multi-functional liposomes showing radiofrequency-triggered release and magnetic resonance imaging for tumor multi-mechanism therapy.

PubMed

Du, Bin; Han, Shuping; Li, Hongyan; Zhao, Feifei; Su, Xiangjie; Cao, Xiaohui; Zhang, Zhenzhong

2015-03-12

Recently, nanoplatforms with multiple functions, such as tumor-targeting drug carriers, MRI, optical imaging, thermal therapy etc., have become popular in the field of cancer research. The present study reports a novel multi-functional liposome for cancer theranostics. A dual targeted drug delivery with radiofrequency-triggered drug release and imaging based on the magnetic field influence was used advantageously for tumor multi-mechanism therapy. In this system, the surface of fullerene (C60) was decorated with iron oxide nanoparticles, and PEGylation formed a hybrid nanosystem (C60-Fe3O4-PEG2000). Thermosensitive liposomes (dipalmitoylphosphatidylcholine, DPPC) with DSPE-PEG2000-folate wrapped up the hybrid nanosystem and docetaxel (DTX), which were designed to combine features of biological and physical (magnetic) drug targeting for fullerene radiofrequency-triggered drug release. The magnetic liposomes not only served as powerful tumor diagnostic magnetic resonance imaging (MRI) contrast agents, but also as powerful agents for photothermal ablation of tumors. Furthermore, a remarkable thermal therapy combined chemotherapy multi-functional liposome nanoplatform converted radiofrequency energy into thermal energy to release drugs from thermosensitive liposomes, which was also observed during both in vitro and in vivo treatment. The multi-functional liposomes also could selectively kill cancer cells in highly localized regions via their excellent active tumor targeting and magnetic targeted abilities.

Immunological Functions of the Membrane Proximal Region of MHC Class II Molecules

PubMed Central

Harton, Jonathan; Jin, Lei; Hahn, Amy; Drake, Jim

2016-01-01

Major histocompatibility complex (MHC) class II molecules present exogenously derived antigen peptides to CD4 T cells, driving activation of naïve T cells and supporting CD4-driven immune functions. However, MHC class II molecules are not inert protein pedestals that simply bind and present peptides. These molecules also serve as multi-functional signaling molecules delivering activation, differentiation, or death signals (or a combination of these) to B cells, macrophages, as well as MHC class II-expressing T cells and tumor cells. Although multiple proteins are known to associate with MHC class II, interaction with STING (stimulator of interferon genes) and CD79 is essential for signaling. In addition, alternative transmembrane domain pairing between class II α and β chains influences association with membrane lipid sub-domains, impacting both signaling and antigen presentation. In contrast to the membrane-distal region of the class II molecule responsible for peptide binding and T-cell receptor engagement, the membrane-proximal region (composed of the connecting peptide, transmembrane domain, and cytoplasmic tail) mediates these “non-traditional” class II functions. Here, we review the literature on the function of the membrane-proximal region of the MHC class II molecule and discuss the impact of this aspect of class II immunobiology on immune regulation and human disease. PMID:27006762

Crammed signaling motifs in the T-cell receptor.

PubMed

Borroto, Aldo; Abia, David; Alarcón, Balbino

2014-09-01

Although the T cell antigen receptor (TCR) is long known to contain multiple signaling subunits (CD3γ, CD3δ, CD3ɛ and CD3ζ), their role in signal transduction is still not well understood. The presence of at least one immunoreceptor tyrosine-based activation motif (ITAM) in each CD3 subunit has led to the idea that the multiplication of such elements essentially serves to amplify signals. However, the evolutionary conservation of non-ITAM sequences suggests that each CD3 subunit is likely to have specific non-redundant roles at some stage of development or in mature T cell function. The CD3ɛ subunit is paradigmatic because in a relatively short cytoplasmic sequence (∼55 amino acids) it contains several docking sites for proteins involved in intracellular trafficking and signaling, proteins whose relevance in T cell activation is slowly starting to be revealed. In this review we will summarize our current knowledge on the signaling effectors that bind directly to the TCR and we will propose a hierarchy in their response to TCR triggering. Copyright © 2014 Elsevier B.V. All rights reserved.

Native architecture of the Chlamydomonas chloroplast revealed by in situ cryo-electron tomography

PubMed Central

Engel, Benjamin D; Schaffer, Miroslava; Kuhn Cuellar, Luis; Villa, Elizabeth; Plitzko, Jürgen M; Baumeister, Wolfgang

2015-01-01

Chloroplast function is orchestrated by the organelle's intricate architecture. By combining cryo-focused ion beam milling of vitreous Chlamydomonas cells with cryo-electron tomography, we acquired three-dimensional structures of the chloroplast in its native state within the cell. Chloroplast envelope inner membrane invaginations were frequently found in close association with thylakoid tips, and the tips of multiple thylakoid stacks converged at dynamic sites on the chloroplast envelope, implicating lipid transport in thylakoid biogenesis. Subtomogram averaging and nearest neighbor analysis revealed that RuBisCO complexes were hexagonally packed within the pyrenoid, with ∼15 nm between their centers. Thylakoid stacks and the pyrenoid were connected by cylindrical pyrenoid tubules, physically bridging the sites of light-dependent photosynthesis and light-independent carbon fixation. Multiple parallel minitubules were bundled within each pyrenoid tubule, possibly serving as conduits for the targeted one-dimensional diffusion of small molecules such as ATP and sugars between the chloroplast stroma and the pyrenoid matrix. DOI: http://dx.doi.org/10.7554/eLife.04889.001 PMID:25584625

TRIP13 impairs mitotic checkpoint surveillance and is associated with poor prognosis in multiple myeloma

PubMed Central

Song, Dongliang; Hu, Liangning; Xie, Bingqian; Wang, Houcai; Gao, Lu; Gao, Minjie; Xu, Hongwei; Xu, Zhijian; Wu, Xiaosong; Zhang, Yiwen; Zhu, Weiliang; Zhan, Fenghuang; Shi, Jumei

2017-01-01

AAA-ATPase TRIP13 is one of the chromosome instability gene recently established in multiple myeloma (MM), the second most common and incurable hematological malignancy. However, the specific function of TRIP13 in MM is largely unknown. Using sequential gene expression profiling, we demonstrated that high TRIP13 expression levels were positively correlated with progression, disease relapse, and poor prognosis in MM patients. Overexpressing human TRIP13 in myeloma cells prompted cell growth and drug resistance, and overexpressing murine TRIP13, which shares 93% sequence identity with human TRIP13, led to colony formation of NIH/3T3 fibroblasts in vitro and tumor formation in vivo. Meanwhile, the knockdown of TRIP13 inhibited myeloma cell growth, induced cell apoptosis, and reduced tumor burden in xenograft MM mice. Mechanistically, we observed that the overexpression of TRIP13 abrogated the spindle checkpoint and induced proteasome-mediated degradation of MAD2 primarily through the Akt pathway. Thus, our results demonstrate that TRIP13 may serve as a biomarker for MM disease development and prognosis, making it a potential target for future therapies. PMID:28157697

Teachers, Curriculum and the Community.

ERIC Educational Resources Information Center

Molnar, Alex

In this essay teachers, school curriculum and their relationship to the society they serve and the community in which they function are discussed. Since educational institutions serve a regulatory function, what goes on in schools mirrors the interests of the status quo in the society. Therefore the question facing educators and community people…

Lodge Programs Serving Family Functions for People with Psychiatric Disabilities.

ERIC Educational Resources Information Center

Onaga, Esther E.; McKinney, Kathleen G.; Pfaff, Judy

2000-01-01

Interviews were conducted with people affiliated with lodges, a community program for people with psychiatric disabilities, about their perceptions of promising practices. Responses validated the notion that the lodge serves many of the functions of a family. Provides excerpts from interviews to supplement this theme. Discusses implications for…

77 FR 25168 - Appraisal Subcommittee (ASC); ASC Rules of Operation; Amended

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-27

... heads of the Bureau of Consumer Financial Protection and the Federal Housing Finance Agency. The ASC Rules of Operation serve as corporate bylaws outlining the ASC's purpose, functions, authority... Title XI. The ASC Rules of Operation serve as corporate bylaws outlining the ASC's purpose, functions...

Identification of Prostate Cancer-Specific Circular RNAs

DTIC Science & Technology

2016-12-01

they often have regulatory functions. For example, circRNAs can serve as endogenous microRNA sponges to neutralize the microRNA function. However, it...circRNAs is the capability to serve as sponges to neutralize the endogenous microRNAs. In this regard, all of these circRNAs had the potential to

Microtubule-based nanomaterials: Exploiting nature's dynamic biopolymers

DOE PAGES

Bachand, George D.; Stevens, Mark J.; Spoerke, Erik David

2015-04-09

For more than a decade now, biomolecular systems have served as an inspiration for the development of synthetic nanomaterials and systems that are capable of reproducing many of unique and emergent behaviors of living systems. In addition, one intriguing element of such systems may be found in a specialized class of proteins known as biomolecular motors that are capable of performing useful work across multiple length scales through the efficient conversion of chemical energy. Microtubule (MT) filaments may be considered within this context as their dynamic assembly and disassembly dissipate energy, and perform work within the cell. MTs are onemore » of three cytoskeletal filaments in eukaryotic cells, and play critical roles in a range of cellular processes including mitosis and vesicular trafficking. Based on their function, physical attributes, and unique dynamics, MTs also serve as a powerful archetype of a supramolecular filament that underlies and drives multiscale emergent behaviors. In this review, we briefly summarize recent efforts to generate hybrid and composite nanomaterials using MTs as biomolecular scaffolds, as well as computational and synthetic approaches to develop synthetic one-dimensional nanostructures that display the enviable attributes of the natural filaments.« less

Maintenance of ventricular fibrillation in heterogeneous ventricle.

PubMed

Arevalo, Hamenegild J; Trayanova, Natalia A

2006-01-01

Although ventricular fibrillation (VF) is the prevalent cause of sudden cardiac death, the mechanisms that underlie VF remain elusive. One possible explanation is that VF is driven by a single robust rotor that is the source of wavefronts that break-up due to functional heterogeneities. Previous 2D computer simulations have proposed that a heterogeneity in background potassium current (IK1) can serve as the substrate for the formation of mother rotor activity. This study incorporates IK1 heterogeneity between the left and right ventricle in a realistic 3D rabbit ventricle model to examine its effects on the organization of VF. Computer simulations show that the IK1 heterogeneity contributes to the initiation and maintenance of VF by providing regions of different refractoriness which serves as sites of wave break and rotor formation. A single rotor that drives the fibrillatory activity in the ventricle is not found in this study. Instead, multiple sites of reentry are recorded throughout the ventricle. Calculation of dominant frequencies for each myocardial node yields no significant difference between the dominant frequency of the LV and the RV. The 3D computer simulations suggest that IK1 spatial heterogeneity alone can not lead to the formation of a stable rotor.

What is orgasm? A model of sexual trance and climax via rhythmic entrainment

PubMed Central

Safron, Adam

2016-01-01

Orgasm is one of the most intense pleasures attainable to an organism, yet its underlying mechanisms remain poorly understood. On the basis of existing literatures, this article introduces a novel mechanistic model of sexual stimulation and orgasm. In doing so, it characterizes the neurophenomenology of sexual trance and climax, describes parallels in dynamics between orgasms and seizures, speculates on possible evolutionary origins of sex differences in orgasmic responding, and proposes avenues for future experimentation. Here, a model is introduced wherein sexual stimulation induces entrainment of coupling mechanical and neuronal oscillatory systems, thus creating synchronized functional networks within which multiple positive feedback processes intersect synergistically to contribute to sexual experience. These processes generate states of deepening sensory absorption and trance, potentially culminating in climax if critical thresholds are surpassed. The centrality of rhythmic stimulation (and its modulation by salience) for surpassing these thresholds suggests ways in which differential orgasmic responding between individuals—or with different partners—may serve as a mechanism for ensuring adaptive mate choice. Because the production of rhythmic stimulation combines honest indicators of fitness with cues relating to potential for investment, differential orgasmic response may serve to influence the probability of continued sexual encounters with specific mates. PMID:27799079

Role of vaccinations as risk factors for ill health in veterans of the Gulf war: cross sectional study

PubMed Central

Hotopf, Matthew; David, Anthony; Hull, Lisa; Ismail, Khalida; Unwin, Catherine; Wessely, Simon

2000-01-01

Objectives To explore the relation between ill health after the Gulf war and vaccines received before or during the conflict. To test the hypothesis that such ill health is limited to military personnel who received multiple vaccines during deployment and that pesticide use modifies any effect. Design Cross sectional study of Gulf war veterans followed for six to eight years after deployment. Setting UK armed forces. Participants Military personnel who served in the Gulf and who still had their vaccine records. Main outcome measures Multisymptom illness as classified by the Centers for Disease Control and Prevention; fatigue; psychological distress; post-traumatic stress reaction; health perception; and physical functioning. Results The response rate for the original survey was 70.4% (n=3284). Of these, 28% (923) had vaccine records. Receipt of multiple vaccines before deployment was associated with only one of the six health outcomes (post-traumatic stress reaction). By contrast five of the six outcomes (all but post-traumatic stress reaction) were associated with multiple vaccines received during deployment. The strongest association was for the multisymptom illness (odds ratio 5.0; 95% confidence interval 2.5 to 9.8). Conclusion Among veterans of the Gulf war there is a specific relation between multiple vaccinations given during deployment and later ill health. Multiple vaccinations in themselves do not seem to be harmful but combined with the “stress” of deployment they may be associated with adverse health outcomes. These results imply that every effort should be made to maintain routine vaccines during peacetime. PMID:10818024

Intrinsic brain connectivity in fibromyalgia is associated with chronic pain intensity.

PubMed

Napadow, Vitaly; LaCount, Lauren; Park, Kyungmo; As-Sanie, Sawsan; Clauw, Daniel J; Harris, Richard E

2010-08-01

Fibromyalgia (FM) is considered to be the prototypical central chronic pain syndrome and is associated with widespread pain that fluctuates spontaneously. Multiple studies have demonstrated altered brain activity in these patients. The objective of this study was to investigate the degree of connectivity between multiple brain networks in patients with FM, as well as how activity in these networks correlates with the level of spontaneous pain. Resting-state functional magnetic resonance imaging (FMRI) data from 18 patients with FM and 18 age-matched healthy control subjects were analyzed using dual-regression independent components analysis, which is a data-driven approach for the identification of independent brain networks. Intrinsic, or resting-state, connectivity was evaluated in multiple brain networks: the default mode network (DMN), the executive attention network (EAN), and the medial visual network (MVN), with the MVN serving as a negative control. Spontaneous pain levels were also analyzed for covariance with intrinsic connectivity. Patients with FM had greater connectivity within the DMN and right EAN (corrected P [P(corr)] < 0.05 versus controls), and greater connectivity between the DMN and the insular cortex, which is a brain region known to process evoked pain. Furthermore, greater intensity of spontaneous pain at the time of the FMRI scan correlated with greater intrinsic connectivity between the insula and both the DMN and right EAN (P(corr) < 0.05). These findings indicate that resting brain activity within multiple networks is associated with spontaneous clinical pain in patients with FM. These findings may also have broader implications for how subjective experiences such as pain arise from a complex interplay among multiple brain networks.

Intrinsic Brain Connectivity in Fibromyalgia is Associated with Chronic Pain Intensity

PubMed Central

Napadow, Vitaly; LaCount, Lauren; Park, Kyungmo; As-Sanie, Suzie; Clauw, Daniel J; Harris, Richard E

2010-01-01

OBJECTIVE Fibromyalgia (FM) is considered to be the prototypical central chronic pain syndrome and is associated with widespread pain that fluctuates spontaneously. Multiple studies have demonstrated altered brain activity in these patients. Our objective was to investigate the degree of connectivity between multiple brain networks in FM, as well as how activity in these networks correlates with spontaneous pain. METHODS Resting functional magnetic resonance imaging (fMRI) data in FM patients (n=18) and age-matched healthy controls (HC, n=18) were analyzed using dual regression independent component analysis (ICA) - a data driven approach used to identify independent brain networks. We evaluated intrinsic, or resting, connectivity in multiple brain networks: the default mode network (DMN), the executive attention network (EAN), and the medial visual network (MVN), with the MVN serving as a negative control. Spontaneous pain levels were also covaried with intrinsic connectivity. RESULTS We found that FM patients had greater connectivity within the DMN and right EAN (rEAN; p<0.05, corrected), and greater connectivity between the DMN and the insular cortex – a brain region known to process evoked pain. Furthermore, greater spontaneous pain at the time of the scan correlated with greater intrinsic connectivity between the insula and both the DMN and rEAN (p<0.05, corrected). CONCLUSION Our findings indicate that resting brain activity within multiple networks is associated with spontaneous clinical pain in FM. These findings may also have broader implications for how subjective experiences such as pain arise from a complex interplay amongst multiple brain networks. PMID:20506181

Fibroblast growth factors in cardiovascular disease: The emerging role of FGF21

PubMed Central

Domouzoglou, Eleni M.; Naka, Katerina K.; Vlahos, Antonios P.; Papafaklis, Michail I.; Michalis, Lampros K.; Tsatsoulis, Agathoklis

2015-01-01

Early detection of risk factors for enhanced primary prevention and novel therapies for treating the chronic consequences of cardiovascular disease are of the utmost importance for reducing morbidity. Recently, fibroblast growth factors (FGFs) have been intensively studied as potential new molecules in the prevention and treatment of cardiovascular disease mainly attributable to metabolic effects and angiogenic actions. Members of the endocrine FGF family have been shown to increase metabolic rate, decrease adiposity, and restore glucose homeostasis, suggesting a multiple metabolic role. Serum levels of FGFs have been associated with established cardiovascular risk factors as well as with the severity and extent of coronary artery disease and could be useful for prediction of cardiovascular death. Furthermore, preclinical investigations and clinical trials have tested FGF administration for therapeutic angiogenesis in ischemic vascular disease, demonstrating a potential role in improving angina and limb function. FGF21 has lately emerged as a potent metabolic regulator with multiple effects that ultimately improve the lipoprotein profile. Early studies show that FGF21 is associated with the presence of atherosclerosis and may play a protective role against plaque formation by improving endothelial function. The present review highlights recent investigations suggesting that FGFs, in particular FGF21, may be useful as markers of cardiovascular risk and may also serve as protective/therapeutic agents in cardiovascular disease. PMID:26232236

Fibroblast growth factors in cardiovascular disease: The emerging role of FGF21.

PubMed

Domouzoglou, Eleni M; Naka, Katerina K; Vlahos, Antonios P; Papafaklis, Michail I; Michalis, Lampros K; Tsatsoulis, Agathoklis; Maratos-Flier, Eleftheria

2015-09-15

Early detection of risk factors for enhanced primary prevention and novel therapies for treating the chronic consequences of cardiovascular disease are of the utmost importance for reducing morbidity. Recently, fibroblast growth factors (FGFs) have been intensively studied as potential new molecules in the prevention and treatment of cardiovascular disease mainly attributable to metabolic effects and angiogenic actions. Members of the endocrine FGF family have been shown to increase metabolic rate, decrease adiposity, and restore glucose homeostasis, suggesting a multiple metabolic role. Serum levels of FGFs have been associated with established cardiovascular risk factors as well as with the severity and extent of coronary artery disease and could be useful for prediction of cardiovascular death. Furthermore, preclinical investigations and clinical trials have tested FGF administration for therapeutic angiogenesis in ischemic vascular disease, demonstrating a potential role in improving angina and limb function. FGF21 has lately emerged as a potent metabolic regulator with multiple effects that ultimately improve the lipoprotein profile. Early studies show that FGF21 is associated with the presence of atherosclerosis and may play a protective role against plaque formation by improving endothelial function. The present review highlights recent investigations suggesting that FGFs, in particular FGF21, may be useful as markers of cardiovascular risk and may also serve as protective/therapeutic agents in cardiovascular disease. Copyright © 2015 the American Physiological Society.

Influence of landscape structure on reef fish assemblages

USGS Publications Warehouse

Grober-Dunsmore, R.; Frazer, T.K.; Beets, J.P.; Lindberg, W.J.; Zwick, P.; Funicelli, N.A.

2008-01-01

Management of tropical marine environments calls for interdisciplinary studies and innovative methodologies that consider processes occurring over broad spatial scales. We investigated relationships between landscape structure and reef fish assemblage structure in the US Virgin Islands. Measures of landscape structure were transformed into a reduced set of composite indices using principal component analyses (PCA) to synthesize data on the spatial patterning of the landscape structure of the study reefs. However, composite indices (e.g., habitat diversity) were not particularly informative for predicting reef fish assemblage structure. Rather, relationships were interpreted more easily when functional groups of fishes were related to individual habitat features. In particular, multiple reef fish parameters were strongly associated with reef context. Fishes responded to benthic habitat structure at multiple spatial scales, with various groups of fishes each correlated to a unique suite of variables. Accordingly, future experiments should be designed to test functional relationships based on the ecology of the organisms of interest. Our study demonstrates that landscape-scale habitat features influence reef fish communities, illustrating promise in applying a landscape ecology approach to better understand factors that structure coral reef ecosystems. Furthermore, our findings may prove useful in design of spatially-based conservation approaches such as marine protected areas (MPAs), because landscape-scale metrics may serve as proxies for areas with high species diversity and abundance within the coral reef landscape. ?? 2007 Springer Science+Business Media B.V.

Sca-1 Identifies a Distinct Androgen-Independent Murine Prostatic Luminal Cell Lineage with Bipotent Potential

PubMed Central

Kwon, Oh-Joon; Zhang, Li; Xin, Li

2016-01-01

Recent lineage tracing studies support the existence of prostate luminal progenitors that possess extensive regenerative capacity, but their identity remains unknown. We show that Sca-1 (Stem Cell Antigen-1) identifies a small population of murine prostate luminal cells that reside in the proximal prostatic ducts adjacent to the urethra. Sca-1+ luminal cells do not express Nkx3.1. They do not carry the secretory function, although they express the androgen receptor. These cells are enriched in the prostates of castrated mice. In the in vitro prostate organoid assay, a small fraction of the Sca-1+ luminal cells are capable of generating budding organoids that are morphologically distinct from those derived from other cell lineages. Histologically, this type of organoid is composed of multiple inner layers of luminal cells surrounded by multiple outer layers of basal cells. When passaged, these organoids retain their morphological and histological features. Finally, the Sca-1+ luminal cells are capable of forming small prostate glands containing both basal and luminal cells in an in vivo prostate regeneration assay. Collectively, our study establishes the androgen-independent and bipotent organoid-forming Sca-1+ luminal cells as a functionally distinct cellular entity. These cells may represent a putative luminal progenitor population and serve as a cellular origin for castration resistant prostate cancer. PMID:26418304

Cold Atom Source Containing Multiple Magneto-Optical Traps

NASA Technical Reports Server (NTRS)

Ramirez-Serrano, Jaime; Kohel, James; Kellogg, James; Lim, Lawrence; Yu, Nan; Maleki, Lute

2007-01-01

An apparatus that serves as a source of a cold beam of atoms contains multiple two-dimensional (2D) magneto-optical traps (MOTs). (Cold beams of atoms are used in atomic clocks and in diverse scientific experiments and applications.) The multiple-2D-MOT design of this cold atom source stands in contrast to single-2D-MOT designs of prior cold atom sources of the same type. The advantages afforded by the present design are that this apparatus is smaller than prior designs.

The Effect of Format and Organization on Extrapolation and Interpolation with Multiple Trend Displays.

ERIC Educational Resources Information Center

Wolfe, Mary L.; Martuza, Victor R.

The major purpose of this experiment was to examine the effects of format (bar graphs vs. tables) and organization (by year vs. by brand) on the speed and accuracy of extrapolation and interpolation with multiple, nonlinear trend displays. Fifty-six undergraduates enrolled in the College of Education at the University of Delaware served as the…

The Effects of DI Flashcards and Math Racetrack on Multiplication Facts for Two Elementary Students with Learning Disabilities

ERIC Educational Resources Information Center

Lund, Kaitlyn; McLaughlin, T. F.; Neyman, Jen; Everson, Mary

2012-01-01

The purpose of this study was to evaluate the effects of a Direct Instruction (DI) flashcard system paired with a math racetrack to teach basic multiplication facts to two elementary students diagnosed with learning disabilities. The study was conducted in a resource room which served intermediate aged elementary students. The school was located…

A Computer System Serving as a Microswitch for Vocal Utterances of Persons with Multiple Disabilities: Two Case Evaluations. Research Report

ERIC Educational Resources Information Center

Lancioni, Giulio E.; Singh, Nirbhay N.; O'Reilly, Mark F.; Oliva, Doretta; Montironi, Gianluigi

2004-01-01

The use of microswitches has been considered a crucial strategy to help individuals with extensive multiple disabilities overcome passivity and achieve control of environmental stimulation (Crawford & Schuster, 1993; Gutowski, 1996; Ko, McConachie, & Jolleff, 1998). In recent years, considerable efforts have been made to extend the evaluation of…

Innovation Incentives and Biomarkers.

