Mediators and Mechanisms of Herpes Simplex Virus Entry into Ocular Cells

PubMed Central

Farooq, Asim V.; Valyi-Nagy, Tibor; Shukla, Deepak

2010-01-01

The entry of herpes simplex virus (HSV) into cells was once thought to be a general process. It is now understood that the virus is able to use multiple mechanisms for entry and spread, including the use of receptors and co-receptors that have been determined to be cell-type specific. This is certainly true for ocular cell types, which is important as the virus may use different mechanisms to gain access to multiple anatomic structures in close proximity, leading to various ocular diseases. There are some patterns that may be utilized by the virus in the eye and elsewhere, including surfing along filopodia in moving from cell to cell. There are common themes as well as intriguing differences in the entry mechanisms of HSV into ocular cells. We discuss these issues in the context of conjunctivitis, keratitis, acute retinal necrosis and other ocular diseases. PMID:20465436

Sound source localization inspired by the ears of the Ormia ochracea

NASA Astrophysics Data System (ADS)

Kuntzman, Michael L.; Hall, Neal A.

2014-07-01

The parasitoid fly Ormia ochracea has the remarkable ability to locate crickets using audible sound. This ability is, in fact, remarkable as the fly's hearing mechanism spans only 1.5 mm which is 50× smaller than the wavelength of sound emitted by the cricket. The hearing mechanism is, for all practical purposes, a point in space with no significant interaural time or level differences to draw from. It has been discovered that evolution has empowered the fly with a hearing mechanism that utilizes multiple vibration modes to amplify interaural time and level differences. Here, we present a fully integrated, man-made mimic of the Ormia's hearing mechanism capable of replicating the remarkable sound localization ability of the special fly. A silicon-micromachined prototype is presented which uses multiple piezoelectric sensing ports to simultaneously transduce two orthogonal vibration modes of the sensing structure, thereby enabling simultaneous measurement of sound pressure and pressure gradient.

Digynic triploidy: utility and challenges of noninvasive prenatal testing

PubMed Central

Fleischer, Julie; Shenoy, Archana; Goetzinger, Katherine; Cottrell, Catherine E; Baldridge, Dustin; White, Frances V; Shinawi, Marwan

2015-01-01

Key Clinical Message Low fraction fetal DNA in noninvasive prenatal testing in the context of fetal growth restriction and multiple congenital anomalies should alert medical professionals to the possibility of digynic triploidy. Single-nucleotide polymorphism microarray can detect the parental origin of triploidy and explain its mechanism. PMID:26185638

Measuring mid-rapidity multiplicity in PHOBOS

NASA Astrophysics Data System (ADS)

Iordanova, Aneta; Back, B. B.; Baker, M. D.; Ballintijn, M.; Barton, D. S.; Betts, R. R.; Bickley, A. A.; Bindel, R.; Busza, W.; Carroll, A.; Chai, Z.; Decowski, M. P.; García, E.; Gburek, T.; George, N.; Gulbrandsen, K.; Halliwell, C.; Hamblen, J.; Hauer, M.; Henderson, C.; Hofman, D. J.; Hollis, R. S.; Holynski, R.; Holzman, B.; Iordanova, A.; Johnson, E.; Kane, J. L.; Khan, N.; Kulinich, P.; Kuo, C. M.; Lin, W. T.; Manly, S.; Mignerey, A. C.; Nouicer, R.; Olszewski, A.; Pak, R.; Reed, C.; Roland, C.; Roland, G.; Sagerer, J.; Seals, H.; Sedykh, I.; Smith, C. E.; Stankiewicz, M. A.; Steinberg, P.; Stephans, G. S. F.; Sukhanov, A.; Tonjes, M. B.; Trzupek, A.; Vale, C.; van Nieuwenhuizen, G. J.; Vaurynovich, S. S.; Verdier, R.; Veres, G. I.; Wenger, E.; Wolfs, F. L. H.; Wosiek, B.; Wozniak, K.; Wyslouch, B.; PHOBOS Collaboration

2005-01-01

Several techniques have been developed by PHOBOS for measuring the multiplicity of charged particles produced in Au + Au collisions. We will discuss one of these techniques (the 'Tracklet' method) which utilizes two-hit tracks which intersect at the reconstructed collision vertex position. The physics that comes from these measurements can give valuable insight into the underlying mechanisms of particle production over a center of mass energy range of surdSNN = 19.6 GeV to the maximum RHIC energy of surdSNN = 200 GeV.

Risk assessment and adaptive runoff utilization in water resource system considering the complex relationship among water supply, electricity generation and environment

NASA Astrophysics Data System (ADS)

Zhou, J.; Zeng, X.; Mo, L.; Chen, L.; Jiang, Z.; Feng, Z.; Yuan, L.; He, Z.

2017-12-01

Generally, the adaptive utilization and regulation of runoff in the source region of China's southwest rivers is classified as a typical multi-objective collaborative optimization problem. There are grim competitions and incidence relation in the subsystems of water supply, electricity generation and environment, which leads to a series of complex problems represented by hydrological process variation, blocked electricity output and water environment risk. Mathematically, the difficulties of multi-objective collaborative optimization focus on the description of reciprocal relationships and the establishment of evolving model of adaptive systems. Thus, based on the theory of complex systems science, this project tries to carry out the research from the following aspects: the changing trend of coupled water resource, the covariant factor and driving mechanism, the dynamic evolution law of mutual feedback dynamic process in the supply-generation-environment coupled system, the environmental response and influence mechanism of coupled mutual feedback water resource system, the relationship between leading risk factor and multiple risk based on evolutionary stability and dynamic balance, the transfer mechanism of multiple risk response with the variation of the leading risk factor, the multidimensional coupled feedback system of multiple risk assessment index system and optimized decision theory. Based on the above-mentioned research results, the dynamic method balancing the efficiency of multiple objectives in the coupled feedback system and optimized regulation model of water resources is proposed, and the adaptive scheduling mode considering the internal characteristics and external response of coupled mutual feedback system of water resource is established. In this way, the project can make a contribution to the optimal scheduling theory and methodology of water resource management under uncertainty in the source region of Southwest River.

Streptococcus pneumoniae Can Utilize Multiple Sources of Hyaluronic Acid for Growth

PubMed Central

Marion, Carolyn; Stewart, Jason M.; Tazi, Mia F.; Burnaugh, Amanda M.; Linke, Caroline M.; Woodiga, Shireen A.

2012-01-01

The mechanisms by which Streptococcus pneumoniae obtains carbohydrates for growth during airway colonization remain to be elucidated. The low concentration of free carbohydrates in the normal human airway suggests that pneumococci must utilize complex glycan structures for growth. The glycosaminoglycan hyaluronic acid is present on the apical surface of airway epithelial cells. As pneumococci express a hyaluronate lyase (Hyl) that cleaves hyaluronic acid into disaccharides, we hypothesized that during colonization pneumococci utilize the released carbohydrates for growth. Hyaluronic acid supported significant pneumococcal growth in an hyl-dependent manner. A phosphoenolpyruvate-dependent phosphotransferase system (PTS) and an unsaturated glucuronyl hydrolase (Ugl) encoded downstream of hyl are also essential for growth on hyaluronic acid. This genomic arrangement is present in several other organisms, suggesting conservation of the utilization mechanism between species. In vivo experiments support the hypothesis that S. pneumoniae utilizes hyaluronic acid as a carbon source during colonization. We also demonstrate that pneumococci can utilize the hyaluronic acid capsule of other bacterial species for growth, suggesting an alternative carbohydrate source for pneumococcal growth. Together, these data support a novel function for pneumococcal degradation of hyaluronic acid in vivo and provide mechanistic details of growth on this glycosaminoglycan. PMID:22311922

Developmental Pathways to Integrated Social Skills: The Roles of Parenting and Early Intervention

ERIC Educational Resources Information Center

Ayoub, Catherine; Vallotton, Claire D.; Mastergeorge, Ann M.

2011-01-01

Dynamic skill theory was utilized to explain the multiple mechanisms and mediating processes influencing development of self-regulatory and language skills in children at 14, 24, and 36 months of age. Relations were found between family risks, parenting-related stresses, and parent-child interactions that contribute either independently or through…

Circulating tumour DNA profiling reveals heterogeneity of EGFR inhibitor resistance mechanisms in lung cancer patients

PubMed Central

Chabon, Jacob J.; Simmons, Andrew D.; Lovejoy, Alexander F.; Esfahani, Mohammad S.; Newman, Aaron M.; Haringsma, Henry J.; Kurtz, David M.; Stehr, Henning; Scherer, Florian; Karlovich, Chris A.; Harding, Thomas C.; Durkin, Kathleen A.; Otterson, Gregory A.; Purcell, W. Thomas; Camidge, D. Ross; Goldman, Jonathan W.; Sequist, Lecia V.; Piotrowska, Zofia; Wakelee, Heather A.; Neal, Joel W.; Alizadeh, Ash A.; Diehn, Maximilian

2016-01-01

Circulating tumour DNA (ctDNA) analysis facilitates studies of tumour heterogeneity. Here we employ CAPP-Seq ctDNA analysis to study resistance mechanisms in 43 non-small cell lung cancer (NSCLC) patients treated with the third-generation epidermal growth factor receptor (EGFR) inhibitor rociletinib. We observe multiple resistance mechanisms in 46% of patients after treatment with first-line inhibitors, indicating frequent intra-patient heterogeneity. Rociletinib resistance recurrently involves MET, EGFR, PIK3CA, ERRB2, KRAS and RB1. We describe a novel EGFR L798I mutation and find that EGFR C797S, which arises in ∼33% of patients after osimertinib treatment, occurs in <3% after rociletinib. Increased MET copy number is the most frequent rociletinib resistance mechanism in this cohort and patients with multiple pre-existing mechanisms (T790M and MET) experience inferior responses. Similarly, rociletinib-resistant xenografts develop MET amplification that can be overcome with the MET inhibitor crizotinib. These results underscore the importance of tumour heterogeneity in NSCLC and the utility of ctDNA-based resistance mechanism assessment. PMID:27283993

Racial Differences in the Usage of Information Technology: Evidence from a National Physician Survey

PubMed Central

Lee, Doohee; Rutsohn, Phil

2012-01-01

Information technology (IT) is a key mechanism for improving the quality of healthcare and containing costs, but racial differences in the utilization of IT among practicing physicians are unknown. The current study, using a national physician survey (n = 6,628), investigated racial differences in the utilization of IT. White physicians and minority physicians were directly compared. We first conducted both descriptive and inferential analyses to detect the difference in IT utilization by race and then performed multiple logistic regressions to test whether race remains significant in relation to IT utilization. Results reveal racial differences in the usage of IT. Compared to their minority counterparts, white physicians underutilized a preventive service reminder system. On the other hand, white physicians favored utilizing electronic communications with patients and exchanging clinical data and images with other providers. PMID:22783155

Osthole: A Review on Its Bioactivities, Pharmacological Properties, and Potential as Alternative Medicine

PubMed Central

Zhang, Zhong-Rong; Leung, Wing Nang; Cheung, Ho Yee; Chan, Chun Wai

2015-01-01

This paper reviews the latest understanding of biological and pharmacological properties of osthole (7-methoxy-8-(3-methyl-2-butenyl)-2H-1-benzopyran-2-one), a natural product found in several medicinal plants such as Cnidium monnieri and Angelica pubescens. In vitro and in vivo experimental results have revealed that osthole demonstrates multiple pharmacological actions including neuroprotective, osteogenic, immunomodulatory, anticancer, hepatoprotective, cardiovascular protective, and antimicrobial activities. In addition, pharmacokinetic studies showed osthole uptake and utilization are fast and efficient in body. Moreover, the mechanisms of multiple pharmacological activities of osthole are very likely related to the modulatory effect on cyclic adenosine monophosphate (cAMP) and cyclic adenosine monophosphate (cGMP) level, though some mechanisms remain unclear. This review aims to summarize the pharmacological properties of osthole and give an overview of the underlying mechanisms, which showcase its potential as a multitarget alternative medicine. PMID:26246843

Structural Inheritance of the Actin Cytoskeletal Organization Determines the Body Axis in Regenerating Hydra.

PubMed

Livshits, Anton; Shani-Zerbib, Lital; Maroudas-Sacks, Yonit; Braun, Erez; Keren, Kinneret

2017-02-07

Understanding how mechanics complement bio-signaling in defining patterns during morphogenesis is an outstanding challenge. Here, we utilize the multicellular polyp Hydra to investigate the role of the actomyosin cytoskeleton in morphogenesis. We find that the supra-cellular actin fiber organization is inherited from the parent Hydra and determines the body axis in regenerating tissue segments. This form of structural inheritance is non-trivial because of the tissue folding and dynamic actin reorganization involved. We further show that the emergence of multiple body axes can be traced to discrepancies in actin fiber alignment at early stages of the regeneration process. Mechanical constraints induced by anchoring regenerating Hydra on stiff wires suppressed the emergence of multiple body axes, highlighting the importance of mechanical feedbacks in defining and stabilizing the body axis. Together, these results constitute an important step toward the development of an integrated view of morphogenesis that incorporates mechanics. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Development of a Novel Therapeutic Paradigm Utilizing a Mammary Gland-Targeted, Bin-1 Knockout Mouse Model

DTIC Science & Technology

2007-03-01

Cell. Biol. 23, 4295 (Jun, 2003). Bin1 Ablation in Mammary Gland Delays Tissue Remodeling and Drives Cancer Progression Mee Young Chang, 1...Basu A, et al. Bin1 functionally interacts with Myc in cells and inhibits cell proliferation by multiple mechanisms. Oncogene 1999;18:3564–73. 5. Pineda

The genome sequence of Bifidobacterium longum subsp. infantis reveals adaptations for milk utilization within the infant microbiome

PubMed Central

Sela, D. A.; Chapman, J.; Adeuya, A.; Kim, J. H.; Chen, F.; Whitehead, T. R.; Lapidus, A.; Rokhsar, D. S.; Lebrilla, C. B.; German, J. B.; Price, N. P.; Richardson, P. M.; Mills, D. A.

2008-01-01

Following birth, the breast-fed infant gastrointestinal tract is rapidly colonized by a microbial consortium often dominated by bifidobacteria. Accordingly, the complete genome sequence of Bifidobacterium longum subsp. infantis ATCC15697 reflects a competitive nutrient-utilization strategy targeting milk-borne molecules which lack a nutritive value to the neonate. Several chromosomal loci reflect potential adaptation to the infant host including a 43 kbp cluster encoding catabolic genes, extracellular solute binding proteins and permeases predicted to be active on milk oligosaccharides. An examination of in vivo metabolism has detected the hallmarks of milk oligosaccharide utilization via the central fermentative pathway using metabolomic and proteomic approaches. Finally, conservation of gene clusters in multiple isolates corroborates the genomic mechanism underlying milk utilization for this infant-associated phylotype. PMID:19033196

Utilizing toxicogenomic data to understand chemical mechanism of action in risk assessment

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

Wilson, Vickie S., E-mail: wilson.vickie@epa.gov; Keshava, Nagalakshmi; Hester, Susan

2013-09-15

The predominant role of toxicogenomic data in risk assessment, thus far, has been one of augmentation of more traditional in vitro and in vivo toxicology data. This article focuses on the current available examples of instances where toxicogenomic data has been evaluated in human health risk assessment (e.g., acetochlor and arsenicals) which have been limited to the application of toxicogenomic data to inform mechanism of action. This article reviews the regulatory policy backdrop and highlights important efforts to ultimately achieve regulatory acceptance. A number of research efforts on specific chemicals that were designed for risk assessment purposes have employed mechanismmore » or mode of action hypothesis testing and generating strategies. The strides made by large scale efforts to utilize toxicogenomic data in screening, testing, and risk assessment are also discussed. These efforts include both the refinement of methodologies for performing toxicogenomics studies and analysis of the resultant data sets. The current issues limiting the application of toxicogenomics to define mode or mechanism of action in risk assessment are discussed together with interrelated research needs. In summary, as chemical risk assessment moves away from a single mechanism of action approach toward a toxicity pathway-based paradigm, we envision that toxicogenomic data from multiple technologies (e.g., proteomics, metabolomics, transcriptomics, supportive RT-PCR studies) can be used in conjunction with one another to understand the complexities of multiple, and possibly interacting, pathways affected by chemicals which will impact human health risk assessment.« less

Customization of biliopancreatic limb length to modulate and sustain antidiabetic effect of gastric bypass surgery.

PubMed

Pal, A; Rhoads, D B; Tavakkoli, A

2018-02-01

Although Roux-en-Y Gastric Bypass (RYGB) remains the most effective treatment for obesity and type 2 diabetes (T2D), many patients fail to achieve remission, or relapse. Increasing intestinal limb lengths of RYGB may improve outcomes, but the mechanistic basis for this remains unclear. We hypothesize biliopancreatic (BP) limb length modulates the antidiabetic effect of RYGB. Rats underwent RYGB with a 20-cm (RYGB-20cm) or 40-cm (RYGB-40cm) BP limb and were compared with control animals. After 2 and 4 wk, portal and systemic blood was sampled during intestinal glucose infusion. Portosystemic gradient was used to calculate intestinal glucose utilization (G util ), absorption (G absorp ), and hormone secretion. Intestinal morphology and gene expression were assessed. At 2 wk, G absorp progressively decreased with increasing BP limb length; this pattern persisted at 4 wk. G util increased ≈70% in both RYGB-20cm and -40cm groups at 2 wk. At 4 wk, G util progressively increased with limb length. Furthermore, Roux limb weight, and expression of hexokinase and preproglucagon, exhibited a similar progressive increase. At 4 wk, glucagon-like peptide-1 and -2 levels were higher after RYGB-40cm, with associated increased secretion. We conclude that BP limb length modulates multiple antidiabetic mechanisms, analogous to the dose-response relationship of a drug. Early postoperatively, a longer BP limb reduces G absorp . Later, G util , Roux limb hypertrophy, hormone secretion, and hormone levels are increased with longer BP limb. Sustained high incretin levels may prevent weight regain and T2D relapse. These data provide the basis for customizing BP limb length according to patient characteristics and desired metabolic effect. NEW & NOTEWORTHY Biliopancreatic limb length in gastric bypass modulates multiple antidiabetic mechanisms, analogous to the dose-response relationship of a drug. With a longer biliopancreatic limb, Roux limb hypertrophy, increased glucose utilization, reduced glucose absorption, and sustained high incretin levels may prevent weight regain and diabetes relapse.

Multiple mechanisms enable invasive species to suppress native species.

PubMed

Bennett, Alison E; Thomsen, Meredith; Strauss, Sharon Y

2011-07-01

Invasive plants represent a significant threat to ecosystem biodiversity. To decrease the impacts of invasive species, a major scientific undertaking of the last few decades has been aimed at understanding the mechanisms that drive invasive plant success. Most studies and theories have focused on a single mechanism for predicting the success of invasive plants and therefore cannot provide insight as to the relative importance of multiple interactions in predicting invasive species' success. We examine four mechanisms that potentially contribute to the success of invasive velvetgrass Holcus lanatus: direct competition, indirect competition mediated by mammalian herbivores, interference competition via allelopathy, and indirect competition mediated by changes in the soil community. Using a combination of field and greenhouse approaches, we focus on the effects of H. lanatus on a common species in California coastal prairies, Erigeron glaucus, where the invasion is most intense. We found that H. lanatus had the strongest effects on E. glaucus via direct competition, but it also influenced the soil community in ways that feed back to negatively influence E. glaucus and other native species after H. lanatus removal. This approach provided evidence for multiple mechanisms contributing to negative effects of invasive species, and it identified when particular strategies were most likely to be important. These mechanisms can be applied to eradication of H. lanatus and conservation of California coastal prairie systems, and they illustrate the utility of an integrated set of experiments for determining the potential mechanisms of invasive species' success.

Development of a Novel Therapeutic Paradigm Utilizing a Mammary Gland-Targeted, Bin-1 Knockout Mouse Model

DTIC Science & Technology

2008-03-01

during Aging, Particularly Lung Cancer Mee Young Chang, 1 Janette Boulden, 1 Jessica B. Katz, 1 Liwei Wang, 3 Thomas J. Meyer, 2 Alejandro Peralta Soler...Bin1 functionally interacts with Myc in cells and inhibits cell proliferation by multiple mechanisms. Oncogene 1999;18:3564–73. 3. Pineda -Lucena A, Ho

Insertion device and method for accurate and repeatable target insertion

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

Gubeli, III, Joseph F.; Shinn, Michelle D.; Bevins, Michael E.

The present invention discloses a device and a method for inserting and positioning a target within a free electron laser, particle accelerator, or other such device that generates or utilizes a beam of energy or particles. The system includes a three-point registration mechanism that insures angular and translational accuracy and repeatability of positioning upon multiple insertions within the same structure.

Integrated System Design for Air Revitalization in Next Generation Crewed Spacecraft

NASA Technical Reports Server (NTRS)

Mulloth, Lila; Perry, Jay; LeVan, Douglas

2004-01-01

The capabilities of NASA's existing environmental control and life support (ECLS) system designs are inadequate for future human space initiatives that involve long-duration space voyages and interplanetary missions. This paper discusses the concept of an integrated system of CO2 removal and trace contaminant control units that utilizes novel gas separation and purification techniques and optimized thermal and mechanical design, for future spacecraft. The integration process will enhance the overall life and economics of the existing systems by eliminating multiple mechanical devices with moving parts.

Utilization of mechanical diagnosis and therapy (MDT) for the treatment of lumbar pain in the presence of known lumbar transverse process fractures: a case study

PubMed Central

Elenburg, J. L.; Foley, B. S.; Roberts, K.; Bayliss, A. J.

2016-01-01

Background Spinal fractures are typically considered a contraindication to mechanical diagnosis and therapy (MDT). Objective and importance The purpose of this case study is to illustrate how MDT was used safely and effectively to treat lumbar pain in a patient with multiple lumbar transverse process fractures. Clinical presentation The subject was a 24-year-old female with left L2-5 transverse process fractures, sustained 10 weeks prior in a pedestrian versus motor vehicle accident. Intervention (and technique) After collaboration with her physiatrist, an MDT examination revealed a presentation consistent with the lumbar derangement syndrome. Conclusion After three visits, utilizing patient generated forces with the extension principle of treatment, her pain, Oswestry disability index (ODI) score, and function all improved. PMID:27559276

Multi-output differential technologies

NASA Astrophysics Data System (ADS)

Bidare, Srinivas R.

1997-01-01

A differential is a very old and proven mechanical device that allows a single input to be split into two outputs having equal torque irrespective of the output speeds. A standard differential is capable of providing only two outputs from a single input. A recently patented multi-output differential technology known as `Plural-Output Differential' allows a single input to be split into many outputs. This new technology is the outcome of a systematic study of complex gear trains (Bidare 1992). The unique feature of a differential (equal torque at different speeds) can be applied to simplify the construction and operation of many complex mechanical devices that require equal torque's or forces at multiple outputs. It is now possible to design a mechanical hand with three or more fingers with equal torque. Since these finger are powered via a differential they are `mechanically intelligent'. A prototype device is operational and has been used to demonstrate the utility and flexibility of the design. In this paper we shall review two devices that utilize the new technology resulting in increased performance, robustness with reduced complexity and cost.

The maintenance of cooperation in multiplex networks with limited and partible resources of agents

NASA Astrophysics Data System (ADS)

Li, Zhaofeng; Shen, Bi; Jiang, Yichuan

2017-02-01

In this paper, we try to explain the maintenance of cooperation in multiplex networks with limited and partible resources of agents: defection brings larger short-term benefit and cooperative agents may become defective because of the unaffordable costs of cooperative behaviors that are performed in multiple layers simultaneously. Recent studies have identified the positive effects of multiple layers on evolutionary cooperation but generally overlook the maximum costs of agents in these synchronous games. By utilizing network effects and designing evolutionary mechanisms, cooperative behaviors become prevailing in public goods games, and agents can allocate personal resources across multiple layers. First, we generalize degree diversity into multiplex networks to improve the prospect for cooperation. Second, to prevent agents allocating all the resources into one layer, a greedy-first mechanism is proposed, in which agents prefer to add additional investments in the higher-payoff layer. It is found that greedy-first agents can perform cooperative behaviors in multiplex networks when one layer is scale-free network and degree differences between conjoint nodes increase. Our work may help to explain the emergence of cooperation in the absence of individual reputation and punishment mechanisms.

Method to Produce Flexible Ceramic Thermal Protection System Resistant to High Aeroacoustic Noise

NASA Technical Reports Server (NTRS)

Sawko, Paul M. (Inventor); Calamito, Dominic P. (Inventor); Jong, Anthony (Inventor)

1997-01-01

A method of producing a three dimensional angle interlock ceramic fiber which is stable to high aeroacoustic noise of about 170 decibels and to high temperatures of about 2500 F is disclosed. The method uses multiple separate strands of a ceramic fiber or ceramic tow suitable for weaving having multiple warp fibers and multiple fill fibers woven with a modified fly-shuttle loom or rapier shuttleless loom which has nip rolls, a modified fabric advancement mechanism and at least eight harnesses in connection with a Dobby pattern chain utilizing sufficient heddles for each warp fiber and a reed which accommodates at least 168 ends per inch. The method produces a multilayered top fabric, rib fabric and single-layered bottom fabric.

Development of a Novel Therapeutic Paradigm Utilizing a Mammary Gland-Targeted, Bin1-Knockout Mouse Model

DTIC Science & Technology

2008-07-01

Remodeling and Drives Cancer Progression Mee Young Chang, 1 Janette Boulden, 1 Erika Sutanto-Ward, 1 James B. Duhadaway, 1 Alejandro Peralta Soler, 1,2...proliferation by multiple mechanisms. Oncogene 1999;18:3564–73. 5. Pineda -Lucena A, Ho CS, Mao DY, et al. A structure- based model of the c-Myc/Bin1 protein

Deformation and Failure Mechanisms of Shape Memory Alloys

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

Daly, Samantha Hayes

2015-04-15

The goal of this research was to understand the fundamental mechanics that drive the deformation and failure of shape memory alloys (SMAs). SMAs are difficult materials to characterize because of the complex phase transformations that give rise to their unique properties, including shape memory and superelasticity. These phase transformations occur across multiple length scales (one example being the martensite-austenite twinning that underlies macroscopic strain localization) and result in a large hysteresis. In order to optimize the use of this hysteretic behavior in energy storage and damping applications, we must first have a quantitative understanding of this transformation behavior. Prior resultsmore » on shape memory alloys have been largely qualitative (i.e., mapping phase transformations through cracked oxide coatings or surface morphology). The PI developed and utilized new approaches to provide a quantitative, full-field characterization of phase transformation, conducting a comprehensive suite of experiments across multiple length scales and tying these results to theoretical and computational analysis. The research funded by this award utilized new combinations of scanning electron microscopy, diffraction, digital image correlation, and custom testing equipment and procedures to study phase transformation processes at a wide range of length scales, with a focus at small length scales with spatial resolution on the order of 1 nanometer. These experiments probe the basic connections between length scales during phase transformation. In addition to the insights gained on the fundamental mechanisms driving transformations in shape memory alloys, the unique experimental methodologies developed under this award are applicable to a wide range of solid-to-solid phase transformations and other strain localization mechanisms.« less

Multiple utility constrained multi-objective programs using Bayesian theory

NASA Astrophysics Data System (ADS)

Abbasian, Pooneh; Mahdavi-Amiri, Nezam; Fazlollahtabar, Hamed

2018-03-01

A utility function is an important tool for representing a DM's preference. We adjoin utility functions to multi-objective optimization problems. In current studies, usually one utility function is used for each objective function. Situations may arise for a goal to have multiple utility functions. Here, we consider a constrained multi-objective problem with each objective having multiple utility functions. We induce the probability of the utilities for each objective function using Bayesian theory. Illustrative examples considering dependence and independence of variables are worked through to demonstrate the usefulness of the proposed model.

The combination of energy-dependent internal adaptation mechanisms and external factors enables Listeria monocytogenes to express a strong starvation survival response during multiple-nutrient starvation.

PubMed

Lungu, Bwalya; Saldivar, Joshua C; Story, Robert; Ricke, Steven C; Johnson, Michael G

2010-05-01

The goal of this study was to characterize the starvation survival response (SSR) of a wild-type Listeria monocytogenes 10403S and an isogenic DeltasigB mutant strain during multiple-nutrient starvation conditions over 28 days. This study examined the effects of inhibitors of protein synthesis, the proton motive force, substrate level phosphorylation, and oxidative phosphorylation on the SSR of L. monocytogenes 10403S and a DeltasigB mutant during multiple-nutrient starvation. The effects of starvation buffer changes on viability were also examined. During multiple-nutrient starvation, both strains expressed a strong SSR, suggesting that L. monocytogenes possesses SigB-independent mechanism(s) for survival during multiple-nutrient starvation. Neither strain was able to express an SSR following starvation buffer changes, indicating that the nutrients/factors present in the starvation buffer could be a source of energy for cell maintenance and survival. Neither the wild-type nor the DeltasigB mutant strain was able to elicit an SSR when exposed to the protein synthesis inhibitor chloramphenicol within the first 4 h of starvation. However, both strains expressed an SSR when exposed to chloramphenicol after 6 h or more of starvation, suggesting that the majority of proteins required to elicit an effective SSR in L. monocytogenes are likely produced somewhere between 4 and 6 h of starvation. The varying SSRs of both strains to the different metabolic inhibitors under aerobic or anaerobic conditions suggested that (1) energy derived from the proton motive force is important for an effective SSR, (2) L. monocytogenes utilizes an anaerobic electron transport during multiple-nutrient starvation conditions, and (3) the glycolytic pathway is an important energy source during multiple-nutrient starvation when oxygen is available, and less important under anaerobic conditions. Collectively, the data suggest that the combination of energy-dependent internal adaptation mechanisms of cells and external nutrients/factors enables L. monocytogenes to express a strong SSR.

The opercular mouth-opening mechanism of largemouth bass functions as a 3D four-bar linkage with three degrees of freedom.

PubMed

Olsen, Aaron M; Camp, Ariel L; Brainerd, Elizabeth L

2017-12-15

The planar, one degree of freedom (1-DoF) four-bar linkage is an important model for understanding the function, performance and evolution of numerous biomechanical systems. One such system is the opercular mechanism in fishes, which is thought to function like a four-bar linkage to depress the lower jaw. While anatomical and behavioral observations suggest some form of mechanical coupling, previous attempts to model the opercular mechanism as a planar four-bar have consistently produced poor model fits relative to observed kinematics. Using newly developed, open source mechanism fitting software, we fitted multiple three-dimensional (3D) four-bar models with varying DoF to in vivo kinematics in largemouth bass to test whether the opercular mechanism functions instead as a 3D four-bar with one or more DoF. We examined link position error, link rotation error and the ratio of output to input link rotation to identify a best-fit model at two different levels of variation: for each feeding strike and across all strikes from the same individual. A 3D, 3-DoF four-bar linkage was the best-fit model for the opercular mechanism, achieving link rotational errors of less than 5%. We also found that the opercular mechanism moves with multiple degrees of freedom at the level of each strike and across multiple strikes. These results suggest that active motor control may be needed to direct the force input to the mechanism by the axial muscles and achieve a particular mouth-opening trajectory. Our results also expand the versatility of four-bar models in simulating biomechanical systems and extend their utility beyond planar or single-DoF systems. © 2017. Published by The Company of Biologists Ltd.

Host-imposed manganese starvation of invading pathogens: two routes to the same destination

PubMed Central

Morey, Jacqueline R.; McDevitt, Christopher A.; Kehl-Fie, Thomas E.

2015-01-01

During infection invading pathogens must acquire all essential nutrients, including first row transition metals, from the host. To combat invaders, the host exploits this fact and restricts the availability of these nutrients using a defense mechanism known as nutritional immunity. While iron sequestration is the most well-known aspect of this defense, recent work has revealed that the host restricts the availability of other essential elements, notably manganese, during infection. Furthermore, these studies have revealed that the host utilizes multiple strategies that extend beyond metal sequestration to prevent bacteria from obtaining these metals. This review will discuss the mechanisms by which bacteria attempt to obtain the essential first row transition metal ion manganese during infection, and the approaches utilized by the host to prevent this occurrence. In addition, this review will discuss the impact of host-imposed manganese starvation on invading bacteria. PMID:25836716

Effects of Ionizing Radiation on DNA Methylation: From Experimental Biology to Clinical Applications

PubMed Central

Miousse, Isabelle R.; Kutanzi, Kristy R.; Koturbash, Igor

2017-01-01

Purpose Ionizing radiation (IR) is a ubiquitous environmental stressor with genotoxic and epigenotoxic capabilities. Terrestrial IR, predominantly a low-linear energy transfer (LET) radiation, is being widely utilized in medicine, as well as in multiple industrial applications. Additionally, an interest in understanding the effects of high-LET irradiation is emerging due to the potential of exposure during space missions and the growing utilization of LET radiation in medicine. Conclusions In this review, we summarize the current knowledge of the effects of IR on DNA methylation, a key epigenetic mechanism regulating the expression of genetic information. We discuss global, repetitive elements and gene-specific DNA methylation in light of exposure to high and low doses of high- or low-LET IR, fractionated IR exposure, and bystander effects. Finally, we describe the mechanisms of IR-induced alterations to DNA methylation and discuss ways in which that understanding can be applied clinically, including utilization of DNA methylation as a predictor of response to radiotherapy and in the manipulation of DNA methylation patterns for tumor radiosensitization. PMID:28134023

Effects of ionizing radiation on DNA methylation: from experimental biology to clinical applications.

PubMed

Miousse, Isabelle R; Kutanzi, Kristy R; Koturbash, Igor

2017-05-01

Ionizing radiation (IR) is a ubiquitous environmental stressor with genotoxic and epigenotoxic capabilities. Terrestrial IR, predominantly a low-linear energy transfer (LET) radiation, is being widely utilized in medicine, as well as in multiple industrial applications. Additionally, an interest in understanding the effects of high-LET irradiation is emerging due to the potential of exposure during space missions and the growing utilization of high-LET radiation in medicine. In this review, we summarize the current knowledge of the effects of IR on DNA methylation, a key epigenetic mechanism regulating the expression of genetic information. We discuss global, repetitive elements and gene-specific DNA methylation in light of exposure to high and low doses of high- or low-LET IR, fractionated IR exposure, and bystander effects. Finally, we describe the mechanisms of IR-induced alterations to DNA methylation and discuss ways in which that understanding can be applied clinically, including utilization of DNA methylation as a predictor of response to radiotherapy and in the manipulation of DNA methylation patterns for tumor radiosensitization.

Opportunities to utilize traditional phenological knowledge to support adaptive management of social-ecological systems vulnerable to changes in climate and fire regimes

Treesearch

Christopher A. Armatas; Tyron J. Venn; Brooke B. McBride; Alan E. Watson; Steve J. Carver

2016-01-01

The field of adaptive management has been embraced by researchers and managers in the United States as an approach to improve natural resource stewardship in the face of uncertainty and complex environmental problems. Integrating multiple knowledge sources and feedback mechanisms is an important step in this approach. Our objective is to contribute to the...

Shock Waves Mitigation at Blunt Bodies Using Needles and Shells Against a Supersonic Flow

NASA Technical Reports Server (NTRS)

Gilinsky, M.; Blankson, I. M.; Sakharov, V. I.; Shvets, A. I.

2004-01-01

The paper contains some experimental and numerical simulation test results on cylindrical blunt body drag reduction using thin spikes or shell mounted in front of a body against a supersonic flow. Experimental tests were conducted using the Aeromechanics and Gas Dynamics Laboratory facilities at the Institute of Mechanics of Moscow State University (IMMSU). Numerical simulations utilizing NASA and IM/MSU codes were conducted at the Hampton University Fluid Mechanics and Acoustics Laboratory. The main purpose of this research is to examine the efficiency of application of multiple spikes for drag reduction and flow stability at the front of a blunt body in different flight conditions, i.e. Mach number, angle of attack, etc. The principal conclusions of these test results are: multiple spike/needle application leads to decrease of drag reduction benefits by comparison with the case of one central mounted needle at the front of a blunt body, but increase lift benefits.

Frequency and amplitude stabilization in MEMS and NEMS oscillators

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

Chen, Changyao; Lopez, Omar Daniel; Czaplewski, David A.

This invention comprises a nonlinear micro- and nano-mechanical resonator that can maintain frequency of operation and amplitude of operation for a period of time after all external power has been removed from the device. Utilizing specific nonlinear dynamics of the micromechanical resonator, mechanical energy at low frequencies can be input and stored in higher frequencies modes, thus using the multiple degrees of freedom of the resonator to extend its energy storage capacity. Furthermore, the energy stored in multiple vibrational modes can be used to maintain the resonator oscillating for a fixed period of time, even without an external power supply.more » This is the first demonstration of an "autonomous" frequency source that can maintain a constant frequency and vibrating amplitude when no external power is provided, making it ideal for applications requiring an oscillator in low power, or limited and intermittent power supplies.« less

Assessment of future crop yield and agricultural sustainable water use in north china plain using multiple crop models

NASA Astrophysics Data System (ADS)

Huang, G.

2016-12-01

Currently, studying crop-water response mechanism has become an important part in the development of new irrigation technology and optimal water allocation in water-scarce regions, which is of great significance to crop growth guidance, sustainable utilization of agricultural water, as well as the sustainable development of regional agriculture. Using multiple crop models(AquaCrop,SWAP,DNDC), this paper presents the results of simulating crop growth and agricultural water consumption of the winter-wheat and maize cropping system in north china plain. These areas are short of water resources, but generates about 23% of grain production for China. By analyzing the crop yields and the water consumption of the traditional flooding irrigation, the paper demonstrates quantitative evaluation of the potential amount of water use that can be reduced by using high-efficient irrigation approaches, such as drip irrigation. To maintain food supply and conserve water resources, the research concludes sustainable irrigation methods for the three provinces for sustainable utilization of agricultural water.

Multiple-image oscilloscope camera

DOEpatents

Yasillo, Nicholas J.

1978-01-01

An optical device for placing automatically a plurality of images at selected locations on one film comprises a stepping motor coupled to a rotating mirror and lens. A mechanical connection from the mirror controls an electronic logical system to allow rotation of the mirror to place a focused image at the desired preselected location. The device is of especial utility when used to place four images on a single film to record oscilloscope views obtained in gamma radiography.

Cortical DNA methylation maintains remote memory.

PubMed

Miller, Courtney A; Gavin, Cristin F; White, Jason A; Parrish, R Ryley; Honasoge, Avinash; Yancey, Christopher R; Rivera, Ivonne M; Rubio, María D; Rumbaugh, Gavin; Sweatt, J David

2010-06-01

A behavioral memory's lifetime represents multiple molecular lifetimes, suggesting the necessity for a self-perpetuating signal. One candidate is DNA methylation, a transcriptional repression mechanism that maintains cellular memory throughout development. We found that persistent, gene-specific cortical hypermethylation was induced in rats by a single, hippocampus-dependent associative learning experience and pharmacologic inhibition of methylation 1 month after learning disrupted remote memory. We propose that the adult brain utilizes DNA methylation to preserve long-lasting memories.

Polymodal Responses in C. elegans Phasmid Neurons Rely on Multiple Intracellular and Intercellular Signaling Pathways

PubMed Central

Zou, Wenjuan; Cheng, Hankui; Li, Shitian; Yue, Xiaomin; Xue, Yadan; Chen, Sixi; Kang, Lijun

2017-01-01

Animals utilize specialized sensory neurons enabling the detection of a wide range of environmental stimuli from the presence of toxic chemicals to that of touch. However, how these neurons discriminate between different kinds of stimuli remains poorly understood. By combining in vivo calcium imaging and molecular genetic manipulation, here we investigate the response patterns and the underlying mechanisms of the C. elegans phasmid neurons PHA/PHB to a variety of sensory stimuli. Our observations demonstrate that PHA/PHB neurons are polymodal sensory neurons which sense harmful chemicals, hyperosmotic solutions and mechanical stimulation. A repulsive concentration of IAA induces calcium elevations in PHA/PHB and both OSM-9 and TAX-4 are essential for IAA-sensing in PHA/PHB. Nevertheless, the PHA/PHB neurons are inhibited by copper and post-synaptically activated by copper removal. Neuropeptide is likely involved in copper removal-induced calcium elevations in PHA/PHB. Furthermore, mechanical stimulation activates PHA/PHB in an OSM-9-dependent manner. Our work demonstrates how PHA/PHB neurons respond to multiple environmental stimuli and lays a foundation for the further understanding of the mechanisms of polymodal signaling, such as nociception, in more complex organisms. PMID:28195191

Navigational Mechanisms of Migrating Monarch Butterflies

PubMed Central

Reppert, Steven M.; Gegear, Robert J.; Merlin, Christine

2010-01-01

Recent studies of the iconic fall migration of monarch butterflies have illuminated the mechanisms behind the navigation south, using a time-compensated sun compass. Skylight cues, such as the sun itself and polarized light, are processed through both eyes and likely integrated in the brain’s central complex, the presumed site of the sun compass. Time compensation is provided by circadian clocks that have a distinctive molecular mechanism and that reside in the antennae. Monarchs may also use a magnetic compass, because they possess two cryptochromes that have the molecular capability for light-dependent magnetoreception. Multiple genomic approaches are being utilized to ultimately identify navigation genes. Monarch butterflies are thus emerging as an excellent model organism to study the molecular and neural basis of long-distance migration. PMID:20627420

An Advice Mechanism for Heterogeneous Robot Teams

NASA Astrophysics Data System (ADS)

Daniluk, Steven

The use of reinforcement learning for robot teams has enabled complex tasks to be performed, but at the cost of requiring a large amount of exploration. Exchanging information between robots in the form of advice is one method to accelerate performance improvements. This thesis presents an advice mechanism for robot teams that utilizes advice from heterogeneous advisers via a method guaranteeing convergence to an optimal policy. The presented mechanism has the capability to use multiple advisers at each time step, and decide when advice should be requested and accepted, such that the use of advice decreases over time. Additionally, collective collaborative, and cooperative behavioural algorithms are integrated into a robot team architecture, to create a new framework that provides fault tolerance and modularity for robot teams.

Immunomodulatory drugs in multiple myeloma: mechanisms of action and clinical experience

PubMed Central

Holstein, Sarah A.; McCarthy, Philip L.

2017-01-01

Over the last two decades, the outcomes for patients with multiple myeloma, a plasma cell malignancy, have dramatically improved. The development of the immunomodulatory drugs (IMiDs) which include thalidomide, lenalidomide, and pomalidomide, has contributed significantly to these improved outcomes. While thalidomide is now less commonly prescribed, lenalidomide is widely used in the treatment of newly diagnosed transplant-eligible and transplant-ineligible patients, in the maintenance setting post-transplant and in the relapsed/refractory setting, while pomalidomide is currently utilized in the relapsed/refractory setting. The IMiDs have been reported to have a multitude of activities, including anti-angiogenic, cytotoxic, and immunomodulatory, however, the more recent discoveries that the IMiDs bind to cereblon and thus regulate the ubiquitination of key transcription factors including IKZF1 and IKZF3, have provided greater insight into their mechanism of action. Here the clinical efficacy of these agents in myeloma is reviewed as well as discussion of structure-function relationship, the molecular mechanisms of action, and the association of IMiDs with second primary malignancies and thrombosis. PMID:28205024

Engagement of S1P₁-degradative mechanisms leads to vascular leak in mice.

PubMed

Oo, Myat Lin; Chang, Sung-Hee; Thangada, Shobha; Wu, Ming-Tao; Rezaul, Karim; Blaho, Victoria; Hwang, Sun-Il; Han, David K; Hla, Timothy

2011-06-01

GPCR inhibitors are highly prevalent in modern therapeutics. However, interference with complex GPCR regulatory mechanisms leads to both therapeutic efficacy and adverse effects. Recently, the sphingosine-1-phosphate (S1P) receptor inhibitor FTY720 (also known as Fingolimod), which induces lymphopenia and prevents neuroinflammation, was adopted as a disease-modifying therapeutic in multiple sclerosis. Although highly efficacious, dose-dependent increases in adverse events have tempered its utility. We show here that FTY720P induces phosphorylation of the C-terminal domain of S1P receptor 1 (S1P₁) at multiple sites, resulting in GPCR internalization, polyubiquitinylation, and degradation. We also identified the ubiquitin E3 ligase WWP2 in the GPCR complex and demonstrated its requirement in FTY720-induced receptor degradation. GPCR degradation was not essential for the induction of lymphopenia, but was critical for pulmonary vascular leak in vivo. Prevention of receptor phosphorylation, internalization, and degradation inhibited vascular leak, which suggests that discrete mechanisms of S1P receptor regulation are responsible for the efficacy and adverse events associated with this class of therapeutics.

Metabolomic analysis reveals key metabolites related to the rapid adaptation of Saccharomyce cerevisiae to multiple inhibitors of furfural, acetic acid, and phenol.

PubMed

Wang, Xin; Li, Bing-Zhi; Ding, Ming-Zhu; Zhang, Wei-Wen; Yuan, Ying-Jin

2013-03-01

During hydrolysis of lignocellulosic biomass, a broad range of inhibitors are generated, which interfere with yeast growth and bioethanol production. In order to improve the strain tolerance to multiple inhibitors--acetic acid, furfural, and phenol (three representative lignocellulose-derived inhibitors) and uncover the underlying tolerant mechanism, an adaptation experiment was performed in which the industrial Saccharomyces cerevisiae was cultivated repeatedly in a medium containing multiple inhibitors. The adaptation occurred quickly, accompanied with distinct increase in growth rate, glucose utilization rate, furfural metabolism rate, and ethanol yield, only after the first transfer. A similar rapid adaptation was also observed for the lab strains of BY4742 and BY4743. The metabolomic analysis was employed to investigate the responses of the industrial S. cereviaise to three inhibitors during the adaptation. The results showed that higher levels of 2-furoic acid, 2, 3-butanediol, intermediates in glycolytic pathway, and amino acids derived from glycolysis, were discovered in the adapted strains, suggesting that enhanced metabolic activity in these pathways may relate to resistance against inhibitors. Additionally, through single-gene knockouts, several genes related to alanine metabolism, GABA shunt, and glycerol metabolism were verified to be crucial for the resistance to multiple inhibitors. This study provides new insights into the tolerance mechanism against multiple inhibitors, and guides for the improvement of tolerant ethanologenic yeast strains for lignocellulose-bioethanol fermentation.

Cancer Stem Cells and Chemoresistance: The Smartest Survives the Raid

PubMed Central

Zhao, Jihe

2016-01-01

Chemoresistant metastatic relapse of minimal residual disease plays a significant role for poor prognosis of cancer. Growing evidence supports a critical role of cancer stem cell (CSC) behind the mechanisms for this deadly disease. This review briefly introduces the basics of the conventional chemotherapies, updates the CSC theories, highlights the molecular and cellular mechanisms by which CSC smartly designs and utilizes multiple lines of self-defense to avoid being killed by chemotherapy, and concisely summarizes recent progress in studies on CSC-targeted therapies in the end, with the hope to help guide future research towards developing more effective therapeutic strategies to eradicate tumor cells in the patients. PMID:26899500

Feasibility of Cell Therapy in Multiple Sclerosis: A Systematic Review of 83 Studies

PubMed Central

Ardeshiry lajimi, Abdolreza; Hagh, Majid Farshdousti; Saki, Najmaldin; Mortaz, Esmaeil; Soleimani, Masoud; Rahim, Fakher

2013-01-01

Multiple Sclerosis is an inflammatory disease of the central nervous system in which T cells experience a second phase of activation, which ultimately leads to axonal demyelination and neurological disability. The recent advances in stem cell therapies may serve as potential treatments for neurological disorders. There are broad types of stem cells such as neural, embryonic, mesenchymal and hematopoietic stem cells with unprecedented hope in treating many debilitating diseases. In this paper we will review the substantial literature regarding experimental and clinical use of these stem cells and possible mechanisms in the treatment of MS. These results may pave the road for the utilization of stem cells for the treatment of MS. PMID:24505515

Highly efficient multiple-layer CdS quantum dot sensitized III-V solar cells.

PubMed

Lin, Chien-Chung; Han, Hau-Vei; Chen, Hsin-Chu; Chen, Kuo-Ju; Tsai, Yu-Lin; Lin, Wein-Yi; Kuo, Hao-Chung; Yu, Peichen

2014-02-01

In this review, the concept of utilization of solar spectrum in order to increase the solar cell efficiency is discussed. Among the three mechanisms, down-shifting effect is investigated in detail. Organic dye, rare-earth minerals and quantum dots are three most popular down-shift materials. While the enhancement of solar cell efficiency was not clearly observed in the past, the advances in quantum dot fabrication have brought strong response out of the hybrid platform of a quantum dot solar cell. A multiple layer structure, including PDMS as the isolation layer, is proposed and demonstrated. With the help of pulse spray system, precise control can be achieved and the optimized concentration can be found.

How does the multifaceted plant hormone salicylic acid combat disease in plants and are similar mechanisms utilized in humans?

PubMed

Dempsey, D'Maris Amick; Klessig, Daniel F

2017-03-23

Salicylic acid (SA) is an important plant hormone that regulates many aspects of plant growth and development, as well as resistance to (a)biotic stress. Efforts to identify SA effector proteins have revealed that SA binds to and alters the activity of multiple plant proteins-this represents a shift from the paradigm that hormones mediate their functions via one or a few receptors. SA and its derivatives also have multiple targets in animals; some of these proteins, like their plant counterparts, are associated with pathological processes. Together, these findings suggest that SA exerts its defense-associated effects in both kingdoms via a large number of targets.

Metameric MIMO-OOK transmission scheme using multiple RGB LEDs.

PubMed

Bui, Thai-Chien; Cusani, Roberto; Scarano, Gaetano; Biagi, Mauro

2018-05-28

In this work, we propose a novel visible light communication (VLC) scheme utilizing multiple different red green and blue triplets each with a different emission spectrum of red, green and blue for mitigating the effect of interference due to different colors using spatial multiplexing. On-off keying modulation is considered and its effect on light emission in terms of flickering, dimming and color rendering is discussed so as to demonstrate how metameric properties have been considered. At the receiver, multiple photodiodes with color filter-tuned on each transmit light emitting diode (LED) are employed. Three different detection mechanisms of color zero forcing, minimum mean square error estimation and minimum mean square error equalization are then proposed. The system performance of the proposed scheme is evaluated both with computer simulations and tests with an Arduino board implementation.

Antiwindup analysis and design approaches for MIMO systems

NASA Technical Reports Server (NTRS)

Marcopoli, Vincent R.; Phillips, Stephen M.

1994-01-01

Performance degradation of multiple-input multiple-output (MIMO) control systems having limited actuators is often handled by augmenting the controller with an antiwindup mechanism, which attempts to maintain system performance when limits are encountered. The goals of this paper are: (1) To develop a method to analyze antiwindup systems to determine precisely what stability and performance degradation is incurred under limited conditions. It is shown that by reformulating limited actuator commands as resulting from multiplicative perturbations to the corresponding controller requests, mu-analysis tools can be utilized to obtain quantitative measures of stability and performance degradation. (2) To propose a linear, time invariant (LTI) criterion on which to base the antiwindup design. These analysis and design methods are illustrated through the evaluation of two competing antiwindup schemes augmenting the controller of a Short Take-Off and Vertical Landing (STOVL) aircraft in transition flight.

Antiwindup analysis and design approaches for MIMO systems

NASA Technical Reports Server (NTRS)

Marcopoli, Vincent R.; Phillips, Stephen M.

1993-01-01

Performance degradation of multiple-input multiple-output (MIMO) control systems having limited actuators is often handled by augmenting the controller with an antiwindup mechanism, which attempts to maintain system performance when limits are encountered. The goals of this paper are: 1) to develop a method to analyze antiwindup systems to determine precisely what stability and performance degradation is incurred under limited conditions. It is shown that by reformulating limited actuator commands as resulting from multiplicative perturbations to the corresponding controller requests, mu-analysis tools can be utilized to obtain quantitative measures of stability and performance degradation. 2) To propose a linear, time invariant (LTI) criterion on which to base the antiwindup design. These analysis and design methods are illustrated through the evaluation of two competing antiwindup schemes augmenting the controller of a Short Take-Off and Vertical Landing (STOVL) aircraft in transition flight.

Three-dimensional fluorescent microscopy via simultaneous illumination and detection at multiple planes.

PubMed

Ma, Qian; Khademhosseinieh, Bahar; Huang, Eric; Qian, Haoliang; Bakowski, Malina A; Troemel, Emily R; Liu, Zhaowei

2016-08-16

The conventional optical microscope is an inherently two-dimensional (2D) imaging tool. The objective lens, eyepiece and image sensor are all designed to capture light emitted from a 2D 'object plane'. Existing technologies, such as confocal or light sheet fluorescence microscopy have to utilize mechanical scanning, a time-multiplexing process, to capture a 3D image. In this paper, we present a 3D optical microscopy method based upon simultaneously illuminating and detecting multiple focal planes. This is implemented by adding two diffractive optical elements to modify the illumination and detection optics. We demonstrate that the image quality of this technique is comparable to conventional light sheet fluorescent microscopy with the advantage of the simultaneous imaging of multiple axial planes and reduced number of scans required to image the whole sample volume.

Programming function into mechanical forms by directed assembly of silk bulk materials

PubMed Central

Patel, Nereus; Duggan, Thomas; Perotto, Giovanni; Shirman, Elijah; Li, Chunmei; Kaplan, David L.; Omenetto, Fiorenzo G.

2017-01-01

We report simple, water-based fabrication methods based on protein self-assembly to generate 3D silk fibroin bulk materials that can be easily hybridized with water-soluble molecules to obtain multiple solid formats with predesigned functions. Controlling self-assembly leads to robust, machinable formats that exhibit thermoplastic behavior consenting material reshaping at the nanoscale, microscale, and macroscale. We illustrate the versatility of the approach by realizing demonstrator devices where large silk monoliths can be generated, polished, and reshaped into functional mechanical components that can be nanopatterned, embed optical function, heated on demand in response to infrared light, or can visualize mechanical failure through colorimetric chemistries embedded in the assembled (bulk) protein matrix. Finally, we show an enzyme-loaded solid mechanical part, illustrating the ability to incorporate biological function within the bulk material with possible utility for sustained release in robust, programmably shapeable mechanical formats. PMID:28028213

Metabolic Engineering for Substrate Co-utilization

NASA Astrophysics Data System (ADS)

Gawand, Pratish

Production of biofuels and bio-based chemicals is being increasingly pursued by chemical industry to reduce its dependence on petroleum. Lignocellulosic biomass (LCB) is an abundant source of sugars that can be used for producing biofuels and bio-based chemicals using fermentation. Hydrolysis of LCB results in a mixture of sugars mainly composed of glucose and xylose. Fermentation of such a sugar mixture presents multiple technical challenges at industrial scale. Most industrial microorganisms utilize sugars in a sequential manner due to the regulatory phenomenon of carbon catabolite repression (CCR). Due to sequential utilization of sugars, the LCB-based fermentation processes suffer low productivities and complicated operation. Performance of fermentation processes can be improved by metabolic engineering of microorganisms to obtain superior characteristics such as high product yield. With increased computational power and availability of complete genomes of microorganisms, use of model-based metabolic engineering is now a common practice. The problem of sequential sugar utilization, however, is a regulatory problem, and metabolic models have never been used to solve such regulatory problems. The focus of this thesis is to use model-guided metabolic engineering to construct industrial strains capable of co-utilizing sugars. First, we develop a novel bilevel optimization algorithm SimUp, that uses metabolic models to identify reaction deletion strategies to force co-utilization of two sugars. We then use SimUp to identify reaction deletion strategies to force glucose-xylose co-utilization in Escherichia coli. To validate SimUp predictions, we construct three mutants with multiple gene knockouts and test them for glucose-xylose utilization characteristics. Two mutants, designated as LMSE2 and LMSE5, are shown to co-utilize glucose and xylose in agreement with SimUp predictions. To understand the molecular mechanism involved in glucose-xylose co-utilization of the mutant LMSE2, the mutant is subjected to targeted and whole genome sequencing. Finally, we use the mutant LMSE2 to produce D-ribose from a mixture of glucose and xylose by overexpressing an endogenous phosphatase. The methods developed in this thesis are anticipated to provide a novel approach to solve sugar co-utilization problem in industrial microorganisms, and provide insights into microbial response to forced co-utilization of sugars.

Wearable multifunctional sensors using printed stretchable conductors made of silver nanowires

NASA Astrophysics Data System (ADS)

Yao, Shanshan; Zhu, Yong

2014-01-01

Considerable efforts have been made to achieve highly sensitive and wearable sensors that can simultaneously detect multiple stimuli such as stretch, pressure, temperature or touch. Here we develop highly stretchable multifunctional sensors that can detect strain (up to 50%), pressure (up to ~1.2 MPa) and finger touch with high sensitivity, fast response time (~40 ms) and good pressure mapping function. The reported sensors utilize the capacitive sensing mechanism, where silver nanowires are used as electrodes (conductors) and Ecoflex is used as a dielectric. The silver nanowire electrodes are screen printed. Our sensors have been demonstrated for several wearable applications including monitoring thumb movement, sensing the strain of the knee joint in patellar reflex (knee-jerk) and other human motions such as walking, running and jumping from squatting, illustrating the potential utilities of such sensors in robotic systems, prosthetics, healthcare and flexible touch panels.Considerable efforts have been made to achieve highly sensitive and wearable sensors that can simultaneously detect multiple stimuli such as stretch, pressure, temperature or touch. Here we develop highly stretchable multifunctional sensors that can detect strain (up to 50%), pressure (up to ~1.2 MPa) and finger touch with high sensitivity, fast response time (~40 ms) and good pressure mapping function. The reported sensors utilize the capacitive sensing mechanism, where silver nanowires are used as electrodes (conductors) and Ecoflex is used as a dielectric. The silver nanowire electrodes are screen printed. Our sensors have been demonstrated for several wearable applications including monitoring thumb movement, sensing the strain of the knee joint in patellar reflex (knee-jerk) and other human motions such as walking, running and jumping from squatting, illustrating the potential utilities of such sensors in robotic systems, prosthetics, healthcare and flexible touch panels. Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr05496a

Impacts of the phenylpyrazole insecticide fipronil on larval fish: time-series gene transcription responses in fathead minnow (Pimephales promelas) following short-term exposure.

PubMed

Beggel, Sebastian; Werner, Inge; Connon, Richard E; Geist, Juergen P

2012-06-01

The utilization of molecular endpoints in ecotoxicology can provide rapid and valuable information on immediate organismal responses to chemical stressors and is increasingly used for mechanistic interpretation of effects at higher levels of biological organization. This study contributes knowledge on the sublethal effects of a commonly used insecticide, the phenylpyrazole fipronil, on larval fathead minnow (Pimephales promelas), utilizing a quantitative transcriptomic approach. Immediately after 24h of exposure to fipronil concentrations of ≥31 μg.L(-1), highly significant changes in gene transcription were observed for aspartoacylase, metallothionein, glucocorticoid receptor, cytochrome P450 3A126 and vitellogenin. Different mechanisms of toxicity were apparent over the course of the experiment, with short-term responses indicating neurotoxic effects. After 6 days of recovery, endocrine effects were observed with vitellogenin being up-regulated 90-fold at 61 μg.L(-1) fipronil. Principal component analysis demonstrated a significant increase in gene transcription changes over time and during the recovery period. In conclusion, multiple mechanisms of action were observed in response to fipronil exposure, and unknown delayed effects would have been missed if transcriptomic responses had only been measured at a single time-point. These challenges can be overcome by the inclusion of multiple endpoints and delayed effects in experimental designs. Copyright © 2012 Elsevier B.V. All rights reserved.

Multiple-hypothesis multiple-model line tracking

NASA Astrophysics Data System (ADS)

Pace, Donald W.; Owen, Mark W.; Cox, Henry

2000-07-01

Passive sonar signal processing generally includes tracking of narrowband and/or broadband signature components observed on a Lofargram or on a Bearing-Time-Record (BTR) display. Fielded line tracking approaches to date have been recursive and single-hypthesis-oriented Kalman- or alpha-beta filters, with no mechanism for considering tracking alternatives beyond the most recent scan of measurements. While adaptivity is often built into the filter to handle changing track dynamics, these approaches are still extensions of single target tracking solutions to multiple target tracking environment. This paper describes an application of multiple-hypothesis, multiple target tracking technology to the sonar line tracking problem. A Multiple Hypothesis Line Tracker (MHLT) is developed which retains the recursive minimum-mean-square-error tracking behavior of a Kalman Filter in a maximum-a-posteriori delayed-decision multiple hypothesis context. Multiple line track filter states are developed and maintained using the interacting multiple model (IMM) state representation. Further, the data association and assignment problem is enhanced by considering line attribute information (line bandwidth and SNR) in addition to beam/bearing and frequency fit. MHLT results on real sonar data are presented to demonstrate the benefits of the multiple hypothesis approach. The utility of the system in cluttered environments and particularly in crossing line situations is shown.

Shared and unique responses of plants to multiple individual stresses and stress combinations: physiological and molecular mechanisms

PubMed Central

Pandey, Prachi; Ramegowda, Venkategowda; Senthil-Kumar, Muthappa

2015-01-01

In field conditions, plants are often simultaneously exposed to multiple biotic and abiotic stresses resulting in substantial yield loss. Plants have evolved various physiological and molecular adaptations to protect themselves under stress combinations. Emerging evidences suggest that plant responses to a combination of stresses are unique from individual stress responses. In addition, plants exhibit shared responses which are common to individual stresses and stress combination. In this review, we provide an update on the current understanding of both unique and shared responses. Specific focus of this review is on heat–drought stress as a major abiotic stress combination and, drought–pathogen and heat–pathogen as examples of abiotic–biotic stress combinations. We also comprehend the current understanding of molecular mechanisms of cross talk in relation to shared and unique molecular responses for plant survival under stress combinations. Thus, the knowledge of shared responses of plants from individual stress studies and stress combinations can be utilized to develop varieties with broad spectrum stress tolerance. PMID:26442037

Advanced bulk processing of lightweight materials for utilization in the transportation sector

NASA Astrophysics Data System (ADS)

Milner, Justin L.

The overall objective of this research is to develop the microstructure of metallic lightweight materials via multiple advanced processing techniques with potentials for industrial utilization on a large scale to meet the demands of the aerospace and automotive sectors. This work focused on (i) refining the grain structure to increase the strength, (ii) controlling the texture to increase formability and (iii) directly reducing processing/production cost of lightweight material components. Advanced processing is conducted on a bulk scale by several severe plastic deformation techniques including: accumulative roll bonding, isolated shear rolling and friction stir processing to achieve the multiple targets of this research. Development and validation of the processing techniques is achieved through wide-ranging experiments along with detailed mechanical and microstructural examination of the processed material. On a broad level, this research will make advancements in processing of bulk lightweight materials facilitating industrial-scale implementation. Where accumulative roll bonding and isolated shear rolling, currently feasible on an industrial scale, processes bulk sheet materials capable of replacing more expensive grades of alloys and enabling low-temperature and high-strain-rate formability. Furthermore, friction stir processing to manufacture lightweight tubes, made from magnesium alloys, has the potential to increase the utilization of these materials in the automotive and aerospace sectors for high strength - high formability applications. With the increased utilization of these advanced processing techniques will significantly reduce the cost associated with lightweight materials for many applications in the transportation sectors.

MIDAS: Mining differentially activated subpaths of KEGG pathways from multi-class RNA-seq data.

PubMed

Lee, Sangseon; Park, Youngjune; Kim, Sun

2017-07-15

Pathway based analysis of high throughput transcriptome data is a widely used approach to investigate biological mechanisms. Since a pathway consists of multiple functions, the recent approach is to determine condition specific sub-pathways or subpaths. However, there are several challenges. First, few existing methods utilize explicit gene expression information from RNA-seq. More importantly, subpath activity is usually an average of statistical scores, e.g., correlations, of edges in a candidate subpath, which fails to reflect gene expression quantity information. In addition, none of existing methods can handle multiple phenotypes. To address these technical problems, we designed and implemented an algorithm, MIDAS, that determines condition specific subpaths, each of which has different activities across multiple phenotypes. MIDAS utilizes gene expression quantity information fully and the network centrality information to determine condition specific subpaths. To test performance of our tool, we used TCGA breast cancer RNA-seq gene expression profiles with five molecular subtypes. 36 differentially activate subpaths were determined. The utility of our method, MIDAS, was demonstrated in four ways. All 36 subpaths are well supported by the literature information. Subsequently, we showed that these subpaths had a good discriminant power for five cancer subtype classification and also had a prognostic power in terms of survival analysis. Finally, in a performance comparison of MIDAS to a recent subpath prediction method, PATHOME, our method identified more subpaths and much more genes that are well supported by the literature information. http://biohealth.snu.ac.kr/software/MIDAS/. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Intestine, immunity, and parenteral nutrition in an era of preferred enteral feeding.

PubMed

Barrett, Meredith; Demehri, Farokh R; Teitelbaum, Daniel H

2015-09-01

To review the benefits of enteral nutrition in contrast to the inflammatory consequences of administration of parenteral nutrition and enteral deprivation. To present the most recent evidence for the mechanisms of these immunologic changes and discuss potential areas for modification to decrease infectious complications of its administration. There is significant data supporting the early initiation of enteral nutrition in both medical and surgical patients unable to meet their caloric goals via oral intake alone. Despite the preference for enteral nutrition, some patients are unable to utilize their gut for nutritious gain and therefore require parenteral nutrition administration, along with its infectious complications. The mechanisms behind these complications are multifactorial and have yet to be fully elucidated. Recent study utilizing both animal and human models has provided further information regarding parenteral nutrition's deleterious effect on intestinal epithelial barrier function along with the complications associated with enterocyte deprivation. Changes associated with parenteral nutrition administration and enteral deprivation are complex with multiple potential areas for modification to allow for safer administration. Recent discovery of the mechanisms behind these changes present exciting areas for future study as to make parenteral nutrition administration in the enterally deprived patient safer.

Luteolin: A Flavonoid that Has Multiple Cardio-Protective Effects and Its Molecular Mechanisms

PubMed Central

Luo, Yuanyuan; Shang, Pingping; Li, Dongye

2017-01-01

Cardiovascular disease (CVD) has become the leading cause of morbidity and mortality worldwide. A well-monitored diet with a sufficient intake of fruits and vegetables has been confirmed as a primary prevention of CVD. Plant constituents such as flavonoids have been shown to confer healthy benefits. Luteolin (Lut), a kind of flavonoid, possesses anti-oxidative, anti-tumor, and anti-inflammatory properties. Recent scientific literature has reported the cardiac protective effects of Lut in vitro and in vivo. Therefore, the aim of this review is to provide an update and detailed overview with cardio-protective molecular mechanisms of Lut with a focus on multiple intrinsic and extrinsic effectors. We further explore how these mechanisms participate in ischemia/reperfusion (I/R) injury, heart failure (HF) and atherosclerosis (AS). A proper understanding of the cardiovascular protective effects and the relative mechanisms of Lut may provide the possibility of new drug design and development for CVD. With the previous studies mainly focused on basic research, we need to advance the prospects of its further clinical utilization against CVD, large prospective clinical trials of Lut are needed to observe its therapeutic effects on patients with I/R injury, HF and AS, especially on the effective therapeutic dosage, and safety of long-term administration. PMID:29056912

Ionospheric Density Enhancements at Low and Middle Latitudes during Superstorms Observed from Multiple Satellites

NASA Astrophysics Data System (ADS)

Lei, J.; Wang, W.; Burns, A. G.; Yue, X.

2014-12-01

The total electron content (TEC) data measured by the Jason, CHAMP, GRACE and SAC-C satellites, the in-situ electron densities from CHAMP and GRACE, and the vertical E×B drifts from the ROCSAT satellite are utilized to examine the ionospheric response to superstorms. The combination of observations from multiple satellites provides a unique global view of positive ionospheric storm effect at low and middle latitudes, especially over Oceans and under sunlit conditions during the main phases of the storms. In this talk, we will focus on the morphology, evolution and driving mechanisms of the storm-time ionosphere and explore the relative contributions of the horizontal and vertical transport effects to the observed positive storm phase at different latitudes.

DOPAMINE POSTSYNAPTIC RECEPTOR EFFECTS OF RESTRICTED SCHEDULES OF ELECTROCONVULSIVE SHOCK

PubMed Central

Andrade, Chittaranjan; Gangadhar, B.N.; Meena, M.; Pradhan, N.

1990-01-01

SUMMMARY Little work is available on the acute and time-dependant dopaminergic effects of single electroconvulsive shock (ECS) and multiple ECS despite the posited clinical utility of such schedules of electroconvulsive therapy (ECT) administration and the posited role of dopaminergic mechanisms in iieuropsychiatric disorders. In this study, using the apomorphine-induced motility-alteration behavioural paradigm, single session multiple ECS was found to produce no significant effect while single ECS behaviourally downregulated dopamine postsynaptic receptor functioning one week after the ECS, which effect was also seen (albeit to a lesser extent) a further week later. These findings indicate a possible application of restricted schedules of ECT to dopamine postsynaptic receptor supersensitivity syndromes. Lines for future research are suggested. PMID:21927479

Mechanical coupling for a rotor shaft assembly of dissimilar materials

DOEpatents

Shi, Jun [Glastonbury, CT; Bombara, David [New Hartford, CT; Green, Kevin E [Broad Brook, CT; Bird, Connic [Rocky Hill, CT; Holowczak, John [South Windsor, CT

2009-05-05

A mechanical coupling for coupling a ceramic disc member to a metallic shaft includes a first wedge clamp and a second wedge clamp. A fastener engages a threaded end of a tie-bolt to sandwich the ceramic disc between the wedge clamps. An axial spring is positioned between the fastener and the second wedge clamp to apply an axial preload along the longitudinal axis. Another coupling utilizes a rotor shaft end of a metallic rotor shaft as one wedge clamp. Still another coupling includes a solid ceramic rotor disc with a multiple of tie-bolts radially displaced from the longitudinal axis to exert the preload on the solid ceramic rotor disc.

Distributed power and control actuation in the thoracic mechanics of a robotic insect.