PubMed

Stern, Ariel D; Alexander, Brian M; Chandra, Amitabh

2018-01-01

Previously, we have discussed the importance of economic incentives in shaping markets for precision medicines. Here we consider incentives for biomarker development, including discovery and establishment. Biomarkers can reveal valuable information regarding diagnosis and prognosis, predict treatment efficacy or toxicity, serve as markers of disease progression, and serve as auxiliary endpoints for clinical trials. Some have multiple uses, while others have a specialized role, resulting in diverse incentives across players in the healthcare system. © 2017, ASCPT.

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

David Kisailus; Lara Estroff; Himadri S. Gupta

The technical presentations and discussions at this symposium disseminated and assessed current research and defined future directions in biomaterials research, with a focus on structure-function relationships in biological and biomimetic composites. The invited and contributed talks covered a diverse range of topics from fundamental biology, physics, chemistry, and materials science to potential applications in developing areas such as light-weight composites, multifunctional and smart materials, biomedical engineering, and nanoscaled sensors. The invited speakers were chosen to create a stimulating program with a mixture of established and junior faculty, industrial and academic researchers, and American and international experts in the field. Thismore » symposium served as an excellent introduction to the area for younger scientists (graduate students and post-doctoral researchers). Direct interactions between participants also helped to promote potential future collaborations involving multiple disciplines and institutions.« less

B-HIT - A Tool for Harvesting and Indexing Biodiversity Data

PubMed Central

Barker, Katharine; Braak, Kyle; Cawsey, E. Margaret; Coddington, Jonathan; Robertson, Tim; Whitacre, Jamie

2015-01-01

With the rapidly growing number of data publishers, the process of harvesting and indexing information to offer advanced search and discovery becomes a critical bottleneck in globally distributed primary biodiversity data infrastructures. The Global Biodiversity Information Facility (GBIF) implemented a Harvesting and Indexing Toolkit (HIT), which largely automates data harvesting activities for hundreds of collection and observational data providers. The team of the Botanic Garden and Botanical Museum Berlin-Dahlem has extended this well-established system with a range of additional functions, including improved processing of multiple taxon identifications, the ability to represent associations between specimen and observation units, new data quality control and new reporting capabilities. The open source software B-HIT can be freely installed and used for setting up thematic networks serving the demands of particular user groups. PMID:26544980

B-HIT - A Tool for Harvesting and Indexing Biodiversity Data.

PubMed

Kelbert, Patricia; Droege, Gabriele; Barker, Katharine; Braak, Kyle; Cawsey, E Margaret; Coddington, Jonathan; Robertson, Tim; Whitacre, Jamie; Güntsch, Anton

2015-01-01

With the rapidly growing number of data publishers, the process of harvesting and indexing information to offer advanced search and discovery becomes a critical bottleneck in globally distributed primary biodiversity data infrastructures. The Global Biodiversity Information Facility (GBIF) implemented a Harvesting and Indexing Toolkit (HIT), which largely automates data harvesting activities for hundreds of collection and observational data providers. The team of the Botanic Garden and Botanical Museum Berlin-Dahlem has extended this well-established system with a range of additional functions, including improved processing of multiple taxon identifications, the ability to represent associations between specimen and observation units, new data quality control and new reporting capabilities. The open source software B-HIT can be freely installed and used for setting up thematic networks serving the demands of particular user groups.

A new role for evoked potentials in MS? Repurposing evoked potentials as biomarkers for clinical trials in MS.

PubMed

Hardmeier, Martin; Leocani, Letizia; Fuhr, Peter

2017-09-01

Evoked potentials (EP) characterize signal conduction in selected tracts of the central nervous system in a quantifiable way. Since alteration of signal conduction is the main mechanism of symptoms and signs in multiple sclerosis (MS), multimodal EP may serve as a representative measure of the functional impairment in MS. Moreover, EP have been shown to be predictive for disease course, and thus might help to select patient groups at high risk of progression for clinical trials. EP can detect deterioration, as well as improvement of impulse propagation, independently from the mechanism causing the change. Therefore, they are candidates for biomarkers with application in clinical phase-II trials. Applicability of EP in multicenter trials has been limited by different standards of registration and assessment.

An airport community noise-impact assessment model

NASA Technical Reports Server (NTRS)

Deloach, R.

1980-01-01

A computer model was developed to assess the noise impact of an airport on the community which it serves. Assessments are made using the Fractional Impact Method by which a single number describes the community aircraft noise environment in terms of exposed population and multiple event noise level. The model is comprised of three elements: a conventional noise footprint model, a site specific population distribution model, and a dose response transfer function. The footprint model provides the noise distribution for a given aircraft operating scenario. This is combined with the site specific population distribution obtained from a national census data base to yield the number of residents exposed to a given level of noise. The dose response relationship relates noise exposure levels to the percentage of individuals highly annoyed by those levels.

Navigation system and method

NASA Technical Reports Server (NTRS)

Taylor, R. E.; Sennott, J. W. (Inventor)

1984-01-01

In a global positioning system (GPS), such as the NAVSTAR/GPS system, wherein the position coordinates of user terminals are obtained by processing multiple signals transmitted by a constellation of orbiting satellites, an acquisition-aiding signal generated by an earth-based control station is relayed to user terminals via a geostationary satellite to simplify user equipment. The aiding signal is FSK modulated on a reference channel slightly offset from the standard GPS channel. The aiding signal identifies satellites in view having best geometry and includes Doppler prediction data as well as GPS satellite coordinates and identification data associated with user terminals within an area being served by the control station and relay satellite. The aiding signal significantly reduces user equipment by simplifying spread spectrum signal demodulation and reducing data processing functions previously carried out at the user terminals.

What is in a name? Understanding the implications of participant terminology.

PubMed

Bibace, Roger; Clegg, Joshua W; Valsiner, Jaan

2009-03-01

The authors discuss the history of research terminology in American psychology with respect to the various labels given to those upon whom we conduct research ("observer"-"subject"-"participant"-"client"). This history is supplemented with an analysis of participant terminology in APA manuals from four historical eras, from the 1950s to the present. The general trend in participant terminology reflects the overall trends in American psychology, beginning with a complex lexicon that admitted both the passive and the active research participant, followed by a dominance of the passive term 'subject' and ending with the terminological ambiguity and multiplicity reflected in contemporary psychology. This selective history serves to contextualize a discussion of the meaning, functions, and implications of the transformations in, and debates over, participant terminology.

Caregiver-Teacher Concordance of Challenging Behaviors in Children with Autism Spectrum Disorder Served in Community Mental Health Settings

PubMed Central

Chlebowski, Colby; Brookman-Frazee, Lauren

2018-01-01

Children with autism spectrum disorder (ASD) exhibit high rates of challenging behaviors that impair functioning and represent the primary presenting problem in mental health (MH) services. Obtaining symptom reports from multiple informants is critical for treatment planning. This study evaluated caregiver-teacher concordance of ratings of the intensity of challenging behaviors in children with ASD receiving MH services, and identified child clinical factors associated with concordance. This sample included 141 children (M = 9.07 years), their caregivers, and teachers. Caregiver-teacher concordance of challenging behaviors was low and impacted by the degree and type of child psychiatric comorbidity. Findings support need for increased attention to the range of psychiatric problems children with ASD present to tailor treatment recommendations and service delivery. PMID:28343342

Programmed Cell Death and Caspase Functions During Neural Development.

PubMed

Yamaguchi, Yoshifumi; Miura, Masayuki

2015-01-01

Programmed cell death (PCD) is a fundamental component of nervous system development. PCD serves as the mechanism for quantitative matching of the number of projecting neurons and their target cells through direct competition for neurotrophic factors in the vertebrate peripheral nervous system. In addition, PCD plays roles in regulating neural cell numbers, canceling developmental errors or noise, and tissue remodeling processes. These findings are mainly derived from genetic studies that prevent cells from dying by apoptosis, which is a major form of PCD and is executed by activation of evolutionarily conserved cysteine protease caspases. Recent studies suggest that caspase activation can be coordinated in time and space at multiple levels, which might underlie nonapoptotic roles of caspases in neural development in addition to apoptotic roles. © 2015 Elsevier Inc. All rights reserved.

Cognition in older patients with multiple sclerosis compared to patients with amnestic mild cognitive impairment and healthy older adults.

PubMed

Roth, Alexandra K; Denney, Douglas R; Burns, Jeffrey M; Lynch, Sharon G

2018-06-25

Progress in the treatment of multiple sclerosis (MS) has resulted in larger numbers of patients living to an advanced age, but little is known about the cognitive status of these individuals. The primary purpose of this study was to identify differences in the cognitive performance between elderly individuals with MS and those with amnestic mild cognitive impairment (aMCI). Three groups ranging in age from 60 to 80 were compared: patients with MS (n = 64), patients with aMCI (n = 58), and healthy adults (n = 70). All participants completed a standard neuropsychological test battery that evaluated domains of attention, processing speed, executive function, memory, language, and visual spatial function. Compared to age- and gender-matched healthy controls, elderly MS patients exhibited a pattern of cognitive impairment centering on information processing speed and memory that was consistent with the deficits observed in other studies of MS patients regardless of age. Compared to aMCI patients, the MS patients exhibited worse performance on measures of processing speed, but better performance on a measure of memory under cued conditions (Selective Reminding Test), a nonspeeded measure of language (Boston Naming Test), and measures of executive function with processing speed statistically controlled (Trail Making Test, Stroop Test). Differences on neuropsychological measures can serve to distinguish aMCI from MS-related cognitive impairment in older patients, but it is essential that these measures control for the deficit in processing speed that is such a primary feature of MS. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Electrochemical biosensor based on functional composite nanofibers for detection of K-ras gene via multiple signal amplification strategy.

PubMed

Wang, Xiaoying; Shu, Guofang; Gao, Chanchan; Yang, Yu; Xu, Qian; Tang, Meng

2014-12-01

An electrochemical biosensor based on functional composite nanofibers for hybridization detection of specific K-ras gene that is highly associated with colorectal cancer via multiple signal amplification strategy has been developed. The carboxylated multiwalled carbon nanotubes (MWCNTs) doped nylon 6 (PA6) composite nanofibers (MWCNTs-PA6) was prepared using electrospinning, which served as the nanosized backbone for thionine (TH) electropolymerization. The functional composite nanofibers [MWCNTs-PA6-PTH, where PTH is poly(thionine)] used as supporting scaffolds for single-stranded DNA1 (ssDNA1) immobilization can dramatically increase the amount of DNA attachment and the hybridization sensitivity. Through the hybridization reaction, a sandwich format of ssDNA1/K-ras gene/gold nanoparticle-labeled ssDNA2 (AuNPs-ssDNA2) was fabricated, and the AuNPs offered excellent electrochemical signal transduction. The signal amplification was further implemented by forming network-like thiocyanuric acid/gold nanoparticles (TA/AuNPs). A significant sensitivity enhancement was obtained; the detection limit was down to 30fM, and the discriminations were up to 54.3 and 51.9% between the K-ras gene and the one-base mismatched sequences including G/C and A/T mismatched bases, respectively. The amenability of this method to the analyses of K-ras gene from the SW480 colorectal cancer cell lysates was demonstrated. The results are basically consistent with those of the K-ras Kit (HRM: high-resolution melt). The method holds promise for the diagnosis and management of cancer. Copyright © 2014 Elsevier Inc. All rights reserved.

Functions of autobiographical memory in Taiwanese and American emerging adults.

PubMed

Liao, Hsiao-Wen; Bluck, Susan; Alea, Nicole; Cheng, Ching-Ling

2016-01-01

The study addresses cultural and person-level factors contributing to emerging adult's use of memory to serve adaptive functions. The focus is on three functions: self-continuity, social-bonding and directing-behaviour. Taiwanese (N = 85, 52 women) and American (N = 95, 51 women) emerging adults completed the Thinking about Life Experiences scale, and measures of trait personality, self-concept clarity and future time perspective. Findings show that individuals from both cultures use memory to serve these three functions, but Taiwanese individuals use memory more frequently than Americans to maintain self-continuity. Culture also interacted with person-level factors: in Taiwan, but not America, memory is more frequently used to create self-continuity in individuals high in conscientiousness. Across cultures, having lower self-concept clarity was related to greater use of memory to create self-continuity. Findings are discussed in terms of how memory serves functions in context and specific aspects of the Taiwanese and American cultural context that may predict the functional use of memory in emerging adulthood.

Caring, Conversing, and Realizing Values: New Directions in Language Studies

ERIC Educational Resources Information Center

Hodges, Bert H.; Steffensen, Sune V.; Martin, James E.

2012-01-01

Language serves many functions for humans, but three of the most important are coordination, learning, and friendship. All of those functions were well served by the conversations from which this special issue emerged, a conference, "Grounding language in perception and (inter) action", held at Gordon College in June 2009. The conference brought…

Can you sequence ecology? Metagenomics of adaptive diversification.

PubMed

Marx, Christopher J

2013-01-01

Few areas of science have benefited more from the expansion in sequencing capability than the study of microbial communities. Can sequence data, besides providing hypotheses of the functions the members possess, detect the evolutionary and ecological processes that are occurring? For example, can we determine if a species is adapting to one niche, or if it is diversifying into multiple specialists that inhabit distinct niches? Fortunately, adaptation of populations in the laboratory can serve as a model to test our ability to make such inferences about evolution and ecology from sequencing. Even adaptation to a single niche can give rise to complex temporal dynamics due to the transient presence of multiple competing lineages. If there are multiple niches, this complexity is augmented by segmentation of the population into multiple specialists that can each continue to evolve within their own niche. For a known example of parallel diversification that occurred in the laboratory, sequencing data gave surprisingly few obvious, unambiguous signs of the ecological complexity present. Whereas experimental systems are open to direct experimentation to test hypotheses of selection or ecological interaction, the difficulty in "seeing ecology" from sequencing for even such a simple system suggests translation to communities like the human microbiome will be quite challenging. This will require both improved empirical methods to enhance the depth and time resolution for the relevant polymorphisms and novel statistical approaches to rigorously examine time-series data for signs of various evolutionary and ecological phenomena within and between species.

Functional diversification of sea urchin ABCC1 (MRP1) by alternative splicing.

PubMed

Gökirmak, Tufan; Campanale, Joseph P; Reitzel, Adam M; Shipp, Lauren E; Moy, Gary W; Hamdoun, Amro

2016-06-01

The multidrug resistance protein (MRP) family encodes a diverse repertoire of ATP-binding cassette (ABC) transporters with multiple roles in development, disease, and homeostasis. Understanding MRP evolution is central to unraveling their roles in these diverse processes. Sea urchins occupy an important phylogenetic position for understanding the evolution of vertebrate proteins and have been an important invertebrate model system for study of ABC transporters. We used phylogenetic analyses to examine the evolution of MRP transporters and functional approaches to identify functional forms of sea urchin MRP1 (also known as SpABCC1). SpABCC1, the only MRP homolog in sea urchins, is co-orthologous to human MRP1, MRP3, and MRP6 (ABCC1, ABCC3, and ABCC6) transporters. However, efflux assays revealed that alternative splicing of exon 22, a region critical for substrate interactions, could diversify functions of sea urchin MRP1. Phylogenetic comparisons also indicate that while MRP1, MRP3, and MRP6 transporters potentially arose from a single transporter in basal deuterostomes, alternative splicing appears to have been the major mode of functional diversification in invertebrates, while duplication may have served a more important role in vertebrates. These results provide a deeper understanding of the evolutionary origins of MRP transporters and the potential mechanisms used to diversify their functions in different groups of animals. Copyright © 2016 the American Physiological Society.

Functional diversification of sea urchin ABCC1 (MRP1) by alternative splicing

PubMed Central

Gökirmak, Tufan; Campanale, Joseph P.; Reitzel, Adam M.; Shipp, Lauren E.; Moy, Gary W.

2016-01-01

The multidrug resistance protein (MRP) family encodes a diverse repertoire of ATP-binding cassette (ABC) transporters with multiple roles in development, disease, and homeostasis. Understanding MRP evolution is central to unraveling their roles in these diverse processes. Sea urchins occupy an important phylogenetic position for understanding the evolution of vertebrate proteins and have been an important invertebrate model system for study of ABC transporters. We used phylogenetic analyses to examine the evolution of MRP transporters and functional approaches to identify functional forms of sea urchin MRP1 (also known as SpABCC1). SpABCC1, the only MRP homolog in sea urchins, is co-orthologous to human MRP1, MRP3, and MRP6 (ABCC1, ABCC3, and ABCC6) transporters. However, efflux assays revealed that alternative splicing of exon 22, a region critical for substrate interactions, could diversify functions of sea urchin MRP1. Phylogenetic comparisons also indicate that while MRP1, MRP3, and MRP6 transporters potentially arose from a single transporter in basal deuterostomes, alternative splicing appears to have been the major mode of functional diversification in invertebrates, while duplication may have served a more important role in vertebrates. These results provide a deeper understanding of the evolutionary origins of MRP transporters and the potential mechanisms used to diversify their functions in different groups of animals. PMID:27053522

The Hierarchical Brain Network for Face Recognition

PubMed Central

Zhen, Zonglei; Fang, Huizhen; Liu, Jia

2013-01-01

Numerous functional magnetic resonance imaging (fMRI) studies have identified multiple cortical regions that are involved in face processing in the human brain. However, few studies have characterized the face-processing network as a functioning whole. In this study, we used fMRI to identify face-selective regions in the entire brain and then explore the hierarchical structure of the face-processing network by analyzing functional connectivity among these regions. We identified twenty-five regions mainly in the occipital, temporal and frontal cortex that showed a reliable response selective to faces (versus objects) across participants and across scan sessions. Furthermore, these regions were clustered into three relatively independent sub-networks in a face-recognition task on the basis of the strength of functional connectivity among them. The functionality of the sub-networks likely corresponds to the recognition of individual identity, retrieval of semantic knowledge and representation of emotional information. Interestingly, when the task was switched to object recognition from face recognition, the functional connectivity between the inferior occipital gyrus and the rest of the face-selective regions were significantly reduced, suggesting that this region may serve as an entry node in the face-processing network. In sum, our study provides empirical evidence for cognitive and neural models of face recognition and helps elucidate the neural mechanisms underlying face recognition at the network level. PMID:23527282

The Relationship Between Age of Gambling Onset and Adolescent Problematic Gambling Severity

PubMed Central

Rahman, Ardeshir S.; Pilver, Corey E.; Desai, Rani A.; Steinberg, Marvin A.; Rugle, Loreen; Krishnan-Sarin, Suchitra; Potenza, Marc N.

2012-01-01

The aim of this study was to characterize the association between problem gambling severity and multiple health, functioning and gambling variables in adolescents aged 13–18 stratified by age of gambling onset. Survey data in 1624 Connecticut high school students stratified by age of gambling onset (≤11 years vs. ≥ 12 years) were analyzed in descriptive analyses and in logistic regression models. Earlier age of onset was associated with problem gambling severity as indexed by a higher frequency of at-risk/problem gambling (ARPG). Most health, functioning and gambling measures were similarly associated with problem gambling severity in the earlier- and later-age-of-gambling-onset groups with the exception of participation in non-strategic forms of gambling, which was more strongly associated with ARPG in the earlier-onset (OR=1.74, 95%CI=[1.26, 2.39]) as compared to later-onset (OR=0.94, 95%CI=[0.60, 1.48]) group (Interaction OR=1.91, 95%CI=[1.18, 3.26]). Post-hoc analysis revealed that earlier-onset ARPG was more strongly associated with multiple forms of non-strategic gambling including lottery (instant, traditional) and slot-machine gambling. The finding that problem gambling severity is more closely associated with multiple non-strategic forms of gambling amongst youth with earlier onset of gambling highlights the relevance of these types of youth gambling. The extent to which non-strategic forms of gambling may serve as a gateway to other forms of gambling or risk behaviors warrants additional study, and efforts targeting youth gambling should consider how best to address non-strategic gambling through education, prevention, treatment and policy efforts. PMID:22410208

Functional Multiple-Set Canonical Correlation Analysis

ERIC Educational Resources Information Center

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

2012-01-01

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

Light metal decorated graphdiyne nanosheets for reversible hydrogen storage.

PubMed

Panigrahi, P; Dhinakaran, A K; Naqvi, S R; Gollu, S R; Ahuja, R; Hussain, T

2018-05-29

The sensitive nature of molecular hydrogen (H 2 ) interaction with the surfaces of pristine and functionalized nanostructures, especially two-dimensional materials, has been a subject of debate for a while now. An accurate approximation of the H 2 adsorption mechanism has vital significance for fields such as H 2 storage applications. Owing to the importance of this issue, we have performed a comprehensive density functional theory (DFT) study by means of several different approximations to investigate the structural, electronic, charge transfer and energy storage properties of pristine and functionalized graphdiyne (GDY) nanosheets. The dopants considered here include the light metals Li, Na, K, Ca, Sc and Ti, which have a uniform distribution over GDY even at high doping concentration due to their strong binding and charge transfer mechanism. Upon 11% of metal functionalization, GDY changes into a metallic state from being a small band-gap semiconductor. Such situations turn the dopants to a partial positive state, which is favorable for adsorption of H 2 molecules. The adsorption mechanism of H 2 on GDY has been studied and compared by different methods like generalized gradient approximation, van der Waals density functional and DFT-D3 functionals. It has been established that each functionalized system anchors multiple H 2 molecules with adsorption energies that fall into a suitable range regardless of the functional used for approximations. A significantly high H 2 storage capacity would guarantee that light metal-doped GDY nanosheets could serve as efficient and reversible H 2 storage materials.

Multiple-User, Multitasking, Virtual-Memory Computer System

NASA Technical Reports Server (NTRS)

Generazio, Edward R.; Roth, Don J.; Stang, David B.

1993-01-01

Computer system designed and programmed to serve multiple users in research laboratory. Provides for computer control and monitoring of laboratory instruments, acquisition and anlaysis of data from those instruments, and interaction with users via remote terminals. System provides fast access to shared central processing units and associated large (from megabytes to gigabytes) memories. Underlying concept of system also applicable to monitoring and control of industrial processes.

Students with Severe to Profound Mental Handicaps and Multiple Disabilities in Rural Schools: Can Their Needs Be Met?

ERIC Educational Resources Information Center

Cates, Dennis L.; Kinnison, Lloyd

The education of students with severe to profound mental handicaps (SPH) or multiple disabilities may be greatly limited in rural settings. A survey investigating this issue in a southwestern state was completed by 136 of 346 directors of special education, 67 of whom worked in rural special education cooperatives. These cooperatives served 393…

Research Priorities to Advance the Health and Health Care of Older Adults with Multiple Chronic Conditions.

PubMed

Tisminetzky, Mayra; Bayliss, Elizabeth A; Magaziner, Jay S; Allore, Heather G; Anzuoni, Kathryn; Boyd, Cynthia M; Gill, Thomas M; Go, Alan S; Greenspan, Susan L; Hanson, Leah R; Hornbrook, Mark C; Kitzman, Dalane W; Larson, Eric B; Naylor, Mary D; Shirley, Benjamin E; Tai-Seale, Ming; Teri, Linda; Tinetti, Mary E; Whitson, Heather E; Gurwitz, Jerry H

2017-07-01

To prioritize research topics relevant to the care of the growing population of older adults with multiple chronic conditions (MCCs). Survey of experts in MCC practice, research, and policy. Topics were derived from white papers, funding announcements, or funded research projects relating to older adults with MCCs. Survey conducted through the Health Care Systems Research Network (HCSRN) and Claude D. Pepper Older Americans Independence Centers (OAICs) Advancing Geriatrics Infrastructure and Network Growth Initiative, a joint endeavor of the HCSRN and OAICs. Individuals affiliated with the HCSRN or OAICs and national MCC experts, including individuals affiliated with funding agencies having MCC-related grant portfolios. A "top box" methodology was used, counting the number of respondents selecting the top response on a 5-point Likert scale and dividing by the total number of responses to calculate a top box percentage for each of 37 topics. The highest-ranked research topics relevant to the health and healthcare of older adults with MCCs were health-related quality of life in older adults with MCCs; development of assessment tools (to assess, e.g., symptom burden, quality of life, function); interactions between medications, disease processes, and health outcomes; disability; implementation of novel (and scalable) models of care; association between clusters of chronic conditions and clinical, financial, and social outcomes; role of caregivers; symptom burden; shared decision-making to enhance care planning; and tools to improve clinical decision-making. Study findings serve to inform the development of a comprehensive research agenda to address the challenges relating to the care of this "high-need, high-cost" population and the healthcare delivery systems responsible for serving it. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

Suicide in the Guard and Reserve: Variables in Mental Health Access and Support

DTIC Science & Technology

2016-06-01

I’ve served for almost ten years in the Air National Guard. My career has consisted of serving in two states, both as a traditional Guardsman working...balancing two careers . Not to mention in recent years, the National Guard and Reserve forces have often faced multiple deployments, which can easily...take a toll on family stability and civilian careers . In response to these predicted stressors, the DoD implemented numerous programs in recent

Structure and Function of Wood

Treesearch

Alex C. Wiedenhoeft

2012-01-01

Wood is a complex biological structure, a composite of many cell types and chemistries acting together to serve the needs of living plant. Attempting to understand wood inthe context of wood technology, we have often overlooked the basic fact that wood evolved over the course of millions of years to serve three main functions in plants-conduction of water from the...

Why Do the Children (Pretend) Play?

PubMed

Lillard, Angeline S

2017-11-01

Pretend play appears to be an evolved behavior because it is universal and appears on a set schedule. However, no specific functions have been determined for pretend play and empirical tests for its functions in humans are elusive. Yet animal play fighting can serve as an analog, as both activities involve as-if, metacommunicative signaling and symbolism. In the rat and some other animals, adaptive functions of play fighting include assisting social behavior and emotion regulation. Research is presented suggesting that pretend play might serve similar functions for humans. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

Future body mass index modelling based on macronutrient profiles and physical activity

PubMed Central

2012-01-01

Background An accurate system of determining the relationship of macronutrient profiles of foods and beverages to the long-term weight impacts of foods is necessary for evidence-based, unbiased front-of-the-package food labels. Methods Data sets on diet, physical activity, and BMI came from the Food and Agriculture Organization (FAO), the World Health Organization (WHO), the Diabetes Control and Complications Trial (DCCT), and Epidemiology Diabetes Intervention and Complications (EDIC). To predict future BMI of individuals, multiple regression derived FAO/WHO and DCCT/EDIC formulas related macronutrient profiles and physical activity (independent variables) to BMI change/year (dependent variable). Similar formulas without physical activity related macronutrient profiles of individual foods and beverages to four-year weight impacts of those items and compared those forecasts to published food group profiling estimates from three large prospective studies by Harvard nutritional epidemiologists. Results FAO/WHO food and beverage formula: four-year weight impact (pounds)=(0.07710 alcohol g+11.95 (381.7+carbohydrates g per serving)*4/(2,613+kilocalories per serving)–304.9 (30.38+dietary fiber g per serving)/(2,613+kilocalories per serving)+19.73 (84.44+total fat g)*9/(2,613+kilocalories per serving)–68.57 (20.45+PUFA g per serving)*9/(2,613+kilocalories per serving))*2.941–12.78 (n=334, R2=0.29, P < 0.0001). DCCT/EDIC formula for four-year weight impact (pounds)=(0.898 (102.2+protein g per serving)*4/(2,297+kilocalories per serving)+1.063 (264.2+carbohydrates g per serving)*4/(2,297+ kilocalories per serving)–13.19 (24.29+dietary fiber g per serving)/ (2,297+kilocalories per serving)+ 0.973 (74.59+(total fat g per serving–PUFA g per serving)*9/(2,297+kilocalories per serving))*85.82–68.11 (n=1,055, R2=0.03, P < 0.0001). (FAO/WHO+ DCCT/EDIC formula forecasts averaged correlated strongly with published food group profiling findings except for potatoes and dairy foods (n=12, r=0.85, P = 0.0004). Formula predictions did not correlate with food group profiling findings for potatoes and dairy products (n=10, r= −0.33 P=0.36). A formula based diet and exercise analysis tool is available to researchers and individuals: http://thehealtheconomy.com/healthTool/. Conclusions Two multiple regression derived formulas from dissimilar databases produced markedly similar estimates of future BMI for 1,055 individuals with type 1 diabetes and female and male cohorts from 167 countries. These formulas predicted the long-term weight impacts of foods and beverages, closely corresponding with most food group profiling estimates from three other databases. If discrepancies with potatoes and dairy products can be resolved, these formulas present a potential basis for a front-of-the-package weight impact rating system. PMID:23106911

Beliefs about Volunteerism, Volunteering Intention, Volunteering Behavior, and Purpose in Life among Chinese Adolescents in Hong Kong

PubMed Central

Law, Ben M. F.; Shek, Daniel T. L.

2009-01-01

The relationships among beliefs about volunteerism, volunteering intention, volunteering behavior, and purpose in life were examined in this study. A total of 5,946 participants completed a series of scales, including the Revised Personal Functions of Volunteerism Scale, Volunteering Intention Scale, and Purpose in Life Scale. The results showed that participants whose purpose in life had different levels also had varied prosocial beliefs about volunteerism, volunteering intention, and volunteering behavior. Purpose in life was associated more strongly with prosocial value function than with other types of beliefs (except understanding function). When different beliefs are grouped, the correlation between purpose in life and other-serving beliefs was higher than that between purpose in life and self-serving beliefs. Purpose in life was also associated with volunteering intention and behavior. Path analyses showed that purpose in life predicted volunteering behavior via beliefs and intention. While other-serving beliefs predicted volunteering behavior directly, self-serving beliefs did not have such direct effect. PMID:19734959

Beliefs about volunteerism, volunteering intention, volunteering behavior, and purpose in life among Chinese adolescents in Hong Kong.

PubMed

Law, Ben M F; Shek, Daniel T L

2009-09-01

The relationships among beliefs about volunteerism, volunteering intention, volunteering behavior, and purpose in life were examined in this study. A total of 5,946 participants completed a series of scales, including the Revised Personal Functions of Volunteerism Scale, Volunteering Intention Scale, and Purpose in Life Scale. The results showed that participants whose purpose in life had different levels also had varied prosocial beliefs about volunteerism, volunteering intention, and volunteering behavior. Purpose in life was associated more strongly with prosocial value function than with other types of beliefs (except understanding function). When different beliefs are grouped, the correlation between purpose in life and other-serving beliefs was higher than that between purpose in life and self-serving beliefs. Purpose in life was also associated with volunteering intention and behavior. Path analyses showed that purpose in life predicted volunteering behavior via beliefs and intention. While other-serving beliefs predicted volunteering behavior directly, self-serving beliefs did not have such direct effect.

Numerical method for accessing the universal scaling function for a multiparticle discrete time asymmetric exclusion process

NASA Astrophysics Data System (ADS)

Chia, Nicholas; Bundschuh, Ralf

2005-11-01

In the universality class of the one-dimensional Kardar-Parisi-Zhang (KPZ) surface growth, Derrida and Lebowitz conjectured the universality of not only the scaling exponents, but of an entire scaling function. Since and Derrida and Lebowitz’s original publication [Phys. Rev. Lett. 80, 209 (1998)] this universality has been verified for a variety of continuous-time, periodic-boundary systems in the KPZ universality class. Here, we present a numerical method for directly examining the entire particle flux of the asymmetric exclusion process (ASEP), thus providing an alternative to more difficult cumulant ratios studies. Using this method, we find that the Derrida-Lebowitz scaling function (DLSF) properly characterizes the large-system-size limit (N→∞) of a single-particle discrete time system, even in the case of very small system sizes (N⩽22) . This fact allows us to not only verify that the DLSF properly characterizes multiple-particle discrete-time asymmetric exclusion processes, but also provides a way to numerically solve for quantities of interest, such as the particle hopping flux. This method can thus serve to further increase the ease and accessibility of studies involving even more challenging dynamics, such as the open-boundary ASEP.

Pharmacological Effects of Biotin in Animals.

PubMed

Riveron-Negrete, Leticia; Fernandez-Mejia, Cristina

2017-01-01

In recent decades, it was found that vitamins affect biological functions in ways other than their long-known functions; niacin is the best example of a water-soluble vitamin known to possess multiple actions. Biotin, also known as vitamin B7 or vitamin H, is a water-soluble B-complex vitamin that serves as a covalently-bound coenzyme of carboxylases. It is now well documented that biotin has actions other than participating in classical enzyme catalysis reactions. Several lines of evidence have demonstrated that pharmacological concentrations of biotin affect glucose and lipid metabolism, hypertension, reproduction, development, and immunity. The effect of biotin on these functions is related to its actions at the transcriptional, translational, and post-translational levels. The bestsupported mechanism involved in the genetic effects of biotin is the soluble guanylate cyclase/protein kinase G (PKG) signaling cascade. Although there are commercially-available products containing pharmacological concentrations of biotin, the toxic effects of biotin have been poorly studied. This review summarizes the known actions and molecular mechanisms of pharmacological doses of biotin in animals and current information regarding biotin toxicity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

[Autism, epilepsy and tuberous sclerosis complex: a functional model linked to mTOR pathway].

PubMed

García-Peñas, Juan José; Carreras-Sááez, Inmaculada

2013-02-22

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder that results from mutations in the TSC1 or TSC2 genes and is associated with hamartoma formation in multiple organ systems. Brain disorders are the origin of more frequent and severe problems and include infantile spasms, intractable epilepsy, brain tumors, cognitive disabilities, and autism. TSC1 or TSC2 encoded proteins modulate cell function via the mTOR signaling cascade and serve as keystones in regulating cell growth and proliferation. AIM. To review the etiopathogenic mechanisms and the natural course of the association of autism and epilepsy in TSC. Both the clinical and the neuroimaging findings of TSC, including early onset epilepsy and the localization of cortical tubers in the temporal lobes, and the molecular understanding of the mTOR signaling pathway, not only involved in cell growth, but also in synaptogenesis, synaptic plasticity and neuronal functioning, have suggested a multimodal origin of autism in these patients. A greater understanding of the pathogenetic mechanisms underlying autism in TSC could help in devising targeted and potentially more effective treatment strategies. Antagonism of the mTOR pathway with rapamycin and everolimus may provide new therapeutic options for these TSC patients.

Type IV Collagens and Basement Membrane Diseases: Cell Biology and Pathogenic Mechanisms.

PubMed

Mao, Mao; Alavi, Marcel V; Labelle-Dumais, Cassandre; Gould, Douglas B

2015-01-01

Basement membranes are highly specialized extracellular matrices. Once considered inert scaffolds, basement membranes are now viewed as dynamic and versatile environments that modulate cellular behaviors to regulate tissue development, function, and repair. Increasing evidence suggests that, in addition to providing structural support to neighboring cells, basement membranes serve as reservoirs of growth factors that direct and fine-tune cellular functions. Type IV collagens are a major component of all basement membranes. They evolved along with the earliest multicellular organisms and have been integrated into diverse fundamental biological processes as time and evolution shaped the animal kingdom. The roles of basement membranes in humans are as complex and diverse as their distributions and molecular composition. As a result, basement membrane defects result in multisystem disorders with ambiguous and overlapping boundaries that likely reflect the simultaneous interplay and integration of multiple cellular pathways and processes. Consequently, there will be no single treatment for basement membrane disorders, and therapies are likely to be as varied as the phenotypes. Understanding tissue-specific pathology and the underlying molecular mechanism is the present challenge; personalized medicine will rely upon understanding how a given mutation impacts diverse cellular functions. Copyright © 2015 Elsevier Inc. All rights reserved.

The stress polarity pathway: AMPK ‘GIV’-es protection against metabolic insults

PubMed Central

Ghosh, Pradipta

2017-01-01

Loss of cell polarity impairs organ development and function; it can also serve as one of the first triggers for oncogenesis. In 2006-2007 two groups simultaneously reported the existence of a special pathway for maintaining epithelial polarity in the face of environmental stressors. In this pathway, AMPK, a key sensor of metabolic stress stabilizes tight junctions, preserves cell polarity, and thereby, maintains epithelial barrier functions. Accumulating evidence since has shown that pharmacologic activation of AMPK by Metformin protects the epithelial barrier against multiple environmental and pathological stressful states and suppresses tumorigenesis. How AMPK protects the epithelium remained unknown until recently Aznar et al. identified GIV/Girdin as a novel effector of AMPK at the cell-cell junctions; phosphorylation of GIV at a single site by AMPK appears to be both necessary and sufficient for strengthening tight junctions and preserving cell polarity and epithelial barrier function in the face of energetic stress. Here we review the fundamentals of this specialized signaling pathway that buttresses cell-cell junctions against stress-induced collapse and discuss its pathophysiologic relevance in the context of a variety of diseases, including cancers, diabetes, aging, and the growing list of beneficial effects of the AMPK-activator, Metformin. PMID:28209925

Multi-Faceted Functions of Secretory IgA at Mucosal Surfaces

PubMed Central

Corthésy, Blaise

2013-01-01

Secretory IgA (SIgA) plays an important role in the protection and homeostatic regulation of intestinal, respiratory, and urogenital mucosal epithelia separating the outside environment from the inside of the body. This primary function of SIgA is referred to as immune exclusion, a process that limits the access of numerous microorganisms and mucosal antigens to these thin and vulnerable mucosal barriers. SIgA has been shown to be involved in avoiding opportunistic pathogens to enter and disseminate in the systemic compartment, as well as tightly controlling the necessary symbiotic relationship existing between commensals and the host. Clearance by peristalsis appears thus as one of the numerous mechanisms whereby SIgA fulfills its function at mucosal surfaces. Sampling of antigen-SIgA complexes by microfold (M) cells, intimate contact occurring with Peyer’s patch dendritic cells (DC), down-regulation of inflammatory processes, modulation of epithelial, and DC responsiveness are some of the recently identified processes to which the contribution of SIgA has been underscored. This review aims at presenting, with emphasis at the biochemical level, how the molecular complexity of SIgA can serve these multiple and non-redundant modes of action. PMID:23874333

Correction of malocclusion and oral rehabilitation in a case of amelogenesis imperfecta by insertion of dental implants followed by Le Fort I distraction osteogenesis of the edentulous atrophic maxilla.

PubMed

Apaydin, Aysegul; Sermet, Bulent; Ureturk, Sevin; Kundakcioglu, Abdulsamet

2014-09-17

Amelogenesis imperfecta refers a group of hereditary diseases affecting the teeth and can present a variety of clinical forms and appearances, compromising esthetic appearance. Amelogenesis imperfecta variably reduces oral health quality and can result in severe psychological problems. We present the management of an amelogenesis imperfecta Angle class III malocclusion case with speech, esthetics and functional problems. This is an example of the rarely presented delayed eruption with multiple morphologic dental alterations and edentulous maxilla.There are only a few available reports in which this method is used method to correct sagittal discrepancies in edentulous patients.Our treatment plan consisted of a preoperative diagnostic and prosthodontics phase (including preparation of guiding prosthesis), followed by a surgical phase of Le Fort I osteotomy, distraction osteogenesis to correct the malocclusion, implant insertion and a follow up final restorative phase. Our treatment strategy attempts to serve patient needs, achieving function and esthetics while also minimizing the risk of reconstruction failure. Treatment not only restored function and esthetics, but also showed a positive psychological impact and thereby improved perceived quality of life.

New ergonomic and functional design of digital conferencing rooms in a clinical environment

NASA Astrophysics Data System (ADS)

Ratib, Osman M.; Amato, Carlos L.; McGill, D. Ric; Liu, Brent J.; Balbona, Joseph A.; McCoy, J. Michael

2003-05-01

Clinical conferences and multidisciplinary medical rounds play a major role in patient management and decision-making relying on presentation of variety of documents: films, charts, videotapes, graphs etc. These conferences and clinical rounds are often carried out in conferencing rooms or department libraries that are usually not suitable for presentation of the data in electronic format. In most instances digital projection equipment is added to existing rooms without proper consideration to functional, ergonomic, acoustical, spatial and environmental requirements. Also, in large academic institutions, the conference rooms serve multiple purposes including as classrooms for teaching and education of students and for administrative meetings among managers and staff. In the migration toward a fully digital hospital we elected to analyze the functional requirements and optimize the ergonomic design of conferencing rooms that can accommodate clinical rounds, multidisciplinary reviews, seminars, formal lectures and department meetings. 3D computer simulation was used for better evaluation and analysis of spatial and ergonomic parameters and for gathering opinions and input from users on different design options. A critical component of the design is the understanding of the different workflow and requirements of different types of conferences and presentations that can be carried out in these conference rooms.

An exploration of adolescent nonsuicidal self-injury and religious coping.

PubMed

Westers, Nicholas J; Rehfuss, Mark; Olson, Lynn; Wiemann, Constance M

2014-01-01

Many adolescents who engage in nonsuicidal self-injury (NSSI) self-identify as religious, but the role of religion in their NSSI is not known. This exploratory study examined the relationship between religious coping and religiousness among adolescents who self-injure and the function of their NSSI. Thirty adolescents aged 12-19 years who had engaged in NSSI participated in an interview and completed questionnaires. Multiple regressions were used to examine the relationship between religious coping and NSSI, and Pearson correlations were used to assess the relationship between religiousness and function of NSSI. Greater use of positive religious coping was associated with lower likelihood of engaging in NSSI to rid oneself of unwanted emotions, whereas greater use of negative religious coping was associated with greater likelihood of engaging in NSSI for this reason as well as to avoid punishment or unwanted responsibility. Higher religiousness was associated with greater use of NSSI to communicate with or gain attention from others, whereas lower religiousness was associated with greater use of NSSI to relieve unwanted emotions. Having a greater understanding of how religious constructs are related to the various functions served by NSSI may inform treatment of this population, particularly among religious youth who self-injure.

A subset of neurons controls the permeability of the peritrophic matrix and midgut structure in Drosophila adults.

PubMed

Kenmoku, Hiroyuki; Ishikawa, Hiroki; Ote, Manabu; Kuraishi, Takayuki; Kurata, Shoichiro

2016-08-01

The metazoan gut performs multiple physiological functions, including digestion and absorption of nutrients, and also serves as a physical and chemical barrier against ingested pathogens and abrasive particles. Maintenance of these functions and structures is partly controlled by the nervous system, yet the precise roles and mechanisms of the neural control of gut integrity remain to be clarified in Drosophila Here, we screened for GAL4 enhancer-trap strains and labeled a specific subsets of neurons, using Kir2.1 to inhibit their activity. We identified an NP3253 line that is susceptible to oral infection by Gram-negative bacteria. The subset of neurons driven by the NP3253 line includes some of the enteric neurons innervating the anterior midgut, and these flies have a disorganized proventricular structure with high permeability of the peritrophic matrix and epithelial barrier. The findings of the present study indicate that neural control is crucial for maintaining the barrier function of the gut, and provide a route for genetic dissection of the complex brain-gut axis in adults of the model organism Drosophila. © 2016. Published by The Company of Biologists Ltd.

Regulation of cerebrospinal fluid (CSF) flow in neurodegenerative, neurovascular and neuroinflammatory disease.

PubMed

Simon, Matthew J; Iliff, Jeffrey J

2016-03-01

Cerebrospinal fluid (CSF) circulation and turnover provides a sink for the elimination of solutes from the brain interstitium, serving an important homeostatic role for the function of the central nervous system. Disruption of normal CSF circulation and turnover is believed to contribute to the development of many diseases, including neurodegenerative conditions such as Alzheimer's disease, ischemic and traumatic brain injury, and neuroinflammatory conditions such as multiple sclerosis. Recent insights into CSF biology suggesting that CSF and interstitial fluid exchange along a brain-wide network of perivascular spaces termed the 'glymphatic' system suggest that CSF circulation may interact intimately with glial and vascular function to regulate basic aspects of brain function. Dysfunction within this glial vascular network, which is a feature of the aging and injured brain, is a potentially critical link between brain injury, neuroinflammation and the development of chronic neurodegeneration. Ongoing research within this field may provide a powerful new framework for understanding the common links between neurodegenerative, neurovascular and neuroinflammatory disease, in addition to providing potentially novel therapeutic targets for these conditions. This article is part of a Special Issue entitled: Neuro Inflammation edited by Helga E. de Vries and Markus Schwaninger. Copyright © 2015 Elsevier B.V. All rights reserved.

Interaction with the Src homology (SH3-SH2) region of the Src-family kinase Hck structures the HIV-1 Nef dimer for kinase activation and effector recruitment.

PubMed

Alvarado, John Jeff; Tarafdar, Sreya; Yeh, Joanne I; Smithgall, Thomas E

2014-10-10

HIV-1 Nef supports high titer viral replication in vivo and is essential for AIDS progression. Nef function depends on interactions with multiple host cell effectors, including Hck and other Src-family kinases. Here we describe the x-ray crystal structure of Nef in complex with the Hck SH3-SH2 regulatory region to a resolution of 1.86 Å. The complex crystallized as a dimer of complexes, with the conserved Nef PXXPXR motif engaging the Hck SH3 domain. A new intercomplex contact was found between SH3 Glu-93, and Nef Arg-105. Mutagenesis of Hck SH3 Glu-93 interfered with Nef·Hck complex formation and kinase activation in cells. The Hck SH2 domains impinge on the N-terminal region of Nef to stabilize a dimer conformation that exposes Asp-123, a residue critical for Nef function. Our results suggest that in addition to serving as a kinase effector for Nef, Hck binding may reorganize the Nef dimer for functional interaction with other signaling partners. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Interaction with the Src Homology (SH3-SH2) Region of the Src-family Kinase Hck Structures the HIV-1 Nef Dimer for Kinase Activation and Effector Recruitment*

PubMed Central

Alvarado, John Jeff; Tarafdar, Sreya; Yeh, Joanne I.; Smithgall, Thomas E.

2014-01-01

HIV-1 Nef supports high titer viral replication in vivo and is essential for AIDS progression. Nef function depends on interactions with multiple host cell effectors, including Hck and other Src-family kinases. Here we describe the x-ray crystal structure of Nef in complex with the Hck SH3-SH2 regulatory region to a resolution of 1.86 Å. The complex crystallized as a dimer of complexes, with the conserved Nef PXXPXR motif engaging the Hck SH3 domain. A new intercomplex contact was found between SH3 Glu-93, and Nef Arg-105. Mutagenesis of Hck SH3 Glu-93 interfered with Nef·Hck complex formation and kinase activation in cells. The Hck SH2 domains impinge on the N-terminal region of Nef to stabilize a dimer conformation that exposes Asp-123, a residue critical for Nef function. Our results suggest that in addition to serving as a kinase effector for Nef, Hck binding may reorganize the Nef dimer for functional interaction with other signaling partners. PMID:25122770

Challenges and opportunities for stem cell therapy in patients with chronic kidney disease

PubMed Central

Hickson, LaTonya J.; Eirin, Alfonso; Lerman, Lilach O.

2016-01-01

Chronic kidney disease (CKD) is a global healthcare burden affecting billions of individuals worldwide. The kidney has limited regenerative capacity from chronic insults, and for the most common causes of CKD, no effective treatment exists to prevent progression to end-stage kidney failure. Therefore, novel interventions, such as regenerative cell-based therapies, need to be developed for CKD. Given the risk of allosensitization, autologous transplantation of cells to boost regenerative potential is preferred. Therefore, verification of cell function and vitality in CKD patients is imperative. Two cell types have been most commonly applied in regenerative medicine. Endothelial progenitor cells contribute to neovasculogenesis primarily through paracrine angiogenic activity and partly by differentiation into mature endothelial cells in situ. Mesenchymal stem cells also exert paracrine effects, including pro-angiogenic, anti-inflammatory, and anti-fibrotic activity. However, in CKD, multiple factors may contribute to reduced cell function, including older age, coexisting cardiovascular disease, diabetes, chronic inflammatory states, and uremia, which may limit the effectiveness of an autologous cell-based therapy approach. This review highlights current knowledge on stem and progenitor cell function and vitality, aspects of the uremic milieu that may serve as a barrier to therapy, and novel methods to improve stem cell function for potential transplantation. PMID:26924058

Structural Diversity in the Dandelion (Taraxacum officinale) Polyphenol Oxidase Family Results in Different Responses to Model Substrates

PubMed Central

Dirks-Hofmeister, Mareike E.; Singh, Ratna; Leufken, Christine M.; Inlow, Jennifer K.; Moerschbacher, Bruno M.

2014-01-01

Polyphenol oxidases (PPOs) are ubiquitous type-3 copper enzymes that catalyze the oxygen-dependent conversion of o-diphenols to the corresponding quinones. In most plants, PPOs are present as multiple isoenzymes that probably serve distinct functions, although the precise relationship between sequence, structure and function has not been addressed in detail. We therefore compared the characteristics and activities of recombinant dandelion PPOs to gain insight into the structure–function relationships within the plant PPO family. Phylogenetic analysis resolved the 11 isoenzymes of dandelion into two evolutionary groups. More detailed in silico and in vitro analyses of four representative PPOs covering both phylogenetic groups were performed. Molecular modeling and docking predicted differences in enzyme-substrate interactions, providing a structure-based explanation for grouping. One amino acid side chain positioned at the entrance to the active site (position HB2+1) potentially acts as a “selector” for substrate binding. In vitro activity measurements with the recombinant, purified enzymes also revealed group-specific differences in kinetic parameters when the selected PPOs were presented with five model substrates. The combination of our enzyme kinetic measurements and the in silico docking studies therefore indicate that the physiological functions of individual PPOs might be defined by their specific interactions with different natural substrates. PMID:24918587

Challenges and opportunities for stem cell therapy in patients with chronic kidney disease.