PubMed

Finio, Benjamin M; Wood, Robert J

2010-12-01

Recent advances in the understanding of biological flight have inspired roboticists to create flapping-wing vehicles on the scale of insects and small birds. While our understanding of the wing kinematics, flight musculature and neuromotor control systems of insects has expanded, in practice it has proven quite difficult to construct an at-scale mechanical device capable of similar flight performance. One of the key challenges is the development of an effective and efficient transmission mechanism to control wing motions. Here we present multiple insect-scale robotic thorax designs capable of producing asymmetric wing kinematics similar to those observed in nature and utilized by dipteran insects to maneuver. Inspired by the thoracic mechanics of dipteran insects, which entail a morphological separation of power and control muscles, these designs show that such distributed actuation can also modulate wing motion in a robotic design.

Design of a Single Motor Based Leg Structure with the Consideration of Inherent Mechanical Stability

NASA Astrophysics Data System (ADS)

Taha Manzoor, Muhammad; Sohail, Umer; Noor-e-Mustafa; Nizami, Muhammad Hamza Asif; Ayaz, Yasar

2017-07-01

The fundamental aspect of designing a legged robot is constructing a leg design that is robust and presents a simple control problem. In this paper, we have successfully designed a robotic leg based on a unique four bar mechanism with only one motor per leg. The leg design parameters used in our platform are extracted from design principles used in biological systems, multiple iterations and previous research findings. These principles guide a robotic leg to have minimal mechanical passive impedance, low leg mass and inertia, a suitable foot trajectory utilizing a practical balance between leg kinematics and robot usage, and the resultant inherent mechanical stability. The designed platform also exhibits the key feature of self-locking. Theoretical tools and software iterations were used to derive these practical features and yield an intuitive sense of the required leg design parameters.

A comparison of outer electron radiation belt dropouts during solar wind stream interface and magnetic cloud driven storms

NASA Astrophysics Data System (ADS)

Ogunjobi, O.; Sivakumar, V.; Mtumela, Z.

2017-06-01

Energetic electrons are trapped in the Earth's radiation belts which occupy a toroidal region between 3 and 7 \\hbox {R}E above the Earth's surface. Rapid loss of electrons from the radiation belts is known as dropouts. The source and loss mechanisms regulating the radiation belts population are not yet understood entirely, particularly during geomagnetic storm times. Nevertheless, the dominant loss mechanism may require an event based study to be better observed. Utilizing multiple data sources from the year 1997-2007, this study identifies radiation belt electron dropouts which are ultimately triggered when solar wind stream interfaces (SI) arrived at Earth, or when magnetic clouds (MC) arrived. Using superposed epoch analysis (SEA) technique, a synthesis of multiple observations is performed to reveal loss mechanism which might, perhaps, be a major contributor to radiation belt losses under SI and MC driven storms. Results show an abrupt slower decaying precipitation of electron peak (about 3000 counts/sec) on SI arrival within 5.05 < L < 6.05, which persist till 0.5 day before gradual recovery. This pattern is interpreted as an indication of depleted electrons from bounce lost cone via precipitating mechanism known as relativistic electron microburst. On the other hand, MC shows a pancake precipitating peak extending to lower L (Plasmapause); indicating a combination of electron cyclotron harmonic (ECH) and whistler mode waves as the contributing mechanisms.

Socioeconomic disparities in the utilization of mechanical thrombectomy for acute ischemic stroke in US hospitals.

PubMed

Brinjikji, W; Rabinstein, A A; McDonald, J S; Cloft, H J

2014-03-01

Previous studies have demonstrated that socioeconomic disparities in the treatment of cerebrovascular diseases exist. We studied a large administrative data base to study disparities in the utilization of mechanical thrombectomy for acute ischemic stroke. With the utilization of the Perspective data base, we studied disparities in mechanical thrombectomy utilization between patient race and insurance status in 1) all patients presenting with acute ischemic stroke and 2) patients presenting with acute ischemic stroke at centers that performed mechanical thrombectomy. We examined utilization rates of mechanical thrombectomy by race/ethnicity (white, black, and Hispanic) and insurance status (Medicare, Medicaid, self-pay, and private). Multivariate logistic regression analysis adjusting for potential confounding variables was performed to study the association between race/insurance status and mechanical thrombectomy utilization. The overall mechanical thrombectomy utilization rate was 0.15% (371/249,336); utilization rate at centers that performed mechanical thrombectomy was 1.0% (371/35,376). In the sample of all patients with acute ischemic stroke, multivariate logistic regression analysis demonstrated that uninsured patients had significantly lower odds of mechanical thrombectomy utilization compared with privately insured patients (OR = 0.52, 95% CI = 0.25-0.95, P = .03), as did Medicare patients (OR = 0.53, 95% CI = 0.41-0.70, P < .0001). Blacks had significantly lower odds of mechanical thrombectomy utilization compared with whites (OR = 0.35, 95% CI = 0.23-0.51, P < .0001). When considering only patients treated at centers performing mechanical thrombectomy, multivariate logistic regression analysis demonstrated that insurance was not associated with significant disparities in mechanical thrombectomy utilization; however, black patients had significantly lower odds of mechanical thrombectomy utilization compared with whites (OR = 0.41, 95% CI = 0.27-0.60, P < .0001). Significant socioeconomic disparities exist in the utilization of mechanical thrombectomy in the United States.

Experimental palaeobiomechanics: What can engineering tell us about evolution in deep time?

NASA Astrophysics Data System (ADS)

Anderson, Philip

2016-04-01

What did Tyrannosaurus rex eat? This is the sort of question that immediately bombards any palaeontologist when interacting with the general public. Even among scientists, how extinct animals moved or fed is a major objective of the palaeobiological research agenda. The last decade has seen a sharp increase in the technology and experimental methods available for collecting biomechanical data, which has greatly improved out ability to examine the function of both live and extinct animals. With new technologies and methods come new pitfalls and opportunities. In this review, I address three aspects of experimental biomechanics that exemplify the challenges and opportunities it provides for addressing deep-time problems in palaeontology. 1) Interpretation: It has never been easier to acquire large amounts of high-quality biomechanical data on extinct animals. However, the lack of behavioural information means that interpreting this data can be problematic. We will never know precisely what a dinosaur ate, but we can explore what constraints there might have been on the mechanical function of its jaws. Palaeobiomechanics defines potential function and becomes especially effective when dealing with multiple examples. 2) Comparison: Understanding the potential function of one extinct animal is interesting; however, examining mechanical features across multiple taxa allows for a greater understanding of biomechanical variation. Comparative studies help identify common trends and underlying mechanical principles which can have long reaching influences on morphological evolution. 3) Evolution: The physical principles established through comparative biomechanical studies can be utilized in phylogenetic comparative methods in order to explore evolutionary morphology across clades. Comparative evolutionary biomechanics offers potential for exploring the evolution of functional systems in deep time utilizing experimental biomechanical data.

Functional connectivity studies of patients with auditory verbal hallucinations.

PubMed

Hoffman, Ralph E; Hampson, Michelle

2011-12-02

Functional connectivity (FC) studies of brain mechanisms leading to auditory verbal hallucinations (AVHs) utilizing functional magnetic resonance imaging (fMRI) data are reviewed. Initial FC studies utilized fMRI data collected during performance of various tasks, which suggested frontotemporal disconnection and/or source-monitoring disturbances. Later FC studies have utilized resting (no-task) fMRI data. These studies have produced a mixed picture of disconnection and hyperconnectivity involving different pathways associated with AVHs. Results of our most recent FC study of AVHs are reviewed in detail. This study suggests that the core mechanism producing AVHs involves not a single pathway, but a more complex functional loop. Components of this loop include Wernicke's area and its right homologue, the left inferior frontal cortex, and the putamen. It is noteworthy that the putamen appears to play a critical role in the generation of spontaneous language, and in determining whether auditory stimuli are registered consciously as percepts. Excessive functional coordination linking this region with the Wernicke's seed region in patients with schizophrenia could, therefore, generate an overabundance of potentially conscious language representations. In our model, intact FC in the other two legs of corticostriatal loop (Wernicke's with left IFG, and left IFG with putamen) appeared to allow hyperconnectivity linking the putamen and Wernicke's area (common to schizophrenia overall) to be expressed as conscious hallucinations of speech. Recommendations for future studies are discussed, including inclusion of multiple methodologies applied to the same subjects in order to compare and contrast different mechanistic hypotheses, utilizing EEG to better parse time-course of neural synchronization leading to AVHs, and ascertaining experiential subtypes of AVHs that may reflect distinct mechanisms.

Rodent Models of Experimental Endometriosis: Identifying Mechanisms of Disease and Therapeutic Targets

PubMed Central

Bruner-Tran, Kaylon L.; Mokshagundam, Shilpa; Herington, Jennifer L.; Ding, Tianbing; Osteen, Kevin G.

2018-01-01

Background: Although it has been more than a century since endometriosis was initially described in the literature, understanding the etiology and natural history of the disease has been challenging. However, the broad utility of murine and rat models of experimental endometriosis has enabled the elucidation of a number of potentially targetable processes which may otherwise promote this disease. Objective: To review a variety of studies utilizing rodent models of endometriosis to illustrate their utility in examining mechanisms associated with development and progression of this disease. Results: Use of rodent models of endometriosis has provided a much broader understanding of the risk factors for the initial development of endometriosis, the cellular pathology of the disease and the identification of potential therapeutic targets. Conclusion: Although there are limitations with any animal model, the variety of experimental endometriosis models that have been developed has enabled investigation into numerous aspects of this disease. Thanks to these models, our under-standing of the early processes of disease development, the role of steroid responsiveness, inflammatory processes and the peritoneal environment has been advanced. More recent models have begun to shed light on how epigenetic alterations con-tribute to the molecular basis of this disease as well as the multiple comorbidities which plague many patients. Continued de-velopments of animal models which aid in unraveling the mechanisms of endometriosis development provide the best oppor-tunity to identify therapeutic strategies to prevent or regress this enigmatic disease.

The role of correlations in uncertainty quantification of transportation relevant fuel models

DOE PAGES

Fridlyand, Aleksandr; Johnson, Matthew S.; Goldsborough, S. Scott; ...

2017-02-03

Large reaction mechanisms are often used to describe the combustion behavior of transportation-relevant fuels like gasoline, where these are typically represented by surrogate blends, e.g., n-heptane/iso-octane/toluene. We describe efforts to quantify the uncertainty in the predictions of such mechanisms at realistic engine conditions, seeking to better understand the robustness of the model as well as the important reaction pathways and their impacts on combustion behavior. In this work, we examine the importance of taking into account correlations among reactions that utilize the same rate rules and those with multiple product channels on forward propagation of uncertainty by Monte Carlo simulations.more » Automated means are developed to generate the uncertainty factor assignment for a detailed chemical kinetic mechanism, by first uniquely identifying each reacting species, then sorting each of the reactions based on the rate rule utilized. Simulation results reveal that in the low temperature combustion regime for iso-octane, the majority of the uncertainty in the model predictions can be attributed to low temperature reactions of the fuel sub-mechanism. The foundational, or small-molecule chemistry (C 0-C 4) only contributes significantly to uncertainties in the predictions at the highest temperatures (Tc=900 K). Accounting for correlations between important reactions is shown to produce non-negligible differences in the estimates of uncertainty. Including correlations among reactions that use the same rate rules increases uncertainty in the model predictions, while accounting for correlations among reactions with multiple branches decreases uncertainty in some cases. Significant non-linear response is observed in the model predictions depending on how the probability distributions of the uncertain rate constants are defined.Finally, we concluded that care must be exercised in defining these probability distributions in order to reduce bias, and physically unrealistic estimates in the forward propagation of uncertainty for a range of UQ activities.« less

Nano- and micro-electromechanical switch dynamics

NASA Astrophysics Data System (ADS)

Pulskamp, Jeffrey S.; Proie, Robert M.; Polcawich, Ronald G.

2013-01-01

This paper reports theoretical analysis and experimental results on the dynamics of piezoelectric MEMS mechanical logic relays. The multiple degree of freedom analytical model, based on modal decomposition, utilizes modal parameters obtained from finite element analysis and an analytical model of piezoelectric actuation. The model accounts for exact device geometry, damping, drive waveform variables, and high electric field piezoelectric nonlinearity. The piezoelectrically excited modal force is calculated directly and provides insight into design optimization for switching speed. The model accurately predicts the propagation delay dependence on actuation voltage of mechanically distinct relay designs. The model explains the observed discrepancies in switching speed of these devices relative to single degree of freedom switching speed models and suggests the strong potential for improved switching speed performance in relays designed for mechanical logic and RF circuits through the exploitation of higher order vibrational modes.

Spacecraft automatic umbilical system

NASA Technical Reports Server (NTRS)

Goldin, R. W.; Jacquemin, G. G.; Johnson, W. H.

1981-01-01

An umbilical system design is described that incorporates all the features specified for a power system to payload interconnect capability. A proof-of-concept prototype of the umbilical system was built to determine experimentally the suitability of the threading characteristics of the ram mechanism and to verify freedom from cross threading. It is concluded that Berthing systems that utilize remote manipulator systems (RMS) can be simplified by using RMS targets, closed circuit TV cameras, tie into the RMS control system, and grapple-fixture and end-effector-like capture and secure mechanisms. To effect a remotely controlled umbilical interconnect in proximity with a manned spacecraft and to provide for extravehicular activity backup and maintenance capabilities, 18 different mechanisms are found to be necessary. The weight impact of proving for maintenance capability in a large multiple connector umbilical system was found to be in the order of +60 percent.

I2 basal stacking fault as a degradation mechanism in reverse gate-biased AlGaN/GaN HEMTs

NASA Astrophysics Data System (ADS)

Lang, A. C.; Hart, J. L.; Wen, J. G.; Miller, D. J.; Meyer, D. J.; Taheri, M. L.

2016-09-01

Here, we present the observation of a bias-induced, degradation-enhancing defect process in plasma-assisted molecular beam epitaxy grown reverse gate-biased AlGaN/GaN high electron mobility transistors (HEMTs), which is compatible with the current theoretical framework of HEMT degradation. Specifically, we utilize both conventional transmission electron microscopy and aberration-corrected transmission electron microscopy to analyze microstructural changes in not only high strained regions in degraded AlGaN/GaN HEMTs but also the extended gate-drain access region. We find a complex defect structure containing an I2 basal stacking fault and offer a potential mechanism for device degradation based on this defect structure. This work supports the reality of multiple failure mechanisms during device operation and identifies a defect potentially involved with device degradation.

Neurotrophin receptor structure and interactions.

PubMed

Yano, H; Chao, M V

2000-03-01

Although ligand-induced dimerization or oligomerization of receptors is a well established mechanism of growth factor signaling, increasing evidence indicates that biological responses are often mediated by receptor trans-signaling mechanisms involving two or more receptor systems. These include G protein-coupled receptors, cytokine, growth factor and trophic factor receptors. Greater flexibility is provided when different signaling pathways are merged through multiple receptor signaling systems. Trophic factors exemplified by NGF and its family members, ciliary neurotrophic factor (CNTF) and glial derived neurotrophic factor (GDNF) all utilize increased tyrosine phosphorylation of cellular substrates to mediate neuronal cell survival. Actions of the NGF family of neurotrophins are not only dictated by ras activation through the Trk family of receptor tyrosine kinases, but also a survival pathway defined by phosphatidylinositol-3-kinase activity (Yao and Cooper, 1995), which gives rise to phosphoinositide intermediates that activate the serine/threonine kinase Akt/PKB (Dudek et al., 1997). Induction of the serine-threonine kinase activity is critical for cell survival, as well as cell proliferation. Hence, for many trophic factors, multiple proteins constitute a functional multisubunit receptor complex that activates ras-dependent and ras-independent intracellular signaling. The NGF receptors provide an example of bidirectional crosstalk. In the presence of TrkA receptors, p75 can participate in the formation of high affinity binding sites and enhanced neurotrophin responsiveness leading to a survival or differentiation signal. In the absence of TrkA receptors, p75 can generate, in only specific cell populations, a death signal. These activities include the induction of NF kappa B (Carter et al., 1996); the hydrolysis of sphingomyelin to ceramide (Dobrowsky et al., 1995); and the pro-apoptotic functions attributed to p75. Receptors are generally drawn and viewed as isolated integral membrane proteins which span the lipid bilayer, with signal transduction proceeding in a linear step-wise fashion. There are now numerous examples which indicate that each receptor acts not only in a linear, independent manner, but can also influence the activity of other cell surface receptors, either directly or through signaling intermediates. Which step and which intermediates are utilized for crosstalk between the receptors is a critical question. For neurotrophins, their primary function in sustaining the viability of neurons is counterbalanced by a receptor mechanism to eliminate cells by an apoptotic mechanism. It is conceivable that this bidirectional system may be utilized selectively during development and in neurodegenerative diseases.

Reliability, Validity and Utility of a Multiple Intelligences Assessment for Career Planning.

ERIC Educational Resources Information Center

Shearer, C. Branton

"The Multiple Intelligences Developmental Assessment Scales" (MIDAS) is a self- (or other-) completed instrument which is based upon the theory of multiple intelligences. The validity, reliability, and utility data regarding the MIDAS are reported here. The measure consists of 7 main scales and 24 subscales which summarize a person's intellectual…

Identifying Martian Hydrothermal Sites: Geological Investigation Utilizing Multiple Datasets

NASA Technical Reports Server (NTRS)

Dohm, J. M.; Baker, V. R.; Anderson, R. C.; Scott, D. H.; Rice, J. W., Jr.; Hare, T. M.

2000-01-01

Comprehensive geological investigations of martian landscapes that may have been modified by magmatic-driven hydrothermal activity, utilizing multiple datasets, will yield prime target sites for future hydrological, mineralogical, and biological investigations.

Code-division multiple-access multiuser demodulator by using quantum fluctuations.

PubMed

Otsubo, Yosuke; Inoue, Jun-Ichi; Nagata, Kenji; Okada, Masato

2014-07-01

We examine the average-case performance of a code-division multiple-access (CDMA) multiuser demodulator in which quantum fluctuations are utilized to demodulate the original message within the context of Bayesian inference. The quantum fluctuations are built into the system as a transverse field in the infinite-range Ising spin glass model. We evaluate the performance measurements by using statistical mechanics. We confirm that the CDMA multiuser modulator using quantum fluctuations achieve roughly the same performance as the conventional CDMA multiuser modulator through thermal fluctuations on average. We also find that the relationship between the quality of the original information retrieval and the amplitude of the transverse field is somehow a "universal feature" in typical probabilistic information processing, viz., in image restoration, error-correcting codes, and CDMA multiuser demodulation.

Code-division multiple-access multiuser demodulator by using quantum fluctuations

NASA Astrophysics Data System (ADS)

Otsubo, Yosuke; Inoue, Jun-ichi; Nagata, Kenji; Okada, Masato

2014-07-01

We examine the average-case performance of a code-division multiple-access (CDMA) multiuser demodulator in which quantum fluctuations are utilized to demodulate the original message within the context of Bayesian inference. The quantum fluctuations are built into the system as a transverse field in the infinite-range Ising spin glass model. We evaluate the performance measurements by using statistical mechanics. We confirm that the CDMA multiuser modulator using quantum fluctuations achieve roughly the same performance as the conventional CDMA multiuser modulator through thermal fluctuations on average. We also find that the relationship between the quality of the original information retrieval and the amplitude of the transverse field is somehow a "universal feature" in typical probabilistic information processing, viz., in image restoration, error-correcting codes, and CDMA multiuser demodulation.

Triassic North American paleodrainage networks and sediment dispersal of the Chinle Formation: A quantitative approach utilizing detrital zircons

NASA Astrophysics Data System (ADS)

Blum, M. D.; Umbarger, K.

2017-12-01

The Triassic Chinle Formation is a fluvial succession deposited in a backarc setting across the present-day Colorado Plateau of the southwestern United States. Existing studies have proposed various mechanisms responsible for the unique stratigraphic architecture and depositional sequences of the Chinle. However, these studies lack necessary age control to correlate stratigraphic patterns with contemporaneous mechanisms. This study will collect new samples for detrital zircon analysis, as well as upgrade existing samples (to n=300) from Dickinson and Gehrels (2008), to improve the resolution of Triassic sediment provenance from source-to-sink. The improved dataset allows appraisal of the multiple provenance terranes that contributed to the Chinle depositional system to delineate and reconstruct paleodrainage patterns. The additional samples will be collected systematically from the base of the Chinle, and vertically throughout the section to capture a regional story of how the continental scale drainage reorganized through time. U-Pb ages of detrital zircons will be utilized to provide quantitative fingerprinting information to constrain interpretations for the origin and transport history of the Chinle fluvial succession in time and space.

Life history trade-offs and community dynamics of small fishes in a seasonally pulsed wetland

USGS Publications Warehouse

DeAngelis, D.L.; Trexler, J.C.; Loftus, W.F.

2005-01-01

We used a one-dimensional, spatially explicit model to simulate the community of small fishes in the freshwater wetlands of southern Florida, USA. The seasonality of rainfall in these wetlands causes annual fluctuations in the amount of flooded area. We modeled fish populations that differed from each other only in efficiency of resource utilization and dispersal ability. The simulations showed that these trade-offs, along with the spatial and temporal variability of the environment, allow coexistence of several species competing exploitatively for a common resource type. This mechanism, while sharing some characteristics with other mechanisms proposed for coexistence of competing species, is novel in detail. Simulated fish densities resembled patterns observed in Everglades empirical data. Cells with hydroperiods less than 6 months accumulated negligible fish biomass. One unique model result was that, when multiple species coexisted, it was possible for one of the coexisting species to have both lower local resource utilization efficiency and lower dispersal ability than one of the other species. This counterintuitive result is a consequence of stronger effects of other competitors on the superior species. ?? 2005 NRC.

Physical Activity Modulates Common Neuroplasticity Substrates in Major Depressive and Bipolar Disorder.

PubMed

Phillips, Cristy

2017-01-01

Mood disorders (MDs) are chronic, recurrent mental diseases that affect millions of individuals worldwide. Although the biogenic amine model has provided some clinical utility, a need remains to better understand the interrelated mechanisms that contribute to neuroplasticity deficits in MDs and the means by which various therapeutics mitigate them. Of those therapeutics being investigated, physical activity (PA) has shown clear and consistent promise. Accordingly, the aims of this review are to (1) explicate key modulators, processes, and interactions that impinge upon multiple susceptibility points to effectuate neuroplasticity deficits in MDs; (2) explore the putative mechanisms by which PA mitigates these features; (3) review protocols used to induce the positive effects of PA in MDs; and (4) highlight implications for clinicians and researchers.

RCT of a Psychological Intervention for Patients With Cancer: I. Mechanisms of Change

PubMed Central

Andersen, Barbara L.; Shelby, Rebecca A.; Golden-Kreutz, Deanna M.

2008-01-01

Little is known about the therapeutic processes contributing to efficacy of psychological interventions for patients with cancer. Data from a randomized clinical trial yielding robust biobehavioral and health effects (B. L. Andersen et al., 2004, 2007) were used to examine associations between process variables, treatment utilization, and outcomes. Novel findings emerged. Patients were highly satisfied with the treatment, but their higher levels of felt support (group cohesion) covaried with lower distress and fewer symptoms. Also, specific. treatment strategies were associated with specific outcomes, including lower distress, improved dietary habits, reduced symptomatology, and higher chemotherapy dose intensity. These data provide a comprehensive test of multiple therapeutic processes and mechanisms for biobehavioral change with an intervention including both intensive and maintenance phases. PMID:18085909

Pharmacology of Antisense Drugs.

PubMed

Bennett, C Frank; Baker, Brenda F; Pham, Nguyen; Swayze, Eric; Geary, Richard S

2017-01-06

Recent studies have led to a greater appreciation of the diverse roles RNAs play in maintaining normal cellular function and how they contribute to disease pathology, broadening the number of potential therapeutic targets. Antisense oligonucleotides are the most direct means to target RNA in a selective manner and have become an established platform technology for drug discovery. There are multiple molecular mechanisms by which antisense oligonucleotides can be used to modulate RNAs in cells, including promoting the degradation of the targeted RNA or modulating RNA function without degradation. Antisense drugs utilizing various antisense mechanisms are demonstrating therapeutic potential for the treatment of a broad variety of diseases. This review focuses on some of the advances that have taken place in translating antisense technology from the bench to the clinic.

Predicting research use in nursing organizations: a multilevel analysis.

PubMed

Estabrooks, Carole A; Midodzi, William K; Cummings, Greta G; Wallin, Lars

2007-01-01

No empirical literature was found that explained how organizational context (operationalized as a composite of leadership, culture, and evaluation) influences research utilization. Similarly, no work was found on the interaction of individuals and contextual factors, or the relative importance or contribution of forces at different organizational levels to either such proposed interactions or, ultimately, to research utilization. To determine independent factors that predict research utilization among nurses, taking into account influences at individual nurse, specialty, and hospital levels. Cross-sectional survey data for 4,421 registered nurses in Alberta, Canada were used in a series of multilevel (three levels) modeling analyses to predict research utilization. A multilevel model was developed in MLwiN version 2.0 and used to: (a) estimate simultaneous effects of several predictors and (b) quantify the amount of explained variance in research utilization that could be apportioned to individual, specialty, and hospital levels. There was significant variation in research utilization (p <.05). Factors (remaining in the final model at statistically significant levels) found to predict more research utilization at the three levels of analysis were as follows. At the individual nurse level (Level 1): time spent on the Internet and lower levels of emotional exhaustion. At the specialty level (Level 2): facilitation, nurse-to-nurse collaboration, a higher context (i.e., of nursing culture, leadership, and evaluation), and perceived ability to control policy. At the hospital level (Level 3): only hospital size was significant in the final model. The total variance in research utilization was 1.04, and the intraclass correlations (the percent contribution by contextual factors) were 4% (variance = 0.04, p <.01) at the hospital level and 8% (variance = 0.09, p <.05) at the specialty level. The contribution attributable to individual factors alone was 87% (variance = 0.91, p <.01). Variation in research utilization was explained mainly by differences in individual characteristics, with specialty- and organizational-level factors contributing relatively little by comparison. Among hospital-level factors, hospital size was the only significant determinant of research utilization. Although organizational determinants explained less variance in the model, they were still statistically significant when analyzed alone. These findings suggest that investigations into mechanisms that influence research utilization must address influences at multiple levels of the organization. Such investigations will require careful attention to both methodological and interpretative challenges present when dealing with multiple units of analysis.

New developments in the treatment of multiple myeloma - clinical utility of daratumumab.

PubMed

McEllistrim, Cian; Krawczyk, Janusz; O'Dwyer, Michael E

2017-01-01

Multiple myeloma is a clonal disorder of plasma cells that is currently considered incurable. CD38 is a 46 kDa type II transmembrane glycoprotein that is highly expressed on myeloma cells. Daratumumab is a first in-class human IgG1 monoclonal antibody that targets CD38, and has antimyeloma effects through several mechanisms. Single-agent trials show surprising activity in heavily pretreated myeloma patients. Trials in the relapsed setting, where daratumumab is added to lenalidomide and dexamethasone or bortezomib and dexamethasone, have demonstrated significantly improved progression-free survival with acceptable toxicity. In this review, we discuss the mechanism of action, pharmacology and pharmacokinetics of daratumumab and review the available clinical data in detail. We examine how daratumumab interferes with transfusion testing due to the expression of CD38 on the red blood cells, leading to potential difficulties releasing blood products. Daratumumab also affects disease assessments in multiple myeloma, including serum protein electrophoresis, immunofixation and flow cytometry. Strategies to mitigate these effects are discussed. The optimal use of daratumumab has yet to be decided, and several trials are ongoing in the relapsed and upfront setting. We discuss the potential upfront role of this exciting therapy, which has significant potential for increased minimal residual disease negativity and improved progression-free survival even in high-risk groups.

New developments in the treatment of multiple myeloma – clinical utility of daratumumab

PubMed Central

McEllistrim, Cian; Krawczyk, Janusz; O’Dwyer, Michael E

2017-01-01

Multiple myeloma is a clonal disorder of plasma cells that is currently considered incurable. CD38 is a 46 kDa type II transmembrane glycoprotein that is highly expressed on myeloma cells. Daratumumab is a first in-class human IgG1 monoclonal antibody that targets CD38, and has antimyeloma effects through several mechanisms. Single-agent trials show surprising activity in heavily pretreated myeloma patients. Trials in the relapsed setting, where daratumumab is added to lenalidomide and dexamethasone or bortezomib and dexamethasone, have demonstrated significantly improved progression-free survival with acceptable toxicity. In this review, we discuss the mechanism of action, pharmacology and pharmacokinetics of daratumumab and review the available clinical data in detail. We examine how daratumumab interferes with transfusion testing due to the expression of CD38 on the red blood cells, leading to potential difficulties releasing blood products. Daratumumab also affects disease assessments in multiple myeloma, including serum protein electrophoresis, immunofixation and flow cytometry. Strategies to mitigate these effects are discussed. The optimal use of daratumumab has yet to be decided, and several trials are ongoing in the relapsed and upfront setting. We discuss the potential upfront role of this exciting therapy, which has significant potential for increased minimal residual disease negativity and improved progression-free survival even in high-risk groups. PMID:28442888

Multi-Stimuli Responsive Macromolecules and Their Assemblies

PubMed Central

Zhuang, Jiaming; Gordon, Mallory; Ventura, Judy; Li, Longyu; Thayumanavan, S.

2013-01-01

In this review, we outline examples that illustrate the design criteria for achieving macromolecular assemblies that incorporate a combination of two or more chemical, physical or biological stimuli-responsive components. Progress in both fundamental investigation into the phase transformations of these polymers in response to multiple stimuli and their utilization in a variety of pratical applications have been highlighted. Using these examples, we aim to explain the origin of employed mechanisms of stimuli responsiveness which may serve as a guideline to inspire future design of multi-stimuli responsive materials. PMID:23765263

Recent progress of TAMA300

NASA Astrophysics Data System (ADS)

Arai, K.; TAMA Collaboration

2008-07-01

Current effort of the TAMA project is focused on establishment of the interferometer operation with a new vibration isolation system, called 'Seismic Attenuation System' (SAS). The SAS employs a multiple stage structure to realize soft spring for all of directions, as well as utilizes active control systems to stabilize mechanical resonances in the low frequency region below 1 Hz. The SASs were installed for four test masses, resulting in improvement of cavity length fluctuation below 150 Hz. We describe the structure of the SAS and its local active control system, and the status of the interferometer.

Schizophrenia-associated methylomic variation: molecular signatures of disease and polygenic risk burden across multiple brain regions.

PubMed

Viana, Joana; Hannon, Eilis; Dempster, Emma; Pidsley, Ruth; Macdonald, Ruby; Knox, Olivia; Spiers, Helen; Troakes, Claire; Al-Saraj, Safa; Turecki, Gustavo; Schalkwyk, Leonard C; Mill, Jonathan

2017-01-01

Genetic association studies provide evidence for a substantial polygenic component to schizophrenia, although the neurobiological mechanisms underlying the disorder remain largely undefined. Building on recent studies supporting a role for developmentally regulated epigenetic variation in the molecular aetiology of schizophrenia, this study aimed to identify epigenetic variation associated with both a diagnosis of schizophrenia and elevated polygenic risk burden for the disease across multiple brain regions. Genome-wide DNA methylation was quantified in 262 post-mortem brain samples, representing tissue from four brain regions (prefrontal cortex, striatum, hippocampus and cerebellum) from 41 schizophrenia patients and 47 controls. We identified multiple disease-associated and polygenic risk score-associated differentially methylated positions and regions, which are not enriched in genomic regions identified in genetic studies of schizophrenia and do not reflect direct genetic effects on DNA methylation. Our study represents the first analysis of epigenetic variation associated with schizophrenia across multiple brain regions and highlights the utility of polygenic risk scores for identifying molecular pathways associated with aetiological variation in complex disease. © The Author 2016. Published by Oxford University Press.

Partial genome assembly for a candidate division OP11 single cell from an anoxic spring (Zodletone Spring, Oklahoma).

PubMed

Youssef, Noha H; Blainey, Paul C; Quake, Stephen R; Elshahed, Mostafa S

2011-11-01

Members of candidate division OP11 are widely distributed in terrestrial and marine ecosystems, yet little information regarding their metabolic capabilities and ecological role within such habitats is currently available. Here, we report on the microfluidic isolation, multiple-displacement-amplification, pyrosequencing, and genomic analysis of a single cell (ZG1) belonging to candidate division OP11. Genome analysis of the ∼270-kb partial genome assembly obtained showed that it had no particular similarity to a specific phylum. Four hundred twenty-three open reading frames were identified, 46% of which had no function prediction. In-depth analysis revealed a heterotrophic lifestyle, with genes encoding endoglucanase, amylopullulanase, and laccase enzymes, suggesting a capacity for utilization of cellulose, starch, and, potentially, lignin, respectively. Genes encoding several glycolysis enzymes as well as formate utilization were identified, but no evidence for an electron transport chain was found. The presence of genes encoding various components of lipopolysaccharide biosynthesis indicates a Gram-negative bacterial cell wall. The partial genome also provides evidence for antibiotic resistance (β-lactamase, aminoglycoside phosphotransferase), as well as antibiotic production (bacteriocin) and extracellular bactericidal peptidases. Multiple mechanisms for stress response were identified, as were elements of type I and type IV secretion systems. Finally, housekeeping genes identified within the partial genome were used to demonstrate the OP11 affiliation of multiple hitherto unclassified genomic fragments from multiple database-deposited metagenomic data sets. These results provide the first glimpse into the lifestyle of a member of a ubiquitous, yet poorly understood bacterial candidate division.

Recent Initiatives in the Republic of Srpska to Enhance Appropriate Use of Antibiotics in Ambulatory Care; Their Influence and Implications.

PubMed

Bojanić, Ljubica; Marković-Peković, Vanda; Škrbić, Ranko; Stojaković, Nataša; Ðermanović, Mirjana; Bojanić, Janja; Fürst, Jurij; Kurdi, Amanj B; Godman, Brian

2018-01-01

Introduction: There are increasing concerns world-wide with growing rates of antibiotic resistance necessitating urgent action. There have been a number of initiatives in the Republic of Srpska in recent years to address this and improve rational antibiotic prescribing and dispensing despite limited resources to fund multiple initiatives. Objective: Analyse antibiotic utilization patterns in the Republic of Srpska following these multiple initiatives as a basis for developing future programmes in the Republic if needed. Methods: Observational retrospective study of total outpatient antibiotic utilization from 2010 to 2015, based on data obtained from the Public Health Institute, alongside documentation of ongoing initiatives to influence utilization. The quality of antibiotic utilization principally assessed according to ESAC, ECDC, and WHO quality indicators and DU 90% (the drug utilization 90%) profile as well as vs. neighboring countries. Results: Following multiple initiatives, antibiotic utilization remained relatively stable in the Republic at 15.6 to 18.4 DIDs, with a decreasing trend in recent years, with rates comparable or lower than neighboring countries. Amoxicillin and the penicillins accounted for 29-40 and 50% of total utilization, respectively. Overall, limited utilization of co-amoxiclav (7-11%), cephalosporins, macrolides, and quinolones, as well as low use of third and fourth generation cephalosporins vs. first and second cephalosporins. However, increasing utilization of co-amoxiclav and azithromycin, as well as higher rates of quinolone utilization compared to some countries, was seen. Conclusions: Multiple interventions in the Republic of Srpska in recent years have resulted in one of the lowest utilization of antibiotics when compared with similar countries, acting as an exemplar to others. However, there are some concerns with current utilization of co-amoxiclav and azithromycin which are being addressed. This will be the subject of future research activities.

Multiscale regression modeling in mouse supraspinatus tendons reveals that dynamic processes act as mediators in structure-function relationships.

PubMed

Connizzo, Brianne K; Adams, Sheila M; Adams, Thomas H; Jawad, Abbas F; Birk, David E; Soslowsky, Louis J

2016-06-14

Recent advances in technology have allowed for the measurement of dynamic processes (re-alignment, crimp, deformation, sliding), but only a limited number of studies have investigated their relationship with mechanical properties. The overall objective of this study was to investigate the role of composition, structure, and the dynamic response to load in predicting tendon mechanical properties in a multi-level fashion mimicking native hierarchical collagen structure. Multiple linear regression models were investigated to determine the relationships between composition/structure, dynamic processes, and mechanical properties. Mediation was then used to determine if dynamic processes mediated structure-function relationships. Dynamic processes were strong predictors of mechanical properties. These predictions were location-dependent, with the insertion site utilizing all four dynamic responses and the midsubstance responding primarily with fibril deformation and sliding. In addition, dynamic processes were moderately predicted by composition and structure in a regionally-dependent manner. Finally, dynamic processes were partial mediators of the relationship between composition/structure and mechanical function, and results suggested that mediation is likely shared between multiple dynamic processes. In conclusion, the mechanical properties at the midsubstance of the tendon are controlled primarily by fibril structure and this region responds to load via fibril deformation and sliding. Conversely, the mechanical function at the insertion site is controlled by many other important parameters and the region responds to load via all four dynamic mechanisms. Overall, this study presents a strong foundation on which to design future experimental and modeling efforts in order to fully understand the complex structure-function relationships present in tendon. Copyright © 2016 Elsevier Ltd. All rights reserved.

Thermodynamics of transport through the ammonium transporter Amt-1 investigated with free energy calculations.

PubMed

Ullmann, R Thomas; Andrade, Susana L A; Ullmann, G Matthias

2012-08-16

Amt-1 from Archaeoglobus fulgidus (AfAmt-1) belongs to the Amt/Rh family of ammonium/ammonia transporting membrane proteins. The transport mode and the precise microscopic permeation mechanism utilized by these proteins are intensely debated. Open questions concern the identity of the transported substrate (ammonia and/or ammonium) and whether the transport is passive or active. To address these questions, we studied the overall thermodynamics of the different transport modes as a function of the environmental conditions. Then, we investigated the thermodynamics of the underlying microscopic transport mechanisms with free energy calculations within a continuum electrostatics model. The formalism developed for this purpose is of general utility in the calculation of binding free energies for ligands with multiple protonation forms or other binding forms. The results of our calculations are compared to the available experimental and theoretical data on Amt/Rh proteins and discussed in light of the current knowledge on the physiological conditions experienced by microorganisms and plants. We found that microscopic models of electroneutral and electrogenic transport modes are in principle thermodynamically viable. However, only the electrogenic variants have a net thermodynamic driving force under the physiological conditions experienced by microorganisms and plants. Thus, the transport mechanism of AfAmt-1 is most likely electrogenic.

Carbon catabolite regulation in Streptomyces: new insights and lessons learned.

PubMed

Romero-Rodríguez, Alba; Rocha, Diana; Ruiz-Villafán, Beatriz; Guzmán-Trampe, Silvia; Maldonado-Carmona, Nidia; Vázquez-Hernández, Melissa; Zelarayán, Augusto; Rodríguez-Sanoja, Romina; Sánchez, Sergio

2017-09-01

One of the most significant control mechanisms of the physiological processes in the genus Streptomyces is carbon catabolite repression (CCR). This mechanism controls the expression of genes involved in the uptake and utilization of alternative carbon sources in Streptomyces and is mostly independent of the phosphoenolpyruvate phosphotransferase system (PTS). CCR also affects morphological differentiation and the synthesis of secondary metabolites, although not all secondary metabolite genes are equally sensitive to the control by the carbon source. Even when the outcome effect of CCR in bacteria is the same, their essential mechanisms can be rather different. Although usually, glucose elicits this phenomenon, other rapidly metabolized carbon sources can also cause CCR. Multiple efforts have been put through to the understanding of the mechanism of CCR in this genus. However, a reasonable mechanism to explain the nature of this process in Streptomyces does not yet exist. Several examples of primary and secondary metabolites subject to CCR will be examined in this review. Additionally, recent advances in the metabolites and protein factors involved in the Streptomyces CCR, as well as their mechanisms will be described and discussed in this review.

Multi-layer network utilizing rewarded spike time dependent plasticity to learn a foraging task

PubMed Central

2017-01-01

Neural networks with a single plastic layer employing reward modulated spike time dependent plasticity (STDP) are capable of learning simple foraging tasks. Here we demonstrate advanced pattern discrimination and continuous learning in a network of spiking neurons with multiple plastic layers. The network utilized both reward modulated and non-reward modulated STDP and implemented multiple mechanisms for homeostatic regulation of synaptic efficacy, including heterosynaptic plasticity, gain control, output balancing, activity normalization of rewarded STDP and hard limits on synaptic strength. We found that addition of a hidden layer of neurons employing non-rewarded STDP created neurons that responded to the specific combinations of inputs and thus performed basic classification of the input patterns. When combined with a following layer of neurons implementing rewarded STDP, the network was able to learn, despite the absence of labeled training data, discrimination between rewarding patterns and the patterns designated as punishing. Synaptic noise allowed for trial-and-error learning that helped to identify the goal-oriented strategies which were effective in task solving. The study predicts a critical set of properties of the spiking neuronal network with STDP that was sufficient to solve a complex foraging task involving pattern classification and decision making. PMID:28961245

The bacterial dicarboxylate transporter, VcINDY, uses a two-domain elevator-type mechanism

PubMed Central

Mulligan, Christopher; Fenollar-Ferrer, Cristina; Fitzgerald, Gabriel A.; Vergara-Jaque, Ariela; Kaufmann, Desirée; Li, Yan; Forrest, Lucy R.; Mindell, Joseph A.

2016-01-01

Secondary transporters use alternating access mechanisms to couple uphill substrate movement to downhill ion flux. Most known transporters utilize a “rocking bundle” motion, where the protein moves around an immobile substrate binding site. However, the glutamate transporter homolog, GltPh, translocates its substrate binding site vertically across the membrane, an “elevator” mechanism. Here, we used the “repeat swap” approach to computationally predict the outward-facing state of the Na+/succinate transporter VcINDY, from Vibrio cholerae. Our model predicts a substantial “elevator”-like movement of vcINDY’s substrate binding site, with a vertical translation of ~15 Å and a rotation of ~43°; multiple disulfide crosslinks which completely inhibit transport provide experimental confirmation and demonstrate that such movement is essential. In contrast, crosslinks across the VcINDY dimer interface preserve transport, revealing an absence of large scale coupling between protomers. PMID:26828963

Screening and characterization of novel bacteriocins from lactic acid bacteria.

PubMed

Zendo, Takeshi

2013-01-01

Bacteriocins produced by lactic acid bacteria (LAB) are expected to be safe antimicrobial agents. While the best studied LAB bacteriocin, nisin A, is widely utilized as a food preservative, various novel ones are required to control undesirable bacteria more effectively. To discover novel bacteriocins at the early step of the screening process, we developed a rapid screening system that evaluates bacteriocins produced by newly isolated LAB based on their antibacterial spectra and molecular masses. By means of this system, various novel bacteriocins were identified, including a nisin variant, nisin Q, a two-peptide bacteriocin, lactococcin Q, a leaderless bacteriocin, lacticin Q, and a circular bacteriocin, lactocyclicin Q. Moreover, some LAB isolates were found to produce multiple bacteriocins. They were characterized as to their structures, mechanisms of action, and biosynthetic mechanisms. Novel LAB bacteriocins and their biosynthetic mechanisms are expected for applications such as food preservation and peptide engineering.

Material properties of biofilms – key methods for understanding permeability and mechanics

PubMed Central

Billings, Nicole; Birjiniuk, Alona; Samad, Tahoura S.; Doyle, Patrick S.; Ribbeck, Katharina

2015-01-01

Microorganisms can form biofilms, which are multicellular communities surrounded by a hydrated extracellular matrix of polymers. Central properties of the biofilm are governed by this extracellular matrix, which provides mechanical stability to the three-dimensional biofilm structure, regulates the ability of the biofilm to adhere to surfaces, and determines the ability of the biofilm to adsorb gasses, solutes, and foreign cells. Despite their critical relevance for understanding and eliminating of biofilms, the materials properties of the extracellular matrix are understudied. Here, we offer the reader a guide to current technologies that can be utilized to specifically assess the permeability and mechanical properties of the biofilm matrix and its interacting components. In particular, we highlight technological advances in instrumentation and interactions between multiple disciplines that have broadened the spectrum of methods available to conduct these studies. We review pioneering work that furthers our understanding of the material properties of biofilms. PMID:25719969

Material properties of biofilms—a review of methods for understanding permeability and mechanics

NASA Astrophysics Data System (ADS)

Billings, Nicole; Birjiniuk, Alona; Samad, Tahoura S.; Doyle, Patrick S.; Ribbeck, Katharina

2015-02-01

Microorganisms can form biofilms, which are multicellular communities surrounded by a hydrated extracellular matrix of polymers. Central properties of the biofilm are governed by this extracellular matrix, which provides mechanical stability to the 3D biofilm structure, regulates the ability of the biofilm to adhere to surfaces, and determines the ability of the biofilm to adsorb gases, solutes, and foreign cells. Despite their critical relevance for understanding and eliminating of biofilms, the materials properties of the extracellular matrix are understudied. Here, we offer the reader a guide to current technologies that can be utilized to specifically assess the permeability and mechanical properties of the biofilm matrix and its interacting components. In particular, we highlight technological advances in instrumentation and interactions between multiple disciplines that have broadened the spectrum of methods available to conduct these studies. We review pioneering work that furthers our understanding of the material properties of biofilms.

Shigella Iron Acquisition Systems and their Regulation.

PubMed

Wei, Yahan; Murphy, Erin R

2016-01-01

Survival of Shigella within the host is strictly dependent on the ability of the pathogen to acquire essential nutrients, such as iron. As an innate immune defense against invading pathogens, the level of bio-available iron within the human host is maintained at exceeding low levels, by sequestration of the element within heme and other host iron-binding compounds. In response to sequestration mediated iron limitation, Shigella produce multiple iron-uptake systems that each function to facilitate the utilization of a specific host-associated source of nutrient iron. As a mechanism to balance the essential need for iron and the toxicity of the element when in excess, the production of bacterial iron acquisition systems is tightly regulated by a variety of molecular mechanisms. This review summarizes the current state of knowledge on the iron-uptake systems produced by Shigella species, their distribution within the genus, and the molecular mechanisms that regulate their production.

Dual-Mechanism and Multimotion Soft Actuators Based on Commercial Plastic Film.

PubMed

Li, Linpeng; Meng, Junxing; Hou, Chengyi; Zhang, Qinghong; Li, Yaogang; Yu, Hao; Wang, Hongzhi

2018-05-02

Soft actuators have attracted a lot of attention owing to their biomimetic performance. However, the development of soft actuators that are easily prepared from readily available raw materials, conveniently utilized, and cost-efficient is still a challenge. Here, we present a simple method to fabricate a polyethylene-based soft actuator. It has controllable anisotropic structure and can realize multiple motions, including bidirectional bending and twisting based on dual mechanisms, which is a rare phenomenon. Especially, the soft actuators can response at a very small temperature difference (Δ T ≥ 2.3 °C); therefore, even skin touch can quickly drive the actuator, which greatly broadens its applications in daily life. The soft actuator could demonstrate a curvature up to 7.8 cm -1 accompanied by powerful actuation. We have shown that it can lift an object 27 times its own weight. We also demonstrate the application of this actuator as intelligent mechanical devices.

Entomopathogenic bacteria use multiple mechanisms for bioactive peptide library design

NASA Astrophysics Data System (ADS)

Cai, Xiaofeng; Nowak, Sarah; Wesche, Frank; Bischoff, Iris; Kaiser, Marcel; Fürst, Robert; Bode, Helge. B.

2017-04-01

The production of natural product compound libraries has been observed in nature for different organisms such as bacteria, fungi and plants; however, little is known about the mechanisms generating such chemically diverse libraries. Here we report mechanisms leading to the biosynthesis of the chemically diverse rhabdopeptide/xenortide peptides (RXPs). They are exclusively present in entomopathogenic bacteria of the genera Photorhabdus and Xenorhabdus that live in symbiosis with nematodes delivering them to insect prey, which is killed and utilized for nutrition by both nematodes and bacteria. Chemical diversity of the biologically active RXPs results from a combination of iterative and flexible use of monomodular nonribosomal peptide synthetases including substrate promiscuity, enzyme cross-talk and enzyme stoichiometry as shown by in vivo and in vitro experiments. Together, this highlights several of nature's methods for diversification, or evolution, of natural products and sheds light on the biosynthesis of the bioactive RXPs.

Characterization of the regulation of a plant polysaccharide utilization operon and its role in biofilm formation in Bacillus subtilis

PubMed Central

Habib, Cameron; Yu, Yiyang; Gozzi, Kevin; Ching, Carly; Shemesh, Moshe

2017-01-01

The soil bacterium Bacillus subtilis is often found in association with plants in the rhizosphere. Previously, plant polysaccharides have been shown to stimulate formation of root-associated multicellular communities, or biofilms, in this bacterium, yet the underlying mechanism is not fully understood. A five-gene gan operon (ganSPQAB) in B. subtilis has recently been shown to be involved in utilization of the plant-derived polysaccharide galactan. Despite these findings, molecular details about the regulation of the operon and the role of the operon in biofilm formation remain elusive. In this study, we performed comprehensive genetic analyses on the regulation of the gan operon. We show that this operon is regulated both by a LacI-like transcription repressor (GanR), which directly binds to pairs of inverted DNA repeats in the promoter region of the operon, and by the catabolite control protein A (CcpA). Derepression can be triggered by the presence of the inducer β-1,4-galactobiose, a hydrolysis product of galactan, or in situ when B. subtilis cells are associated with plant roots. In addition to the transcriptional regulation, the encoded ß-galactosidase GanA (by ganA), which hydrolyzes ß-1,4-galactobiose into galactose, is inhibited at the enzymatic level by the catalytic product galactose. Thus, the galactan utilization pathway is under complex regulation involving both positive and negative feedback mechanisms in B. subtilis. We discuss about the biological significance of such complex regulation as well as a hypothesis of biofilm induction by galactan via multiple mechanisms. PMID:28617843

Proposal for quantum many-body simulation and torsional matter-wave interferometry with a levitated nanodiamond

NASA Astrophysics Data System (ADS)

Ma, Yue; Hoang, Thai M.; Gong, Ming; Li, Tongcang; Yin, Zhang-qi

2017-08-01

Hybrid spin-mechanical systems have great potential in sensing, macroscopic quantum mechanics, and quantum information science. In order to induce strong coupling between an electron spin and the center-of-mass motion of a mechanical oscillator, a large magnetic gradient usually is required, which is difficult to achieve. Here we show that strong coupling between the electron spin of a nitrogen-vacancy (NV) center and the torsional vibration of an optically levitated nanodiamond can be achieved in a uniform magnetic field. Thanks to the uniform magnetic field, multiple spins can strongly couple to the torsional vibration at the same time. We propose utilizing this coupling mechanism to realize the Lipkin-Meshkov-Glick (LMG) model by an ensemble of NV centers in a levitated nanodiamond. The quantum phase transition in the LMG model and finite number effects can be observed with this system. We also propose generating torsional superposition states and realizing torsional matter-wave interferometry with spin-torsional coupling.

Utilizing Multifaceted Rasch Measurement through Facets to Evaluate Science Education Data Sets Composed of Judges, Respondents, and Rating Scale Items: An Exemplar Utilizing the Elementary Science Teaching Analysis Matrix Instrument

ERIC Educational Resources Information Center

Boone, William J.; Townsend, J. Scott; Staver, John R.

2016-01-01

When collecting data, science education researchers frequently have multiple respondents evaluate multiple artifacts using multiple criteria. Herein, the authors introduce Multifaceted Rasch Measurement (MFRM) analysis and explain why MFRM must be used when "judges'" data are collected. The authors use data from elementary science…

System and method for optimal load and source scheduling in context aware homes

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

Shetty, Pradeep; Foslien Graber, Wendy; Mangsuli, Purnaprajna R.

A controller for controlling energy consumption in a home includes a constraints engine to define variables for multiple appliances in the home corresponding to various home modes and persona of an occupant of the home. A modeling engine models multiple paths of energy utilization of the multiple appliances to place the home into a desired state from a current context. An optimal scheduler receives the multiple paths of energy utilization and generates a schedule as a function of the multiple paths and a selected persona to place the home in a desired state.

Physical Activity Modulates Common Neuroplasticity Substrates in Major Depressive and Bipolar Disorder

PubMed Central

2017-01-01

Mood disorders (MDs) are chronic, recurrent mental diseases that affect millions of individuals worldwide. Although the biogenic amine model has provided some clinical utility, a need remains to better understand the interrelated mechanisms that contribute to neuroplasticity deficits in MDs and the means by which various therapeutics mitigate them. Of those therapeutics being investigated, physical activity (PA) has shown clear and consistent promise. Accordingly, the aims of this review are to (1) explicate key modulators, processes, and interactions that impinge upon multiple susceptibility points to effectuate neuroplasticity deficits in MDs; (2) explore the putative mechanisms by which PA mitigates these features; (3) review protocols used to induce the positive effects of PA in MDs; and (4) highlight implications for clinicians and researchers. PMID:28529805

Methods for structuring scientific knowledge from many areas related to aging research.

PubMed

Zhavoronkov, Alex; Cantor, Charles R

2011-01-01

Aging and age-related disease represents a substantial quantity of current natural, social and behavioral science research efforts. Presently, no centralized system exists for tracking aging research projects across numerous research disciplines. The multidisciplinary nature of this research complicates the understanding of underlying project categories, the establishment of project relations, and the development of a unified project classification scheme. We have developed a highly visual database, the International Aging Research Portfolio (IARP), available at AgingPortfolio.org to address this issue. The database integrates information on research grants, peer-reviewed publications, and issued patent applications from multiple sources. Additionally, the database uses flexible project classification mechanisms and tools for analyzing project associations and trends. This system enables scientists to search the centralized project database, to classify and categorize aging projects, and to analyze the funding aspects across multiple research disciplines. The IARP is designed to provide improved allocation and prioritization of scarce research funding, to reduce project overlap and improve scientific collaboration thereby accelerating scientific and medical progress in a rapidly growing area of research. Grant applications often precede publications and some grants do not result in publications, thus, this system provides utility to investigate an earlier and broader view on research activity in many research disciplines. This project is a first attempt to provide a centralized database system for research grants and to categorize aging research projects into multiple subcategories utilizing both advanced machine algorithms and a hierarchical environment for scientific collaboration.

Fluorescence-based detection and quantification of features of cellular senescence.

PubMed

Cho, Sohee; Hwang, Eun Seong

2011-01-01

Cellular senescence is a spontaneous organismal defense mechanism against tumor progression which is raised upon the activation of oncoproteins or other cellular environmental stresses that must be circumvented for tumorigenesis to occur. It involves growth-arrest state of normal cells after a number of active divisions. There are multiple experimental routes that can drive cells into a state of senescence. Normal somatic cells and cancer cells enter a state of senescence upon overexpression of oncogenic Ras or Raf protein or by imposing certain kinds of stress such as cellular tumor suppressor function. Both flow cytometry and confocal imaging analysis techniques are very useful in quantitative analysis of cellular senescence phenomenon. They allow quantitative estimates of multiple different phenotypes expressed in multiple cell populations simultaneously. Here we review the various types of fluorescence methodologies including confocal imaging and flow cytometry that are frequently utilized to study a variety of senescence. First, we discuss key cell biological changes occurring during senescence and review the current understanding on the mechanisms of these changes with the goal of improving existing protocols and further developing new ones. Next, we list specific senescence phenotypes associated with each cellular trait along with the principles of their assay methods and the significance of the assay outcomes. We conclude by selecting appropriate references that demonstrate a typical example of each method. Copyright © 2011 Elsevier Inc. All rights reserved.

Comparative analysis on flexibility requirements of typical Cryogenic Transfer lines

NASA Astrophysics Data System (ADS)

Jadon, Mohit; Kumar, Uday; Choukekar, Ketan; Shah, Nitin; Sarkar, Biswanath

2017-04-01

The cryogenic systems and their applications; primarily in large Fusion devices, utilize multiple cryogen transfer lines of various sizes and complexities to transfer cryogenic fluids from plant to the various user/ applications. These transfer lines are composed of various critical sections i.e. tee section, elbows, flexible components etc. The mechanical sustainability (under failure circumstances) of these transfer lines are primary requirement for safe operation of the system and applications. The transfer lines need to be designed for multiple design constraints conditions like line layout, support locations and space restrictions. The transfer lines are subjected to single load and multiple load combinations, such as operational loads, seismic loads, leak in insulation vacuum loads etc. [1]. The analytical calculations and flexibility analysis using professional software are performed for the typical transfer lines without any flexible component, the results were analysed for functional and mechanical load conditions. The failure modes were identified along the critical sections. The same transfer line was then refurbished with the flexible components and analysed for failure modes. The flexible components provide additional flexibility to the transfer line system and make it safe. The results obtained from the analytical calculations were compared with those obtained from the flexibility analysis software calculations. The optimization of the flexible component’s size and selection was performed and components were selected to meet the design requirements as per code.

An fMRI investigation of the effects of attempted naming on word retrieval in aphasia

PubMed Central

Heath, Shiree; McMahon, Katie L.; Nickels, Lyndsey A.; Angwin, Anthony; MacDonald, Anna D.; van Hees, Sophia; McKinnon, Eril; Johnson, Kori; Copland, David A.

2015-01-01

In healthy controls, picture naming performance can be facilitated by a single prior exposure to the same picture (“priming”). This priming phenomenon is utilized in the treatment of aphasia, which often includes repeated picture naming as part of a therapeutic task. The current study sought to determine whether single and/or multiple exposures facilitate subsequent naming in aphasia and whether such facilitatory effects act through normal priming mechanisms. A functional magnetic resonance imaging paradigm was employed to explore the beneficial effects of attempted naming in two individuals with aphasia and a control group. The timing and number of prior exposures was manipulated, with investigation of both short-term effects (single prior exposure over a period of minutes) and long-term effects (multiple presentations over a period of days). Following attempted naming, both short-term and long-term facilitated items showed improvement for controls, while only the long-term condition showed benefits at a behavioral level for the participants with aphasia. At a neural level, effects of long-term facilitation were noted in the left precuneus for one participant with aphasia, a result also identified for the equivalent contrast in controls. It appears that multiple attempts are required to improve naming performance in the presence of anomia and that for some individuals with aphasia the source of facilitation may be similar to unimpaired mechanisms engaged outside the language network. PMID:26074801

The Association Between Stimulant, Opioid, and Multiple Drug Use on Behavioral Health Care Utilization in a Safety-Net Health System.

PubMed

Calcaterra, Susan L; Keniston, Angela; Blum, Joshua; Crume, Tessa; Binswanger, Ingrid A

2015-01-01

Prior studies show an association between drug use and health care utilization. The relationship between specific drug type and emergent/urgent, inpatient, outpatient, and behavioral health care utilization has not been examined. We aimed to determine if multiple drug use was associated with increased utilization of behavioral health care. To assess health care utilization, we conducted a retrospective cohort study of patients who accessed health care at a safety-net medical center and affiliated clinics. Using electronic health records, we categorized patients who used stimulants, opioids, or multiple drugs based on urine toxicology screening tests and/or International Classification of Diseases, 9th Revision (ICD-9). Remaining patients were categorized as patients without identified drug use. Health care utilization by drug use group and visit type was determined using a negative binomial regression model. Associations were reported as incidence rate ratios. Utilization was described by rates of health care-related visits for inpatient, emergent/urgent, outpatient, and behavioral health care among patients who used drugs, categorized by drug types, compared with patients without identified drug use. Of 95,198 index visits, 4.6% (n=4340) were by patients who used drugs. Opioid and multiple drug users had significantly higher rates of behavioral health care visits than patients without identified drug use (opioid incidence rate ratio [IRR]=7.2; 95% confidence interval [CI]: 3.8-13.8; multiple drug use IRR=5.6, 95% CI: 3.3-9.7). Patients who used stimulants were less likely to use behavioral health services (IRR=1.3, 95% CI: 0.9-2.0) when compared with opioid and multiple drug users, but were more likely to use inpatient (IRR=1.6, 95% CI: 1.4-1.8) and emergent/urgent care (IRR=1.4, 95% CI: 1.3-1.5) services as compared with patients without identified drug use. Integrated medical and mental health care and drug treatment may reduce utilization of costly health care services and improve patient outcomes. How to capture and deliver primary care and behavioral health care to patients who use stimulants needs further investigation.

Oxytocin (OXT)-stimulated inhibition of Kir7.1 activity is through PIP2-dependent Ca2+ response of the oxytocin receptor in the retinal pigment epithelium in vitro.

PubMed

York, Nathaniel; Halbach, Patrick; Chiu, Michelle A; Bird, Ian M; Pillers, De-Ann M; Pattnaik, Bikash R

2017-09-01

Oxytocin (OXT) is a neuropeptide that activates the oxytocin receptor (OXTR), a rhodopsin family G-protein coupled receptor. Our localization of OXTR to the retinal pigment epithelium (RPE), in close proximity to OXT in the adjacent photoreceptor neurons, leads us to propose that OXT plays an important role in RPE-retinal communication. An increase of RPE [Ca 2+ ] i in response to OXT stimulation implies that the RPE may utilize oxytocinergic signaling as a mechanism by which it accomplishes some of its many roles. In this study, we used an established human RPE cell line, a HEK293 heterologous OXTR expression system, and pharmacological inhibitors of Ca 2+ signaling to demonstrate that OXTR utilizes capacitative Ca 2+ entry (CCE) mechanisms to sustain an increase in cytoplasmic Ca 2+ . These findings demonstrate how multiple functional outcomes of OXT-OXTR signaling could be integrated via a single pathway. In addition, the activated OXTR was able to inhibit the Kir7.1 channel, an important mediator of sub retinal waste transport and K + homeostasis. Published by Elsevier Inc.

Vemurafenib: an evidence-based review of its clinical utility in the treatment of metastatic melanoma.

PubMed

Swaika, Abhisek; Crozier, Jennifer A; Joseph, Richard W

2014-01-01

The discovery of BRAF mutations in the majority of patients with metastatic melanoma combined with the identification of highly selective BRAF inhibitors have revolutionized the treatment of patients with metastatic melanoma. The first highly specific BRAF inhibitor, vemurafenib, began clinical testing in 2008 and moved towards a rapid approval in 2011. Vemurafenib induced responses in ~50% of patients with metastatic BRAF-mutant melanoma and demonstrated improved overall survival in a randomized Phase III trial. Furthermore, vemurafenib is well-tolerated with a low toxicity profile and rapid onset of action. Finally, vemurafenib is active even in patients with widely metastatic disease. Despite the success of vemurafenib in treating patients with BRAF-mutant metastatic melanoma, most, if not all, patients ultimately develop resistance resulting in disease progression at a median time of ~6 months. Multiple mechanisms of resistance have been described and rationale strategies are underway to combat resistance. This review highlights the development, clinical utility, resistance mechanisms, and future use of vemurafenib both in melanoma and other malignancies. We consulted PubMed, Scopus, MEDLINE, ASCO annual symposium abstracts, and http://clinicaltrials.gov/ for the purpose of this review.

Vemurafenib: an evidence-based review of its clinical utility in the treatment of metastatic melanoma

PubMed Central

Swaika, Abhisek; Crozier, Jennifer A; Joseph, Richard W

2014-01-01

The discovery of BRAF mutations in the majority of patients with metastatic melanoma combined with the identification of highly selective BRAF inhibitors have revolutionized the treatment of patients with metastatic melanoma. The first highly specific BRAF inhibitor, vemurafenib, began clinical testing in 2008 and moved towards a rapid approval in 2011. Vemurafenib induced responses in ~50% of patients with metastatic BRAF-mutant melanoma and demonstrated improved overall survival in a randomized Phase III trial. Furthermore, vemurafenib is well-tolerated with a low toxicity profile and rapid onset of action. Finally, vemurafenib is active even in patients with widely metastatic disease. Despite the success of vemurafenib in treating patients with BRAF-mutant metastatic melanoma, most, if not all, patients ultimately develop resistance resulting in disease progression at a median time of ~6 months. Multiple mechanisms of resistance have been described and rationale strategies are underway to combat resistance. This review highlights the development, clinical utility, resistance mechanisms, and future use of vemurafenib both in melanoma and other malignancies. We consulted PubMed, Scopus, MEDLINE, ASCO annual symposium abstracts, and http://clinicaltrials.gov/ for the purpose of this review. PMID:24966667

Transdisciplinary Research and Evaluation for Community Health Initiatives

PubMed Central

Harper, Gary W.; Neubauer, Leah C.; Bangi, Audrey K.; Francisco, Vincent T.

2010-01-01

Transdisciplinary research and evaluation projects provide valuable opportunities to collaborate on interventions to improve the health and well-being of individuals and communities. Given team members’ diverse backgrounds and roles or responsibilities in such projects, members’ perspectives are significant in strengthening a project’s infrastructure and improving its organizational functioning. This article presents an evaluation mechanism that allows team members to express the successes and challenges incurred throughout their involvement in a multisite transdisciplinary research project. Furthermore, their feedback is used to promote future sustainability and growth. Guided by a framework known as organizational development, the evaluative process was conducted by a neutral entity, the Quality Assurance Team. A mixed-methods approach was utilized to garner feedback and clarify how the research project goals could be achieved more effectively and efficiently. The multiple benefits gained by those involved in this evaluation and implications for utilizing transdisciplinary research and evaluation teams for health initiatives are detailed. PMID:18936267

40 CFR 86.1806-04 - On-board diagnostics.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 2002). (vii) As an alternative to the above standards, heavy-duty vehicles may conform to the... standards shall utilize multiplicative factors from the California vehicle type (i.e. LEV II, ULEV II... standards shall utilize the Tier 2 Bin 4 emission standards and the CARB ULEV II multiplicative factors to...

Underestimation of Variance of Predicted Health Utilities Derived from Multiattribute Utility Instruments.

PubMed

Chan, Kelvin K W; Xie, Feng; Willan, Andrew R; Pullenayegum, Eleanor M

2017-04-01

Parameter uncertainty in value sets of multiattribute utility-based instruments (MAUIs) has received little attention previously. This false precision leads to underestimation of the uncertainty of the results of cost-effectiveness analyses. The aim of this study is to examine the use of multiple imputation as a method to account for this uncertainty of MAUI scoring algorithms. We fitted a Bayesian model with random effects for respondents and health states to the data from the original US EQ-5D-3L valuation study, thereby estimating the uncertainty in the EQ-5D-3L scoring algorithm. We applied these results to EQ-5D-3L data from the Commonwealth Fund (CWF) Survey for Sick Adults ( n = 3958), comparing the standard error of the estimated mean utility in the CWF population using the predictive distribution from the Bayesian mixed-effect model (i.e., incorporating parameter uncertainty in the value set) with the standard error of the estimated mean utilities based on multiple imputation and the standard error using the conventional approach of using MAUI (i.e., ignoring uncertainty in the value set). The mean utility in the CWF population based on the predictive distribution of the Bayesian model was 0.827 with a standard error (SE) of 0.011. When utilities were derived using the conventional approach, the estimated mean utility was 0.827 with an SE of 0.003, which is only 25% of the SE based on the full predictive distribution of the mixed-effect model. Using multiple imputation with 20 imputed sets, the mean utility was 0.828 with an SE of 0.011, which is similar to the SE based on the full predictive distribution. Ignoring uncertainty of the predicted health utilities derived from MAUIs could lead to substantial underestimation of the variance of mean utilities. Multiple imputation corrects for this underestimation so that the results of cost-effectiveness analyses using MAUIs can report the correct degree of uncertainty.

Poxviruses Utilize Multiple Strategies to Inhibit Apoptosis

PubMed Central

Nichols, Daniel Brian; De Martini, William; Cottrell, Jessica

2017-01-01

Cells have multiple means to induce apoptosis in response to viral infection. Poxviruses must prevent activation of cellular apoptosis to ensure successful replication. These viruses devote a substantial portion of their genome to immune evasion. Many of these immune evasion products expressed during infection antagonize cellular apoptotic pathways. Poxvirus products target multiple points in both the extrinsic and intrinsic apoptotic pathways, thereby mitigating apoptosis during infection. Interestingly, recent evidence indicates that poxviruses also hijack cellular means of eliminating apoptotic bodies as a means to spread cell to cell through a process called apoptotic mimicry. Poxviruses are the causative agent of many human and veterinary diseases. Further, there is substantial interest in developing these viruses as vectors for a variety of uses including vaccine delivery and as oncolytic viruses to treat certain human cancers. Therefore, an understanding of the molecular mechanisms through which poxviruses regulate the cellular apoptotic pathways remains a top research priority. In this review, we consider anti-apoptotic strategies of poxviruses focusing on three relevant poxvirus genera: Orthopoxvirus, Molluscipoxvirus, and Leporipoxvirus. All three genera express multiple products to inhibit both extrinsic and intrinsic apoptotic pathways with many of these products required for virulence. PMID:28786952

Characterization and detection of a widely distributed gene cluster that predicts anaerobic choline utilization by human gut bacteria.

PubMed

Martínez-del Campo, Ana; Bodea, Smaranda; Hamer, Hilary A; Marks, Jonathan A; Haiser, Henry J; Turnbaugh, Peter J; Balskus, Emily P

2015-04-14

Elucidation of the molecular mechanisms underlying the human gut microbiota's effects on health and disease has been complicated by difficulties in linking metabolic functions associated with the gut community as a whole to individual microorganisms and activities. Anaerobic microbial choline metabolism, a disease-associated metabolic pathway, exemplifies this challenge, as the specific human gut microorganisms responsible for this transformation have not yet been clearly identified. In this study, we established the link between a bacterial gene cluster, the choline utilization (cut) cluster, and anaerobic choline metabolism in human gut isolates by combining transcriptional, biochemical, bioinformatic, and cultivation-based approaches. Quantitative reverse transcription-PCR analysis and in vitro biochemical characterization of two cut gene products linked the entire cluster to growth on choline and supported a model for this pathway. Analyses of sequenced bacterial genomes revealed that the cut cluster is present in many human gut bacteria, is predictive of choline utilization in sequenced isolates, and is widely but discontinuously distributed across multiple bacterial phyla. Given that bacterial phylogeny is a poor marker for choline utilization, we were prompted to develop a degenerate PCR-based method for detecting the key functional gene choline TMA-lyase (cutC) in genomic and metagenomic DNA. Using this tool, we found that new choline-metabolizing gut isolates universally possessed cutC. We also demonstrated that this gene is widespread in stool metagenomic data sets. Overall, this work represents a crucial step toward understanding anaerobic choline metabolism in the human gut microbiota and underscores the importance of examining this microbial community from a function-oriented perspective. Anaerobic choline utilization is a bacterial metabolic activity that occurs in the human gut and is linked to multiple diseases. While bacterial genes responsible for choline fermentation (the cut gene cluster) have been recently identified, there has been no characterization of these genes in human gut isolates and microbial communities. In this work, we use multiple approaches to demonstrate that the pathway encoded by the cut genes is present and functional in a diverse range of human gut bacteria and is also widespread in stool metagenomes. We also developed a PCR-based strategy to detect a key functional gene (cutC) involved in this pathway and applied it to characterize newly isolated choline-utilizing strains. Both our analyses of the cut gene cluster and this molecular tool will aid efforts to further understand the role of choline metabolism in the human gut microbiota and its link to disease. Copyright © 2015 Martínez-del Campo et al.