PubMed

Hickson, LaTonya J; Eirin, Alfonso; Lerman, Lilach O

2016-04-01

Chronic kidney disease (CKD) is a global health care burden affecting billions of individuals worldwide. The kidney has limited regenerative capacity from chronic insults, and for the most common causes of CKD, no effective treatment exists to prevent progression to end-stage kidney failure. Therefore, novel interventions, such as regenerative cell-based therapies, need to be developed for CKD. Given the risk of allosensitization, autologous transplantation of cells to boost regenerative potential is preferred. Therefore, verification of cell function and vitality in CKD patients is imperative. Two cell types have been most commonly applied in regenerative medicine. Endothelial progenitor cells contribute to neovasculogenesis primarily through paracrine angiogenic activity and partly by differentiation into mature endothelial cells in situ. Mesenchymal stem cells also exert paracrine effects, including proangiogenic, anti-inflammatory, and antifibrotic activity. However, in CKD, multiple factors may contribute to reduced cell function, including older age, coexisting cardiovascular disease, diabetes, chronic inflammatory states, and uremia, which may limit the effectiveness of an autologous cell-based therapy approach. This Review highlights current knowledge on stem and progenitor cell function and vitality, aspects of the uremic milieu that may serve as a barrier to therapy, and novel methods to improve stem cell function for potential transplantation. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Rac-mediated Stimulation of Phospholipase Cγ2 Amplifies B Cell Receptor-induced Calcium Signaling*♦

PubMed Central

Walliser, Claudia; Tron, Kyrylo; Clauss, Karen; Gutman, Orit; Kobitski, Andrei Yu.; Retlich, Michael; Schade, Anja; Röcker, Carlheinz; Henis, Yoav I.; Nienhaus, G. Ulrich; Gierschik, Peter

2015-01-01

The Rho GTPase Rac is crucially involved in controlling multiple B cell functions, including those regulated by the B cell receptor (BCR) through increased cytosolic Ca2+. The underlying molecular mechanisms and their relevance to the functions of intact B cells have thus far remained unknown. We have previously shown that the activity of phospholipase Cγ2 (PLCγ2), a key constituent of the BCR signalosome, is stimulated by activated Rac through direct protein-protein interaction. Here, we use a Rac-resistant mutant of PLCγ2 to functionally reconstitute cultured PLCγ2-deficient DT40 B cells and to examine the effects of the Rac-PLCγ2 interaction on BCR-mediated changes of intracellular Ca2+ and regulation of Ca2+-regulated and nuclear-factor-of-activated-T-cell-regulated gene transcription at the level of single, intact B cells. The results show that the functional Rac-PLCγ2 interaction causes marked increases in the following: (i) sensitivity of B cells to BCR ligation; (ii) BCR-mediated Ca2+ release from intracellular stores; (iii) Ca2+ entry from the extracellular compartment; and (iv) nuclear translocation of the Ca2+-regulated nuclear factor of activated T cells. Hence, Rac-mediated stimulation of PLCγ2 activity serves to amplify B cell receptor-induced Ca2+ signaling. PMID:25903139

Evoked itch perception is associated with changes in functional brain connectivity.

PubMed

Desbordes, Gaëlle; Li, Ang; Loggia, Marco L; Kim, Jieun; Schalock, Peter C; Lerner, Ethan; Tran, Thanh N; Ring, Johannes; Rosen, Bruce R; Kaptchuk, Ted J; Pfab, Florian; Napadow, Vitaly

2015-01-01

Chronic itch, a highly debilitating condition, has received relatively little attention in the neuroimaging literature. Recent studies suggest that brain regions supporting itch in chronic itch patients encompass sensorimotor and salience networks, and corticostriatal circuits involved in motor preparation for scratching. However, how these different brain areas interact with one another in the context of itch is still unknown. We acquired BOLD fMRI scans in 14 atopic dermatitis patients to investigate resting-state functional connectivity before and after allergen-induced itch exacerbated the clinical itch perception in these patients. A seed-based analysis revealed decreased functional connectivity from baseline resting state to the evoked-itch state between several itch-related brain regions, particularly the insular and cingulate cortices and basal ganglia, where decreased connectivity was significantly correlated with increased levels of perceived itch. In contrast, evoked itch increased connectivity between key nodes of the frontoparietal control network (superior parietal lobule and dorsolateral prefrontal cortex), where higher increase in connectivity was correlated with a lesser increase in perceived itch, suggesting that greater interaction between nodes of this executive attention network serves to limit itch sensation via enhanced top-down regulation. Overall, our results provide the first evidence of itch-dependent changes in functional connectivity across multiple brain regions.

Statistics of cosmic density profiles from perturbation theory

NASA Astrophysics Data System (ADS)

Bernardeau, Francis; Pichon, Christophe; Codis, Sandrine

2014-11-01

The joint probability distribution function (PDF) of the density within multiple concentric spherical cells is considered. It is shown how its cumulant generating function can be obtained at tree order in perturbation theory as the Legendre transform of a function directly built in terms of the initial moments. In the context of the upcoming generation of large-scale structure surveys, it is conjectured that this result correctly models such a function for finite values of the variance. Detailed consequences of this assumption are explored. In particular the corresponding one-cell density probability distribution at finite variance is computed for realistic power spectra, taking into account its scale variation. It is found to be in agreement with Λ -cold dark matter simulations at the few percent level for a wide range of density values and parameters. Related explicit analytic expansions at the low and high density tails are given. The conditional (at fixed density) and marginal probability of the slope—the density difference between adjacent cells—and its fluctuations is also computed from the two-cell joint PDF; it also compares very well to simulations. It is emphasized that this could prove useful when studying the statistical properties of voids as it can serve as a statistical indicator to test gravity models and/or probe key cosmological parameters.

Signal Transduction Pathways of TNAP: Molecular Network Analyses.

PubMed

Négyessy, László; Györffy, Balázs; Hanics, János; Bányai, Mihály; Fonta, Caroline; Bazsó, Fülöp

2015-01-01

Despite the growing body of evidence pointing on the involvement of tissue non-specific alkaline phosphatase (TNAP) in brain function and diseases like epilepsy and Alzheimer's disease, our understanding about the role of TNAP in the regulation of neurotransmission is severely limited. The aim of our study was to integrate the fragmented knowledge into a comprehensive view regarding neuronal functions of TNAP using objective tools. As a model we used the signal transduction molecular network of a pyramidal neuron after complementing with TNAP related data and performed the analysis using graph theoretic tools. The analyses show that TNAP is in the crossroad of numerous pathways and therefore is one of the key players of the neuronal signal transduction network. Through many of its connections, most notably with molecules of the purinergic system, TNAP serves as a controller by funnelling signal flow towards a subset of molecules. TNAP also appears as the source of signal to be spread via interactions with molecules involved among others in neurodegeneration. Cluster analyses identified TNAP as part of the second messenger signalling cascade. However, TNAP also forms connections with other functional groups involved in neuronal signal transduction. The results indicate the distinct ways of involvement of TNAP in multiple neuronal functions and diseases.

Lipid Droplets and Peroxisomes: Key Players in Cellular Lipid Homeostasis or A Matter of Fat—Store ’em Up or Burn ’em Down

PubMed Central

Kohlwein, Sepp D.; Veenhuis, Marten; van der Klei, Ida J.

2013-01-01

Lipid droplets (LDs) and peroxisomes are central players in cellular lipid homeostasis: some of their main functions are to control the metabolic flux and availability of fatty acids (LDs and peroxisomes) as well as of sterols (LDs). Both fatty acids and sterols serve multiple functions in the cell—as membrane stabilizers affecting membrane fluidity, as crucial structural elements of membrane-forming phospholipids and sphingolipids, as protein modifiers and signaling molecules, and last but not least, as a rich carbon and energy source. In addition, peroxisomes harbor enzymes of the malic acid shunt, which is indispensable to regenerate oxaloacetate for gluconeogenesis, thus allowing yeast cells to generate sugars from fatty acids or nonfermentable carbon sources. Therefore, failure of LD and peroxisome biogenesis and function are likely to lead to deregulated lipid fluxes and disrupted energy homeostasis with detrimental consequences for the cell. These pathological consequences of LD and peroxisome failure have indeed sparked great biomedical interest in understanding the biogenesis of these organelles, their functional roles in lipid homeostasis, interaction with cellular metabolism and other organelles, as well as their regulation, turnover, and inheritance. These questions are particularly burning in view of the pandemic development of lipid-associated disorders worldwide. PMID:23275493

Structural diversity in the dandelion (Taraxacum officinale) polyphenol oxidase family results in different responses to model substrates.

PubMed

Dirks-Hofmeister, Mareike E; Singh, Ratna; Leufken, Christine M; Inlow, Jennifer K; Moerschbacher, Bruno M

2014-01-01

Polyphenol oxidases (PPOs) are ubiquitous type-3 copper enzymes that catalyze the oxygen-dependent conversion of o-diphenols to the corresponding quinones. In most plants, PPOs are present as multiple isoenzymes that probably serve distinct functions, although the precise relationship between sequence, structure and function has not been addressed in detail. We therefore compared the characteristics and activities of recombinant dandelion PPOs to gain insight into the structure-function relationships within the plant PPO family. Phylogenetic analysis resolved the 11 isoenzymes of dandelion into two evolutionary groups. More detailed in silico and in vitro analyses of four representative PPOs covering both phylogenetic groups were performed. Molecular modeling and docking predicted differences in enzyme-substrate interactions, providing a structure-based explanation for grouping. One amino acid side chain positioned at the entrance to the active site (position HB2+1) potentially acts as a "selector" for substrate binding. In vitro activity measurements with the recombinant, purified enzymes also revealed group-specific differences in kinetic parameters when the selected PPOs were presented with five model substrates. The combination of our enzyme kinetic measurements and the in silico docking studies therefore indicate that the physiological functions of individual PPOs might be defined by their specific interactions with different natural substrates.

Surface immobilized azomethine for multiple component exchange.

PubMed

Lerond, Michael; Bélanger, Daniel; Skene, W G

2017-09-27

Diazonium chemistry concomitant with in situ electrochemical reduction was used to graft an aryl aldehyde to indium-tin oxide (ITO) coated glass substrates. This served as an anchor for preparing electroactive azomethines that were covalently bonded to the transparent electrode. The immobilized azomethines could undergo multiple step-wise component exchanges with different arylamines. The write-erase-write sequences were electrochemically confirmed. The azomethines could also be reversibly hydrolyzed. This was exploited for multiple azomethine-hydrolysis cycles resulting in discrete electroactive immobilized azomethines. The erase-rewrite sequences were also electrochemically confirmed.

The endothelial glycocalyx

PubMed Central

Yang, Yimu; Schmidt, Eric P.

2013-01-01

Once thought to be a structure of small size and uncertain significance, the endothelial glycocalyx is now known to be an important regulator of endothelial function. Studies of the systemic vasculature have demonstrated that the glycocalyx forms a substantial in vivo endothelial surface layer (ESL) critical to inflammation, barrier function and mechanotransduction. The pulmonary ESL is significantly thicker than the systemic ESL, suggesting unique physiologic function. We have recently demonstrated that the pulmonary ESL regulates exposure of endothelial surface adhesion molecules, thereby serving as a barrier to neutrophil adhesion and extravasation. While the pulmonary ESL is not a critical structural component of the endothelial barrier to fluid and protein, it serves a major role in the mechanotransduction of vascular pressure, with impact on the active regulation of endothelial permeability. It is likely that the ESL serves numerous additional functions in vascular physiology, representing a fertile area for future investigation. PMID:24073386

Impact of PACS On The Organization Of Radiology Departments

NASA Astrophysics Data System (ADS)

Zielonka, Jason S.

1983-05-01

The radiologist serves as a consultant to other physicians in the practice of clinical medicine; the image obtained and the reported interpretation of that image represent the service rendered and are therefore of major importance (medically, legally and economically) to the radiologist. Because many radiology departments are organized along subspecialty lines or (in the case of a single department serving several institutions) along combined institutional and subspecialty lines, many patients may undergo diagnostic evaluation sequences in which several studies are performed and multiple simultaneous consultations may result. In the past, the lack of availability of multiple copies of the study (for multiple interested parties) has prevented the effective tailoring of subsequent examinations until the prior exam results were available; the advent of digital networks for PACS may result in a significant change in this procedure and, accordingly, in the pattern of interpretation, internal referral and organization of radiology departments. In addition, since clinicians may have access to studies directly and, possibly, prior to official interpretation, the nature of the relationship between the clinician and the radiologist may be altered by PACS.

Structure and function of wood

Treesearch

Alex Wiedenhoeft

2010-01-01

Wood is a complex biological structure, a composite of many chemistries and cell types acting together to serve the needs of a living plant. Attempting to understand wood in the context of wood technology, we have often overlooked the key and basic fact that wood evolved over the course of millions of years to serve three main functions in plants― conduction of water...

Digital dashboard design using multiple data streams for disease surveillance with influenza surveillance as an example.

PubMed

Cheng, Calvin K Y; Ip, Dennis K M; Cowling, Benjamin J; Ho, Lai Ming; Leung, Gabriel M; Lau, Eric H Y

2011-10-14

Great strides have been made exploring and exploiting new and different sources of disease surveillance data and developing robust statistical methods for analyzing the collected data. However, there has been less research in the area of dissemination. Proper dissemination of surveillance data can facilitate the end user's taking of appropriate actions, thus maximizing the utility of effort taken from upstream of the surveillance-to-action loop. The aims of the study were to develop a generic framework for a digital dashboard incorporating features of efficient dashboard design and to demonstrate this framework by specific application to influenza surveillance in Hong Kong. Based on the merits of the national websites and principles of efficient dashboard design, we designed an automated influenza surveillance digital dashboard as a demonstration of efficient dissemination of surveillance data. We developed the system to synthesize and display multiple sources of influenza surveillance data streams in the dashboard. Different algorithms can be implemented in the dashboard for incorporating all surveillance data streams to describe the overall influenza activity. We designed and implemented an influenza surveillance dashboard that utilized self-explanatory figures to display multiple surveillance data streams in panels. Indicators for individual data streams as well as for overall influenza activity were summarized in the main page, which can be read at a glance. Data retrieval function was also incorporated to allow data sharing in standard format. The influenza surveillance dashboard serves as a template to illustrate the efficient synthesization and dissemination of multiple-source surveillance data, which may also be applied to other diseases. Surveillance data from multiple sources can be disseminated efficiently using a dashboard design that facilitates the translation of surveillance information to public health actions.

Digital Dashboard Design Using Multiple Data Streams for Disease Surveillance With Influenza Surveillance as an Example

PubMed Central

Cheng, Calvin KY; Ip, Dennis KM; Cowling, Benjamin J; Ho, Lai Ming; Leung, Gabriel M

2011-01-01

Background Great strides have been made exploring and exploiting new and different sources of disease surveillance data and developing robust statistical methods for analyzing the collected data. However, there has been less research in the area of dissemination. Proper dissemination of surveillance data can facilitate the end user's taking of appropriate actions, thus maximizing the utility of effort taken from upstream of the surveillance-to-action loop. Objective The aims of the study were to develop a generic framework for a digital dashboard incorporating features of efficient dashboard design and to demonstrate this framework by specific application to influenza surveillance in Hong Kong. Methods Based on the merits of the national websites and principles of efficient dashboard design, we designed an automated influenza surveillance digital dashboard as a demonstration of efficient dissemination of surveillance data. We developed the system to synthesize and display multiple sources of influenza surveillance data streams in the dashboard. Different algorithms can be implemented in the dashboard for incorporating all surveillance data streams to describe the overall influenza activity. Results We designed and implemented an influenza surveillance dashboard that utilized self-explanatory figures to display multiple surveillance data streams in panels. Indicators for individual data streams as well as for overall influenza activity were summarized in the main page, which can be read at a glance. Data retrieval function was also incorporated to allow data sharing in standard format. Conclusions The influenza surveillance dashboard serves as a template to illustrate the efficient synthesization and dissemination of multiple-source surveillance data, which may also be applied to other diseases. Surveillance data from multiple sources can be disseminated efficiently using a dashboard design that facilitates the translation of surveillance information to public health actions. PMID:22001082

The phenomena of Pine's "four psychologies": their contrast and interplay as exhibited in the Beatles' "white album".

PubMed

Brog, M A

1995-01-01

Psychoanalytically informed clinicians are frequently challenged with recognizing and integrating into their work the diverse phenomena central to differing psychoanalytic theoretical frameworks. In addressing this dilemma, Pine has formulated a "multiple model" that recognizes the qualitatively different psychological phenomena and the distinct motivational forces emphasized by what he calls "the four psychologies of psychoanalysis," the psychologies of drive, ego, object relations and self. This model makes it possible to describe individual personality organizations in terms of psychological hierarchies of the phenomena of the four psychologies. Use of this model promotes a particular kind of listening stance that facilitates recognition and use of a wide variety of clinical data. The usefulness of this model is demonstrated through its application to a creative work, the Beatles' "White Album." This application shows the utility of Pine's psychological hierarchies in describing differing personality organizations, the "multiple functions" mental events can represent through serving the motives of multiple psychologies, and the frequent interactions that occur between the differing psychological phenomena. Pine's model facilitates a recognition that an important quality found in works by the Beatles is their demonstration in strikingly clear form, of the qualitatively different aspects of human experience emphasized by the four psychologies. The accessibility of Beatles music makes it a potentially valuable teaching tool for demonstrating Pine's model.

State dependent arrival in bulk retrial queueing system with immediate Bernoulli feedback, multiple vacations and threshold

NASA Astrophysics Data System (ADS)

Niranjan, S. P.; Chandrasekaran, V. M.; Indhira, K.

2017-11-01

The objective of this paper is to analyse state dependent arrival in bulk retrial queueing system with immediate Bernoulli feedback, multiple vacations, threshold and constant retrial policy. Primary customers are arriving into the system in bulk with different arrival rates λ a and λ b . If arriving customers find the server is busy then the entire batch will join to orbit. Customer from orbit request service one by one with constant retrial rate γ. On the other hand if an arrival of customers finds the server is idle then customers will be served in batches according to general bulk service rule. After service completion, customers may request service again with probability δ as feedback or leave from the system with probability 1 - δ. In the service completion epoch, if the orbit size is zero then the server leaves for multiple vacations. The server continues the vacation until the orbit size reaches the value ‘N’ (N > b). At the vacation completion, if the orbit size is ‘N’ then the server becomes ready to provide service for customers from the main pool or from the orbit. For the designed queueing model, probability generating function of the queue size at an arbitrary time will be obtained by using supplementary variable technique. Various performance measures will be derived with suitable numerical illustrations.

Measuring Geographic Inequalities: Dealing with Multiple Health Resources by Data Envelopment Analysis

PubMed Central

Dlouhý, Martin

2018-01-01

The existence of geographic differences in health resources, health expenditures, the utilization of health services, and health outcomes have been documented by a lot of studies from various countries of the world. In a publicly financed health system, equal access is one of the main objectives of the national health policy. That is why inequalities in the geographic allocation of health resources are an important health policy issue. Measures of inequality express the complexity of variation in the observed variable by a single number, and there is a variety of inequality measures available. The objective of this study is to develop a measure of the geographic inequality in the case of multiple health resources. The measure uses data envelopment analysis (DEA), which is a non-parametric method of production function estimation, to transform multiple resources into a single virtual health resource. The study shows that the DEA originally developed for measuring efficiency can be used successfully to measure inequality. For the illustrative purpose, the inequality measure is calculated for the Czech Republic. The values of separate Robin Hood Indexes (RHIs) are 6.64% for physicians and 3.96% for nurses. In the next step, we use combined RHI for both health resources. Its value 5.06% takes into account that the combinations of two health resources serve regional populations. PMID:29541631

Martian sedimentary deposits

NASA Technical Reports Server (NTRS)

Dehon, Rene

1992-01-01

The objectives are characterization of flow through outflow channels, sedimentation associated with Martian outflow systems, and documentation of Martian lakes. Over the period of the grant much, but not all, of the study centered on the Maja Valles outflow. Maja served as an example in which the effects of multiple channel routing and ponding could be studied. Maja Valles also served as the test case for calculating flow through an outflow system. Applying the lessons learned in Maja Valles and comparisons and contrast required a scrutiny of other channels.

The Responsive Amygdala: Treatment-induced Alterations in Functional Connectivity in Pediatric Complex Regional Pain Syndrome

PubMed Central

Simons, LE; Pielech, M; Erpelding, N; Linnman, C; Moulton, E; Sava, S; Lebel, A; Serrano, P; Sethna, N; Berde, C; Becerra, L; Borsook, D

2014-01-01

The amygdala is a key brain region with efferent and afferent neural connections that involve complex behaviors such as pain, reward, fear and anxiety. This study evaluated resting state functional connectivity of the amygdala with cortical and subcortical regions in a group of chronic pain patients (pediatric complex regional pain syndrome) with age-gender matched controls before and after intensive physical-biobehavioral pain treatment. Our main findings include (1) enhanced functional connectivity from the amygdala to multiple cortical, subcortical, and cerebellar regions in patients compared to controls, with differences predominantly in the left amygdala in the pre-treated condition (disease state); (2) dampened hyperconnectivity from the left amygdala to the motor cortex, parietal lobe, and cingulate cortex after intensive pain rehabilitation treatment within patients with nominal differences observed among healthy controls from Time 1 to Time 2 (treatment effects); (3) functional connectivity to several regions key to fear circuitry (prefrontal cortex, bilateral middle temporal lobe, bilateral cingulate, hippocampus) correlated with higher pain-related fear scores and (4) decreases in pain-related fear associated with decreased connectivity between the amygdala and the motor and somatosensory cortex, cingulate, and frontal areas. Our data suggest that there are rapid changes in amygdala connectivity following an aggressive treatment program in children with chronic pain and intrinsic amygdala functional connectivity activity serving as a potential indicator of treatment response. PMID:24861582

A 3/2-Approximation Algorithm for Multiple Depot Multiple Traveling Salesman Problem

NASA Astrophysics Data System (ADS)

Xu, Zhou; Rodrigues, Brian

As an important extension of the classical traveling salesman problem (TSP), the multiple depot multiple traveling salesman problem (MDMTSP) is to minimize the total length of a collection of tours for multiple vehicles to serve all the customers, where each vehicle must start or stay at its distinct depot. Due to the gap between the existing best approximation ratios for the TSP and for the MDMTSP in literature, which are 3/2 and 2, respectively, it is an open question whether or not a 3/2-approximation algorithm exists for the MDMTSP. We have partially addressed this question by developing a 3/2-approximation algorithm, which runs in polynomial time when the number of depots is a constant.

Interview: interview with P Jeffrey Conn. Interview by Hannah Coaker.

PubMed

Conn, P Jeffrey

2013-09-01

Dr Conn is the Lee E Limbird Professor of Pharmacology at Vanderbilt University and Director of the Vanderbilt Center for Neuroscience Drug Discovery (VCNDD). Dr Conn received a PhD in Pharmacology from Vanderbilt in 1986 and pursued postdoctoral studies at Yale University. He served as a professor of Pharmacology at Emory University from 1988 to 2000, before moving to Merck and Co. (PA, USA) as head of the Department of Neuroscience. Dr Conn moved to Vanderbilt University in 2003 where he is the founding director of the VCNDD, with a primary mission of facilitating translation of recent advances in basic science to novel therapeutics. The VCNDD consists of approximately 100 full-time scientists and has advanced novel molecules from four major programs as development candidates for clinical testing with industry partners. Dr Conn has served in editorial positions with multiple international journals and has served the scientific advisory boards of multiple foundations and companies. He has received numerous awards based on the impact of his basic and translational research. Dr Conn's current research is focused on development of novel treatment strategies for schizophrenia, Parkinson's disease and other serious brain disorders. Interview conducted by Hannah Coaker, Assistant Commissioning Editor.

Conducting Research on the International Space Station Using the EXPRESS Rack Facilities

NASA Technical Reports Server (NTRS)

Thompson, Sean W.; Lake, Robert E.

2014-01-01

EXPRESS Racks provide capability for payload access to ISS resources. The successful on-orbit operations and versatility of the EXPRESS Rack has facilitated the operations of many scientific areas, with the promise of continued payload support for years to come. EXPRESS Racks are currently deployed in the US Lab, Columbus and JEM. Process improvements and enhancements continue to improve the accommodations and make the integration and operations process more efficient. Payload Integration Managers serve as the primary interface between the ISS Program and EXPRESS Payload Developers. EXPRESS Project coordinates across multiple functional areas and organizations to ensure integrated EXPRESS Rack and subrack products and hardware are complete, accurate, on time, safe, and certified for flight. NASA is planning to expand the EXPRESS payload capacity by developing new Basic Express Racks expected to be on ISS in 2018.

Unprotected Left Main Disease: Indications and Optimal Strategies for Percutaneous Intervention.

PubMed

Li, Jun; Patel, Sandeep M; Parikh, Manish A; Parikh, Sahil A

2016-03-01

Although the incidence of left main (LM) coronary artery disease is relatively low in patients undergoing routine angiography, it is a common presentation in patients with acute coronary syndromes. With the current interventional tools and techniques, percutaneous intervention for LM disease has become a viable alternative to the traditional coronary artery bypass grafting. Factors that contribute to the success and appropriateness of percutaneous intervention for LM disease include coronary anatomy and patient-specific factors such as left ventricular function. Multiple considerations should be taken into account prior to intervention, including hemodynamic support if necessary, intravascular imaging to guide therapy, and stent technique. This review provides an overview of the current body of literature to support the use of percutaneous intervention in LM disease and serves as guideline for the interventionalist approaching LM revascularization.

Space Station communications and tracking systems modeling and RF link simulation

NASA Technical Reports Server (NTRS)

Tsang, Chit-Sang; Chie, Chak M.; Lindsey, William C.

1986-01-01

In this final report, the effort spent on Space Station Communications and Tracking System Modeling and RF Link Simulation is described in detail. The effort is mainly divided into three parts: frequency division multiple access (FDMA) system simulation modeling and software implementation; a study on design and evaluation of a functional computerized RF link simulation/analysis system for Space Station; and a study on design and evaluation of simulation system architecture. This report documents the results of these studies. In addition, a separate User's Manual on Space Communications Simulation System (SCSS) (Version 1) documents the software developed for the Space Station FDMA communications system simulation. The final report, SCSS user's manual, and the software located in the NASA JSC system analysis division's VAX 750 computer together serve as the deliverables from LinCom for this project effort.

Studies on optimization of growth parameters for L-asparaginase production by Streptomyces ginsengisoli.

PubMed

Deshpande, Neelima; Choubey, Prachi; Agashe, Manasi

2014-01-01

A species of Streptomyces, Streptomyces ginsengisoli, a river isolate, was evaluated for production of an enzyme, L-asparaginase, with multiple functions mainly anticancer activity. The actinomycete was subjected to submerged fermentation by "shake flask" method. The quantity of L-asparaginase produced was estimated as 3.23 μ mol/mL/min. The effect of various culture conditions on L-asparaginase production was studied by adopting a method of variation in one factor at a time. Of the various conditions tested, glucose (followed by starch) and peptone served as good carbon and nitrogen sources, respectively, for maximal production of enzyme at pH 8. The temperature of 30 °C and an incubation period of 5 days with 0.05 g% asparagine concentration were found to be optimum for L-asparaginase production.

Studies on Optimization of Growth Parameters for L-Asparaginase Production by Streptomyces ginsengisoli

PubMed Central

Choubey, Prachi; Agashe, Manasi

2014-01-01

A species of Streptomyces, Streptomyces ginsengisoli, a river isolate, was evaluated for production of an enzyme, L-asparaginase, with multiple functions mainly anticancer activity. The actinomycete was subjected to submerged fermentation by “shake flask” method. The quantity of L-asparaginase produced was estimated as 3.23 μmol/mL/min. The effect of various culture conditions on L-asparaginase production was studied by adopting a method of variation in one factor at a time. Of the various conditions tested, glucose (followed by starch) and peptone served as good carbon and nitrogen sources, respectively, for maximal production of enzyme at pH 8. The temperature of 30°C and an incubation period of 5 days with 0.05 g% asparagine concentration were found to be optimum for L-asparaginase production. PMID:24616652

A large dataset of protein dynamics in the mammalian heart proteome.

PubMed

Lau, Edward; Cao, Quan; Ng, Dominic C M; Bleakley, Brian J; Dincer, T Umut; Bot, Brian M; Wang, Ding; Liem, David A; Lam, Maggie P Y; Ge, Junbo; Ping, Peipei

2016-03-15

Protein stability is a major regulatory principle of protein function and cellular homeostasis. Despite limited understanding on mechanisms, disruption of protein turnover is widely implicated in diverse pathologies from heart failure to neurodegenerations. Information on global protein dynamics therefore has the potential to expand the depth and scope of disease phenotyping and therapeutic strategies. Using an integrated platform of metabolic labeling, high-resolution mass spectrometry and computational analysis, we report here a comprehensive dataset of the in vivo half-life of 3,228 and the expression of 8,064 cardiac proteins, quantified under healthy and hypertrophic conditions across six mouse genetic strains commonly employed in biomedical research. We anticipate these data will aid in understanding key mitochondrial and metabolic pathways in heart diseases, and further serve as a reference for methodology development in dynamics studies in multiple organ systems.

Tail regeneration affects the digestive performance of a Mediterranean lizard

NASA Astrophysics Data System (ADS)

Sagonas, Kostas; Karambotsi, Niki; Bletsa, Aristoula; Reppa, Aikaterini; Pafilis, Panayiotis; Valakos, Efstratios D.

2017-04-01

In caudal autotomy, lizards shed their tail to escape from an attacking predator. Since the tail serves multiple functions, caudal regeneration is of pivotal importance. However, it is a demanding procedure that requires substantial energy and nutrients. Therefore, lizards have to increase energy income to fuel the extraordinary requirements of the regenerating tail. We presumed that autotomized lizards would adjust their digestion to acquire this additional energy. To clarify the effects of tail regeneration on digestion, we compared the digestive performance before autotomy, during regeneration, and after its completion. Tail regeneration indeed increased gut passage time but did not affect digestive performance in a uniform pattern: though protein income was maximized, lipid and sugar acquisition remained stable. This divergence in proteins may be attributed to their particular role in tail reconstruction, as they are the main building blocks for tissue formation.

Application of advanced preclinical models and methods in anesthetic neurotoxicity research.

PubMed

Wang, Cheng; Zhang, Xuan; Liu, Fang

2017-05-01

Recently, there has been increasing concern regarding the potential of anesthetics to disturb the long-term function of the central nervous system (CNS). The field of anesthesia-related toxicology, therefore, has engaged multiple scientific disciplines and utilized a variety of pre-clinical research models in an attempt to identify the basic characteristics of the anesthetic agents that may produce acute and/or chronic adverse effects on the CNS. This review discusses how the application of advanced research approaches and models, such as the nonhuman primate, neural stem cell-derived organotypic slice cultures and/or organs-on-chips systems, can serve as translational models of infantile anesthetic exposure. Utilization of these models may expeditiously decrease the uncertainty in the risk posed to children by postnatal anesthetic exposure. Copyright © 2017. Published by Elsevier Inc.

Extended mission/lunar rover, executive summary

NASA Technical Reports Server (NTRS)

1992-01-01

The design project selected to be undertaken by the 1991/92 Aerospace Design Group was that of conceptually designing an Extended Mission Rover for use on the Lunar Surface. This vehicle would serve the function as a mobile base of sorts, and be able to provide future astronauts with a mobile 'shirt-sleeve' self-sufficient living and working environment. Some of the proposed missions would be planetary surface exploration, construction and maintenance, hardware set-up and in-situ resource experimentation. The need for this type of vehicle has already been declared in the Stafford Group's report on the future of America's Space Program, entitled 'America at the Threshold: America's Space Exploration Initiative'. In the four architectures described within the report, the concept of a pressurized vehicle occurred multiple times. The approximate time frame that this vehicle would be put into use is 2010-2030.

Multiple polymer architectures of human Polyhomeotic homolog 3 (PHC3) SAM

PubMed Central

Nanyes, David R.; Junco, Sarah E.; Taylor, Alexander B.; Robinson, Angela K.; Patterson, Nicolle L.; Shivarajpur, Ambika; Halloran, Jonathan; Hale, Seth M.; Kaur, Yogeet; Hart, P. John; Kim, Chongwoo A.

2014-01-01

The self-association of sterile alpha motifs (SAMs) into a helical polymer architecture is a critical functional component of many different and diverse array of proteins. For the Drosophila Polycomb group (PcG) protein Polyhomeotic (Ph), its SAM polymerization serves as the structural foundation to cluster multiple PcG complexes, helping to maintain a silenced chromatin state. Ph SAM shares 64% sequence identity with its human ortholog, PHC3 SAM, and both SAMs polymerize. However, in the context of their larger protein regions, PHC3 SAM forms longer polymers compared to Ph SAM. Motivated to establish the precise structural basis for the differences, if any, between Ph and PHC3 SAM, we determined the crystal structure of the PHC3 SAM polymer. PHC3 SAM utilizes the same SAM-SAM interaction as the Ph SAM six-fold repeat polymer. Yet, PHC3 SAM polymerizes utilizing just five SAMs per turn of the helical polymer rather than the typical six per turn observed for all SAM polymers reported to date. Structural analysis suggested that malleability of the PHC3 SAM would allow formation of not just the five-fold repeat structure but possibly others. Indeed, a second PHC3 SAM polymer in a different crystal form forms a six-fold repeat polymer. These results suggest that the polymers formed by PHC3 SAM, and likely others, are quite dynamic. The functional consequence of the variable PHC3 SAM polymers may be to create different chromatin architectures. PMID:25044168

Characterization of mitosis-specific phosphorylation of tumor-associated microtubule-associated protein.

PubMed

Hong, Kyung Uk; Kim, Hyun-Jun; Bae, Chang-Dae; Park, Joobae

2009-11-30

Tumor-associated microtubule-associated protein (TMAP), also known as cytoskeleton associated protein 2 (CKAP2), has been recently shown to be involved in the assembly and maintenance of mitotic spindle and also plays an essential role in maintaining the fidelity of chromosome segregation during mitosis. We have previously reported that TMAP is phosphorylated at multiple residues specifically during mitosis, and characterized the mechanism and functional importance of phosphorylation at one of the mitosis-specific phosphorylation residues (i.e., Thr-622). However, the phosphorylation events at the remaining mitotic phosphorylation sites of TMAP have not been fully characterized in detail. Here, we report on generation and characterization of phosphorylated Thr-578- and phosphorylated Thr-596-specific antibodies. Using the antibodies, we show that phosphorylation of TMAP at Thr-578 and Thr-596 indeed occurs specifically during mitosis. Immunofluorescent staining using the antibodies shows that these residues become phosphorylated starting at prophase and then become rapidly dephosphorylated soon after initiation of anaphase. Subtle differences in the kinetics of phosphorylation between Thr-578 and Thr-596 imply that they may be under different mechanisms of phosphorylation during mitosis. Unlike the phosphorylation-deficient mutant form for Thr-622, the mutant in which both Thr-578 and Thr-596 had been mutated to alanines did not induce significant delay in progression of mitosis. These results show that the majority of mitosis-specific phosphorylation of TMAP is limited to pre-anaphase stages and suggest that the multiple phosphorylation may not act in concert but serve diverse functions.

Methods for Studying Ciliary-Mediated Chemoresponse in Paramecium.

PubMed

Valentine, Megan Smith; Van Houten, Judith L

2016-01-01

Paramecium is a useful model organism for the study of ciliary-mediated chemical sensing and response. Here we describe ways to take advantage of Paramecium to study chemoresponse.Unicellular organisms like the ciliated protozoan Paramecium sense and respond to chemicals in their environment (Van Houten, Ann Rev Physiol 54:639-663, 1992; Van Houten, Trends Neurosci 17:62-71, 1994). A thousand or more cilia that cover Paramecium cells serve as antennae for chemical signals, similar to ciliary function in a large variety of metazoan cell types that have primary or motile cilia (Berbari et al., Curr Biol 19(13):R526-R535, 2009; Singla V, Reiter J, Science 313:629-633, 2006). The Paramecium cilia also produce the motor output of the detection of chemical cues by controlling swimming behavior. Therefore, in Paramecium the cilia serve multiple roles of detection and response.We present this chapter in three sections to describe the methods for (1) assaying populations of cells for their behavioral responses to chemicals (attraction and repulsion), (2) characterization of the chemoreceptors and associated channels of the cilia using proteomics and binding assays, and (3) electrophysiological analysis of individual cells' responses to chemicals. These methods are applied to wild type cells, mutants, transformed cells that express tagged proteins, and cells depleted of gene products by RNA Interference (RNAi).

Smart sensor for real-time quantification of common symptoms present in unhealthy plants.

PubMed

Contreras-Medina, Luis M; Osornio-Rios, Roque A; Torres-Pacheco, Irineo; Romero-Troncoso, Rene de J; Guevara-González, Ramon G; Millan-Almaraz, Jesus R

2012-01-01

Plant responses to physiological function disorders are called symptoms and they are caused principally by pathogens and nutritional deficiencies. Plant symptoms are commonly used as indicators of the health and nutrition status of plants. Nowadays, the most popular method to quantify plant symptoms is based on visual estimations, consisting on evaluations that raters give based on their observation of plant symptoms; however, this method is inaccurate and imprecise because of its obvious subjectivity. Computational Vision has been employed in plant symptom quantification because of its accuracy and precision. Nevertheless, the systems developed so far lack in-situ, real-time and multi-symptom analysis. There exist methods to obtain information about the health and nutritional status of plants based on reflectance and chlorophyll fluorescence, but they use expensive equipment and are frequently destructive. Therefore, systems able of quantifying plant symptoms overcoming the aforementioned disadvantages that can serve as indicators of health and nutrition in plants are desirable. This paper reports an FPGA-based smart sensor able to perform non-destructive, real-time and in-situ analysis of leaf images to quantify multiple symptoms presented by diseased and malnourished plants; this system can serve as indicator of the health and nutrition in plants. The effectiveness of the proposed smart-sensor was successfully tested by analyzing diseased and malnourished plants.

Complimentary mechanisms of dual checkpoint blockade expand unique T-cell repertoires and activate adaptive anti-tumor immunity in triple-negative breast tumors

PubMed Central

Wei, Junping; Yang, Xiao Yi; Lei, Gangjun; Wang, Tao; Liu, Cong-Xiao; Morse, Michael A.; Gouin, Kenneth; Knott, Simon R. V.; Hartman, Zachary C.

2018-01-01

ABSTRACT Triple-negative breast cancer (TNBC) is an aggressive and molecularly diverse breast cancer subtype typified by the presence of p53 mutations (∼80%), elevated immune gene signatures and neoantigen expression, as well as the presence of tumor infiltrating lymphocytes (TILs). As these factors are hypothesized to be strong immunologic prerequisites for the use of immune checkpoint blockade (ICB) antibodies, multiple clinical trials testing single ICBs have advanced to Phase III, with early indications of heterogeneous response rates of <20% to anti-PD1 and anti-PDL1 ICB. While promising, these modest response rates highlight the need for mechanistic studies to understand how different ICBs function, how their combination impacts functionality and efficacy, as well as what immunologic parameters predict efficacy to different ICBs regimens in TNBC. To address these issues, we tested anti-PD1 and anti-CTLA4 in multiple models of TNBC and found that their combination profoundly enhanced the efficacy of either treatment alone. We demonstrate that this efficacy is due to anti-CTLA4-driven expansion of an individually unique T-cell receptor (TCR) repertoire whose functionality is enhanced by both intratumoral Treg suppression and anti-PD1 blockade of tumor expressed PDL1. Notably, the individuality of the TCR repertoire was observed regardless of whether the tumor cells expressed a nonself antigen (ovalbumin) or if tumor-specific transgenic T-cells were transferred prior to sequencing. However, responsiveness was strongly correlated with systemic measures of tumor-specific T-cell and B-cell responses, which along with systemic assessment of TCR expansion, may serve as the most useful predictors for clinical responsiveness in future clinical trials of TNBC utilizing anti-PD1/anti-CTLA4 ICB. PMID:29721371

The Neuropathology of Obesity: Insights from Human Disease

PubMed Central

Lee, Edward B.; Mattson, Mark P.

2013-01-01

Obesity, a pathologic state defined by excess adipose tissue, is a significant public health problem as it affects a large proportion of individuals and is linked with increased risk for numerous chronic diseases. Obesity is the result of fundamental changes associated with modern society including overnutrition and sedentary lifestyles. Proper energy homeostasis is dependent on normal brain function as the master metabolic regulator which integrates peripheral signals, modulates autonomic outflow and controls feeding behavior. Therefore, many human brain diseases are associated with obesity. This review explores the neuropathology of obesity by examining brain diseases which either cause or are influenced by obesity. First, several genetic and acquired brain diseases are discussed as a means to understand the central regulation of peripheral metabolism. These diseases range from monogenetic causes of obesity (leptin deficiency, MC4R deficiency, Bardet-Biedl syndrome and others) to complex neurodevelopmental disorders (Prader-Willi syndrome and Sim1 deficiency) and neurodegenerative conditions (frontotemporal dementia and Gourmand’s syndrome) and serve to highlight the central regulatory mechanisms which have evolved to maintain energy homeostasis. Next, to examine the effect of obesity on the brain, chronic neuropathologic conditions (epilepsy, multiple sclerosis and Alzheimer’s disease) are discussed as examples of obesity leading to maladaptive processes which exacerbate chronic disease. Thus obesity is associated with multiple pathways including abnormal metabolism, altered hormonal signaling and increased inflammation which act in concert to promote downstream neuropathology. Finally, the effect of anti-obesity interventions is discussed in terms of brain structure and function. Together, understanding human diseases and anti-obesity interventions leads to insights into the bidirectional interaction between peripheral metabolism and central brain function, highlighting the need for continued clinicopathologic and mechanistic studies of the neuropathology of obesity. PMID:24096619

Regulation of flower development in Arabidopsis by SCF complexes.

PubMed

Ni, Weimin; Xie, Daoxin; Hobbie, Lawrence; Feng, Baomin; Zhao, Dazhong; Akkara, Joseph; Ma, Hong

2004-04-01

SCF complexes are the largest and best studied family of E3 ubiquitin protein ligases that facilitate the ubiquitylation of proteins targeted for degradation. The SCF core components Skp1, Cul1, and Rbx1 serve in multiple SCF complexes involving different substrate-specific F-box proteins that are involved in diverse processes including cell cycle and development. In Arabidopsis, mutations in the F-box gene UNUSUAL FLORAL ORGANS (UFO) result in a number of defects in flower development. However, functions of the core components Cul1 and Rbx1 in flower development are poorly understood. In this study we analyzed floral phenotypes caused by altering function of Cul1 or Rbx1, as well as the effects of mutations in ASK1 and ASK2. Plants homozygous for a point mutation in the AtCUL1 gene showed reduced floral organ number and several defects in each of the four whorls. Similarly, plants with reduced AtRbx1 expression due to RNA interference also exhibited floral morphological defects. In addition, compared to the ask1 mutant, plants homozygous for ask1 and heterozygous for ask2 displayed enhanced reduction of B function, as well as other novel defects of flower development, including carpelloid sepals and an inhibition of petal development. Genetic analyses demonstrate that AGAMOUS (AG) is required for the novel phenotypes observed in the first and second whorls. Furthermore, the genetic interaction between UFO and AtCUL1 supports the idea that UFO regulates multiple aspects of flower development as a part of SCF complexes. These results suggest that SCF complexes regulate several aspects of floral development in Arabidopsis.

Graded hypoxia acts through a network of distributed peripheral oxygen chemoreceptors to produce changes in respiratory behaviour and plasticity.

PubMed

Janes, Tara A; Xu, Fenglian; Syed, Naweed I

2015-07-01

Respiratory behaviour relies critically upon sensory feedback from peripheral oxygen chemoreceptors. During environmental or systemic hypoxia, chemoreceptor input modulates respiratory central pattern generator activity to produce reflex-based increases in respiration and also shapes respiratory plasticity over longer timescales. The best-studied oxygen chemoreceptors are undoubtedly the mammalian carotid bodies; however, questions remain regarding this complex organ's role in shaping respiration in response to varying oxygen levels. Furthermore, many taxa possess distinct oxygen chemoreceptors located within the lungs, airways and cardiovasculature, but the functional advantage of multiple chemoreceptor sites is unclear. In this study, it is demonstrated that a distributed network of peripheral oxygen chemoreceptors exists in Lymnaea stagnalis and significantly modulates aerial respiration. Specifically, Lymnaea breath frequency and duration represent parameters that are shaped by interactions between hypoxic severity and its time-course. Using a combination of behaviour and electrophysiology approaches, the chemosensory pathways underlying hypoxia-induced changes in breath frequency/duration were explored. The current findings demonstrate that breath frequency is uniquely modulated by the known osphradial ganglion oxygen chemoreceptors during moderate hypoxia, while a newly discovered area of pneumostome oxygen chemoreception serves a similar function specifically during more severe hypoxia. Together, these findings suggest that multiple oxygen chemosensory sites, each with their own sensory and modulatory properties, act synergistically to form a functionally distributed network that dynamically shapes respiration in response to changing systemic or environmental oxygen levels. These distributed networks may represent an evolutionarily conserved strategy vis-à-vis respiratory adaptability and have significant implications for the understanding of fundamental respiratory control systems. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Analysis of NFU-1 metallocofactor binding-site substitutions-impacts on iron-sulfur cluster coordination and protein structure and function.

PubMed

Wesley, Nathaniel A; Wachnowsky, Christine; Fidai, Insiya; Cowan, J A

2017-11-01

Iron-sulfur (Fe/S) clusters are ancient prosthetic groups found in numerous metalloproteins and are conserved across all kingdoms of life due to their diverse, yet essential functional roles. Genetic mutations to a specific subset of mitochondrial Fe/S cluster delivery proteins are broadly categorized as disease-related under multiple mitochondrial dysfunction syndrome (MMDS), with symptoms indicative of a general failure of the metabolic system. Multiple mitochondrial dysfunction syndrome 1 (MMDS1) arises as a result of the missense mutation in NFU1, an Fe/S cluster scaffold protein, which substitutes a glycine near the Fe/S cluster-binding pocket to a cysteine (p.Gly208Cys). This substitution has been shown to promote protein dimerization such that cluster delivery to NFU1 is blocked, preventing downstream cluster trafficking. However, the possibility of this additional cysteine, located adjacent to the cluster-binding site, serving as an Fe/S cluster ligand has not yet been explored. To fully understand the consequences of this Gly208Cys replacement, complementary substitutions at the Fe/S cluster-binding pocket for native and Gly208Cys NFU1 were made, along with six other variants. Herein, we report the results of an investigation on the effect of these substitutions on both cluster coordination and NFU1 structure and function. The data suggest that the G208C substitution does not contribute to cluster binding. Rather, replacement of the glycine at position 208 changes the oligomerization state as a result of global structural alterations that result in the downstream effects manifest as MMDS1, but does not perturb the coordination chemistry of the Fe-S cluster. © 2017 Federation of European Biochemical Societies.

Target gene analysis by microarrays and chromatin immunoprecipitation identifies HEY proteins as highly redundant bHLH repressors.

PubMed

Heisig, Julia; Weber, David; Englberger, Eva; Winkler, Anja; Kneitz, Susanne; Sung, Wing-Kin; Wolf, Elmar; Eilers, Martin; Wei, Chia-Lin; Gessler, Manfred

2012-01-01

HEY bHLH transcription factors have been shown to regulate multiple key steps in cardiovascular development. They can be induced by activated NOTCH receptors, but other upstream stimuli mediated by TGFß and BMP receptors may elicit a similar response. While the basic and helix-loop-helix domains exhibit strong similarity, large parts of the proteins are still unique and may serve divergent functions. The striking overlap of cardiac defects in HEY2 and combined HEY1/HEYL knockout mice suggested that all three HEY genes fulfill overlapping function in target cells. We therefore sought to identify target genes for HEY proteins by microarray expression and ChIPseq analyses in HEK293 cells, cardiomyocytes, and murine hearts. HEY proteins were found to modulate expression of their target gene to a rather limited extent, but with striking functional interchangeability between HEY factors. Chromatin immunoprecipitation revealed a much greater number of potential binding sites that again largely overlap between HEY factors. Binding sites are clustered in the proximal promoter region especially of transcriptional regulators or developmental control genes. Multiple lines of evidence suggest that HEY proteins primarily act as direct transcriptional repressors, while gene activation seems to be due to secondary or indirect effects. Mutagenesis of putative DNA binding residues supports the notion of direct DNA binding. While class B E-box sequences (CACGYG) clearly represent preferred target sequences, there must be additional and more loosely defined modes of DNA binding since many of the target promoters that are efficiently bound by HEY proteins do not contain an E-box motif. These data clearly establish the three HEY bHLH factors as highly redundant transcriptional repressors in vitro and in vivo, which explains the combinatorial action observed in different tissues with overlapping expression.

Target Gene Analysis by Microarrays and Chromatin Immunoprecipitation Identifies HEY Proteins as Highly Redundant bHLH Repressors

PubMed Central

Englberger, Eva; Winkler, Anja; Kneitz, Susanne; Sung, Wing-Kin; Wolf, Elmar; Eilers, Martin; Wei, Chia-Lin; Gessler, Manfred

2012-01-01

HEY bHLH transcription factors have been shown to regulate multiple key steps in cardiovascular development. They can be induced by activated NOTCH receptors, but other upstream stimuli mediated by TGFß and BMP receptors may elicit a similar response. While the basic and helix-loop-helix domains exhibit strong similarity, large parts of the proteins are still unique and may serve divergent functions. The striking overlap of cardiac defects in HEY2 and combined HEY1/HEYL knockout mice suggested that all three HEY genes fulfill overlapping function in target cells. We therefore sought to identify target genes for HEY proteins by microarray expression and ChIPseq analyses in HEK293 cells, cardiomyocytes, and murine hearts. HEY proteins were found to modulate expression of their target gene to a rather limited extent, but with striking functional interchangeability between HEY factors. Chromatin immunoprecipitation revealed a much greater number of potential binding sites that again largely overlap between HEY factors. Binding sites are clustered in the proximal promoter region especially of transcriptional regulators or developmental control genes. Multiple lines of evidence suggest that HEY proteins primarily act as direct transcriptional repressors, while gene activation seems to be due to secondary or indirect effects. Mutagenesis of putative DNA binding residues supports the notion of direct DNA binding. While class B E-box sequences (CACGYG) clearly represent preferred target sequences, there must be additional and more loosely defined modes of DNA binding since many of the target promoters that are efficiently bound by HEY proteins do not contain an E-box motif. These data clearly establish the three HEY bHLH factors as highly redundant transcriptional repressors in vitro and in vivo, which explains the combinatorial action observed in different tissues with overlapping expression. PMID:22615585

Complimentary mechanisms of dual checkpoint blockade expand unique T-cell repertoires and activate adaptive anti-tumor immunity in triple-negative breast tumors.