Multiple Regulatory Systems Coordinate DNA Replication with Cell Growth in Bacillus subtilis

PubMed Central

Murray, Heath; Koh, Alan

2014-01-01

In many bacteria the rate of DNA replication is linked with cellular physiology to ensure that genome duplication is coordinated with growth. Nutrient-mediated growth rate control of DNA replication initiation has been appreciated for decades, however the mechanism(s) that connects these cell cycle activities has eluded understanding. In order to help address this fundamental question we have investigated regulation of DNA replication in the model organism Bacillus subtilis. Contrary to the prevailing view we find that changes in DnaA protein level are not sufficient to account for nutrient-mediated growth rate control of DNA replication initiation, although this regulation does require both DnaA and the endogenous replication origin. We go on to report connections between DNA replication and several essential cellular activities required for rapid bacterial growth, including respiration, central carbon metabolism, fatty acid synthesis, phospholipid synthesis, and protein synthesis. Unexpectedly, the results indicate that multiple regulatory systems are involved in coordinating DNA replication with cell physiology, with some of the regulatory systems targeting oriC while others act in a oriC-independent manner. We propose that distinct regulatory systems are utilized to control DNA replication in response to diverse physiological and chemical changes. PMID:25340815

Multiple regulatory systems coordinate DNA replication with cell growth in Bacillus subtilis.

PubMed

Murray, Heath; Koh, Alan

2014-10-01

In many bacteria the rate of DNA replication is linked with cellular physiology to ensure that genome duplication is coordinated with growth. Nutrient-mediated growth rate control of DNA replication initiation has been appreciated for decades, however the mechanism(s) that connects these cell cycle activities has eluded understanding. In order to help address this fundamental question we have investigated regulation of DNA replication in the model organism Bacillus subtilis. Contrary to the prevailing view we find that changes in DnaA protein level are not sufficient to account for nutrient-mediated growth rate control of DNA replication initiation, although this regulation does require both DnaA and the endogenous replication origin. We go on to report connections between DNA replication and several essential cellular activities required for rapid bacterial growth, including respiration, central carbon metabolism, fatty acid synthesis, phospholipid synthesis, and protein synthesis. Unexpectedly, the results indicate that multiple regulatory systems are involved in coordinating DNA replication with cell physiology, with some of the regulatory systems targeting oriC while others act in a oriC-independent manner. We propose that distinct regulatory systems are utilized to control DNA replication in response to diverse physiological and chemical changes.

Translating evidence based violence and drug use prevention to obesity prevention: development and construction of the pathways program.

PubMed

Sakuma, Kari-Lyn K; Riggs, Nathaniel R; Pentz, Mary Ann

2012-04-01

Effective school-based obesity prevention programs are needed to prevent and reduce the growing obesity risk among youth. Utilizing the evidence-rich areas of violence and substance use prevention, translation science may provide an efficient means for developing curricula across multiple health behaviors. This paper introduces Pathways to Health, a school-based obesity prevention program that was developed by translating from evidence-based violence and drug use prevention programs, Promoting Alternative THinking Strategies and the Midwestern Prevention Project STAR (STAR). We illustrate how a hypothesized underlying behavior change mechanism in two domains of risk behavior, violence and substance use, can be applied to obesity prevention. A 4-step translational process is provided and may be relevant for use in developing other curricula to address multiple health risk behaviors. Practical application and decision points are also provided.

Translating evidence based violence and drug use prevention to obesity prevention: development and construction of the Pathways program

PubMed Central

Sakuma, Kari-Lyn K.; Riggs, Nathaniel R.; Pentz, Mary Ann

2012-01-01

Effective school-based obesity prevention programs are needed to prevent and reduce the growing obesity risk among youth. Utilizing the evidence-rich areas of violence and substance use prevention, translation science may provide an efficient means for developing curricula across multiple health behaviors. This paper introduces Pathways to Health, a school-based obesity prevention program that was developed by translating from evidence-based violence and drug use prevention programs, Promoting Alternative THinking Strategies and the Midwestern Prevention Project STAR (STAR). We illustrate how a hypothesized underlying behavior change mechanism in two domains of risk behavior, violence and substance use, can be applied to obesity prevention. A 4-step translational process is provided and may be relevant for use in developing other curricula to address multiple health risk behaviors. Practical application and decision points are also provided. PMID:21987475

Studies of ambient noise in shallow water environments off Mexico and Alaska: characteristics, metrics and time-synchronization applications

NASA Astrophysics Data System (ADS)

Guerra, Melania

Sound in the ocean originates from multiple mechanisms, both natural and anthropogenic. Collectively, underwater ambient noise accumulates valuable information about both its sources and the oceanic environment that propagates this noise. Characterizing the features of ambient noise source mechanisms is challenging, but essential, for properly describing an acoustic environment. Disturbances to a local acoustic environment may affect many aquatic species that have adapted to be heavily dependent on this particular sense for survival functions. In the case of marine mammals, which are federally protected, demand exists for understanding such potential impacts, which drives important scientific efforts that utilize passive acoustic monitoring (PAM) tools to inform regulatory decisions. This dissertation presents two independent studies that use PAM data to investigate the characteristics of source mechanisms that dominate ambient noise in two diverse shallow water environments. The study in Chapter 2 directly addresses the concern of how anthropogenic activities can degrade the effectiveness of PAM. In the Alaskan Beaufort Sea, an environment where ambient noise is normally dominated by natural causes, seismic surveys create impulsive sounds to map the composition of the bottom. By inspecting single-sensor PAM data, the spectral characteristics of seismic survey airgun reverberation are measured, and their contribution to the overall ambient noise is quantified. This work is relevant to multiple ongoing mitigation protocols that rely on PAM to acoustically detect marine mammal presence during industrial operations. Meanwhile, Chapter 3 demonstrates that by analyzing data from multiple PAM sensors, features embedded in both directional and omnidirectional ambient noise can be used to develop new time-synchronization processing techniques for aligning autonomous elements of an acoustic array, a tool commonly used in PAM for detecting and tracking marine mammals. Using the time-synchronization procedures shown here, arrays may be built out of stand-alone recorders that simplify the deployment logistics and can be arranged in multiple configurations. Given increasing economic pressures worldwide, anthropogenic activities in the ocean are only expected to expand, and their ambient noise contributions will continue to rise. These studies provide baseline knowledge and practical tools to help properly assess the impact of such source mechanisms in shallow-water acoustic environments.

Optimum design of bolted composite lap joints under mechanical and thermal loading

NASA Astrophysics Data System (ADS)

Kradinov, Vladimir Yurievich

A new approach is developed for the analysis and design of mechanically fastened composite lap joints under mechanical and thermal loading. Based on the combined complex potential and variational formulation, the solution method satisfies the equilibrium equations exactly while the boundary conditions are satisfied by minimizing the total potential. This approach is capable of modeling finite laminate planform dimensions, uniform and variable laminate thickness, laminate lay-up, interaction among bolts, bolt torque, bolt flexibility, bolt size, bolt-hole clearance and interference, insert dimensions and insert material properties. Comparing to the finite element analysis, the robustness of the method does not decrease when modeling the interaction of many bolts; also, the method is more suitable for parametric study and design optimization. The Genetic Algorithm (GA), a powerful optimization technique for multiple extrema functions in multiple dimensions search spaces, is applied in conjunction with the complex potential and variational formulation to achieve optimum designs of bolted composite lap joints. The objective of the optimization is to acquire such a design that ensures the highest strength of the joint. The fitness function for the GA optimization is based on the average stress failure criterion predicting net-section, shear-out, and bearing failure modes in bolted lap joints. The criterion accounts for the stress distribution in the thickness direction at the bolt location by applying an approach utilizing a beam on an elastic foundation formulation.

Possible designs of medication monitors. Final report

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

Moulding, T.S.

A medication monitor is a device which utilizes radioactive material and photographic film to determine when patients remove medication from a dispenser. The material presents multiple, largely mechanical, ideas for making this type of dispenser so it can be used for a wide range of medication regimens. The description includes using the idea of a digital clock and memory chips for the time recording system. It also includes details on (1) choice of radioactive source and method of sealing source, (2) methods of locking or sealing medication monitors, (3) detailed instructions for using existing devices, (4) a simplified film developmentmore » system, (5) a mechanical and electronic means for creating a dispenser to reduce the chance of suicidal overdosage, and (6) an electronic means to allow a patient to compensate for medication forgotten without taking an excessive dose of medication.« less

Initial experience with the unrestricted introduction of sugammadex at a large academic medical center: a retrospective observational study examining postoperative mechanical ventilation and efficiency outcomes.

PubMed

Reilly-Shah, Vikas N O'; Lynde, Grant C; Mitchell, Matthew L; Maffeo, Carla L; Jabaley, Craig S; Wolf, Francis A

2018-05-30

Sugammadex can rapidly reverse deep neuromuscular blockade, but due to cost questions remain as to its optimal utilization. After introduction for unrestricted use at an academic medical center, we hypothesized that reductions would be demonstrated in the primary outcome of post-anesthesia care unit (PACU) mechanical ventilation (MV) and secondary outcomes of PACU length of stay (LOS), and emergence time (surgery end to anesthesia end time in PACU). We conducted a retrospective observational study of patients undergoing general anesthesia over a 12-month period. Using multiple variable penalized logistic regression in a one group before-and-after design, we compared categorized rates of PACU MV to examine the effect of sugammadex introduction following a post-hoc chart review to ascertain the reason for postoperative MV. Additionally, multiple variable linear regression was used to assess for differences in PACU LOS and emergence time within a propensity matched set of patients receiving neostigmine or sugammadex. 7,217 cases met inclusion criteria: 3,798 before and 3,419 after the introduction of sugammadex. The incidence of PACU MV was 2.3% before and 1.8% after (p=0.118). PACU MV due to residual neuromuscular blockade (rNMB) decreased from 0.63% to 0.20% (p=0.005). Ventilation due to other causes was unchanged. PACU LOS and emergence time were unchanged in a propensity matched set of 1,444 cases. We identified rNMB as an important contributor to PACU MV utilization and observed a significant decrease after sugammadex was introduced. The selected efficiency measures may not have been sufficiently granular to identify improvements following introduction.

Dimethyl Fumarate Protects Neural Stem/Progenitor Cells and Neurons from Oxidative Damage through Nrf2-ERK1/2 MAPK Pathway.

PubMed

Wang, Qin; Chuikov, Sergei; Taitano, Sophina; Wu, Qi; Rastogi, Arjun; Tuck, Samuel J; Corey, Joseph M; Lundy, Steven K; Mao-Draayer, Yang

2015-06-17

Multiple sclerosis (MS) is the most common multifocal inflammatory demyelinating disease of the central nervous system (CNS). Due to the progressive neurodegenerative nature of MS, developing treatments that exhibit direct neuroprotective effects are needed. Tecfidera™ (BG-12) is an oral formulation of the fumaric acid esters (FAE), containing the active metabolite dimethyl fumarate (DMF). Although BG-12 showed remarkable efficacy in lowering relapse rates in clinical trials, its mechanism of action in MS is not yet well understood. In this study, we reported the potential neuroprotective effects of dimethyl fumarate (DMF) on mouse and rat neural stem/progenitor cells (NPCs) and neurons. We found that DMF increased the frequency of the multipotent neurospheres and the survival of NPCs following oxidative stress with hydrogen peroxide (H2O2) treatment. In addition, utilizing the reactive oxygen species (ROS) assay, we showed that DMF reduced ROS production induced by H2O2. DMF also decreased oxidative stress-induced apoptosis. Using motor neuron survival assay, DMF significantly promoted survival of motor neurons under oxidative stress. We further analyzed the expression of oxidative stress-induced genes in the NPC cultures and showed that DMF increased the expression of transcription factor nuclear factor-erythroid 2-related factor 2 (Nrf2) at both levels of RNA and protein. Furthermore, we demonstrated the involvement of Nrf2-ERK1/2 MAPK pathway in DMF-mediated neuroprotection. Finally, we utilized SuperArray gene screen technology to identify additional anti-oxidative stress genes (Gstp1, Sod2, Nqo1, Srxn1, Fth1). Our data suggests that analysis of anti-oxidative stress mechanisms may yield further insights into new targets for treatment of multiple sclerosis (MS).

Dimethyl Fumarate Protects Neural Stem/Progenitor Cells and Neurons from Oxidative Damage through Nrf2-ERK1/2 MAPK Pathway

PubMed Central

Wang, Qin; Chuikov, Sergei; Taitano, Sophina; Wu, Qi; Rastogi, Arjun; Tuck, Samuel J.; Corey, Joseph M.; Lundy, Steven K.; Mao-Draayer, Yang

2015-01-01

Multiple sclerosis (MS) is the most common multifocal inflammatory demyelinating disease of the central nervous system (CNS). Due to the progressive neurodegenerative nature of MS, developing treatments that exhibit direct neuroprotective effects are needed. Tecfidera™ (BG-12) is an oral formulation of the fumaric acid esters (FAE), containing the active metabolite dimethyl fumarate (DMF). Although BG-12 showed remarkable efficacy in lowering relapse rates in clinical trials, its mechanism of action in MS is not yet well understood. In this study, we reported the potential neuroprotective effects of dimethyl fumarate (DMF) on mouse and rat neural stem/progenitor cells (NPCs) and neurons. We found that DMF increased the frequency of the multipotent neurospheres and the survival of NPCs following oxidative stress with hydrogen peroxide (H2O2) treatment. In addition, utilizing the reactive oxygen species (ROS) assay, we showed that DMF reduced ROS production induced by H2O2. DMF also decreased oxidative stress-induced apoptosis. Using motor neuron survival assay, DMF significantly promoted survival of motor neurons under oxidative stress. We further analyzed the expression of oxidative stress-induced genes in the NPC cultures and showed that DMF increased the expression of transcription factor nuclear factor-erythroid 2-related factor 2 (Nrf2) at both levels of RNA and protein. Furthermore, we demonstrated the involvement of Nrf2-ERK1/2 MAPK pathway in DMF-mediated neuroprotection. Finally, we utilized SuperArray gene screen technology to identify additional anti-oxidative stress genes (Gstp1, Sod2, Nqo1, Srxn1, Fth1). Our data suggests that analysis of anti-oxidative stress mechanisms may yield further insights into new targets for treatment of multiple sclerosis (MS). PMID:26090715

Multiple Intimate Partner Violence Experiences: Knowledge, Access, Utilization and Barriers to Utilization of Resources by Women of the African Diaspora.

PubMed

Sabri, Bushra; Huerta, Julia; Alexander, Kamila A; St Vil, Noelle M; Campbell, Jacquelyn C; Callwood, Gloria B

2015-11-01

This study examined knowledge, access, utilization, and barriers to use of resources among Black women exposed to multiple types of intimate partner violence in Baltimore, Maryland and the U.S. Virgin Islands (USVI). We analyzed quantitative survey data collected by 163 women recruited from primary care, prenatal or family planning clinics in Baltimore and the USVI. In addition we analyzed qualitative data from in-depth interviews with 11 women. Quantitative data were analyzed using descriptive statistics and qualitative data were analyzed using thematic analysis. A substantial proportion of Black women with multiple types of violence experiences lacked knowledge of, did not have access to, and did not use resources. Barriers to resource use were identified at the individual, relationship, and community levels. There is need for programs to develop awareness, promote access and utilization of resources, and eliminate barriers to resource use among abused Black women.

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

Elmagarmid, A.K.

The availability of distributed data bases is directly affected by the timely detection and resolution of deadlocks. Consequently, mechanisms are needed to make deadlock detection algorithms resilient to failures. Presented first is a centralized algorithm that allows transactions to have multiple requests outstanding. Next, a new distributed deadlock detection algorithm (DDDA) is presented, using a global detector (GD) to detect global deadlocks and local detectors (LDs) to detect local deadlocks. This algorithm essentially identifies transaction-resource interactions that m cause global (multisite) deadlocks. Third, a deadlock detection algorithm utilizing a transaction-wait-for (TWF) graph is presented. It is a fully disjoint algorithmmore » that allows multiple outstanding requests. The proposed algorithm can achieve improved overall performance by using multiple disjoint controllers coupled with the two-phase property while maintaining the simplicity of centralized schemes. Fourth, an algorithm that combines deadlock detection and avoidance is given. This algorithm uses concurrent transaction controllers and resource coordinators to achieve maximum distribution. The language of CSP is used to describe this algorithm. Finally, two efficient deadlock resolution protocols are given along with some guidelines to be used in choosing a transaction for abortion.« less

Membrane Repair: Mechanisms and Pathophysiology

PubMed Central

Cooper, Sandra T.; McNeil, Paul L.

2015-01-01

Eukaryotic cells have been confronted throughout their evolution with potentially lethal plasma membrane injuries, including those caused by osmotic stress, by infection from bacterial toxins and parasites, and by mechanical and ischemic stress. The wounded cell can survive if a rapid repair response is mounted that restores boundary integrity. Calcium has been identified as the key trigger to activate an effective membrane repair response that utilizes exocytosis and endocytosis to repair a membrane tear, or remove a membrane pore. We here review what is known about the cellular and molecular mechanisms of membrane repair, with particular emphasis on the relevance of repair as it relates to disease pathologies. Collective evidence reveals membrane repair employs primitive yet robust molecular machinery, such as vesicle fusion and contractile rings, processes evolutionarily honed for simplicity and success. Yet to be fully understood is whether core membrane repair machinery exists in all cells, or whether evolutionary adaptation has resulted in multiple compensatory repair pathways that specialize in different tissues and cells within our body. PMID:26336031

Underlying neural mechanisms of mirror therapy: Implications for motor rehabilitation in stroke.

PubMed

Arya, Kamal Narayan

2016-01-01

Mirror therapy (MT) is a valuable method for enhancing motor recovery in poststroke hemiparesis. The technique utilizes the mirror-illusion created by the movement of sound limb that is perceived as the paretic limb. MT is a simple and economical technique than can stimulate the brain noninvasively. The intervention unquestionably has neural foundation. But the underlying neural mechanisms inducing motor recovery are still unclear. In this review, the neural-modulation due to MT has been explored. Multiple areas of the brain such as the occipital lobe, dorsal frontal area and corpus callosum are involved during the simple MT regime. Bilateral premotor cortex, primary motor cortex, primary somatosensory cortex, and cerebellum also get reorganized to enhance the function of the damaged brain. The motor areas of the lesioned hemisphere receive visuo-motor processing information through the parieto-occipital lobe. The damaged motor cortex responds variably to the MT and may augment true motor recovery. Mirror neurons may also play a possible role in the cortico-stimulatory mechanisms occurring due to the MT.

Multiple policies to enhance prescribing efficiency for established medicines in Europe with a particular focus on demand-side measures: findings and future implications.

PubMed

Godman, Brian; Wettermark, Bjorn; van Woerkom, Menno; Fraeyman, Jessica; Alvarez-Madrazo, Samantha; Berg, Christian; Bishop, Iain; Bucsics, Anna; Campbell, Stephen; Finlayson, Alexander E; Fürst, Jurij; Garuoliene, Kristina; Herholz, Harald; Kalaba, Marija; Laius, Ott; Piessnegger, Jutta; Sermet, Catherine; Schwabe, Ulrich; Vlahović-Palčevski, Vera V; Markovic-Pekovic, Vanda; Vončina, Luka; Malinowska, Kamila; Zara, Corinne; Gustafsson, Lars L

2014-01-01

The appreciable growth in pharmaceutical expenditure has resulted in multiple initiatives across Europe to lower generic prices and enhance their utilization. However, considerable variation in their use and prices. Assess the influence of multiple supply and demand-side initiatives across Europe for established medicines to enhance prescribing efficiency before a decision to prescribe a particular medicine. Subsequently utilize the findings to suggest potential future initiatives that countries could consider. An analysis of different methodologies involving cross national and single country retrospective observational studies on reimbursed use and expenditure of PPIs, statins, and renin-angiotensin inhibitor drugs among European countries. Nature and intensity of the various initiatives appreciably influenced prescribing behavior and expenditure, e.g., multiple measures resulted in reimbursed expenditure for PPIs in Scotland in 2010 56% below 2001 levels despite a 3-fold increase in utilization and in the Netherlands, PPI expenditure fell by 58% in 2010 vs. 2000 despite a 3-fold increase in utilization. A similar picture was seen with prescribing restrictions, i.e., (i) more aggressive follow-up of prescribing restrictions for patented statins and ARBs resulted in a greater reduction in the utilization of patented statins in Austria vs. Norway and lower utilization of patented ARBs vs. generic ACEIs in Croatia than Austria. However, limited impact of restrictions on esomeprazole in Norway with the first prescription or recommendation in hospital where restrictions do not apply. Similar findings when generic losartan became available in Western Europe. Multiple demand-side measures are needed to influence prescribing patterns. When combined with supply-side measures, activities can realize appreciable savings. Health authorities cannot rely on a "spill over" effect between classes to affect changes in prescribing.

Multiple policies to enhance prescribing efficiency for established medicines in Europe with a particular focus on demand-side measures: findings and future implications

PubMed Central

Godman, Brian; Wettermark, Bjorn; van Woerkom, Menno; Fraeyman, Jessica; Alvarez-Madrazo, Samantha; Berg, Christian; Bishop, Iain; Bucsics, Anna; Campbell, Stephen; Finlayson, Alexander E.; Fürst, Jurij; Garuoliene, Kristina; Herholz, Harald; Kalaba, Marija; Laius, Ott; Piessnegger, Jutta; Sermet, Catherine; Schwabe, Ulrich; Vlahović-Palčevski, Vera V.; Markovic-Pekovic, Vanda; Vončina, Luka; Malinowska, Kamila; Zara, Corinne; Gustafsson, Lars L.

2014-01-01

Introduction: The appreciable growth in pharmaceutical expenditure has resulted in multiple initiatives across Europe to lower generic prices and enhance their utilization. However, considerable variation in their use and prices. Objective: Assess the influence of multiple supply and demand-side initiatives across Europe for established medicines to enhance prescribing efficiency before a decision to prescribe a particular medicine. Subsequently utilize the findings to suggest potential future initiatives that countries could consider. Method: An analysis of different methodologies involving cross national and single country retrospective observational studies on reimbursed use and expenditure of PPIs, statins, and renin-angiotensin inhibitor drugs among European countries. Results: Nature and intensity of the various initiatives appreciably influenced prescribing behavior and expenditure, e.g., multiple measures resulted in reimbursed expenditure for PPIs in Scotland in 2010 56% below 2001 levels despite a 3-fold increase in utilization and in the Netherlands, PPI expenditure fell by 58% in 2010 vs. 2000 despite a 3-fold increase in utilization. A similar picture was seen with prescribing restrictions, i.e., (i) more aggressive follow-up of prescribing restrictions for patented statins and ARBs resulted in a greater reduction in the utilization of patented statins in Austria vs. Norway and lower utilization of patented ARBs vs. generic ACEIs in Croatia than Austria. However, limited impact of restrictions on esomeprazole in Norway with the first prescription or recommendation in hospital where restrictions do not apply. Similar findings when generic losartan became available in Western Europe. Conclusions: Multiple demand-side measures are needed to influence prescribing patterns. When combined with supply-side measures, activities can realize appreciable savings. Health authorities cannot rely on a “spill over” effect between classes to affect changes in prescribing. PMID:24987370

An Effective Mechanism for Virtual Machine Placement using Aco in IAAS Cloud

NASA Astrophysics Data System (ADS)

Shenbaga Moorthy, Rajalakshmi; Fareentaj, U.; Divya, T. K.

2017-08-01

Cloud computing provides an effective way to dynamically provide numerous resources to meet customer demands. A major challenging problem for cloud providers is designing efficient mechanisms for optimal virtual machine Placement (OVMP). Such mechanisms enable the cloud providers to effectively utilize their available resources and obtain higher profits. In order to provide appropriate resources to the clients an optimal virtual machine placement algorithm is proposed. Virtual machine placement is NP-Hard problem. Such NP-Hard problem can be solved using heuristic algorithm. In this paper, Ant Colony Optimization based virtual machine placement is proposed. Our proposed system focuses on minimizing the cost spending in each plan for hosting virtual machines in a multiple cloud provider environment and the response time of each cloud provider is monitored periodically, in such a way to minimize delay in providing the resources to the users. The performance of the proposed algorithm is compared with greedy mechanism. The proposed algorithm is simulated in Eclipse IDE. The results clearly show that the proposed algorithm minimizes the cost, response time and also number of migrations.

Bioinspired Multifunctional Paper-Based rGO Composites for Solar-Driven Clean Water Generation.

PubMed

Lou, Jinwei; Liu, Yang; Wang, Zhongyong; Zhao, Dengwu; Song, Chengyi; Wu, Jianbo; Dasgupta, Neil; Zhang, Wang; Zhang, Di; Tao, Peng; Shang, Wen; Deng, Tao

2016-06-15

Reusing polluted water through various decontamination techniques has appeared as one of the most practical approaches to address the global shortage of clean water. Rather than relying on single decontamination mechanism, herein we report the preparation and utilization of paper-based composites for multifunctional solar-driven clean water generation that is inspired by the multiple water purification approaches in biological systems. The reduced graphene oxide (rGO) sheets within such composites can efficiently remove organic contaminants through physical adsorption mechanism. Under solar irradiation, the floating rGO composites can instantly generate localized heating, which not only can directly generate clean water through distillation mechanism but also significantly enhance adsorption removal performance with the assistance of upward vapor flow. Such porous-structured paper-based composites allow for facile incorporation of photocatalysts to regenerate clean water out of contaminated water with combined adsorption, photodegradation, and interfacial heat-assisted distillation mechanisms. Within a homemade all-in-one water treatment device, the practical applicability of the composites for multifunctional clean water generation has been demonstrated.

Receiver-Assisted Congestion Control to Achieve High Throughput in Lossy Wireless Networks

NASA Astrophysics Data System (ADS)

Shi, Kai; Shu, Yantai; Yang, Oliver; Luo, Jiarong

2010-04-01

Many applications would require fast data transfer in high-speed wireless networks nowadays. However, due to its conservative congestion control algorithm, Transmission Control Protocol (TCP) cannot effectively utilize the network capacity in lossy wireless networks. In this paper, we propose a receiver-assisted congestion control mechanism (RACC) in which the sender performs loss-based control, while the receiver is performing delay-based control. The receiver measures the network bandwidth based on the packet interarrival interval and uses it to compute a congestion window size deemed appropriate for the sender. After receiving the advertised value feedback from the receiver, the sender then uses the additive increase and multiplicative decrease (AIMD) mechanism to compute the correct congestion window size to be used. By integrating the loss-based and the delay-based congestion controls, our mechanism can mitigate the effect of wireless losses, alleviate the timeout effect, and therefore make better use of network bandwidth. Simulation and experiment results in various scenarios show that our mechanism can outperform conventional TCP in high-speed and lossy wireless environments.

Cost-Effectiveness and Cost-Utility of Internet-Based Computer Tailoring for Smoking Cessation

PubMed Central

Evers, Silvia MAA; de Vries, Hein; Hoving, Ciska

2013-01-01

Background Although effective smoking cessation interventions exist, information is limited about their cost-effectiveness and cost-utility. Objective To assess the cost-effectiveness and cost-utility of an Internet-based multiple computer-tailored smoking cessation program and tailored counseling by practice nurses working in Dutch general practices compared with an Internet-based multiple computer-tailored program only and care as usual. Methods The economic evaluation was embedded in a randomized controlled trial, for which 91 practice nurses recruited 414 eligible smokers. Smokers were randomized to receive multiple tailoring and counseling (n=163), multiple tailoring only (n=132), or usual care (n=119). Self-reported cost and quality of life were assessed during a 12-month follow-up period. Prolonged abstinence and 24-hour and 7-day point prevalence abstinence were assessed at 12-month follow-up. The trial-based economic evaluation was conducted from a societal perspective. Uncertainty was accounted for by bootstrapping (1000 times) and sensitivity analyses. Results No significant differences were found between the intervention arms with regard to baseline characteristics or effects on abstinence, quality of life, and addiction level. However, participants in the multiple tailoring and counseling group reported significantly more annual health care–related costs than participants in the usual care group. Cost-effectiveness analysis, using prolonged abstinence as the outcome measure, showed that the mere multiple computer-tailored program had the highest probability of being cost-effective. Compared with usual care, in this group €5100 had to be paid for each additional abstinent participant. With regard to cost-utility analyses, using quality of life as the outcome measure, usual care was probably most efficient. Conclusions To our knowledge, this was the first study to determine the cost-effectiveness and cost-utility of an Internet-based smoking cessation program with and without counseling by a practice nurse. Although the Internet-based multiple computer-tailored program seemed to be the most cost-effective treatment, the cost-utility was probably highest for care as usual. However, to ease the interpretation of cost-effectiveness results, future research should aim at identifying an acceptable cutoff point for the willingness to pay per abstinent participant. PMID:23491820

Assessment of Multiple Physician Competencies in Postgraduate Training: Utility of the Structured Oral Examination

ERIC Educational Resources Information Center

Jefferies, Ann; Simmons, Brian; Ng, Eugene; Skidmore, Martin

2011-01-01

Competency based medical education involves assessing physicians-in-training in multiple roles. Training programs are challenged by the need to introduce appropriate yet feasible assessment methods. We therefore examined the utility of a structured oral examination (SOE) in the assessment of the 7 CanMEDS roles (Medical Expert, Communicator,…

Control of skeletal muscle perfusion at the onset of dynamic exercise

NASA Technical Reports Server (NTRS)

Delp, M. D.

1999-01-01

At the onset of exercise there is a rapid increase in skeletal muscle vascular conductance and blood flow. Several mechanisms involved in the regulation of muscle perfusion have been proposed to initiate this hyperemic response, including neural, metabolic, endothelial, myogenic, and muscle pump mechanisms. Investigators utilizing pharmacological blockade of cholinergic muscarinic receptors and sympathectomy have concluded that neither sympathetic cholinergic nor adrenergic neural mechanisms are involved in the initial hyperemia. Studies have also shown that the time course for vasoactive metabolite release, diffusion, accumulation, and action is too long to account for the rapid increase in vascular conductance at the initiation of exercise. Furthermore, there is little or no evidence to support an endothelium or myogenic mechanism as the initiating factor in the muscle hyperemia. Thus, the rise in muscle blood flow does not appear to be explained by known neural, metabolic, endothelial, or myogenic influences. However, the initial hyperemia is consistent with the mechanical effects of the muscle pump to increase the arteriovenous pressure gradient across muscle. Because skeletal muscle blood flow is regulated by multiple and redundant mechanisms, it is likely that neural, metabolic, and possibly endothelial factors become important modulators of mechanically induced exercise hyperemia following the first 5-10 s of exercise.

Bandwidth auction for SVC streaming in dynamic multi-overlay

NASA Astrophysics Data System (ADS)

Xiong, Yanting; Zou, Junni; Xiong, Hongkai

2010-07-01

In this paper, we study the optimal bandwidth allocation for scalable video coding (SVC) streaming in multiple overlays. We model the whole bandwidth request and distribution process as a set of decentralized auction games between the competing peers. For the upstream peer, a bandwidth allocation mechanism is introduced to maximize the aggregate revenue. For the downstream peer, a dynamic bidding strategy is proposed. It achieves maximum utility and efficient resource usage by collaborating with a content-aware layer dropping/adding strategy. Also, the convergence of the proposed auction games is theoretically proved. Experimental results show that the auction strategies can adapt to dynamic join of competing peers and video layers.

miR-150 exerts antileukemia activity in vitro and in vivo through regulating genes in multiple pathways

PubMed Central

Fang, Zhi Hong; Wang, Si Li; Zhao, Jin Tao; Lin, Zhi Juan; Chen, Lin Yan; Su, Rui; Xie, Si Ting; Carter, Bing Z; Xu, Bing

2016-01-01

MicroRNAs, a class of small noncoding RNAs, have been implicated to regulate gene expression in virtually all important biological processes. Although accumulating evidence demonstrates that miR-150, an important regulator in hematopoiesis, is deregulated in various types of hematopoietic malignancies, the precise mechanisms of miR-150 action are largely unknown. In this study, we found that miR-150 is downregulated in samples from patients with acute lymphoblastic leukemia, acute myeloid leukemia, and chronic myeloid leukemia, and normalized after patients achieved complete remission. Restoration of miR-150 markedly inhibited growth and induced apoptosis of leukemia cells, and reduced tumorigenicity in a xenograft leukemia murine model. Microarray analysis identified multiple novel targets of miR-150, which were validated by quantitative real-time PCR and luciferase reporter assay. Gene ontology and pathway analysis illustrated potential roles of these targets in small-molecule metabolism, transcriptional regulation, RNA metabolism, proteoglycan synthesis in cancer, mTOR signaling pathway, or Wnt signaling pathway. Interestingly, knockdown one of four miR-150 targets (EIF4B, FOXO4B, PRKCA, and TET3) showed an antileukemia activity similar to that of miR-150 restoration. Collectively, our study demonstrates that miR-150 functions as a tumor suppressor through multiple mechanisms in human leukemia and provides a rationale for utilizing miR-150 as a novel therapeutic agent for leukemia treatment. PMID:27899822

Dust Tolerant Commodity Transfer Interface Mechanisms for Planetary Surfaces

NASA Technical Reports Server (NTRS)

Townsend, Ivan I.; Mueller, Robert P.; Tamasy, Gabor J.

2014-01-01

Regolith is present on most planetary surfaces such as Earth's moon, Mars, and Asteroids. If human crews and robotic machinery are to operate on these regolith covered surfaces, they must face the consequences of interacting with regolith fines which consist of particles below 100 microns in diameter down to as small as submicron scale particles. Such fine dust will intrude into mechanisms and interfaces causing a variety of problems such as contamination of clean fluid lines, jamming of mechanisms and damaging connector seals and couplings. Since multiple elements must be assembled in space for system level functionality, it will be inevitable that interfaces will be necessary for structural connections, and to pass commodities such as cryogenic liquid propellants, purge and buffer gases, water, breathing air, pressurizing gases, heat exchange fluids, power and data. When fine regolith dust is present in the environment it can be lofted into interfaces where it can compromise the utility of the interface by preventing the connections from being successfully mated, or by inducing fluid leaks or degradation of power and data transmission. A dust tolerant, hand held "quick-disconnect" cryogenic fluids connector housing has been developed at NASA KSC which can be used by astronaut crews to connect flex lines that will transfer propellants and other useful fluids to the end user. In addition, a dust tolerant, automated, cryogenic fluid, multiple connector, power and data interface mechanism prototype has been developed, fabricated and demonstrated by NASA at Kennedy Space Center (KSC). The design and operation of these prototypes are explained and discussed.

Statistical grand rounds: understanding the mechanism: mediation analysis in randomized and nonrandomized studies.

PubMed

Mascha, Edward J; Dalton, Jarrod E; Kurz, Andrea; Saager, Leif

2013-10-01

In comparative clinical studies, a common goal is to assess whether an exposure, or intervention, affects the outcome of interest. However, just as important is to understand the mechanism(s) for how the intervention affects outcome. For example, if preoperative anemia was shown to increase the risk of postoperative complications by 15%, it would be important to quantify how much of that effect was due to patients receiving intraoperative transfusions. Mediation analysis attempts to quantify how much, if any, of the effect of an intervention on outcome goes though prespecified mediator, or "mechanism" variable(s), that is, variables sitting on the causal pathway between exposure and outcome. Effects of an exposure on outcome can thus be divided into direct and indirect, or mediated, effects. Mediation is claimed when 2 conditions are true: the exposure affects the mediator and the mediator (adjusting for the exposure) affects the outcome. Understanding how an intervention affects outcome can validate or invalidate one's original hypothesis and also facilitate further research to modify the responsible factors, and thus improve patient outcome. We discuss the proper design and analysis of studies investigating mediation, including the importance of distinguishing mediator variables from confounding variables, the challenge of identifying potential mediators when the exposure is chronic versus acute, and the requirements for claiming mediation. Simple designs are considered, as well as those containing multiple mediators, multiple outcomes, and mixed data types. Methods are illustrated with data collected by the National Surgical Quality Improvement Project (NSQIP) and utilized in a companion paper which assessed the effects of preoperative anemic status on postoperative outcomes.

Wind farm electrical system

DOEpatents

Erdman, William L.; Lettenmaier, Terry M.

2006-07-04

An approach to wind farm design using variable speed wind turbines with low pulse number electrical output. The output of multiple wind turbines are aggregated to create a high pulse number electrical output at a point of common coupling with a utility grid network. Power quality at each individual wind turbine falls short of utility standards, but the aggregated output at the point of common coupling is within acceptable tolerances for utility power quality. The approach for aggregating low pulse number electrical output from multiple wind turbines relies upon a pad mounted transformer at each wind turbine that performs phase multiplication on the output of each wind turbine. Phase multiplication converts a modified square wave from the wind turbine into a 6 pulse output. Phase shifting of the 6 pulse output from each wind turbine allows the aggregated output of multiple wind turbines to be a 24 pulse approximation of a sine wave. Additional filtering and VAR control is embedded within the wind farm to take advantage of the wind farm's electrical impedence characteristics to further enhance power quality at the point of common coupling.

Allocation and management issues in multiple-transaction open access transmission networks

NASA Astrophysics Data System (ADS)

Tao, Shu

This thesis focuses on some key issues related to allocation and management by the independent grid operator (IGO) of unbundled services in multiple-transaction open access transmission networks. The three unbundled services addressed in the thesis are transmission real power losses, reactive power support requirements from generation sources, and transmission congestion management. We develop the general framework that explicitly represents multiple transactions undertaken simultaneously in the transmission grid. This framework serves as the basis for formulating various problems treated in the thesis. We use this comprehensive framework to develop a physical-flow-based mechanism to allocate the total transmission losses to each transaction using the system. An important property of the allocation scheme is its capability to effectively deal with counter flows that result in the presence of specific transactions. Using the loss allocation results as the basis, we construct the equivalent loss compensation concept and apply it to develop flexible and effective procedures for compensating losses in multiple-transaction networks. We present a new physical-flow-based mechanism for allocating the reactive power support requirements provided by generators in multiple-transaction networks. The allocatable reactive support requirements are formulated as the sum of two specific components---the voltage magnitude variation component and the voltage angle variation component. The formulation utilizes the multiple-transaction framework and makes use of certain simplifying approximations. The formulation leads to a natural allocation as a function of the amount of each transaction. The physical interpretation of each allocation as a sensitivity of the reactive output of a generator is discussed. We propose a congestion management allocation scheme for multiple-transaction networks. The proposed scheme determines the allocation of congestion among the transactions on a physical-flow basis. It also proposes a congestion relief scheme that removes the congestion attributed to each transaction on the network in a least-cost manner to the IGO and determines the appropriate transmission charges to each transaction for its transmission usage. The thesis provides a compendium of problems that are natural extensions of the research results reported here and appear to be good candidates for future work.

Bimorphic polymeric photomechanical actuator

NASA Technical Reports Server (NTRS)

Sarkisov, Sergey S. (Inventor); Curley, Michael J. (Inventor); Adamovsky, Grigory (Inventor); Sarkisov, Jr., Sergey S. (Inventor); Fields, Aisha B. (Inventor)

2006-01-01

A bimorphic polymeric photomechanical actuator, in one embodiment using polyvinylidene fluoride (PVDF) as a photosensitive body, transmitting light over fiber optic cables, and controlling the shape and pulse duration of the light pulse to control movement of the actuator. Multiple light beams are utilized to generate different ranges of motion for the actuator from a single photomechanical body and alternative designs use multiple light beams and multiple photomechanical bodies to provide controlled movement. Actuator movement using one or more ranges of motion is utilized to control motion to position an actuating element in three dimensional space.

Identification of drug-resistant subpopulations in canine hemangiosarcoma

PubMed Central

Khammanivong, A.; Gorden, B. H.; Frantz, A. M.; Graef, A. J.; Dickerson, E. B.

2017-01-01

Canine hemangiosarcoma is a rapidly progressive disease that is poorly responsive to conventional chemotherapy. Despite numerous attempts to advance treatment options and improve outcomes, drug resistance remains a hurdle to successful therapy. To address this problem, we used recently characterized progenitor cell populations derived from canine hemangiosarcoma cell lines and grown as non-adherent spheres to identify potential drug resistance mechanisms as well as drug-resistant cell populations. Cells from sphere-forming cultures displayed enhanced resistance to chemotherapy drugs, expansion of dye-excluding side populations and altered ATP-binding cassette (ABC) transporter expression. Invasion studies demonstrated variability between cell lines as well as between sphere and monolayer cell populations. Collectively, our results suggest that sphere cell populations contain distinct subpopulations of drug-resistant cells that utilize multiple mechanisms to evade cytotoxic drugs. Our approach represents a new tool for the study of drug resistance in hemangiosarcoma, which could alter approaches for treating this disease. PMID:25112808

A broadband damper design inspired by cartilage-like relaxation mechanisms

NASA Astrophysics Data System (ADS)

Liu, Lejie; Usta, Ahmet D.; Eriten, Melih

2017-10-01

In this study, we introduce a broadband damper design inspired by the cartilage-like relaxation mechanisms. In particular, we study broadband (static to 10 kHz) dissipative properties of model cartilage systems by probe-based static and dynamic indentation, and validate that fractional Zener models can simulate the empirical data up to a desirable accuracy within the frequency range of interest. Utilizing these observations, we design a composite damper design where a poroelastic layer is sandwiched between two hard materials, and load transfer occurs across interfaces with multiple length scales. Modeling those interfaces with fractional Zener elements in parallel configuration, and manipulating the distribution of the Zener elements across different peak relaxation frequencies, we obtain a relatively constant loss factor within an unprecedented frequency range (3-3 kHz). We also discuss how these findings can be employed in a practical damping design.

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

PubMed

Galluzzi, Lorenzo; Vitale, Ilio; Aaronson, Stuart A; Abrams, John M; Adam, Dieter; Agostinis, Patrizia; Alnemri, Emad S; Altucci, Lucia; Amelio, Ivano; Andrews, David W; Annicchiarico-Petruzzelli, Margherita; Antonov, Alexey V; Arama, Eli; Baehrecke, Eric H; Barlev, Nickolai A; Bazan, Nicolas G; Bernassola, Francesca; Bertrand, Mathieu J M; Bianchi, Katiuscia; Blagosklonny, Mikhail V; Blomgren, Klas; Borner, Christoph; Boya, Patricia; Brenner, Catherine; Campanella, Michelangelo; Candi, Eleonora; Carmona-Gutierrez, Didac; Cecconi, Francesco; Chan, Francis K-M; Chandel, Navdeep S; Cheng, Emily H; Chipuk, Jerry E; Cidlowski, John A; Ciechanover, Aaron; Cohen, Gerald M; Conrad, Marcus; Cubillos-Ruiz, Juan R; Czabotar, Peter E; D'Angiolella, Vincenzo; Dawson, Ted M; Dawson, Valina L; De Laurenzi, Vincenzo; De Maria, Ruggero; Debatin, Klaus-Michael; DeBerardinis, Ralph J; Deshmukh, Mohanish; Di Daniele, Nicola; Di Virgilio, Francesco; Dixit, Vishva M; Dixon, Scott J; Duckett, Colin S; Dynlacht, Brian D; El-Deiry, Wafik S; Elrod, John W; Fimia, Gian Maria; Fulda, Simone; García-Sáez, Ana J; Garg, Abhishek D; Garrido, Carmen; Gavathiotis, Evripidis; Golstein, Pierre; Gottlieb, Eyal; Green, Douglas R; Greene, Lloyd A; Gronemeyer, Hinrich; Gross, Atan; Hajnoczky, Gyorgy; Hardwick, J Marie; Harris, Isaac S; Hengartner, Michael O; Hetz, Claudio; Ichijo, Hidenori; Jäättelä, Marja; Joseph, Bertrand; Jost, Philipp J; Juin, Philippe P; Kaiser, William J; Karin, Michael; Kaufmann, Thomas; Kepp, Oliver; Kimchi, Adi; Kitsis, Richard N; Klionsky, Daniel J; Knight, Richard A; Kumar, Sharad; Lee, Sam W; Lemasters, John J; Levine, Beth; Linkermann, Andreas; Lipton, Stuart A; Lockshin, Richard A; López-Otín, Carlos; Lowe, Scott W; Luedde, Tom; Lugli, Enrico; MacFarlane, Marion; Madeo, Frank; Malewicz, Michal; Malorni, Walter; Manic, Gwenola; Marine, Jean-Christophe; Martin, Seamus J; Martinou, Jean-Claude; Medema, Jan Paul; Mehlen, Patrick; Meier, Pascal; Melino, Sonia; Miao, Edward A; Molkentin, Jeffery D; Moll, Ute M; Muñoz-Pinedo, Cristina; Nagata, Shigekazu; Nuñez, Gabriel; Oberst, Andrew; Oren, Moshe; Overholtzer, Michael; Pagano, Michele; Panaretakis, Theocharis; Pasparakis, Manolis; Penninger, Josef M; Pereira, David M; Pervaiz, Shazib; Peter, Marcus E; Piacentini, Mauro; Pinton, Paolo; Prehn, Jochen H M; Puthalakath, Hamsa; Rabinovich, Gabriel A; Rehm, Markus; Rizzuto, Rosario; Rodrigues, Cecilia M P; Rubinsztein, David C; Rudel, Thomas; Ryan, Kevin M; Sayan, Emre; Scorrano, Luca; Shao, Feng; Shi, Yufang; Silke, John; Simon, Hans-Uwe; Sistigu, Antonella; Stockwell, Brent R; Strasser, Andreas; Szabadkai, Gyorgy; Tait, Stephen W G; Tang, Daolin; Tavernarakis, Nektarios; Thorburn, Andrew; Tsujimoto, Yoshihide; Turk, Boris; Vanden Berghe, Tom; Vandenabeele, Peter; Vander Heiden, Matthew G; Villunger, Andreas; Virgin, Herbert W; Vousden, Karen H; Vucic, Domagoj; Wagner, Erwin F; Walczak, Henning; Wallach, David; Wang, Ying; Wells, James A; Wood, Will; Yuan, Junying; Zakeri, Zahra; Zhivotovsky, Boris; Zitvogel, Laurence; Melino, Gerry; Kroemer, Guido

2018-03-01

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field.

Interstitial atoms enable joint twinning and transformation induced plasticity in strong and ductile high-entropy alloys.

PubMed

Li, Zhiming; Tasan, Cemal Cem; Springer, Hauke; Gault, Baptiste; Raabe, Dierk

2017-01-12

High-entropy alloys (HEAs) consisting of multiple principle elements provide an avenue for realizing exceptional mechanical, physical and chemical properties. We report a novel strategy for designing a new class of HEAs incorporating the additional interstitial element carbon. This results in joint activation of twinning- and transformation-induced plasticity (TWIP and TRIP) by tuning the matrix phase's instability in a metastable TRIP-assisted dual-phase HEA. Besides TWIP and TRIP, such alloys benefit from massive substitutional and interstitial solid solution strengthening as well as from the composite effect associated with its dual-phase structure. Nanosize particle formation and grain size reduction are also utilized. The new interstitial TWIP-TRIP-HEA thus unifies all metallic strengthening mechanisms in one material, leading to twice the tensile strength compared to a single-phase HEA with similar composition, yet, at identical ductility.

Pop-out in visual search of moving targets in the archer fish.

PubMed

Ben-Tov, Mor; Donchin, Opher; Ben-Shahar, Ohad; Segev, Ronen

2015-03-10

Pop-out in visual search reflects the capacity of observers to rapidly detect visual targets independent of the number of distracting objects in the background. Although it may be beneficial to most animals, pop-out behaviour has been observed only in mammals, where neural correlates are found in primary visual cortex as contextually modulated neurons that encode aspects of saliency. Here we show that archer fish can also utilize this important search mechanism by exhibiting pop-out of moving targets. We explore neural correlates of this behaviour and report the presence of contextually modulated neurons in the optic tectum that may constitute the neural substrate for a saliency map. Furthermore, we find that both behaving fish and neural responses exhibit additive responses to multiple visual features. These findings suggest that similar neural computations underlie pop-out behaviour in mammals and fish, and that pop-out may be a universal search mechanism across all vertebrates.

Mesocarbon Microbead Carbon-Supported Magnesium Hydroxide Nanoparticles: Turning Spent Li-ion Battery Anode into a Highly Efficient Phosphate Adsorbent for Wastewater Treatment

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

Zhang, Yan; Guo, Xingming; Wu, Feng

Phosphorus in water eutrophication has become a serious problem threatening the environment. However, the development of efficient adsorbents for phosphate removal from water is lagging. In this work, we recovered the waste material, graphitized carbon, from spent lithium ion batteries and modified it with nanostructured Mg(OH)2 on the surface to treat excess phosphate. This phosphate adsorbent shows one of the highest phosphate adsorption capacities to date, 588.4 mg/g (1 order of magnitude higher than previously reported carbon-based adsorbents), and exhibits decent stability. A heterogeneous multilayer adsorption mechanism was proposed on the basis of multiple adsorption results. This highly efficient adsorbentmore » from spent Li-ion batteries displays great potential to be utilized in industry, and the mechanism study paved a way for further design of the adsorbent for phosphate adsorption.« less

Interstitial atoms enable joint twinning and transformation induced plasticity in strong and ductile high-entropy alloys

NASA Astrophysics Data System (ADS)

Li, Zhiming; Tasan, Cemal Cem; Springer, Hauke; Gault, Baptiste; Raabe, Dierk

2017-01-01

High-entropy alloys (HEAs) consisting of multiple principle elements provide an avenue for realizing exceptional mechanical, physical and chemical properties. We report a novel strategy for designing a new class of HEAs incorporating the additional interstitial element carbon. This results in joint activation of twinning- and transformation-induced plasticity (TWIP and TRIP) by tuning the matrix phase’s instability in a metastable TRIP-assisted dual-phase HEA. Besides TWIP and TRIP, such alloys benefit from massive substitutional and interstitial solid solution strengthening as well as from the composite effect associated with its dual-phase structure. Nanosize particle formation and grain size reduction are also utilized. The new interstitial TWIP-TRIP-HEA thus unifies all metallic strengthening mechanisms in one material, leading to twice the tensile strength compared to a single-phase HEA with similar composition, yet, at identical ductility.

mdtmFTP and its evaluation on ESNET SDN testbed

DOE PAGES

Zhang, Liang; Wu, Wenji; DeMar, Phil; ...

2017-04-21

In this paper, to address the high-performance challenges of data transfer in the big data era, we are developing and implementing mdtmFTP: a high-performance data transfer tool for big data. mdtmFTP has four salient features. First, it adopts an I/O centric architecture to execute data transfer tasks. Second, it more efficiently utilizes the underlying multicore platform through optimized thread scheduling. Third, it implements a large virtual file mechanism to address the lots-of-small-files (LOSF) problem. In conclusion, mdtmFTP integrates multiple optimization mechanisms, including–zero copy, asynchronous I/O, pipelining, batch processing, and pre-allocated buffer pools–to enhance performance. mdtmFTP has been extensively tested andmore » evaluated within the ESNET 100G testbed. Evaluations show that mdtmFTP can achieve higher performance than existing data transfer tools, such as GridFTP, FDT, and BBCP.« less

Trojan Horse Antibiotics—A Novel Way to Circumvent Gram-Negative Bacterial Resistance?

PubMed Central

Tillotson, Glenn S.

2016-01-01

Antibiotic resistance has been emerged as a major global health problem. In particular, gram-negative species pose a significant clinical challenge as bacteria develop or acquire more resistance mechanisms. Often, these bacteria possess multiple resistance mechanisms, thus nullifying most of the major classes of drugs. Novel approaches to this issue are urgently required. However, the challenges of developing new agents are immense. Introducing novel agents is fraught with hurdles, thus adapting known antibiotic classes by altering their chemical structure could be a way forward. A chemical addition to existing antibiotics known as a siderophore could be a solution to the gram-negative resistance issue. Siderophore molecules rely on the bacterial innate need for iron ions and thus can utilize a Trojan Horse approach to gain access to the bacterial cell. The current approaches to using this potential method are reviewed. PMID:27773991

Trojan Horse Antibiotics-A Novel Way to Circumvent Gram-Negative Bacterial Resistance?

PubMed

Tillotson, Glenn S

2016-01-01

Antibiotic resistance has been emerged as a major global health problem. In particular, gram-negative species pose a significant clinical challenge as bacteria develop or acquire more resistance mechanisms. Often, these bacteria possess multiple resistance mechanisms, thus nullifying most of the major classes of drugs. Novel approaches to this issue are urgently required. However, the challenges of developing new agents are immense. Introducing novel agents is fraught with hurdles, thus adapting known antibiotic classes by altering their chemical structure could be a way forward. A chemical addition to existing antibiotics known as a siderophore could be a solution to the gram-negative resistance issue. Siderophore molecules rely on the bacterial innate need for iron ions and thus can utilize a Trojan Horse approach to gain access to the bacterial cell. The current approaches to using this potential method are reviewed.

High data rate modem simulation for the space station multiple-access communications system

NASA Technical Reports Server (NTRS)

Horan, Stephen

1987-01-01

The communications system for the space station will require a space based multiple access component to provide communications between the space based program elements and the station. A study was undertaken to investigate two of the concerns of this multiple access system, namely, the issues related to the frequency spectrum utilization and the possibilities for higher order (than QPSK) modulation schemes for use in possible modulators and demodulators (modems). As a result of the investigation, many key questions about the frequency spectrum utilization were raised. At this point, frequency spectrum utilization is seen as an area requiring further work. Simulations were conducted using a computer aided communications system design package to provide a straw man modem structure to be used for both QPSK and 8-PSK channels.

Optic nerve head component responses of the multifocal electroretinogram in MS.

PubMed

Frohman, Teresa C; Beh, Shin Chien; Saidha, Shiv; Schnurman, Zane; Conger, Darrel; Conger, Amy; Ratchford, John N; Lopez, Carmen; Galetta, Steven L; Calabresi, Peter A; Balcer, Laura J; Green, Ari J; Frohman, Elliot M

2013-08-06

To employ a novel stimulation paradigm in order to elicit multifocal electroretinography (mfERG)-induced optic nerve head component (ONHC) responses, believed to be contingent upon the transformation in electrical transmission properties of retinal ganglion cell axons from membrane to saltatory conduction mechanisms, as they traverse the lamina cribrosa and obtain oligodendrocyte myelin. We further sought to characterize abnormalities in ONHC responses in eyes from patients with multiple sclerosis (MS). In 10 normal subjects and 7 patients with MS (including eyes with and without a history of acute optic neuritis), we utilized a novel mfERG stimulation paradigm that included interleaved global flashes in order to elicit the ONHC responses from 103 retinal patches of pattern-reversal stimulation. The number of abnormal or absent ONHC responses was significantly increased in MS patient eyes compared to normal subject eyes (p < 0.001, by general estimating equation modeling, and accounting for age and within-subject, intereye correlations). Studying the relationship between ONHC abnormalities and alterations in validated structural and functional measures of the visual system may facilitate the ability to dissect and characterize the pathobiological mechanisms that contribute to tissue damage in MS, and may have utility to detect and monitor neuroprotective or restorative effects of novel therapies.

Applying a cloud computing approach to storage architectures for spacecraft

NASA Astrophysics Data System (ADS)

Baldor, Sue A.; Quiroz, Carlos; Wood, Paul

As sensor technologies, processor speeds, and memory densities increase, spacecraft command, control, processing, and data storage systems have grown in complexity to take advantage of these improvements and expand the possible missions of spacecraft. Spacecraft systems engineers are increasingly looking for novel ways to address this growth in complexity and mitigate associated risks. Looking to conventional computing, many solutions have been executed to solve both the problem of complexity and heterogeneity in systems. In particular, the cloud-based paradigm provides a solution for distributing applications and storage capabilities across multiple platforms. In this paper, we propose utilizing a cloud-like architecture to provide a scalable mechanism for providing mass storage in spacecraft networks that can be reused on multiple spacecraft systems. By presenting a consistent interface to applications and devices that request data to be stored, complex systems designed by multiple organizations may be more readily integrated. Behind the abstraction, the cloud storage capability would manage wear-leveling, power consumption, and other attributes related to the physical memory devices, critical components in any mass storage solution for spacecraft. Our approach employs SpaceWire networks and SpaceWire-capable devices, although the concept could easily be extended to non-heterogeneous networks consisting of multiple spacecraft and potentially the ground segment.

Multiple Intimate Partner Violence Experiences: Knowledge, Access, Utilization and Barriers to Utilization of Resources by Women of the African Diaspora

PubMed Central

Sabri, Bushra; Huerta, Julia; Alexander, Kamila A.; St.Vil, Noelle M.; Campbell, Jacquelyn C.; Callwood, Gloria B.

2016-01-01

Objective This study examined knowledge, access, utilization, and barriers to use of resources among Black women exposed to multiple types of intimate partner violence in Baltimore, Maryland and the U.S. Virgin Islands (USVI). Methods We analyzed quantitative survey data collected by 163 women recruited from primary care, prenatal or family planning clinics in Baltimore and the USVI. In addition we analyzed qualitative data from in-depth interviews with 11 women. Quantitative data were analyzed using descriptive statistics and qualitative data were analyzed using thematic analysis. Results A substantial proportion of Black women with multiple types of violence experiences lacked knowledge of, did not have access to, and did not use resources. Barriers to resource use were identified at the individual, relationship, and community levels. Conclusion There is need for programs to develop awareness, promote access and utilization of resources, and eliminate barriers to resource use among abused Black women. PMID:26548679

Automated macromolecular crystallization screening

DOEpatents

Segelke, Brent W.; Rupp, Bernhard; Krupka, Heike I.

2005-03-01

An automated macromolecular crystallization screening system wherein a multiplicity of reagent mixes are produced. A multiplicity of analysis plates is produced utilizing the reagent mixes combined with a sample. The analysis plates are incubated to promote growth of crystals. Images of the crystals are made. The images are analyzed with regard to suitability of the crystals for analysis by x-ray crystallography. A design of reagent mixes is produced based upon the expected suitability of the crystals for analysis by x-ray crystallography. A second multiplicity of mixes of the reagent components is produced utilizing the design and a second multiplicity of reagent mixes is used for a second round of automated macromolecular crystallization screening. In one embodiment the multiplicity of reagent mixes are produced by a random selection of reagent components.

A software toolbox for robotics

NASA Technical Reports Server (NTRS)

Sanwal, J. C.

1985-01-01

A method for programming cooperating manipulators, which is guided by a geometric description of the task to be performed, is given. For this a suitable language must be used and a method for describing the workplace and the objects in it in geometric terms. A task level command language and its implementation for concurrently driven multiple robot arm is described. The language is suitable for driving a cell in which manipulators, end effectors, and sensors are controlled by their own dedicated processors. These processors can communicate with each other through a communication network. A mechanism for keeping track of the history of the commands already executed allows the command language for the manipulators to be event driven. A frame based world modeling system is utilized to describe the objects in the work environment and any relationships that hold between these objects. This system provides a versatile tool for managing information about the world model. Default actions normally needed are invoked when the data base is updated or accessed. Most of the first level error recovery is also invoked by the database by utilizing the concepts of demons. The package can be utilized to generate task level commands in a problem solver or a planner.

Evidence against global attention filters selective for absolute bar-orientation in human vision.

PubMed

Inverso, Matthew; Sun, Peng; Chubb, Charles; Wright, Charles E; Sperling, George

2016-01-01

The finding that an item of type A pops out from an array of distractors of type B typically is taken to support the inference that human vision contains a neural mechanism that is activated by items of type A but not by items of type B. Such a mechanism might be expected to yield a neural image in which items of type A produce high activation and items of type B low (or zero) activation. Access to such a neural image might further be expected to enable accurate estimation of the centroid of an ensemble of items of type A intermixed with to-be-ignored items of type B. Here, it is shown that as the number of items in stimulus displays is increased, performance in estimating the centroids of horizontal (vertical) items amid vertical (horizontal) distractors degrades much more quickly and dramatically than does performance in estimating the centroids of white (black) items among black (white) distractors. Together with previous findings, these results suggest that, although human vision does possess bottom-up neural mechanisms sensitive to abrupt local changes in bar-orientation, and although human vision does possess and utilize top-down global attention filters capable of selecting multiple items of one brightness or of one color from among others, it cannot use a top-down global attention filter capable of selecting multiple bars of a given absolute orientation and filtering bars of the opposite orientation in a centroid task.

Multiple-attribute group decision making with different formats of preference information on attributes.

PubMed

Xu, Zeshui

2007-12-01

Interval utility values, interval fuzzy preference relations, and interval multiplicative preference relations are three common uncertain-preference formats used by decision-makers to provide their preference information in the process of decision making under fuzziness. This paper is devoted in investigating multiple-attribute group-decision-making problems where the attribute values are not precisely known but the value ranges can be obtained, and the decision-makers provide their preference information over attributes by three different uncertain-preference formats i.e., 1) interval utility values; 2) interval fuzzy preference relations; and 3) interval multiplicative preference relations. We first utilize some functions to normalize the uncertain decision matrix and then transform it into an expected decision matrix. We establish a goal-programming model to integrate the expected decision matrix and all three different uncertain-preference formats from which the attribute weights and the overall attribute values of alternatives can be obtained. Then, we use the derived overall attribute values to get the ranking of the given alternatives and to select the best one(s). The model not only can reflect both the subjective considerations of all decision-makers and the objective information but also can avoid losing and distorting the given objective and subjective decision information in the process of information integration. Furthermore, we establish some models to solve the multiple-attribute group-decision-making problems with three different preference formats: 1) utility values; 2) fuzzy preference relations; and 3) multiplicative preference relations. Finally, we illustrate the applicability and effectiveness of the developed models with two practical examples.

Combined electromechanical impedance and fiber optic diagnosis of aerospace structures

NASA Astrophysics Data System (ADS)

Schlavin, Jon; Zagrai, Andrei; Clemens, Rebecca; Black, Richard J.; Costa, Joey; Moslehi, Behzad; Patel, Ronak; Sotoudeh, Vahid; Faridian, Fereydoun

2014-03-01

Electromechanical impedance is a popular diagnostic method for assessing structural conditions at high frequencies. It has been utilized, and shown utility, in aeronautic, space, naval, civil, mechanical, and other types of structures. By contrast, fiber optic sensing initially found its niche in static strain measurement and low frequency structural dynamic testing. Any low frequency limitations of the fiber optic sensing, however, are mainly governed by its hardware elements. As hardware improves, so does the bandwidth (frequency range * number of sensors) provided by the appropriate enabling fiber optic sensor interrogation system. In this contribution we demonstrate simultaneous high frequency measurements using fiber optic and electromechanical impedance structural health monitoring technologies. A laboratory specimen imitating an aircraft wing structure, incorporating surfaces with adjustable boundary conditions, was instrumented with piezoelectric and fiber optic sensors. Experiments were conducted at different structural boundary conditions associated with deterioration of structural health. High frequency dynamic responses were collected at multiple locations on a laboratory wing specimen and conclusions were drawn about correspondence between structural damage and dynamic signatures as well as correlation between electromechanical impedance and fiber optic sensors spectra. Theoretical investigation of the effect of boundary conditions on electromechanical impedance spectra is presented and connection to low frequency structural dynamics is suggested. It is envisioned that acquisition of high frequency structural dynamic responses with multiple fiber optic sensors may open new diagnostic capabilities for fiber optic sensing technologies.

Application of a high-throughput relative chemical stability assay to screen therapeutic protein formulations by assessment of conformational stability and correlation to aggregation propensity.

PubMed

Rizzo, Joseph M; Shi, Shuai; Li, Yunsong; Semple, Andrew; Esposito, Jessica J; Yu, Shenjiang; Richardson, Daisy; Antochshuk, Valentyn; Shameem, Mohammed

2015-05-01

In this study, an automated high-throughput relative chemical stability (RCS) assay was developed in which various therapeutic proteins were assessed to determine stability based on the resistance to denaturation post introduction to a chaotrope titration. Detection mechanisms of both intrinsic fluorescence and near UV circular dichroism (near-UV CD) are demonstrated. Assay robustness was investigated by comparing multiple independent assays and achieving r(2) values >0.95 for curve overlays. The complete reversibility of the assay was demonstrated by intrinsic fluorescence, near-UV CD, and biologic potency. To highlight the method utility, we compared the RCS assay with differential scanning calorimetry and dynamic scanning fluorimetry methodologies. Utilizing C1/2 values obtained from the RCS assay, formulation rank-ordering of 12 different mAb formulations was performed. The prediction of long-term stability on protein aggregation is obtained by demonstrating a good correlation with an r(2) of 0.83 between RCS and empirical aggregation propensity data. RCS promises to be an extremely useful tool to aid in candidate formulation development efforts based on the complete reversibility of the method to allow for multiple assessments without protein loss and the strong correlation between the C1/2 data obtained and accelerated stability under stressed conditions. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Evaluation of metabolites extraction strategies for identifying different brain regions and their relationship with alcohol preference and gender difference using NMR metabolomics.

PubMed

Wang, Jie; Zeng, Hao-Long; Du, Hongying; Liu, Zeyuan; Cheng, Ji; Liu, Taotao; Hu, Ting; Kamal, Ghulam Mustafa; Li, Xihai; Liu, Huili; Xu, Fuqiang

2018-03-01

Metabolomics generate a profile of small molecules from cellular/tissue metabolism, which could directly reflect the mechanisms of complex networks of biochemical reactions. Traditional metabolomics methods, such as OPLS-DA, PLS-DA are mainly used for binary class discrimination. Multiple groups are always involved in the biological system, especially for brain research. Multiple brain regions are involved in the neuronal study of brain metabolic dysfunctions such as alcoholism, Alzheimer's disease, etc. In the current study, 10 different brain regions were utilized for comparative studies between alcohol preferring and non-preferring rats, male and female rats respectively. As many classes are involved (ten different regions and four types of animals), traditional metabolomics methods are no longer efficient for showing differentiation. Here, a novel strategy based on the decision tree algorithm was employed for successfully constructing different classification models to screen out the major characteristics of ten brain regions at the same time. Subsequently, this method was also utilized to select the major effective brain regions related to alcohol preference and gender difference. Compared with the traditional multivariate statistical methods, the decision tree could construct acceptable and understandable classification models for multi-class data analysis. Therefore, the current technology could also be applied to other general metabolomics studies involving multi class data. Copyright © 2017 Elsevier B.V. All rights reserved.

Are socioeconomic disparities in health behavior mediated by differential media use? Test of the communication inequality theory.

PubMed

Ishikawa, Yoshiki; Kondo, Naoki; Kawachi, Ichiro; Viswanath, Kasisomayajula

2016-11-01

Communication inequality has been offered as one potential mechanism through which social determinants influence multiple health behaviors. The purpose of this study was to examine the underlying mechanisms between communication inequality and health behaviors. Data from a nationally representative cross-sectional survey of 18,426 people aged 18 years and above in the United States were used for secondary analysis. Measures included socio-demographic characteristics, social participation (structural social capital), health media use (TV, print, and the Internet), and five health behaviors (physical activity, cigarette smoking, alcohol use, and intake of fruit and vegetable). Path analysis was performed to examine the linkages between social determinants, health media use, social participation, and social gradients in health behaviors. Path analysis revealed that socioeconomic gradients in health behaviors is mediated by: 1) inequalities in health media use; 2) disparities in social participation, which leads to differential media use; and 3) disparities in social participation that are not mediated by media use. Consistent with the theory of communication inequality, socioeconomic disparities in media use partially mediate disparities in multiple health behaviors. To address health inequalities, it is important to utilize health media to target populations with low socioeconomic statuses. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Persistent activation of microglia and NADPH drive hippocampal dysfunction in experimental multiple sclerosis

PubMed Central

Di Filippo, Massimiliano; de Iure, Antonio; Giampà, Carmela; Chiasserini, Davide; Tozzi, Alessandro; Orvietani, Pier Luigi; Ghiglieri, Veronica; Tantucci, Michela; Durante, Valentina; Quiroga-Varela, Ana; Mancini, Andrea; Costa, Cinzia; Sarchielli, Paola; Fusco, Francesca Romana; Calabresi, Paolo

2016-01-01

Cognitive impairment is common in multiple sclerosis (MS). Unfortunately, the synaptic and molecular mechanisms underlying MS-associated cognitive dysfunction are largely unknown. We explored the presence and the underlying mechanism of cognitive and synaptic hippocampal dysfunction during the remission phase of experimental MS. Experiments were performed in a chronic-relapsing experimental autoimmune encephalomyelitis (EAE) model of MS, after the resolution of motor deficits. Immunohistochemistry and patch-clamp recordings were performed in the CA1 hippocampal area. The hole-board was utilized as cognitive/behavioural test. In the remission phase of experimental MS, hippocampal microglial cells showed signs of activation, CA1 hippocampal synapses presented an impaired long-term potentiation (LTP) and an alteration of spatial tests became evident. The activation of hippocampal microglia mediated synaptic and cognitive/behavioural alterations during EAE. Specifically, LTP blockade was found to be caused by the reactive oxygen species (ROS)-producing enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. We suggest that in the remission phase of experimental MS microglia remains activated, causing synaptic dysfunctions mediated by NADPH oxidase. Inhibition of microglial activation and NADPH oxidase may represent a promising strategy to prevent neuroplasticity impairment associated with active neuro-inflammation, with the aim to improve cognition and counteract MS disease progression. PMID:26887636

A 590 kb deletion caused by non-allelic homologous recombination between two LINE-1 elements in a patient with mesomelia-synostosis syndrome.

PubMed

Kohmoto, Tomohiro; Naruto, Takuya; Watanabe, Miki; Fujita, Yuji; Ujiro, Sae; Okamoto, Nana; Horikawa, Hideaki; Masuda, Kiyoshi; Imoto, Issei

2017-04-01

Mesomelia-synostoses syndrome (MSS) is a rare, autosomal-dominant, syndromal osteochondrodysplasia characterized by mesomelic limb shortening, acral synostoses, and multiple congenital malformations due to a non-recurrent deletion at 8q13 that always encompasses two coding-genes, SULF1 and SLCO5A1. To date, five unrelated patients have been reported worldwide, and MMS was previously proposed to not be a genomic disorder associated with deletions recurring from non-allelic homologous recombination (NAHR) in at least two analyzed cases. We conducted targeted gene panel sequencing and subsequent array-based copy number analysis in an 11-year-old undiagnosed Japanese female patient with multiple congenital anomalies that included mesomelic limb shortening and detected a novel 590 Kb deletion at 8q13 encompassing the same gene set as reported previously, resulting in the diagnosis of MSS. Breakpoint sequences of the deleted region in our case demonstrated the first LINE-1s (L1s)-mediated unequal NAHR event utilizing two distant L1 elements as homology substrates in this disease, which may represent a novel causative mechanism of the 8q13 deletion, expanding the range of mechanisms involved in the chromosomal rearrangements responsible for MSS. © 2017 Wiley Periodicals, Inc.

Neural Plasticity in Multiple Sclerosis: The Functional and Molecular Background

PubMed Central

Glabinski, Andrzej

2015-01-01

Multiple sclerosis is an autoimmune neurodegenerative disorder resulting in motor dysfunction and cognitive decline. The inflammatory and neurodegenerative changes seen in the brains of MS patients lead to progressive disability and increasing brain atrophy. The most common type of MS is characterized by episodes of clinical exacerbations and remissions. This suggests the presence of compensating mechanisms for accumulating damage. Apart from the widely known repair mechanisms like remyelination, another important phenomenon is neuronal plasticity. Initially, neuroplasticity was connected with the developmental stages of life; however, there is now growing evidence confirming that structural and functional reorganization occurs throughout our lifetime. Several functional studies, utilizing such techniques as fMRI, TBS, or MRS, have provided valuable data about the presence of neuronal plasticity in MS patients. CNS ability to compensate for neuronal damage is most evident in RR-MS; however it has been shown that brain plasticity is also preserved in patients with substantial brain damage. Regardless of the numerous studies, the molecular background of neuronal plasticity in MS is still not well understood. Several factors, like IL-1β, BDNF, PDGF, or CB1Rs, have been implicated in functional recovery from the acute phase of MS and are thus considered as potential therapeutic targets. PMID:26229689

Designing shear-thinning

NASA Astrophysics Data System (ADS)

Nelson, Arif Z.; Ewoldt, Randy H.

2017-11-01

Design in fluid mechanics often focuses on optimizing geometry (airfoils, surface textures, microfluid channels), but here we focus on designing fluids themselves. The dramatically shear-thinning ``yield-stress fluid'' is currently the most utilized non-Newtonian fluid phenomenon. These rheologically complex materials, which undergo a reversible transition from solid-like to liquid-like fluid flow, are utilized in pedestrian products such as paint and toothpaste, but also in emerging applications like direct-write 3D printing. We present a paradigm for yield-stress fluid design that considers constitutive model representation, material property databases, available predictive scaling laws, and the many ways to achieve a yield stress fluid, flipping the typical structure-to-rheology analysis to become the inverse: rheology-to-structure with multiple possible materials as solutions. We describe case studies of 3D printing inks and other flow scenarios where designed shear-thinning enables performance remarkably beyond that of Newtonian fluids. This work was supported by Wm. Wrigley Jr. Company and the National Science Foundation under Grant No. CMMI-1463203.

Free-piston reciprocating cryogenic expander utilizing phase controller

NASA Astrophysics Data System (ADS)

Cha, Jeongmin; Park, Jiho; Kim, Kyungjoong; Jeong, Sangkwon

2017-02-01

In a free-piston expander which eliminates mechanical linkages, a prescribed behaviour of the free-piston movement is the key to an expander performance. In this paper, we have proposed an idea of reducing complexity of the free-piston expander. It is to replace both multiple solenoid valves and reservoirs that are indispensable in a previous machine with a combination of a single orifice-reservoir assembly. It functions as a phase controller like that of a pulse tube refrigerator so that it generates time-delay of pressure variation between the warm-end and the reservoir resulting in the intended expansion of the cold-end volume down to the pre-set reservoir pressure. The modeling of this unique free-piston reciprocating expander utilizing phase controller is developed to understand and predict the performance of the new-type expander. Additionally, the operating parameters are analysed at the specified conditions to enable one to develop a more efficient free-piston type cryogenic expander.

Advanced ceramic coating development for industrial/utility gas turbine applications

NASA Technical Reports Server (NTRS)

Andersson, C. A.; Lau, S. K.; Bratton, R. J.; Lee, S. Y.; Rieke, K. L.; Allen, J.; Munson, K. E.

1982-01-01

The effects of ceramic coatings on the lifetimes of metal turbine components and on the performance of a utility turbine, as well as of the turbine operational cycle on the ceramic coatings were determined. When operating the turbine under conditions of constant cooling flow, the first row blades run 55K cooler, and as a result, have 10 times the creep rupture life, 10 times the low cycle fatigue life and twice the corrosion life with only slight decreases in both specific power and efficiency. When operating the turbine at constant metal temperature and reduced cooling flow, both specific power and efficiency increases, with no change in component lifetime. The most severe thermal transient of the turbine causes the coating bond stresses to approach 60% of the bond strengths. Ceramic coating failures was studied. Analytic models based on fracture mechanics theories, combined with measured properties quantitatively assessed both single and multiple thermal cycle failures which allowed the prediction of coating lifetime. Qualitative models for corrosion failures are also presented.

Crystal structure of Bombyx mori arylphorins reveals a 3:3 heterohexamer with multiple papain cleavage sites

PubMed Central

Hou, Yong; Li, Jianwei; Li, Yi; Dong, Zhaoming; Xia, Qingyou; Yuan, Y Adam

2014-01-01

In holometabolous insects, the accumulation and utilization of storage proteins (SPs), including arylphorins and methionine-rich proteins, are critical for the insect metamorphosis. SPs function as amino acids reserves, which are synthesized in fat body, secreted into the larval hemolymph and taken up by fat body shortly before pupation. However, the detailed molecular mechanisms of digestion and utilization of SPs during development are largely unknown. Here, we report the crystal structure of Bombyx mori arylphorins at 2.8 Å, which displays a heterohexameric structural arrangement formed by trimerization of dimers comprising two structural similar arylphorins. Our limited proteolysis assay and microarray data strongly suggest that papain-like proteases are the major players for B. mori arylphorins digestion in vitro and in vivo. Consistent with the biochemical data, dozens of papain cleavage sites are mapped on the surface of the heterohexameric structure of B. mori arylphorins. Hence, our results provide the insightful information to understand the metamorphosis of holometabolous insects at molecular level. PMID:24639361

Effectiveness of an audience response system in teaching pharmacology to baccalaureate nursing students.

PubMed

Vana, Kimberly D; Silva, Graciela E; Muzyka, Diann; Hirani, Lorraine M

2011-06-01

It has been proposed that students' use of an audience response system, commonly called clickers, may promote comprehension and retention of didactic material. Whether this method actually improves students' grades, however, is still not determined. The purpose of this study was to evaluate whether a lecture format utilizing multiple-choice PowerPoint slides and an audience response system was more effective than a lecture format using only multiple-choice PowerPoint slides in the comprehension and retention of pharmacological knowledge in baccalaureate nursing students. The study also assessed whether the additional use of clickers positively affected students' satisfaction with their learning. Results from 78 students who attended lecture classes with multiple-choice PowerPoint slides plus clickers were compared with those of 55 students who utilized multiple-choice PowerPoint slides only. Test scores between these two groups were not significantly different. A satisfaction questionnaire showed that 72.2% of the control students did not desire the opportunity to use clickers. Of the group utilizing the clickers, 92.3% recommend the use of this system in future courses. The use of multiple-choice PowerPoint slides and an audience response system did not seem to improve the students' comprehension or retention of pharmacological knowledge as compared with those who used solely multiple-choice PowerPoint slides.

Detection of the actinides and cesium from environmental samples

NASA Astrophysics Data System (ADS)

Snow, Mathew Spencer

Detection of the actinides and cesium in the environment is important for a variety of applications ranging from environmental remediation to safeguards and nuclear forensics. The utilization of multiple different elemental concentrations and isotopic ratios together can significantly improve the ability to attribute contamination to a unique source term and/or generation process; however, the utilization of multiple elemental "signatures" together from environmental samples requires knowledge of the impact of chemical fractionation for various elements under a variety of environmental conditions (including predominantly aqueous versus arid conditions). The research reported in this dissertation focuses on three major areas: 1. Improving the understanding of actinide-mineral interactions at ultra-low concentrations. Chapter 2 reports a batch sorption and modeling study of Np(V) sorption to the mineral goethite from attomolar to micromolar concentrations. 2. Improving the detection capabilities for Thermal Ionization Mass Spectrometry (TIMS) analyses of ultra-trace cesium from environmental samples. Chapter 4 reports a new method which significantly improves the chemical yields, purification, sample processing time, and ultimately, the detection limits for TIMS analyses of femtogram quantities of cesium from a variety of environmental sample matrices. 3. Demonstrating how actinide and cesium concentrations and isotopic ratios from environmental samples can be utilized together to determine a wealth of information including environmental transport mechanisms (e.g. aqueous versus arid transport) and information on the processes which generated the original material. Chapters1, 3 and 5 demonstrate these principles using Pu, Am, Np, and Cs concentrations and isotopic ratios from contaminated soils taken near the Subsurface Disposal Area (SDA) of Idaho National Laboratory (INL) (a low level radioactive waste disposal site in southeastern Idaho).

Rapid dissolution of ZnO nanocrystals in acidic cancer microenvironment leading to preferential apoptosis

NASA Astrophysics Data System (ADS)

Sasidharan, Abhilash; Chandran, Parwathy; Menon, Deepthy; Raman, Sreerekha; Nair, Shantikumar; Koyakutty, Manzoor

2011-09-01

The microenvironment of cancer plays a very critical role in the survival, proliferation and drug resistance of solid tumors. Here, we report an interesting, acidic cancer microenvironment-mediated dissolution-induced preferential toxicity of ZnO nanocrystals (NCs) against cancer cells while leaving primary cells unaffected. Irrespective of the size-scale (5 and 200 nm) and surface chemistry differences (silica, starch or polyethylene glycol coating), ZnO NCs exhibited multiple stress mechanisms against cancer cell lines (IC50 ~150 μM) while normal human primary cells (human dermal fibroblast, lymphocytes, human umbilical vein endothelial cells) remain less affected. Flow cytometry and confocal microscopy studies revealed that ZnO NCs undergo rapid preferential dissolution in acidic (pH ~5-6) cancer microenvironment causing elevated ROS stress, mitochondrial superoxide formation, depolarization of mitochondrial membrane, and cell cycle arrest at S/G2 phase leading to apoptosis. In effect, by elucidating the unique toxicity mechanism of ZnO NCs, we show that ZnO NCs can destabilize cancer cells by utilizing its own hostile acidic microenvironment, which is otherwise critical for its survival.The microenvironment of cancer plays a very critical role in the survival, proliferation and drug resistance of solid tumors. Here, we report an interesting, acidic cancer microenvironment-mediated dissolution-induced preferential toxicity of ZnO nanocrystals (NCs) against cancer cells while leaving primary cells unaffected. Irrespective of the size-scale (5 and 200 nm) and surface chemistry differences (silica, starch or polyethylene glycol coating), ZnO NCs exhibited multiple stress mechanisms against cancer cell lines (IC50 ~150 μM) while normal human primary cells (human dermal fibroblast, lymphocytes, human umbilical vein endothelial cells) remain less affected. Flow cytometry and confocal microscopy studies revealed that ZnO NCs undergo rapid preferential dissolution in acidic (pH ~5-6) cancer microenvironment causing elevated ROS stress, mitochondrial superoxide formation, depolarization of mitochondrial membrane, and cell cycle arrest at S/G2 phase leading to apoptosis. In effect, by elucidating the unique toxicity mechanism of ZnO NCs, we show that ZnO NCs can destabilize cancer cells by utilizing its own hostile acidic microenvironment, which is otherwise critical for its survival. Electronic supplementary information (ESI) available: FTIR data, MTT assay and zinc ion release. See DOI: 10.1039/c1nr10272a

Crystal structure of LGR4-Rspo1 complex: insights into the divergent mechanisms of ligand recognition by leucine-rich repeat G-protein-coupled receptors (LGRs).

PubMed

Xu, Jin-Gen; Huang, Chunfeng; Yang, Zhengfeng; Jin, Mengmeng; Fu, Panhan; Zhang, Ni; Luo, Jian; Li, Dali; Liu, Mingyao; Zhou, Yan; Zhu, Yongqun

2015-01-23

Leucine-rich repeat G-protein-coupled receptors (LGRs) are a unique class of G-protein-coupled receptors characterized by a large extracellular domain to recognize ligands and regulate many important developmental processes. Among the three groups of LGRs, group B members (LGR4-6) recognize R-spondin family proteins (Rspo1-4) to stimulate Wnt signaling. In this study, we successfully utilized the "hybrid leucine-rich repeat technique," which fused LGR4 with the hagfish VLR protein, to obtain two recombinant human LGR4 proteins, LGR415 and LGR49. We determined the crystal structures of ligand-free LGR415 and the LGR49-Rspo1 complex. LGR4 exhibits a twisted horseshoe-like structure. Rspo1 adopts a flat and β-fold architecture and is bound in the concave surface of LGR4 in the complex through electrostatic and hydrophobic interactions. All the Rspo1-binding residues are conserved in LGR4-6, suggesting that LGR4-6 bind R-spondins through an identical surface. Structural analysis of our LGR4-Rspo1 complex with the previously determined LGR4 and LGR5 structures revealed that the concave surface of LGR4 is the sole binding site for R-spondins, suggesting a one-site binding model of LGR4-6 in ligand recognition. The molecular mechanism of LGR4-6 is distinct from the two-step mechanism of group A receptors LGR1-3 and the multiple-interface binding model of group C receptors LGR7-8, suggesting LGRs utilize the divergent mechanisms for ligand recognition. Our structures, together with previous reports, provide a comprehensive understanding of the ligand recognition by LGRs. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

National Trends (2009-2013) for Palliative Care Utilization for Patients Receiving Prolonged Mechanical Ventilation.

PubMed

Chatterjee, Kshitij; Goyal, Abhinav; Kakkera, Krishna; Harrington, Sarah; Corwin, Howard L

2018-05-04

Patients requiring mechanical ventilation have high morbidity and mortality. Providing palliative care services has been suggested as a way to improve comprehensive management of critically ill patients. We examined the trend in the utilization of palliative care among adults who require prolonged mechanical ventilation. Primary objectives were to determine the trend in palliative care utilization over time, predictors for palliative care utilization, and palliative care impact on hospital length of stay. Retrospective, cross-sectional study. The National Inpatient Sample data between 2009 and 2013 was used for this study. Adults (age ≥ 18 yr) who underwent prolonged mechanical ventilation (≥ 96 consecutive hr) were studied. Palliative care and mechanical ventilation were identified using the corresponding International Classification of Diseases, 9th revision, Clinical Modification, codes. A total of 1,751,870 hospitalizations with prolonged mechanical ventilation were identified between 2009 and 2013. The utilization of palliative care increased yearly from 6.5% in 2009 to 13.1% in 2013 (p < 0.001). Among the mechanically ventilated patients who died, palliative care increased from 15.9% in 2009 to 33.3% in 2013 (p < 0.001). Median hospital length of stay for patients with and without palliative care was 13 and 17 days, respectively (p < 0.001). Patients discharged to either short- or long-term care facilities had a shorter length of stay if palliative care was provided (15 vs 19 d; p < 0.001). The factors associated with a higher palliative care utilization included older age, malignancy, larger hospitals in urban areas, and teaching hospitals. Non-Caucasian race was associated with lower palliative care utilization. Among patients who undergo prolonged mechanical ventilation, palliative care utilization is increasing, particularly in patients who die during hospitalization. Using palliative care for mechanically ventilated patients who are discharged to either short- or long-term care facilities is associated with a shorter hospital length of stay.

Integrating Monetary and Non-monetary Reenlistment Incentives Utilizing the Combinatorial Retention Auction Mechanism (CRAM)

DTIC Science & Technology

2008-12-01

NAVAL POSTGRADUATE SCHOOL MONTEREY, CALIFORNIA THESIS INTEGRATING MONETARY AND NON-MONETARY REENLISTMENT INCENTIVES UTILIZING THE...Monetary and Non- monetary Reenlistment Incentives Utilizing the Combinatorial Retention Auction Mechanism (CRAM) 6. AUTHOR(S) Brooke Zimmerman 5...iii Approved for public release; distribution is unlimited INTEGRATING MONETARY AND NON-MONETARY REENLISTMENT INCENTIVES UTILIZING THE

Multiple-Array Detection, Association and Location of Infrasound and Seismo-Acoustic Events - Utilization of Ground Truth Information

DTIC Science & Technology

2010-09-01

MULTIPLE-ARRAY DETECTION, ASSOCIATION AND LOCATION OF INFRASOUND AND SEISMO-ACOUSTIC EVENTS – UTILIZATION OF GROUND TRUTH INFORMATION Stephen J...and infrasound data from seismo-acoustic arrays and apply the methodology to regional networks for validation with ground truth information. In the...initial year of the project automated techniques for detecting, associating and locating infrasound signals were developed. Recently, the location

Multiple traumatic brain injury and concussive symptoms among deployed military personnel.

PubMed

Bryan, Craig J

2013-01-01

To identify if concussive symptoms occur with greater frequency among military personnel with multiple lifetime TBIs and if a history of TBI increases risk for subsequent TBI. One hundred and sixty-one military personnel referred to a TBI clinic for evaluation and treatment of suspected head injury at a military clinic in Iraq. Military patients completed standardized self-report measures of concussion, depression and post-traumatic stress symptoms; clinical interview; and physical examination. Group comparisons were made according to number of lifetime TBIs and logistic regression was utilized to determine the association of past TBIs on current TBI. Patients with one or more previous TBIs were more likely to report concussion symptoms immediately following a recent injury and during the evaluation. Although differences between single and multiple TBI groups were observed, these did not reach the level of statistical significance. A history of any TBI increased the likelihood of current TBI diagnosis, but this relationship was no longer significant when adjusting for injury mechanism, depression and post-traumatic stress symptoms. Among deployed military personnel, the relationship of previous TBI with recent TBI and concussive symptoms may be largely explained by the presence of psychological symptoms.

Fuzzy adaptive interacting multiple model nonlinear filter for integrated navigation sensor fusion.

PubMed

Tseng, Chien-Hao; Chang, Chih-Wen; Jwo, Dah-Jing

2011-01-01

In this paper, the application of the fuzzy interacting multiple model unscented Kalman filter (FUZZY-IMMUKF) approach to integrated navigation processing for the maneuvering vehicle is presented. The unscented Kalman filter (UKF) employs a set of sigma points through deterministic sampling, such that a linearization process is not necessary, and therefore the errors caused by linearization as in the traditional extended Kalman filter (EKF) can be avoided. The nonlinear filters naturally suffer, to some extent, the same problem as the EKF for which the uncertainty of the process noise and measurement noise will degrade the performance. As a structural adaptation (model switching) mechanism, the interacting multiple model (IMM), which describes a set of switching models, can be utilized for determining the adequate value of process noise covariance. The fuzzy logic adaptive system (FLAS) is employed to determine the lower and upper bounds of the system noise through the fuzzy inference system (FIS). The resulting sensor fusion strategy can efficiently deal with the nonlinear problem for the vehicle navigation. The proposed FUZZY-IMMUKF algorithm shows remarkable improvement in the navigation estimation accuracy as compared to the relatively conventional approaches such as the UKF and IMMUKF.

Organization of microtubule assemblies in Dictyostelium syncytia depends on the microtubule crosslinker, Ase1

PubMed Central

Tikhonenko, Irina; Irizarry, Karen; Khodjakov, Alexey; Koonce, Michael P.

2015-01-01

It has long been known that the interphase microtubule (MT) array is a key cellular scaffold that provides structural support and directs organelle trafficking in eukaryotic cells. Although in animal cells, a combination of centrosome nucleating properties and polymer dynamics at the distal microtubule ends is generally sufficient to establish a radial, polar array of MTs, little is known about how effector proteins (motors and crosslinkers) are coordinated to produce the diversity of interphase MT array morphologies found in nature. This diversity is particularly important in multinucleated environments where multiple MT arrays must coexist and function. We initiate here a study to address the higher ordered coordination of multiple, independent MT arrays in a common cytoplasm. Deletion of a MT crosslinker of the MAP65/Ase1/PRC1 family disrupts the spatial integrity of multiple arrays in Dictyostelium discoideum, reducing the distance between centrosomes and increasing the intermingling of MTs with opposite polarity. This result, coupled with previous dynein disruptions suggest a robust mechanism by which interphase MT arrays can utilize motors and crosslinkers to sense their position and minimize overlap in a common cytoplasm. PMID:26298292

Multiple Optical Traps with a Single-Beam Optical Tweezer Utilizing Surface Micromachined Planar Curved Grating

NASA Astrophysics Data System (ADS)

Kuo, Ju-Nan; Chen, Kuan-Yu

2010-11-01

In this paper, we present a single-beam optical tweezer integrated with a planar curved diffraction grating for microbead manipulation. Various curvatures of the surface micromachined planar curved grating are systematically investigated. The planar curved grating was fabricated using multiuser micro-electro-mechanical-system (MEMS) processes (MUMPs). The angular separation and the number of diffracted orders were determined. Experimental results indicate that the diffraction patterns and curvature of the planar curved grating are closely related. As the curvature of the planar curved grating increases, the vertical diffraction angle increases, resulting in the strip patterns of the planar curved grating. A single-beam optical tweezer integrated with a planar curved diffraction grating was developed. We demonstrate a technique for creating multiple optical traps from a single laser beam using the developed planar curved grating. The strip patterns of the planar curved grating that resulted from diffraction were used to trap one row of polystyrene beads.

IOPA: I/O-aware parallelism adaption for parallel programs

PubMed Central

Liu, Tao; Liu, Yi; Qian, Chen; Qian, Depei

2017-01-01

With the development of multi-/many-core processors, applications need to be written as parallel programs to improve execution efficiency. For data-intensive applications that use multiple threads to read/write files simultaneously, an I/O sub-system can easily become a bottleneck when too many of these types of threads exist; on the contrary, too few threads will cause insufficient resource utilization and hurt performance. Therefore, programmers must pay much attention to parallelism control to find the appropriate number of I/O threads for an application. This paper proposes a parallelism control mechanism named IOPA that can adjust the parallelism of applications to adapt to the I/O capability of a system and balance computing resources and I/O bandwidth. The programming interface of IOPA is also provided to programmers to simplify parallel programming. IOPA is evaluated using multiple applications with both solid state and hard disk drives. The results show that the parallel applications using IOPA can achieve higher efficiency than those with a fixed number of threads. PMID:28278236

[A consensual therapeutic recommendation for type 2 diabetes mellitus by the Slovak Diabetes Society (2018)].

PubMed

Martinka, Emil; Uličiansky, Vladimír; Mokáň, Marián; Tkáč, Ivan; Galajda, Peter; Dókušová, Silvia; Schroner, Zbynek

2018-01-01

Type 2 diabetes mellitus is a heterogeneous medical condition involving multiple pathophysiological mechanisms. Its successful treatment requires an individualized approach and frequently combined therapy with utilizing its effect on multiple levels. Current possibilities enable the employment of such procedures to an incomparably greater extent than before. The effects of different classes of oral antidiabetic drugs on the reduction of glycemia and HbA1c is mutually comparable. However differences are observed in the proportions of patients who met the required criteria, regarding the increase in weight, incidence of hypoglycemia as well as the effect on cardiovascular, renal or oncologic morbidity and mortality, and severity of specific adverse effects, potential risks and contraindications. The presented text provides the reader with the information about the Consensual therapeutic algorithm for the treatment of type 2 diabetes mellitus in compliance with SPC, the ADA/EASD amended indicative limitations and recommendations, formulated by the Committee of the Slovak Diabetes Society.Key words: biguanides - gliflozins - gliptins - glitazones - GLP-1-receptor agonists - insulin - sulfonylurea.

Modeling joint restoration strategies for interdependent infrastructure systems.

PubMed

Zhang, Chao; Kong, Jingjing; Simonovic, Slobodan P

2018-01-01

Life in the modern world depends on multiple critical services provided by infrastructure systems which are interdependent at multiple levels. To effectively respond to infrastructure failures, this paper proposes a model for developing optimal joint restoration strategy for interdependent infrastructure systems following a disruptive event. First, models for (i) describing structure of interdependent infrastructure system and (ii) their interaction process, are presented. Both models are considering the failure types, infrastructure operating rules and interdependencies among systems. Second, an optimization model for determining an optimal joint restoration strategy at infrastructure component level by minimizing the economic loss from the infrastructure failures, is proposed. The utility of the model is illustrated using a case study of electric-water systems. Results show that a small number of failed infrastructure components can trigger high level failures in interdependent systems; the optimal joint restoration strategy varies with failure occurrence time. The proposed models can help decision makers to understand the mechanisms of infrastructure interactions and search for optimal joint restoration strategy, which can significantly enhance safety of infrastructure systems.

IOPA: I/O-aware parallelism adaption for parallel programs.

PubMed

Liu, Tao; Liu, Yi; Qian, Chen; Qian, Depei

2017-01-01

With the development of multi-/many-core processors, applications need to be written as parallel programs to improve execution efficiency. For data-intensive applications that use multiple threads to read/write files simultaneously, an I/O sub-system can easily become a bottleneck when too many of these types of threads exist; on the contrary, too few threads will cause insufficient resource utilization and hurt performance. Therefore, programmers must pay much attention to parallelism control to find the appropriate number of I/O threads for an application. This paper proposes a parallelism control mechanism named IOPA that can adjust the parallelism of applications to adapt to the I/O capability of a system and balance computing resources and I/O bandwidth. The programming interface of IOPA is also provided to programmers to simplify parallel programming. IOPA is evaluated using multiple applications with both solid state and hard disk drives. The results show that the parallel applications using IOPA can achieve higher efficiency than those with a fixed number of threads.

Relationship among several measurements of slipperiness obtained in a laboratory environment.

PubMed

Chang, Wen-Ruey; Chang, Chien-Chi

2018-04-01

Multiple sensing mechanisms could be used in forming responses to avoid slips, but previous studies, correlating only two parameters, revealed a limited picture of this complex system. In this study, the participants walked as fast as possible without a slip under 15 conditions of different degrees of slipperiness. The relationships among various response parameters, including perceived slipperiness rating, utilized coefficient of friction (UCOF), slipmeter measurement and kinematic parameters, were evaluated. The results showed that the UCOF, perceived rating and heel angle had higher adjusted R 2 values as dependent variables in the multiple linear regressions with the remaining variables in the final pool as independent variables. Although each variable in the final data pool could reflect some measurement of slipperiness, these three variables are more inclusive than others in representing the other variables and were bigger predictors of other variables, so they could be better candidates for measurements of slipperiness. Copyright © 2017 Elsevier Ltd. All rights reserved.

Fusion peptides from oncogenic chimeric proteins as putative specific biomarkers of cancer.

PubMed

Conlon, Kevin P; Basrur, Venkatesha; Rolland, Delphine; Wolfe, Thomas; Nesvizhskii, Alexey I; MacCoss, Michael J; Lim, Megan S; Elenitoba-Johnson, Kojo S J

2013-10-01

Chromosomal translocations encoding chimeric fusion proteins constitute one of the most common mechanisms underlying oncogenic transformation in human cancer. Fusion peptides resulting from such oncogenic chimeric fusions, though unique to specific cancer subtypes, are unexplored as cancer biomarkers. Here we show, using an approach termed fusion peptide multiple reaction monitoring mass spectrometry, the direct identification of different cancer-specific fusion peptides arising from protein chimeras that are generated from the juxtaposition of heterologous genes fused by recurrent chromosomal translocations. Using fusion peptide multiple reaction monitoring mass spectrometry in a clinically relevant scenario, we demonstrate the specific, sensitive, and unambiguous detection of a specific diagnostic fusion peptide in clinical samples of anaplastic large cell lymphoma, but not in a diverse array of benign lymph nodes or other forms of primary malignant lymphomas and cancer-derived cell lines. Our studies highlight the utility of fusion peptides as cancer biomarkers and carry broad implications for the use of protein biomarkers in cancer detection and monitoring.

Towards multicaloric effect with ferroelectrics

NASA Astrophysics Data System (ADS)

Liu, Yang; Zhang, Guangzu; Li, Qi; Bellaiche, Laurent; Scott, James F.; Dkhil, Brahim; Wang, Qing

2016-12-01

Utilizing thermal changes in solid-state materials strategically offers caloric-based alternatives to replace current vapor-compression technology. To make full use of multiple forms of the entropy and achieve higher efficiency for designs of cooling devices, the multicaloric effect appears as a cutting-edge concept encouraging researchers to search for multicaloric materials with outstanding caloric properties. Here we report the multicaloric effect in BaTi O3 single crystals driven simultaneously by mechanical and electric fields and described via a thermodynamic phenomenological model. It is found that the multicaloric behavior is mainly dominated by the mechanical field rather than the electric field, since the paraelectric-to-ferroelectric transition is more sensitive to mechanical field than to electric field. The use of uniaxial stress competes favorably with pressure due to its much higher caloric strength and negligible elastic thermal change. It is revealed that multicaloric response can be significantly larger than just the sum of mechanocaloric and electrocaloric effects in temperature regions far above the Curie temperature but cannot exceed this limit near the Curie temperature. Our results also show the advantage of the multicaloric effect over the mechanically mediated electrocaloric effect or electrically mediated mechanocaloric effect. Our findings therefore highlight the importance of ferroelectric materials to develop multicaloric cooling.

Involvement of multiple distinct Bordetella receptor proteins in the utilization of iron liberated from transferrin by host catecholamine stress hormones

PubMed Central

Armstrong, Sandra K.; Brickman, Timothy J.; Suhadolc, Ryan J.

2012-01-01

Summary Bordetella bronchiseptica is a pathogen that can acquire iron using its native alcaligin siderophore system, but can also use the catechol xenosiderophore enterobactin via the BfeA outer membrane receptor. Transcription of bfeA is positively controlled by a regulator that requires induction by enterobactin. Catecholamine hormones also induce bfeA transcription and B. bronchiseptica can use the catecholamine norepinephrine for growth on transferrin. In this study, B. bronchiseptica was shown to use catecholamines to obtain iron from both transferrin and lactoferrin in the absence of siderophore. In the presence of siderophore, norepinephrine augmented transferrin utilization by B. bronchiseptica, as well as siderophore function in vitro. Genetic analysis identified BfrA, BfrD and BfrE as TonB dependent outer membrane catecholamine receptors. The BfeA enterobactin receptor was found to not be involved directly in catecholamine utilization; however, the BfrA, BfrD and BfrE catecholamine receptors could serve as receptors for enterobactin and its degradation product 2,3-dihydroxybenzoic acid. Thus, there is a functional link between enterobactin-dependent and catecholamine-dependent transferrin utilization. This investigation characterizes a new B. bronchiseptica mechanism for iron uptake from transferrin that uses host stress hormones that not only deliver iron directly to catecholamine receptors, but also potentiate siderophore activity by acting as iron shuttles. PMID:22458330

Trauma exposure and cigarette smoking: the impact of negative affect and affect-regulatory smoking motives.

PubMed

Farris, Samantha G; Zvolensky, Michael J; Beckham, Jean C; Vujanovic, Anka A; Schmidt, Norman B

2014-01-01

Cognitive-affective mechanisms related to the maintenance of smoking among trauma-exposed individuals are largely unknown. Cross-sectional data from trauma-exposed treatment-seeking smokers (n = 283) were utilized to test a series of multiple mediator models of trauma exposure and smoking, as mediated by the sequential effects of negative affect and affect-modulation smoking motives. The sequential effects of both mediators indirectly predicted the effect of greater trauma exposure types on nicotine dependence, a biochemical index of smoking, perceived barriers to smoking cessation, and greater withdrawal-related problems during past quit attempts. Negative affect and affect-modulation motives for smoking may contribute to the trauma-smoking association.

Nanotechnology use with cosmeceuticals.

PubMed

Golubovic-Liakopoulos, Nevenka; Simon, Sanford R; Shah, Bhavdeep

2011-09-01

The skin is a complex organ and its aging is a complex process. Cutaneous aging is influenced by factors such as sun exposure, genetics, stress and the environment. While skin laxity, rhytides, and dyschromia appear on the surface, these processes originate in deeper layers including the dermis and subcutaneous tissues. Until recently, most topical skin treatments were applied to, and consequently only affected the skin surface. Skin care has evolved to be scientifically based, and as knowledge increases about the physiology of the skin, novel methods of maintaining its health and appearance are developed. New generation skin care products are targeting multiple aging mechanisms by utilizing functional active ingredients in combination with innovative delivery systems. Copyright © 2011 Elsevier Inc. All rights reserved.

Public health agenda setting in a global context: the International Labor Organization's decent work agenda.

PubMed

Di Ruggiero, Erica; Cohen, Joanna E; Cole, Donald C; Forman, Lisa

2015-04-01

We drew on two agenda-setting theories usually applied at the state or national level to assess their utility at the global level: Kingdon's multiple streams theory and Baumgartner and Jones's punctuated equilibrium theory. We illustrate our analysis with findings from a qualitative study of the International Labor Organization's Decent Work Agenda. We found that both theories help explain the agenda-setting mechanisms that operate in the global context, including how windows of opportunity open and what role institutions play as policy entrepreneurs. Future application of these theories could help characterize power struggles between global actors, whose voices are heard or silenced, and their impact on global policy agenda setting.

Fundamental understanding and rational design of high energy structural microbatteries

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

Wang, Yuxing; Li, Qiuyan; Cartmell, Samuel

Microbatteries play a critical role in determining the lifetime of downsized sensors, wearable devices and medical applications, etc. More often, structural batteries are required from the perspective of aesthetics and space utilization, which is however rarely explored. Herein, we discuss the fundamental issues associated with the rational design of practically usable high energy microbatteries. The tubular shape of the cell further allows the flexible integration of microelectronics. A functioning acoustic micro-transmitter continuously powered by this tubular battery has been successfully demonstrated. Multiple design features adopted to accommodate large mechanical stress during the rolling process are discussed providing new insights inmore » designing the structural microbatteries for emerging technologies.« less

Trauma Exposure and Cigarette Smoking: The Impact of Negative Affect and Affect-Regulatory Smoking Motives

PubMed Central

Farris, Samantha G.; Zvolensky, Michael J.; Beckham, Jean C.; Vujanovic, Anka A.; Schmidt, Norman B.

2014-01-01

Cognitive-affective mechanisms related to the maintenance of smoking among trauma-exposed individuals are largely unknown. Cross-sectional data from trauma-exposed treatment-seeking smokers (n = 283) were utilized to test a series of multiple mediator models of trauma exposure and smoking, as mediated by the sequential effects of negative affect and affect-modulation smoking motives. The sequential effects of both mediators indirectly predicted the effect of greater trauma exposure types on nicotine dependence, a biochemical index of smoking, perceived barriers to smoking cessation, and greater withdrawal-related problems during past quit attempts. Negative affect and affect-modulation motives for smoking may contribute to the trauma-smoking association. PMID:25299617

Neural basis of quasi-rational decision making.

PubMed

Lee, Daeyeol

2006-04-01

Standard economic theories conceive homo economicus as a rational decision maker capable of maximizing utility. In reality, however, people tend to approximate optimal decision-making strategies through a collection of heuristic routines. Some of these routines are driven by emotional processes, and others are adjusted iteratively through experience. In addition, routines specialized for social decision making, such as inference about the mental states of other decision makers, might share their origins and neural mechanisms with the ability to simulate or imagine outcomes expected from alternative actions that an individual can take. A recent surge of collaborations across economics, psychology and neuroscience has provided new insights into how such multiple elements of decision making interact in the brain.

Emerging Relationships between Exercise, Sensory Nerves, and Neuropathic Pain

PubMed Central

Cooper, Michael A.; Kluding, Patricia M.; Wright, Douglas E.

2016-01-01

The utilization of physical activity as a therapeutic tool is rapidly growing in the medical community and the role exercise may offer in the alleviation of painful disease states is an emerging research area. The development of neuropathic pain is a complex mechanism, which clinicians and researchers are continually working to better understand. The limited therapies available for alleviation of these pain states are still focused on pain abatement and as opposed to treating underlying mechanisms. The continued research into exercise and pain may address these underlying mechanisms, but the mechanisms which exercise acts through are still poorly understood. The objective of this review is to provide an overview of how the peripheral nervous system responds to exercise, the relationship of inflammation and exercise, and experimental and clinical use of exercise to treat pain. Although pain is associated with many conditions, this review highlights pain associated with diabetes as well as experimental studies on nerve damages-associated pain. Because of the global effects of exercise across multiple organ systems, exercise intervention can address multiple problems across the entire nervous system through a single intervention. This is a double-edged sword however, as the global interactions of exercise also require in depth investigations to include and identify the many changes that can occur after physical activity. A continued investment into research is necessary to advance the adoption of physical activity as a beneficial remedy for neuropathic pain. The following highlights our current understanding of how exercise alters pain, the varied pain models used to explore exercise intervention, and the molecular pathways leading to the physiological and pathological changes following exercise intervention. PMID:27601974

Distributed controller clustering in software defined networks.

PubMed

Abdelaziz, Ahmed; Fong, Ang Tan; Gani, Abdullah; Garba, Usman; Khan, Suleman; Akhunzada, Adnan; Talebian, Hamid; Choo, Kim-Kwang Raymond

2017-01-01

Software Defined Networking (SDN) is an emerging promising paradigm for network management because of its centralized network intelligence. However, the centralized control architecture of the software-defined networks (SDNs) brings novel challenges of reliability, scalability, fault tolerance and interoperability. In this paper, we proposed a novel clustered distributed controller architecture in the real setting of SDNs. The distributed cluster implementation comprises of multiple popular SDN controllers. The proposed mechanism is evaluated using a real world network topology running on top of an emulated SDN environment. The result shows that the proposed distributed controller clustering mechanism is able to significantly reduce the average latency from 8.1% to 1.6%, the packet loss from 5.22% to 4.15%, compared to distributed controller without clustering running on HP Virtual Application Network (VAN) SDN and Open Network Operating System (ONOS) controllers respectively. Moreover, proposed method also shows reasonable CPU utilization results. Furthermore, the proposed mechanism makes possible to handle unexpected load fluctuations while maintaining a continuous network operation, even when there is a controller failure. The paper is a potential contribution stepping towards addressing the issues of reliability, scalability, fault tolerance, and inter-operability.

Non-obstructive prosthetic aortic valve thrombosis presenting with acute myocardial infarction and stroke in a patient with inadequate low-molecular-weight heparin treatment. The unlucky patient and the (pseudo)prudent physician.

PubMed

Paci, Anna Maria; Lattanzi, Fabio; Cabani, Enrico; Conti, Umberto; De Tommasi, Salvatore Mario

2007-04-01

Non-obstructive prosthetic valve thrombosis is a rare and underestimated complication in patients with left-sided mechanical heart valves. Systemic embolisation, mainly involving the cerebral circulation, often represents the first clinical manifestation. We report a case of multiple, successive embolizations in the coronary and cerebral circulation, presenting with an acute myocardial infarction and stroke in a patient with latent, non-obstructive thrombosis of a mechanical bileaflet aortic valve. Because of scheduled urological surgery, chronic vitamin K antagonist treatment had previously been discontinued and replaced with low-molecular-weight heparin, at inadequate dosage. Following coronary arteriography, brain computed tomography scan and transoesophageal echocardiography, thrombolysis was performed successfully. This case emphasises the utility of performing transoesophageal echocardiography routinely in the presence of ischaemic signs in patients with mechanical heart valves. In patients requiring discontinuation of oral anticoagulant therapy, accurate management and continuous monitoring of alternative medications are needed in order to avoid severe thromboembolic complications.

Implications of genetic research on the role of the serotonin in depression: emphasis on the serotonin type 1A receptor and the serotonin transporter.

PubMed

Neumeister, Alexander; Young, Theresa; Stastny, Juergen

2004-08-01

Serotonin systems appear to play a key role in the pathophysiology of major depressive disorder. Consequently, ongoing research determines whether serotonin related genes account for the very robust differential behavioral and neural mechanisms that discriminate patients with depression from healthy controls. Serotonin type 1(A) receptors and the serotonin transporters are reduced in depression, and recent genetic research in animals and humans has implicated both in depression. Preclinical studies have utilized a variety of animal models that have been used to explain pathophysiological mechanisms in humans, although it is not clear at all whether these models constitute relevant models for depression in humans. However, data from preclinical studies can generate hypotheses that are tested in humans by combining genetic data with behavioral and physiological challenge paradigms and neuroimaging. These studies will enhance our understanding about combined influences from multiple interacting genes, as well as from environmental factors on brain circuits and their function, and about how these mechanisms may contribute to the pathophysiology of neuropsychiatric disorders.

Streptococcus oralis Neuraminidase Modulates Adherence to Multiple Carbohydrates on Platelets.

PubMed

Singh, Anirudh K; Woodiga, Shireen A; Grau, Margaret A; King, Samantha J

2017-03-01

Adherence to host surfaces is often mediated by bacterial binding to surface carbohydrates. Although it is widely appreciated that some bacterial species express glycosidases, previous studies have not considered whether bacteria bind to multiple carbohydrates within host glycans as they are modified by bacterial glycosidases. Streptococcus oralis is a leading cause of subacute infective endocarditis. Binding to platelets is a critical step in disease; however, the mechanisms utilized by S. oralis remain largely undefined. Studies revealed that S. oralis , like Streptococcus gordonii and Streptococcus sanguinis , binds platelets via terminal sialic acid. However, unlike those organisms, S. oralis produces a neuraminidase, NanA, which cleaves terminal sialic acid. Further studies revealed that following NanA-dependent removal of terminal sialic acid, S. oralis bound exposed β-1,4-linked galactose. Adherence to both these carbohydrates required Fap1, the S. oralis member of the serine-rich repeat protein (SRRP) family of adhesins. Mutation of a conserved residue required for sialic acid binding by other SRRPs significantly reduced platelet binding, supporting the hypothesis that Fap1 binds this carbohydrate. The mechanism by which Fap1 contributes to β-1,4-linked galactose binding remains to be defined; however, binding may occur via additional domains of unknown function within the nonrepeat region, one of which shares some similarity with a carbohydrate binding module. This study is the first demonstration that an SRRP is required to bind β-1,4-linked galactose and the first time that one of these adhesins has been shown to be required for binding of multiple glycan receptors. Copyright © 2017 American Society for Microbiology.

Role of dimethyl fumarate in oxidative stress of multiple sclerosis: A review.

PubMed

Suneetha, A; Raja Rajeswari, K

2016-04-15

Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS affecting both white and grey matter. Inflammation and oxidative stress are also thought to promote tissue damage in multiple sclerosis. Recent data point at an important role of anti-oxidative pathways for tissue protection in chronic MS, particularly involving the transcription factor nuclear factor (erythroid-derived 2)-related factor 2 (Nrf2). Thus, novel therapeutics enhancing cellular resistance to free radicals could prove useful for MS treatment. Oxidative stress and anti-oxidative pathways are important players in MS pathophysiology and constitute a promising target for future MS therapy with dimethyl fumarate. The clinical utility of DMF in multiple sclerosis is being explored through phase III trials with BG-12, which is an oral therapeutic agent. Currently a wide research is going on to find out the exact mechanism of DMF, till date it is not clear. Based on strong signals of nephrotoxicity in non-humans and the theoretical risk of renal cell cancer from intracellular accumulation of fumarate, post-marketing study of a large population of patients will be necessary to fully assess the long-term safety of dimethyl fumarate. The current treatment goals are to shorten the duration and severity of relapses, prolong the time between relapses, and delay progression of disability. In this regard, dimethyl fumarate offers a promising alternative to orally administered fingolimod (GILENYA) or teriflunomide (AUBAGIO), which are currently marketed in the United States under FDA-mandated Risk Evaluation and Mitigation Strategy (REMS) programs because of serious safety concerns. More clinical experience with all three agents will be necessary to differentiate the tolerability of long-term therapy for patients diagnosed with multiple sclerosis. This write-up provides the detailed information of dimethyl fumarate in treating the neuro disease, multiple sclerosis and its mechanism involved via oxidative stress pathway. The rapid screening methods are also need to be developed to estimate DMF in biological samples to perform and proceed for further investigations. Copyright © 2016 Elsevier B.V. All rights reserved.

Multiple Signals Govern Utilization of a Polysaccharide in the Gut Bacterium Bacteroides thetaiotaomicron.

PubMed

Schwalm, Nathan D; Townsend, Guy E; Groisman, Eduardo A

2016-10-11

The utilization of simple sugars is widespread across all domains of life. In contrast, the breakdown of complex carbohydrates is restricted to a subset of organisms. A regulatory paradigm for integration of complex polysaccharide breakdown with simple sugar utilization was established in the mammalian gut symbiont Bacteroides thetaiotaomicron, whereby sensing of monomeric fructose regulates catabolism of both fructose and polymeric fructans. We now report that a different regulatory paradigm governs utilization of monomeric arabinose and the arabinose polymer arabinan. We establish that (i) arabinan utilization genes are controlled by a transcriptional activator that responds to arabinan and by a transcriptional repressor that responds to arabinose, (ii) arabinose utilization genes are regulated directly by the arabinose-responding repressor but indirectly by the arabinan-responding activator, and (iii) activation of both arabinan and arabinose utilization genes requires a pleiotropic transcriptional regulator necessary for survival in the mammalian gut. Genomic analysis predicts that this paradigm is broadly applicable to the breakdown of other polysaccharides in both B. thetaiotaomicron and other gut Bacteroides spp. The uncovered mechanism enables regulation of polysaccharide utilization genes in response to both the polysaccharide and its breakdown products. Breakdown of complex polysaccharides derived from "dietary fiber" is achieved by the mammalian gut microbiota. This breakdown creates a critical nutrient source for both the microbiota and its mammalian host. Because the availability of individual polysaccharides fluctuates with variations in the host diet, members of the microbiota strictly control expression of polysaccharide utilization genes. Our findings define a regulatory architecture that controls the breakdown of a polysaccharide by a gut bacterium in response to three distinct signals. This architecture integrates perception of a complex polysaccharide and its monomeric constituent as well as feedback of central metabolism. Moreover, it is broadly applicable to several prominent members of the mammalian gut microbiota. The identified regulatory strategy may contribute to the abundance of gut Bacteroides, despite fluctuations in the host diet. Copyright © 2016 Schwalm et al.

The contrasting role of male relatedness in different mechanisms of sexual selection in red junglefowl

PubMed Central

Tan, Cedric Kai Wei; Doyle, Philippa; Bagshaw, Emma; Richardson, David S.; Wigby, Stuart; Pizzari, Tommaso

2017-01-01

In structured populations, competition for reproductive opportunities should be relaxed among related males. The few tests of this prediction often neglect the fact that sexual selection acts through multiple mechanisms, both before and after mating. We performed experiments to study the role of within‐group male relatedness across pre‐ and postcopulatory mechanisms of sexual selection in social groups of red junglefowl, Gallus gallus, in which two related males and one unrelated male competed over females unrelated to all the males. We confirm theoretical expectations that, after controlling for male social status, competition over mating was reduced among related males. However, this effect was contrasted by other sexual selection mechanisms. First, females biased male mating in favor of the unrelated male, and might also favor his inseminations after mating. Second, males invested more—rather than fewer—sperm in postcopulatory competition with relatives. A number of factors may contribute to explain this counterintuitive pattern of sperm allocation, including trade‐offs between male investment in pre‐ versus postcopulatory competition, differences in the relative relatedness of pre‐ versus postcopulatory competitors, and female bias in sperm utilization in response to male relatedness. Collectively, these results reveal that within‐group male relatedness may have contrasting effects in different mechanisms of sexual selection. PMID:27925168

A Flexible Domain-Domain Hinge Promotes an Induced-fit Dominant Mechanism for the Loading of Guide-DNA into Argonaute Protein in Thermus thermophilus.

PubMed

Zhu, Lizhe; Jiang, Hanlun; Sheong, Fu Kit; Cui, Xuefeng; Gao, Xin; Wang, Yanli; Huang, Xuhui

2016-03-17

Argonaute proteins (Ago) are core components of the RNA Induced Silencing Complex (RISC) that load and utilize small guide nucleic acids to silence mRNAs or cleave foreign DNAs. Despite the essential role of Ago in gene regulation and defense against virus, the molecular mechanism of guide-strand loading into Ago remains unclear. We explore such a mechanism in the bacterium Thermus thermophilus Ago (TtAgo), via a computational approach combining molecular dynamics, bias-exchange metadynamics, and protein-DNA docking. We show that apo TtAgo adopts multiple closed states that are unable to accommodate guide-DNA. Conformations able to accommodate the guide are beyond the reach of thermal fluctuations from the closed states. These results suggest an induced-fit dominant mechanism for guide-strand loading in TtAgo, drastically different from the two-step mechanism for human Ago 2 (hAgo2) identified in our previous study. Such a difference between TtAgo and hAgo2 is found to mainly originate from the distinct rigidity of their L1-PAZ hinge. Further comparison among known Ago structures from various species indicates that the L1-PAZ hinge may be flexible in general for prokaryotic Ago's but rigid for eukaryotic Ago's.

Decision Utility, Incentive Salience, and Cue-Triggered "Wanting"

PubMed

Berridge, Kent C; Aldridge, J Wayne

2009-01-01

This chapter examines brain mechanisms of reward utility operating at particular decision moments in life-moments such as when one encounters an image, sound, scent, or other cue associated in the past with a particular reward or perhaps just when one vividly imagines that cue. Such a cue can often trigger a sudden motivational urge to pursue its reward and sometimes a decision to do so. Drawing on a utility taxonomy that distinguishes among subtypes of reward utility-predicted utility, decision utility, experienced utility, and remembered utility-it is shown how cue-triggered cravings, such as an addict's surrender to relapse, can hang on special transformations by brain mesolimbic systems of one utility subtype, namely, decision utility. The chapter focuses on a particular form of decision utility called incentive salience, a type of "wanting" for rewards that is amplified by brain mesolimbic systems. Sudden peaks of intensity of incentive salience, caused by neurobiological mechanisms, can elevate the decision utility of a particular reward at the moment its cue occurs. An understanding of what happens at such moments leads to a better understanding of the mechanisms at work in decision making in general.

Time delay spectrum conditioner

DOEpatents

Greiner, Norman R.

1980-01-01

A device for delaying specified frequencies of a multiple frequency laser beam. The device separates the multiple frequency beam into a series of spatially separated single frequency beams. The propagation distance of the single frequency beam is subsequently altered to provide the desired delay for each specific frequency. Focusing reflectors can be utilized to provide a simple but nonadjustable system or, flat reflectors with collimating and focusing optics can be utilized to provide an adjustable system.

Comparative study on legislation of utilization of construction wastes as resources in china and abroad

NASA Astrophysics Data System (ADS)

Wenfeng, Liu; Zhaomeng, Wang; Hongmei, Hou

2018-05-01

The dilemma of the “Building wastes Besieged City” has gradually become a national problem. Historical experience in the world shows that establishing a systematic and complete legal system is an effective way and powerful weapon to ensure the comprehensive utilization of building wastes resources. Based on the domestic conditions, the state focuses on the problems and learns from the legislation experience of Chinese and foreign construction wastes recycling laws and regulations, to design the legal system form multiple fields, multiple angles, and multiple levels as much as possible to achieve maximum environmental, social, and economic benefits. This article mainly summarizes the characteristics and outstanding experience of the legislation of the comprehensive utilization of construction wastes as resources in foreign countries, as well as the existing problems of Chinese relevant legal regulations, and provides reference for future research and implementation of relevant legislation.

Indirect Measurement of Energy Density of Soft PZT Ceramic Utilizing Mechanical Stress

NASA Astrophysics Data System (ADS)

Unruan, Muangjai; Unruan, Sujitra; Inkong, Yutthapong; Yimnirun, Rattikorn

2017-11-01

This paper reports on an indirect measurement of energy density of soft PZT ceramic utilizing mechanical stress. The method works analogous to the Olsen cycle and allows for a large amount of electro-mechanical energy conversion. A maximum energy density of 350 kJ/m3/cycle was found under 0-312 MPa and 1-20 kV/cm of applied mechanical stress and electric field, respectively. The obtained result is substantially higher than the results reported in previous studies of PZT materials utilizing a direct piezoelectric effect.

Equilibrium in a Production Economy

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

Chiarolla, Maria B., E-mail: maria.chiarolla@uniroma1.it; Haussmann, Ulrich G., E-mail: uhaus@math.ubc.ca

2011-06-15

Consider a closed production-consumption economy with multiple agents and multiple resources. The resources are used to produce the consumption good. The agents derive utility from holding resources as well as consuming the good produced. They aim to maximize their utility while the manager of the production facility aims to maximize profits. With the aid of a representative agent (who has a multivariable utility function) it is shown that an Arrow-Debreu equilibrium exists. In so doing we establish technical results that will be used to solve the stochastic dynamic problem (a case with infinite dimensional commodity space so the General Equilibriummore » Theory does not apply) elsewhere.« less

Spike timing precision of neuronal circuits.

PubMed

Kilinc, Deniz; Demir, Alper

2018-06-01

Spike timing is believed to be a key factor in sensory information encoding and computations performed by the neurons and neuronal circuits. However, the considerable noise and variability, arising from the inherently stochastic mechanisms that exist in the neurons and the synapses, degrade spike timing precision. Computational modeling can help decipher the mechanisms utilized by the neuronal circuits in order to regulate timing precision. In this paper, we utilize semi-analytical techniques, which were adapted from previously developed methods for electronic circuits, for the stochastic characterization of neuronal circuits. These techniques, which are orders of magnitude faster than traditional Monte Carlo type simulations, can be used to directly compute the spike timing jitter variance, power spectral densities, correlation functions, and other stochastic characterizations of neuronal circuit operation. We consider three distinct neuronal circuit motifs: Feedback inhibition, synaptic integration, and synaptic coupling. First, we show that both the spike timing precision and the energy efficiency of a spiking neuron are improved with feedback inhibition. We unveil the underlying mechanism through which this is achieved. Then, we demonstrate that a neuron can improve on the timing precision of its synaptic inputs, coming from multiple sources, via synaptic integration: The phase of the output spikes of the integrator neuron has the same variance as that of the sample average of the phases of its inputs. Finally, we reveal that weak synaptic coupling among neurons, in a fully connected network, enables them to behave like a single neuron with a larger membrane area, resulting in an improvement in the timing precision through cooperation.

Multiple fault separation and detection by joint subspace learning for the health assessment of wind turbine gearboxes

NASA Astrophysics Data System (ADS)

Du, Zhaohui; Chen, Xuefeng; Zhang, Han; Zi, Yanyang; Yan, Ruqiang

2017-09-01

The gearbox of a wind turbine (WT) has dominant failure rates and highest downtime loss among all WT subsystems. Thus, gearbox health assessment for maintenance cost reduction is of paramount importance. The concurrence of multiple faults in gearbox components is a common phenomenon due to fault induction mechanism. This problem should be considered before planning to replace the components of the WT gearbox. Therefore, the key fault patterns should be reliably identified from noisy observation data for the development of an effective maintenance strategy. However, most of the existing studies focusing on multiple fault diagnosis always suffer from inappropriate division of fault information in order to satisfy various rigorous decomposition principles or statistical assumptions, such as the smooth envelope principle of ensemble empirical mode decomposition and the mutual independence assumption of independent component analysis. Thus, this paper presents a joint subspace learning-based multiple fault detection (JSL-MFD) technique to construct different subspaces adaptively for different fault patterns. Its main advantage is its capability to learn multiple fault subspaces directly from the observation signal itself. It can also sparsely concentrate the feature information into a few dominant subspace coefficients. Furthermore, it can eliminate noise by simply performing coefficient shrinkage operations. Consequently, multiple fault patterns are reliably identified by utilizing the maximum fault information criterion. The superiority of JSL-MFD in multiple fault separation and detection is comprehensively investigated and verified by the analysis of a data set of a 750 kW WT gearbox. Results show that JSL-MFD is superior to a state-of-the-art technique in detecting hidden fault patterns and enhancing detection accuracy.

Geophysical Factor Resolving of Rainfall Mechanism for Super Typhoons by Using Multiple Spatiotemporal Components Analysis

NASA Astrophysics Data System (ADS)

Huang, Chien-Lin; Hsu, Nien-Sheng

2016-04-01

This study develops a novel methodology to resolve the geophysical cause of typhoon-induced rainfall considering diverse dynamic co-evolution at multiple spatiotemporal components. The multi-order hidden patterns of complex hydrological process in chaos are detected to understand the fundamental laws of rainfall mechanism. The discovered spatiotemporal features are utilized to develop a state-of-the-art descriptive statistical model for mechanism validation, modeling and further prediction during typhoons. The time series of hourly typhoon precipitation from different types of moving track, atmospheric field and landforms are respectively precede the signal analytical process to qualify each type of rainfall cause and to quantify the corresponding affected degree based on the measured geophysical atmospheric-hydrological variables. This study applies the developed methodology in Taiwan Island which is constituted by complex diverse landform formation. The identified driving-causes include: (1) cloud height to ground surface; (2) co-movement effect induced by typhoon wind field with monsoon; (3) stem capacity; (4) interaction between typhoon rain band and terrain; (5) structural intensity variance of typhoon; and (6) integrated cloudy density of rain band. Results show that: (1) for the central maximum wind speed exceeding 51 m/sec, Causes (1) and (3) are the primary ones to generate rainfall; (2) for the typhoon moving toward the direction of 155° to 175°, Cause (2) is the primary one; (3) for the direction of 90° to 155°, Cause (4) is the primary one; (4) for the typhoon passing through mountain chain which above 3500 m, Cause (5) is the primary one; and (5) for the moving speed lower than 18 km/hr, Cause (6) is the primary one. Besides, the multiple geophysical component-based precipitation modeling can achieve 81% of average accuracy and 0.732 of average correlation coefficient (CC) within average 46 hours of duration, that improve their predictability.

Distinct Domains of CheA Confer Unique Functions in Chemotaxis and Cell Length in Azospirillum brasilense Sp7.

PubMed

Gullett, Jessica M; Bible, Amber; Alexandre, Gladys

2017-07-01

Chemotaxis is the movement of cells in response to gradients of diverse chemical cues. Motile bacteria utilize a conserved chemotaxis signal transduction system to bias their motility and navigate through a gradient. A central regulator of chemotaxis is the histidine kinase CheA. This cytoplasmic protein interacts with membrane-bound receptors, which assemble into large polar arrays, to propagate the signal. In the alphaproteobacterium Azospirillum brasilense , Che1 controls transient increases in swimming speed during chemotaxis, but it also biases the cell length at division. However, the exact underlying molecular mechanisms for Che1-dependent control of multiple cellular behaviors are not known. Here, we identify specific domains of the CheA1 histidine kinase implicated in modulating each of these functions. We show that CheA1 is produced in two isoforms: a membrane-anchored isoform produced as a fusion with a conserved seven-transmembrane domain of unknown function (TMX) at the N terminus and a soluble isoform similar to prototypical CheA. Site-directed and deletion mutagenesis combined with behavioral assays confirm the role of CheA1 in chemotaxis and implicate the TMX domain in mediating changes in cell length. Fluorescence microscopy further reveals that the membrane-anchored isoform is distributed around the cell surface while the soluble isoform localizes at the cell poles. Together, the data provide a mechanism for the role of Che1 in controlling multiple unrelated cellular behaviors via acquisition of a new domain in CheA1 and production of distinct functional isoforms. IMPORTANCE Chemotaxis provides a significant competitive advantage to bacteria in the environment, and this function has been transferred laterally multiple times, with evidence of functional divergence in different genomic contexts. The molecular principles that underlie functional diversification of chemotaxis in various genomic contexts are unknown. Here, we provide a molecular mechanism by which a single CheA protein controls two unrelated functions: chemotaxis and cell length. Acquisition of this multifunctionality is seemingly a recent evolutionary event. The findings illustrate a mechanism by which chemotaxis function may be co-opted to regulate additional cellular functions. Copyright © 2017 American Society for Microbiology.

Distinct Domains of CheA Confer Unique Functions in Chemotaxis and Cell Length in Azospirillum brasilense Sp7

PubMed Central

Gullett, Jessica M.

2017-01-01

ABSTRACT Chemotaxis is the movement of cells in response to gradients of diverse chemical cues. Motile bacteria utilize a conserved chemotaxis signal transduction system to bias their motility and navigate through a gradient. A central regulator of chemotaxis is the histidine kinase CheA. This cytoplasmic protein interacts with membrane-bound receptors, which assemble into large polar arrays, to propagate the signal. In the alphaproteobacterium Azospirillum brasilense, Che1 controls transient increases in swimming speed during chemotaxis, but it also biases the cell length at division. However, the exact underlying molecular mechanisms for Che1-dependent control of multiple cellular behaviors are not known. Here, we identify specific domains of the CheA1 histidine kinase implicated in modulating each of these functions. We show that CheA1 is produced in two isoforms: a membrane-anchored isoform produced as a fusion with a conserved seven-transmembrane domain of unknown function (TMX) at the N terminus and a soluble isoform similar to prototypical CheA. Site-directed and deletion mutagenesis combined with behavioral assays confirm the role of CheA1 in chemotaxis and implicate the TMX domain in mediating changes in cell length. Fluorescence microscopy further reveals that the membrane-anchored isoform is distributed around the cell surface while the soluble isoform localizes at the cell poles. Together, the data provide a mechanism for the role of Che1 in controlling multiple unrelated cellular behaviors via acquisition of a new domain in CheA1 and production of distinct functional isoforms. IMPORTANCE Chemotaxis provides a significant competitive advantage to bacteria in the environment, and this function has been transferred laterally multiple times, with evidence of functional divergence in different genomic contexts. The molecular principles that underlie functional diversification of chemotaxis in various genomic contexts are unknown. Here, we provide a molecular mechanism by which a single CheA protein controls two unrelated functions: chemotaxis and cell length. Acquisition of this multifunctionality is seemingly a recent evolutionary event. The findings illustrate a mechanism by which chemotaxis function may be co-opted to regulate additional cellular functions. PMID:28416707

Effects of cancer comorbidity on disease management: making the case for diabetes education (a report from the SOAR program).

PubMed

Irizarry, Lauren; Li, Qijuan E; Duncan, Ian; Thurston, Andrew L; Fitzner, Karen A; Edwards, Beatrice J; McKoy-Bent, Judith M; Tulas, Katrina M; McKoy, June M

2013-02-01

Individuals with type II diabetes have an increased risk of cancer diagnosis (relative risk [RR]=1.12-2.50) and mortality (RR=1.4) compared to normoglycemic individuals. Biologic mechanisms, including mitogenic effects of insulin, hyperglycemia, and increased oxidative stress, as well as behavioral factors (eg, difficulty managing the comorbidity) may explain the elevated risk. To investigate the effects of the comorbidity on disease management, the authors compared diabetes education utilization in individuals with diabetes-cancer co-morbidity to utilization by individuals with diabetes in the absence of cancer. The effect of diabetes education on outcomes was further assessed in the subset of individuals with diabetes-cancer comorbidity. Administrative claims data were used for this analysis. The study population included individuals >60 years of age and members of both commercial and Medicare Advantage health plans from a private national database of payer data, but excluded Medicare fee for service and Medicaid patients. Most of these individuals were eligible to receive reimbursement for diabetes education. Diabetes education utilization was identified using procedure codes. Outcomes were assessed for a 3-year time period. There was little difference in diabetes education utilization between individuals with diabetes in the absence of cancer (3.8% utilization) and those with diabetes-cancer comorbidity (3.5% utilization). Individuals who receive diabetes education are more likely to have multiple HbA1c tests per year, fewer emergency department visits, fewer hospital admissions, and lower care-associated costs (except for outpatient and pharmacy averages). When diabetes coexists with cancer, management of diabetes often lags, making diabetes education an imperative.

Stratified cost-utility analysis of C-Leg versus mechanical knees: Findings from an Italian sample of transfemoral amputees.

PubMed

Cutti, Andrea Giovanni; Lettieri, Emanuele; Del Maestro, Martina; Radaelli, Giovanni; Luchetti, Martina; Verni, Gennero; Masella, Cristina

2017-06-01

The fitting rate of the C-Leg electronic knee (Otto-Bock, D) has increased steadily over the last 15 years. Current cost-utility studies, however, have not considered the patients' characteristics. To complete a cost-utility analysis involving C-Leg and mechanical knee users; "age at the time of enrollment," "age at the time of first prosthesis," and "experience with the current type of prosthesis" are assumed as non-nested stratification parameters. Cohort retrospective. In all, 70 C-Leg and 57 mechanical knee users were selected. For each stratification criteria, we evaluated the cost-utility of C-Leg versus mechanical knees by computing the incremental cost-utility ratio, that is, the ratio of the "difference in cost" and the "difference in utility" of the two technologies. Cost consisted of acquisition, maintenance, transportation, and lodging expenses. Utility was measured in terms of quality-adjusted life years, computed on the basis of participants' answers to the EQ-5D questionnaire. Patients over 40 years at the time of first prosthesis were the only group featuring an incremental cost-utility ratio (88,779 €/quality-adjusted life year) above the National Institute for Health and Care Excellence practical cost-utility threshold (54,120 €/quality-adjusted live year): C-Leg users experience a significant improvement of "mobility," but limited outcomes on "usual activities," "self-care," "depression/anxiety," and reduction of "pain/discomfort." The stratified cost-utility results have relevant clinical implications and provide useful information for practitioners in tailoring interventions. Clinical relevance A cost-utility analysis that considered patients characteristics provided insights on the "affordability" of C-Leg compared to mechanical knees. In particular, results suggest that C-Leg has a significant impact on "mobility" for first-time prosthetic users over 40 years, but implementation of specific low-cost physical/psychosocial interventions is required to retun within cost-utility thresholds.

A Mechanomodulatory Device to Minimize Incisional Scar Formation

PubMed Central

Wong, Victor W.; Beasley, Bill; Zepeda, John; Dauskardt, Reinhold H.; Yock, Paul G.; Longaker, Michael T.; Gurtner, Geoffrey C.

2013-01-01

Objective To mechanically control the wound environment and prevent cutaneous scar formation. Approach We subjected various material substrates to biomechanical testing to investigate their ability to modulate skin behavior. Combinations of elastomeric materials, adhesives, and strain applicators were evaluated to develop topical stress-shielding devices. Noninvasive imaging modalities were utilized to characterize anatomic site-specific differences in skin biomechanical properties in humans. The devices were tested in a validated large animal model of hypertrophic scarring. Phase I within-patient controlled clinical trials were conducted to confirm their safety and efficacy in scar reduction in patients undergoing abdominoplasty surgery. Results Among the tested materials and device applicators, a polymer device was developed that effectively off-loaded high tension wounds and blocked pro-fibrotic pathways and excess scar formation in red Duroc swine. In humans, different anatomic sites exhibit unique biomechanical properties that may correlate with the propensity to form scars. In the clinical trial, utilization of this device significantly reduced incisional scar formation and improved scar appearance for up to 12 months compared with control incisions that underwent routine postoperative care. Innovation This is the first device that is able to precisely control the mechanical environment of incisional wounds and has been demonstrated in multiple clinical trials to significantly reduce scar formation after surgery. Conclusion Mechanomodulatory strategies to control the incisional wound environment can significantly reduce pathologic scarring and fibrosis after surgery. PMID:24527342

Multiple bio-analytical methods to reveal possible molecular mechanisms of developmental toxicity in zebrafish embryos/larvae exposed to tris(2-butoxyethyl) phosphate.

PubMed

Han, Zhihua; Wang, Qiangwei; Fu, Jie; Chen, Hongshan; Zhao, Ye; Zhou, Bingsheng; Gong, Zhiyuan; Wei, Si; Li, Jun; Liu, Hongling; Zhang, Xiaowei; Liu, Chunsheng; Yu, Hongxia

2014-05-01

The flame retardant tris(2-butoxyethyl) phosphate (TBEP) is a frequently detected contaminant in the environment, wildlife and human milk. The potentially toxic effects of TBEP and their underlying molecular mechanisms have not been elucidated. Here, zebrafish embryos were exposed to different concentrations of TBEP from 4 hours of post-fertilization (hpf) to 120 hpf, and effects on embryonic development and global protein expression patterns examined. Our results demonstrate that treatment with TBEP (0.8-100mg/L) causes a concentration- and time-dependent decrease in embryonic survival and the hatching percentage. The median lethal concentration was 10.7 mg/L at 120 hpf. Furthermore, exposure to 150 or 800 μg/L TBEP inhibited the degradation and utilization of vitellogenins and down-regulated the expression of proteins related to cation binding, and lipid transport, uptake and metabolism, accompanied by a decrease in heart rate and body length. Exposure to TBEP (150 or 800 μg/L) also decreased the expression of proteins involved in cell proliferation and DNA repair, and led to an increased number of apoptotic cells in the tail region. Collectively, our results suggest that exposure to TBEP causes toxicity in the developing zebrafish by inhibiting the degradation and utilization of nutrients from the mother and inducing apoptosis. Copyright © 2014 Elsevier B.V. All rights reserved.