PubMed

Crosby, Erika J; Wei, Junping; Yang, Xiao Yi; Lei, Gangjun; Wang, Tao; Liu, Cong-Xiao; Agarwal, Pankaj; Korman, Alan J; Morse, Michael A; Gouin, Kenneth; Knott, Simon R V; Lyerly, H Kim; Hartman, Zachary C

2018-01-01

Triple-negative breast cancer (TNBC) is an aggressive and molecularly diverse breast cancer subtype typified by the presence of p53 mutations (∼80%), elevated immune gene signatures and neoantigen expression, as well as the presence of tumor infiltrating lymphocytes (TILs). As these factors are hypothesized to be strong immunologic prerequisites for the use of immune checkpoint blockade (ICB) antibodies, multiple clinical trials testing single ICBs have advanced to Phase III, with early indications of heterogeneous response rates of <20% to anti-PD1 and anti-PDL1 ICB. While promising, these modest response rates highlight the need for mechanistic studies to understand how different ICBs function, how their combination impacts functionality and efficacy, as well as what immunologic parameters predict efficacy to different ICBs regimens in TNBC. To address these issues, we tested anti-PD1 and anti-CTLA4 in multiple models of TNBC and found that their combination profoundly enhanced the efficacy of either treatment alone. We demonstrate that this efficacy is due to anti-CTLA4-driven expansion of an individually unique T-cell receptor (TCR) repertoire whose functionality is enhanced by both intratumoral Treg suppression and anti-PD1 blockade of tumor expressed PDL1. Notably, the individuality of the TCR repertoire was observed regardless of whether the tumor cells expressed a nonself antigen (ovalbumin) or if tumor-specific transgenic T-cells were transferred prior to sequencing. However, responsiveness was strongly correlated with systemic measures of tumor-specific T-cell and B-cell responses, which along with systemic assessment of TCR expansion, may serve as the most useful predictors for clinical responsiveness in future clinical trials of TNBC utilizing anti-PD1/anti-CTLA4 ICB.

Understanding and Communicating through Narratives

DTIC Science & Technology

2012-05-17

distinctions, and may affect the fundamental contents of personal identity . It comes as no surprise that because of these influences stories are...activists.”16 Narrative serves an inherently strategic role, it serves as living embodiment of identity and ideology at personal, organizational, and as...applied by Freeman, national level. This identity function is one of the most critical functions of narrative. The logic expressed by the identity

Vision Assessment and Program Manual for Severely Handicapped and/or Deaf-Blind Students. Bay Area Severely Handicapped Deaf Blind Project.

ERIC Educational Resources Information Center

Sailor, Wayne; And Others

Intended for teachers of deaf-blind and severely handicapped students as well as for resource or itinerant teachers in the area of vision who have recently begun to serve low functioning students, the manual provides information on vision and on vision assessment. The manual serves three functions. It: (1) prepares teachers for participation in…

Spiraling Light with Magnetic Metamaterial Quarter-Wave Turbines.

PubMed

Zeng, Jinwei; Luk, Ting S; Gao, Jie; Yang, Xiaodong

2017-09-19

Miniaturized quarter-wave plate devices empower spin to orbital angular momentum conversion and vector polarization formation, which serve as bridges connecting conventional optical beam and structured light. Enabling the manipulability of additional dimensions as the complex polarization and phase of light, quarter-wave plate devices are essential for exploring a plethora of applications based on orbital angular momentum or vector polarization, such as optical sensing, holography, and communication. Here we propose and demonstrate the magnetic metamaterial quarter-wave turbines at visible wavelength to produce radially and azimuthally polarized vector vortices from circularly polarized incident beam. The magnetic metamaterials function excellently as quarter-wave plates at single wavelength and maintain the quarter-wave phase retardation in broadband, while the turbine blades consist of multiple polar sections, each of which contains homogeneously oriented magnetic metamaterial gratings near azimuthal or radial directions to effectively convert circular polarization to linear polarization and induce phase shift under Pancharatnum-Berry's phase principle. The perspective concept of multiple polar sections of magnetic metamaterials can extend to other analogous designs in the strongly coupled nanostructures to accomplish many types of light phase-polarization manipulation and structured light conversion in the desired manner.

A clustering-based fuzzy wavelet neural network model for short-term load forecasting.

PubMed

Kodogiannis, Vassilis S; Amina, Mahdi; Petrounias, Ilias

2013-10-01

Load forecasting is a critical element of power system operation, involving prediction of the future level of demand to serve as the basis for supply and demand planning. This paper presents the development of a novel clustering-based fuzzy wavelet neural network (CB-FWNN) model and validates its prediction on the short-term electric load forecasting of the Power System of the Greek Island of Crete. The proposed model is obtained from the traditional Takagi-Sugeno-Kang fuzzy system by replacing the THEN part of fuzzy rules with a "multiplication" wavelet neural network (MWNN). Multidimensional Gaussian type of activation functions have been used in the IF part of the fuzzyrules. A Fuzzy Subtractive Clustering scheme is employed as a pre-processing technique to find out the initial set and adequate number of clusters and ultimately the number of multiplication nodes in MWNN, while Gaussian Mixture Models with the Expectation Maximization algorithm are utilized for the definition of the multidimensional Gaussians. The results corresponding to the minimum and maximum power load indicate that the proposed load forecasting model provides significantly accurate forecasts, compared to conventional neural networks models.

Immune Ecosystem of Virus-Infected Host Tissues.

PubMed

Maarouf, Mohamed; Rai, Kul Raj; Goraya, Mohsan Ullah; Chen, Ji-Long

2018-05-06

Virus infected host cells serve as a central immune ecological niche during viral infection and replication and stimulate the host immune response via molecular signaling. The viral infection and multiplication process involves complex intracellular molecular interactions between viral components and the host factors. Various types of host cells are also involved to modulate immune factors in delicate and dynamic equilibrium to maintain a balanced immune ecosystem in an infected host tissue. Antiviral host arsenals are equipped to combat or eliminate viral invasion. However, viruses have evolved with strategies to counter against antiviral immunity or hijack cellular machinery to survive inside host tissue for their multiplication. However, host immune systems have also evolved to neutralize the infection; which, in turn, either clears the virus from the infected host or causes immune-mediated host tissue injury. A complex relationship between viral pathogenesis and host antiviral defense could define the immune ecosystem of virus-infected host tissues. Understanding of the molecular mechanism underlying this ecosystem would uncover strategies to modulate host immune function for antiviral therapeutics. This review presents past and present updates of immune-ecological components of virus infected host tissue and explains how viruses subvert the host immune surveillances.

Direct Profiling the Post-Translational Modification Codes of a Single Protein Immobilized on a Surface Using Cu-free Click Chemistry.

PubMed

Kim, Kyung Lock; Park, Kyeng Min; Murray, James; Kim, Kimoon; Ryu, Sung Ho

2018-05-23

Combinatorial post-translational modifications (PTMs), which can serve as dynamic "molecular barcodes", have been proposed to regulate distinct protein functions. However, studies of combinatorial PTMs on single protein molecules have been hindered by a lack of suitable analytical methods. Here, we describe erasable single-molecule blotting (eSiMBlot) for combinatorial PTM profiling. This assay is performed in a highly multiplexed manner and leverages the benefits of covalent protein immobilization, cyclic probing with different antibodies, and single molecule fluorescence imaging. Especially, facile and efficient covalent immobilization on a surface using Cu-free click chemistry permits multiple rounds (>10) of antibody erasing/reprobing without loss of antigenicity. Moreover, cumulative detection of coregistered multiple data sets for immobilized single-epitope molecules, such as HA peptide, can be used to increase the antibody detection rate. Finally, eSiMBlot enables direct visualization and quantitative profiling of combinatorial PTM codes at the single-molecule level, as we demonstrate by revealing the novel phospho-codes of ligand-induced epidermal growth factor receptor. Thus, eSiMBlot provides an unprecedentedly simple, rapid, and versatile platform for analyzing the vast number of combinatorial PTMs in biological pathways.

Layered nano-gratings by electron beam writing to form 3-level diffractive optical elements for 3D phase-offset holographic lithography.

PubMed

Yuan, Liang Leon; Herman, Peter R

2015-12-21

A multi-level nanophotonic structure is a major goal in providing advanced optical functionalities as found in photonic crystals and metamaterials. A three-level nano-grating phase mask has been fabricated in an electron-beam resist (ma-N) to meet the requirement of holographic generation of a diamond-like 3D nanostructure in photoresist by a single exposure step. A 2D mask with 600 nm periodicity is presented for generating first order diffracted beams with a preferred π/2 phase shift on the X- and Y-axes and with sufficient 1(st) order diffraction efficiency of 3.5% at 800 nm wavelength for creating a 3D periodic nanostructure in SU-8 photoresist. The resulting 3D structure is anticipated to provide an 8% complete photonic band gap (PBG) upon silicon inversion. A thin SiO2 layer was used to isolate the grating layers and multiple spin-coating steps served to planarize the final resist layer. A reversible soft coating (aquaSAVE) was introduced to enable SEM inspection and verification of each insulating grating layer. This e-beam lithographic method is extensible to assembling multiple layers of a nanophotonic structure.

'Fish matters': the relevance of fish skin biology to investigative dermatology.

PubMed

Rakers, Sebastian; Gebert, Marina; Uppalapati, Sai; Meyer, Wilfried; Maderson, Paul; Sell, Anne F; Kruse, Charli; Paus, Ralf

2010-04-01

Fish skin is a multi-purpose tissue that serves numerous vital functions including chemical and physical protection, sensory activity, behavioural purposes or hormone metabolism. Further, it is an important first-line defense system against pathogens, as fish are continuously exposed to multiple microbial challenges in their aquatic habitat. Fish skin excels in highly developed antimicrobial features, many of which have been preserved throughout evolution, and infection defense principles employed by piscine skin are still operative in human skin. This review argues that it is both rewarding and important for investigative dermatologists to revive their interest in fish skin biology, as it provides insights into numerous fundamental issues that are of major relevance to mammalian skin. The basic molecular insights provided by zebrafish in vivo-genomics for genetic, regeneration and melanoma research, the complex antimicrobial defense systems of fish skin and the molecular controls of melanocyte stem cells are just some of the fascinating examples that illustrate the multiple potential uses of fish skin models in investigative dermatology. We synthesize the essentials of fish skin biology and highlight selected aspects that are of particular comparative interest to basic and clinically applied human skin research.

Direct Profiling the Post-Translational Modification Codes of a Single Protein Immobilized on a Surface Using Cu-free Click Chemistry

PubMed Central

2018-01-01

Combinatorial post-translational modifications (PTMs), which can serve as dynamic “molecular barcodes”, have been proposed to regulate distinct protein functions. However, studies of combinatorial PTMs on single protein molecules have been hindered by a lack of suitable analytical methods. Here, we describe erasable single-molecule blotting (eSiMBlot) for combinatorial PTM profiling. This assay is performed in a highly multiplexed manner and leverages the benefits of covalent protein immobilization, cyclic probing with different antibodies, and single molecule fluorescence imaging. Especially, facile and efficient covalent immobilization on a surface using Cu-free click chemistry permits multiple rounds (>10) of antibody erasing/reprobing without loss of antigenicity. Moreover, cumulative detection of coregistered multiple data sets for immobilized single-epitope molecules, such as HA peptide, can be used to increase the antibody detection rate. Finally, eSiMBlot enables direct visualization and quantitative profiling of combinatorial PTM codes at the single-molecule level, as we demonstrate by revealing the novel phospho-codes of ligand-induced epidermal growth factor receptor. Thus, eSiMBlot provides an unprecedentedly simple, rapid, and versatile platform for analyzing the vast number of combinatorial PTMs in biological pathways.

45 CFR 2553.61 - When may a sponsor serve as a volunteer station?

Code of Federal Regulations, 2012 CFR

2012-10-01

... 45 Public Welfare 4 2012-10-01 2012-10-01 false When may a sponsor serve as a volunteer station... FOR NATIONAL AND COMMUNITY SERVICE THE RETIRED AND SENIOR VOLUNTEER PROGRAM Responsibilities of a Volunteer Station § 2553.61 When may a sponsor serve as a volunteer station? The sponsor may function as a...

45 CFR 2553.61 - When may a sponsor serve as a volunteer station?

Code of Federal Regulations, 2014 CFR

2014-10-01

... 45 Public Welfare 4 2014-10-01 2014-10-01 false When may a sponsor serve as a volunteer station... FOR NATIONAL AND COMMUNITY SERVICE THE RETIRED AND SENIOR VOLUNTEER PROGRAM Responsibilities of a Volunteer Station § 2553.61 When may a sponsor serve as a volunteer station? The sponsor may function as a...

45 CFR 2553.61 - When may a sponsor serve as a volunteer station?

Code of Federal Regulations, 2013 CFR

2013-10-01

... 45 Public Welfare 4 2013-10-01 2013-10-01 false When may a sponsor serve as a volunteer station... FOR NATIONAL AND COMMUNITY SERVICE THE RETIRED AND SENIOR VOLUNTEER PROGRAM Responsibilities of a Volunteer Station § 2553.61 When may a sponsor serve as a volunteer station? The sponsor may function as a...

45 CFR 2553.61 - When may a sponsor serve as a volunteer station?

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 4 2010-10-01 2010-10-01 false When may a sponsor serve as a volunteer station... FOR NATIONAL AND COMMUNITY SERVICE THE RETIRED AND SENIOR VOLUNTEER PROGRAM Responsibilities of a Volunteer Station § 2553.61 When may a sponsor serve as a volunteer station? The sponsor may function as a...

45 CFR 2553.61 - When may a sponsor serve as a volunteer station?

Code of Federal Regulations, 2011 CFR

2011-10-01

... 45 Public Welfare 4 2011-10-01 2011-10-01 false When may a sponsor serve as a volunteer station... FOR NATIONAL AND COMMUNITY SERVICE THE RETIRED AND SENIOR VOLUNTEER PROGRAM Responsibilities of a Volunteer Station § 2553.61 When may a sponsor serve as a volunteer station? The sponsor may function as a...

The life cycle of chondrocytes in the developing skeleton

PubMed Central

Shum, Lillian; Nuckolls, Glen

2002-01-01

Cartilage serves multiple functions in the developing embryo and in postnatal life. Genetic mutations affecting cartilage development are relatively common and lead to skeletal malformations, dysfunction or increased susceptibility to disease or injury. Characterization of these mutations and investigation of the molecular pathways in which these genes function have contributed to an understanding of the mechanisms regulating skeletal patterning, chondrogenesis, endochondral ossification and joint formation. Extracellular growth and differentiation factors including bone morphogenetic proteins, fibroblast growth factors, parathyroid hormone-related peptide, extracellular matrix components, and members of the hedgehog and Wnt families provide important signals for the regulation of cell proliferation, differentiation and apoptosis. Transduction of these signals within the developing mesenchymal cells and chondrocytes results in changes in gene expression mediated by transcription factors including Smads, Msx2, Sox9, signal transducer and activator of transcription (STAT), and core-binding factor alpha 1. Further investigation of the interactions of these signaling pathways will contribute to an understanding of cartilage growth and development, and will allow for the development of strategies for the early detection, prevention and treatment of diseases and disorders affecting the skeleton. PMID:11879545

The neurosciences and the search for a unified psychology: the science and esthetics of a single framework

PubMed Central

Stam, Henderikus J.

2015-01-01

The search for a so-called unified or integrated theory has long served as a goal for some psychologists, even if the search is often implicit. But if the established sciences do not have an explicitly unified set of theories, then why should psychology? After examining this question again I argue that psychology is in fact reasonably unified around its methods and its commitment to functional explanations, an indeterminate functionalism. The question of the place of the neurosciences in this framework is complex. On the one hand, the neuroscientific project will not likely renew and synthesize the disparate arms of psychology. On the other hand, their reformulation of what it means to be human will exert an influence in multiple ways. One way to capture that influence is to conceptualize the brain in terms of a technology that we interact with in a manner that we do not yet fully understand. In this way we maintain both a distance from neuro-reductionism and refrain from committing to an unfettered subjectivity. PMID:26500571

The role of lipids in host microbe interactions.

PubMed

Lang, Roland; Mattner, Jochen

2017-06-01

Lipids are one of the major subcellular constituents and serve as signal molecules, energy sources, metabolic precursors and structural membrane components in various organisms. The function of lipids can be modified by multiple biochemical processes such as (de-)phosphorylation or (de-)glycosylation, and the organization of fatty acids into distinct cellular pools and subcellular compartments plays a pivotal role for the morphology and function of various cell populations. Thus, lipids regulate, for example, phagosome formation and maturation within host cells and thus, are critical for the elimination of microbial pathogens. Vice versa, microbial pathogens can manipulate the lipid composition of phagosomal membranes in host cells, and thus avoid their delivery to phagolysosomes. Lipids of microbial origin belong also to the strongest and most versatile inducers of mammalian immune responses upon engagement of distinct receptors on myeloid and lymphoid cells. Furthermore, microbial lipid toxins can induce membrane injuries and cell death. Thus, we will review here selected examples for mutual host-microbe interactions within the broad and divergent universe of lipids in microbial defense, tissue injury and immune evasion.

Common hyperspectral image database design

NASA Astrophysics Data System (ADS)

Tian, Lixun; Liao, Ningfang; Chai, Ali

2009-11-01

This paper is to introduce Common hyperspectral image database with a demand-oriented Database design method (CHIDB), which comprehensively set ground-based spectra, standardized hyperspectral cube, spectral analysis together to meet some applications. The paper presents an integrated approach to retrieving spectral and spatial patterns from remotely sensed imagery using state-of-the-art data mining and advanced database technologies, some data mining ideas and functions were associated into CHIDB to make it more suitable to serve in agriculture, geological and environmental areas. A broad range of data from multiple regions of the electromagnetic spectrum is supported, including ultraviolet, visible, near-infrared, thermal infrared, and fluorescence. CHIDB is based on dotnet framework and designed by MVC architecture including five main functional modules: Data importer/exporter, Image/spectrum Viewer, Data Processor, Parameter Extractor, and On-line Analyzer. The original data were all stored in SQL server2008 for efficient search, query and update, and some advance Spectral image data Processing technology are used such as Parallel processing in C#; Finally an application case is presented in agricultural disease detecting area.

Osteoblastic molecular scaffold Gab1 is required for maintaining bone homeostasis.

PubMed

Weng, Tujun; Mao, Fengfeng; Wang, Youliang; Sun, Qiang; Li, Ruixin; Yang, Guan; Zhang, Xizheng; Luo, Jincai; Feng, Gen-Sheng; Yang, Xiao

2010-03-01

The Grb2-associated binder 1 (Gab1), which serves as a scaffolding adaptor protein, plays a crucial role in transmitting key signals that control cell growth, differentiation and function from multiple receptors. However, its biological role in osteoblast activity and postnatal bone metabolism remains unclear. To elucidate the in vivo function of Gab1 in postnatal bone remodeling, we generated osteoblast-specific Gab1 knockout mice. Disruption of Gab1 expression in osteoblasts led to decreased trabecular bone mass with a reduced bone formation rate and a decreased bone resorption. Bones from Gab1 mutants also exhibited inferior mechanical properties. Moreover, primary osteoblasts from Gab1 mutant mice demonstrated markedly suppressed osteoblast mineralization, increased susceptibility to apoptosis and decreased expression of receptor activator of NF-kappaB ligand (RANKL). Activation of serine-threonine Akt kinase and extracellular signal-regulated kinase in response to insulin and insulin-like growth factor 1 was attenuated in Gab1 mutant osteoblasts. Our results show that Gab1-mediated signals in osteoblasts are crucial for normal postnatal bone homeostasis.

The presence and significance of polar meibum and tear lipids.

PubMed

Pucker, Andrew D; Haworth, Kristina M

2015-01-01

The ocular tear film is a complex structure composed of a number of elements. While all of these components serve valuable functional and structural roles, the external lipid layer has been a focus because it is known to play a critical role in dry eye. Traditionally, meibomian gland phospholipids have been considered to be the vital amphiphilic molecules needed to create an interphase between the outer nonpolar lipid layer and inner aqueous layers, yet recent work has called this theory into question. The purpose of this review is to clarify the current understanding of the origins, identity, and significance of polar tear lipids. Studies indicate that both phospholipids and ω-hydroxy fatty acids likely play a critical role in tear film stability. Studies also indicate that polar lipids likely originate from multiple sources and that they are integrally involved in ocular surface disease. Additional studies are needed to fully understand the origins and significance of polar tear lipids, because to date only correlational evidence has described their hypothesized origins and functions. Copyright © 2015 Elsevier Inc. All rights reserved.

Maternal Religiosity, Family Resources and Stressors, and Parent-Child Attachment Security in Northern Ireland.

PubMed

Goeke-Morey, Marcie C; Cairns, Ed; Merrilees, Christine E; Schermerhorn, Alice C; Shirlow, Peter; Cummings, E Mark

2013-02-01

This study explores the associations between mothers' religiosity, and families' and children's functioning in a stratified random sample of 695 Catholic and Protestant mother-child dyads in socially deprived areas in Belfast, Northern Ireland, a region which has experienced centuries of sectarian conflict between Protestant Unionists and Catholics Nationalists. Findings based on mother and child surveys indicated that even in this context of historical political violence associated with religious affiliation, mothers' religiosity played a consistently positive role, including associations with multiple indicators of better family functioning (i.e., more cohesion and behavioral control and less conflict, psychological distress, and adjustment problems) and greater parent-child attachment security. Mothers' religiosity also moderated the association between parent-child attachment security and family resources and family stressors, enhancing positive effects of cohesion and mother behavioral control on mother-child attachment security, and providing protection against risks associated with mothers' psychological distress. Findings are discussed in terms of implications for understanding the role of religiosity in serving as a protective or risk factor for children and families.

Structure, function, and control of the human musculoskeletal network

PubMed Central

Murphy, Andrew C.; Muldoon, Sarah F.; Baker, David; Lastowka, Adam; Bennett, Brittany; Yang, Muzhi

2018-01-01

The human body is a complex organism, the gross mechanical properties of which are enabled by an interconnected musculoskeletal network controlled by the nervous system. The nature of musculoskeletal interconnection facilitates stability, voluntary movement, and robustness to injury. However, a fundamental understanding of this network and its control by neural systems has remained elusive. Here we address this gap in knowledge by utilizing medical databases and mathematical modeling to reveal the organizational structure, predicted function, and neural control of the musculoskeletal system. We constructed a highly simplified whole-body musculoskeletal network in which single muscles connect to multiple bones via both origin and insertion points. We demonstrated that, using this simplified model, a muscle’s role in this network could offer a theoretical prediction of the susceptibility of surrounding components to secondary injury. Finally, we illustrated that sets of muscles cluster into network communities that mimic the organization of control modules in primary motor cortex. This novel formalism for describing interactions between the muscular and skeletal systems serves as a foundation to develop and test therapeutic responses to injury, inspiring future advances in clinical treatments. PMID:29346370

Silibinin: an old drug for hematological disorders.

PubMed

Zou, Hai; Zhu, Xing-Xing; Zhang, Guo-Bing; Ma, Yuan; Wu, Yi; Huang, Dong-Sheng

2017-10-24

Silibinin (silybin), a non-toxic natural polyphenolic flavonoid, is the principal and the most biologically active component of silymarin. It is efficient in the treatment of acute and chronic liver disorders caused by toxins, drug, alcohol, hepatitis, and gall bladder disorders. Further, in our previous studies, we explored the anti-cancer efficacy in common cancers, such as lung, prostatic, colon, breast, bladder, as well as, hepatocellular carcinoma. Interestingly, silibinin is still not solely limited to the treatment of these diseases. Recent research endeavors suggest that silibinin may function diversely and serve as a novel therapy for hematological disorders. It discovered several interesting viewpoints in the widely studied mechanisms of silibinin in the hematological disorders. In this report, we review the up-to-date findings of more potency roles of silibinin in β-thalassemia (β-TM), acute myeloid leukemia (AML), anaplastic large cell lymphoma (ALCL) and multiple myelomas (MM) therapy and attempt to clarify the mechanisms underlying its effects. There are two viewpoints: First, The functional mechanisms of silibinin in AML cells via regulating cell differentiation to exert anti-cancer effect; Second, combination treatment strategy may be a good choice.

Cultural evolution of military camouflage.

PubMed

Talas, Laszlo; Baddeley, Roland J; Cuthill, Innes C

2017-07-05

While one has evolved and the other been consciously created, animal and military camouflage are expected to show many similar design principles. Using a unique database of calibrated photographs of camouflage uniform patterns, processed using texture and colour analysis methods from computer vision, we show that the parallels with biology are deeper than design for effective concealment. Using two case studies we show that, like many animal colour patterns, military camouflage can serve multiple functions. Following the dissolution of the Warsaw Pact, countries that became more Western-facing in political terms converged on NATO patterns in camouflage texture and colour. Following the break-up of the former Yugoslavia, the resulting states diverged in design, becoming more similar to neighbouring countries than the ancestral design. None of these insights would have been obtained using extant military approaches to camouflage design, which focus solely on concealment. Moreover, our computational techniques for quantifying pattern offer new tools for comparative biologists studying animal coloration.This article is part of the themed issue 'Animal coloration: production, perception, function and application'. © 2017 The Author(s).

Decapping activators in Saccharomyces cerevisiae act by multiple mechanisms.