Multiple-Array Detection, Association and Location of Infrasound and Seismo-Acoustic Event-Utilization of Ground Truth Information (Postprint)

DTIC Science & Technology

2012-05-07

AFRL-RV-PS- AFRL-RV-PS- TP-2012-0017 TP-2012-0017 MULTIPLE-ARRAY DETECTION, ASSOCIATION AND LOCATION OF INFRASOUND AND SEISMO-ACOUSTIC...ASSOCIATION AND LOCATION OF 5a. CONTRACT NUMBER FA8718-08-C-0008 INFRASOUND AND SEISMO-ACOUSTIC EVENT – UTILIZATION OF GROUND-TRUTH... infrasound signals from both correlated and uncorrelated noise. Approaches to this problem are implementation of the F-detector, which employs the F

Jumping translocations of 1q12 in multiple myeloma: a novel mechanism for deletion of 17p in cytogenetically defined high-risk disease.

PubMed

Sawyer, Jeffrey R; Tian, Erming; Heuck, Christoph J; Epstein, Joshua; Johann, Donald J; Swanson, Charles M; Lukacs, Janet L; Johnson, Marian; Binz, Regina; Boast, Angela; Sammartino, Gael; Usmani, Saad; Zangari, Maurizio; Waheed, Sarah; van Rhee, Frits; Barlogie, Bart

2014-04-17

Multiple myeloma (MM) is a B-cell malignancy driven in part by increasing copy number alterations (CNAs) during disease progression. Prognostically significant CNAs accumulate during clonal evolution and include gains of 1q21 and deletions of 17p, among others. Unfortunately, the mechanisms underlying the accumulation of CNAs and resulting subclonal heterogeneity in high-risk MM are poorly understood. To investigate the impact of jumping translocations of 1q12 (JT1q12) on receptor chromosomes (RCs) and subsequent clonal evolution, we analyzed specimens from 86 patients selected for unbalanced 1q12 aberrations by G-banding. Utilizing spectral karyotyping and locus-specific fluorescence in situ hybridization, we identified 10 patients with unexpected focal amplifications of an RC that subsequently translocated as part of a sequential JT1q12 to one or more additional RCs. Four patients exhibited amplification and translocation of 8q24 (MYC), 3 showed amplification of 16q11, and 1 each displayed amplification of 18q21.3 (BCL2), 18q23, or 4p16 (FGFR3). Unexpectedly, in 6 of 14 patients with the combination of the t(4;14) and deletion of 17p, we identified the loss of 17p as resulting from a JT1q12. Here, we provide evidence that the JT1q12 is a mechanism for the simultaneous gain of 1q21 and deletion of 17p in cytogenetically defined high-risk disease.

Intersections of pathways involving biotin and iron relative to therapeutic mechanisms for progressive multiple sclerosis.

PubMed

Heidker, Rebecca M; Emerson, Mitchell R; LeVine, Steven M

2016-12-01

While there are a variety of therapies for relapsing remitting multiple sclerosis (MS), there is a lack of treatments for progressive MS. An early study indicated that high dose biotin therapy has beneficial effects in approximately 12-15% of patients with progressive MS. The mechanisms behind the putative improvements seen with biotin therapy are not well understood, but have been postulated to include: 1) improving mitochondrial function which is impaired in MS, 2) increasing synthesis of lipids and cholesterol to facilitate remyelination, and 3) affecting gene expression. We suggest one reason that a greater percentage of patients with MS didn't respond to biotin therapy is the inaccessibility or lack of other nutrients, such as iron. In addition to biotin, iron (or heme) is necessary for energy production, biosynthesis of cholesterol and lipids, and for some protective mechanisms. Both biotin and iron are required for myelination during development, and by inference, remyelination. However, iron can also play a role in the pathology of MS. Increased deposition of iron can occur in some CNS structures possibly promoting oxidative damage while low iron levels can occur in other areas. Thus, the potential, detrimental effects of iron need to be considered together with the need for iron to support metabolic demands associated with repair and/or protective processes. We propose the optimal utilization of iron may be necessary to maximize the beneficial effects of biotin. This review will examine the interactions between biotin and iron in pathways that may have therapeutic or pathogenic implications for MS.

Structure Determination of Cisplatin-Amino Acid Analogues by Infrared Multiple Photon Dissociation Action Spectroscopy

NASA Astrophysics Data System (ADS)

He, Chenchen; Bao, Xun; Zhu, Yanlong; Strobehn, Stephen; Kimutai, Bett; Nei, Y.-W.; Chow, C. S.; Rodgers, M. T.; Gao, Juehan; Oomens, J.

2015-06-01

To gain a better understanding of the binding mechanism and assist in the optimization of relevant drug and chemical probe design, both experimental and theoretical studies were performed on a series of amino acid-linked cisplatin derivatives, including glycine-, lysine-, and ornithine-linked cisplatin, Gplatin, Kplatin, and Oplatin, respectively. Cisplatin, the first FDA-approved platinum-based anticancer drug, has been widely used in cancer chemotherapy. Its pharmacological mechanism has been identified as its ability to coordinate to genomic DNA, and guanine is its major target. In previous reports, cisplatin was successfully utilized as a chemical probe to detect solvent accessible sites in ribosomal RNA (rRNA). Among the amino-acid-linked cisplatin derivatives, Oplatin exhibits preference for adenine over guanine. The mechanism behind its different selectivity compared to cisplatin may relate to its potential of forming a hydrogen bond between the carboxylate group in Pt (II) complex and the 6-amino moiety of adenosine stabilizes A-Oplatin products. Tandem mass spectrometry analysis also indicates that different coordination sites of Oplatin on adenosine affect glycosidic bond stability. Infrared multiple photon dissociation (IRMPD) action spectroscopy experiments were performed on all three amino acid-linked cisplatin to characterize their structures. An extensive theoretical study has been performed on Gplatin to guide the selection of the most effective theory and basis set based on its geometric information. The results for Gplatin provide the foundation for characterization of the more complex amino acid-linked cisplatin derivatives, Oplatin and Kplatin. Structural and energetic information elucidated for these compounds, particularly Oplatin reveal the reason for its alternative selectivity compared to cisplatin.

Deep Sequencing Reveals Direct Targets of Gammaherpesvirus-Induced mRNA Decay and Suggests That Multiple Mechanisms Govern Cellular Transcript Escape

PubMed Central

Clyde, Karen; Glaunsinger, Britt A.

2011-01-01

One characteristic of lytic infection with gammaherpesviruses, including Kaposi's sarcoma-associated herpesvirus (KSHV), Epstein-Barr virus (EBV) and murine herpesvirus 68 (MHV68), is the dramatic suppression of cellular gene expression in a process known as host shutoff. The alkaline exonuclease proteins (KSHV SOX, MHV-68 muSOX and EBV BGLF5) have been shown to induce shutoff by destabilizing cellular mRNAs. Here we extend previous analyses of cellular mRNA abundance during lytic infection to characterize the effects of SOX and muSOX, in the absence of other viral genes, utilizing deep sequencing technology (RNA-seq). Consistent with previous observations during lytic infection, the majority of transcripts are downregulated in cells expressing either SOX or muSOX, with muSOX acting as a more potent shutoff factor than SOX. Moreover, most cellular messages fall into the same expression class in both SOX- and muSOX-expressing cells, indicating that both factors target similar pools of mRNAs. More abundant mRNAs are more efficiently downregulated, suggesting a concentration effect in transcript targeting. However, even among highly expressed genes there are mRNAs that escape host shutoff. Further characterization of select escapees reveals multiple mechanisms by which cellular genes can evade downregulation. While some mRNAs are directly refractory to SOX, the steady state levels of others remain unchanged, presumably as a consequence of downstream effects on mRNA biogenesis. Collectively, these studies lay the framework for dissecting the mechanisms underlying the susceptibility of mRNA to destruction during lytic gammaherpesvirus infection. PMID:21573023

Ceruloplasmin ferroxidase activity stimulates cellular iron uptake by a trivalent cation-specific transport mechanism

NASA Technical Reports Server (NTRS)

Attieh, Z. K.; Mukhopadhyay, C. K.; Seshadri, V.; Tripoulas, N. A.; Fox, P. L.

1999-01-01

The balance required to maintain appropriate cellular and tissue iron levels has led to the evolution of multiple mechanisms to precisely regulate iron uptake from transferrin and low molecular weight iron chelates. A role for ceruloplasmin (Cp) in vertebrate iron metabolism is suggested by its potent ferroxidase activity catalyzing conversion of Fe2+ to Fe3+, by identification of yeast copper oxidases homologous to Cp that facilitate high affinity iron uptake, and by studies of "aceruloplasminemic" patients who have extensive iron deposits in multiple tissues. We have recently shown that Cp increases iron uptake by cultured HepG2 cells. In this report, we investigated the mechanism by which Cp stimulates cellular iron uptake. Cp stimulated the rate of non-transferrin 55Fe uptake by iron-deficient K562 cells by 2-3-fold, using a transferrin receptor-independent pathway. Induction of Cp-stimulated iron uptake by iron deficiency was blocked by actinomycin D and cycloheximide, consistent with a transcriptionally induced or regulated transporter. Cp-stimulated iron uptake was completely blocked by unlabeled Fe3+ and by other trivalent cations including Al3+, Ga3+, and Cr3+, but not by divalent cations. These results indicate that Cp utilizes a trivalent cation-specific transporter. Cp ferroxidase activity was required for iron uptake as shown by the ineffectiveness of two ferroxidase-deficient Cp preparations, copper-deficient Cp and thiomolybdate-treated Cp. We propose a model in which iron reduction and subsequent re-oxidation by Cp are essential for an iron uptake pathway with high ion specificity.

A latent class multiple constraint multiple discrete-continuous extreme value model of time use and goods consumption.

DOT National Transportation Integrated Search

2016-06-01

This paper develops a microeconomic theory-based multiple discrete continuous choice model that considers: (a) that both goods consumption and time allocations (to work and non-work activities) enter separately as decision variables in the utility fu...

Global isotope metabolomics reveals adaptive strategies for nitrogen assimilation

DOE PAGES

Kurczy, Michael E.; Forsberg, Erica M.; Thorgersen, Michael P.; ...

2016-04-05

Nitrogen cycling is a microbial metabolic process essential for global ecological/agricultural balance. To investigate the link between the well-established ammonium and the alternative nitrate assimilation metabolic pathways, global isotope metabolomics was employed to examine three nitrate reducing bacteria using 15NO 3 as a nitrogen source. In contrast to a control ( Pseudomonas stutzeri RCH2), the results show that two of the isolates from Oak Ridge, Tennessee ( Pseudomonas N2A2 and N2E2) utilize nitrate and ammonia for assimilation concurrently with differential labeling observed across multiple classes of metabolites including amino acids and nucleotides. The data reveal that the N2A2 and N2E2more » strains conserve nitrogen-containing metabolites, indicating that the nitrate assimilation pathway is a conservation mechanism for the assimilation of nitrogen. Co-utilization of nitrate and ammonia is likely an adaption to manage higher levels of nitrite since the denitrification pathways utilized by the N2A2 and N2E2 strains from the Oak Ridge site are predisposed to the accumulation of the toxic nitrite. In conclusion, the use of global isotope metabolomics allowed for this adaptive strategy to be investigated, which would otherwise not have been possible to decipher.« less

Global isotope metabolomics reveals adaptive strategies for nitrogen assimilation

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

Kurczy, Michael E.; Forsberg, Erica M.; Thorgersen, Michael P.

Nitrogen cycling is a microbial metabolic process essential for global ecological/agricultural balance. To investigate the link between the well-established ammonium and the alternative nitrate assimilation metabolic pathways, global isotope metabolomics was employed to examine three nitrate reducing bacteria using 15NO 3 as a nitrogen source. In contrast to a control ( Pseudomonas stutzeri RCH2), the results show that two of the isolates from Oak Ridge, Tennessee ( Pseudomonas N2A2 and N2E2) utilize nitrate and ammonia for assimilation concurrently with differential labeling observed across multiple classes of metabolites including amino acids and nucleotides. The data reveal that the N2A2 and N2E2more » strains conserve nitrogen-containing metabolites, indicating that the nitrate assimilation pathway is a conservation mechanism for the assimilation of nitrogen. Co-utilization of nitrate and ammonia is likely an adaption to manage higher levels of nitrite since the denitrification pathways utilized by the N2A2 and N2E2 strains from the Oak Ridge site are predisposed to the accumulation of the toxic nitrite. In conclusion, the use of global isotope metabolomics allowed for this adaptive strategy to be investigated, which would otherwise not have been possible to decipher.« less

Defense Mechanisms: Discussions and Bibliographies; General or Multiple, and Specific.

ERIC Educational Resources Information Center

Pedrini, D. T.; Pedrini, Bonnie C.

This publication considers some Freudian ego mechanisms. The first discussion and bibliography concerns defense mechanisms, in general or in multiple; after which, the discussions and bibliographies concern specific defense mechanisms: denial; displacement, substitution, sublimation; fixation; identification, introjection, incorporation,…

Development of compositional and contextual communicable congruence in robots by using dynamic neural network models.

PubMed

Park, Gibeom; Tani, Jun

2015-12-01

The current study presents neurorobotics experiments on acquisition of skills for "communicable congruence" with human via learning. A dynamic neural network model which is characterized by its multiple timescale dynamics property was utilized as a neuromorphic model for controlling a humanoid robot. In the experimental task, the humanoid robot was trained to generate specific sequential movement patterns as responding to various sequences of imperative gesture patterns demonstrated by the human subjects by following predefined compositional semantic rules. The experimental results showed that (1) the adopted MTRNN can achieve generalization by learning in the lower feature perception level by using a limited set of tutoring patterns, (2) the MTRNN can learn to extract compositional semantic rules with generalization in its higher level characterized by slow timescale dynamics, (3) the MTRNN can develop another type of cognitive capability for controlling the internal contextual processes as situated to on-going task sequences without being provided with cues for explicitly indicating task segmentation points. The analysis on the dynamic property developed in the MTRNN via learning indicated that the aforementioned cognitive mechanisms were achieved by self-organization of adequate functional hierarchy by utilizing the constraint of the multiple timescale property and the topological connectivity imposed on the network configuration. These results of the current research could contribute to developments of socially intelligent robots endowed with cognitive communicative competency similar to that of human. Copyright © 2015 Elsevier Ltd. All rights reserved.

Calculating utilization rates for rubber tired grapple skidders in the Southern United States

Treesearch

Jason D. Thompson

2001-01-01

Utilization rate is an important factor in calculating machine rates for forest harvesting machines. Machine rates allow an evaluation of harvesting system costs and facilitate comparisons between different systems and machines. There are many factors that affect utilization rate. These include mechanical delays, non-mechanical delays, operational lost time, and...

Decision Utility, Incentive Salience, and Cue-Triggered “Wanting”

PubMed Central

Berridge, Kent C.; Aldridge, J. Wayne

2010-01-01

This chapter examines brain mechanisms of reward utility operating at particular decision moments in life—moments such as when one encounters an image, sound, scent, or other cue associated in the past with a particular reward or perhaps just when one vividly imagines that cue. Such a cue can often trigger a sudden motivational urge to pursue its reward and sometimes a decision to do so. Drawing on a utility taxonomy that distinguishes among subtypes of reward utility—predicted utility, decision utility, experienced utility, and remembered utility—it is shown how cue-triggered cravings, such as an addict’s surrender to relapse, can hang on special transformations by brain mesolimbic systems of one utility subtype, namely, decision utility. The chapter focuses on a particular form of decision utility called incentive salience, a type of “wanting” for rewards that is amplified by brain mesolimbic systems. Sudden peaks of intensity of incentive salience, caused by neurobiological mechanisms, can elevate the decision utility of a particular reward at the moment its cue occurs. An understanding of what happens at such moments leads to a better understanding of the mechanisms at work in decision making in general. PMID:25309963

Latent Class Models for Teacher Observation Data

ERIC Educational Resources Information Center

Halpin, Peter F.

2016-01-01

Recent research on multiple measures of teaching effectiveness has redefined the role of in-classroom observations in teacher evaluation systems. In particular, most states now mandate that teachers are observed on multiple occasions during the school year, and it is increasingly common that multiple raters are utilized across the different rating…

Evolutionary Scheduler for the Deep Space Network

NASA Technical Reports Server (NTRS)

Guillaume, Alexandre; Lee, Seungwon; Wang, Yeou-Fang; Zheng, Hua; Chau, Savio; Tung, Yu-Wen; Terrile, Richard J.; Hovden, Robert

2010-01-01

A computer program assists human schedulers in satisfying, to the maximum extent possible, competing demands from multiple spacecraft missions for utilization of the transmitting/receiving Earth stations of NASA s Deep Space Network. The program embodies a concept of optimal scheduling to attain multiple objectives in the presence of multiple constraints.

Multiple Rap1 effectors control Epac1-mediated tightening of endothelial junctions.

PubMed

Pannekoek, Willem-Jan; Vliem, Marjolein J; Bos, Johannes L

2018-02-17

Epac1 and Rap1 mediate cAMP-induced tightening of endothelial junctions. We have previously found that one of the mechanisms is the inhibition of Rho-mediated tension in radial stress fibers by recruiting the RhoGAP ArhGAP29 in a complex containing the Rap1 effectors Rasip1 and Radil. However, other mechanisms have been proposed as well, most notably the induction of tension in circumferential actin cables by Cdc42 and its GEF FGD5. Here, we have investigated how Rap1 controls FGD5/Cdc42 and how this interconnects with Radil/Rasip1/ArhGAP29. Using endothelial barrier measurements, we show that Rho inhibition is not sufficient to explain the barrier stimulating effect of Rap1. Indeed, Cdc42-mediated tension is induced at cell-cell contacts upon Rap1 activation and this is required for endothelial barrier function. Depletion of potential Rap1 effectors identifies AF6 to mediate Rap1 enhanced tension and concomitant Rho-independent barrier function. When overexpressed in HEK293T cells, AF6 is found in a complex with FGD5 and Radil. From these results we conclude that Rap1 utilizes multiple pathways to control tightening of endothelial junctions, possibly through a multiprotein effector complex, in which AF6 functions to induce tension in circumferential actin cables.

Identification of drug-resistant subpopulations in canine hemangiosarcoma.

PubMed

Khammanivong, A; Gorden, B H; Frantz, A M; Graef, A J; Dickerson, E B

2016-09-01

Canine hemangiosarcoma is a rapidly progressive disease that is poorly responsive to conventional chemotherapy. Despite numerous attempts to advance treatment options and improve outcomes, drug resistance remains a hurdle to successful therapy. To address this problem, we used recently characterized progenitor cell populations derived from canine hemangiosarcoma cell lines and grown as non-adherent spheres to identify potential drug resistance mechanisms as well as drug-resistant cell populations. Cells from sphere-forming cultures displayed enhanced resistance to chemotherapy drugs, expansion of dye-excluding side populations and altered ATP-binding cassette (ABC) transporter expression. Invasion studies demonstrated variability between cell lines as well as between sphere and monolayer cell populations. Collectively, our results suggest that sphere cell populations contain distinct subpopulations of drug-resistant cells that utilize multiple mechanisms to evade cytotoxic drugs. Our approach represents a new tool for the study of drug resistance in hemangiosarcoma, which could alter approaches for treating this disease. © 2014 John Wiley & Sons Ltd.

Role of TIM-4 in exosome-dependent entry of HIV-1 into human immune cells

PubMed Central

Sims, Brian; Farrow, Anitra L; Williams, Sparkle D; Bansal, Anju; Krendelchtchikov, Alexandre; Gu, Linlin; Matthews, Qiana L

2017-01-01

Exosomes, 30–200 nm nanostructures secreted from donor cells and internalized by recipient cells, can play an important role in the cellular entry of some viruses. These microvesicles are actively secreted into various body fluids, including blood, urine, saliva, cerebrospinal fluid, and breast milk. We successfully isolated exosomes from human breast milk and plasma. The size and concentration of purified exosomes were measured by nanoparticle tracking, while Western blotting confirmed the presence of the exosomal-associated proteins CD9 and CD63, clathrin, and T cell immunoglobulin and mucin proteins (TIMs). Through viral infection assays, we determined that HIV-1 utilizes an exosome-dependent mechanism for entry into human immune cells. The virus contains high amounts of phosphatidylserine (PtdSer) and may bind PtdSer receptors, such as TIMs. This mechanism is supported by our findings that exosomes from multiple sources increased HIV-1 entry into T cells and macrophages, and viral entry was potently blocked with anti-TIM-4 antibodies. PMID:28740388

Making the EZ Choice

NASA Technical Reports Server (NTRS)

2001-01-01

Analytical Mechanics Associates, Inc. (AMA), of Hampton, Virginia, created the EZopt software application through Small Business Innovation Research (SBIR) funding from NASA's Langley Research Center. The new software is a user-friendly tool kit that provides quick and logical solutions to complex optimal control problems. In its most basic form, EZopt converts process data into math equations and then proceeds to utilize those equations to solve problems within control systems. EZopt successfully proved its advantage when applied to short-term mission planning and onboard flight computer implementation. The technology has also solved multiple real-life engineering problems faced in numerous commercial operations. For instance, mechanical engineers use EZopt to solve control problems with robots, while chemical plants implement the application to overcome situations with batch reactors and temperature control. In the emerging field of commercial aerospace, EZopt is able to optimize trajectories for launch vehicles and perform potential space station- keeping tasks. Furthermore, the software also helps control electromagnetic devices in the automotive industry.

Coordinating DNA polymerase traffic during high and low fidelity synthesis.

PubMed

Sutton, Mark D

2010-05-01

With the discovery that organisms possess multiple DNA polymerases (Pols) displaying different fidelities, processivities, and activities came the realization that mechanisms must exist to manage the actions of these diverse enzymes to prevent gratuitous mutations. Although many of the Pols encoded by most organisms are largely accurate, and participate in DNA replication and DNA repair, a sizeable fraction display a reduced fidelity, and act to catalyze potentially error-prone translesion DNA synthesis (TLS) past lesions that persist in the DNA. Striking the proper balance between use of these different enzymes during DNA replication, DNA repair, and TLS is essential for ensuring accurate duplication of the cell's genome. This review highlights mechanisms that organisms utilize to manage the actions of their different Pols. A particular emphasis is placed on discussion of current models for how different Pols switch places with each other at the replication fork during high fidelity replication and potentially error-pone TLS. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Flexible Mechanical Conveyors for Regolith Extraction and Transport

NASA Technical Reports Server (NTRS)

Walton, Otis R.; Vollmer, Hubert J.

2013-01-01

A report describes flexible mechanical conveying systems for transporting fine cohesive regolith under microgravity and vacuum conditions. They are totally enclosed, virtually dust-free, and can include enough flexibility in the conveying path to enable an expanded range of extraction and transport scenarios, including nonlinear drill-holes and excavation of enlarged subsurface openings without large entry holes. The design of the conveyors is a modification of conventional screw conveyors such that the central screw-shaft and the outer housing or conveyingtube have a degree of bending flexibility, allowing the conveyors to become nonlinear conveying systems that can convey around gentle bends. The central flexible shaft is similar to those used in common tools like a weed whacker, consisting of multiple layers of tightly wound wires around a central wire core. Utilization of compliant components (screw blade or outer wall) increases the robustness of the conveying, allowing an occasional oversized particle to pass hough the conveyor without causing a jam or stoppage

Bayesian Knowledge Fusion in Prognostics and Health Management—A Case Study

NASA Astrophysics Data System (ADS)

Rabiei, Masoud; Modarres, Mohammad; Mohammad-Djafari, Ali

2011-03-01

In the past few years, a research effort has been in progress at University of Maryland to develop a Bayesian framework based on Physics of Failure (PoF) for risk assessment and fleet management of aging airframes. Despite significant achievements in modelling of crack growth behavior using fracture mechanics, it is still of great interest to find practical techniques for monitoring the crack growth instances using nondestructive inspection and to integrate such inspection results with the fracture mechanics models to improve the predictions. The ultimate goal of this effort is to develop an integrated probabilistic framework for utilizing all of the available information to come up with enhanced (less uncertain) predictions for structural health of the aircraft in future missions. Such information includes material level fatigue models and test data, health monitoring measurements and inspection field data. In this paper, a case study of using Bayesian fusion technique for integrating information from multiple sources in a structural health management problem is presented.

The SH2 domain of Abl kinases regulates kinase autophosphorylation by controlling activation loop accessibility.

PubMed

Lamontanara, Allan Joaquim; Georgeon, Sandrine; Tria, Giancarlo; Svergun, Dmitri I; Hantschel, Oliver

2014-11-17

The activity of protein kinases is regulated by multiple molecular mechanisms, and their disruption is a common driver of oncogenesis. A central and almost universal control element of protein kinase activity is the activation loop that utilizes both conformation and phosphorylation status to determine substrate access. In this study, we use recombinant Abl tyrosine kinases and conformation-specific kinase inhibitors to quantitatively analyse structural changes that occur after Abl activation. Allosteric SH2-kinase domain interactions were previously shown to be essential for the leukemogenesis caused by the Bcr-Abl oncoprotein. We find that these allosteric interactions switch the Abl activation loop from a closed to a fully open conformation. This enables the trans-autophosphorylation of the activation loop and requires prior phosphorylation of the SH2-kinase linker. Disruption of the SH2-kinase interaction abolishes activation loop phosphorylation. Our analysis provides a molecular mechanism for the SH2 domain-dependent activation of Abl that may also regulate other tyrosine kinases.

The SH2 domain of Abl kinases regulates kinase autophosphorylation by controlling activation loop accessibility

NASA Astrophysics Data System (ADS)

Lamontanara, Allan Joaquim; Georgeon, Sandrine; Tria, Giancarlo; Svergun, Dmitri I.; Hantschel, Oliver

2014-11-01

The activity of protein kinases is regulated by multiple molecular mechanisms, and their disruption is a common driver of oncogenesis. A central and almost universal control element of protein kinase activity is the activation loop that utilizes both conformation and phosphorylation status to determine substrate access. In this study, we use recombinant Abl tyrosine kinases and conformation-specific kinase inhibitors to quantitatively analyse structural changes that occur after Abl activation. Allosteric SH2-kinase domain interactions were previously shown to be essential for the leukemogenesis caused by the Bcr-Abl oncoprotein. We find that these allosteric interactions switch the Abl activation loop from a closed to a fully open conformation. This enables the trans-autophosphorylation of the activation loop and requires prior phosphorylation of the SH2-kinase linker. Disruption of the SH2-kinase interaction abolishes activation loop phosphorylation. Our analysis provides a molecular mechanism for the SH2 domain-dependent activation of Abl that may also regulate other tyrosine kinases.

Multi-reflective acoustic wave device

DOEpatents

Andle, Jeffrey C.

2006-02-21

An acoustic wave device, which utilizes multiple localized reflections of acoustic wave for achieving an infinite impulse response while maintaining high tolerance for dampening effects, is disclosed. The device utilized a plurality of electromechanically significant electrodes disposed on most of the active surface. A plurality of sensors utilizing the disclosed acoustic wave mode device are also described.

Periplasmic Cytophaga hutchinsonii Endoglucanases Are Required for Use of Crystalline Cellulose as the Sole Source of Carbon and Energy

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

Zhu, Yongtao; Han, Lanlan; Hefferon, Kathleen L.

2016-06-03

The soil bacteriumCytophaga hutchinsoniiactively digests crystalline cellulose by a poorly understood mechanism. Genome analyses identified nine genes predicted to encode endoglucanases with roles in this process. No predicted cellobiohydrolases, which are usually involved in the utilization of crystalline cellulose, were identified. Chromosomal deletions were performed in eight of the endoglucanase-encoding genes:cel5A,cel5B,cel5C,cel9A,cel9B,cel9C,cel9E, andcel9F. Each mutant retained the ability to digest crystalline cellulose, although the deletion ofcel9Ccaused a modest decrease in cellulose utilization. Strains with multiple deletions were constructed to identify the critical cellulases. Cells of a mutant lacking bothcel5Bandcel9Cwere completely deficient in growth on cellulose. Cell fractionation and biochemical analyses indicatemore » that Cel5B and Cel9C are periplasmic nonprocessive endoglucanases. The requirement of periplasmic endoglucanases for cellulose utilization suggests that cellodextrins are transported across the outer membrane during this process. Bioinformatic analyses predict that Cel5A, Cel9A, Cel9B, Cel9D, and Cel9E are secreted across the outer membrane by the type IX secretion system, which has been linked to cellulose utilization. These secreted endoglucanases may perform the initial digestion within amorphous regions on the cellulose fibers, releasing oligomers that are transported into the periplasm for further digestion by Cel5B and Cel9C. The results suggest that both cell surface and periplasmic endoglucanases are required for the growth ofC. hutchinsoniion cellulose and that novel cell surface proteins may solubilize and transport cellodextrins across the outer membrane. IMPORTANCEThe bacteriumCytophaga hutchinsoniidigests crystalline cellulose by an unknown mechanism. It lacks processive cellobiohydrolases that are often involved in cellulose digestion. Critical cellulolytic enzymes were identified by genetic analyses. Intracellular (periplasmic) nonprocessive endoglucanases performed an important role in cellulose utilization. The results suggest a model involving partial digestion at the cell surface, solubilization and uptake of cellodextrins across the outer membrane by an unknown mechanism, and further digestion within the periplasm. The ability to sequester cellodextrins and digest them intracellularly may limit losses of soluble cellobiose to other organisms.C. hutchinsoniiuses an unusual approach to digest cellulose and is a potential source of novel proteins to increase the efficiency of conversion of cellulose into soluble sugars and biofuels.« less

Targeting polyamine metabolism for cancer therapy and prevention

PubMed Central

Murray-Stewart, Tracy R.; Woster, Patrick M.; Casero, Robert A.

2017-01-01

The chemically simple, biologically complex eukaryotic polyamines, spermidine and spermine, are positively charged alkylamines involved in many crucial cellular processes. Along with their diamine precursor putrescine, their normally high intracellular concentrations require fine attenuation by multiple regulatory mechanisms to keep these essential molecules within strict physiologic ranges. Since the metabolism of and requirement for polyamines are frequently dysregulated in neoplastic disease, the metabolic pathway and functions of polyamines provide rational drug targets; however, these targets have been difficult to exploit for chemotherapy. It is the goal of this article to review the latest findings in the field that demonstrate the potential utility of targeting the metabolism and function of polyamines as strategies for both chemotherapy and, possibly more importantly, chemoprevention. PMID:27679855

Fundamental understanding and rational design of high energy structural microbatteries

DOE PAGES

Wang, Yuxing; Li, Qiuyan; Cartmell, Samuel; ...

2017-11-21

We present that microbatteries play a critical role in determining the lifetime of downsized sensors, wearable devices, medical applications, and animal acoustic telemetry transmitters among others. More often, structural batteries are required from the perspective of aesthetics and space utilization, which is however rarely explored. Herein, we discuss the fundamental issues associated with the rational design of practically usable high energy microbatteries. The tubular shape of the cell further allows the flexible integration of microelectronics. A functioning acoustic micro-transmitter continuously powered by this tubular battery has been successfully demonstrated. Finally, multiple design features adopted to accommodate large mechanical stress duringmore » the rolling process are discussed providing new insights in designing the structural microbatteries for emerging technologies.« less

Deconstructing mammalian reproduction: using knockouts to define fertility pathways.

PubMed

Roy, Angshumoy; Matzuk, Martin M

2006-02-01

Reproduction is the sine qua non for the propagation of species and continuation of life. It is a complex biological process that is regulated by multiple factors during the reproductive life of an organism. Over the past decade, the molecular mechanisms regulating reproduction in mammals have been rapidly unraveled by the study of a vast number of mouse gene knockouts with impaired fertility. The use of reverse genetics to generate null mutants in mice through targeted disruption of specific genes has enabled researchers to identify essential regulators of spermatogenesis and oogenesis in vivo and model human disorders affecting reproduction. This review focuses on the merits, utility, and the variations of the knockout technology in studies of reproduction in mammals.

A high-throughput screen for mitochondrial function reveals known and novel mitochondrial toxicants in a library of environmental agents

PubMed Central

Datta, Sandipan; Sahdeo, Sunil; Gray, Jennifer A.; Morriseau, Christophe; Hammock, Bruce D.; Cortopassi, Gino

2016-01-01

Mitochondrial toxicity is emerging as a major mechanism underlying serious human health consequences. This work performs a high-throughput screen (HTS) of 176 environmental chemicals for mitochondrial toxicity utilizing a previously reported biosensor platform. This established HTS confirmed known mitochondrial toxins and identified novel mitotochondrial uncouplers such as 2, 2′-Methylenebis(4-chlorophenol) and pentachlorophenol. It also identified a mitochondrial ‘structure activity relationship’ (SAR) in the sense that multiple environmental chlorophenols are mitochondrial inhibitors and uncouplers. This study demonstrates proof-of-concept that a mitochondrial HTS assay detects known and novel environmental mitotoxicants, and could be used to quickly evaluate human health risks from mitotoxicants in the environment. PMID:27717841

Public Health Agenda Setting in a Global Context: The International Labor Organization’s Decent Work Agenda

PubMed Central

Cohen, Joanna E.; Cole, Donald C.; Forman, Lisa

2015-01-01

We drew on two agenda-setting theories usually applied at the state or national level to assess their utility at the global level: Kingdon’s multiple streams theory and Baumgartner and Jones’s punctuated equilibrium theory. We illustrate our analysis with findings from a qualitative study of the International Labor Organization’s Decent Work Agenda. We found that both theories help explain the agenda-setting mechanisms that operate in the global context, including how windows of opportunity open and what role institutions play as policy entrepreneurs. Future application of these theories could help characterize power struggles between global actors, whose voices are heard or silenced, and their impact on global policy agenda setting. PMID:25713966

The CRISPR-Cas system in Enterobacteriaceae.

PubMed

Medina-Aparicio, Liliana; Dávila, Sonia; Rebollar-Flores, Javier E; Calva, Edmundo; Hernández-Lucas, Ismael

2018-02-01

In nature, microorganisms are constantly exposed to multiple viral infections and thus have developed many strategies to survive phage attack and invasion by foreign DNA. One of such strategies is the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated proteins (Cas) bacterial immunological system. This defense mechanism is widespread in prokaryotes including several families such as Enterobacteriaceae. Much knowledge about the CRISPR-Cas system has been generated, including its biological functions, transcriptional regulation, distribution, utility as a molecular marker and as a tool for specific genome editing. This review focuses on these aspects and describes the state of the art of the CRISPR-Cas system in the Enterobacteriaceae bacterial family. © FEMS 2018. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Fundamental understanding and rational design of high energy structural microbatteries

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

Wang, Yuxing; Li, Qiuyan; Cartmell, Samuel

We present that microbatteries play a critical role in determining the lifetime of downsized sensors, wearable devices, medical applications, and animal acoustic telemetry transmitters among others. More often, structural batteries are required from the perspective of aesthetics and space utilization, which is however rarely explored. Herein, we discuss the fundamental issues associated with the rational design of practically usable high energy microbatteries. The tubular shape of the cell further allows the flexible integration of microelectronics. A functioning acoustic micro-transmitter continuously powered by this tubular battery has been successfully demonstrated. Finally, multiple design features adopted to accommodate large mechanical stress duringmore » the rolling process are discussed providing new insights in designing the structural microbatteries for emerging technologies.« less

Simultaneous Tracking of Multiple Points Using a Wiimote

NASA Astrophysics Data System (ADS)

Skeffington, Alex; Scully, Kyle

2012-11-01

This paper reviews the construction of an inexpensive motion tracking and data logging system, which can be used for a wide variety of teaching experiments ranging from entry-level physics courses to advanced courses. The system utilizes an affordable infrared camera found in a Nintendo Wiimote to track IR LEDs mounted to the objects to be tracked. Two quick experiments are presented using the motion tracking system to demonstrate the diversity of tasks this system can handle. The first experiment uses the Wiimote to record the harmonic motion of oscillating masses on a near-frictionless surface, while the second experiment uses the Wiimote as part of a feedback mechanism in a rotational system. The construction, capabilities, demonstrations, and suggested improvements of the system are reported here.

Single-step methods for predicting orbital motion considering its periodic components

NASA Astrophysics Data System (ADS)

Lavrov, K. N.

1989-01-01

Modern numerical methods for integration of ordinary differential equations can provide accurate and universal solutions to celestial mechanics problems. The implicit single sequence algorithms of Everhart and multiple step computational schemes using a priori information on periodic components can be combined to construct implicit single sequence algorithms which combine their advantages. The construction and analysis of the properties of such algorithms are studied, utilizing trigonometric approximation of the solutions of differential equations containing periodic components. The algorithms require 10 percent more machine memory than the Everhart algorithms, but are twice as fast, and yield short term predictions valid for five to ten orbits with good accuracy and five to six times faster than algorithms using other methods.

Copper-catalyzed azide–alkyne cycloaddition (CuAAC) and beyond: new reactivity of copper(i) acetylides†

PubMed Central

Hein, Jason E.

2011-01-01

Copper-catalyzed azide–alkyne cycloaddition (CuAAC) is a widely utilized, reliable, and straightforward way for making covalent connections between building blocks containing various functional groups. It has been used in organic synthesis, medicinal chemistry, surface and polymer chemistry, and bioconjugation applications. Despite the apparent simplicity of the reaction, its mechanism involves multiple reversible steps involving coordination complexes of copper(i) acetylides of varying nuclearity. Understanding and controlling these equilibria is of paramount importance for channeling the reaction into the productive catalytic cycle. This tutorial review examines the history of the development of the CuAAC reaction, its key mechanistic aspects, and highlights the features that make it useful to practitioners in different fields of chemical science. PMID:20309487

Effects of physical attractiveness on political beliefs.

PubMed

Peterson, Rolfe Daus; Palmer, Carl L

2017-01-01

Physical attractiveness is an important social factor in our daily interactions. Scholars in social psychology provide evidence that attractiveness stereotypes and the "halo effect" are prominent in affecting the traits we attribute to others. However, the interest in attractiveness has not directly filtered down to questions of political behavior beyond candidates and elites. Utilizing measures of attractiveness across multiple surveys, we examine the relationship between attractiveness and political beliefs. Controlling for socioeconomic status, we find that more attractive individuals are more likely to report higher levels of political efficacy, identify as conservative, and identify as Republican. These findings suggest an additional mechanism for political socialization that has further implications for understanding how the body intertwines with the social nature of politics.

Topographical disorientation in a patient with late-onset blindness with multiple acute ischemic brain lesions.

PubMed

Han, Yu-Hsuan; Pai, Ming-Chyi; Hong, Chi-Tzong

2011-02-01

The neurological basis for topographical disorientation has recently shifted from a model of navigation utilizing egocentric techniques alone, to multiple parallel systems of topographical cognition including egocentric and allocentric strategies. We explored if this hypothesis may be applicable to a patient with late-onset blindness. A 72-year-old male with bilateral blindness experienced a sudden inability to navigate after suffering a stroke. Multiple lesions scattered bilaterally throughout the parietal-occipital lobes were found. Deficits in the neural correlates underlying egocentric or allocentric strategies may result in topographical disorientation, even if one appears to be the predominant orientation strategy utilized. Copyright © 2010 Elsevier Ltd. All rights reserved.

Catabolite regulation analysis of Escherichia coli for acetate overflow mechanism and co-consumption of multiple sugars based on systems biology approach using computer simulation.

PubMed

Matsuoka, Yu; Shimizu, Kazuyuki

2013-10-20

It is quite important to understand the basic principle embedded in the main metabolism for the interpretation of the fermentation data. For this, it may be useful to understand the regulation mechanism based on systems biology approach. In the present study, we considered the perturbation analysis together with computer simulation based on the models which include the effects of global regulators on the pathway activation for the main metabolism of Escherichia coli. Main focus is the acetate overflow metabolism and the co-fermentation of multiple carbon sources. The perturbation analysis was first made to understand the nature of the feed-forward loop formed by the activation of Pyk by FDP (F1,6BP), and the feed-back loop formed by the inhibition of Pfk by PEP in the glycolysis. Those together with the effect of transcription factor Cra caused by FDP level affected the glycolysis activity. The PTS (phosphotransferase system) acts as the feed-back system by repressing the glucose uptake rate for the increase in the glucose uptake rate. It was also shown that the increased PTS flux (or glucose consumption rate) causes PEP/PYR ratio to be decreased, and EIIA-P, Cya, cAMP-Crp decreased, where cAMP-Crp in turn repressed TCA cycle and more acetate is formed. This was further verified by the detailed computer simulation. In the case of multiple carbon sources such as glucose and xylose, it was shown that the sequential utilization of carbon sources was observed for wild type, while the co-consumption of multiple carbon sources with slow consumption rates were observed for the ptsG mutant by computer simulation, and this was verified by experiments. Moreover, the effect of a specific gene knockout such as Δpyk on the metabolic characteristics was also investigated based on the computer simulation. Copyright © 2013 Elsevier B.V. All rights reserved.

Determinants of postnatal care utilization in urban community among women in Debre Birhan Town, Northern Shewa, Ethiopia.

PubMed

Angore, Banchalem Nega; Tufa, Efrata Girma; Bisetegen, Fithamlak Solomon

2018-04-19

Reducing maternal mortality and improving maternal health care through increased utilization of postnatal care utilization is a global and local priority. However studies that have been carried out in Ethiopia regarding determinants are limited. So This study aims to assess the magnitude of postnatal care utilization and its determinants in Debre Birhan Town, North Ethiopia. A community-based cross-sectional study was conducted from March 1 to April 25, 2015, in Debre Birhan Town. Data were collected through face-to-face interviews using structured pre-tested questionnaires. The data were entered and cleaned in Epi Info version 3.5 and analyzed using SPSS version 20. Bivariate and multiple logistic regression analyses were used. Variable with p value less than or equal to 0.2 at bivariate analysis were entered into multiple logistic regression. Significance was declared at 0.05 in multiple logistic regressions and considered to be an independent factor. From the total respondents, we found that 327 (83.3%) mothers utilized the postnatal care services. Single mothers were less likely to utilize postnatal care services than those mothers who are married and live together [adjusted odds ratio (AOR) = 0.06, 95% CI (0.01, 0.45)]. This study revealed that respondent's knowledge about postnatal care services is an important predictor of postnatal care utilization [AOR = 0.03, 95% CI (0.00, 0.44)] and mothers who delivered in a health care facility were more likely to receive PNC than mothers who did not deliver in a health care facility [AOR = 0.65, 95% CI (0.58, 0.94)]. The postnatal care utilization rate in Debre Birhan town was 83.3%. Marital status, maternal knowledge, and place of delivery were predictors of postnatal care service utilization. So specific attention should be directed towards the improvement of women's education since the perception of the need for PNC services were positively correlated with the mother's education.

Mixture of autoregressive modeling orders and its implication on single trial EEG classification

PubMed Central

Atyabi, Adham; Shic, Frederick; Naples, Adam

2016-01-01

Autoregressive (AR) models are of commonly utilized feature types in Electroencephalogram (EEG) studies due to offering better resolution, smoother spectra and being applicable to short segments of data. Identifying correct AR’s modeling order is an open challenge. Lower model orders poorly represent the signal while higher orders increase noise. Conventional methods for estimating modeling order includes Akaike Information Criterion (AIC), Bayesian Information Criterion (BIC) and Final Prediction Error (FPE). This article assesses the hypothesis that appropriate mixture of multiple AR orders is likely to better represent the true signal compared to any single order. Better spectral representation of underlying EEG patterns can increase utility of AR features in Brain Computer Interface (BCI) systems by increasing timely & correctly responsiveness of such systems to operator’s thoughts. Two mechanisms of Evolutionary-based fusion and Ensemble-based mixture are utilized for identifying such appropriate mixture of modeling orders. The classification performance of the resultant AR-mixtures are assessed against several conventional methods utilized by the community including 1) A well-known set of commonly used orders suggested by the literature, 2) conventional order estimation approaches (e.g., AIC, BIC and FPE), 3) blind mixture of AR features originated from a range of well-known orders. Five datasets from BCI competition III that contain 2, 3 and 4 motor imagery tasks are considered for the assessment. The results indicate superiority of Ensemble-based modeling order mixture and evolutionary-based order fusion methods within all datasets. PMID:28740331

Integrative proteomics, genomics, and translational immunology approaches reveal mutated forms of Proteolipid Protein 1 (PLP1) and mutant-specific immune response in multiple sclerosis.

PubMed

Qendro, Veneta; Bugos, Grace A; Lundgren, Debbie H; Glynn, John; Han, May H; Han, David K

2017-03-01

In order to gain mechanistic insights into multiple sclerosis (MS) pathogenesis, we utilized a multi-dimensional approach to test the hypothesis that mutations in myelin proteins lead to immune activation and central nervous system autoimmunity in MS. Mass spectrometry-based proteomic analysis of human MS brain lesions revealed seven unique mutations of PLP1; a key myelin protein that is known to be destroyed in MS. Surprisingly, in-depth genomic analysis of two MS patients at the genomic DNA and mRNA confirmed mutated PLP1 in RNA, but not in the genomic DNA. Quantification of wild type and mutant PLP RNA levels by qPCR further validated the presence of mutant PLP RNA in the MS patients. To seek evidence linking mutations in abundant myelin proteins and immune-mediated destruction of myelin, specific immune response against mutant PLP1 in MS patients was examined. Thus, we have designed paired, wild type and mutant peptide microarrays, and examined antibody response to multiple mutated PLP1 in sera from MS patients. Consistent with the idea of different patients exhibiting unique mutation profiles, we found that 13 out of 20 MS patients showed antibody responses against specific but not against all the mutant-PLP1 peptides. Interestingly, we found mutant PLP-directed antibody response against specific mutant peptides in the sera of pre-MS controls. The results from integrative proteomic, genomic, and immune analyses reveal a possible mechanism of mutation-driven pathogenesis in human MS. The study also highlights the need for integrative genomic and proteomic analyses for uncovering pathogenic mechanisms of human diseases. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ply cracking in composite laminates

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

Han, Youngmyong.

1989-01-01

Ply cracking behavior and accompanying stiffness changes in thermoset as well as thermoplastic matrix composites under various loading conditions are investigated. Specific topics addressed are: analytical model development for property degradations due to ply cracking under general in-plane loading; crack initiation and multiplication under static loading; and crack multiplication under cyclic loading. A model was developed to calculate the energy released due to ply cracking in a composite laminate subjected to general in-plane loading. The method is based on the use of a second order polynomial to represent the crack opening displacement and the concept of a through-the-thickness inherent flaw.more » The model is then used in conjunction with linear elastic fracture mechanics to predict the progressive ply cracking as well as first ply cracking. A resistance curve for crack multiplication is proposed as a means of characterizing the resistance to ply cracking in composite laminates. A methodology of utilizing the resistance curve to assess the crack density or overloading is also discussed. The method was applied to the graphite/thermoplastic polyimide composite to predict progressive ply cracking. However, unlike the thermoset matrix composites, a strength model is found to fit the experimental results better than the fracture mechanics based model. A set of closed form equations is also developed to calculate the accompanying stiffness changes due to the ply cracking. The effect of thermal residual stress is included in the analysis. A new method is proposed to characterize transverse ply cracking of symmetric balanced laminates under cyclic loading. The method is based on the concept of a through-the-thickness inherent flaw, the Paris law, and the resistance curve. Only two constants are needed to predict the crack density as a function of fatigue cycles.« less

Novel patch modelling method for efficient simulation and prediction uncertainty analysis of multi-scale groundwater flow and transport processes

NASA Astrophysics Data System (ADS)

Sreekanth, J.; Moore, Catherine

2018-04-01

The application of global sensitivity and uncertainty analysis techniques to groundwater models of deep sedimentary basins are typically challenged by large computational burdens combined with associated numerical stability issues. The highly parameterized approaches required for exploring the predictive uncertainty associated with the heterogeneous hydraulic characteristics of multiple aquifers and aquitards in these sedimentary basins exacerbate these issues. A novel Patch Modelling Methodology is proposed for improving the computational feasibility of stochastic modelling analysis of large-scale and complex groundwater models. The method incorporates a nested groundwater modelling framework that enables efficient simulation of groundwater flow and transport across multiple spatial and temporal scales. The method also allows different processes to be simulated within different model scales. Existing nested model methodologies are extended by employing 'joining predictions' for extrapolating prediction-salient information from one model scale to the next. This establishes a feedback mechanism supporting the transfer of information from child models to parent models as well as parent models to child models in a computationally efficient manner. This feedback mechanism is simple and flexible and ensures that while the salient small scale features influencing larger scale prediction are transferred back to the larger scale, this does not require the live coupling of models. This method allows the modelling of multiple groundwater flow and transport processes using separate groundwater models that are built for the appropriate spatial and temporal scales, within a stochastic framework, while also removing the computational burden associated with live model coupling. The utility of the method is demonstrated by application to an actual large scale aquifer injection scheme in Australia.

Variants of CEP68 Gene Are Associated with Acute Urticaria/Angioedema Induced by Multiple Non-Steroidal Anti-Inflammatory Drugs

PubMed Central

Cornejo-García, José Antonio; Flores, Carlos; Plaza-Serón, María C.; Acosta-Herrera, Marialbert; Blanca-López, Natalia; Doña, Inmaculada; Torres, María J.; Mayorga, Cristobalina; Guéant-Rodríguez, Rosa M.; Ayuso, Pedro; Fernández, Javier; Laguna, José J.; Agúndez, José A. G.; García-Martín, Elena; Guéant, Jean-Louis; Canto, Gabriela; Blanca, Miguel

2014-01-01

Non-steroidal anti-inflammatory drugs (NSAIDs) are the most consumed drugs worldwide because of their efficacy and utility in the treatment of pain and inflammatory diseases. However, they are also responsible for an important number of adverse effects including hypersensitivity reactions. The most important group of these reactions is triggered by non-immunological, pharmacological mechanisms catalogued under the denomination of cross-intolerance (CRI), with acute urticaria/angioedema induced by multiple NSAIDs (MNSAID-UA) the most frequently associated clinical entity. A recent genome-wide association study identified the gene encoding the centrosomal protein of 68 KDa (CEP68) as the major locus associated with aspirin intolerance susceptibility in asthmatics. In this study, we aimed to assess the role of this locus in susceptibility to CRI to NSAIDs by examining 53 common gene variants in a total of 635 patients that were classified as MNSAID-UA (n = 399), airway exacerbations (n = 110) or blended pattern (n = 126), and 425 controls. We found in the MNSAID-UA group a number of variants (17) associated (lowest p-value = 1.13×10−6), including the non-synonymous Gly74Ser variant (rs7572857) previously associated with aspirin intolerance susceptibility in asthmatics. Although not being significant in the context of multiple testing, eight of these variants were also associated with exacerbated respiratory disease or blended reactions. Our results suggest that CEP68 gene variants may play an important role in MNSAID-UA susceptibility and, despite the different regulatory mechanisms involved depending on the specific affected organ, in the development of hypersensitivity reactions to NSAIDs. PMID:24618698

Mu-opiate receptors measured by positron emission tomography are increased in temporal lobe epilepsy.

PubMed

Frost, J J; Mayberg, H S; Fisher, R S; Douglass, K H; Dannals, R F; Links, J M; Wilson, A A; Ravert, H T; Rosenbaum, A E; Snyder, S H

1988-03-01

Neurochemical studies in animal models of epilepsy have demonstrated the importance of multiple neurotransmitters and their receptors in mediating seizures. The role of opiate receptors and endogenous opioid peptides in seizure mechanisms is well developed and is the basis for measuring opiate receptors in patients with epilepsy. Patients with complex partial seizures due to unilateral temporal seizure foci were studied by positron emission tomography using 11C-carfentanil to measure mu-opiate receptors and 18F-fluoro-deoxy-D-glucose to measure glucose utilization. Opiate receptor binding is greater in the temporal neocortex on the side of the electrical focus than on the opposite side. Modeling studies indicate that the increase in binding is due to an increase in affinity or the number of unoccupied receptors. No significant asymmetry of 11C-carfentanil binding was detected in the amygdala or hippocampus. Glucose utilization correlated inversely with 11C-carfentanil binding in the temporal neocortex. Increased opiate receptors in the temporal neocortex may represent a tonic anticonvulsant system that limits the spread of electrical activity from other temporal lobe structures.

Vibration measurements of the Daniel K. Inouye Solar Telescope mount, Coudé rotator, and enclosure assemblies

NASA Astrophysics Data System (ADS)

McBride, William R.; McBride, Daniel R.

2016-08-01

The Daniel K. Inouye Solar Telescope (DKIST) will be the largest solar telescope in the world, with a 4-meter off-axis primary mirror and 16 meter rotating Coudé laboratory within the telescope pier. The off-axis design requires a mount similar to an 8-meter on-axis telescope. Both the telescope mount and the Coudé laboratory utilize a roller bearing technology in place of the more commonly used hydrostatic bearings. The telescope enclosure utilizes a crawler mechanism for the altitude axis. As these mechanisms have not previously been used in a telescope, understanding the vibration characteristics and the potential impact on the telescope image is important. This paper presents the methodology used to perform jitter measurements of the enclosure and the mount bearings and servo system in a high-noise environment utilizing seismic accelerometers and high dynamic-range data acquisition equipment, along with digital signal processing (DSP) techniques. Data acquisition and signal processing were implemented in MATLAB. In the factory acceptance testing of the telescope mount, multiple accelerometers were strategically located to capture the six axes-of-motion of the primary and secondary mirror dummies. The optical sensitivity analysis was used to map these mirror mount displacements and rotations into units of image motion on the focal plane. Similarly, tests were done with the Coudé rotator, treating the entire rotating instrument lab as a rigid body. Testing was performed by recording accelerometer data while the telescope control system performed tracking operations typical of various observing scenarios. The analysis of the accelerometer data utilized noise-averaging fast Fourier transform (FFT) routines, spectrograms, and periodograms. To achieve adequate dynamic range at frequencies as low as 3Hz, the use of special filters and advanced windowing functions were necessary. Numerous identical automated tests were compared to identify and select the data sets with the lowest level of external interference. Similar testing was performed on the telescope enclosure during the factory test campaign. The vibration of the enclosure altitude and azimuth mechanisms were characterized. This paper details jitter tests using accelerometers placed in locations that allowed the motion of the assemblies to be measured while the control system performed various moves typical of on-sky observations. The measurements were converted into the rigid body motion of the structures and mapped into image motion using the telescope's optical sensitivity analysis.

Multiple paths in complex tasks

NASA Technical Reports Server (NTRS)

Galanter, Eugene; Wiegand, Thomas; Mark, Gloria

1987-01-01

The relationship between utility judgments of subtask paths and the utility of the task as a whole was examined. The convergent validation procedure is based on the assumption that measurements of the same quantity done with different methods should covary. The utility measures of the subtasks were obtained during the performance of an aircraft flight controller navigation task. Analyses helped decide among various models of subtask utility combination, whether the utility ratings of subtask paths predict the whole tasks utility rating, and indirectly, whether judgmental models need to include the equivalent of cognitive noise.

Key design elements of a data utility for national biosurveillance: event-driven architecture, caching, and Web service model.

PubMed

Tsui, Fu-Chiang; Espino, Jeremy U; Weng, Yan; Choudary, Arvinder; Su, Hoah-Der; Wagner, Michael M

2005-01-01

The National Retail Data Monitor (NRDM) has monitored over-the-counter (OTC) medication sales in the United States since December 2002. The NRDM collects data from over 18,600 retail stores and processes over 0.6 million sales records per day. This paper describes key architectural features that we have found necessary for a data utility component in a national biosurveillance system. These elements include event-driven architecture to provide analyses of data in near real time, multiple levels of caching to improve query response time, high availability through the use of clustered servers, scalable data storage through the use of storage area networks and a web-service function for interoperation with affiliated systems. The methods and architectural principles are relevant to the design of any production data utility for public health surveillance-systems that collect data from multiple sources in near real time for use by analytic programs and user interfaces that have substantial requirements for time-series data aggregated in multiple dimensions.

Mechanisms of buffer therapy resistance.

PubMed

Bailey, Kate M; Wojtkowiak, Jonathan W; Cornnell, Heather H; Ribeiro, Maria C; Balagurunathan, Yoganand; Hashim, Arig Ibrahim; Gillies, Robert J

2014-04-01

Many studies have shown that the acidity of solid tumors contributes to local invasion and metastasis. Oral pH buffers can specifically neutralize the acidic pH of tumors and reduce the incidence of local invasion and metastatic formation in multiple murine models. However, this effect is not universal as we have previously observed that metastasis is not inhibited by buffers in some tumor models, regardless of buffer used. B16-F10 (murine melanoma), LL/2 (murine lung) and HCT116 (human colon) tumors are resistant to treatment with lysine buffer therapy, whereas metastasis is potently inhibited by lysine buffers in MDA-MB-231 (human breast) and PC3M (human prostate) tumors. In the current work, we confirmed that sensitive cells utilized a pH-dependent mechanism for successful metastasis supported by a highly glycolytic phenotype that acidifies the local tumor microenvironment resulting in morphological changes. In contrast, buffer-resistant cell lines exhibited a pH-independent metastatic mechanism involving constitutive secretion of matrix degrading proteases without elevated glycolysis. These results have identified two distinct mechanisms of experimental metastasis, one of which is pH-dependent (buffer therapy sensitive cells) and one which is pH-independent (buffer therapy resistant cells). Further characterization of these models has potential for therapeutic benefit. Copyright © 2014 Neoplasia Press, Inc. Published by Elsevier Inc. All rights reserved.

Mechanisms of buffer therapy resistance

PubMed Central

Bailey, Kate M.; Wojtkowiak, Jonathan W.; Cornnell, Heather H.; Ribeiro, Maria C.; Balagurunathan, Yoganand; Hashim, Arig Ibrahim; Gillies, Robert J.

2014-01-01

Many studies have shown that the acidity of solid tumors contributes to local invasion and metastasis. Oral pH buffers can specifically neutralize the acidic pH of tumors and reduce the incidence of local invasion and metastatic formation in multiple murine models. However, this effect is not universal as we have previously observed that metastasis is not inhibited by buffers in some tumor models, regardless of buffer used. B16-F10 (murine melanoma), LL/2 (murine lung) and HCT116 (human colon) tumors are resistant to treatment with lysine buffer therapy, whereas metastasis is potently inhibited by lysine buffers in MDA-MB-231 (human breast) and PC3M (human prostate) tumors. In the current work, we confirmed that sensitive cells utilized a pH-dependent mechanism for successful metastasis supported by a highly glycolytic phenotype that acidifies the local tumor microenvironment resulting in morphological changes. In contrast, buffer-resistant cell lines exhibited a pH-independent metastatic mechanism involving constitutive secretion of matrix degrading proteases without elevated glycolysis. These results have identified two distinct mechanisms of experimental metastasis, one of which is pH-dependent (buffer therapy sensitive cells) and one which is pH-independent (buffer therapy resistant cells). Further characterization of these models has potential for therapeutic benefit. PMID:24862761

Insight into drug resistance mechanisms and discovery of potential inhibitors against wild-type and L1196M mutant ALK from FDA-approved drugs.

PubMed

Li, Jianzong; Liu, Wei; Luo, Hao; Bao, Jinku

2016-09-01

Anaplastic lymphoma kinase (ALK) plays a crucial role in multiple malignant cancers. It is known as a well-established target for the treatment of ALK-dependent cancers. Even though substantial efforts have been made to develop ALK inhibitors, only crizotinib, ceritinib, and alectinib had been approved by the U.S. Food and Drug Administration for patients with ALK-positive non-small cell lung cancer (NSCLC). The secondary mutations with drug-resistance bring up difficulties to develop effective drugs for ALK-positive cancers. To give a comprehensive understanding of molecular mechanism underlying inhibitor response to ALK tyrosine kinase mutations, we established an accurate assessment for the extensive profile of drug against ALK mutations by means of computational approaches. The molecular mechanics-generalized Born surface area (MM-GBSA) method based on molecular dynamics (MD) simulation was carried out to calculate relative binding free energies for receptor-drug systems. In addition, the structure-based virtual screening was utilized to screen effective inhibitors targeting wild-type ALK and the gatekeeper mutation L1196M from 3180 approved drugs. Finally, the mechanism of drug resistance was discussed, several novel potential wild-type and L1196M mutant ALK inhibitors were successfully identified.

Mechanism Design for Incentivizing Social Media Contributions

NASA Astrophysics Data System (ADS)

Singh, Vivek K.; Jain, Ramesh; Kankanhalli, Mohan

Despite recent advancements in user-driven social media platforms, tools for studying user behavior patterns and motivations remain primitive. We highlight the voluntary nature of user contributions and that users can choose when (and when not) to contribute to the common media pool. A Game theoretic framework is proposed to study the dynamics of social media networks where contribution costs are individual but gains are common. We model users as rational selfish agents, and consider domain attributes like voluntary participation, virtual reward structure, network effect, and public-sharing to model the dynamics of this interaction. The created model describes the most appropriate contribution strategy from each user's perspective and also highlights issues like 'free-rider' problem and individual rationality leading to irrational (i.e. sub-optimal) group behavior. We also consider the perspective of the system designer who is interested in finding the best incentive mechanisms to influence the selfish end-users so that the overall system utility is maximized. We propose and compare multiple mechanisms (based on optimal bonus payment, social incentive leveraging, and second price auction) to study how a system designer can exploit the selfishness of its users, to design incentive mechanisms which improve the overall task-completion probability and system performance, while possibly still benefiting the individual users.

Genotype Reconstruction of Paternity in European Lobsters (Homarus gammarus).

PubMed

Ellis, Charlie D; Hodgson, David J; André, Carl; Sørdalen, Tonje K; Knutsen, Halvor; Griffiths, Amber G F

2015-01-01

Decapod crustaceans exhibit considerable variation in fertilisation strategies, ranging from pervasive single paternity to the near-ubiquitous presence of multiple paternity, and such knowledge of mating systems and behaviour are required for the informed management of commercially-exploited marine fisheries. We used genetic markers to assess the paternity of individual broods in the European lobster, Homarus gammarus, a species for which paternity structure is unknown. Using 13 multiplexed microsatellite loci, three of which are newly described in this study, we genotyped 10 eggs from each of 34 females collected from an Atlantic peninsula in the south-western United Kingdom. Single reconstructed paternal genotypes explained all observed progeny genotypes in each of the 34 egg clutches, and each clutch was fertilised by a different male. Simulations indicated that the probability of detecting multiple paternity was in excess of 95% if secondary sires account for at least a quarter of the brood, and in excess of 99% where additional sire success was approximately equal. Our results show that multiple paternal fertilisations are either absent, unusual, or highly skewed in favour of a single male among H. gammarus in this area. Potential mechanisms upholding single paternal fertilisation are discussed, along with the prospective utility of parentage assignments in evaluations of hatchery stocking and other fishery conservation approaches in light of this finding.

In vivo optical modulation of neural signals using monolithically integrated two-dimensional neural probe arrays

PubMed Central

Son, Yoojin; Jenny Lee, Hyunjoo; Kim, Jeongyeon; Shin, Hyogeun; Choi, Nakwon; Justin Lee, C.; Yoon, Eui-Sung; Yoon, Euisik; Wise, Kensall D.; Geun Kim, Tae; Cho, Il-Joo

2015-01-01

Integration of stimulation modalities (e.g. electrical, optical, and chemical) on a large array of neural probes can enable an investigation of important underlying mechanisms of brain disorders that is not possible through neural recordings alone. Furthermore, it is important to achieve this integration of multiple functionalities in a compact structure to utilize a large number of the mouse models. Here we present a successful optical modulation of in vivo neural signals of a transgenic mouse through our compact 2D MEMS neural array (optrodes). Using a novel fabrication method that embeds a lower cladding layer in a silicon substrate, we achieved a thin silicon 2D optrode array that is capable of delivering light to multiple sites using SU-8 as a waveguide core. Without additional modification to the microelectrodes, the measured impedance of the multiple microelectrodes was below 1 MΩ at 1 kHz. In addition, with a low background noise level (±25 μV), neural spikes from different individual neurons were recorded on each microelectrode. Lastly, we successfully used our optrodes to modulate the neural activity of a transgenic mouse through optical stimulation. These results demonstrate the functionality of the 2D optrode array and its potential as a next-generation tool for optogenetic applications. PMID:26494437

Computational and biochemical characterization of two partially overlapping interfaces and multiple weak-affinity K-Ras dimers

NASA Astrophysics Data System (ADS)

Prakash, Priyanka; Sayyed-Ahmad, Abdallah; Cho, Kwang-Jin; Dolino, Drew M.; Chen, Wei; Li, Hongyang; Grant, Barry J.; Hancock, John F.; Gorfe, Alemayehu A.

2017-01-01

Recent studies found that membrane-bound K-Ras dimers are important for biological function. However, the structure and thermodynamic stability of these complexes remained unknown because they are hard to probe by conventional approaches. Combining data from a wide range of computational and experimental approaches, here we describe the structure, dynamics, energetics and mechanism of assembly of multiple K-Ras dimers. Utilizing a range of techniques for the detection of reactive surfaces, protein-protein docking and molecular simulations, we found that two largely polar and partially overlapping surfaces underlie the formation of multiple K-Ras dimers. For validation we used mutagenesis, electron microscopy and biochemical assays under non-denaturing conditions. We show that partial disruption of a predicted interface through charge reversal mutation of apposed residues reduces oligomerization while introduction of cysteines at these positions enhanced dimerization likely through the formation of an intermolecular disulfide bond. Free energy calculations indicated that K-Ras dimerization involves direct but weak protein-protein interactions in solution, consistent with the notion that dimerization is facilitated by membrane binding. Taken together, our atomically detailed analyses provide unique mechanistic insights into K-Ras dimer formation and membrane organization as well as the conformational fluctuations and equilibrium thermodynamics underlying these processes.

Correlation of digital health use and chronic pain coping strategies.

PubMed

Ranney, Megan L; Duarte, Cassandra; Baird, Janette; Patry, Emily J; Green, Traci C

2016-01-01

Digital health is an increasingly popular tool for patient engagement, having shown great success in arenas such as medication adherence, management of chronic conditions, and patient safety. Given the growth of chronic pain diagnoses, it is imperative to find new technologies to improve care for this particular population. Little research has catalogued the use of digital health in the chronic pain patient population. This manuscript's objective was to describe current patterns of digital health usage among chronic pain patients and how digital health use correlates with health care utilization and health outcomes. A cross-sectional survey was administered to patients with a self-identified chronic pain diagnosis participating in 'Patients Like Me' ® (PLM), an organization that directly collects data from patients experiencing chronic health conditions, with emphasis on patient-centered outcomes and experiences interacting with the health care system. Validated measures of healthcare utilization, chronic pain management, and digital health use were adapted for the survey. Digital health was defined as the use of online sites, social media, and mobile phone applications before, during, or after healthcare utilization. Descriptive statistics, chi square tests, logistic regression, and linear regression were used as appropriate for analysis. Among 565 respondents (mean age 51.3, 87.2% female, 45.7% publicly insured), most participants (89.5%) reported some digital health use. Females and users below the age of 50 were more likely to use multiple forms of digital health. Healthcare utilization, education level, and race/ethnicity did not correlate with digital health use. Patients using more types of digital health reported significantly higher levels of pain coping skills in the realms of social support, relaxation, and exercise. Digital health use is common among a wide range of patients with chronic pain diagnoses. The use of multiple forms of digital health is associated with improved chronic pain coping mechanisms. Future work should explore the directional relationship between digital health tools and chronic pain coping skills, as well as which components of digital health have the most effect on chronic pain management and other patient-centered outcomes.

Correlation of digital health use and chronic pain coping strategies

PubMed Central

Duarte, Cassandra; Baird, Janette; Patry, Emily J.; Green, Traci C.

2016-01-01

Background Digital health is an increasingly popular tool for patient engagement, having shown great success in arenas such as medication adherence, management of chronic conditions, and patient safety. Given the growth of chronic pain diagnoses, it is imperative to find new technologies to improve care for this particular population. Little research has catalogued the use of digital health in the chronic pain patient population. This manuscript’s objective was to describe current patterns of digital health usage among chronic pain patients and how digital health use correlates with health care utilization and health outcomes. Methods A cross-sectional survey was administered to patients with a self-identified chronic pain diagnosis participating in ‘Patients Like Me’® (PLM), an organization that directly collects data from patients experiencing chronic health conditions, with emphasis on patient-centered outcomes and experiences interacting with the health care system. Validated measures of healthcare utilization, chronic pain management, and digital health use were adapted for the survey. Digital health was defined as the use of online sites, social media, and mobile phone applications before, during, or after healthcare utilization. Descriptive statistics, chi square tests, logistic regression, and linear regression were used as appropriate for analysis. Results Among 565 respondents (mean age 51.3, 87.2% female, 45.7% publicly insured), most participants (89.5%) reported some digital health use. Females and users below the age of 50 were more likely to use multiple forms of digital health. Healthcare utilization, education level, and race/ethnicity did not correlate with digital health use. Patients using more types of digital health reported significantly higher levels of pain coping skills in the realms of social support, relaxation, and exercise. Conclusions Digital health use is common among a wide range of patients with chronic pain diagnoses. The use of multiple forms of digital health is associated with improved chronic pain coping mechanisms. Future work should explore the directional relationship between digital health tools and chronic pain coping skills, as well as which components of digital health have the most effect on chronic pain management and other patient-centered outcomes. PMID:28293608

40 CFR 63.1329 - Process contact cooling towers provisions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... viscosity multiple end finisher process that utilizes a process contact cooling tower shall comply with... high viscosity multiple end finisher process and who is subject or becomes subject to 40 CFR part 60...

40 CFR 63.1329 - Process contact cooling towers provisions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... viscosity multiple end finisher process that utilizes a process contact cooling tower shall comply with... high viscosity multiple end finisher process, and who is subject or becomes subject to 40 CFR part 60...

Therapeutic effects of multiple nutritional supplements on the hypertensive indices of cardiovascular distress

NASA Astrophysics Data System (ADS)

Okereke, Emmanuel O.