PubMed

Nissan, Tracy; Rajyaguru, Purusharth; She, Meipei; Song, Haiwei; Parker, Roy

2010-09-10

Eukaryotic mRNA degradation often occurs in a process whereby translation initiation is inhibited and the mRNA is targeted for decapping. In yeast cells, Pat1, Scd6, Edc3, and Dhh1 all function to promote decapping by an unknown mechanism(s). We demonstrate that purified Scd6 and a region of Pat1 directly repress translation in vitro by limiting the formation of a stable 48S preinitiation complex. Moreover, while Pat1, Edc3, Dhh1, and Scd6 all bind the decapping enzyme, only Pat1 and Edc3 enhance its activity. We also identify numerous direct interactions between Pat1, Dcp1, Dcp2, Dhh1, Scd6, Edc3, Xrn1, and the Lsm1-7 complex. These observations identify three classes of decapping activators that function to directly repress translation initiation and/or stimulate Dcp1/2. Moreover, Pat1 is identified as critical in mRNA decay by first inhibiting translation initiation, then serving as a scaffold to recruit components of the decapping complex, and finally activating Dcp2. Copyright © 2010 Elsevier Inc. All rights reserved.

Src regulates sequence-dependent beta-2 adrenergic receptor recycling via cortactin phosphorylation*

PubMed Central

Vistein, Rachel; Puthenveedu, Manojkumar A.

2014-01-01

The recycling of internalized signaling receptors, which has direct functional consequences, is subject to multiple sequence and biochemical requirements. Why signaling receptors recycle via a specialized pathway, unlike many other proteins that recycle by bulk, is a fundamental unanswered question. Here we show that these specialized pathways allow selective control of signaling receptor recycling by heterologous signaling. Using assays to visualize receptor recycling in living cells, we show that the recycling of the beta-2 adrenergic receptor (B2AR), a prototypic signaling receptor, is regulated by Src family kinases. The target of Src is cortactin, an essential factor for B2AR sorting into specialized recycling microdomains on the endosome. Phosphorylation of a single cortactin residue, Y466, regulates the rate of fission of B2AR recycling vesicles from these microdomains, and, therefore, the rate of delivery of B2AR to the cell surface. Together, our results indicate that actin-stabilized microdomains that mediate signaling receptor recycling can serve as a functional point of convergence for crosstalk between signaling pathways. PMID:25077552

Abdominal surgery process modeling framework for simulation using spreadsheets.

PubMed

Boshkoska, Biljana Mileva; Damij, Talib; Jelenc, Franc; Damij, Nadja

2015-08-01

We provide a continuation of the existing Activity Table Modeling methodology with a modular spreadsheets simulation. The simulation model developed is comprised of 28 modeling elements for the abdominal surgery cycle process. The simulation of a two-week patient flow in an abdominal clinic with 75 beds demonstrates the applicability of the methodology. The simulation does not include macros, thus programming experience is not essential for replication or upgrading the model. Unlike the existing methods, the proposed solution employs a modular approach for modeling the activities that ensures better readability, the possibility of easily upgrading the model with other activities, and its easy extension and connectives with other similar models. We propose a first-in-first-served approach for simulation of servicing multiple patients. The uncertain time duration of the activities is modeled using the function "rand()". The patients movements from one activity to the next one is tracked with nested "if()" functions, thus allowing easy re-creation of the process without the need of complex programming. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Attenuation of Diabetes-induced Cardiac and Subcellular Defects by Sulphur-containing Amino Acids.

PubMed

Tappia, Paramjit S; Adameova, Adriana; Dhalla, Naranjan S

2018-01-30

Patients with diabetes mellitus have an increased risk of mortality due to cardiovascular complications. Supplementation with specific sulphur-containing amino acids is rapidly emerging as a possible therapeutic adjuvant for diabetes and associated cardiovascular complications. It is well-known that oxidative stress plays an important role in the pathogenesis of diabetes-induced cardiovascular disease, which is invariably associated with abnormal blood lipid profile, insulin resistance and other symptoms of metabolic syndrome. Cysteine and taurine are among the most common sulphur-containing amino acids and their cellular levels decline during diabetes that may contribute to the development of the cardiomyopathy. Although sulphur-containing agents exert multiple actions on cellular and subcellular functions in the heart, they also exhibit antioxidant properties and thus may exert beneficial effects in different pathophysiological conditions. It is concluded that reduction of oxidative stress by cysteine and taurine may serve as an important mechanism for the attenuation of diabetes-induced subcellular and functional abnormalities in the heart. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A brief historical perspective on the advent of brain oscillations in the biological and psychological disciplines.

PubMed

Karakaş, Sirel; Barry, Robert J

2017-04-01

We aim to review the historical evolution that has led to the study of the brain (body)-mind relationship based on brain oscillations, to outline and illustrate the principles of neuro-oscillatory dynamics using research findings. The paper addresses the relevant developments in behavioral sciences after Wundt established the science of psychology, and developments in the neurosciences after alpha and gamma oscillations were discovered by Berger and Adrian, respectively. Basic neuroscientific studies have led to a number of principles: (1) spontaneous EEG is composed of a set of oscillatory components, (2) the brain responds with oscillatory activity, (3) poststimulus oscillatory activity is a function of prestimulus activity, (4) the brain response results from a superposition of oscillatory components, (5) there are multiplicities with regard to oscillations and functions, and (6) oscillations are spatially integrated. Findings of clinical studies suggest that oscillatory responses can serve as biomarkers for neuropsychiatric disorders. However, the field of psychology is still making limited use of neuro-oscillatory dynamics for a bio-behavioral understanding of cognitive-affective processes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Billions for biodefense: federal agency biodefense funding, FY2009-FY2010.

PubMed

Franco, Crystal

2009-09-01

Since 2001, the United States government has spent substantial resources on preparing the nation against a bioterrorist attack. Earlier articles in this series analyzed civilian biodefense funding by the federal government for fiscal years (FY) 2001 through 2009. This article updates those figures with budgeted amounts for FY2010, specifically analyzing the budgets and allocations for biodefense at the Departments of Health and Human Services, Defense, Homeland Security, Agriculture, and State; the Environmental Protection Agency; and the National Science Foundation. This year's article also provides an assessment of the proportion of the biodefense budget that serves multiple programmatic goals and benefits, including research into infectious disease pathogenesis and immunology, public health planning and preparedness, and disaster response efforts. The FY2010 federal budget for civilian biodefense totals $6.05 billion. Of that total, $4.96 billion is budgeted for programs that serve multiple goals and provide manifold benefits.

The role of nitric oxide in melanoma.

PubMed

Yarlagadda, Keerthi; Hassani, John; Foote, Isaac P; Markowitz, Joseph

2017-12-01

Nitric oxide (NO) is a small gaseous signaling molecule that mediates its effects in melanoma through free radical formation and enzymatic processes. Investigations have demonstrated multiple roles for NO in melanoma pathology via immune surveillance, apoptosis, angiogenesis, melanogenesis, and on the melanoma cell itself. In general, elevated levels of NO prognosticate a poor outcome for melanoma patients. However, there are processes where the relative concentration of NO in different environments may also serve to limit melanoma proliferation. This review serves to outline the roles of NO in melanoma development and proliferation. As demonstrated by multiple in vivo murine models and observations from human tissue, NO may promote melanoma formation and proliferation through its interaction via inhibitory immune cells, inhibition of apoptosis, stimulation of pro-tumorigenic cytokines, activation of tumor associated macrophages, alteration of angiogenic processes, and stimulation of melanoma formation itself. Copyright © 2017 Elsevier B.V. All rights reserved.

Limiting the public cost of stationary battery deployment by combining applications

NASA Astrophysics Data System (ADS)

Stephan, A.; Battke, B.; Beuse, M. D.; Clausdeinken, J. H.; Schmidt, T. S.

2016-07-01

Batteries could be central to low-carbon energy systems with high shares of intermittent renewable energy sources. However, the investment attractiveness of batteries is still perceived as low, eliciting calls for policy to support deployment. Here we show how the cost of battery deployment can potentially be minimized by introducing an aspect that has been largely overlooked in policy debates and underlying analyses: the fact that a single battery can serve multiple applications. Batteries thereby can not only tap into different value streams, but also combine different risk exposures. To address this gap, we develop a techno-economic model and apply it to the case of lithium-ion batteries serving multiple stationary applications in Germany. Our results show that batteries could be attractive for investors even now if non-market barriers impeding the combination of applications were removed. The current policy debate should therefore be refocused so as to encompass the removal of such barriers.

Endovascular Skills for Trauma and Resuscitative Surgery (ESTARS) Course: Curriculum Development, Content Validation, and Program Assessment

DTIC Science & Technology

2014-01-01

fundamental endovascular training for trauma surgeons. METHODS: ESTARS 2-day course incorporated pretest / posttest examinations, precourse materials...and 17 multiple true/false items. The purpose of the test was pri- marily formative; the same items were used for pretesting and posttesting , and the... pretest served as a learning tool focusing learners on the content of importance. Mean scores were computed, treating each item as one point (multiple

Mean centering, multicollinearity, and moderators in multiple regression: The reconciliation redux.

PubMed

Iacobucci, Dawn; Schneider, Matthew J; Popovich, Deidre L; Bakamitsos, Georgios A

2017-02-01

In this article, we attempt to clarify our statements regarding the effects of mean centering. In a multiple regression with predictors A, B, and A × B (where A × B serves as an interaction term), mean centering A and B prior to computing the product term can clarify the regression coefficients (which is good) and the overall model fit R 2 will remain undisturbed (which is also good).

Dopaminergic Reward Sensitivity Can Promote Adolescent Health: A New Perspective on the Mechanism of Ventral Striatum Activation

PubMed Central

Telzer, Eva H.

2015-01-01

The prevailing view in the field of adolescent brain development is that heightened activity in the mesolimbic dopaminergic reward system serves as a liability, orienting adolescents towards risky behaviors, increasing their sensitivity to social evaluation and loss, and resulting in compromised well-being. Several findings inconsistent with this deficit view challenge the perspective that adolescent reward sensitivity largely serves as a liability and highlights the potential adaptive function that heightened striatal reactivity can serve. The goal of this review is to refine our understanding of dopaminergic reward sensitivity in adolescence. I review several studies showing that ventral striatum activation serves an adaptive function for adolescents’ health and well being relating to declines in both risk taking and depression and increases in cognitive persistence and achievement. PMID:26708774

Protein function prediction--the power of multiplicity.

PubMed

Rentzsch, Robert; Orengo, Christine A

2009-04-01

Advances in experimental and computational methods have quietly ushered in a new era in protein function annotation. This 'age of multiplicity' is marked by the notion that only the use of multiple tools, multiple evidence and considering the multiple aspects of function can give us the broad picture that 21st century biology will need to link and alter micro- and macroscopic phenotypes. It might also help us to undo past mistakes by removing errors from our databases and prevent us from producing more. On the downside, multiplicity is often confusing. We therefore systematically review methods and resources for automated protein function prediction, looking at individual (biochemical) and contextual (network) functions, respectively.

Hepatic function imaging using dynamic Gd-EOB-DTPA enhanced MRI and pharmacokinetic modeling.

PubMed

Ning, Jia; Yang, Zhiying; Xie, Sheng; Sun, Yongliang; Yuan, Chun; Chen, Huijun

2017-10-01

To determine whether pharmacokinetic modeling parameters with different output assumptions of dynamic contrast-enhanced MRI (DCE-MRI) using Gd-EOB-DTPA correlate with serum-based liver function tests, and compare the goodness of fit of the different output assumptions. A 6-min DCE-MRI protocol was performed in 38 patients. Four dual-input two-compartment models with different output assumptions and a published one-compartment model were used to calculate hepatic function parameters. The Akaike information criterion fitting error was used to evaluate the goodness of fit. Imaging-based hepatic function parameters were compared with blood chemistry using correlation with multiple comparison correction. The dual-input two-compartment model assuming venous flow equals arterial flow plus portal venous flow and no bile duct output better described the liver tissue enhancement with low fitting error and high correlation with blood chemistry. The relative uptake rate Kir derived from this model was found to be significantly correlated with direct bilirubin (r = -0.52, P = 0.015), prealbumin concentration (r = 0.58, P = 0.015), and prothrombin time (r = -0.51, P = 0.026). It is feasible to evaluate hepatic function by proper output assumptions. The relative uptake rate has the potential to serve as a biomarker of function. Magn Reson Med 78:1488-1495, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

An empirical study of rape in the context of multiple murder.

PubMed

DeLisi, Matt

2014-03-01

In recent years, multiple homicide offending has received increased research attention from criminologists; however, there is mixed evidence about the role of rape toward the perpetration of multiple murder. Drawing on criminal career data from a nonprobability sample of 618 confined male homicide offenders selected from eight U.S. states, the current study examines the role of rape as a predictor of multiple homicide offending. Bivariate analyses indicated a significant association between rape and murder charges. Multivariate path regression models indicated that rape had a significant and robust association with multiple murder. This relationship withstood the confounding effects of kidnapping, prior prison confinement, and prior murder, rape, and kidnapping. These results provide evidence that rape potentially serves as a gateway to multiple murder for some serious offenders. Suggestions for future research are proffered.

Relations between the functions of autobiographical memory and psychological wellbeing.

PubMed

Waters, Theodore E A

2014-01-01

Researchers have proposed that autobiographical memory serves three basic functions in everyday life: self-definition, social connection, and directing behaviour (e.g., Bluck, Alea, Habermas, & Rubin, 2005). However, no research has examined relations between the functions of autobiographical memory and healthy functioning (i.e., psychological wellbeing). The present research examined the relations between the self, social, and directive functions of autobiographical memory and three factors of psychological wellbeing in single and recurring autobiographical memories. A total of 103 undergraduate students were recruited and provided ratings of each function for four autobiographical memories (two single, two recurring events). Results found that individuals who use their autobiographical memories to serve self, social, and directive functions reported higher levels of Purpose and Communion and Positive Relationships, and that these relations differ slightly by event type.

Multifaceted role of lipids in Mycobacterium leprae.

PubMed

Kaur, Gurkamaljit; Kaur, Jagdeep

2017-03-01

Mycobacterium leprae must adopt a metabolic strategy and undergo various metabolic alterations upon infection to survive inside the human body for years in a dormant state. A change in lipid homeostasis upon infection is highly pronounced in Mycobacterium leprae. Lipids play an essential role in the survival and pathogenesis of mycobacteria. Lipids are present in several forms and serve multiple roles from being a source of nutrition, providing rigidity, evading the host immune response to serving as virulence factors, etc. The synthesis and degradation of lipids is a highly regulated process and is the key to future drug designing and diagnosis for mycobacteria. In the current review, an account of the distinct roles served by lipids, the mechanism of their synthesis and degradation has been elucidated.

I have my own lease-So why the service plan again? Perspectives on service planning in supportive housing.

PubMed

Choy-Brown, Mimi; Hamovitch, Emily K; Cuervo, Carolina; Stanhope, Victoria

2016-12-01

This study aimed to understand multiple stakeholder perspectives implementing a recovery-oriented approach to service planning in supportive housing programs serving people with lived experience of mental illnesses. Multiple stakeholders (N = 57) were recruited to participate in focus groups (N = 8), including 4 with tenants, 2 with service coordinators, 1 with supervisors, and 1 with leadership. Supportive housing programs were purposively sampled from a recovery-oriented organization serving 1,500 people annually. Stakeholders' experiences with service planning and implementing a recovery-oriented approach to service planning were explored. The authors conducted inductive thematic analyses combined with a conceptual matrix, which yielded themes across and within multiple stakeholder focus groups. Three themes emerged: (a) an institutional reminder-service planning experiences elicited negative emotions and served to remind people of experiences in institutional settings, (b) one-size-fits-all service planning-stakeholders perceived the use of quality assurance tools within the planning process as rigid to others' interests beyond their own, and (c) rules and regulations-reconciling funder requirements (e.g., completion dates) while also tailoring services to tenants' particular situations challenged providers. Even in a recovery-oriented organization, findings suggest that service planning in supportive housing has limitations in responding to each tenant's iterative recovery process. Further, in this context where people can make their home, stakeholders questioned whether the very presence of ongoing service planning activities is problematic. However, tenant-service coordinator relationships predicated on mutual respect and esteem overcame some service planning limitations. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Epithelial adhesion molecules and the regulation of intestinal homeostasis during neutrophil transepithelial migration

PubMed Central

Sumagin, Ronen; Parkos, Charles A

2014-01-01

Epithelial adhesion molecules play essential roles in regulating cellular function and maintaining mucosal tissue homeostasis. Some form epithelial junctional complexes to provide structural support for epithelial monolayers and act as a selectively permeable barrier separating luminal contents from the surrounding tissue. Others serve as docking structures for invading viruses and bacteria, while also regulating the immune response. They can either obstruct or serve as footholds for the immune cells recruited to mucosal surfaces. Currently, it is well appreciated that adhesion molecules collectively serve as environmental cue sensors and trigger signaling events to regulate epithelial function through their association with the cell cytoskeleton and various intracellular adapter proteins. Immune cells, particularly neutrophils (PMN) during transepithelial migration (TEM), can modulate adhesion molecule expression, conformation, and distribution, significantly impacting epithelial function and tissue homeostasis. This review discusses the roles of key intestinal epithelial adhesion molecules in regulating PMN trafficking and outlines the potential consequences on epithelial function. PMID:25838976

Red trap colour of the carnivorous plant Drosera rotundifolia does not serve a prey attraction or camouflage function

PubMed Central

Foot, G.; Rice, S. P.; Millett, J.

2014-01-01

The traps of many carnivorous plants are red in colour. This has been widely hypothesized to serve a prey attraction function; colour has also been hypothesized to function as camouflage, preventing prey avoidance. We tested these two hypotheses in situ for the carnivorous plant Drosera rotundifolia. We conducted three separate studies: (i) prey attraction to artificial traps to isolate the influence of colour; (ii) prey attraction to artificial traps on artificial backgrounds to control the degree of contrast and (iii) observation of prey capture by D. rotundifolia to determine the effects of colour on prey capture. Prey were not attracted to green traps and were deterred from red traps. There was no evidence that camouflaged traps caught more prey. For D. rotundifolia, there was a relationship between trap colour and prey capture. However, trap colour may be confounded with other leaf traits. Thus, we conclude that for D. rotundifolia, red trap colour does not serve a prey attraction or camouflage function. PMID:24740904

Red trap colour of the carnivorous plant Drosera rotundifolia does not serve a prey attraction or camouflage function.

PubMed

Foot, G; Rice, S P; Millett, J

2014-01-01

The traps of many carnivorous plants are red in colour. This has been widely hypothesized to serve a prey attraction function; colour has also been hypothesized to function as camouflage, preventing prey avoidance. We tested these two hypotheses in situ for the carnivorous plant Drosera rotundifolia. We conducted three separate studies: (i) prey attraction to artificial traps to isolate the influence of colour; (ii) prey attraction to artificial traps on artificial backgrounds to control the degree of contrast and (iii) observation of prey capture by D. rotundifolia to determine the effects of colour on prey capture. Prey were not attracted to green traps and were deterred from red traps. There was no evidence that camouflaged traps caught more prey. For D. rotundifolia, there was a relationship between trap colour and prey capture. However, trap colour may be confounded with other leaf traits. Thus, we conclude that for D. rotundifolia, red trap colour does not serve a prey attraction or camouflage function.

Measurement of the multiple-muon charge ratio in the MINOS Far Detector

DOE PAGES

Adamson, P.; Anghel, I.; Aurisano, A.; ...

2016-03-30

The charge ratio, R μ = N μ+/N μ-, for cosmogenic multiple-muon events observed at an underground depth of 2070 mwe has been measured using the magnetized MINOS Far Detector. The multiple-muon events, recorded nearly continuously from August 2003 until April 2012, comprise two independent data sets imaged with opposite magnetic field polarities, the comparison of which allows the systematic uncertainties of the measurement to be minimized. The multiple-muon charge ratio is determined to be R μ = 1.104±0.006(stat)more » $$+0.009\\atop{-0.010}$$(syst). As a result, this measurement complements previous determinations of single-muon and multiple-muon charge ratios at underground sites and serves to constrain models of cosmic-ray interactions at TeV energies.« less

Toward standardized reporting for a cohort study on functioning: The Swiss Spinal Cord Injury Cohort Study.

PubMed

Prodinger, Birgit; Ballert, Carolina S; Brach, Mirjam; Brinkhof, Martin W G; Cieza, Alarcos; Hug, Kerstin; Jordan, Xavier; Post, Marcel W M; Scheel-Sailer, Anke; Schubert, Martin; Tennant, Alan; Stucki, Gerold

2016-02-01

Functioning is an important outcome to measure in cohort studies. Clear and operational outcomes are needed to judge the quality of a cohort study. This paper outlines guiding principles for reporting functioning in cohort studies and addresses some outstanding issues. Principles of how to standardize reporting of data from a cohort study on functioning, by deriving scores that are most useful for further statistical analysis and reporting, are outlined. The Swiss Spinal Cord Injury Cohort Study Community Survey serves as a case in point to provide a practical application of these principles. Development of reporting scores must be conceptually coherent and metrically sound. The International Classification of Functioning, Disability and Health (ICF) can serve as the frame of reference for this, with its categories serving as reference units for reporting. To derive a score for further statistical analysis and reporting, items measuring a single latent trait must be invariant across groups. The Rasch measurement model is well suited to test these assumptions. Our approach is a valuable guide for researchers and clinicians, as it fosters comparability of data, strengthens the comprehensiveness of scope, and provides invariant, interval-scaled data for further statistical analyses of functioning.

WATERSHED BASED SURVEY DESIGNS

EPA Science Inventory

The development of watershed-based design and assessment tools will help to serve the multiple goals for water quality monitoring required under the Clean Water Act, including assessment of regional condition to meet Section 305(b), identification of impaired water bodies or wate...

WATERSHED-BASED SURVEY DESIGNS

EPA Science Inventory

Water-based sampling design and assessment tools help serve the multiple goals for water quality monitoring required under the Clean Water Act, including assessment of regional conditions to meet Section 305(b), identification if impaired water bodies or watersheds to meet Sectio...

North Cascades Stehekin Valley Vehicle Decision Document.

DOT National Transportation Integrated Search

2007-08-31

This document serves as technical substantiation in support of a procurement for a fleet of vehicles to be used to operate a scheduled shuttle operation with multiple stops at North Cascades National Park Service Complex (NOCA), in the Stehekin Valle...

A latent variable approach to study gene-environment interactions in the presence of multiple correlated exposures.

PubMed

Sánchez, Brisa N; Kang, Shan; Mukherjee, Bhramar

2012-06-01

Many existing cohort studies initially designed to investigate disease risk as a function of environmental exposures have collected genomic data in recent years with the objective of testing for gene-environment interaction (G × E) effects. In environmental epidemiology, interest in G × E arises primarily after a significant effect of the environmental exposure has been documented. Cohort studies often collect rich exposure data; as a result, assessing G × E effects in the presence of multiple exposure markers further increases the burden of multiple testing, an issue already present in both genetic and environment health studies. Latent variable (LV) models have been used in environmental epidemiology to reduce dimensionality of the exposure data, gain power by reducing multiplicity issues via condensing exposure data, and avoid collinearity problems due to presence of multiple correlated exposures. We extend the LV framework to characterize gene-environment interaction in presence of multiple correlated exposures and genotype categories. Further, similar to what has been done in case-control G × E studies, we use the assumption of gene-environment (G-E) independence to boost the power of tests for interaction. The consequences of making this assumption, or the issue of how to explicitly model G-E association has not been previously investigated in LV models. We postulate a hierarchy of assumptions about the LV model regarding the different forms of G-E dependence and show that making such assumptions may influence inferential results on the G, E, and G × E parameters. We implement a class of shrinkage estimators to data adaptively trade-off between the most restrictive to most flexible form of G-E dependence assumption and note that such class of compromise estimators can serve as a benchmark of model adequacy in LV models. We demonstrate the methods with an example from the Early Life Exposures in Mexico City to Neuro-Toxicants Study of lead exposure, iron metabolism genes, and birth weight. © 2011, The International Biometric Society.

Automated hierarchical classification of protein domain subfamilies based on functionally-divergent residue signatures

PubMed Central

2012-01-01

Background The NCBI Conserved Domain Database (CDD) consists of a collection of multiple sequence alignments of protein domains that are at various stages of being manually curated into evolutionary hierarchies based on conserved and divergent sequence and structural features. These domain models are annotated to provide insights into the relationships between sequence, structure and function via web-based BLAST searches. Results Here we automate the generation of conserved domain (CD) hierarchies using a combination of heuristic and Markov chain Monte Carlo (MCMC) sampling procedures and starting from a (typically very large) multiple sequence alignment. This procedure relies on statistical criteria to define each hierarchy based on the conserved and divergent sequence patterns associated with protein functional-specialization. At the same time this facilitates the sequence and structural annotation of residues that are functionally important. These statistical criteria also provide a means to objectively assess the quality of CD hierarchies, a non-trivial task considering that the protein subgroups are often very distantly related—a situation in which standard phylogenetic methods can be unreliable. Our aim here is to automatically generate (typically sub-optimal) hierarchies that, based on statistical criteria and visual comparisons, are comparable to manually curated hierarchies; this serves as the first step toward the ultimate goal of obtaining optimal hierarchical classifications. A plot of runtimes for the most time-intensive (non-parallelizable) part of the algorithm indicates a nearly linear time complexity so that, even for the extremely large Rossmann fold protein class, results were obtained in about a day. Conclusions This approach automates the rapid creation of protein domain hierarchies and thus will eliminate one of the most time consuming aspects of conserved domain database curation. At the same time, it also facilitates protein domain annotation by identifying those pattern residues that most distinguish each protein domain subgroup from other related subgroups. PMID:22726767

Functionalized graphene oxide serves as a novel vaccine nano-adjuvant for robust stimulation of cellular immunity

NASA Astrophysics Data System (ADS)

Xu, Ligeng; Xiang, Jian; Liu, Ye; Xu, Jun; Luo, Yinchan; Feng, Liangzhu; Liu, Zhuang; Peng, Rui

2016-02-01

Benefiting from their unique physicochemical properties, graphene derivatives have attracted great attention in biomedicine. In this study, we carefully engineered graphene oxide (GO) as a vaccine adjuvant for immunotherapy using urease B (Ure B) as the model antigen. Ure B is a specific antigen for Helicobacter pylori, which is a class I carcinogen for gastric cancer. Polyethylene glycol (PEG) and various types of polyethylenimine (PEI) were used as coating polymers. Compared with single-polymer modified GOs (GO-PEG and GO-PEI), certain dual-polymer modified GOs (GO-PEG-PEI) can act as a positive modulator to promote the maturation of dendritic cells (DCs) and enhance their cytokine secretion through the activation of multiple toll-like receptor (TLR) pathways while showing low toxicity. Moreover, this GO-PEG-PEI can serve as an antigen carrier to effectively shuttle antigens into DCs. These two advantages enable GO-PEG-PEI to serve as a novel vaccine adjuvant. In the subsequent in vivo experiments, compared with free Ure B and clinically used aluminum-adjuvant-based vaccine (Alum-Ure B), GO-PEG-PEI-Ure B induces stronger cellular immunity via intradermal administration, suggesting promising applications in cancer immunotherapy. Our work not only presents a novel, highly effective GO-based vaccine nano-adjuvant, but also highlights the critical roles of surface chemistry for the rational design of nano-adjuvants.Benefiting from their unique physicochemical properties, graphene derivatives have attracted great attention in biomedicine. In this study, we carefully engineered graphene oxide (GO) as a vaccine adjuvant for immunotherapy using urease B (Ure B) as the model antigen. Ure B is a specific antigen for Helicobacter pylori, which is a class I carcinogen for gastric cancer. Polyethylene glycol (PEG) and various types of polyethylenimine (PEI) were used as coating polymers. Compared with single-polymer modified GOs (GO-PEG and GO-PEI), certain dual-polymer modified GOs (GO-PEG-PEI) can act as a positive modulator to promote the maturation of dendritic cells (DCs) and enhance their cytokine secretion through the activation of multiple toll-like receptor (TLR) pathways while showing low toxicity. Moreover, this GO-PEG-PEI can serve as an antigen carrier to effectively shuttle antigens into DCs. These two advantages enable GO-PEG-PEI to serve as a novel vaccine adjuvant. In the subsequent in vivo experiments, compared with free Ure B and clinically used aluminum-adjuvant-based vaccine (Alum-Ure B), GO-PEG-PEI-Ure B induces stronger cellular immunity via intradermal administration, suggesting promising applications in cancer immunotherapy. Our work not only presents a novel, highly effective GO-based vaccine nano-adjuvant, but also highlights the critical roles of surface chemistry for the rational design of nano-adjuvants. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr09208f

The Scientific Filesystem

PubMed Central

Sochat, Vanessa

2018-01-01

Abstract Background Here, we present the Scientific Filesystem (SCIF), an organizational format that supports exposure of executables and metadata for discoverability of scientific applications. The format includes a known filesystem structure, a definition for a set of environment variables describing it, and functions for generation of the variables and interaction with the libraries, metadata, and executables located within. SCIF makes it easy to expose metadata, multiple environments, installation steps, files, and entry points to render scientific applications consistent, modular, and discoverable. A SCIF can be installed on a traditional host or in a container technology such as Docker or Singularity. We start by reviewing the background and rationale for the SCIF, followed by an overview of the specification and the different levels of internal modules (“apps”) that the organizational format affords. Finally, we demonstrate that SCIF is useful by implementing and discussing several use cases that improve user interaction and understanding of scientific applications. SCIF is released along with a client and integration in the Singularity 2.4 software to quickly install and interact with SCIF. When used inside of a reproducible container, a SCIF is a recipe for reproducibility and introspection of the functions and users that it serves. Results We use SCIF to evaluate container software, provide metrics, serve scientific workflows, and execute a primary function under different contexts. To encourage collaboration and sharing of applications, we developed tools along with an open source, version-controlled, tested, and programmatically accessible web infrastructure. SCIF and associated resources are available at https://sci-f.github.io. The ease of using SCIF, especially in the context of containers, offers promise for scientists’ work to be self-documenting and programatically parseable for maximum reproducibility. SCIF opens up an abstraction from underlying programming languages and packaging logic to work with scientific applications, opening up new opportunities for scientific software development. PMID:29718213

From policy to practice: Addressing snack quality, consumption, and price in afterschool programs

PubMed Central

Beets, Michael W.; Tilley, Falon; Weaver, Robert G.; Turner-McGrievy, Brie; Moore, Justin B.; Webster, Collin

2013-01-01

Objective To evaluate a community partnership between afterschool programs (ASPs) and grocery store to provide discounted pricing on snacks to meet the National Afterschool Association Healthy Eating Standards that call for serving a fruit/vegetable (FV) daily, while eliminating sugar-based foods/beverages. Methods A single-group, pre- with multiple post-test design (Spring 2011–2013) in four large-scale ASPs serving 500 children/day was used along with direct observation of snacks served, consumed, and cost. Results At baseline FV, sugar-sweetened beverages (SSB), and desserts were served 0.1±0.5, 1.7±2.0, and 2.0±1.4 days/wk. By Spring 2013, FV increased to 5.0±0.0 days/wk, while SSB and desserts were eliminated. Eighty-four percent of children consumed the fruit; 59% consumed the vegetables. Cost associated with purchasing snacks resulted in a $2,000–$3,000 savings over a standard 180day school year. Conclusions and Implications This partnership can serve as a model for successfully meeting nutrition policies established for ASP snacks. PMID:24268299

Full-Body Gaze Control Mechanisms Elicited During Locomotion: Effects Of VOR Adaptation

NASA Technical Reports Server (NTRS)

Mulavara, A. P.; Houser, J.; Peters, B.; Miller, C.; Richards, J.; Marshburn, A.; Brady, R.; Cohen, H.; Bloomberg, J. J.

2004-01-01

Control of locomotion requires precise interaction between several sensorimotor subsystems. During locomotion the performer must satisfy two performance criteria: maintain stable forward translation and to stabilize gaze (McDonald, et al., 1997). Precise coordination demands integration of multiple sensorimotor subsystems for fulfilling both criteria. In order to test the general hypothesis that the whole body can serve as an integrated gaze stabilization system, we have previously investigated how the multiple, interdependent full-body sensorimotor subsystems respond to changes in gaze stabilization task constraints during locomotion (Mulavara and Bloomberg, 2003). The results suggest that the full body contributes to gaze stabilization during locomotion, and that its different functional elements respond to changes in visual task constraints. The goal of this study was to determine how the multiple, interdependent, full-body sensorimotor subsystems aiding gaze stabilization during locomotion are functionally coordinated after the vestibulo-ocular reflex (VOR) gain has been altered. We investigated the potential of adaptive remodeling of the full-body gaze control system following exposure to visual-vestibular conflict known to adaptively reduce the VOR. Subjects (n=14) walked (6.4 km/h) on the treadmill before and after they were exposed to 0.5X manifying lenses worn for 30 minutes during self-generated sinusoidal vertical head rotations performed while seated. In this study we measured: temporal parameters of gait, full body sagittal plane segmental kinematics of the head, trunk, thigh, shank and foot, accelerations along the vertical axis at the head and the shank, and the vertical forces acting on the support surface. Results indicate that, following exposure to the 0.5X minifying lenses, there was a significant increase in the duration of stance and stride times, alteration in the amplitude of head movement with respect to space and a significant increase in the amount of knee flexion during the initial stance phase of the gait cycle. This study provides further evidence that the full body contributes to gaze stabilization during locomotion, and that different functional elements are responsive to changes in visual task constraints and are subject to adaptive alteration following exposure to visual-vestibular conflict.

Functional Innovations and the Conquest of the Oceans by Acanthomorph Fishes.

PubMed

Wainwright, Peter C; Longo, Sarah J

2017-06-05

The world's oceans are home to many fantastic creatures, including about 16,000 species of actinopterygian, or ray-finned, fishes. Notably, 85% of marine fish species come from a single actinopterygian subgroup, the acanthomorph or spiny-rayed fishes. Here, we review eight functional innovations found in marine acanthomorphs that have been instrumental in the adaptive radiation of this group in the marine realm. Jaw protrusion substantially enhances the suction feeding mechanism found in all fish. Fin spines serve as a major deterrent to predators and enhance the locomotor function of fins. Pharyngognathy, a specialization of the second pair of jaws in the pharynx, enhances the ability of fishes to process hard and tough prey. Endothermy allows fishes to function at high levels of physiological performance in cold waters and facilitates frequent movement across strong thermal gradients found in the open ocean. Intramandibular joints enhance feeding for fishes that bite and scrape prey attached to hard surfaces. Antifreeze proteins prevent ice crystal growth in extracellular fluids, allowing fish to function in cold waters that would otherwise freeze them. Air-breathing allowed fishes at the water's edge to exploit terrestrial habitats. Finally, bioluminescence functions in communication, attracting prey and in hiding from predators, particularly for fishes of the deep ocean. All of these innovations have evolved multiple times in fishes. The frequent occurrence of convergent evolution of these complex functional novelties speaks to the persistence and potency of the selective forces in marine environments that challenge fishes and stimulate innovation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Handgrip Strength Related to Long-Term Electromyography: Application for Assessing Functional Decline in Parkinson Disease.

PubMed

Jones, Gareth R; Roland, Kaitlyn P; Neubauer, Noelannah A; Jakobi, Jennifer M

2017-02-01

To determine which clinical measures of physical function (ie, gait, balance, and grip strength) best represent long-term electromyography in persons with Parkinson disease (PD) compared with those without PD. Cross-sectional study. Local community. A sample (N=37) of men and women with PD (n=23) and those without PD (n=14), living independently at home, older than 50 years of age, from the local community. Not applicable. Measures of gait, balance, and grip strength were completed, and electromyography was examined in biceps brachii, triceps brachii, vastus lateralis, and biceps femoris during a 6.5-hour day. Muscle activity was quantified through burst in electromyography (>2% of the normalized maximum voluntary exertion with a continuous activity period of >0.1s). Stepwise multiple regression models were used to determine the proportion of variance in burst characteristics explained by clinical measures of physical function in PD. Grip strength was the best predictor of muscle activity in persons with PD (R 2 =.17-.33; P<.04), whereas gait characteristics explained muscle activity in healthy controls (R 2 =.40-.82; P<.04). Grip strength could serve as an effective clinical assessment tool to determine changes in muscle activity, which is a precursor to functional loss in persons with PD. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Light-Harvesting Complex Protein LHCBM9 Is Critical for Photosystem II Activity and Hydrogen Production in Chlamydomonas reinhardtii[C][W

PubMed Central

Grewe, Sabrina; Ballottari, Matteo; Alcocer, Marcelo; D’Andrea, Cosimo; Blifernez-Klassen, Olga; Hankamer, Ben; Mussgnug, Jan H.; Bassi, Roberto; Kruse, Olaf

2014-01-01

Photosynthetic organisms developed multiple strategies for balancing light-harvesting versus intracellular energy utilization to survive ever-changing environmental conditions. The light-harvesting complex (LHC) protein family is of paramount importance for this function and can form light-harvesting pigment protein complexes. In this work, we describe detailed analyses of the photosystem II (PSII) LHC protein LHCBM9 of the microalga Chlamydomonas reinhardtii in terms of expression kinetics, localization, and function. In contrast to most LHC members described before, LHCBM9 expression was determined to be very low during standard cell cultivation but strongly increased as a response to specific stress conditions, e.g., when nutrient availability was limited. LHCBM9 was localized as part of PSII supercomplexes but was not found in association with photosystem I complexes. Knockdown cell lines with 50 to 70% reduced amounts of LHCBM9 showed reduced photosynthetic activity upon illumination and severe perturbation of hydrogen production activity. Functional analysis, performed on isolated PSII supercomplexes and recombinant LHCBM9 proteins, demonstrated that presence of LHCBM9 resulted in faster chlorophyll fluorescence decay and reduced production of singlet oxygen, indicating upgraded photoprotection. We conclude that LHCBM9 has a special role within the family of LHCII proteins and serves an important protective function during stress conditions by promoting efficient light energy dissipation and stabilizing PSII supercomplexes. PMID:24706511

Biomarkers of selenium status

USDA-ARS?s Scientific Manuscript database

The essential trace element selenium (Se) has multiple biological activities, which depend on the level of Se intake. Relatively low Se intakes determine the expression of selenoenzymes in which it serves as an essential constituent. Higher intakes have been shown to have anti-tumorigenic potentia...

Helping agencies improve their planning analysis techniques.

DOT National Transportation Integrated Search

2011-11-18

This report summarizes the results of a peer review of the AZTDM. The peer review was : supported by the Travel Model Improvement Program (TMIP), which is sponsored by FHWA. : The peer review of a travel model can serve multiple purposes, including i...

Linking Transportation System Improvements To New Business Development In Eastern Washington

DOT National Transportation Integrated Search

1994-02-01

An extensive highway, rail, barge and air system serves the transportation needs of eastern Washington's businesses and industries. Future public investment in this system will be guided by multiple criteria ranging from improved public safety to enh...

Multiple 60-Minute Massages per Week Offer Relief for Chronic Neck Pain

MedlinePlus

... 4-week wait list, which served as the control group. Therapists used a wide range of massage techniques ... provide significant benefits compared with the wait-list control group. However, beneficial effects of 60-minute massages increased ...

Instructing cells with programmable peptide DNA hybrids

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

Freeman, Ronit; Stephanopoulos, Nicholas; Alvarez, Zaida

The native extracellular matrix is a space in which signals can be displayed dynamically and reversibly, positioned with nanoscale precision, and combined synergistically to control cell function. Here we describe a molecular system that can be programmed to control these three characteristics. In this approach we immobilize peptide-DNA (P-DNA) molecules on a surface through complementary DNA tethers directing cells to adhere and spread reversibly over multiple cycles. The DNA can also serve as a molecular ruler to control the distance-dependent synergy between two peptides. Finally, we use two orthogonal DNA handles to regulate two different bioactive signals, with the abilitymore » to independently up- or downregulate each over time. This enabled us to discover that neural stem cells, derived from the murine spinal cord and organized as neurospheres, can be triggered to migrate out in response to an exogenous signal but then regroup into a neurosphere as the signal is removed.« less

Stills, status, stocks and science: the laboratories at Apothecaries' Hall in the nineteenth century.

PubMed

Simmons, Anna

2014-05-01

This paper focuses on one site of chemistry that served multiple functions over its lifetime and played a pivotal role in the development of British pharmaceutical manufacturing. At the beginning of the nineteenth century, the Society of Apothecaries' premises in Blackfriars housed the largest pharmaceutical manufacturing laboratories in London and supplied drugs for use throughout the British Empire. Under the guidance of William Brande, the laboratories developed as sites of teaching, research and consultancy, activities which shaped the Society's public image and enhanced its commercial, regulatory and professional roles. However, as competition from other pharmaceutical firms increased, inherent contradictions in the Society's various remits, combined with its conservative approach to business, meant that there was no clear direction for the laboratories' development. In an era of growing specialisation, this multifunctional site became increasingly outdated by the end of the nineteenth century.

The Nature of Self-Regulatory Fatigue and "Ego Depletion": Lessons From Physical Fatigue.

PubMed

Evans, Daniel R; Boggero, Ian A; Segerstrom, Suzanne C

2015-07-30

Self-regulation requires overriding a dominant response and leads to temporary self-regulatory fatigue. Existing theories of the nature and causes of self-regulatory fatigue highlight physiological substrates such as glucose, or psychological processes such as motivation, but these explanations are incomplete on their own. Historically, theories of physical fatigue demonstrate a similar pattern of useful but incomplete explanations, as recent views of physical fatigue emphasize the roles of both physiological and psychological factors. In addition to accounting for multiple inputs, these newer views also explain how fatigue can occur even in the presence of sufficient resources. Examining these newer theories of physical fatigue can serve as a foundation on which to build a more comprehensive understanding of self-regulatory fatigue that integrates possible neurobiological underpinnings of physical and self-regulatory fatigue, and suggests the possible function of self-regulatory fatigue. © 2015 by the Society for Personality and Social Psychology, Inc.

METHODOLOGICAL PLURALISM AND MIXED METHODOLOGY TO STRENGTHEN COMMUNITY PSYCHOLOGY RESEARCH: AN EXAMPLE FROM OXFORD HOUSE

PubMed Central

May, Emily M.; Hunter, Bronwyn A.; Jason, Leonard A.

2017-01-01

This article evaluates how a plurality of research methods has served a research program that has functioned in a much-needed area of research: the role of housing and recovery residences in addiction recovery. The review focuses on one mutually supportive recovery residence model, called Oxford House, which represents more than 1,700 democratic, self-governing residences. To date, there has been no comprehensive evaluation of the research methods used with Oxford House or any other recovery residence. In this article, research methods, including study designs and data analyses, are summarized for 114 peer-reviewed empirical studies that included data on Oxford Houses or Oxford House residents. This review of a pluralistic research program can inform community researchers about the value of recovery residences, the many ways in which recovery residences may be assessed, and the benefits of using multiple methods. Implications for future recovery residence research are discussed. PMID:28839344

Syntheses and Functionalizations of Porphyrin Macrocycles

PubMed Central

Vicente, Maria da G.H.; Smith, Kevin M.

2014-01-01

Porphyrin macrocycles have been the subject of intense study in the last century because they are widely distributed in nature, usually as metal complexes of either iron or magnesium. As such, they serve as the prosthetic groups in a wide variety of primary metabolites, such as hemoglobins, myoglobins, cytochromes, catalases, peroxidases, chlorophylls, and bacteriochlorophylls; these compounds have multiple applications in materials science, biology and medicine. This article describes current methodology for preparation of simple, symmetrical model porphyrins, as well as more complex protocols for preparation of unsymmetrically substituted porphyrin macrocycles similar to those found in nature. The basic chemical reactivity of porphyrins and metalloporphyrin is also described, including electrophilic and nucleophilic reactions, oxidations, reductions, and metal-mediated cross-coupling reactions. Using the synthetic approaches and reactivity profiles presented, eventually almost any substituted porphyrin system can be prepared for applications in a variety of areas, including in catalysis, electron transport, model biological systems and therapeutics. PMID:25484638

Mood disorders: A potential link between ghrelin and leptin on human body?

PubMed

Zarouna, Stalo; Wozniak, Greta; Papachristou, Anastasia Ioannis

2015-05-20

Leptin and ghrelin are two hormones associated with multiple physiological functions, especially energy balance. Leptin is an adipocyte-secreted hormone discovered in 1950 and ghrelin which was found in 1999, is a peptide hormone produced and secreted in the stomach. A number of previous studies showed that these hormones could be associated with different types of mood disorders. The results of previous studies, nevertheless, are confounded by diverse sample selection and different methodologies. A search for related articles in the PubMed database was attempted. The search covered studies, reports, reviews and editorials published in the last ten years. Older references served as auxiliary sources for comparison purposes. However, due to the different results of the studies, there is a need for more investigation in order to establish the exact biochemical mechanisms that are responsible for these diseases and ghrelin's and leptin's effects on mood.

Youth-Adult Partnerships and Youth Identity Style.

PubMed

Ramey, Heather L; Rose-Krasnor, Linda; Lawford, Heather L

2017-02-01

Youth-adult partnerships (e.g., youth leading programs, participating as members of advisory boards) are a common and widely recommended practice in youth work and youth-serving program settings. Although researchers have suggested that these opportunities contribute to youth's identity development, empirical evidence is lacking. In the current study, we tested associations between identity style and degree of youth voice, collaborative youth-adult relationships, and youth's program engagement in 194 youth participating in youth-adult partnerships (M age  = 17.6, 62 % female). We found that these characteristics of youth-adult partnerships predicted higher informational identity style, although only program engagement emerged as a unique predictor. Furthermore, exploratory analysis indicated that these associations were moderated by the type of organization. The findings suggest the need for more research on the multiple dimensions of youth-adult partnerships and their association with youth functioning, as well as pointing to the importance of the broader organizational context of youth-adult partnerships.

3D Printing and Assay Development for Point-of-Care Applications

NASA Astrophysics Data System (ADS)

Jagadeesh, Shreesha

Existing centralized labs do not serve patients adequately in remote areas. To enable universal timely healthcare, there is a need to develop low cost, portable systems that can diagnose multiple disease (Point-of-Care (POC) devices). Future POC diagnostics can be more multi-functional if medical device vendors can develop interoperability standards. This thesis developed the following medical diagnostic modules: Plasma from 25 microl blood was extracted through a filter membrane to demonstrate a 3D printed sample preparation module. Sepsis biomarker, C - reactive protein, was quantified through adsorption on nylon beads to demonstrate bead-based assay suitable for 3D printed disposable cartridge module. Finally, a modular fluorescent detection kit was built using 3D printed parts to detect CD4 cells in a disposable cartridge from ChipCare Corp. Due to the modularity enabled by 3D printing technique, the developed units can be easily adapted to detect other diseases.

Structure-guided development of dual β2 adrenergic/dopamine D2 receptor agonists.

PubMed

Weichert, Dietmar; Stanek, Markus; Hübner, Harald; Gmeiner, Peter

2016-06-15

Aiming to discover dual-acting β2 adrenergic/dopamine D2 receptor ligands, a structure-guided approach for the evolution of GPCR agonists that address multiple targets was elaborated. Starting from GPCR crystal structures, we describe the design, synthesis and biological investigation of a defined set of compounds leading to the identification of the benzoxazinone (R)-3, which shows agonist properties at the adrenergic β2 receptor and substantial G protein-promoted activation at the D2 receptor. This directed approach yielded molecular probes with tuned dual activity. The congener desOH-3 devoid of the benzylic hydroxyl function was shown to be a β2 adrenergic antagonist/D2 receptor agonist with Ki values in the low nanomolar range. The compounds may serve as a promising starting point for the investigation and treatment of neurological disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

A large dataset of protein dynamics in the mammalian heart proteome

PubMed Central

Lau, Edward; Cao, Quan; Ng, Dominic C.M.; Bleakley, Brian J.; Dincer, T. Umut; Bot, Brian M.; Wang, Ding; Liem, David A.; Lam, Maggie P.Y.; Ge, Junbo; Ping, Peipei

2016-01-01

Protein stability is a major regulatory principle of protein function and cellular homeostasis. Despite limited understanding on mechanisms, disruption of protein turnover is widely implicated in diverse pathologies from heart failure to neurodegenerations. Information on global protein dynamics therefore has the potential to expand the depth and scope of disease phenotyping and therapeutic strategies. Using an integrated platform of metabolic labeling, high-resolution mass spectrometry and computational analysis, we report here a comprehensive dataset of the in vivo half-life of 3,228 and the expression of 8,064 cardiac proteins, quantified under healthy and hypertrophic conditions across six mouse genetic strains commonly employed in biomedical research. We anticipate these data will aid in understanding key mitochondrial and metabolic pathways in heart diseases, and further serve as a reference for methodology development in dynamics studies in multiple organ systems. PMID:26977904

METHODOLOGICAL PLURALISM AND MIXED METHODOLOGY TO STRENGTHEN COMMUNITY PSYCHOLOGY RESEARCH: AN EXAMPLE FROM OXFORD HOUSE.

PubMed

May, Emily M; Hunter, Bronwyn A; Jason, Leonard A

2017-01-01

This article evaluates how a plurality of research methods has served a research program that has functioned in a much-needed area of research: the role of housing and recovery residences in addiction recovery. The review focuses on one mutually supportive recovery residence model, called Oxford House, which represents more than 1,700 democratic, self-governing residences. To date, there has been no comprehensive evaluation of the research methods used with Oxford House or any other recovery residence. In this article, research methods, including study designs and data analyses, are summarized for 114 peer-reviewed empirical studies that included data on Oxford Houses or Oxford House residents. This review of a pluralistic research program can inform community researchers about the value of recovery residences, the many ways in which recovery residences may be assessed, and the benefits of using multiple methods. Implications for future recovery residence research are discussed.

Electric Power System for High Altitude UAV Technology Survey

NASA Technical Reports Server (NTRS)

1997-01-01

Electric powertrain technologies with application to high altitude Unmanned Aerial Vehicles (UAV) are assessed. One hundred twenty five solar electric UAV configurations and missions were simulated. Synergistic design opportunities were investigated with the premise that specific benefits may be realized, for example, if a single component can serve multiple functions, such as a battery being used for energy storage as well as for a structural component of the aircraft. For each UAV mission simulation, the airframe structure, powertrain configuration (type of solar cells, energy storage options) and performance baseline (1997 or 2001) were specified. It has been found that the use of the high efficiency (multijunction) solar cells or the use of the synergistic amorphous silicon solar cell configuration yields aircraft that can accomplish the majority of the missions of interest for any latitude between 0 deg and 55 deg, hence, a single versatile aircraft can be constructed and implemented to accomplish these missions.