2000-09-01

This quasi-experiment study examined the therapeutic effects of multiple nutritional supplements on the hypertensive indices of cardiovascular distress. By utilizing drug interventions that reduced cardiovascular distress through changes in the hypertensive indices, previous studies have shown that improvements in life expectancy, lowering of health care costs in later years, and reduction in all-cause mortality were achieved. In fact, individuals without risk factors or with low risk factors for cardiovascular disease in young adulthood or middle age were healthier, had a greater life expectancy, and incurred lower health care costs in later years. The hypertensive indices of interest include elevated heart rate (HR), systolic blood pressure (Ps), diastolic blood pressure (PD), mean arterial blood pressure (MABP), pulse pressure (PP), and mechanical disadvantages of the heart MDH. Mechanical disadvantage of the heart is a term that has been developed for the purposes of this study. The alternative hypotheses for this study proposed to show a significant change in the relevant hypertensive indices of cardiovascular distress in volunteers after a minimum of 45 days treatment with multiple nutritional supplements. The target population was all middle-aged (30 to 65 years) volunteer hypertensives in Nigeria (West Africa), who were randomly assigned to either the experimental group or control group, controlling for individuals who were on any form of medication, smokers, alcoholics, and those who were pregnant or on contraceptives. Treatment involved multiple doses of the various vitamins, minerals, essential amino acids, essential fatty acids, and accessory nutrients in their complementary combinations that influence various levels of cardiovascular function. After 45 days of treatment, the differences between the mean sores of the experimental group and control group on Ps, PD, MABP, and PP were found to be statistically significant, at p ≤ .05 cut-off level for rejecting the null hypothesis for each dependent variable on a one-tailed student's t test. The same results were not demonstrated for HR and MDH. In summary, the therapeutic effects of multiple nutritional supplements on the hypertensive indices of cardiovascular distress could provide a cost-effective, safe, healthy, and reliable way of preventing cardiovascular disease.

Optimizing utility owner participation in the project development and delivery process.

DOT National Transportation Integrated Search

2013-04-01

Coordination with utility owners during the project development and delivery process involves multiple : activities, such as requesting and collecting data about the location and characteristics of existing facilities to : identifying and analyzing u...

A Quantile Regression Approach to Understanding the Relations Between Morphological Awareness, Vocabulary, and Reading Comprehension in Adult Basic Education Students

PubMed Central

Tighe, Elizabeth L.; Schatschneider, Christopher

2015-01-01

The purpose of this study was to investigate the joint and unique contributions of morphological awareness and vocabulary knowledge at five reading comprehension levels in Adult Basic Education (ABE) students. We introduce the statistical technique of multiple quantile regression, which enabled us to assess the predictive utility of morphological awareness and vocabulary knowledge at multiple points (quantiles) along the continuous distribution of reading comprehension. To demonstrate the efficacy of our multiple quantile regression analysis, we compared and contrasted our results with a traditional multiple regression analytic approach. Our results indicated that morphological awareness and vocabulary knowledge accounted for a large portion of the variance (82-95%) in reading comprehension skills across all quantiles. Morphological awareness exhibited the greatest unique predictive ability at lower levels of reading comprehension whereas vocabulary knowledge exhibited the greatest unique predictive ability at higher levels of reading comprehension. These results indicate the utility of using multiple quantile regression to assess trajectories of component skills across multiple levels of reading comprehension. The implications of our findings for ABE programs are discussed. PMID:25351773

Compression and neutron and ion beams emission mechanisms within a plasma focus device

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

Yousefi, H. R.; Mohanty, S. R.; Nakada, Y.

This paper reports some results of investigations of the neutron emission from middle energy Mather-type plasma focus. Multiple compressions were observed, and it seems that multiple compression regimes can occur at low pressure, while single compression appeared at higher pressure, which is favorable for neutron production. The multiple compression mechanism can be attributed to the (m=0 type) instability. The m=0 type instability is a necessary condition for fusion activity and x-ray production, but is not sufficient by itself. Accompanying the multiple compressions, multiple deuteron and neutron pulses were detected, which implies that there are different kinds of acceleration mechanisms.

A Robust CRISPR/Cas9 System for Convenient, High-Efficiency Multiplex Genome Editing in Monocot and Dicot Plants.

PubMed

Ma, Xingliang; Zhang, Qunyu; Zhu, Qinlong; Liu, Wei; Chen, Yan; Qiu, Rong; Wang, Bin; Yang, Zhongfang; Li, Heying; Lin, Yuru; Xie, Yongyao; Shen, Rongxin; Chen, Shuifu; Wang, Zhi; Chen, Yuanling; Guo, Jingxin; Chen, Letian; Zhao, Xiucai; Dong, Zhicheng; Liu, Yao-Guang

2015-08-01

CRISPR/Cas9 genome targeting systems have been applied to a variety of species. However, most CRISPR/Cas9 systems reported for plants can only modify one or a few target sites. Here, we report a robust CRISPR/Cas9 vector system, utilizing a plant codon optimized Cas9 gene, for convenient and high-efficiency multiplex genome editing in monocot and dicot plants. We designed PCR-based procedures to rapidly generate multiple sgRNA expression cassettes, which can be assembled into the binary CRISPR/Cas9 vectors in one round of cloning by Golden Gate ligation or Gibson Assembly. With this system, we edited 46 target sites in rice with an average 85.4% rate of mutation, mostly in biallelic and homozygous status. We reasoned that about 16% of the homozygous mutations in rice were generated through the non-homologous end-joining mechanism followed by homologous recombination-based repair. We also obtained uniform biallelic, heterozygous, homozygous, and chimeric mutations in Arabidopsis T1 plants. The targeted mutations in both rice and Arabidopsis were heritable. We provide examples of loss-of-function gene mutations in T0 rice and T1 Arabidopsis plants by simultaneous targeting of multiple (up to eight) members of a gene family, multiple genes in a biosynthetic pathway, or multiple sites in a single gene. This system has provided a versatile toolbox for studying functions of multiple genes and gene families in plants for basic research and genetic improvement. Copyright © 2015 The Author. Published by Elsevier Inc. All rights reserved.

The contrasting role of male relatedness in different mechanisms of sexual selection in red junglefowl.

PubMed

Tan, Cedric Kai Wei; Doyle, Philippa; Bagshaw, Emma; Richardson, David S; Wigby, Stuart; Pizzari, Tommaso

2017-02-01

In structured populations, competition for reproductive opportunities should be relaxed among related males. The few tests of this prediction often neglect the fact that sexual selection acts through multiple mechanisms, both before and after mating. We performed experiments to study the role of within-group male relatedness across pre- and postcopulatory mechanisms of sexual selection in social groups of red junglefowl, Gallus gallus, in which two related males and one unrelated male competed over females unrelated to all the males. We confirm theoretical expectations that, after controlling for male social status, competition over mating was reduced among related males. However, this effect was contrasted by other sexual selection mechanisms. First, females biased male mating in favor of the unrelated male, and might also favor his inseminations after mating. Second, males invested more-rather than fewer-sperm in postcopulatory competition with relatives. A number of factors may contribute to explain this counterintuitive pattern of sperm allocation, including trade-offs between male investment in pre- versus postcopulatory competition, differences in the relative relatedness of pre- versus postcopulatory competitors, and female bias in sperm utilization in response to male relatedness. Collectively, these results reveal that within-group male relatedness may have contrasting effects in different mechanisms of sexual selection. © 2016 The Author(s). Evolution published by Wiley Periodicals, Inc. on behalf of The Society for the Study of Evolution.

Cognitive Model of Trust Dynamics Predicts Human Behavior within and between Two Games of Strategic Interaction with Computerized Confederate Agents

PubMed Central

Collins, Michael G.; Juvina, Ion; Gluck, Kevin A.

2016-01-01

When playing games of strategic interaction, such as iterated Prisoner's Dilemma and iterated Chicken Game, people exhibit specific within-game learning (e.g., learning a game's optimal outcome) as well as transfer of learning between games (e.g., a game's optimal outcome occurring at a higher proportion when played after another game). The reciprocal trust players develop during the first game is thought to mediate transfer of learning effects. Recently, a computational cognitive model using a novel trust mechanism has been shown to account for human behavior in both games, including the transfer between games. We present the results of a study in which we evaluate the model's a priori predictions of human learning and transfer in 16 different conditions. The model's predictive validity is compared against five model variants that lacked a trust mechanism. The results suggest that a trust mechanism is necessary to explain human behavior across multiple conditions, even when a human plays against a non-human agent. The addition of a trust mechanism to the other learning mechanisms within the cognitive architecture, such as sequence learning, instance-based learning, and utility learning, leads to better prediction of the empirical data. It is argued that computational cognitive modeling is a useful tool for studying trust development, calibration, and repair. PMID:26903892

Characteristics of psychiatric hospitalizations with multiple mechanical restraint episodes versus hospitalization with a single mechanical restraint episode.

PubMed

Guzman-Parra, Jose; Guzik, Justyna; Garcia-Sanchez, Juan A; Pino-Benitez, Isabel; Aguilera-Serrano, Carlos; Mayoral-Cleries, Fermin

2016-10-30

We investigated the characteristics of multiple episodes of mechanical restraint versus a single episode in a psychiatric ward of a public general hospital. The following characteristics were associated with multiple restraints: young age, length of hospital stay, not being readmitted within 30 days from previous discharge, and admission in the previous year before the implementation of an intervention program to reduce mechanical restraint. The study suggests that both organizational factors and patients' disturbed behaviour are associated with the risk of being mechanically restrained several times. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Mechanism of saline groundwater migration under the influence of deep groundwater exploitation in the North China Plain

NASA Astrophysics Data System (ADS)

Han, D.; Cao, G.; Currell, M. J.

2016-12-01

Understanding the mechanism of salt water transport in response to the exploitation of deep freshwater has long been one of the major regional environmental hydrogeological problems and scientific challenges in the North China Plain. It is also the key to a correct understanding of the sources of deep groundwater pumpage. This study will look at the Hengshui - Cangzhou region as a region with typical vertical salt water distribution, and high levels of groundwater exploitation, integrating a variety of techniques in geology, hydrogeology, geophysics, hydrodynamics, and hydrochemistry - stable isotopes. Information about the problem will be determined using multiple lines of evidence, including field surveys of drilling and water sampling, as well as laboratory experiments and physical and numerical simulations. The project will characterize and depict the migration characteristics of salt water bodies and their relationship with the geological structure and deep ground water resources. The work will reveal the freshwater-saltwater interface shape; determine the mode and mechanism of hydrodynamic transport and salt transport; estimate the vertical migration time of salt water in a thick aquitard; and develop accurate hydrogeological conceptual models. This work will utilize groundwater variable density flow- solute transport numerical models to simulate the water and salt transport processes in vertical one-dimensional (typical bore) and two-dimensional (typical cross-section) space. Both inversion of the downward movement of saltwater caused by groundwater exploitation through history, and examining future saltwater migration trends under groundwater exploitation scenarios will be conducted, to quantitatively evaluate the impact of salt water migration to the deep groundwater body in the North China Plain. The research results will provide a scientific basis for the sustainable utilization of deep groundwater resources in this area.

Drosophila Nociceptors Mediate Larval Aversion to Dry Surface Environments Utilizing Both the Painless TRP Channel and the DEG/ENaC Subunit, PPK1

PubMed Central

Johnson, Wayne A.; Carder, Justin W.

2012-01-01

A subset of sensory neurons embedded within the Drosophila larval body wall have been characterized as high-threshold polymodal nociceptors capable of responding to noxious heat and noxious mechanical stimulation. They are also sensitized by UV-induced tissue damage leading to both thermal hyperalgesia and allodynia very similar to that observed in vertebrate nociceptors. We show that the class IV multiple-dendritic(mdIV) nociceptors are also required for a normal larval aversion to locomotion on to a dry surface environment. Drosophila melanogaster larvae are acutely susceptible to desiccation displaying a strong aversion to locomotion on dry surfaces severely limiting the distance of movement away from a moist food source. Transgenic inactivation of mdIV nociceptor neurons resulted in larvae moving inappropriately into regions of low humidity at the top of the vial reflected as an increased overall pupation height and larval desiccation. This larval lethal desiccation phenotype was not observed in wild-type controls and was completely suppressed by growth in conditions of high humidity. Transgenic hyperactivation of mdIV nociceptors caused a reciprocal hypersensitivity to dry surfaces resulting in drastically decreased pupation height but did not induce the writhing nocifensive response previously associated with mdIV nociceptor activation by noxious heat or harsh mechanical stimuli. Larvae carrying mutations in either the Drosophila TRP channel, Painless, or the degenerin/epithelial sodium channel subunit Pickpocket1(PPK1), both expressed in mdIV nociceptors, showed the same inappropriate increased pupation height and lethal desiccation observed with mdIV nociceptor inactivation. Larval aversion to dry surfaces appears to utilize the same or overlapping sensory transduction pathways activated by noxious heat and harsh mechanical stimulation but with strikingly different sensitivities and disparate physiological responses. PMID:22403719

Formalizing the Role of Agent-Based Modeling in Causal Inference and Epidemiology

PubMed Central

Marshall, Brandon D. L.; Galea, Sandro

2015-01-01

Calls for the adoption of complex systems approaches, including agent-based modeling, in the field of epidemiology have largely centered on the potential for such methods to examine complex disease etiologies, which are characterized by feedback behavior, interference, threshold dynamics, and multiple interacting causal effects. However, considerable theoretical and practical issues impede the capacity of agent-based methods to examine and evaluate causal effects and thus illuminate new areas for intervention. We build on this work by describing how agent-based models can be used to simulate counterfactual outcomes in the presence of complexity. We show that these models are of particular utility when the hypothesized causal mechanisms exhibit a high degree of interdependence between multiple causal effects and when interference (i.e., one person's exposure affects the outcome of others) is present and of intrinsic scientific interest. Although not without challenges, agent-based modeling (and complex systems methods broadly) represent a promising novel approach to identify and evaluate complex causal effects, and they are thus well suited to complement other modern epidemiologic methods of etiologic inquiry. PMID:25480821

Design and Control of a Pneumatically Actuated Transtibial Prosthesis.

PubMed

Zheng, Hao; Shen, Xiangrong

2015-04-01

This paper presents the design and control of a pneumatically actuated transtibial prosthesis, which utilizes a pneumatic cylinder-type actuator to power the prosthetic ankle joint to support the user's locomotion. The pneumatic actuator has multiple advantages over the traditional electric motor, such as light weight, low cost, and high power-to-weight ratio. The objective of this work is to develop a compact and lightweight transtibial prosthesis, leveraging the multiple advantages provided by this highly competitive actuator. In this paper, the design details of the prosthesis are described, including the determination of performance specifications, the layout of the actuation mechanism, and the calculation of the torque capacity. Through the authors' design calculation, the prosthesis is able to provide sufficient range of motion and torque capacity to support the locomotion of a 75 kg individual. The controller design is also described, including the underlying biomechanical analysis and the formulation of the finite-state impedance controller. Finally, the human subject testing results are presented, with the data indicating that the prosthesis is able to generate a natural walking gait and sufficient power output for its amputee user.

A program for sustained improvement in preventing ventilator associated pneumonia in an intensive care setting

PubMed Central

2012-01-01

Background Ventilator-associated pneumonia (VAP) is a common infection in the intensive care unit (ICU) and associated with a high mortality. Methods A quasi-experimental study was conducted in a medical-surgical ICU. Multiple interventions to optimize VAP prevention were performed from October 2008 to December 2010. All of these processes, including the Institute for Healthcare Improvement’s (IHI) ventilator bundle plus oral decontamination with chlorhexidine and continuous aspiration of subglottic secretions (CASS), were adopted for patients undergoing mechanical ventilation. Results We evaluated a total of 21,984 patient-days, and a total of 6,052 ventilator-days (ventilator utilization rate of 0.27). We found VAP rates of 1.3 and 2.0 per 1,000 ventilator days respectively in 2009 and 2010, achieving zero incidence of VAP several times during 12 months, whenever VAP bundle compliance was over 90%. Conclusion These results suggest that it is possible to reduce VAP rates to near zero and sustain these rates, but it requires a complex process involving multiple performance measures and interventions that must be permanently monitored. PMID:23020101

A program for sustained improvement in preventing ventilator associated pneumonia in an intensive care setting.

PubMed

Caserta, Raquel A; Marra, Alexandre R; Durão, Marcelino S; Silva, Cláudia Vallone; Pavao dos Santos, Oscar Fernando; Neves, Henrique Sutton de Sousa; Edmond, Michael B; Timenetsky, Karina Tavares

2012-09-29

Ventilator-associated pneumonia (VAP) is a common infection in the intensive care unit (ICU) and associated with a high mortality. A quasi-experimental study was conducted in a medical-surgical ICU. Multiple interventions to optimize VAP prevention were performed from October 2008 to December 2010. All of these processes, including the Institute for Healthcare Improvement's (IHI) ventilator bundle plus oral decontamination with chlorhexidine and continuous aspiration of subglottic secretions (CASS), were adopted for patients undergoing mechanical ventilation. We evaluated a total of 21,984 patient-days, and a total of 6,052 ventilator-days (ventilator utilization rate of 0.27). We found VAP rates of 1.3 and 2.0 per 1,000 ventilator days respectively in 2009 and 2010, achieving zero incidence of VAP several times during 12 months, whenever VAP bundle compliance was over 90%. These results suggest that it is possible to reduce VAP rates to near zero and sustain these rates, but it requires a complex process involving multiple performance measures and interventions that must be permanently monitored.

Interrelated Roles for the Aryl Hydrocarbon Receptor and Hypoxia Inducible Factor-1α in the Immune Response to Infection

PubMed Central

Wagage, Sagie; Hunter, Christopher A.

2015-01-01

Cells of the immune system utilize multiple mechanisms to respond to environmental signals and recent studies have demonstrated roles for two closely related proteins, the aryl hydrocarbon receptor (AHR) and hypoxia inducible factor-1α (HIF1α), in these processes. The AHR is a transcription factor that is activated by diverse ligands found in the diet and environmental pollution as well as by microbial and host-derived products. In contrast, HIF1α is a transcription factor that is active under low oxygen conditions and mediates cellular responses to hypoxia. These evolutionarily conserved proteins have roles in the interrelated processes of metabolism, tumorigenesis, and vascular development. Additionally, the AHR and HIF1α have multiple effects on innate and adaptive immunity. This article provides an overview of the biology of these transcription factors and reviews the effects of AHR and HIF1α signaling on immunity to infection. There are many parallels between these two pathways and their functions highlight the importance of AHR and HIF1α activity particularly at barrier surfaces in coordinating responses to pathogens.

Simulation of the M13 life cycle II: Investigation of the control mechanisms of M13 infection and establishment of the carrier state.

PubMed

Smeal, Steven W; Schmitt, Margaret A; Pereira, Ronnie Rodrigues; Prasad, Ashok; Fisk, John D

2017-01-01

Bacteriophage M13 is a true parasite of bacteria, able to co-opt the infected cell and control the production of progeny across many cellular generations. Here, our genetically-structured simulation of M13 is applied to quantitatively dissect the interplay between the host cellular environment and the controlling interactions governing the phage life cycle during the initial establishment of infection and across multiple cell generations. Multiple simulations suggest that phage-encoded feedback interactions constrain the utilization of host DNA polymerase, RNA polymerase and ribosomes. The simulation reveals the importance of p5 translational attenuation in controlling the production of phage double-stranded DNA and suggests an underappreciated role for p5 translational self-attenuation in resource allocation. The control elements active in a single generation are sufficient to reproduce the experimentally-observed multigenerational curing of the phage infection. Understanding the subtleties of regulation will be important for maximally exploiting M13 particles as scaffolds for nanoscale devices. Copyright © 2016 Elsevier Inc. All rights reserved.

Strain and deformations engineered germanene bilayer double gate-field effect transistor by first principles

NASA Astrophysics Data System (ADS)

Meher Abhinav, E.; Chandrasekaran, Gopalakrishnan; Kasmir Raja, S. V.

2017-10-01

Germanene, silicene, stanene, phosphorene and graphene are some of single atomic materials with novel properties. In this paper, we explored bilayer germanene-based Double Gate-Field Effect Transistor (DG-FET) with various strains and deformations using Density Functional Theory (DFT) and Green's approach by first-principle calculations. The DG-FET of 1.6 nm width, 6 nm channel length (Lch) and HfO2 as gate dielectric has been modeled. For intrinsic deformation of germanene bilayer, we have enforced minute mechanical deformation of wrap and twist (5°) and ripple (0.5 Å) on germanene bilayer channel material. By using NEGF formalism, I-V Characteristics of various strains and deformation tailored DG-FET was calculated. Our results show that rough edge and single vacancy (5-9) in bilayer germanene diminishes the current around 47% and 58% respectively as compared with pristine bilayer germanene. In case of strain tailored bilayer DG-FET, multiple NDR regions were observed which can be utilized in building stable multiple logic states in digital circuits and high frequency oscillators using negative resistive techniques.

Modeling joint restoration strategies for interdependent infrastructure systems

PubMed Central

Simonovic, Slobodan P.

2018-01-01

Life in the modern world depends on multiple critical services provided by infrastructure systems which are interdependent at multiple levels. To effectively respond to infrastructure failures, this paper proposes a model for developing optimal joint restoration strategy for interdependent infrastructure systems following a disruptive event. First, models for (i) describing structure of interdependent infrastructure system and (ii) their interaction process, are presented. Both models are considering the failure types, infrastructure operating rules and interdependencies among systems. Second, an optimization model for determining an optimal joint restoration strategy at infrastructure component level by minimizing the economic loss from the infrastructure failures, is proposed. The utility of the model is illustrated using a case study of electric-water systems. Results show that a small number of failed infrastructure components can trigger high level failures in interdependent systems; the optimal joint restoration strategy varies with failure occurrence time. The proposed models can help decision makers to understand the mechanisms of infrastructure interactions and search for optimal joint restoration strategy, which can significantly enhance safety of infrastructure systems. PMID:29649300

Advantages offered by high average power picosecond lasers

NASA Astrophysics Data System (ADS)

Moorhouse, C.

2011-03-01

As electronic devices shrink in size to reduce material costs, device size and weight, thinner material thicknesses are also utilized. Feature sizes are also decreasing, which is pushing manufacturers towards single step laser direct write process as an attractive alternative to conventional, multiple step photolithography processes by eliminating process steps and the cost of chemicals. The fragile nature of these thin materials makes them difficult to machine either mechanically or with conventional nanosecond pulsewidth, Diode Pumped Solids State (DPSS) lasers. Picosecond laser pulses can cut materials with reduced damage regions and selectively remove thin films due to the reduced thermal effects of the shorter pulsewidth. Also, the high repetition rate allows high speed processing for industrial applications. Selective removal of thin films for OLED patterning, silicon solar cells and flat panel displays is discussed, as well as laser cutting of transparent materials with low melting point such as Polyethylene Terephthalate (PET). For many of these thin film applications, where low pulse energy and high repetition rate are required, throughput can be increased by the use of a novel technique to using multiple beams from a single laser source is outlined.

Design and Control of a Pneumatically Actuated Transtibial Prosthesis

PubMed Central

Zheng, Hao; Shen, Xiangrong

2015-01-01

This paper presents the design and control of a pneumatically actuated transtibial prosthesis, which utilizes a pneumatic cylinder-type actuator to power the prosthetic ankle joint to support the user's locomotion. The pneumatic actuator has multiple advantages over the traditional electric motor, such as light weight, low cost, and high power-to-weight ratio. The objective of this work is to develop a compact and lightweight transtibial prosthesis, leveraging the multiple advantages provided by this highly competitive actuator. In this paper, the design details of the prosthesis are described, including the determination of performance specifications, the layout of the actuation mechanism, and the calculation of the torque capacity. Through the authors’ design calculation, the prosthesis is able to provide sufficient range of motion and torque capacity to support the locomotion of a 75 kg individual. The controller design is also described, including the underlying biomechanical analysis and the formulation of the finite-state impedance controller. Finally, the human subject testing results are presented, with the data indicating that the prosthesis is able to generate a natural walking gait and sufficient power output for its amputee user. PMID:26146497

Monitoring Replication Protein A (RPA) dynamics in homologous recombination through site-specific incorporation of non-canonical amino acids

PubMed Central

Pokhrel, Nilisha; Origanti, Sofia; Davenport, Eric Parker; Gandhi, Disha; Kaniecki, Kyle; Mehl, Ryan A.; Greene, Eric C.; Dockendorff, Chris

2017-01-01

Abstract An essential coordinator of all DNA metabolic processes is Replication Protein A (RPA). RPA orchestrates these processes by binding to single-stranded DNA (ssDNA) and interacting with several other DNA binding proteins. Determining the real-time kinetics of single players such as RPA in the presence of multiple DNA processors to better understand the associated mechanistic events is technically challenging. To overcome this hurdle, we utilized non-canonical amino acids and bio-orthogonal chemistry to site-specifically incorporate a chemical fluorophore onto a single subunit of heterotrimeric RPA. Upon binding to ssDNA, this fluorescent RPA (RPAf) generates a quantifiable change in fluorescence, thus serving as a reporter of its dynamics on DNA in the presence of multiple other DNA binding proteins. Using RPAf, we describe the kinetics of facilitated self-exchange and exchange by Rad51 and mediator proteins during various stages in homologous recombination. RPAf is widely applicable to investigate its mechanism of action in processes such as DNA replication, repair and telomere maintenance. PMID:28934470

Distributed controller clustering in software defined networks

PubMed Central

Gani, Abdullah; Akhunzada, Adnan; Talebian, Hamid; Choo, Kim-Kwang Raymond

2017-01-01

Software Defined Networking (SDN) is an emerging promising paradigm for network management because of its centralized network intelligence. However, the centralized control architecture of the software-defined networks (SDNs) brings novel challenges of reliability, scalability, fault tolerance and interoperability. In this paper, we proposed a novel clustered distributed controller architecture in the real setting of SDNs. The distributed cluster implementation comprises of multiple popular SDN controllers. The proposed mechanism is evaluated using a real world network topology running on top of an emulated SDN environment. The result shows that the proposed distributed controller clustering mechanism is able to significantly reduce the average latency from 8.1% to 1.6%, the packet loss from 5.22% to 4.15%, compared to distributed controller without clustering running on HP Virtual Application Network (VAN) SDN and Open Network Operating System (ONOS) controllers respectively. Moreover, proposed method also shows reasonable CPU utilization results. Furthermore, the proposed mechanism makes possible to handle unexpected load fluctuations while maintaining a continuous network operation, even when there is a controller failure. The paper is a potential contribution stepping towards addressing the issues of reliability, scalability, fault tolerance, and inter-operability. PMID:28384312

Immunotherapeutics in Pediatric Autoimmune Central Nervous System Disease: Agents and Mechanisms.

PubMed

Nosadini, Margherita; Sartori, Stefano; Sharma, Suvasini; Dale, Russell C

2017-08-01

Beyond the major advances produced by careful clinical-radiological phenotyping and biomarker development in autoimmune central nervous system disorders, a comprehensive knowledge of the range of available immune therapies and a deeper understanding of their action should benefit therapeutic decision-making. This review discusses the agents used in neuroimmunology and their mechanisms of action. First-line treatments typically include corticosteroids, intravenous immunoglobulin, and plasmapheresis, while for severe disease second-line "induction" agents such as rituximab or cyclophosphamide are used. Steroid-sparing agents such as mycophenolate, azathioprine, or methotrexate are often used in potentially relapsing or corticosteroid-dependent diseases. Lessons from adult neuroimmunology and rheumatology could be translated into pediatric autoimmune central nervous system disease in the future, including the potential utility of monoclonal antibodies targeting lymphocytes, adhesion molecules for lymphocytic migration, cytokines or their receptors, or complement. Finally, many agents used in other fields have multiple mechanisms of action, including immunomodulation, with potential usefulness in neuroimmunology, such as antibiotics, psychotropic drugs, probiotics, gut health, and ketogenic diet. All currently accepted and future potential agents have adverse effects, which can be severe; therefore, a "risk-versus-benefit" determination should guide therapeutic decision-making. Copyright © 2017 Elsevier Inc. All rights reserved.

The Rho GTPase effector ROCK regulates cyclin A, cyclin D1, and p27Kip1 levels by distinct mechanisms.

PubMed

Croft, Daniel R; Olson, Michael F

2006-06-01

The members of the Rho GTPase family are well known for their regulation of actin cytoskeletal structures. In addition, they influence progression through the cell cycle. The RhoA and RhoC proteins regulate numerous effector proteins, with a central and vital signaling role mediated by the ROCK I and ROCK II serine/threonine kinases. The requirement for ROCK function in the proliferation of numerous cell types has been revealed by studies utilizing ROCK-selective inhibitors such as Y-27632. However, the mechanisms by which ROCK signaling promotes cell cycle progression have not been thoroughly characterized. Using a conditionally activated ROCK-estrogen receptor fusion protein, we found that ROCK activation is sufficient to stimulate G1/S cell cycle progression in NIH 3T3 mouse fibroblasts. Further analysis revealed that ROCK acts via independent pathways to alter the levels of cell cycle regulatory proteins: cyclin D1 and p21(Cip1) elevation via Ras and the mitogen-activated protein kinase pathway, increased cyclin A via LIM kinase 2, and reduction of p27(Kip1) protein levels. Therefore, the influence of ROCK on cell cycle regulatory proteins occurs by multiple independent mechanisms.

A Mutator Phenotype Promoting the Emergence of Spontaneous Oxidative Stress-Resistant Mutants in Campylobacter jejuni.

PubMed

Dai, Lei; Sahin, Orhan; Tang, Yizhi; Zhang, Qijing

2017-12-15

Campylobacter jejuni is a leading cause of foodborne illnesses worldwide. As a microaerophilic organism, C. jejuni must be able to defend against oxidative stress encountered both in the host and in the environment. How Campylobacter utilizes a mutation-based mechanism for adaptation to oxidative stress is still unknown. Here we present a previously undescribed phenotypic and genetic mechanism that promotes the emergence of oxidative stress-resistant mutants. Specifically, we showed that a naturally occurring mutator phenotype, resulting from a loss of function mutation in the DNA repair enzyme MutY, increased oxidative stress resistance (OX R ) in C. jejuni We further demonstrated that MutY malfunction did not directly contribute to the OX R phenotype but increased the spontaneous mutation rate in the peroxide regulator gene perR , which functions as a repressor for multiple genes involved in oxidative stress resistance. Mutations in PerR resulted in loss of its DNA binding function and derepression of PerR-controlled oxidative stress defense genes, thereby conferring an OX R phenotype and facilitating Campylobacter survival under oxidative stress. These findings reveal a new mechanism that promotes the emergence of spontaneous OX R mutants in bacterial organisms. IMPORTANCE Although a mutator phenotype has been shown to promote antibiotic resistance in many bacterial species, little is known about its contribution to the emergence of OX R mutants. This work describes the link between a mutator phenotype and the enhanced emergence of OX R mutants as well as its underlying mechanism involving DNA repair and mutations in PerR. Since DNA repair systems and PerR are well conserved in many bacterial species, especially in Gram positives, the same mechanism may operate in multiple bacterial species. Additionally, we developed a novel method that allows for rapid quantification of spontaneous OX R mutants in a bacterial population. This method represents a technical innovation and may also be applied to other bacterial species. These findings significantly advance our understanding of bacterial mechanisms for survival under oxidative stress. Copyright © 2017 American Society for Microbiology.

Experimental study and numerical simulation on the structural and mechanical properties of Typha leaves through multimodal microscopy approaches.

PubMed

Liu, Jingjing; Zhang, Zhihui; Yu, Zhenglei; Liang, Yunhong; Li, Xiujuan; Ren, Luquan

2018-01-01

The Typha leaf, with special multi-level structure, low density and excellent mechanical properties, is an ideal bionic prototype utilized for lightweight design. In order to further study the relationship between the structure and mechanical properties, the three-dimensional macroscopic morphology of Typha leaves was characterized by micro computed tomography (Micro-CT) and its internal microstructure was observed by scanning electron microscopy (SEM). The combination of experimental and computational research was carried out in this paper, to reveal and verify the effect of multi-level structure on the mechanical properties. A universal testing machine and a self-developed mechanical testing apparatus with high precision and low load were used to measure the mechanical properties of the axial compression and lateral bending of the leaves, respectively. Three models with different internal structures were established based on the above-mentioned three-dimensional morphologies. The result demonstrated that the structure of partitions and diaphragms within the Typha leaf could form a reinforcement ribs structure which could provide multiple load paths and make the process of compression and bending difficult. The further nonlinear finite element analysis through LS-DYNA proved that internal structure could improve the ability of the models to resist compression and deformation. The investigation can be the reference for lightweight thin-walled structure design and inspire the application of the bionic structural materials. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mechanics of oriented electrospun nanofibrous scaffolds for annulus fibrosus tissue engineering.

PubMed

Nerurkar, Nandan L; Elliott, Dawn M; Mauck, Robert L

2007-08-01

Engineering a functional replacement for the annulus fibrosus (AF) of the intervertebral disc is contingent upon recapitulation of AF structure, composition, and mechanical properties. In this study, we propose a new paradigm for AF tissue engineering that focuses on the reconstitution of anatomic fiber architecture and uses constitutive modeling to evaluate construct function. A modified electrospinning technique was utilized to generate aligned nanofibrous polymer scaffolds for engineering the basic functional unit of the AF, a single lamella. Scaffolds were tested in uniaxial tension at multiple fiber orientations, demonstrating a nonlinear dependence of modulus on fiber angle that mimicked the nonlinearity and anisotropy of native AF. A homogenization model previously applied to native AF successfully described scaffold mechanical response, and parametric studies demonstrated that nonfibrillar matrix, along with fiber connectivity, are key contributors to tensile mechanics for engineered AF. We demonstrated that AF cells orient themselves along the aligned scaffolds and deposit matrix that contributes to construct mechanics under loading conditions relevant to the in vivo environment. The homogenization model was applied to cell-seeded constructs and provided quantitative measures for the evolution of matrix and interfibrillar interactions. Finally, the model demonstrated that at fiber angles of the AF (28 degrees -44 degrees ), engineered material behaved much like native tissue, suggesting that engineered constructs replicate the physiologic behavior of the single AF lamella. Constitutive modeling provides a powerful tool for analysis of engineered AF neo-tissue and native AF tissue alike, highlighting key mechanical design criteria for functional AF tissue engineering.

Persistent inflammation, immunosuppression, and catabolism and the development of chronic critical illness after surgery.

PubMed

Efron, Philip A; Mohr, Alicia M; Bihorac, Azra; Horiguchi, Hiroyuki; Hollen, McKenzie K; Segal, Mark S; Baker, Henry V; Leeuwenburgh, Christiaan; Moldawer, Lyle L; Moore, Frederick A; Brakenridge, Scott C

2018-05-25

As early as the 1990s, chronic critical illness, a distinct syndrome of persistent high-acuity illness requiring management in the ICU, was reported under a variety of descriptive terms including the "neuropathy of critical illness," "myopathy of critical illness," "ICU-acquired weakness," and most recently "post-intensive care unit syndrome." The widespread implementation of targeted shock resuscitation, improved organ support modalities, and evidence-based protocolized ICU care has resulted in significantly decreased in-hospital mortality within surgical ICUs, specifically by reducing early multiple organ failure deaths. However, a new phenotype of multiple organ failure has now emerged with persistent but manageable organ dysfunction, high resource utilization, and discharge to prolonged care facilities. This new multiple organ failure phenotype is now clinically associated with the rapidly increasing incidence of chronic critical illness in critically ill surgery patients. Although the underlying pathophysiology driving chronic critical illness remains incompletely described, the persistent inflammation, immunosuppression, and catabolism syndrome has been proposed as a mechanistic framework in which to explain the increased incidence of chronic critical illness in surgical ICUs. The purpose of this review is to provide a historic perspective of the epidemiologic evolution of multiple organ failure into persistent inflammation, immunosuppression, and catabolism syndrome; describe the mechanism that drives and sustains chronic critical illness, and review the long-term outcomes of surgical patients who develop chronic critical illness. Copyright © 2018 Elsevier Inc. All rights reserved.

Dtest Testing Software

NASA Technical Reports Server (NTRS)

Jain, Abhinandan; Cameron, Jonathan M.; Myint, Steven

2013-01-01

This software runs a suite of arbitrary software tests spanning various software languages and types of tests (unit level, system level, or file comparison tests). The dtest utility can be set to automate periodic testing of large suites of software, as well as running individual tests. It supports distributing multiple tests over multiple CPU cores, if available. The dtest tool is a utility program (written in Python) that scans through a directory (and its subdirectories) and finds all directories that match a certain pattern and then executes any tests in that directory as described in simple configuration files.

Gene discovery for enzymes involved in limonene modification or utilization by the mountain pine beetle-associated pathogen Grosmannia clavigera.

PubMed

Wang, Ye; Lim, Lynette; Madilao, Lina; Lah, Ljerka; Bohlmann, Joerg; Breuil, Colette

2014-08-01

To successfully colonize and eventually kill pine trees, Grosmannia clavigera (Gs cryptic species), the main fungal pathogen associated with the mountain pine beetle (Dendroctonus ponderosae), has developed multiple mechanisms to overcome host tree chemical defenses, of which terpenoids are a major component. In addition to a monoterpene efflux system mediated by a recently discovered ABC transporter, Gs has genes that are highly induced by monoterpenes and that encode enzymes that modify or utilize monoterpenes [especially (+)-limonene]. We showed that pine-inhabiting Ophiostomale fungi are tolerant to monoterpenes, but only a few, including Gs, are known to utilize monoterpenes as a carbon source. Gas chromatography-mass spectrometry (GC-MS) revealed that Gs can modify (+)-limonene through various oxygenation pathways, producing carvone, p-mentha-2,8-dienol, perillyl alcohol, and isopiperitenol. It can also degrade (+)-limonene through the C-1-oxygenated pathway, producing limonene-1,2-diol as the most abundant intermediate. Transcriptome sequencing (RNA-seq) data indicated that Gs may utilize limonene 1,2-diol through beta-oxidation and then valine and tricarboxylic acid (TCA) metabolic pathways. The data also suggested that at least two gene clusters, located in genome contigs 108 and 161, were highly induced by monoterpenes and may be involved in monoterpene degradation processes. Further, gene knockouts indicated that limonene degradation required two distinct Baeyer-Villiger monooxygenases (BVMOs), an epoxide hydrolase and an enoyl coenzyme A (enoyl-CoA) hydratase. Our work provides information on enzyme-mediated limonene utilization or modification and a more comprehensive understanding of the interaction between an economically important fungal pathogen and its host's defense chemicals.

Gene Discovery for Enzymes Involved in Limonene Modification or Utilization by the Mountain Pine Beetle-Associated Pathogen Grosmannia clavigera

PubMed Central

Wang, Ye; Lim, Lynette; Madilao, Lina; Lah, Ljerka; Bohlmann, Joerg

2014-01-01

To successfully colonize and eventually kill pine trees, Grosmannia clavigera (Gs cryptic species), the main fungal pathogen associated with the mountain pine beetle (Dendroctonus ponderosae), has developed multiple mechanisms to overcome host tree chemical defenses, of which terpenoids are a major component. In addition to a monoterpene efflux system mediated by a recently discovered ABC transporter, Gs has genes that are highly induced by monoterpenes and that encode enzymes that modify or utilize monoterpenes [especially (+)-limonene]. We showed that pine-inhabiting Ophiostomale fungi are tolerant to monoterpenes, but only a few, including Gs, are known to utilize monoterpenes as a carbon source. Gas chromatography-mass spectrometry (GC-MS) revealed that Gs can modify (+)-limonene through various oxygenation pathways, producing carvone, p-mentha-2,8-dienol, perillyl alcohol, and isopiperitenol. It can also degrade (+)-limonene through the C-1-oxygenated pathway, producing limonene-1,2-diol as the most abundant intermediate. Transcriptome sequencing (RNA-seq) data indicated that Gs may utilize limonene 1,2-diol through beta-oxidation and then valine and tricarboxylic acid (TCA) metabolic pathways. The data also suggested that at least two gene clusters, located in genome contigs 108 and 161, were highly induced by monoterpenes and may be involved in monoterpene degradation processes. Further, gene knockouts indicated that limonene degradation required two distinct Baeyer-Villiger monooxygenases (BVMOs), an epoxide hydrolase and an enoyl coenzyme A (enoyl-CoA) hydratase. Our work provides information on enzyme-mediated limonene utilization or modification and a more comprehensive understanding of the interaction between an economically important fungal pathogen and its host's defense chemicals. PMID:24837377

Binary variable multiple-model multiple imputation to address missing data mechanism uncertainty: Application to a smoking cessation trial

PubMed Central

Siddique, Juned; Harel, Ofer; Crespi, Catherine M.; Hedeker, Donald

2014-01-01

The true missing data mechanism is never known in practice. We present a method for generating multiple imputations for binary variables that formally incorporates missing data mechanism uncertainty. Imputations are generated from a distribution of imputation models rather than a single model, with the distribution reflecting subjective notions of missing data mechanism uncertainty. Parameter estimates and standard errors are obtained using rules for nested multiple imputation. Using simulation, we investigate the impact of missing data mechanism uncertainty on post-imputation inferences and show that incorporating this uncertainty can increase the coverage of parameter estimates. We apply our method to a longitudinal smoking cessation trial where nonignorably missing data were a concern. Our method provides a simple approach for formalizing subjective notions regarding nonresponse and can be implemented using existing imputation software. PMID:24634315

An application of the Aggregate Exposure Pathway (AEP) and Adverse Outcome Pathway (AOP) frameworks to mechanistically integrate data sources across multiple species into cumulative risk assessment (CRA)

EPA Science Inventory

Toxicologists use dose-response data from both in vivo and in vitro experiments to evaluate the effects of chemical contaminants on organisms. Cumulative risk assessments (CRAs) consider the effects of multiple stressors on multiple endpoints, and utilize environmental exposure ...

Examining Measurement Invariance and Differential Item Functioning with Discrete Latent Construct Indicators: A Note on a Multiple Testing Procedure

ERIC Educational Resources Information Center

Raykov, Tenko; Dimitrov, Dimiter M.; Marcoulides, George A.; Li, Tatyana; Menold, Natalja

2018-01-01

A latent variable modeling method for studying measurement invariance when evaluating latent constructs with multiple binary or binary scored items with no guessing is outlined. The approach extends the continuous indicator procedure described by Raykov and colleagues, utilizes similarly the false discovery rate approach to multiple testing, and…

Hierarchical representation of shapes in visual cortex—from localized features to figural shape segregation

PubMed Central

Tschechne, Stephan; Neumann, Heiko

2014-01-01

Visual structures in the environment are segmented into image regions and those combined to a representation of surfaces and prototypical objects. Such a perceptual organization is performed by complex neural mechanisms in the visual cortex of primates. Multiple mutually connected areas in the ventral cortical pathway receive visual input and extract local form features that are subsequently grouped into increasingly complex, more meaningful image elements. Such a distributed network of processing must be capable to make accessible highly articulated changes in shape boundary as well as very subtle curvature changes that contribute to the perception of an object. We propose a recurrent computational network architecture that utilizes hierarchical distributed representations of shape features to encode surface and object boundary over different scales of resolution. Our model makes use of neural mechanisms that model the processing capabilities of early and intermediate stages in visual cortex, namely areas V1–V4 and IT. We suggest that multiple specialized component representations interact by feedforward hierarchical processing that is combined with feedback signals driven by representations generated at higher stages. Based on this, global configurational as well as local information is made available to distinguish changes in the object's contour. Once the outline of a shape has been established, contextual contour configurations are used to assign border ownership directions and thus achieve segregation of figure and ground. The model, thus, proposes how separate mechanisms contribute to distributed hierarchical cortical shape representation and combine with processes of figure-ground segregation. Our model is probed with a selection of stimuli to illustrate processing results at different processing stages. We especially highlight how modulatory feedback connections contribute to the processing of visual input at various stages in the processing hierarchy. PMID:25157228

Hydrogen peroxide priming modulates abiotic oxidative stress tolerance: insights from ROS detoxification and scavenging

PubMed Central

Hossain, Mohammad A.; Bhattacharjee, Soumen; Armin, Saed-Moucheshi; Qian, Pingping; Xin, Wang; Li, Hong-Yu; Burritt, David J.; Fujita, Masayuki; Tran, Lam-Son P.

2015-01-01

Plants are constantly challenged by various abiotic stresses that negatively affect growth and productivity worldwide. During the course of their evolution, plants have developed sophisticated mechanisms to recognize external signals allowing them to respond appropriately to environmental conditions, although the degree of adjustability or tolerance to specific stresses differs from species to species. Overproduction of reactive oxygen species (ROS; hydrogen peroxide, H2O2; superoxide, O2⋅-; hydroxyl radical, OH⋅ and singlet oxygen, 1O2) is enhanced under abiotic and/or biotic stresses, which can cause oxidative damage to plant macromolecules and cell structures, leading to inhibition of plant growth and development, or to death. Among the various ROS, freely diffusible and relatively long-lived H2O2 acts as a central player in stress signal transduction pathways. These pathways can then activate multiple acclamatory responses that reinforce resistance to various abiotic and biotic stressors. To utilize H2O2 as a signaling molecule, non-toxic levels must be maintained in a delicate balancing act between H2O2 production and scavenging. Several recent studies have demonstrated that the H2O2-priming can enhance abiotic stress tolerance by modulating ROS detoxification and by regulating multiple stress-responsive pathways and gene expression. Despite the importance of the H2O2-priming, little is known about how this process improves the tolerance of plants to stress. Understanding the mechanisms of H2O2-priming-induced abiotic stress tolerance will be valuable for identifying biotechnological strategies to improve abiotic stress tolerance in crop plants. This review is an overview of our current knowledge of the possible mechanisms associated with H2O2-induced abiotic oxidative stress tolerance in plants, with special reference to antioxidant metabolism. PMID:26136756

Mechanism of chimera formation during the Multiple Displacement Amplification reaction.

PubMed

Lasken, Roger S; Stockwell, Timothy B

2007-04-12

Multiple Displacement Amplification (MDA) is a method used for amplifying limiting DNA sources. The high molecular weight amplified DNA is ideal for DNA library construction. While this has enabled genomic sequencing from one or a few cells of unculturable microorganisms, the process is complicated by the tendency of MDA to generate chimeric DNA rearrangements in the amplified DNA. Determining the source of the DNA rearrangements would be an important step towards reducing or eliminating them. Here, we characterize the major types of chimeras formed by carrying out an MDA whole genome amplification from a single E. coli cell and sequencing by the 454 Life Sciences method. Analysis of 475 chimeras revealed the predominant reaction mechanisms that create the DNA rearrangements. The highly branched DNA synthesized in MDA can assume many alternative secondary structures. DNA strands extended on an initial template can be displaced becoming available to prime on a second template creating the chimeras. Evidence supports a model in which branch migration can displace 3'-ends freeing them to prime on the new templates. More than 85% of the resulting DNA rearrangements were inverted sequences with intervening deletions that the model predicts. Intramolecular rearrangements were favored, with displaced 3'-ends reannealing to single stranded 5'-strands contained within the same branched DNA molecule. In over 70% of the chimeric junctions, the 3' termini had initiated priming at complimentary sequences of 2-21 nucleotides (nts) in the new templates. Formation of chimeras is an important limitation to the MDA method, particularly for whole genome sequencing. Identification of the mechanism for chimera formation provides new insight into the MDA reaction and suggests methods to reduce chimeras. The 454 sequencing approach used here will provide a rapid method to assess the utility of reaction modifications.

Hierarchical representation of shapes in visual cortex-from localized features to figural shape segregation.

PubMed

Tschechne, Stephan; Neumann, Heiko

2014-01-01

Visual structures in the environment are segmented into image regions and those combined to a representation of surfaces and prototypical objects. Such a perceptual organization is performed by complex neural mechanisms in the visual cortex of primates. Multiple mutually connected areas in the ventral cortical pathway receive visual input and extract local form features that are subsequently grouped into increasingly complex, more meaningful image elements. Such a distributed network of processing must be capable to make accessible highly articulated changes in shape boundary as well as very subtle curvature changes that contribute to the perception of an object. We propose a recurrent computational network architecture that utilizes hierarchical distributed representations of shape features to encode surface and object boundary over different scales of resolution. Our model makes use of neural mechanisms that model the processing capabilities of early and intermediate stages in visual cortex, namely areas V1-V4 and IT. We suggest that multiple specialized component representations interact by feedforward hierarchical processing that is combined with feedback signals driven by representations generated at higher stages. Based on this, global configurational as well as local information is made available to distinguish changes in the object's contour. Once the outline of a shape has been established, contextual contour configurations are used to assign border ownership directions and thus achieve segregation of figure and ground. The model, thus, proposes how separate mechanisms contribute to distributed hierarchical cortical shape representation and combine with processes of figure-ground segregation. Our model is probed with a selection of stimuli to illustrate processing results at different processing stages. We especially highlight how modulatory feedback connections contribute to the processing of visual input at various stages in the processing hierarchy.

Improved design of hammerhead ribozyme for selective digestion of target RNA through recognition of site-specific adenosine-to-inosine RNA editing

PubMed Central

Fukuda, Masatora; Kurihara, Kei; Yamaguchi, Shota; Oyama, Yui; Deshimaru, Masanobu

2014-01-01

Adenosine-to-inosine (A-to-I) RNA editing is an endogenous regulatory mechanism involved in various biological processes. Site-specific, editing-state–dependent degradation of target RNA may be a powerful tool both for analyzing the mechanism of RNA editing and for regulating biological processes. Previously, we designed an artificial hammerhead ribozyme (HHR) for selective, site-specific RNA cleavage dependent on the A-to-I RNA editing state. In the present work, we developed an improved strategy for constructing a trans-acting HHR that specifically cleaves target editing sites in the adenosine but not the inosine state. Specificity for unedited sites was achieved by utilizing a sequence encoding the intrinsic cleavage specificity of a natural HHR. We used in vitro selection methods in an HHR library to select for an extended HHR containing a tertiary stabilization motif that facilitates HHR folding into an active conformation. By using this method, we successfully constructed highly active HHRs with unedited-specific cleavage. Moreover, using HHR cleavage followed by direct sequencing, we demonstrated that this ribozyme could cleave serotonin 2C receptor (HTR2C) mRNA extracted from mouse brain, depending on the site-specific editing state. This unedited-specific cleavage also enabled us to analyze the effect of editing state at the E and C sites on editing at other sites by using direct sequencing for the simultaneous quantification of the editing ratio at multiple sites. Our approach has the potential to elucidate the mechanism underlying the interdependencies of different editing states in substrate RNA with multiple editing sites. PMID:24448449

Mechanism of chimera formation during the Multiple Displacement Amplification reaction

PubMed Central

Lasken, Roger S; Stockwell, Timothy B

2007-01-01

Background Multiple Displacement Amplification (MDA) is a method used for amplifying limiting DNA sources. The high molecular weight amplified DNA is ideal for DNA library construction. While this has enabled genomic sequencing from one or a few cells of unculturable microorganisms, the process is complicated by the tendency of MDA to generate chimeric DNA rearrangements in the amplified DNA. Determining the source of the DNA rearrangements would be an important step towards reducing or eliminating them. Results Here, we characterize the major types of chimeras formed by carrying out an MDA whole genome amplification from a single E. coli cell and sequencing by the 454 Life Sciences method. Analysis of 475 chimeras revealed the predominant reaction mechanisms that create the DNA rearrangements. The highly branched DNA synthesized in MDA can assume many alternative secondary structures. DNA strands extended on an initial template can be displaced becoming available to prime on a second template creating the chimeras. Evidence supports a model in which branch migration can displace 3'-ends freeing them to prime on the new templates. More than 85% of the resulting DNA rearrangements were inverted sequences with intervening deletions that the model predicts. Intramolecular rearrangements were favored, with displaced 3'-ends reannealing to single stranded 5'-strands contained within the same branched DNA molecule. In over 70% of the chimeric junctions, the 3' termini had initiated priming at complimentary sequences of 2–21 nucleotides (nts) in the new templates. Conclusion Formation of chimeras is an important limitation to the MDA method, particularly for whole genome sequencing. Identification of the mechanism for chimera formation provides new insight into the MDA reaction and suggests methods to reduce chimeras. The 454 sequencing approach used here will provide a rapid method to assess the utility of reaction modifications. PMID:17430586

Magnetic resonance imaging correlates of bee sting induced multiple organ dysfunction syndrome: A case report.

PubMed

Das, Sushant K; Zeng, Li-Chuan; Li, Bing; Niu, Xiang-Ke; Wang, Jing-Liang; Bhetuwal, Anup; Yang, Han-Feng

2014-09-28

Occasionally systemic complications with high risk of death, such as multiple organ dysfunction syndrome (MODS), can occur following multiple bee stings. This case study reports a patient who presented with MODS, i.e., acute kidney injury, hepatic and cardiac dysfunction, after multiple bee stings. The standard clinical findings were then correlated with magnetic resonance imaging (MRI) findings, which demonstrates that MRI may be utilized as a simpler tool to use than other multiple diagnostics.

M-OSCE as a method to measure dental hygiene students' critical thinking: a pilot study.

PubMed

McComas, Martha J; Wright, Rebecca A; Mann, Nancy K; Cooper, Mary D; Jacks, Mary E

2013-04-01

Educators in all academic disciplines have been encouraged to utilize assessment strategies to evaluate students' critical thinking. The purpose of this study was to assess the viability of the modified objective structured clinical examination (m-OSCE) to evaluate critical thinking in dental hygiene education. This evaluation utilized a convenience sample of senior dental hygiene students. Students participated in the m-OSCE in which portions of a patient case were revealed at four stations. The exam consisted of multiple-choice questions intended to measure students' ability to utilize critical thinking skills. Additionally, there was one fill-in-the-blank question and a treatment plan that was completed at the fifth station. The results of this study revealed that the m-OSCE did not reliably measure dental hygiene students' critical thinking. Statistical analysis found no satisfactory reliability within the multiple-choice questions and moderately reliable results within the treatment planning portion of the examination. In addition, the item analysis found gaps in students' abilities to transfer clinical evidence/data to basic biomedical knowledge as demonstrated through the multiple-choice questioning results. This outcome warrants further investigation of the utility of the m-OSCE, with a focus on modifications to the evaluation questions, grading rubric, and patient case.

The relationship between motivation, monetary compensation, and data quality among US- and India-based workers on Mechanical Turk.

PubMed

Litman, Leib; Robinson, Jonathan; Rosenzweig, Cheskie

2015-06-01

In this study, we examined data quality among Amazon Mechanical Turk (MTurk) workers based in India, and the effect of monetary compensation on their data quality. Recent studies have shown that work quality is independent of compensation rates, and that compensation primarily affects the quantity but not the quality of work. However, the results of these studies were generally based on compensation rates below the minimum wage, and far below a level that was likely to play a practical role in the lives of workers. In this study, compensation rates were set around the minimum wage in India. To examine data quality, we developed the squared discrepancy procedure, which is a task-based quality assurance approach for survey tasks whose goal is to identify inattentive participants. We showed that data quality is directly affected by compensation rates for India-based participants. We also found that data were of a lesser quality among India-based than among US participants, even when optimal payment strategies were utilized. We additionally showed that the motivation of MTurk users has shifted, and that monetary compensation is now reported to be the primary reason for working on MTurk, among both US- and India-based workers. Overall, MTurk is a constantly evolving marketplace where multiple factors can contribute to data quality. High-quality survey data can be acquired on MTurk among India-based participants when an appropriate pay rate is provided and task-specific quality assurance procedures are utilized.

Surfactant Therapy of ALI and ARDS

PubMed Central

Raghavendran, K; Willson, D; Notter, RH

2011-01-01

This article examines exogenous lung surfactant replacement therapy and its utility in mitigating clinical acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS). Biophysical research has documented that lung surfactant dysfunction can be reversed or mitigated by increasing surfactant concentration, and multiple studies in animals with ALI/ARDS have shown that respiratory function and pulmonary mechanics in vivo can be improved by exogenous surfactant administration. Exogenous surfactant therapy is a routine intervention in neonatal intensive care, and is life-saving in preventing or treating the neonatal respiratory distress syndrome (NRDS) in premature infants. In applications relevant for lung injury-related respiratory failure and ALI/ARDS, surfactant therapy has been shown to be beneficial in term infants with pneumonia and meconium aspiration lung injury, and in children up to age 21 with direct pulmonary forms of ALI/ARDS. However, extension of exogenous surfactant therapy to adults with respiratory failure and clinical ALI/ARDS remains a challenge. Coverage here reviews clinical studies of surfactant therapy in pediatric and adult patients with ALI/ARDS, particularly focusing on its potential advantages in patients with direct pulmonary forms of these syndromes. Also discussed is the rationale for mechanism-based therapies utilizing exogenous surfactant in combination with agents targeting other aspects of the multifaceted pathophysiology of inflammatory lung injury. Additional factors affecting the efficacy of exogenous surfactant therapy in ALI/ARDS are also described, including the difficulty of effectively delivering surfactants to injured lungs and the existence of activity differences between clinical surfactant drugs. PMID:21742216

Glycosides from Medicinal Plants as Potential Anticancer Agents: Emerging Trends towards Future Drugs.

PubMed

Khan, Haroon; Saeedi, Mina; Nabavi, Seyed Mohammad; Mubarak, Mohammad S; Bishayee, Anupam

2018-04-03

Cancer continues to be a global burden, despite the advancement of various technological and pharmaceutical improvements over the past two decades. Methods for treating cancer include surgery, radiotherapy and chemotherapy in addition to other specialized techniques. On the other hand, medicinal plants have been traditionally employed either as the complementary medicine or dietary agents in the treatment and management of cancer. Medicinal plants are a rich source of secondary metabolites with interesting biological and pharmacological activities. Among these metabolites, glycosides are naturally occurring substances and have outstanding therapeutic potential and clinical utility. Different medical research engines such GoogleScholar, PubMed, SpringerLink, ScienceDirect were used to collect related literature on the subject matter. In this regard, only peer reviewed journals were considered. Emerging results showed that numerous glycosides isolated from various plants possessed marked anticancer activity against a variety of cancer cell lines. Accordingly, the aim of the present review is to shed light on the anticancer effects of glycosides, analyze possible mechanisms of action, and highlight the role of these natural agents as complementary and alternative medicine in combating and managing cancer. The glycosides isolated from different plants demonstrated potent cytotoxic effects against various cancer cell lines in initial preclinical studies. The anticancer effect was mediated through multiple mechanisms; however further detail studies are needed to understand the full potential of glycosides for clinical utility. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Citrate-based fluorescent materials for low-cost chloride sensing in the diagnosis of Cystic Fibrosis.

PubMed

Kim, Jimin P; Xie, Zhiwei; Creer, Michael; Liu, Zhiwen; Yang, Jian

2017-01-01

Chloride is an essential electrolyte that maintains homeostasis within the body, where abnormal chloride levels in biological fluids may indicate various diseases such as Cystic Fibrosis. However, current analytical solutions for chloride detection fail to meet the clinical needs of both high performance and low material or labor costs, hindering translation into clinical settings. Here we present a new class of fluorescence chloride sensors derived from a facile citrate -based synthesis platform that utilize dynamic quenching mechanisms. Based on this low-cost platform, we demonstrate for the first time a selective sensing strategy that uses a single fluorophore to detect multiple halides simultaneously, promising both selectivity and automation to improve performance and reduce labor costs. We also demonstrate the clinical utility of citrate-based sensors as a new sweat chloride test method for the diagnosis of Cystic Fibrosis by performing analytical validation with sweat controls and clinical validation with sweat from individuals with or without Cystic Fibrosis. Lastly, molecular modeling studies reveal the structural mechanism behind chloride sensing, serving to expand this class of fluorescence sensors with improved chloride sensitivities. Thus citrate-based fluorescent materials may enable low-cost, automated multi-analysis systems for simpler, yet accurate, point-of-care diagnostics that can be readily translated into clinical settings. More broadly, a wide range of medical, industrial, and environmental applications can be achieved with such a facile synthesis platform, demonstrated in our citrate-based biodegradable polymers with intrinsic fluorescence sensing.

Multiple-stripe lithiation mechanism of individual SnO2 nanowires in a flooding geometry

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

Zhong, Li; Liu, Xiao H.; Wang, G. F.

2011-06-17

The atomic scale lithiation mechanism of individual SnO2 nanowires in a flooding geometry with the entire wires being immersed in the electrolyte was revealed by in-situ transmission electron microscopy. The lithiation initiated multiple stripes with width of a few nanometer parallel to {020} planes transversing the entire wires, serving as multiple reaction fronts for late stage of lithiation. Inside the stripes, we identified high density of dislocations and enlarged inter-planar spacing, which provide effective path for lithium ion transport. The density of the stripes increased with further lithiation, and eventually they merged with one another, causing a large enlongation andmore » volume expansion and the crystalline to amorphous phase transformation. This multiple stripes and multiple reaction fronts lithiation mechanism is unexpected and differs completely from the expected core-shell lithiation mechanism.« less

One-year trajectories of care and resource utilization for recipients of prolonged mechanical ventilation: a cohort study.

PubMed

Unroe, Mark; Kahn, Jeremy M; Carson, Shannon S; Govert, Joseph A; Martinu, Tereza; Sathy, Shailaja J; Clay, Alison S; Chia, Jessica; Gray, Alice; Tulsky, James A; Cox, Christopher E

2010-08-03

Growing numbers of critically ill patients receive prolonged mechanical ventilation. Little is known about the patterns of care as patients transition from acute care hospitals to postacute care facilities or about the associated resource utilization. To describe 1-year trajectories of care and resource utilization for patients receiving prolonged mechanical ventilation. 1-year prospective cohort study. 5 intensive care units at Duke University Medical Center, Durham, North Carolina. 126 patients receiving prolonged mechanical ventilation (defined as ventilation for >or=4 days with tracheostomy placement or ventilation for >or=21 days without tracheostomy), as well as their 126 surrogates and 54 intensive care unit physicians, enrolled consecutively over 1 year. Patients and surrogates were interviewed in the hospital, as well as 3 and 12 months after discharge, to determine patient survival, functional status, and facility type and duration of postdischarge care. Physicians were interviewed in the hospital to elicit prognoses. Institutional billing records were used to assign costs for acute care, outpatient care, and interfacility transportation. Medicare claims data were used to assign costs for postacute care. 103 (82%) hospital survivors had 457 separate transitions in postdischarge care location (median, 4 transitions [interquartile range, 3 to 5 transitions]), including 68 patients (67%) who were readmitted at least once. Patients spent an average of 74% (95% CI, 68% to 80%) of all days alive in a hospital or postacute care facility or receiving home health care. At 1 year, 11 patients (9%) had a good outcome (alive with no functional dependency), 33 (26%) had a fair outcome (alive with moderate dependency), and 82 (65%) had a poor outcome (either alive with complete functional dependency [4 patients; 21%] or dead [56 patients; 44%]). Patients with poor outcomes were older, had more comorbid conditions, and were more frequently discharged to a postacute care facility than patients with either fair or good outcomes (P < 0.05 for all). The mean cost per patient was $306,135 (SD, $285,467), and total cohort cost was $38.1 million, for an estimated $3.5 million per independently functioning survivor at 1 year. The results of this single-center study may not be applicable to other centers. Patients receiving prolonged mechanical ventilation have multiple transitions of care, resulting in substantial health care costs and persistent, profound disability. The optimism of surrogate decision makers should be balanced by discussions of these outcomes when considering a course of prolonged life support. None.

Integrating Multiple Social Statuses in Health Disparities Research: The Case of Lung Cancer

PubMed Central

Williams, David R; Kontos, Emily Z; Viswanath, K; Haas, Jennifer S; Lathan, Christopher S; MacConaill, Laura E; Chen, Jarvis; Ayanian, John Z

2012-01-01

Objective To illustrate the complex patterns that emerge when race/ethnicity, socioeconomic status (SES), and gender are considered simultaneously in health care disparities research and to outline the needed research to understand them by using disparities in lung cancer risks, treatment, and outcomes as an example. Principal Findings SES, gender, and race/ethnicity are social categories that are robust predictors of variations in health and health services utilization. These are usually considered separately, but intersectionality theory indicates that the impact of each depends on the others. Each reflects historically and culturally contingent variations in social, economic, and political status. Distinct patterns of risk and resilience emerge at the intersections of multiple social categories and shape the experience of health, health care access, utilization, quality, and outcomes where these categories intersect. Intersectional approaches call for greater attention to understand social processes at multiple levels of society and require the collection of relevant data and utilization of appropriate analytic approaches to understand how multiple risk factors and resources combine to affect the distribution of disease and its management. Conclusions Understanding how race/ethnicity, gender, and SES are interactive, interdependent, and social identities can provide new knowledge to enhance our efforts to effectively address health disparities. PMID:22568674

Students' Difficulties With Multiple Representations in Introductory Mechanics

ERIC Educational Resources Information Center

Nguyen, Dong-Hai; Rebello, N. Sanjay

2011-01-01

Research in physics education indicates that the use of multiple representations in teaching and learning helps students become better problem-solvers. We report on a study to investigate students' difficulties in solving mechanics problems presented in multiple representations. We conducted teaching/learning interviews with 20 students in a…

Disconnection as a Mechanism for Cognitive Dysfunction in Multiple Sclerosis

ERIC Educational Resources Information Center

Dineen, R. A.; Vilisaar, J.; Hlinka, J.; Bradshaw, C. M.; Morgan, P. S.; Constantinescu, C. S.; Auer, D. P.

2009-01-01

Disconnection of cognitively important processing regions by injury to the interconnecting white matter provides a potential mechanism for cognitive dysfunction in multiple sclerosis. The contribution of tract-specific white matter injury to dysfunction in different cognitive domains in patients with multiple sclerosis has not previously been…

Parallelizing ATLAS Reconstruction and Simulation: Issues and Optimization Solutions for Scaling on Multi- and Many-CPU Platforms

NASA Astrophysics Data System (ADS)

Leggett, C.; Binet, S.; Jackson, K.; Levinthal, D.; Tatarkhanov, M.; Yao, Y.

2011-12-01

Thermal limitations have forced CPU manufacturers to shift from simply increasing clock speeds to improve processor performance, to producing chip designs with multi- and many-core architectures. Further the cores themselves can run multiple threads as a zero overhead context switch allowing low level resource sharing (Intel Hyperthreading). To maximize bandwidth and minimize memory latency, memory access has become non uniform (NUMA). As manufacturers add more cores to each chip, a careful understanding of the underlying architecture is required in order to fully utilize the available resources. We present AthenaMP and the Atlas event loop manager, the driver of the simulation and reconstruction engines, which have been rewritten to make use of multiple cores, by means of event based parallelism, and final stage I/O synchronization. However, initial studies on 8 andl6 core Intel architectures have shown marked non-linearities as parallel process counts increase, with as much as 30% reductions in event throughput in some scenarios. Since the Intel Nehalem architecture (both Gainestown and Westmere) will be the most common choice for the next round of hardware procurements, an understanding of these scaling issues is essential. Using hardware based event counters and Intel's Performance Tuning Utility, we have studied the performance bottlenecks at the hardware level, and discovered optimization schemes to maximize processor throughput. We have also produced optimization mechanisms, common to all large experiments, that address the extreme nature of today's HEP code, which due to it's size, places huge burdens on the memory infrastructure of today's processors.

Longitudinal associations of hypersomnolence and depression in the Wisconsin Sleep Cohort Study.

PubMed

Plante, David T; Finn, Laurel A; Hagen, Erika W; Mignot, Emmanuel; Peppard, Paul E

2017-01-01

Hypersomnolence is common in depression, however longitudinal associations of excessive daytime sleepiness (EDS), long habitual sleep duration, and objective sleep propensity with depressive symptomatology are not well established. Data from adults participating in the Wisconsin Sleep Cohort Study who had multiple assessments at 4-year intervals were utilized in analyses. Conditional (intrasubject) logistic regression estimated the likelihood of development of depression and three primary hypersomnolence measures: subjective EDS [Epworth Sleepiness Scale (ESS) >10], habitual sleep duration ≥9h/day, and increased physiological sleep propensity [multiple sleep latency test (MSLT) mean sleep latency <8min]. After adjusting for all covariates, the odds for development of depression were significantly increased 1.67-fold (95% CI 1.02-2.73, p=0.04) in participants who also developed subjective EDS. However, development of increased physiological sleep propensity on the MSLT was associated with a trend towards reduced odds for development of depression (odds ratio 0.50, 95% CI 0.24-1.06, p=0.07). No significant longitudinal association between excessive sleep duration and depression was observed. Depression was not verified by psychiatric interview and an objective measure of sleep duration was not utilized. Our results demonstrate a significant longitudinal association between increased subjective EDS and depression. However, increased physiological sleep propensity on the MSLT was paradoxically marginally protective against the development of depression. Further research is indicated to determine the mechanism underling divergent effects of various aspects of hypersomnolence on the course of mood disorders. Copyright © 2016 Elsevier B.V. All rights reserved.

Lunar surface mining for automated acquisition of helium-3: Methods, processes, and equipment

NASA Technical Reports Server (NTRS)

Li, Y. T.; Wittenberg, L. J.

1992-01-01

In this paper, several techniques considered for mining and processing the regolith on the lunar surface are presented. These techniques have been proposed and evaluated based primarily on the following criteria: (1) mining operations should be relatively simple; (2) procedures of mineral processing should be few and relatively easy; (3) transferring tonnages of regolith on the Moon should be minimized; (4) operations outside the lunar base should be readily automated; (5) all equipment should be maintainable; and (6) economic benefit should be sufficient for commercial exploitation. The economic benefits are not addressed in this paper; however, the energy benefits have been estimated to be between 250 and 350 times the mining energy. A mobile mining scheme is proposed that meets most of the mining objectives. This concept uses a bucket-wheel excavator for excavating the regolith, several mechanical electrostatic separators for beneficiation of the regolith, a fast-moving fluidized bed reactor to heat the particles, and a palladium diffuser to separate H2 from the other solar wind gases. At the final stage of the miner, the regolith 'tailings' are deposited directly into the ditch behind the miner and cylinders of the valuable solar wind gases are transported to a central gas processing facility. During the production of He-3, large quantities of valuable H2, H2O, CO, CO2, and N2 are produced for utilization at the lunar base. For larger production of He-3 the utilization of multiple-miners is recommended rather than increasing their size. Multiple miners permit operations at more sites and provide redundancy in case of equipment failure.

Lunar surface mining for automated acquisition of helium-3: Methods, processes, and equipment

NASA Astrophysics Data System (ADS)

Li, Y. T.; Wittenberg, L. J.

1992-09-01

In this paper, several techniques considered for mining and processing the regolith on the lunar surface are presented. These techniques have been proposed and evaluated based primarily on the following criteria: (1) mining operations should be relatively simple; (2) procedures of mineral processing should be few and relatively easy; (3) transferring tonnages of regolith on the Moon should be minimized; (4) operations outside the lunar base should be readily automated; (5) all equipment should be maintainable; and (6) economic benefit should be sufficient for commercial exploitation. The economic benefits are not addressed in this paper; however, the energy benefits have been estimated to be between 250 and 350 times the mining energy. A mobile mining scheme is proposed that meets most of the mining objectives. This concept uses a bucket-wheel excavator for excavating the regolith, several mechanical electrostatic separators for beneficiation of the regolith, a fast-moving fluidized bed reactor to heat the particles, and a palladium diffuser to separate H2 from the other solar wind gases. At the final stage of the miner, the regolith 'tailings' are deposited directly into the ditch behind the miner and cylinders of the valuable solar wind gases are transported to a central gas processing facility. During the production of He-3, large quantities of valuable H2, H2O, CO, CO2, and N2 are produced for utilization at the lunar base. For larger production of He-3 the utilization of multiple-miners is recommended rather than increasing their size. Multiple miners permit operations at more sites and provide redundancy in case of equipment failure.

A stretchable and flexible system for skin-mounted measurement of motion tracking and physiological signals.

PubMed

Pinghung Wei; Raj, Milan; Yung-Yu Hsu; Morey, Briana; DePetrillo, Paolo; McGrane, Bryan; Xianyan Wang; Lin, Monica; Keen, Bryan; Papakyrikos, Cole; Lowe, Jared; Ghaffari, Roozbeh

2014-01-01

In this paper, we present a stretchable wearable system capable of i) measuring multiple physiological parameters and ii) transmitting data via radio frequency to a smart phone. The electrical architecture consists of ultra thin sensors (<; 20 μm thick) and a conformal network of associated active and passive electronics in a mesh-like geometry that can mechanically couple with the curvilinear surfaces of the human body. Spring-like metal interconnects between individual chips on board the device allow the system to accommodate strains approaching ~30% A representative example of a smart patch that measures movement and electromyography (EMG) signals highlights the utility of this new class of medical skin-mounted system in monitoring a broad range of neuromuscular and cardiovascular diseases.

The Roles of Glutamine in the Intestine and Its Implication in Intestinal Diseases

PubMed Central

Kim, Min-Hyun; Kim, Hyeyoung

2017-01-01

Glutamine, the most abundant free amino acid in the human body, is a major substrate utilized by intestinal cells. The roles of glutamine in intestinal physiology and management of multiple intestinal diseases have been reported. In gut physiology, glutamine promotes enterocyte proliferation, regulates tight junction proteins, suppresses pro-inflammatory signaling pathways, and protects cells against apoptosis and cellular stresses during normal and pathologic conditions. As glutamine stores are depleted during severe metabolic stress including trauma, sepsis, and inflammatory bowel diseases, glutamine supplementation has been examined in patients to improve their clinical outcomes. In this review, we discuss the physiological roles of glutamine for intestinal health and its underlying mechanisms. In addition, we discuss the current evidence for the efficacy of glutamine supplementation in intestinal diseases. PMID:28498331

Chewing the fat: lipid metabolism and homeostasis during M. tuberculosis infection.

PubMed

Lovewell, Rustin R; Sassetti, Christopher M; VanderVen, Brian C

2016-02-01

The interplay between Mycobacterium tuberculosis lipid metabolism, the immune response and lipid homeostasis in the host creates a complex and dynamic pathogen-host interaction. Advances in imaging and metabolic analysis techniques indicate that M. tuberculosis preferentially associates with foamy cells and employs multiple physiological systems to utilize exogenously derived fatty-acids and cholesterol. Moreover, novel insights into specific host pathways that control lipid accumulation during infection, such as the PPARγ and LXR transcriptional regulators, have begun to reveal mechanisms by which host immunity alters the bacterial micro-environment. As bacterial lipid metabolism and host lipid regulatory pathways are both important, yet inherently complex, components of active tuberculosis, delineating the heterogeneity in lipid trafficking within disease states remains a major challenge for therapeutic design. Copyright © 2015. Published by Elsevier Ltd.

Intersection of Stress, Social Disadvantage, and Life Course Processes: Reframing Trauma and Mental Health.

PubMed

Nurius, Paula S; Uehara, Edwina; Zatzick, Douglas F

2013-04-01

This paper describes the intersection of converging lines of research on the social structural, psychosocial, and physiological factors involved in the production of stress and implications for the field of mental health. Of particular interest are the stress sensitization consequences stemming from exposure to adversity over the life course. Contemporary stress sensitization theory provides important clinical utility in articulating mechanisms through which these multiple levels exert influence on mental health. Stress sensitization models (a) extend understanding of neurobiological and functional contexts within which extreme stressors operate and (b) make clear how these can influence psychologically traumatic outcomes. The value of interventions that are sensitive to current contexts as well as life course profiles of cumulative stress are illustrated through recent treatment innovations.

Recent advances in systemic therapy: Advances in systemic therapy for HER2-positive metastatic breast cancer.

PubMed

Morrow, Phuong Khanh H; Zambrana, Francisco; Esteva, Francisco J

2009-01-01

Human epidermal growth factor receptor (HER)2 over-expression is associated with a shortened disease-free interval and poor survival. Although the addition of trastuzumab to chemotherapy in the first-line setting has improved response rates, progression-free survival, and overall survival, response rates declined when trastuzumab was used beyond the first-line setting because of multiple mechanisms of resistance. Studies have demonstrated the clinical utility of continuing trastuzumab beyond progression, and further trials to explore this concept are ongoing. New tyrosine kinase inhibitors, monoclonal antibodies, PTEN (phosphatase and tensin homolog) pathway regulators, HER2 antibody-drug conjugates, and inhibitors of heat shock protein-90 are being evaluated to determine whether they may have a role to play in treating trastuzumab-resistant metastatic breast cancer.

Intersection of Stress, Social Disadvantage, and Life Course Processes: Reframing Trauma and Mental Health

PubMed Central

Nurius, Paula S.; Uehara, Edwina; Zatzick, Douglas F.

2015-01-01

This paper describes the intersection of converging lines of research on the social structural, psychosocial, and physiological factors involved in the production of stress and implications for the field of mental health. Of particular interest are the stress sensitization consequences stemming from exposure to adversity over the life course. Contemporary stress sensitization theory provides important clinical utility in articulating mechanisms through which these multiple levels exert influence on mental health. Stress sensitization models (a) extend understanding of neurobiological and functional contexts within which extreme stressors operate and (b) make clear how these can influence psychologically traumatic outcomes. The value of interventions that are sensitive to current contexts as well as life course profiles of cumulative stress are illustrated through recent treatment innovations. PMID:25729337

Cryogenic temperature control by means of energy storage materials. [for long space voyages

NASA Technical Reports Server (NTRS)

Grodzka, P. G.; Picklesimer, E. A.; Connor, L. E.

1977-01-01

An investigation was conducted to study the concept of thermal control by means of physical or chemical reaction heats for applications involving the storage of cryogens during long-term space voyages. The investigation included some preliminary experimental tests of energy storage material (ESM) effectiveness. The materials considered can store and liberate large amounts of thermal energy by means of mechanisms such as sensible heat, heat of fusion, and physical or chemical reaction heat. A differential thermal analysis was utilized in the laboratory tests. Attention is given to the evaluation of cryogenic ESM thermal control concepts, the experimental determination of phase change materials characteristics, and adsorption ESMs. It is found that an ESM shield surrounded by multiple layer insulation provides the best protection for a cryogen store.

Multiple gap photovoltaic device

DOEpatents

Dalal, Vikram L.

1981-01-01

A multiple gap photovoltaic device having a transparent electrical contact adjacent a first cell which in turn is adjacent a second cell on an opaque electrical contact, includes utilizing an amorphous semiconductor as the first cell and a crystalline semiconductor as the second cell.

WATER QUALITY IN SOURCE WATER, TREATMENT, AND DISTRIBUTION SYSTEMS

EPA Science Inventory

Most drinking water utilities practice the multiple-barrier concept as the guiding principle for providing safe water. This chapter discusses multiple barriers as they relate to the basic criteria for selecting and protecting source waters, including known and potential sources ...

Accommodations for Multiple Choice Tests

ERIC Educational Resources Information Center

Trammell, Jack

2011-01-01

Students with learning or learning-related disabilities frequently struggle with multiple choice assessments due to difficulty discriminating between items, filtering out distracters, and framing a mental best answer. This Practice Brief suggests accommodations and strategies that disability service providers can utilize in conjunction with…

Next Steps Toward Understanding Human Habitation of Space: Environmental Impacts and Mechanisms

NASA Technical Reports Server (NTRS)

Globus, Ruth

2016-01-01

Entry into low earth orbit and beyond causes profound shifts in environmental conditions that have the potential to influence human productivity, long term health, and even survival. We now have evidence that microgravity, radiation and/or confinement in space can lead to demonstrably detrimental changes in the cardiovascular (e.g. vessel function, orthostatic intolerance), musculoskeletal (muscle atrophy, bone loss) and nervous (eye, neurovestibular) systems of astronauts. Because of both the limited number of astronauts who have flown (especially females) and the high degree of individual variability in the human population, important unanswered questions about responses to the space environment remain: What are the sex differences with respect to specific physiological systems? Are the responses age-dependent and/or reversible after return to Earth? Do observed detrimental changes that resemble accelerated aging progress continuously over time or plateau? What are the mechanisms of the biological responses? Answering these important questions certainly demands a multi-pronged approach, and the study of multicellular model organisms (such as rodents and flies) already has provided opportunities for exploring those questions in some detail. Recent long duration spaceflight experiments with rodents show that mice in space provide a mammalian model that uniquely combines the influence of reduced gravitational loading with increased physical activity. In addition, multiple investigators have shown that ground-based models that simulate aspects of spaceflight (including rodent hind limb unloading to mimic weightlessness and exposure to ionizing radiation), cause various transient and persistent detrimental consequences in multiple physiological systems. In general, we have found that adverse skeletal effects of simulated weightlessness and space radiation when combined, can be quantitatively, if not qualitatively, different from the influence of each environmental factor alone implying at least some shared underlying mechanisms. Thus, both ground based and spaceflight research utilizing model organisms provide the opportunity to better understand environmental factors and biological mechanisms that contribute to human health and survival in space.

Opportunities and Challenges for Niosomes as Drug Delivery Systems.

PubMed

Thakkar, Miloni; Brijesh, S

2016-01-01

With the increase in drug resistance observed in most infectious diseases as well as some forms of cancer, and with the chances of development of new drug molecules to address this issue looking bleak, one of the most plausible ways to disease treatment is combination therapy. Combination therapy would ensure delay in drug resistance, if utilized rationally. However, the biggest difficulty in employing combination therapy are adverse effects due to potential drug-drug interactions and patient compliance due to multiple routes of administration or multiple dosing that may be required. To overcome these issues, researchers have utilized nanoparticle-based systems that can hold multiple drugs in a single carrier. There are several nanocarrier systems available for such purposes. However, the focus of this review will be non-ionic surfactant-based systems (niosomes) for delivery of multiple therapeutic agents. Niosomes are artificially prepared drug delivery carriers. They are structurally similar to liposomes albeit more stable than them. Literature pertaining to combination drug delivery and various drug delivery systems was reviewed. It was conceptualized that many of the methods used to prepare various types of carriers for combination delivery of drugs may be used for niosomal systems as well. We envisage that niosomes may effectively be utilized to package older drugs in newer ways. The review will thus focus on techniques that may be used for the formulation of niosomes, ways to encapsulate multiple-drug moieties, and challenges associated in preparing and optimizing such systems.

Status and Trends in the U.S. Voluntary Green Power Market (2015 Data)

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

O'Shaughnessy, Eric; Liu, Chang; Heeter, Jenny

The voluntary green power market refers to the sale and procurement of renewable energy for voluntary purposes by residential and commercial customers. This report reviews seven green power procurement mechanisms: utility green pricing programs, utility green tariffs, voluntary unbundled renewable energy certificates, competitive supplier green power, community choice aggregations, voluntary power purchase agreements (PPAs), and community solar. This report details the status of trends of those seven green power procurement mechanisms in 2015. Three trends -- significant growth of the voluntary PPA project pipeline, innovative green power mechanisms developed by utilities, and geographic expansion of green power mechanisms -- suggestmore » that the green power market is likely to continue to grow in coming years.« less

Progressive multiple sclerosis: from pathogenic mechanisms to treatment.

PubMed

Correale, Jorge; Gaitán, María I; Ysrraelit, María C; Fiol, Marcela P

2017-03-01

During the past decades, better understanding of relapsing-remitting multiple sclerosis disease mechanisms have led to the development of several disease-modifying therapies, reducing relapse rates and severity, through immune system modulation or suppression. In contrast, current therapeutic options for progressive multiple sclerosis remain comparatively disappointing and challenging. One possible explanation is a lack of understanding of pathogenic mechanisms driving progressive multiple sclerosis. Furthermore, diagnosis is usually retrospective, based on history of gradual neurological worsening with or without occasional relapses, minor remissions or plateaus. In addition, imaging methods as well as biomarkers are not well established. Magnetic resonance imaging studies in progressive multiple sclerosis show decreased blood-brain barrier permeability, probably reflecting compartmentalization of inflammation behind a relatively intact blood-brain barrier. Interestingly, a spectrum of inflammatory cell types infiltrates the leptomeninges during subpial cortical demyelination. Indeed, recent magnetic resonance imaging studies show leptomeningeal contrast enhancement in subjects with progressive multiple sclerosis, possibly representing an in vivo marker of inflammation associated to subpial demyelination. Treatments for progressive disease depend on underlying mechanisms causing central nervous system damage. Immunity sheltered behind an intact blood-brain barrier, energy failure, and membrane channel dysfunction may be key processes in progressive disease. Interfering with these mechanisms may provide neuroprotection and prevent disability progression, while potentially restoring activity and conduction along damaged axons by repairing myelin. Although most previous clinical trials in progressive multiple sclerosis have yielded disappointing results, important lessons have been learnt, improving the design of novel ones. This review discusses mechanisms involved in progressive multiple sclerosis, correlations between histopathology and magnetic resonance imaging studies, along with possible new therapeutic approaches. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Reconceptualizing the Model of Multiple Dimensions of Identity: The Role of Meaning-Making Capacity in the Construction of Multiple Identities

ERIC Educational Resources Information Center

Abes, Elisa S.; Jones, Susan R.; McEwen, Marylu K.

2007-01-01

We reconceptualize Jones and McEwen's (2000) model of multiple dimensions of identity by incorporating meaning making, based on the results of Abes and Jones's (2004) study of lesbian college students. Narratives of three students who utilize different orders of Kegan's (1994) meaning making (formulaic, transitional, and foundational, as described…

Multiple Time Series Node Synchronization Utilizing Ambient Reference

DTIC Science & Technology

2014-12-31

assessment, is the need for fine scale synchronization among communicating nodes and across multiple domains. The severe requirements that Special...processing targeted to performance assessment, is the need for fine scale synchronization among communicating nodes and across multiple domains. The...research community and it is well documented and characterized. The datasets considered from this project (listed below) were used to derive the

Application of a Utility Analysis to Evaluate a Novel Assessment Tool for Clinically Oriented Physiology and Pharmacology

ERIC Educational Resources Information Center

Cramer, Nicholas; Asmar, Abdo; Gorman, Laurel; Gros, Bernard; Harris, David; Howard, Thomas; Hussain, Mujtaba; Salazar, Sergio; Kibble, Jonathan D.

2016-01-01

Multiple-choice questions are a gold-standard tool in medical school for assessment of knowledge and are the mainstay of licensing examinations. However, multiple-choice questions items can be criticized for lacking the ability to test higher-order learning or integrative thinking across multiple disciplines. Our objective was to develop a novel…

Applying a Multiple Group Causal Indicator Modeling Framework to the Reading Comprehension Skills of Third, Seventh, and Tenth Grade Students

ERIC Educational Resources Information Center

Tighe, Elizabeth L.; Wagner, Richard K.; Schatschneider, Christopher

2015-01-01

This study demonstrates the utility of applying a causal indicator modeling framework to investigate important predictors of reading comprehension in third, seventh, and tenth grade students. The results indicated that a 4-factor multiple indicator multiple indicator cause (MIMIC) model of reading comprehension provided adequate fit at each grade…

Multiple-Use Site Demand Analysis: An Application to the Boundary Waters Canoe Area Wilderness.

ERIC Educational Resources Information Center

Peterson, George L.; And Others

1982-01-01

A single-site, multiple-use model for analyzing trip demand is derived from a multiple site regional model based on utility maximizing choice theory. The model is used to analyze and compare trips to the Boundary Waters Canoe Area Wilderness for several types of use. Travel cost elasticities of demand are compared and discussed. (Authors/JN)

Key Design Elements of a Data Utility for National Biosurveillance: Event-driven Architecture, Caching, and Web Service Model

PubMed Central

Tsui, Fu-Chiang; Espino, Jeremy U.; Weng, Yan; Choudary, Arvinder; Su, Hoah-Der; Wagner, Michael M.

2005-01-01

The National Retail Data Monitor (NRDM) has monitored over-the-counter (OTC) medication sales in the United States since December 2002. The NRDM collects data from over 18,600 retail stores and processes over 0.6 million sales records per day. This paper describes key architectural features that we have found necessary for a data utility component in a national biosurveillance system. These elements include event-driven architecture to provide analyses of data in near real time, multiple levels of caching to improve query response time, high availability through the use of clustered servers, scalable data storage through the use of storage area networks and a web-service function for interoperation with affiliated systems. The methods and architectural principles are relevant to the design of any production data utility for public health surveillance—systems that collect data from multiple sources in near real time for use by analytic programs and user interfaces that have substantial requirements for time-series data aggregated in multiple dimensions. PMID:16779138

A Quantile Regression Approach to Understanding the Relations Among Morphological Awareness, Vocabulary, and Reading Comprehension in Adult Basic Education Students.

PubMed

Tighe, Elizabeth L; Schatschneider, Christopher

2016-07-01

The purpose of this study was to investigate the joint and unique contributions of morphological awareness and vocabulary knowledge at five reading comprehension levels in adult basic education (ABE) students. We introduce the statistical technique of multiple quantile regression, which enabled us to assess the predictive utility of morphological awareness and vocabulary knowledge at multiple points (quantiles) along the continuous distribution of reading comprehension. To demonstrate the efficacy of our multiple quantile regression analysis, we compared and contrasted our results with a traditional multiple regression analytic approach. Our results indicated that morphological awareness and vocabulary knowledge accounted for a large portion of the variance (82%-95%) in reading comprehension skills across all quantiles. Morphological awareness exhibited the greatest unique predictive ability at lower levels of reading comprehension whereas vocabulary knowledge exhibited the greatest unique predictive ability at higher levels of reading comprehension. These results indicate the utility of using multiple quantile regression to assess trajectories of component skills across multiple levels of reading comprehension. The implications of our findings for ABE programs are discussed. © Hammill Institute on Disabilities 2014.

Tremor evidence for dynamically triggered creep events on the deep San Andreas Fault

NASA Astrophysics Data System (ADS)

Peng, Z.; Shelly, D. R.; Hill, D. P.; Aiken, C.

2010-12-01

Deep tectonic tremor has been observed along major subduction zones and the San Andreas fault (SAF) in central and southern California. It appears to reflect deep fault slip, and it is often seen to be triggered by small stresses, including passing seismic waves from large regional and teleseismic earthquakes. Here we examine tremor activity along the Parkfield-Cholame section of the SAF from mid-2001 to early 2010, scrutinizing its relationship with regional and teleseismic earthquakes. Based on similarities in the shape and timing of seismic waveforms, we conclude that triggered and ambient tremor share common sources and a common physical mechanism. Utilizing this similarity in waveforms, we detect tremor triggered by numerous large events, including previously unreported triggering from the recent 2009 Mw7.3 Honduras, 2009 Mw8.1 Samoa, and 2010 Mw8.8 Chile earthquakes at teleseismic distances, and the relatively small 2007 Mw5.4 Alum Rock and 2008 Mw5.4 Chino Hills earthquakes at regional distances. We also find multiple examples of systematic migration in triggered tremor, similar to ambient tremor migration episodes observed at other times. Because these episodes propagate much more slowly than the triggering waves, the migration likely reflects a small, triggered creep event. As with ambient tremor bursts, triggered tremor at times persists for multiple days, probably indicating a somewhat larger creep event. This activity provides a clear example of delayed dynamic triggering, with a mechanism perhaps also relevant for triggering of regular earthquakes.

Analysis of the outer membrane proteome and secretome of Bacteroides fragilis reveals a multiplicity of secretion mechanisms.

PubMed

Wilson, Marlena M; Anderson, D Eric; Bernstein, Harris D

2015-01-01

Bacteroides fragilis is a widely distributed member of the human gut microbiome and an opportunistic pathogen. Cell surface molecules produced by this organism likely play important roles in colonization, communication with other microbes, and pathogenicity, but the protein composition of the outer membrane (OM) and the mechanisms used to transport polypeptides into the extracellular space are poorly characterized. Here we used LC-MS/MS to analyze the OM proteome and secretome of B. fragilis NCTC 9343 grown under laboratory conditions. Of the 229 OM proteins that we identified, 108 are predicted to be lipoproteins, and 61 are predicted to be TonB-dependent transporters. Based on their proximity to genes encoding TonB-dependent transporters, many of the lipoprotein genes likely encode proteins involved in nutrient or small molecule uptake. Interestingly, protease accessibility and biotinylation experiments indicated that an unusually large fraction of the lipoproteins are cell-surface exposed. We also identified three proteins that are members of a novel family of autotransporters, multiple potential type I protein secretion systems, and proteins that appear to be components of a type VI secretion apparatus. The secretome consisted of lipoproteins and other proteins that might be substrates of the putative type I or type VI secretion systems. Our proteomic studies show that B. fragilis differs considerably from well-studied Gram-negative bacteria such as Escherichia coli in both the spectrum of OM proteins that it produces and the range of secretion strategies that it utilizes.

Thromboprophylaxis in Head and Neck Microvascular Reconstruction.

PubMed

Abraham, Manoj; Badhey, Arvind; Hu, Shirley; Kadakia, Sameep; Rasamny, J K; Moscatello, Augustine; Ducic, Yadranko

2018-06-01

Head and neck patients undergoing microvascular reconstruction are at high risk for thromboembolism. While the prevention of thromboembolism has become an essential aspect of care, within the field of microsurgery, concern for anastomotic complications have hindered the creation of an accepted regimen. The aim of this review was to evaluate the risks and benefits of prophylactic agents for thromboprophylaxis. A literature search was conducted in MEDLINE, Cochrane Library, and PubMed/NCBI databases. Articles discussing thromboprophylaxis in otolaryngology, head and neck surgery, or microvascular reconstruction were considered in the review from the past 30 years. The majority of patients undergoing microvascular surgery have multiple risk factors for thrombus formation. Several consensus guidelines exist for the prophylaxis in patients who are critically ill, undergoing surgery, or with malignancy. Significant evidence supports the routine use of mechanical means, such as early mobilization and pneumatic compression along with subcutaneous heparin. Low-molecular-weight heparin is also frequently utilized, although results are largely divided. Data on aspirin remain equivocal. Studies on microvascular failure and flap loss have demonstrated little to no association with chemoprophylaxis. The evidence for postoperative thromboprophylaxis regimens in patients undergoing head and neck free tissue transfer is variable. Multiple studies have supported the use of unfractionated heparin or low-molecular-weight heparin. There appears to be an expert consensus for the combined use of mechanical prophylactic methods and chemical prophylaxis. Prospective randomized trials are required to validate the most effective combination of chemoprophylaxis agents.

Impact of Fast Charging on Life of EV Batteries

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

Neubauer, Jeremy; Wood, Eric; Burton, Evan

2015-05-03

Utilization of public charging infrastructure is heavily dependent on user-specific travel behavior. The availability of fast chargers can positively affect the utility of battery electric vehicles, even given infrequent use. Estimated utilization rates do not appear frequent enough to significantly impact battery life. Battery thermal management systems are critical in mitigating dangerous thermal conditions on long distance tours with multiple fast charge events.

Multiplex electric discharge gas laser system

NASA Technical Reports Server (NTRS)

Laudenslager, James B. (Inventor); Pacala, Thomas J. (Inventor)

1987-01-01

A multiple pulse electric discharge gas laser system is described in which a plurality of pulsed electric discharge gas lasers are supported in a common housing. Each laser is supplied with excitation pulses from a separate power supply. A controller, which may be a microprocessor, is connected to each power supply for controlling the application of excitation pulses to each laser so that the lasers can be fired simultaneously or in any desired sequence. The output light beams from the individual lasers may be combined or utilized independently, depending on the desired application. The individual lasers may include multiple pairs of discharge electrodes with a separate power supply connected across each electrode pair so that multiple light output beams can be generated from a single laser tube and combined or utilized separately.

A Cloud-enabled Service-oriented Spatial Web Portal for Facilitating Arctic Data Discovery, Integration, and Utilization

NASA Astrophysics Data System (ADS)

dias, S. B.; Yang, C.; Li, Z.; XIA, J.; Liu, K.; Gui, Z.; Li, W.

2013-12-01

Global climate change has become one of the biggest concerns for human kind in the 21st century due to its broad impacts on society and ecosystems across the world. Arctic has been observed as one of the most vulnerable regions to the climate change. In order to understand the impacts of climate change on the natural environment, ecosystems, biodiversity and others in the Arctic region, and thus to better support the planning and decision making process, cross-disciplinary researches are required to monitor and analyze changes of Arctic regions such as water, sea level, biodiversity and so on. Conducting such research demands the efficient utilization of various geospatially referenced data, web services and information related to Arctic region. In this paper, we propose a cloud-enabled and service-oriented Spatial Web Portal (SWP) to support the discovery, integration and utilization of Arctic related geospatial resources, serving as a building block of polar CI. This SWP leverages the following techniques: 1) a hybrid searching mechanism combining centralized local search, distributed catalogue search and specialized Internet search for effectively discovering Arctic data and web services from multiple sources; 2) a service-oriented quality-enabled framework for seamless integration and utilization of various geospatial resources; and 3) a cloud-enabled parallel spatial index building approach to facilitate near-real time resource indexing and searching. A proof-of-concept prototype is developed to demonstrate the feasibility of the proposed SWP, using an example of analyzing the Arctic snow cover change over the past 50 years.

Class-Wide Access to a Commercial Step 1 Question Bank During Preclinical Organ-Based Modules: A Pilot Project.

PubMed

Baños, James H; Pepin, Mark E; Van Wagoner, Nicholas

2018-03-01

The authors examined the usefulness of a commercially available Step 1 question bank as a formative academic support tool throughout organ-based modules in an integrated preclinical medical curriculum. The authors also determined the extent to which correlation between question bank utilization and academic metrics varied with Medical College Admission Test (MCAT) scores. In 2015, a cohort of 185 first-year medical students at University of Alabama School of Medicine were provided with 18-month full access to a commercially available Step 1 question bank of over 2,100 items throughout organ-based modules, although there were no requirements for use. Data on student use of the question bank were collected via an online administrative portal. Relationships between question bank utilization and academic outcomes including exams, module grades, and United States Medical Licensing Examination (USMLE) Step 1 were determined using multiple linear regression. MCAT scores and number of items attempted in the question bank significantly predicted all academic measures, with question bank utilization as the stronger predictor. The association between question bank utilization and academic outcome was stronger for individuals with lower MCAT scores. The findings elucidate a novel academic support mechanism that, for some programs, may help bridge the gap between holistic and mission-based admissions practices and a residency match process that places a premium on USMLE exam scores. Distributed formative use of USMLE Step 1 practice questions may be of value as an academic support tool that benefits all students, but particularly those entering with lower MCAT scores.

MsmK, an ATPase, Contributes to Utilization of Multiple Carbohydrates and Host Colonization of Streptococcus suis.

PubMed

Tan, Mei-Fang; Gao, Ting; Liu, Wan-Quan; Zhang, Chun-Yan; Yang, Xi; Zhu, Jia-Wen; Teng, Mu-Ye; Li, Lu; Zhou, Rui

2015-01-01

Acquisition and metabolism of carbohydrates are essential for host colonization and pathogenesis of bacterial pathogens. Different bacteria can uptake different lines of carbohydrates via ABC transporters, in which ATPase subunits energize the transport though ATP hydrolysis. Some ABC transporters possess their own ATPases, while some share a common ATPase. Here we identified MsmK, an ATPase from Streptococcus suis, an emerging zoonotic bacterium causing dead infections in pigs and humans. Genetic and biochemistry studies revealed that the MsmK was responsible for the utilization of raffinose, melibiose, maltotetraose, glycogen and maltotriose. In infected mice, the msmK-deletion mutant showed significant defects of survival and colonization when compared with its parental and complementary strains. Taken together, MsmK is an ATPase that contributes to multiple carbohydrates utilization and host colonization of S. suis. This study gives new insight into our understanding of the carbohydrates utilization and its relationship to the pathogenesis of this zoonotic pathogen.

MsmK, an ATPase, Contributes to Utilization of Multiple Carbohydrates and Host Colonization of Streptococcus suis

PubMed Central

Tan, Mei-Fang; Gao, Ting; Liu, Wan-Quan; Zhang, Chun-Yan; Yang, Xi; Zhu, Jia-Wen; Teng, Mu-Ye; Li, Lu; Zhou, Rui

2015-01-01

Acquisition and metabolism of carbohydrates are essential for host colonization and pathogenesis of bacterial pathogens. Different bacteria can uptake different lines of carbohydrates via ABC transporters, in which ATPase subunits energize the transport though ATP hydrolysis. Some ABC transporters possess their own ATPases, while some share a common ATPase. Here we identified MsmK, an ATPase from Streptococcus suis, an emerging zoonotic bacterium causing dead infections in pigs and humans. Genetic and biochemistry studies revealed that the MsmK was responsible for the utilization of raffinose, melibiose, maltotetraose, glycogen and maltotriose. In infected mice, the msmK-deletion mutant showed significant defects of survival and colonization when compared with its parental and complementary strains. Taken together, MsmK is an ATPase that contributes to multiple carbohydrates utilization and host colonization of S. suis. This study gives new insight into our understanding of the carbohydrates utilization and its relationship to the pathogenesis of this zoonotic pathogen. PMID:26222651

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

Agalgaonkar, Yashodhan P.; Hammerstrom, Donald J.

The Pacific Northwest Smart Grid Demonstration (PNWSGD) was a smart grid technology performance evaluation project that included multiple U.S. states and cooperation from multiple electric utilities in the northwest region. One of the local objectives for the project was to achieve improved distribution system reliability. Toward this end, some PNWSGD utilities automated their distribution systems, including the application of fault detection, isolation, and restoration and advanced metering infrastructure. In light of this investment, a major challenge was to establish a correlation between implementation of these smart grid technologies and actual improvements of distribution system reliability. This paper proposes using Welch’smore » t-test to objectively determine and quantify whether distribution system reliability is improving over time. The proposed methodology is generic, and it can be implemented by any utility after calculation of the standard reliability indices. The effectiveness of the proposed hypothesis testing approach is demonstrated through comprehensive practical results. It is believed that wider adoption of the proposed approach can help utilities to evaluate a realistic long-term performance of smart grid technologies.« less

Neurotoxicity

MedlinePlus

... disorders such as Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, and dementia. Also being studied are the mechanisms ... disorders such as Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, and dementia. Also being studied are the mechanisms ...

MFAM: Multiple Frequency Adaptive Model-Based Indoor Localization Method.

PubMed

Tuta, Jure; Juric, Matjaz B

2018-03-24

This paper presents MFAM (Multiple Frequency Adaptive Model-based localization method), a novel model-based indoor localization method that is capable of using multiple wireless signal frequencies simultaneously. It utilizes indoor architectural model and physical properties of wireless signal propagation through objects and space. The motivation for developing multiple frequency localization method lies in the future Wi-Fi standards (e.g., 802.11ah) and the growing number of various wireless signals present in the buildings (e.g., Wi-Fi, Bluetooth, ZigBee, etc.). Current indoor localization methods mostly rely on a single wireless signal type and often require many devices to achieve the necessary accuracy. MFAM utilizes multiple wireless signal types and improves the localization accuracy over the usage of a single frequency. It continuously monitors signal propagation through space and adapts the model according to the changes indoors. Using multiple signal sources lowers the required number of access points for a specific signal type while utilizing signals, already present in the indoors. Due to the unavailability of the 802.11ah hardware, we have evaluated proposed method with similar signals; we have used 2.4 GHz Wi-Fi and 868 MHz HomeMatic home automation signals. We have performed the evaluation in a modern two-bedroom apartment and measured mean localization error 2.0 to 2.3 m and median error of 2.0 to 2.2 m. Based on our evaluation results, using two different signals improves the localization accuracy by 18% in comparison to 2.4 GHz Wi-Fi-only approach. Additional signals would improve the accuracy even further. We have shown that MFAM provides better accuracy than competing methods, while having several advantages for real-world usage.

MFAM: Multiple Frequency Adaptive Model-Based Indoor Localization Method

PubMed Central

Juric, Matjaz B.

2018-01-01

This paper presents MFAM (Multiple Frequency Adaptive Model-based localization method), a novel model-based indoor localization method that is capable of using multiple wireless signal frequencies simultaneously. It utilizes indoor architectural model and physical properties of wireless signal propagation through objects and space. The motivation for developing multiple frequency localization method lies in the future Wi-Fi standards (e.g., 802.11ah) and the growing number of various wireless signals present in the buildings (e.g., Wi-Fi, Bluetooth, ZigBee, etc.). Current indoor localization methods mostly rely on a single wireless signal type and often require many devices to achieve the necessary accuracy. MFAM utilizes multiple wireless signal types and improves the localization accuracy over the usage of a single frequency. It continuously monitors signal propagation through space and adapts the model according to the changes indoors. Using multiple signal sources lowers the required number of access points for a specific signal type while utilizing signals, already present in the indoors. Due to the unavailability of the 802.11ah hardware, we have evaluated proposed method with similar signals; we have used 2.4 GHz Wi-Fi and 868 MHz HomeMatic home automation signals. We have performed the evaluation in a modern two-bedroom apartment and measured mean localization error 2.0 to 2.3 m and median error of 2.0 to 2.2 m. Based on our evaluation results, using two different signals improves the localization accuracy by 18% in comparison to 2.4 GHz Wi-Fi-only approach. Additional signals would improve the accuracy even further. We have shown that MFAM provides better accuracy than competing methods, while having several advantages for real-world usage. PMID:29587352

Variable Acceleration Force Calibration System (VACS)

NASA Technical Reports Server (NTRS)

Rhew, Ray D.; Parker, Peter A.; Johnson, Thomas H.; Landman, Drew

2014-01-01

Conventionally, force balances have been calibrated manually, using a complex system of free hanging precision weights, bell cranks, and/or other mechanical components. Conventional methods may provide sufficient accuracy in some instances, but are often quite complex and labor-intensive, requiring three to four man-weeks to complete each full calibration. To ensure accuracy, gravity-based loading is typically utilized. However, this often causes difficulty when applying loads in three simultaneous, orthogonal axes. A complex system of levers, cranks, and cables must be used, introducing increased sources of systematic error, and significantly increasing the time and labor intensity required to complete the calibration. One aspect of the VACS is a method wherein the mass utilized for calibration is held constant, and the acceleration is changed to thereby generate relatively large forces with relatively small test masses. Multiple forces can be applied to a force balance without changing the test mass, and dynamic forces can be applied by rotation or oscillating acceleration. If rotational motion is utilized, a mass is rigidly attached to a force balance, and the mass is exposed to a rotational field. A large force can be applied by utilizing a large rotational velocity. A centrifuge or rotating table can be used to create the rotational field, and fixtures can be utilized to position the force balance. The acceleration may also be linear. For example, a table that moves linearly and accelerates in a sinusoidal manner may also be utilized. The test mass does not have to move in a path that is parallel to the ground, and no re-leveling is therefore required. Balance deflection corrections may be applied passively by monitoring the orientation of the force balance with a three-axis accelerometer package. Deflections are measured during each test run, and adjustments with respect to the true applied load can be made during the post-processing stage. This paper will present the development and testing of the VASC concept.

Optimal Energy Management for a Smart Grid using Resource-Aware Utility Maximization

NASA Astrophysics Data System (ADS)

Abegaz, Brook W.; Mahajan, Satish M.; Negeri, Ebisa O.

2016-06-01

Heterogeneous energy prosumers are aggregated to form a smart grid based energy community managed by a central controller which could maximize their collective energy resource utilization. Using the central controller and distributed energy management systems, various mechanisms that harness the power profile of the energy community are developed for optimal, multi-objective energy management. The proposed mechanisms include resource-aware, multi-variable energy utility maximization objectives, namely: (1) maximizing the net green energy utilization, (2) maximizing the prosumers' level of comfortable, high quality power usage, and (3) maximizing the economic dispatch of energy storage units that minimize the net energy cost of the energy community. Moreover, an optimal energy management solution that combines the three objectives has been implemented by developing novel techniques of optimally flexible (un)certainty projection and appliance based pricing decomposition in an IBM ILOG CPLEX studio. A real-world, per-minute data from an energy community consisting of forty prosumers in Amsterdam, Netherlands is used. Results show that each of the proposed mechanisms yields significant increases in the aggregate energy resource utilization and welfare of prosumers as compared to traditional peak-power reduction methods. Furthermore, the multi-objective, resource-aware utility maximization approach leads to an optimal energy equilibrium and provides a sustainable energy management solution as verified by the Lagrangian method. The proposed resource-aware mechanisms could directly benefit emerging energy communities in the world to attain their energy resource utilization targets.

Transport pathways and enhancement mechanisms within localized and non-localized transport regions in skin treated with low-frequency sonophoresis and sodium lauryl sulfate.

PubMed

Polat, Baris E; Figueroa, Pedro L; Blankschtein, Daniel; Langer, Robert

2011-02-01

Recent advances in transdermal drug delivery utilizing low-frequency sonophoresis (LFS) and sodium lauryl sulfate (SLS) have revealed that skin permeability enhancement is not homogenous across the skin surface. Instead, highly perturbed skin regions, known as localized transport regions (LTRs), exist. Despite these findings, little research has been conducted to identify intrinsic properties and formation mechanisms of LTRs and the surrounding less-perturbed non-LTRs. By independently analyzing LTR, non-LTR, and total skin samples treated at multiple LFS frequencies, we found that the pore radii (r(pore)) within non-LTRs are frequency-independent, ranging from 18.2 to 18.5 Å, but significantly larger than r(pore) of native skin samples (13.6 Å). Conversely, r(pore) within LTRs increase significantly with decreasing frequency from 161 to 276 Å and to ∞ (>300 Å) for LFS/SLS-treated skin at 60, 40, and 20 kHz, respectively. Our findings suggest that different mechanisms contribute to skin permeability enhancement within each skin region. We propose that the enhancement mechanism within LTRs is the frequency-dependent process of cavitation-induced microjet collapse at the skin surface, whereas the increased r(pore) values in non-LTRs are likely due to SLS perturbation, with enhanced penetration of SLS into the skin resulting from the frequency-independent process of microstreaming. Copyright © 2010 Wiley-Liss, Inc.

Transport Pathways and Enhancement Mechanisms within Localized and Non-Localized Transport Regions in Skin Treated with Low-Frequency Sonophoresis and Sodium Lauryl Sulfate

PubMed Central

Polat, Baris E.; Figueroa, Pedro L.; Blankschtein, Daniel; Langer, Robert

2011-01-01

Recent advances in transdermal drug delivery utilizing low-frequency sonophoresis (LFS) and sodium lauryl sulfate (SLS) have revealed that skin permeability enhancement is not homogenous across the skin surface. Instead, highly perturbed skin regions, known as localized transport regions (LTRs), exist. Despite these findings, little research has been conducted to identify intrinsic properties and formation mechanisms of LTRs and the surrounding less-perturbed non-LTRs. By independently analyzing LTR, non-LTR, and total skin samples treated at multiple LFS frequencies, we found that the pore radii (rpore) within non-LTRs are frequency-independent, ranging from 18.2 – 18.5 Å, but significantly larger than rpore of native skin samples (13.6 Å). Conversely, rpore within LTRs increases significantly with decreasing frequency from 161 Å, to 276 Å, and to ∞ (>300Å) for LFS/SLS-treated skin at 60 kHz, 40 kHz, and 20 kHz, respectively. Our findings suggest that different mechanisms contribute to skin permeability enhancement within each skin region. We propose that the enhancement mechanism within LTRs is the frequency-dependent process of cavitation-induced microjet collapse at the skin surface, while the increased rpore values in non-LTRs are likely due to SLS perturbation, with enhanced penetration of SLS into the skin resulting from the frequency-independent process of microstreaming. PMID:20740667

Theoretical analysis of degradation mechanisms in the formation of morphogen gradients

NASA Astrophysics Data System (ADS)

Bozorgui, Behnaz; Teimouri, Hamid; Kolomeisky, Anatoly B.

2015-07-01

Fundamental biological processes of development of tissues and organs in multicellular organisms are governed by various signaling molecules, which are called morphogens. It is known that spatial and temporal variations in the concentration profiles of signaling molecules, which are frequently referred as morphogen gradients, lead to a cell differentiation via activating specific genes in a concentration-dependent manner. It is widely accepted that the establishment of the morphogen gradients involves multiple biochemical reactions and diffusion processes. One of the critical elements in the formation of morphogen gradients is a degradation of signaling molecules. We develop a new theoretical approach that provides a comprehensive description of the degradation mechanisms. It is based on the idea that the degradation works as an effective potential that drives the signaling molecules away from the source region. Utilizing the method of first-passage processes, the dynamics of the formation of morphogen gradients for various degradation mechanisms is explicitly evaluated. It is found that linear degradation processes lead to a dynamic behavior specified by times to form the morphogen gradients that depend linearly on the distance from the source. This is because the effective potential due to the degradation is quite strong. At the same time, nonlinear degradation mechanisms yield a quadratic scaling in the morphogen gradients formation times since the effective potentials are much weaker. Physical-chemical explanations of these phenomena are presented.

Cross-Resistance of UV- or Chlorine Dioxide-Resistant Echovirus 11 to Other Disinfectants

PubMed Central

Zhong, Qingxia; Carratalà, Anna; Ossola, Rachele; Bachmann, Virginie; Kohn, Tamar

2017-01-01

The emergence of waterborne viruses with resistance to disinfection has been demonstrated in the laboratory and in the environment. Yet, the implications of such resistance for virus control remain obscure. In this study we investigate if viruses with resistance to a given disinfection method exhibit cross-resistance to other disinfectants. Chlorine dioxide (ClO2)- or UV-resistant populations of echovirus 11 were exposed to five inactivating treatments (free chlorine, ClO2, UV radiation, sunlight, and heat), and the extent of cross-resistance was determined. The ClO2-resistant population exhibited cross-resistance to free chlorine, but to none of the other inactivating treatments tested. We furthermore demonstrated that ClO2 and free chlorine act by a similar mechanism, in that they mainly inhibit the binding of echovirus 11 to its host cell. As such, viruses with host binding mechanisms that can withstand ClO2 treatment were also better able to withstand oxidation by free chlorine. Conversely, the UV-resistant population was not significantly cross-resistant to any other disinfection treatment. Overall, our results indicate that viruses with resistance to multiple disinfectants exist, but that they can be controlled by inactivating methods that operate by a distinctly different mechanism. We therefore suggest to utilize two disinfection barriers that act by different mechanisms in order to control disinfection-resistant viruses. PMID:29046672

A coupled piezoelectric-electromagnetic energy harvesting technique for achieving increased power output through damping matching

NASA Astrophysics Data System (ADS)

Challa, Vinod R.; Prasad, M. G.; Fisher, Frank T.

2009-09-01

Vibration energy harvesting is being pursued as a means to power wireless sensors and ultra-low power autonomous devices. From a design standpoint, matching the electrical damping induced by the energy harvesting mechanism to the mechanical damping in the system is necessary for maximum efficiency. In this work two independent energy harvesting techniques are coupled to provide higher electrical damping within the system. Here the coupled energy harvesting device consists of a primary piezoelectric energy harvesting device to which an electromagnetic component is added to better match the total electrical damping to the mechanical damping in the system. The first coupled device has a resonance frequency of 21.6 Hz and generates a peak power output of ~332 µW, compared to 257 and 244 µW obtained from the optimized, stand-alone piezoelectric and electromagnetic energy harvesting devices, respectively, resulting in a 30% increase in power output. A theoretical model has been developed which closely agrees with the experimental results. A second coupled device, which utilizes the d33 piezoelectric mode, shows a 65% increase in power output in comparison to the corresponding stand-alone, single harvesting mode devices. This work illustrates the design considerations and limitations that one must consider to enhance device performance through the coupling of multiple harvesting mechanisms within a single energy harvesting device.

A model for one-dimensional morphoelasticity and its application to fibroblast-populated collagen lattices.

PubMed

Menon, Shakti N; Hall, Cameron L; McCue, Scott W; McElwain, D L Sean

2017-10-01

The mechanical behaviour of solid biological tissues has long been described using models based on classical continuum mechanics. However, the classical continuum theories of elasticity and viscoelasticity cannot easily capture the continual remodelling and associated structural changes in biological tissues. Furthermore, models drawn from plasticity theory are difficult to apply and interpret in this context, where there is no equivalent of a yield stress or flow rule. In this work, we describe a novel one-dimensional mathematical model of tissue remodelling based on the multiplicative decomposition of the deformation gradient. We express the mechanical effects of remodelling as an evolution equation for the effective strain, a measure of the difference between the current state and a hypothetical mechanically relaxed state of the tissue. This morphoelastic model combines the simplicity and interpretability of classical viscoelastic models with the versatility of plasticity theory. A novel feature of our model is that while most models describe growth as a continuous quantity, here we begin with discrete cells and develop a continuum representation of lattice remodelling based on an appropriate limit of the behaviour of discrete cells. To demonstrate the utility of our approach, we use this framework to capture qualitative aspects of the continual remodelling observed in fibroblast-populated collagen lattices, in particular its contraction and its subsequent sudden re-expansion when remodelling is interrupted.

A physiological perspective for utility or futility of alcohol-based hand rub gel against nausea-vomiting: is it P-6 acupoint or transnasal aroma?

PubMed

Gupta, Deepak; Mazumdar, Ashish; Stellini, Michael

2014-09-01

Nausea-vomiting is a common and unpleasant phenomenon with numerous underlying mechanisms and pathways that are not always well elucidated. In clinical practice, refractory nausea-vomiting is encountered in several settings. Antiemetic medications may reduce these symptoms but are not always effective in all patients. In the absence of a well-defined optimal strategy for management of nausea-vomiting, the search for better approaches to treat this distressing symptom continues. One of the alternative treatment approaches is a compounded formulation called ABHR gel that is comprised of multiple antiemetic medications and has been shown to be useful for symptomatic relief in some patients with refractory nausea-vomiting. It has been suggested that alternative mechanisms should be explored to explain the perceived efficacy of ABHR gel, because transdermal absorption leading to nil-to-minimal or subtherapeutic blood concentrations of active ingredients does not explain the role of ABHR gel in the treatment of nausea-vomiting. In the current paper, we discuss possible mechanisms that may explain ABHR transdermal gel's efficacy. Compounded ABHR transdermal gel formulation's efficacy in antagonizing nausea-vomiting that has been recently questioned may be explained by alternative mechanisms mediated through the P-6 acupoint stimulation and facial-nasal, cooling-related counterstimulation. © The Author(s) 2013.

Fibrin Networks Support Recurring Mechanical Loads by Adapting their Structure across Multiple Scales.

PubMed

Kurniawan, Nicholas A; Vos, Bart E; Biebricher, Andreas; Wuite, Gijs J L; Peterman, Erwin J G; Koenderink, Gijsje H

2016-09-06

Tissues and cells sustain recurring mechanical loads that span a wide range of loading amplitudes and timescales as a consequence of exposure to blood flow, muscle activity, and external impact. Both tissues and cells derive their mechanical strength from fibrous protein scaffolds, which typically have a complex hierarchical structure. In this study, we focus on a prototypical hierarchical biomaterial, fibrin, which is one of the most resilient naturally occurring biopolymers and forms the structural scaffold of blood clots. We show how fibrous networks composed of fibrin utilize irreversible changes in their hierarchical structure at different scales to maintain reversible stress stiffening up to large strains. To trace the origin of this paradoxical resilience, we systematically tuned the microstructural parameters of fibrin and used a combination of optical tweezers and fluorescence microscopy to measure the interactions of single fibrin fibers for the first time, to our knowledge. We demonstrate that fibrin networks adapt to moderate strains by remodeling at the network scale through the spontaneous formation of new bonds between fibers, whereas they adapt to high strains by plastic remodeling of the fibers themselves. This multiscale adaptation mechanism endows fibrin gels with the remarkable ability to sustain recurring loads due to shear flows and wound stretching. Our findings therefore reveal a microscopic mechanism by which tissues and cells can balance elastic nonlinearity and plasticity, and thus can provide microstructural insights into cell-driven remodeling of tissues. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Utilization of data and modeling at multiple scales to compare varying formulations of the soil resistance term affecting evaporative flux from the soil surface.

NASA Astrophysics Data System (ADS)

Smits, K. M.; Forsythe, L.; Riley, W. J.; Bisht, G.

2016-12-01

Land Surface Models (LSMs) are used to predict heat, energy, and momentum fluxesoccurring at the land surface and the resulting effects in the soil and atmosphere at various scales.Evaporation from bare soil is an integral component of the water balance that is very difficult toaccurately predict since it is complexly affected by the coupled effects of atmospheric conditions andsoil properties. Inaccurate or simplifying assumptions can have drastic effects on regional and globalLSM predictions and cause available LSMs to predict conflicting values for the soil moistureconditions and surface fluxes (e.g. evapotranspiration, infiltration, run off). The goal of this work isto see how heterogeneities in soil properties can be properly represented with a soil resistance termthat accounts for physically based parameters of the soil system at the land-atmosphere interface.Utilizing a comprehensive, experimental dataset generated from a soil with known, heterogeneousproperties under highly controlled atmospheric conditions, we are able to compare the effectivenessof various parameterizations in two different models. The first being a multiphase, non-equilibrium,and non-isothermal model that minimizes the dependence on fitting parameters. The effects ofcertain mechanisms are better understood at this fine scale and incorporated into the land surfacecomponent of the Accelerated Climate Modeling for Energy project (ALM), which is focused oncapturing the interactions between the surface and the atmosphere at larger scales. The formulationsof the resistance parameter, soil water retention curve (SWRC), and diffusivity through partiallysaturated porous media are of particular interest. The fine scale model was used in conjunction withthe experimental data to test formulations before implementing them into the ACME Land Model(ALM). Effects of these alterations were compared to the existing mechanisms in ALM and thentested against lab and field scale data sets. Initial findings suggest the Tang and Riley (2013a) soilresistance more accurately reproduces results lab and field results on multiple scales whereheterogeneity is present. Further understanding of soil resistance will lead to more robust landsurface models which decrease the reliance on such empirical relationships.

Demonstration of a novel Xp22.2 microdeletion as the cause of familial extreme skewing of X-inactivation utilizing case-parent trio SNP microarray analysis.

PubMed

Mason, Jane A; Aung, Hnin T; Nandini, Adayapalam; Woods, Rickie G; Fairbairn, David J; Rowell, John A; Young, David; Susman, Rachel D; Brown, Simon A; Hyland, Valentine J; Robertson, Jeremy D

2018-05-01

We report a kindred referred for molecular investigation of severe hemophilia A in a young female in which extremely skewed X-inactivation was observed in both the proband and her clinically normal mother. Bidirectional Sanger sequencing of all F8 gene coding regions and exon/intron boundaries was undertaken. Methylation-sensitive restriction enzymes were utilized to investigate skewed X-inactivation using both a classical human androgen receptor (HUMARA) assay, and a novel method targeting differential methylation patterns in multiple informative X-chromosome SNPs. Illumina Whole-Genome Infinium microarray analysis was performed in the case-parent trio (proband and both parents), and the proband's maternal grandmother. The proband was a cytogenetically normal female with severe hemophilia A resulting from a heterozygous F8 pathogenic variant inherited from her similarly affected father. No F8 mutation was identified in the proband's mother, however, both the proband and her mother both demonstrated completely skewed X-chromosome inactivation (100%) in association with a previously unreported 2.3 Mb deletion at Xp22.2. At least three disease-associated genes (FANCB, AP1S2, and PIGA) were contained within the deleted region. We hypothesize that true "extreme" skewing of X-inactivation (≥95%) is a rare occurrence, but when defined correctly there is a high probability of finding an X-chromosome disease-causing variant or larger deletion resulting in X-inactivation through a survival disadvantage or cell lethal mechanism. We postulate that the 2.3 Mb Xp22.2 deletion identified in our kindred arose de novo in the proband's mother (on the grandfather's homolog), and produced extreme skewing of X-inactivation via a "cell lethal" mechanism. We introduce a novel multitarget approach for X-inactivation analysis using multiple informative differentially methylated SNPs, as an alternative to the classical single locus (HUMARA) method. We propose that for females with unexplained severe phenotypic expression of an X-linked recessive disorder trio-SNP microarray should be undertaken in combination with X-inactivation analysis. © 2018 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.

Visualizing long-term single-molecule dynamics in vivo by stochastic protein labeling.

PubMed

Liu, Hui; Dong, Peng; Ioannou, Maria S; Li, Li; Shea, Jamien; Pasolli, H Amalia; Grimm, Jonathan B; Rivlin, Patricia K; Lavis, Luke D; Koyama, Minoru; Liu, Zhe

2018-01-09

Our ability to unambiguously image and track individual molecules in live cells is limited by packing of multiple copies of labeled molecules within the resolution limit. Here we devise a universal genetic strategy to precisely control copy number of fluorescently labeled molecules in a cell. This system has a dynamic range of ∼10,000-fold, enabling sparse labeling of proteins expressed at different abundance levels. Combined with photostable labels, this system extends the duration of automated single-molecule tracking by two orders of magnitude. We demonstrate long-term imaging of synaptic vesicle dynamics in cultured neurons as well as in intact zebrafish. We found axon initial segment utilizes a "waterfall" mechanism gating synaptic vesicle transport polarity by promoting anterograde transport processivity. Long-time observation also reveals that transcription factor hops between clustered binding sites in spatially restricted subnuclear regions, suggesting that topological structures in the nucleus shape local gene activities by a sequestering mechanism. This strategy thus greatly expands the spatiotemporal length scales of live-cell single-molecule measurements, enabling new experiments to quantitatively understand complex control of molecular dynamics in vivo.

Neurotoxicity in Preclinical Models of Occupational Exposure to Organophosphorus Compounds.

PubMed

Voorhees, Jaymie R; Rohlman, Diane S; Lein, Pamela J; Pieper, Andrew A

2016-01-01

Organophosphorus (OPs) compounds are widely used as insecticides, plasticizers, and fuel additives. These compounds potently inhibit acetylcholinesterase (AChE), the enzyme that inactivates acetylcholine at neuronal synapses, and acute exposure to high OP levels can cause cholinergic crisis in humans and animals. Evidence further suggests that repeated exposure to lower OP levels insufficient to cause cholinergic crisis, frequently encountered in the occupational setting, also pose serious risks to people. For example, multiple epidemiological studies have identified associations between occupational OP exposure and neurodegenerative disease, psychiatric illness, and sensorimotor deficits. Rigorous scientific investigation of the basic science mechanisms underlying these epidemiological findings requires valid preclinical models in which tightly-regulated exposure paradigms can be correlated with neurotoxicity. Here, we review the experimental models of occupational OP exposure currently used in the field. We found that animal studies simulating occupational OP exposures do indeed show evidence of neurotoxicity, and that utilization of these models is helping illuminate the mechanisms underlying OP-induced neurological sequelae. Still, further work is necessary to evaluate exposure levels, protection methods, and treatment strategies, which taken together could serve to modify guidelines for improving workplace conditions globally.

Refurbishment and Automation of Thermal Vacuum Facilities at NASA/GSFC

NASA Technical Reports Server (NTRS)

Dunn, Jamie; Gomez, Carlos; Donohue, John; Johnson, Chris; Palmer, John; Sushon, Janet

1999-01-01

The thermal vacuum facilities located at the Goddard Space Flight Center (GSFC) have supported both manned and unmanned space flight since the 1960s. Of the eleven facilities, currently ten of the systems are scheduled for refurbishment or replacement as part of a five-year implementation. Expected return on investment includes the reduction in test schedules, improvements in safety of facility operations, and reduction in the personnel support required for a test. Additionally, GSFC will become a global resource renowned for expertise in thermal engineering, mechanical engineering, and for the automation of thermal vacuum facilities and tests. Automation of the thermal vacuum facilities includes the utilization of Programmable Logic Controllers (PLCs), the use of Supervisory Control and Data Acquisition (SCADA) systems, and the development of a centralized Test Data Management System. These components allow the computer control and automation of mechanical components such as valves and pumps. The project of refurbishment and automation began in 1996 and has resulted in complete computer control of one facility (Facility 281), and the integration of electronically controlled devices and PLCs in multiple others.

Refurbishment and Automation of Thermal Vacuum Facilities at NASA/GSFC

NASA Technical Reports Server (NTRS)

Dunn, Jamie; Gomez, Carlos; Donohue, John; Johnson, Chris; Palmer, John; Sushon, Janet

1998-01-01

The thermal vacuum facilities located at the Goddard Space Flight Center (GSFC) have supported both manned and unmanned space flight since the 1960s. Of the eleven facilities, currently ten of the systems are scheduled for refurbishment or replacement as part of a five-year implementation. Expected return on investment includes the reduction in test schedules, improvements in safety of facility operations, and reduction in the personnel support required for a test. Additionally, GSFC will become a global resource renowned for expertise in thermal engineering, mechanical engineering, and for the automation of thermal vacuum facilities and tests. Automation of the thermal vacuum facilities includes the utilization of Programmable Logic Controllers (PLCs), the use of Supervisory Control and Data Acquisition (SCADA) systems, and the development of a centralized Test Data Management System. These components allow the computer control and automation of mechanical components such as valves and pumps. The project of refurbishment and automation began in 1996 and has resulted in complete computer control of one facility (Facility 281), and the integration of electronically controlled devices and PLCs in multiple others.

Coordination of size-control, reproduction and generational memory in freshwater planarians

NASA Astrophysics Data System (ADS)

Yang, Xingbo; Kaj, Kelson; Schwab, David; Collins, Eva-Maria

Uncovering the mechanisms that control size, growth, and division rates of systems reproducing through binary division means understanding basic principles of their life cycle. Recent work has focused on how division rates are regulated in bacteria and yeast, but this question has not yet been addressed in more complex, multicellular organisms. We have acquired a unique large-scale data set on the growth and asexual reproduction of two freshwater planarian species, Dugesia japonica and Dugesia tigrina, which reproduce by transverse fission and succeeding regeneration of head and tail pieces into new worms. We developed a new additive theoretical model that mixes multiple size control strategies based on worm size, growth, and waiting time. Our model quantifies the proportions of each strategy in the mixed dynamics, revealing the ability of the two planarian species to utilize different strategies in a coordinated manner for size control. Additionally, we found that head and tail offspring of both species employ different mechanisms to monitor and trigger their reproduction cycles. Finally, we show that generation-dependent memory effects in planarians need to be taken into account to accurately capture the experimental data.

A systematic review of neuroprotective strategies after cardiac arrest: from bench to bedside (Part I – Protection via specific pathways)

PubMed Central

2014-01-01

Neurocognitive deficits are a major source of morbidity in survivors of cardiac arrest. Treatment options that could be implemented either during cardiopulmonary resuscitation or after return of spontaneous circulation to improve these neurological deficits are limited. We conducted a literature review of treatment protocols designed to evaluate neurologic outcome and survival following cardiac arrest with associated global cerebral ischemia. The search was limited to investigational therapies that were utilized to treat global cerebral ischemia associated with cardiac arrest. In this review we discuss potential mechanisms of neurologic protection following cardiac arrest including actions of several medical gases such as xenon, argon, and nitric oxide. The 3 included mechanisms are: 1. Modulation of neuronal cell death; 2. Alteration of oxygen free radicals; and 3. Improving cerebral hemodynamics. Only a few approaches have been evaluated in limited fashion in cardiac arrest patients and results show inconclusive neuroprotective effects. Future research focusing on combined neuroprotective strategies that target multiple pathways are compelling in the setting of global brain ischemia resulting from cardiac arrest. PMID:24808942

Study on additional carrier sensing for IEEE 802.15.4 wireless sensor networks.

PubMed

Lee, Bih-Hwang; Lai, Ruei-Lung; Wu, Huai-Kuei; Wong, Chi-Ming

2010-01-01

Wireless sensor networks based on the IEEE 802.15.4 standard are able to achieve low-power transmissions in the guise of low-rate and short-distance wireless personal area networks (WPANs). The slotted carrier sense multiple access with collision avoidance (CSMA/CA) is used for contention mechanism. Sensor nodes perform a backoff process as soon as the clear channel assessment (CCA) detects a busy channel. In doing so they may neglect the implicit information of the failed CCA detection and further cause the redundant sensing. The blind backoff process in the slotted CSMA/CA will cause lower channel utilization. This paper proposes an additional carrier sensing (ACS) algorithm based on IEEE 802.15.4 to enhance the carrier sensing mechanism for the original slotted CSMA/CA. An analytical Markov chain model is developed to evaluate the performance of the ACS algorithm. Both analytical and simulation results show that the proposed algorithm performs better than IEEE 802.15.4, which in turn significantly improves throughput, average medium access control (MAC) delay and power consumption of CCA detection.

Ephedrine QoS: An Antidote to Slow, Congested, Bufferless NoCs

PubMed Central

Fang, Juan; Yao, Zhicheng; Sui, Xiufeng; Bao, Yungang

2014-01-01

Datacenters consolidate diverse applications to improve utilization. However when multiple applications are colocated on such platforms, contention for shared resources like networks-on-chip (NoCs) can degrade the performance of latency-critical online services (high-priority applications). Recently proposed bufferless NoCs (Nychis et al.) have the advantages of requiring less area and power, but they pose challenges in quality-of-service (QoS) support, which usually relies on buffer-based virtual channels (VCs). We propose QBLESS, a QoS-aware bufferless NoC scheme for datacenters. QBLESS consists of two components: a routing mechanism (QBLESS-R) that can substantially reduce flit deflection for high-priority applications and a congestion-control mechanism (QBLESS-CC) that guarantees performance for high-priority applications and improves overall system throughput. We use trace-driven simulation to model a 64-core system, finding that, when compared to BLESS, a previous state-of-the-art bufferless NoC design, QBLESS, improves performance of high-priority applications by an average of 33.2% and reduces network-hops by an average of 42.8%. PMID:25250386

Exploring the modulation of hypoxia-inducible factor (HIF)-1α by volatile anesthetics as a possible mechanism underlying volatile anesthetic-induced CNS injury.

PubMed

Giles, Emma K; Lawrence, Andrew J; Duncan, Jhodie R

2014-09-01

This review summarizes recent research on the potential cognitive and behavioural abnormalities induced by exposure to volatile anesthetics and suggests a role of hypoxia-inducible factor (HIF)-1α in mediating these events. Volatile anesthetics are widely utilized in clinical and research settings, yet the long-term safety of exposure to these agents is under debate. Findings from various animal models suggest volatile anesthetics induce widespread apoptosis in the central nervous system (CNS) that correlates with lasting deficits in learning and memory. Longitudinal analysis of clinical data highlight an increased risk of developmental disorders later in life when children are exposed to volatile anesthetics, particularly when exposures occur over multiple sessions. However, the mechanisms underlying these events have yet to be established. Considering the extensive use of volatile anesthetics, it is crucial that these events are better understood. The possible role of HIF-1α in volatile anesthetic-induced CNS abnormalities will be suggested and areas requiring urgent attention will be outlined.

The Role of Brincidofovir in Preparation for a Potential Smallpox Outbreak.

PubMed

Foster, Scott A; Parker, Scott; Lanier, Randall

2017-10-30

Smallpox (variola) virus is considered a Category A bioterrorism agent due to its ability to spread rapidly and the high morbidity and mortality rates associated with infection. Current recommendations recognize the importance of oral antivirals and call for having at least two smallpox antivirals with different mechanisms of action available in the event of a smallpox outbreak. Multiple antivirals are recommended due in large part to the propensity of viruses to become resistant to antiviral therapy, especially monotherapy. Advances in synthetic biology heighten concerns that a bioterror attack with variola would utilize engineered resistance to antivirals and potentially vaccines. Brincidofovir, an oral antiviral in late stage development, has proven effective against orthopoxviruses in vitro and in vivo, has a different mechanism of action from tecovirimat (the only oral smallpox antiviral currently in the US Strategic National Stockpile), and has a resistance profile that reduces concerns in the scenario of a bioterror attack using genetically engineered smallpox. Given the devastating potential of smallpox as a bioweapon, preparation of a multi-pronged defense that accounts for the most obvious bioengineering possibilities is strategically imperative.

Experimental characterization and computational modeling of unimorph shape memory polymer actuators incorporating transverse curvature in the substrate

NASA Astrophysics Data System (ADS)

Cantrell, Jason T.

This document outlines in detail the research performed by applying shape memory polymers in a generic unimorph actuator configuration. A set of experiments designed to investigate the influence of transverse curvature, the relative widths of shape memory polymer and composite substrates, and shape memory polymer thickness on actuator recoverability after multiple thermo-mechanical cycles is presented in detail. A theoretical model of the moment required to maintain shape fixity with minimal shape retention loss was developed and experimentally validated for unimorph composite actuators of varying cross-sectional areas. Theoretical models were also developed and evaluated to determine the relationship between the materials neutral axes and thermal stability during a thermo-mechanical cycle. Research was conducted on the incorporation of shape memory polymers on micro air vehicle wings to maximize shape fixity and shape recoverability while minimizing the volume of shape memory polymer on the wing surface. Applications based research also included experimentally evaluating the feasibility of shape memory polymers on deployable satellite antenna ribs both with and without resistance heaters which could be utilized to assist in antenna deployment.

Comparing Multiple-Group Multinomial Log-Linear Models for Multidimensional Skill Distributions in the General Diagnostic Model. Research Report. ETS RR-08-35

ERIC Educational Resources Information Center

Xu, Xueli; von Davier, Matthias

2008-01-01

The general diagnostic model (GDM) utilizes located latent classes for modeling a multidimensional proficiency variable. In this paper, the GDM is extended by employing a log-linear model for multiple populations that assumes constraints on parameters across multiple groups. This constrained model is compared to log-linear models that assume…

Software For Nearly Optimal Packing Of Cargo

NASA Technical Reports Server (NTRS)

Fennel, Theron R.; Daughtrey, Rodney S.; Schwaab, Doug G.

1994-01-01

PACKMAN computer program used to find nearly optimal arrangements of cargo items in storage containers, subject to such multiple packing objectives as utilization of volumes of containers, utilization of containers up to limits on weights, and other considerations. Automatic packing algorithm employed attempts to find best positioning of cargo items in container, such that volume and weight capacity of container both utilized to maximum extent possible. Written in Common LISP.

Balloon-Occluded Retrograde Transvenous Obliteration of a Gastric Vascular Malformation: An Innovative Approach to Treatment of a Rare Condition

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

Hansing, Catherine E., E-mail: catherine.e.hansing.mil@mail.mil; Marquardt, Joseph P.; Sutton, Daniel M.

Arteriovenous malformations (AVMs) are a high-flow form of a vascular malformation, which can be found anywhere in the body. While historically treated surgically, a multidisciplinary approach utilizing multiple specialties and treatment modalities is now commonly employed. In order to effectively treat an AVM, the nidus must be targeted and eradicated, which can be done via multiple approaches. We present the case of a 43-year-old male with a gastric wall AVM, which was initially incompletely treated using a percutaneous transarterial approach. The gastric AVM was noted to have dominant drainage through a gastrorenal shunt; therefore, Balloon-occluded Retrograde Transvenous Obliteration (BRTO) wasmore » utilized to eradicate the AVM nidus. This case illustrates the utility of Interventional Radiology, specifically BRTO, as another treatment option for challenging AVMs.« less

Dynamic Binding of Identity and Location Information: A Serial Model of Multiple Identity Tracking

ERIC Educational Resources Information Center

Oksama, Lauri; Hyona, Jukka

2008-01-01

Tracking of multiple moving objects is commonly assumed to be carried out by a fixed-capacity parallel mechanism. The present study proposes a serial model (MOMIT) to explain performance accuracy in the maintenance of multiple moving objects with distinct identities. A serial refresh mechanism is postulated, which makes recourse to continuous…

The changing pattern of prenatal care utilization in the United States, 1981-1995, using different prenatal care indices.

PubMed

Kogan, M D; Martin, J A; Alexander, G R; Kotelchuck, M; Ventura, S J; Frigoletto, F D

1998-05-27

Two measures traditionally used to examine adequacy of prenatal care indicate that prenatal care utilization remained unchanged through the 1980s and only began to rise slightly in the 1990s. In recent years, new measures have been developed that include a category for women who receive more than the recommended amount of care (intensive utilization). To compare the older and newer indices in the monitoring of prenatal care trends in the United States from 1981 to 1995, for the overall population and for selected subpopulations. Second, to examine factors associated with receiving intensive utilization. Cross-sectional and trend analysis of national birth records. The United States. All live births between 1981 and 1995 (N=54 million). Trends in prenatal care utilization, according to 4 indices (the older indices: the Institute of Medicine Index and the trimester that care began, and the newer indices: the R-GINDEX and the Adequacy of Prenatal Care Utilization Index). Multiple logistic regression was used to assess the risk of intensive prenatal care use in 1981 and 1995. The newer indices showed a steadily increasing trend toward more prenatal care use throughout the study period (R-GINDEX, intensive or adequate use, 32.7% in 1981 to 47.1 % in 1995; the Adequacy of Prenatal Care Utilization Index, intensive use, 18.4% in 1981 to 28.8% in 1995), especially for intensive utilization. Women having a multiple birth were much more likely to have had intensive utilization in 1995 compared with 1981 (R-GINDEX, 22.8% vs 8.5%). Teenagers were more likely to begin care later than adults, but similar proportions of teens and adults had intensive utilization. Intensive use among low-risk women also increased steadily each year. Factors associated with a greater likelihood of receiving intensive use in 1981 and 1995 were having a multiple birth, primiparity, being married, and maternal age of 35 years or older. The proportion of women who began care early and received at least the recommended number of visits increased between 1981 and 1995. This change was undetected by more traditional prenatal care indices. These increases have cost and practice implications and suggest a paradox since previous studies have shown that rates of preterm delivery and low birth weight did not improve during this time.

Recent developments on SMA actuators: predicting the actuation fatigue life for variable loading schemes

NASA Astrophysics Data System (ADS)

Wheeler, Robert W.; Lagoudas, Dimitris C.

2017-04-01

Shape memory alloys (SMAs), due to their ability to repeatably recover substantial deformations under applied mechanical loading, have the potential to impact the aerospace, automotive, biomedical, and energy industries as weight and volume saving replacements for conventional actuators. While numerous applications of SMA actuators have been flight tested and can be found in industrial applications, these actuators are generally limited to non-critical components, are not widely implemented and frequently one-off designs, and are generally overdesigned due to a lack of understanding of the effect of the loading path on the fatigue life and the lack of an accurate method for predicting actuator lifetimes. In recent years, multiple research efforts have increased our understanding of the actuation fatigue process of SMAs. These advances can be utilized to predict the fatigue lives and failure loads in SMA actuators. Additionally, these prediction methods can be implemented in order to intelligently design actuators in accordance with their fatigue and failure limits. In the following paper, both simple and complex thermomechanical loading paths have been considered. Experimental data was utilized from two material systems: equiatomic Nickel-Titanium and Nickelrich Nickel-Titanium.

Animal models of Parkinson's disease: limits and relevance to neuroprotection studies.

PubMed

Bezard, Erwan; Yue, Zhenyu; Kirik, Deniz; Spillantini, Maria Grazia

2013-01-01

Over the last two decades, significant strides has been made toward acquiring a better knowledge of both the etiology and pathogenesis of Parkinson's disease (PD). Experimental models are of paramount importance to obtain greater insights into the pathogenesis of the disease. Thus far, neurotoxin-based animal models have been the most popular tools employed to produce selective neuronal death in both in vitro and in vivo systems. These models have been commonly referred to as the pathogenic models. The current trend in modeling PD revolves around what can be called the disease gene-based models or etiologic models. The value of utilizing multiple models with a different mechanism of insult rests on the premise that dopamine-producing neurons die by stereotyped cascades that can be activated by a range of insults, from neurotoxins to downregulation and overexpression of disease-related genes. In this position article, we present the relevance of both pathogenic and etiologic models as well as the concept of clinically relevant designs that, we argue, should be utilized in the preclinical development phase of new neuroprotective therapies before embarking into clinical trials. Copyright © 2013 Movement Disorders Society.

The effect of garlic supplements and phytochemicals on the ADMET properties of drugs.

PubMed

Berginc, Katja; Kristl, Albin

2012-03-01

Garlic supplements have received wide public attention because of their health-beneficial effects. Although these products are considered as innocuous, several case reports and studies have shown the capacity of individual garlic phytochemicals/supplements to interfere with drug pharmacokinetics. This review covers recently published literature on garlic chemistry and composition, and provides a thorough review of published studies evaluating drug-garlic interactions. The authors illustrate the mechanisms underlying pharmacokinetic interactions, which could serve as important highlights in further research to explain results for drugs with narrow therapeutic indices or for drugs, utilizing multiple absorption, distribution and metabolism pathways. To increase the relevance of further research on safety and efficacy of garlic supplements and phytochemicals, their composition should be addressed before conducting in vitro or in vivo research. It is also strongly recommended to characterize in vitro formulation performance to assess the rate and extent of garlic phytochemical release in order to anticipate the in vivo impact on the pharmacokinetics of concomitantly consumed drugs. The main conclusion of this review is that the impact of garlic on different stages of pharmacokinetics, especially on drug absorption and metabolism, is drug specific and dependent on the type/quality of utilized supplement.

87. ARAIII. GCRE reactor building (ARA608) Mechanical equipment room. Utility ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

87. ARA-III. GCRE reactor building (ARA-608) Mechanical equipment room. Utility air receiver, dryer, and compressor sit on their foundations prior to grouting. December 22, 1958. Ineel photo no. 58-6429. Photographer: Ken Mansfield. - Idaho National Engineering Laboratory, Army Reactors Experimental Area, Scoville, Butte County, ID

Advanced Image Processing for NASA Applications

NASA Technical Reports Server (NTRS)

LeMoign, Jacqueline

2007-01-01

The future of space exploration will involve cooperating fleets of spacecraft or sensor webs geared towards coordinated and optimal observation of Earth Science phenomena. The main advantage of such systems is to utilize multiple viewing angles as well as multiple spatial and spectral resolutions of sensors carried on multiple spacecraft but acting collaboratively as a single system. Within this framework, our research focuses on all areas related to sensing in collaborative environments, which means systems utilizing intracommunicating spatially distributed sensor pods or crafts being deployed to monitor or explore different environments. This talk will describe the general concept of sensing in collaborative environments, will give a brief overview of several technologies developed at NASA Goddard Space Flight Center in this area, and then will concentrate on specific image processing research related to that domain, specifically image registration and image fusion.

High-Performance, Multi-Node File Copies and Checksums for Clustered File Systems

NASA Technical Reports Server (NTRS)

Kolano, Paul Z.; Ciotti, Robert B.

2012-01-01

Modern parallel file systems achieve high performance using a variety of techniques, such as striping files across multiple disks to increase aggregate I/O bandwidth and spreading disks across multiple servers to increase aggregate interconnect bandwidth. To achieve peak performance from such systems, it is typically necessary to utilize multiple concurrent readers/writers from multiple systems to overcome various singlesystem limitations, such as number of processors and network bandwidth. The standard cp and md5sum tools of GNU coreutils found on every modern Unix/Linux system, however, utilize a single execution thread on a single CPU core of a single system, and hence cannot take full advantage of the increased performance of clustered file systems. Mcp and msum are drop-in replacements for the standard cp and md5sum programs that utilize multiple types of parallelism and other optimizations to achieve maximum copy and checksum performance on clustered file systems. Multi-threading is used to ensure that nodes are kept as busy as possible. Read/write parallelism allows individual operations of a single copy to be overlapped using asynchronous I/O. Multinode cooperation allows different nodes to take part in the same copy/checksum. Split-file processing allows multiple threads to operate concurrently on the same file. Finally, hash trees allow inherently serial checksums to be performed in parallel. Mcp and msum provide significant performance improvements over standard cp and md5sum using multiple types of parallelism and other optimizations. The total speed-ups from all improvements are significant. Mcp improves cp performance over 27x, msum improves md5sum performance almost 19x, and the combination of mcp and msum improves verified copies via cp and md5sum by almost 22x. These improvements come in the form of drop-in replacements for cp and md5sum, so are easily used and are available for download as open source software at http://mutil.sourceforge.net.

Utility of Inferential Norming with Smaller Sample Sizes

ERIC Educational Resources Information Center

Zhu, Jianjun; Chen, Hsin-Yi

2011-01-01

We examined the utility of inferential norming using small samples drawn from the larger "Wechsler Intelligence Scales for Children-Fourth Edition" (WISC-IV) standardization data set. The quality of the norms was estimated with multiple indexes such as polynomial curve fit, percentage of cases receiving the same score, average absolute…

Generalized Cartographic and Simultaneous Representation of Utility Networks for Decision-Support Systems and Crisis Management in Urban Environments

NASA Astrophysics Data System (ADS)

Becker, T.; König, G.

2015-10-01

Cartographic visualizations of crises are used to create a Common Operational Picture (COP) and enforce Situational Awareness by presenting relevant information to the involved actors. As nearly all crises affect geospatial entities, geo-data representations have to support location-specific analysis throughout the decision-making process. Meaningful cartographic presentation is needed for coordinating the activities of crisis manager in a highly dynamic situation, since operators' attention span and their spatial memories are limiting factors during the perception and interpretation process. Situational Awareness of operators in conjunction with a COP are key aspects in decision-making process and essential for making well thought-out and appropriate decisions. Considering utility networks as one of the most complex and particularly frequent required systems in urban environment, meaningful cartographic presentation of multiple utility networks with respect to disaster management do not exist. Therefore, an optimized visualization of utility infrastructure for emergency response procedures is proposed. The article will describe a conceptual approach on how to simplify, aggregate, and visualize multiple utility networks and their components to meet the requirements of the decision-making process and to support Situational Awareness.

Factors influencing behavior guidance: a survey of practicing pediatric dentists.

PubMed

Juntgen, Laura M; Sanders, Brian J; Walker, Laquia A; Jones, James E; Weddell, James A; Tomlin, Angela M; Eckert, George; Maupome, Gerardo

2013-01-01

The purpose of this study was to identify factors influencing behavior guidance technique utilization among practicing pediatric dentists and explore potential barriers to the incorporation of previously unused techniques. The data for this study were obtained from a web-based survey containing 15 multiple choice questions concerning the practitioners' past, current, and anticipated future behavior guidance technique utilization. Most respondents received hands-on training in 10 of the American Academy of Pediatric Dentistry behavior guidance techniques. The type of training was associated with the practitioners' level of comfort using a given technique upon graduation and with the current frequency of technique utilization. Residency type impacted hands-on behavior guidance training, with 39 percent of respondents reporting no intravenous sedation training. The type of practice was associated with the frequency of behavior guidance technique utilization, as was graduation decade. Currently practicing dentists cited legal concerns, parental acceptance to change, and limited resources as perceived obstacles in the incorporation of new techniques. Behavior guidance technique selection and utilization among practicing pediatric dentists was influenced by multiple factors, including advanced education training, residency type, graduation decade, and practice type. Obstacles to the incorporation of previously unused techniques appear to be multifactorial.

User-Centric Multi-Criteria Information Retrieval

NASA Technical Reports Server (NTRS)

Wolfe, Shawn R.; Zhang, Yi

2009-01-01

Information retrieval models usually represent content only, and not other considerations, such as authority, cost, and recency. How could multiple criteria be utilized in information retrieval, and how would it affect the results? In our experiments, using multiple user-centric criteria always produced better results than a single criteria.

Minimum Fuel Trajectory Design in Multiple Dynamical Environments Utilizing Direct Transcription Methods and Particle Swarm Optimization

DTIC Science & Technology

2016-03-01

89 3.1.3 NLP Improvement...3.2.1.2 NLP Improvement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98 3.2.2 Multiple-burn Planar LEO to GEO Transfer...101 3.2.2.1 PSO Initial Guess Generation . . . . . . . . . . . . . . . . . . . . . 101 3.2.2.2 NLP Improvement

A reference set of health utilities for long-term survivors of prostate cancer: population-based data from Ontario, Canada.

PubMed

Krahn, Murray D; Bremner, Karen E; Alibhai, Shabbir M H; Ni, Andy; Tomlinson, George; Laporte, Audrey; Naglie, Gary

2013-12-01

To measure quality of life (QOL) and utilities for prostate cancer (PC) patients and determine their predictors. A population-based, community-dwelling, geographically diverse sample of long-term PC survivors in Ontario, Canada, was identified from the Ontario Cancer Registry and contacted through their referring physician. Consenting patients completed questionnaires by mail: Health Utilities Index (HUI 2/3), Patient Oriented Prostate Utility Scale PORPUS-U (utility), PORPUS-P (health profile), Functional Assessment of Cancer Therapy-Prostate (FACT-P), and Prostate Cancer Index (PCI). Clinical data were obtained from chart reviews. Regression models determined the effects of a series of variables on QOL and utility. We received questionnaires and reviewed charts for 585 patients (mean age 72.6, 2-13 years postdiagnosis). Mean utility scores were as follows: PORPUS-U = 0.92, HUI2 = 0.85, and HUI3 = 0.78. Mean health profile scores were as follows: PORPUS-P = 71.7, PCI sexual, urinary, and bowel function = 23.7, 79.1, and 84.6, respectively (0 = worst, 100 = best), and FACT-P = 125.1 (0 = worst, 156 = best). In multiple regression analyses, comorbidity and PCI urinary, sexual, and bowel function were significant predictors of other QOL measures. With all variables, 32-50 % of the variance in utilities was explained. Many variables affect global QOL of PC survivors; only prostate symptoms and comorbidity have independent effects. Our model allows estimation of the effects of multiple factors on utilities. These utilities for long-term outcomes of PC and its treatment are valuable for decision/cost-effectiveness models of PC treatment.

Does the utilization of dental services associate with masticatory performance in a Japanese urban population?: the Suita study

PubMed Central

Kikui, Miki; Kida, Momoyo; Kosaka, Takayuki; Yamamoto, Masaaki; Yoshimuta, Yoko; Yasui, Sakae; Nokubi, Takashi; Maeda, Yoshinobu; Kokubo, Yoshihiro; Watanabe, Makoto; Miyamoto, Yoshihiro

2015-01-01

Abstract There are numerous reports on the relationship between regular utilization of dental care services and oral health, but most are based on questionnaires and subjective evaluation. Few have objectively evaluated masticatory performance and its relationship to utilization of dental care services. The purpose of this study was to identify the effect of regular utilization of dental services on masticatory performance. The subjects consisted of 1804 general residents of Suita City, Osaka Prefecture (760 men and 1044 women, mean age 66.5 ± 7.9 years). Regular utilization of dental services and oral hygiene habits (frequency of toothbrushing and use of interdental aids) was surveyed, and periodontal status, occlusal support, and masticatory performance were measured. Masticatory performance was evaluated by a chewing test using gummy jelly. The correlation between age, sex, regular dental utilization, oral hygiene habits, periodontal status or occlusal support, and masticatory performance was analyzed using Spearman's correlation test and t‐test. In addition, multiple linear regression analysis was carried out to investigate the relationship of regular dental utilization with masticatory performance after controlling for other factors. Masticatory performance was significantly correlated to age when using Spearman's correlation test, and to regular dental utilization, periodontal status, or occlusal support with t‐test. Multiple linear regression analysis showed that regular utilization of dental services was significantly related to masticatory performance even after adjusting for age, sex, oral hygiene habits, periodontal status, and occlusal support (standardized partial regression coefficient β = 0.055). These findings suggested that the regular utilization of dental care services is an important factor influencing masticatory performance in a Japanese urban population. PMID:29744141

Does the utilization of dental services associate with masticatory performance in a Japanese urban population?: the Suita study.

PubMed

Kikui, Miki; Ono, Takahiro; Kida, Momoyo; Kosaka, Takayuki; Yamamoto, Masaaki; Yoshimuta, Yoko; Yasui, Sakae; Nokubi, Takashi; Maeda, Yoshinobu; Kokubo, Yoshihiro; Watanabe, Makoto; Miyamoto, Yoshihiro

2015-12-01

There are numerous reports on the relationship between regular utilization of dental care services and oral health, but most are based on questionnaires and subjective evaluation. Few have objectively evaluated masticatory performance and its relationship to utilization of dental care services. The purpose of this study was to identify the effect of regular utilization of dental services on masticatory performance. The subjects consisted of 1804 general residents of Suita City, Osaka Prefecture (760 men and 1044 women, mean age 66.5 ± 7.9 years). Regular utilization of dental services and oral hygiene habits (frequency of toothbrushing and use of interdental aids) was surveyed, and periodontal status, occlusal support, and masticatory performance were measured. Masticatory performance was evaluated by a chewing test using gummy jelly. The correlation between age, sex, regular dental utilization, oral hygiene habits, periodontal status or occlusal support, and masticatory performance was analyzed using Spearman's correlation test and t -test. In addition, multiple linear regression analysis was carried out to investigate the relationship of regular dental utilization with masticatory performance after controlling for other factors. Masticatory performance was significantly correlated to age when using Spearman's correlation test, and to regular dental utilization, periodontal status, or occlusal support with t -test. Multiple linear regression analysis showed that regular utilization of dental services was significantly related to masticatory performance even after adjusting for age, sex, oral hygiene habits, periodontal status, and occlusal support (standardized partial regression coefficient β  = 0.055). These findings suggested that the regular utilization of dental care services is an important factor influencing masticatory performance in a Japanese urban population.

Mindfulness Meditation for Fibromyalgia: Mechanistic and Clinical Considerations.

PubMed

Adler-Neal, Adrienne L; Zeidan, Fadel

2017-09-01

Fibromyalgia is a disorder characterized by widespread pain and a spectrum of psychological comorbidities, rendering treatment difficult and often a financial burden. Fibromyalgia is a complicated chronic pain condition that requires a multimodal therapeutic approach to optimize treatment efficacy. Thus, it has been postulated that mind-body techniques may prove fruitful in treating fibromyalgia. Mindfulness meditation, a behavioral technique premised on non-reactive sensory awareness, attenuates pain and improves mental health outcomes. However, the impact of mindfulness meditation on fibromyalgia-related outcomes has not been comprehensively characterized. The present review delineates the existing evidence supporting the effectiveness and hypothesized mechanisms of mindfulness meditation in treating fibromyalgia-related outcomes. Mindfulness-based interventions premised on cultivating acceptance, non-attachment, and social engagement may be most effective in decreasing fibromyalgia-related pain and psychological symptoms. Mindfulness-based therapies may alleviate fibromyalgia-related outcomes through multiple neural, psychological, and physiological processes. Mindfulness meditation may provide an effective complementary treatment approach for fibromyalgia patients, especially when combined with other reliable techniques (exercise; cognitive behavioral therapy). However, characterizing the specific analgesic mechanisms supporting mindfulness meditation is a critical step to fostering the clinical validity of this technique. Identification of the specific analgesic mechanisms supporting mindfulness-based pain relief could be utilized to better design behavioral interventions to specifically target fibromyalgia-related outcomes.

HTLV-1 Tax Functions as a Ubiquitin E3 Ligase for Direct IKK Activation via Synthesis of Mixed-Linkage Polyubiquitin Chains.

PubMed

Wang, Chong; Long, Wenying; Peng, Chao; Hu, Lin; Zhang, Qiong; Wu, Ailing; Zhang, Xiaoqing; Duan, Xiaotao; Wong, Catherine C L; Tanaka, Yuetsu; Xia, Zongping

2016-04-01

The HTLV-1 oncoprotein Tax plays a key role in CD4+ T cell transformation by promoting cell proliferation and survival, mainly through permanent activation of the NK-κB pathway and induction of many NF-κB target genes. Elucidating the underlying molecular mechanism is therefore critical in understanding HTLV-1-mediated transformation. Current studies have suggested multiple but controversial mechanisms regarding Tax-induced IKK activation mainly due to blending of primary Tax-induced IKK activation events and secondary IKK activation events induced by cytokines secreted by the primary Tax-induced IKK-NF-κB activation events. We reconstituted Tax-stimulated IKK activation in a cell-free system to dissect the essential cellular components for primary IKK activation by Tax and studied the underlying biochemical mechanism. We found that Tax is a putative E3 ubiquitin ligase, which, together with UbcH2, UhcH5c, or UbcH7, catalyzes the assembly of free mixed-linkage polyubiquitin chains. These free mixed-linkage polyubiquitin chains are then responsible for direct IKK activation by binding to the NEMO subunit of IKK. Our studies revealed the biochemical function of Tax in the process of IKK activation, which utilizes the minimal cellular ubiquitination components for NF-κB activation.

HTLV-1 Tax Functions as a Ubiquitin E3 Ligase for Direct IKK Activation via Synthesis of Mixed-Linkage Polyubiquitin Chains

PubMed Central

Wang, Chong; Long, Wenying; Peng, Chao; Hu, Lin; Zhang, Qiong; Wu, Ailing; Zhang, Xiaoqing; Duan, Xiaotao; Wong, Catherine C. L.; Tanaka, Yuetsu; Xia, Zongping

2016-01-01

The HTLV-1 oncoprotein Tax plays a key role in CD4+ T cell transformation by promoting cell proliferation and survival, mainly through permanent activation of the NK-κB pathway and induction of many NF-κB target genes. Elucidating the underlying molecular mechanism is therefore critical in understanding HTLV-1-mediated transformation. Current studies have suggested multiple but controversial mechanisms regarding Tax-induced IKK activation mainly due to blending of primary Tax-induced IKK activation events and secondary IKK activation events induced by cytokines secreted by the primary Tax-induced IKK-NF-κB activation events. We reconstituted Tax-stimulated IKK activation in a cell-free system to dissect the essential cellular components for primary IKK activation by Tax and studied the underlying biochemical mechanism. We found that Tax is a putative E3 ubiquitin ligase, which, together with UbcH2, UhcH5c, or UbcH7, catalyzes the assembly of free mixed-linkage polyubiquitin chains. These free mixed-linkage polyubiquitin chains are then responsible for direct IKK activation by binding to the NEMO subunit of IKK. Our studies revealed the biochemical function of Tax in the process of IKK activation, which utilizes the minimal cellular ubiquitination components for NF-κB activation. PMID:27082114

Predictive representations can link model-based reinforcement learning to model-free mechanisms.

PubMed

Russek, Evan M; Momennejad, Ida; Botvinick, Matthew M; Gershman, Samuel J; Daw, Nathaniel D

2017-09-01

Humans and animals are capable of evaluating actions by considering their long-run future rewards through a process described using model-based reinforcement learning (RL) algorithms. The mechanisms by which neural circuits perform the computations prescribed by model-based RL remain largely unknown; however, multiple lines of evidence suggest that neural circuits supporting model-based behavior are structurally homologous to and overlapping with those thought to carry out model-free temporal difference (TD) learning. Here, we lay out a family of approaches by which model-based computation may be built upon a core of TD learning. The foundation of this framework is the successor representation, a predictive state representation that, when combined with TD learning of value predictions, can produce a subset of the behaviors associated with model-based learning, while requiring less decision-time computation than dynamic programming. Using simulations, we delineate the precise behavioral capabilities enabled by evaluating actions using this approach, and compare them to those demonstrated by biological organisms. We then introduce two new algorithms that build upon the successor representation while progressively mitigating its limitations. Because this framework can account for the full range of observed putatively model-based behaviors while still utilizing a core TD framework, we suggest that it represents a neurally plausible family of mechanisms for model-based evaluation.

Predictive representations can link model-based reinforcement learning to model-free mechanisms

PubMed Central

Botvinick, Matthew M.

2017-01-01

Humans and animals are capable of evaluating actions by considering their long-run future rewards through a process described using model-based reinforcement learning (RL) algorithms. The mechanisms by which neural circuits perform the computations prescribed by model-based RL remain largely unknown; however, multiple lines of evidence suggest that neural circuits supporting model-based behavior are structurally homologous to and overlapping with those thought to carry out model-free temporal difference (TD) learning. Here, we lay out a family of approaches by which model-based computation may be built upon a core of TD learning. The foundation of this framework is the successor representation, a predictive state representation that, when combined with TD learning of value predictions, can produce a subset of the behaviors associated with model-based learning, while requiring less decision-time computation than dynamic programming. Using simulations, we delineate the precise behavioral capabilities enabled by evaluating actions using this approach, and compare them to those demonstrated by biological organisms. We then introduce two new algorithms that build upon the successor representation while progressively mitigating its limitations. Because this framework can account for the full range of observed putatively model-based behaviors while still utilizing a core TD framework, we suggest that it represents a neurally plausible family of mechanisms for model-based evaluation. PMID:28945743

Thalamocortical dynamics of the McCollough effect: boundary-surface alignment through perceptual learning.

PubMed

Grossberg, Stephen; Hwang, Seungwoo; Mingolla, Ennio

2002-05-01

This article further develops the FACADE neural model of 3-D vision and figure-ground perception to quantitatively explain properties of the McCollough effect (ME). The model proposes that many ME data result from visual system mechanisms whose primary function is to adaptively align, through learning, boundary and surface representations that are positionally shifted due to the process of binocular fusion. For example, binocular boundary representations are shifted by binocular fusion relative to monocular surface representations, yet the boundaries must become positionally aligned with the surfaces to control binocular surface capture and filling-in. The model also includes perceptual reset mechanisms that use habituative transmitters in opponent processing circuits. Thus the model shows how ME data may arise from a combination of mechanisms that have a clear functional role in biological vision. Simulation results with a single set of parameters quantitatively fit data from 13 experiments that probe the nature of achromatic/chromatic and monocular/binocular interactions during induction of the ME. The model proposes how perceptual learning, opponent processing, and habituation at both monocular and binocular surface representations are involved, including early thalamocortical sites. In particular, it explains the anomalous ME utilizing these multiple processing sites. Alternative models of the ME are also summarized and compared with the present model.

ISS External Contamination Environment for Space Science Utilization

NASA Technical Reports Server (NTRS)

Soares, Carlos; Mikatarian, Ron; Steagall, Courtney; Huang, Alvin; Koontz, Steven; Worthy, Erica

2014-01-01

(1) The International Space Station is the largest and most complex on-orbit platform for space science utilization in low Earth orbit, (2) Multiple sites for external payloads, with exposure to the associated natural and induced environments, are available to support a variety of space science utilization objectives, (3) Contamination is one of the induced environments that can impact performance, mission success and science utilization on the vehicle, and (4)The ISS has been designed, built and integrated with strict contamination requirements to provide low levels of induced contamination on external payload assets.

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

Anderson, Mathew; Bowen, Brian; Coles, Dwight

The Middleware Automated Deployment Utilities consists the these three components: MAD: Utility designed to automate the deployment of java applications to multiple java application servers. The product contains a front end web utility and backend deployment scripts. MAR: Web front end to maintain and update the components inside database. MWR-Encrypt: Web utility to convert a text string to an encrypted string that is used by the Oracle Weblogic application server. The encryption is done using the built in functions if the Oracle Weblogic product and is mainly used to create an encrypted version of a database password.

Method and Apparatus for Reducing Noise from Near Ocean Surface Sources

DTIC Science & Technology

2001-10-01

reducing the acoustic noise from near-surface 4 sources using an array processing technique that utilizes 5 Multiple Signal Classification ( MUSIC ...sources without 13 degrading the signal level and quality of the TOI. The present 14 invention utilizes a unique application of the MUSIC beamforming...specific algorithm that utilizes a 5 MUSIC technique and estimates the direction of arrival (DOA) of 6 the acoustic signal signals and generates output

Utilizing the Zero-One Linear Programming Constraints to Draw Multiple Sets of Matched Samples from a Non-Treatment Population as Control Groups for the Quasi-Experimental Design

ERIC Educational Resources Information Center

Li, Yuan H.; Yang, Yu N.; Tompkins, Leroy J.; Modarresi, Shahpar

2005-01-01

The statistical technique, "Zero-One Linear Programming," that has successfully been used to create multiple tests with similar characteristics (e.g., item difficulties, test information and test specifications) in the area of educational measurement, was deemed to be a suitable method for creating multiple sets of matched samples to be…

Heterogeneity of reward mechanisms.

PubMed

Lajtha, A; Sershen, H

2010-06-01

The finding that many drugs that have abuse potential and other natural stimuli such as food or sexual activity cause similar chemical changes in the brain, an increase in extracellular dopamine (DA) in the shell of the nucleus accumbens (NAccS), indicated some time ago that the reward mechanism is at least very similar for all stimuli and that the mechanism is relatively simple. The presently available information shows that the mechanisms involved are more complex and have multiple elements. Multiple brain regions, multiple receptors, multiple distinct neurons, multiple transmitters, multiple transporters, circuits, peptides, proteins, metabolism of transmitters, and phosphorylation, all participate in reward mechanisms. The system is variable, is changed during development, is sex-dependent, and is influenced by genetic differences. Not all of the elements participate in the reward of all stimuli. Different set of mechanisms are involved in the reward of different drugs of abuse, yet different mechanisms in the reward of natural stimuli such as food or sexual activity; thus there are different systems that distinguish different stimuli. Separate functions of the reward system such as anticipation, evaluation, consummation and identification; all contain function-specific elements. The level of the stimulus also influences the participation of the elements of the reward system, there are possible reactions to even below threshold stimuli, and excessive stimuli can change reward to aversion involving parts of the system. Learning and memory of past reward is an important integral element of reward and addictive behavior. Many of the reward elements are altered by repeated or chronic stimuli, and chronic exposure to one drug is likely to alter the response to another stimulus. To evaluate and identify the reward stimulus thus requires heterogeneity of the reward components in the brain.

High-Performance Anti-Retransmission Deception Jamming Utilizing Range Direction Multiple Input and Multiple Output (MIMO) Synthetic Aperture Radar (SAR).

PubMed

Wang, Ruijia; Chen, Jie; Wang, Xing; Sun, Bing

2017-01-09

Retransmission deception jamming seriously degrades the Synthetic Aperture Radar (SAR) detection efficiency and can mislead SAR image interpretation by forming false targets. In order to suppress retransmission deception jamming, this paper proposes a novel multiple input and multiple output (MIMO) SAR structure range direction MIMO SAR, whose multiple channel antennas are vertical to the azimuth. First, based on the multiple channels of range direction MIMO SAR, the orthogonal frequency division multiplexing (OFDM) linear frequency modulation (LFM) signal was adopted as the transmission signal of each channel, which is defined as a sub-band signal. This sub-band signal corresponds to the transmission channel. Then, all of the sub-band signals are modulated with random initial phases and concurrently transmitted. The signal form is more complex and difficult to intercept. Next, the echoes of the sub-band signal are utilized to synthesize a wide band signal after preprocessing. The proposed method will increase the signal to interference ratio and peak amplitude ratio of the signal to resist retransmission deception jamming. Finally, well-focused SAR imagery is obtained using a conventional imaging method where the retransmission deception jamming strength is degraded and defocused. Simulations demonstrated the effectiveness of the proposed method.

High-Performance Anti-Retransmission Deception Jamming Utilizing Range Direction Multiple Input and Multiple Output (MIMO) Synthetic Aperture Radar (SAR)

PubMed Central

Wang, Ruijia; Chen, Jie; Wang, Xing; Sun, Bing

2017-01-01

Retransmission deception jamming seriously degrades the Synthetic Aperture Radar (SAR) detection efficiency and can mislead SAR image interpretation by forming false targets. In order to suppress retransmission deception jamming, this paper proposes a novel multiple input and multiple output (MIMO) SAR structure range direction MIMO SAR, whose multiple channel antennas are vertical to the azimuth. First, based on the multiple channels of range direction MIMO SAR, the orthogonal frequency division multiplexing (OFDM) linear frequency modulation (LFM) signal was adopted as the transmission signal of each channel, which is defined as a sub-band signal. This sub-band signal corresponds to the transmission channel. Then, all of the sub-band signals are modulated with random initial phases and concurrently transmitted. The signal form is more complex and difficult to intercept. Next, the echoes of the sub-band signal are utilized to synthesize a wide band signal after preprocessing. The proposed method will increase the signal to interference ratio and peak amplitude ratio of the signal to resist retransmission deception jamming. Finally, well-focused SAR imagery is obtained using a conventional imaging method where the retransmission deception jamming strength is degraded and defocused. Simulations demonstrated the effectiveness of the proposed method. PMID:28075367

MultiGeMS: detection of SNVs from multiple samples using model selection on high-throughput sequencing data.

PubMed

Murillo, Gabriel H; You, Na; Su, Xiaoquan; Cui, Wei; Reilly, Muredach P; Li, Mingyao; Ning, Kang; Cui, Xinping

2016-05-15

Single nucleotide variant (SNV) detection procedures are being utilized as never before to analyze the recent abundance of high-throughput DNA sequencing data, both on single and multiple sample datasets. Building on previously published work with the single sample SNV caller genotype model selection (GeMS), a multiple sample version of GeMS (MultiGeMS) is introduced. Unlike other popular multiple sample SNV callers, the MultiGeMS statistical model accounts for enzymatic substitution sequencing errors. It also addresses the multiple testing problem endemic to multiple sample SNV calling and utilizes high performance computing (HPC) techniques. A simulation study demonstrates that MultiGeMS ranks highest in precision among a selection of popular multiple sample SNV callers, while showing exceptional recall in calling common SNVs. Further, both simulation studies and real data analyses indicate that MultiGeMS is robust to low-quality data. We also demonstrate that accounting for enzymatic substitution sequencing errors not only improves SNV call precision at low mapping quality regions, but also improves recall at reference allele-dominated sites with high mapping quality. The MultiGeMS package can be downloaded from https://github.com/cui-lab/multigems xinping.cui@ucr.edu Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Bioinspired legged-robot based on large deformation of flexible skeleton.

PubMed

Mayyas, Mohammad

2014-11-11

In this article we present STARbot, a bioinspired legged robot capable of multiple locomotion modalities by using large deformation of its skeleton. We construct STARbot by using origami-style folding of flexible laminates. The long-term goal is to provide a robotic platform with maximum mobility on multiple surfaces. This paper particularly studies the quasistatic model of STARbot's leg under different conditions. We describe the large elastic deformation of a leg under external force, payload, and friction by using a set of non-dimensional, nonlinear approximate equations. We developed a test mechanism that models the motion of a leg in STARbot. We augmented several foot shapes and then tested them on soft to rough grounds. Both simulation and experimental findings were in good agreement. We utilized the model to develop several scales of tri and quad STARbot. We demonstrated the capability of these robots to locomote by combining their leg deformations with their foot motions. The combination provided a design platform for an active suspension STARbot with controlled foot locomotion. This included the ability of STARbot to change size, run over obstacles, walk and slide. Furthermore, in this paper we discuss a cost effective manufacturing and production method for manufacturing STARbot.

How protein materials balance strength, robustness, and adaptability

PubMed Central

Buehler, Markus J.; Yung, Yu Ching

2010-01-01

Proteins form the basis of a wide range of biological materials such as hair, skin, bone, spider silk, or cells, which play an important role in providing key functions to biological systems. The focus of this article is to discuss how protein materials are capable of balancing multiple, seemingly incompatible properties such as strength, robustness, and adaptability. To illustrate this, we review bottom-up materiomics studies focused on the mechanical behavior of protein materials at multiple scales, from nano to macro. We focus on alpha-helix based intermediate filament proteins as a model system to explain why the utilization of hierarchical structural features is vital to their ability to combine strength, robustness, and adaptability. Experimental studies demonstrating the activation of angiogenesis, the growth of new blood vessels, are presented as an example of how adaptability of structure in biological tissue is achieved through changes in gene expression that result in an altered material structure. We analyze the concepts in light of the universality and diversity of the structural makeup of protein materials and discuss the findings in the context of potential fundamental evolutionary principles that control their nanoscale structure. We conclude with a discussion of multiscale science in biology and de novo materials design. PMID:20676305

Making objective decisions in mechanical engineering problems

NASA Astrophysics Data System (ADS)

Raicu, A.; Oanta, E.; Sabau, A.

2017-08-01

Decision making process has a great influence in the development of a given project, the goal being to select an optimal choice in a given context. Because of its great importance, the decision making was studied using various science methods, finally being conceived the game theory that is considered the background for the science of logical decision making in various fields. The paper presents some basic ideas regarding the game theory in order to offer the necessary information to understand the multiple-criteria decision making (MCDM) problems in engineering. The solution is to transform the multiple-criteria problem in a one-criterion decision problem, using the notion of utility, together with the weighting sum model or the weighting product model. The weighted importance of the criteria is computed using the so-called Step method applied to a relation of preferences between the criteria. Two relevant examples from engineering are also presented. The future directions of research consist of the use of other types of criteria, the development of computer based instruments for decision making general problems and to conceive a software module based on expert system principles to be included in the Wiki software applications for polymeric materials that are already operational.

Dynamic load mitigation using dissipative elastic metamaterials with multiple Maxwell-type oscillators

NASA Astrophysics Data System (ADS)

Alamri, Sagr; Li, Bing; Tan, K. T.

2018-03-01

Dissipative elastic metamaterials have attracted increased attention in recent times. This paper presents the development of a dissipative elastic metamaterial with multiple Maxwell-type resonators for stress wave attenuation. The mechanism of the dissipation effect on the vibration characteristics is systematically investigated by mass-spring-damper models with single and dual resonators. Based on the parameter optimization, it is revealed that a broadband wave attenuation region (stopping band) can be obtained by properly utilizing interactions from resonant motions and viscoelastic effects of the Maxwell-type oscillators. The relevant numerical verifications are conducted for various cases, and excellent agreement between the numerical and theoretical frequency response functions is shown. The design of this dissipative metamaterial system is further applied for dynamic load mitigation and blast wave attenuation. Moreover, the transient response in the continuum model is designed and analyzed for more robust design. By virtue of the bandgap merging effect induced by the Maxwell-type damper, the transient blast wave can be almost completely suppressed in the low frequency range. A significantly improved performance of the proposed dissipative metamaterials for stress wave mitigation is verified in both time and frequency domains.

Overview and diagnosis of multiple sclerosis.

PubMed

Hunter, Samuel F

2016-06-01

Multiple sclerosis (MS), a chronic inflammatory disease of unknown etiology, involves an immunemediated attack of the central nervous system (CNS) that produces demyelination and axonal/neuronal damage, resulting in characteristic multifocal lesions apparent on magnetic resonance imaging and a variety of neurologic manifestations. The disease pathology is characterized by multifocal lesions within the CNS, in both the white matter and gray matter, with perivenular inflammatory cell infiltrates, demyelination, axonal transection, neuronal degeneration, and gliosis. MS pathogenesis is complex, as it involves both T- and B-cell mechanisms and is heterogeneous in presentation. Relatively recently, the historical 4 core clinical categories of MS were revised in an effort to improve characterization of the clinical course, better identify where a given patient is positioned in the disease spectrum, and to guide clinical studies. In young and middle-aged adults, MS is one of the most common contributors to neurologic disability, and it exerts detrimental effects on a patient's productivity and health-related quality of life. Typically, patients with MS have a long life span, although healthcare utilization increases over time. As a consequence, the disease places a substantial burden on patients and their caregivers/families, as well as employers, the healthcare system, and society.

Comprehensive security framework for the communication and storage of medical images

NASA Astrophysics Data System (ADS)

Slik, David; Montour, Mike; Altman, Tym

2003-05-01

Confidentiality, integrity verification and access control of medical imagery and associated metadata is critical for the successful deployment of integrated healthcare networks that extend beyond the department level. As medical imagery continues to become widely accessed across multiple administrative domains and geographically distributed locations, image data should be able to travel and be stored on untrusted infrastructure, including public networks and server equipment operated by external entities. Given these challenges associated with protecting large-scale distributed networks, measures must be taken to protect patient identifiable information while guarding against tampering, denial of service attacks, and providing robust audit mechanisms. The proposed framework outlines a series of security practices for the protection of medical images, incorporating Transport Layer Security (TLS), public and secret key cryptography, certificate management and a token based trusted computing base. It outlines measures that can be utilized to protect information stored within databases, online and nearline storage, and during transport over trusted and untrusted networks. In addition, it provides a framework for ensuring end-to-end integrity of image data from acquisition to viewing, and presents a potential solution to the challenges associated with access control across multiple administrative domains and institution user bases.

Trust-region based return mapping algorithm for implicit integration of elastic-plastic constitutive models

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

Lester, Brian; Scherzinger, William

2017-01-19

Here, a new method for the solution of the non-linear equations forming the core of constitutive model integration is proposed. Specifically, the trust-region method that has been developed in the numerical optimization community is successfully modified for use in implicit integration of elastic-plastic models. Although attention here is restricted to these rate-independent formulations, the proposed approach holds substantial promise for adoption with models incorporating complex physics, multiple inelastic mechanisms, and/or multiphysics. As a first step, the non-quadratic Hosford yield surface is used as a representative case to investigate computationally challenging constitutive models. The theory and implementation are presented, discussed, andmore » compared to other common integration schemes. Multiple boundary value problems are studied and used to verify the proposed algorithm and demonstrate the capabilities of this approach over more common methodologies. Robustness and speed are then investigated and compared to existing algorithms. Through these efforts, it is shown that the utilization of a trust-region approach leads to superior performance versus a traditional closest-point projection Newton-Raphson method and comparable speed and robustness to a line search augmented scheme.« less

Trust-region based return mapping algorithm for implicit integration of elastic-plastic constitutive models

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

Lester, Brian T.; Scherzinger, William M.

2017-01-19

A new method for the solution of the non-linear equations forming the core of constitutive model integration is proposed. Specifically, the trust-region method that has been developed in the numerical optimization community is successfully modified for use in implicit integration of elastic-plastic models. Although attention here is restricted to these rate-independent formulations, the proposed approach holds substantial promise for adoption with models incorporating complex physics, multiple inelastic mechanisms, and/or multiphysics. As a first step, the non-quadratic Hosford yield surface is used as a representative case to investigate computationally challenging constitutive models. The theory and implementation are presented, discussed, and comparedmore » to other common integration schemes. Multiple boundary value problems are studied and used to verify the proposed algorithm and demonstrate the capabilities of this approach over more common methodologies. Robustness and speed are then investigated and compared to existing algorithms. As a result through these efforts, it is shown that the utilization of a trust-region approach leads to superior performance versus a traditional closest-point projection Newton-Raphson method and comparable speed and robustness to a line search augmented scheme.« less

Analysis of Sequence Data Under Multivariate Trait-Dependent Sampling.

PubMed

Tao, Ran; Zeng, Donglin; Franceschini, Nora; North, Kari E; Boerwinkle, Eric; Lin, Dan-Yu

2015-06-01

High-throughput DNA sequencing allows for the genotyping of common and rare variants for genetic association studies. At the present time and for the foreseeable future, it is not economically feasible to sequence all individuals in a large cohort. A cost-effective strategy is to sequence those individuals with extreme values of a quantitative trait. We consider the design under which the sampling depends on multiple quantitative traits. Under such trait-dependent sampling, standard linear regression analysis can result in bias of parameter estimation, inflation of type I error, and loss of power. We construct a likelihood function that properly reflects the sampling mechanism and utilizes all available data. We implement a computationally efficient EM algorithm and establish the theoretical properties of the resulting maximum likelihood estimators. Our methods can be used to perform separate inference on each trait or simultaneous inference on multiple traits. We pay special attention to gene-level association tests for rare variants. We demonstrate the superiority of the proposed methods over standard linear regression through extensive simulation studies. We provide applications to the Cohorts for Heart and Aging Research in Genomic Epidemiology Targeted Sequencing Study and the National Heart, Lung, and Blood Institute Exome Sequencing Project.

Targeting cancer by binding iron: Dissecting cellular signaling pathways

PubMed Central

Lui, Goldie Y.L.; Kovacevic, Zaklina; Richardson, Vera; Merlot, Angelica M.; Kalinowski, Danuta S.; Richardson, Des R.

2015-01-01

Newer and more potent therapies are urgently needed to effectively treat advanced cancers that have developed resistance and metastasized. One such strategy is to target cancer cell iron metabolism, which is altered compared to normal cells and may facilitate their rapid proliferation. This is supported by studies reporting the anti-neoplastic activities of the clinically available iron chelators, desferrioxamine and deferasirox. More recently, ligands of the di-2-pyridylketone thiosemicarbazone (DpT) class have demonstrated potent and selective anti-proliferative activity across multiple cancer-types in vivo, fueling studies aimed at dissecting their molecular mechanisms of action. In the past five years alone, significant advances have been made in understanding how chelators not only modulate cellular iron metabolism, but also multiple signaling pathways implicated in tumor progression and metastasis. Herein, we discuss recent research on the targeting of iron in cancer cells, with a focus on the novel and potent DpT ligands. Several key studies have revealed that iron chelation can target the AKT, ERK, JNK, p38, STAT3, TGF-β, Wnt and autophagic pathways to subsequently inhibit cellular proliferation, the epithelial-mesenchymal transition (EMT) and metastasis. These developments emphasize that these novel therapies could be utilized clinically to effectively target cancer. PMID:26125440

Monitoring Replication Protein A (RPA) dynamics in homologous recombination through site-specific incorporation of non-canonical amino acids.

PubMed

Pokhrel, Nilisha; Origanti, Sofia; Davenport, Eric Parker; Gandhi, Disha; Kaniecki, Kyle; Mehl, Ryan A; Greene, Eric C; Dockendorff, Chris; Antony, Edwin

2017-09-19

An essential coordinator of all DNA metabolic processes is Replication Protein A (RPA). RPA orchestrates these processes by binding to single-stranded DNA (ssDNA) and interacting with several other DNA binding proteins. Determining the real-time kinetics of single players such as RPA in the presence of multiple DNA processors to better understand the associated mechanistic events is technically challenging. To overcome this hurdle, we utilized non-canonical amino acids and bio-orthogonal chemistry to site-specifically incorporate a chemical fluorophore onto a single subunit of heterotrimeric RPA. Upon binding to ssDNA, this fluorescent RPA (RPAf) generates a quantifiable change in fluorescence, thus serving as a reporter of its dynamics on DNA in the presence of multiple other DNA binding proteins. Using RPAf, we describe the kinetics of facilitated self-exchange and exchange by Rad51 and mediator proteins during various stages in homologous recombination. RPAf is widely applicable to investigate its mechanism of action in processes such as DNA replication, repair and telomere maintenance. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Targeting Transcriptional Regulators of CD8+ T Cell Dysfunction to Boost Anti-Tumor Immunity

PubMed Central

Waugh, Katherine A.; Leach, Sonia M.; Slansky, Jill E.

2015-01-01

Transcription is a dynamic process influenced by the cellular environment: healthy, transformed, and otherwise. Genome-wide mRNA expression profiles reflect the collective impact of pathways modulating cell function under different conditions. In this review we focus on the transcriptional pathways that control tumor infiltrating CD8+ T cell (TIL) function. Simultaneous restraint of overlapping inhibitory pathways may confer TIL resistance to multiple mechanisms of suppression traditionally referred to as exhaustion, tolerance, or anergy. Although decades of work have laid a solid foundation of altered transcriptional networks underlying various subsets of hypofunctional or “dysfunctional” CD8+ T cells, an understanding of the relevance in TIL has just begun. With recent technological advances, it is now feasible to further elucidate and utilize these pathways in immunotherapy platforms that seek to increase TIL function. PMID:26393659

Towards ultrahigh resting-state functional connectivity in the mouse brain using photoacoustic microscopy

NASA Astrophysics Data System (ADS)

Hariri, Ali; Bely, Nicholas; Chen, Chen; Nasiriavanaki, Mohammadreza

2016-03-01

The increasing use of mouse models for human brain disease studies, coupled with the fact that existing high-resolution functional imaging modalities cannot be easily applied to mice, presents an emerging need for a new functional imaging modality. Utilizing both mechanical and optical scanning in the photoacoustic microscopy, we can image spontaneous cerebral hemodynamic fluctuations and their associated functional connections in the mouse brain. The images is going to be acquired noninvasively with a fast frame rate, a large field of view, and a high spatial resolution. We developed an optical resolution photoacoustic microscopy (OR-PAM) with diode laser. Laser light was raster scanned due to XY-stage movement. Images from ultra-high OR-PAM can then be used to study brain disorders such as stroke, Alzheimer's, schizophrenia, multiple sclerosis, autism, and epilepsy.

Recombination Promoted by DNA Viruses: Phage λ to Herpes Simplex Virus

PubMed Central

Weller, Sandra K.; Sawitzke, James A.

2015-01-01

The purpose of this review is to explore recombination strategies in DNA viruses. Homologous recombination is a universal genetic process that plays multiple roles in the biology of all organisms, including viruses. Recombination and DNA replication are interconnected, with recombination being essential for repairing DNA damage and supporting replication of the viral genome. Recombination also creates genetic diversity, and viral recombination mechanisms have important implications for understanding viral origins as well as the dynamic nature of viral-host interactions. Both bacteriophage λ and herpes simplex virus (HSV) display high rates of recombination, both utilizing their own proteins and commandeering cellular proteins to promote recombination reactions. We focus primarily on λ and HSV, as they have proven amenable to both genetic and biochemical analysis and have recently been shown to exhibit some surprising similarities that will guide future studies. PMID:25002096

Retrospective Analysis of Communication Events - Understanding the Dynamics of Collaborative Multi-Party Discourse

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

Cowell, Andrew J.; Haack, Jereme N.; McColgin, Dave W.

2006-06-08

This research is aimed at understanding the dynamics of collaborative multi-party discourse across multiple communication modalities. Before we can truly make sig-nificant strides in devising collaborative communication systems, there is a need to understand how typical users utilize com-putationally supported communications mechanisms such as email, instant mes-saging, video conferencing, chat rooms, etc., both singularly and in conjunction with traditional means of communication such as face-to-face meetings, telephone calls and postal mail. Attempting to un-derstand an individual’s communications profile with access to only a single modal-ity is challenging at best and often futile. Here, we discuss the development of RACE –more » Retrospective Analysis of Com-munications Events – a test-bed prototype to investigate issues relating to multi-modal multi-party discourse.« less

Multi-resonant wideband energy harvester based on a folded asymmetric M-shaped cantilever

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

Wu, Meng; Mao, Haiyang; Li, Zhigang

2015-07-15

This article reports a compact wideband piezoelectric vibration energy harvester consisting of three proof masses and an asymmetric M-shaped cantilever. The M-shaped beam comprises a main beam and two folded and dimension varied auxiliary beams interconnected through the proof mass at the end of the main cantilever. Such an arrangement constitutes a three degree-of-freedom vibrating body, which can tune the resonant frequencies of its first three orders close enough to obtain a utility wide bandwidth. The finite element simulation results and the experimental results are well matched. The operation bandwidth comprises three adjacent voltage peaks on account of the frequencymore » interval shortening mechanism. The result shows that the proposed piezoelectric energy harvester could be efficient and adaptive in practical vibration circumstance based on multiple resonant modes.« less

Partitioning-based mechanisms under personalized differential privacy.

PubMed

Li, Haoran; Xiong, Li; Ji, Zhanglong; Jiang, Xiaoqian

2017-05-01

Differential privacy has recently emerged in private statistical aggregate analysis as one of the strongest privacy guarantees. A limitation of the model is that it provides the same privacy protection for all individuals in the database. However, it is common that data owners may have different privacy preferences for their data. Consequently, a global differential privacy parameter may provide excessive privacy protection for some users, while insufficient for others. In this paper, we propose two partitioning-based mechanisms, privacy-aware and utility-based partitioning, to handle personalized differential privacy parameters for each individual in a dataset while maximizing utility of the differentially private computation. The privacy-aware partitioning is to minimize the privacy budget waste, while utility-based partitioning is to maximize the utility for a given aggregate analysis. We also develop a t -round partitioning to take full advantage of remaining privacy budgets. Extensive experiments using real datasets show the effectiveness of our partitioning mechanisms.

Partitioning-based mechanisms under personalized differential privacy

PubMed Central

Li, Haoran; Xiong, Li; Ji, Zhanglong; Jiang, Xiaoqian

2017-01-01

Differential privacy has recently emerged in private statistical aggregate analysis as one of the strongest privacy guarantees. A limitation of the model is that it provides the same privacy protection for all individuals in the database. However, it is common that data owners may have different privacy preferences for their data. Consequently, a global differential privacy parameter may provide excessive privacy protection for some users, while insufficient for others. In this paper, we propose two partitioning-based mechanisms, privacy-aware and utility-based partitioning, to handle personalized differential privacy parameters for each individual in a dataset while maximizing utility of the differentially private computation. The privacy-aware partitioning is to minimize the privacy budget waste, while utility-based partitioning is to maximize the utility for a given aggregate analysis. We also develop a t-round partitioning to take full advantage of remaining privacy budgets. Extensive experiments using real datasets show the effectiveness of our partitioning mechanisms. PMID:28932827

Two-step emulsification process for water-in-oil-in-water multiple emulsions stabilized by lamellar liquid crystals.

PubMed

Ito, Toshifumi; Tsuji, Yukitaka; Aramaki, Kenji; Tonooka, Noriaki

2012-01-01

Multiple emulsions, also called complex emulsions or multiphase emulsions, include water-in-oil-in-water (W/O/W)-type and oil-in-water-in-oil (O/W/O)-type emulsions. W/O/W-type multiple emulsions, obtained by utilizing lamellar liquid crystal with a layer structure showing optical anisotropy at the periphery of emulsion droplets, are superior in stability to O/W/O-type emulsions. In this study, we investigated a two-step emulsification process for a W/O/W-type multiple emulsion utilizing liquid crystal emulsification. We found that a W/O/W-type multiple emulsion containing lamellar liquid crystal can be prepared by mixing a W/O-type emulsion (prepared by primary emulsification) with a lamellar liquid crystal obtained from poly(oxyethylene) stearyl ether, cetyl alcohol, and water, and by dispersing and emulsifying the mixture in an outer aqueous phase. When poly(oxyethylene) stearyl ether and cetyl alcohol are each used in a given amount and the amount of water added is varied from 0 to 15 g (total amount of emulsion, 100 g), a W/O/W-type multiple emulsion is efficiently prepared. When the W/O/W-type multiple emulsion was held in a thermostatic bath at 25°C, the droplet size distribution showed no change 0, 30, or 60 days after preparation. Moreover, the W/O/W-type multiple emulsion strongly encapsulated Uranine in the inner aqueous phase as compared with emulsions prepared by one-step emulsification.

Multiple-cycle Simulation of a Pulse Detonation Engine Ejector

NASA Technical Reports Server (NTRS)

Yungster, S.; Perkins, H. D.

2002-01-01

This paper presents the results of a study involving single and multiple-cycle numerical simulations of various PDE-ejector configurations utilizing hydrogen-oxygen mixtures. The objective was to investigate the thrust, impulse and mass flow rate characteristics of these devices. The results indicate that ejector systems can utilize the energy stored in the strong shock wave exiting the detonation tube to augment the impulse obtained from the detonation tube alone. Impulse augmentation ratios of up to 1.9 were achieved. The axial location of the converging-diverging ejectors relative to the end of the detonation tube were shown to affect the performance of the system.

Raccoon spatial requirements and multi-scale habitat selection within an intensively managed central Appalachian forest

USGS Publications Warehouse

Owen, Sheldon F.; Berl, Jacob L.; Edwards, John W.; Ford, W. Mark; Wood, Petra Bohall

2015-01-01

We studied a raccoon (Procyon lotor) population within a managed central Appalachian hardwood forest in West Virginia to investigate the effects of intensive forest management on raccoon spatial requirements and habitat selection. Raccoon home-range (95% utilization distribution) and core-area (50% utilization distribution) size differed between sexes with males maintaining larger (2×) home ranges and core areas than females. Home-range and core-area size did not differ between seasons for either sex. We used compositional analysis to quantify raccoon selection of six different habitat types at multiple spatial scales. Raccoons selected riparian corridors (riparian management zones [RMZ]) and intact forests (> 70 y old) at the core-area spatial scale. RMZs likely were used by raccoons because they provided abundant denning resources (i.e., large-diameter trees) as well as access to water. Habitat composition associated with raccoon foraging locations indicated selection for intact forests, riparian areas, and regenerating harvest (stands <10 y old). Although raccoons were able to utilize multiple habitat types for foraging resources, a selection of intact forest and RMZs at multiple spatial scales indicates the need of mature forest (with large-diameter trees) for this species in managed forests in the central Appalachians.

The predictive utility of neuropsychological symptom validity testing as it relates to psychological presentation.

PubMed

Zakzanis, Konstantine K; Gammada, Emnet; Jeffay, Eliyas

2012-01-01

The present study examined the relationship between multiple neuropsychological symptom validity tests (SVTs) and psychological presentation. More formally, we set out to determine if performance on neuropsychological SVTs was related to psychological symptom credibility and which specific neuropsychological SVTs were most associated with noncredible psychological presentation. Archival records from 106 litigating examinees were utilized in this study. Our results illustrate that neuropsychological SVTs are modestly related to psychological symptom credibility and that specific neuropsychological SVTs are variably associated to this end. We conclude that when multiple, but not independent, neuropsychological SVTs are employed within the context of a neuropsychological examination, they do have clinical utility as it relates to credibility of psychological presentation and these constructs do share variance reciprocally in clinically meaningful ways. When independently employed, however, the observed relationship is modest at best. Hence, to place clinical opinion on firmer scientific grounds within the context of a neuropsychological examination, multiple cognitive SVTs, in hand with psychological test instruments that include validity indexes, are essential to derive opinion that is based on science rather than faith in the instance of litigation when an incentive to manifest disability for the sake of an external reward holds probable.

Chemotherapeutic treatment of naturally acquired generalized demodicosis.

PubMed

Folz, S D; Kratzer, D D; Conklin, R D; Nowakowski, L H; Kakuk, T J; Rector, D L

1983-08-01

Fifty-two dogs naturally parasitized with Demodex canis and having the generalized form of the disease were utilized to evaluate the efficacy and safety of single or multiple topical treatments with a liquid concentrate formulation of amitraz. Ten dogs (5 treated, 5 controls) were utilized to evaluate a single treatment. A single topical treatment with the miticide did not significantly reduce the incidence of dogs with mites, however, significant clinical improvement resulted. Side-effects were not observed after treatment. Forty-two dogs (26 treated, 16 controls) were utilized to evaluate multiple topical treatments with the liquid concentrate. A series of 3-6 treatments was applied topically at 14-day intervals. The dogs treated with the miticide received an average of 4.5 topical treatments. All (100%) of the dogs responded clinically, and the mean rate of improvement at four weeks post-treatment was 99.1%. Most dogs (96.2%) were cleared of mites after 3-6 treatments, and Mitaban did not cause any dermatologic, ocular, or other clinical side-effects. Multiple treatments with the liquid concentrate were highly efficacious and safe for treatment of generalized demodicosis. Control dogs did not improve clinically and retained mite populations.

Energy Analysis of a Complementary Heating System Combining Solar Energy and Coal for a Rural Residential Building in Northwest China.

PubMed

Zhen, Xiaofei; Li, Jinping; Abdalla Osman, Yassir Idris; Feng, Rong; Zhang, Xuemin; Kang, Jian

2018-01-01

In order to utilize solar energy to meet the heating demands of a rural residential building during the winter in the northwestern region of China, a hybrid heating system combining solar energy and coal was built. Multiple experiments to monitor its performance were conducted during the winter in 2014 and 2015. In this paper, we analyze the efficiency of the energy utilization of the system and describe a prototype model to determine the thermal efficiency of the coal stove in use. Multiple linear regression was adopted to present the dual function of multiple factors on the daily heat-collecting capacity of the solar water heater; the heat-loss coefficient of the storage tank was detected as well. The prototype model shows that the average thermal efficiency of the stove is 38%, which means that the energy input for the building is divided between the coal and solar energy, 39.5% and 60.5% energy, respectively. Additionally, the allocation of the radiation of solar energy projecting into the collecting area of the solar water heater was obtained which showed 49% loss with optics and 23% with the dissipation of heat, with only 28% being utilized effectively.

Superresolution Imaging Captures Carbohydrate Utilization Dynamics in Human Gut Symbionts

PubMed Central

Karunatilaka, Krishanthi S.; Cameron, Elizabeth A.; Martens, Eric C.; Koropatkin, Nicole M.

2014-01-01

ABSTRACT Gut microbes play a key role in human health and nutrition by catabolizing a wide variety of glycans via enzymatic activities that are not encoded in the human genome. The ability to recognize and process carbohydrates strongly influences the structure of the gut microbial community. While the effects of diet on the microbiota are well documented, little is known about the molecular processes driving metabolism. To provide mechanistic insight into carbohydrate catabolism in gut symbionts, we studied starch processing in real time in the model Bacteroides thetaiotaomicron starch utilization system (Sus) by single-molecule fluorescence. Although previous studies have explored Sus protein structure and function, the transient interactions, assembly, and collaboration of these outer membrane proteins have not yet been elucidated in live cells. Our live-cell superresolution imaging reveals that the polymeric starch substrate dynamically recruits Sus proteins, serving as an external scaffold for bacterial membrane assembly of the Sus complex, which may promote efficient capturing and degradation of starch. Furthermore, by simultaneously localizing multiple Sus outer membrane proteins on the B. thetaiotaomicron cell surface, we have characterized the dynamics and stoichiometry of starch-induced Sus complex assembly on the molecular scale. Finally, based on Sus protein knockout strains, we have discerned the mechanism of starch-induced Sus complex assembly in live anaerobic cells with nanometer-scale resolution. Our insights into the starch-induced outer membrane protein assembly central to this conserved nutrient uptake mechanism pave the way for the development of dietary or pharmaceutical therapies to control Bacteroidetes in the intestinal tract to enhance human health and treat disease. PMID:25389179

Multiplexed Molecular Imaging of Fresh Tissue Surfaces Enabled by Convection-Enhanced Topical Staining with SERS-Coded Nanoparticles.

PubMed

Wang, Yu W; Doerksen, Josh D; Kang, Soyoung; Walsh, Daniel; Yang, Qian; Hong, Daniel; Liu, Jonathan T C

2016-10-01

There is a need for intraoperative imaging technologies to guide breast-conserving surgeries and to reduce the high rates of re-excision for patients in which residual tumor is found at the surgical margins during postoperative pathology analyses. Feasibility studies have shown that utilizing topically applied surface-enhanced Raman scattering (SERS) nanoparticles (NPs), in conjunction with the ratiometric imaging of targeted versus untargeted NPs, enables the rapid visualization of multiple cell-surface biomarkers of cancer that are overexpressed at the surfaces of freshly excised breast tissues. In order to reliably and rapidly perform multiplexed Raman-encoded molecular imaging of large numbers of biomarkers (with five or more NP flavors), an enhanced staining method has been developed in which tissue surfaces are cyclically dipped into an NP-staining solution and subjected to high-frequency mechanical vibration. This dipping and mechanical vibration (DMV) method promotes the convection of the SERS NPs at fresh tissue surfaces, which accelerates their binding to their respective biomarker targets. By utilizing a custom-developed device for automated DMV staining, this study demonstrates the ability to simultaneously image four cell-surface biomarkers of cancer at the surfaces of fresh human breast tissues with a mixture of five flavors of SERS NPs (four targeted and one untargeted control) topically applied for 5 min and imaged at a spatial resolution of 0.5 mm and a raster-scanned imaging rate of >5 cm 2 min -1 . © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Integrative Utilization of Microenvironments, Biomaterials and Computational Techniques for Advanced Tissue Engineering.

PubMed

Shamloo, Amir; Mohammadaliha, Negar; Mohseni, Mina

2015-10-20

This review aims to propose the integrative implementation of microfluidic devices, biomaterials, and computational methods that can lead to a significant progress in tissue engineering and regenerative medicine researches. Simultaneous implementation of multiple techniques can be very helpful in addressing biological processes. Providing controllable biochemical and biomechanical cues within artificial extracellular matrix similar to in vivo conditions is crucial in tissue engineering and regenerative medicine researches. Microfluidic devices provide precise spatial and temporal control over cell microenvironment. Moreover, generation of accurate and controllable spatial and temporal gradients of biochemical factors is attainable inside microdevices. Since biomaterials with tunable properties are a worthwhile option to construct artificial extracellular matrix, in vitro platforms that simultaneously utilize natural, synthetic, or engineered biomaterials inside microfluidic devices are phenomenally advantageous to experimental studies in the field of tissue engineering. Additionally, collaboration between experimental and computational methods is a useful way to predict and understand mechanisms responsible for complex biological phenomena. Computational results can be verified by using experimental platforms. Computational methods can also broaden the understanding of the mechanisms behind the biological phenomena observed during experiments. Furthermore, computational methods are powerful tools to optimize the fabrication of microfluidic devices and biomaterials with specific features. Here we present a succinct review of the benefits of microfluidic devices, biomaterial, and computational methods in the case of tissue engineering and regeneration medicine. Furthermore, some breakthroughs in biological phenomena including the neuronal axon development, cancerous cell migration and blood vessel formation via angiogenesis by virtue of the aforementioned approaches are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

Genetic characteristics and pathogenic mechanisms of periodontal pathogens.

PubMed

Amano, A; Chen, C; Honma, K; Li, C; Settem, R P; Sharma, A

2014-05-01

Periodontal disease is caused by a group of bacteria that utilize a variety of strategies and molecular mechanisms to evade or overcome host defenses. Recent research has uncovered new evidence illuminating interesting aspects of the virulence of these bacteria and their genomic variability. This paper summarizes some of the strategies utilized by the major species - Aggregatibacter actinomycetemcomitans, Tannerella forsythia, Treponema denticola, and Porphyromonas gingivalis - implicated in the pathogenesis of periodontal disease. Whole-genome sequencing of 14 diverse A. actinomycetemcomitans strains has revealed variations in their genetic content (ranging between 0.4% and 19.5%) and organization. Strikingly, isolates from human periodontal sites showed no genomic changes during persistent colonization. T. forsythia manipulates the cytokine responses of macrophages and monocytes through its surface glycosylation. Studies have revealed that bacterial surface-expressed O-linked glycans modulate T-cell responses during periodontal inflammation. Periodontal pathogens belonging to the "red complex" consortium express neuraminidases, which enables them to scavenge sialic acid from host glycoconjugates. Analysis of recent data has demonstrated that the cleaved sialic acid acts as an important nutrient for bacterial growth and a molecule for the decoration of bacteria surfaces to help evade the host immune attack. In addition, bacterial entry into host cells is also an important prerequisite for the lifestyle of periodontal pathogens such as P. gingivalis. Studies have shown that, after its entry into the cell, this bacterium uses multiple sorting pathways destined for autophagy, lysosomes, or recycling pathways. In addition, P. gingivalis releases outer membrane vesicles which enter cells via endocytosis and cause cellular functional impairment.

Novel image encryption algorithm based on multiple-parameter discrete fractional random transform

NASA Astrophysics Data System (ADS)

Zhou, Nanrun; Dong, Taiji; Wu, Jianhua

2010-08-01

A new method of digital image encryption is presented by utilizing a new multiple-parameter discrete fractional random transform. Image encryption and decryption are performed based on the index additivity and multiple parameters of the multiple-parameter fractional random transform. The plaintext and ciphertext are respectively in the spatial domain and in the fractional domain determined by the encryption keys. The proposed algorithm can resist statistic analyses effectively. The computer simulation results show that the proposed encryption algorithm is sensitive to the multiple keys, and that it has considerable robustness, noise immunity and security.

Overview of Sparse Graph for Multiple Access in Future Mobile Networks

NASA Astrophysics Data System (ADS)

Lei, Jing; Li, Baoguo; Li, Erbao; Gong, Zhenghui

2017-10-01

Multiple access via sparse graph, such as low density signature (LDS) and sparse code multiple access (SCMA), is a promising technique for future wireless communications. This survey presents an overview of the developments in this burgeoning field, including transmitter structures, extrinsic information transform (EXIT) chart analysis and comparisons with existing multiple access techniques. Such technique enables multiple access under overloaded conditions to achieve a satisfactory performance. Message passing algorithm is utilized for multi-user detection in the receiver, and structures of the sparse graph are illustrated in detail. Outlooks and challenges of this technique are also presented.

A Proposal for Better Drug Utilization and Education in Tompkins County (New York)

ERIC Educational Resources Information Center

Rivkin, Lawrence S.

1976-01-01

This proposal contains a mechanism to provide the population with useful drug information at the time of purchase. This mechanism may also provide the system with useful information concerning drug utilization by the consuming public. Such information is vital to health planners and others interested in health care delivery. (Author)

Electromagnetic energy coupling mechanism with matrix architecture control

NASA Technical Reports Server (NTRS)

Hughes, Eli (Inventor); Knowles, Gareth (Inventor)

2006-01-01

The present invention relates generally to reconfigurable, solid-state matrix arrays comprising multiple rows and columns of reconfigurable secondary mechanisms that are independently tuned. Specifically, the invention relates to reconfigurable devices comprising multiple, solid-state mechanisms characterized by at least one voltage-varied parameter disposed within a flexible, multi-laminate film, which are suitable for use as magnetic conductors, ground surfaces, antennas, varactors, ferrotunable substrates, or other active or passive electronic mechanisms.

Arynes and Heteroarynes in the Synthesis of Dibenzocinnolines, Diazaxanthyledenes, and Triptycenes

NASA Astrophysics Data System (ADS)

Suh, Sung-Eun

Arynes are known as useful synthons in organic synthesis. In particular, reactions accompanying multiple arynes have been employed for the construction of arenes and heteroarenes of complex molecules. Employing known reactivity modes of arynes such as cycloadditions, nucleophilic addition, bond insertion, Alder-ene, annulation, desaturation, and polymerization, a wide variety of transformation of reactive starting materials led to the development of novel fluorophores and energy materials, as well as the synthesis of natural products. Harnessing the highly reactive arynes, the triple aryne-tetrazine (TAT) reaction was disclosed as a novel metal-free synthetic method for the preparation of dibenzo[de,g]cinnoline derivatives in a single operation. Dibenzo[de,g]cinnolines have been shown as potential fluorescent probes in cells. For the mechanism, multiple mechanistic steps of the TAT reaction were scrutinized by isolation of intermediates and byproducts as well as a computational study on the transition states and the competitive reactions pathways. A facile two-step synthesis of the reported structure of xylopyridine A was developed from a pyridyne precursor and 2-fluorobenzoic acid utilizing a pyridyne insertion reaction followed by reductive coupling. Simple transformation of the reported xylopyridine A structure have given photoactivatable dyes and specific organelle staining probes in either live or fixed cells and tissues, exhibiting high quantum yields, photostability, cell permeability and low toxicity. On the basis of these results, the synthesis of multistage photoactivatable dyes was designed and studied. Utilization of arynes allowed access to the synthesis of 9-substituted triptycene derivatives which have been recognized as three-way junction binders. Accompanying solid-phase peptide synthesis, the rapid diversification of the triptycene scaffold was achieved for screening in a nucleic acid junction binding assay.

Social Networks Across Common Cancer Types: The Evidence, Gaps, and Areas of Potential Impact.

PubMed

Rice, L J; Halbert, C H

2017-01-01

Although the association between social context and health has been demonstrated previously, much less is known about network interactions by gender, race/ethnicity, and sociodemographic characteristics. Given the variability in cancer outcomes among groups, research on these relationships may have important implications for addressing cancer health disparities. We examined the literature on social networks and cancer across the cancer continuum among adults. Relevant studies (N=16) were identified using two common databases: PubMed and Google Scholar. Most studies used a prospective cohort study design (n=9), included women only (n=11), and were located in the United States (n=14). Seventy-five percent of the studies reviewed used a validated scale or validated items to measure social networks (n=12). Only one study examined social network differences by race, 57.1% (n=8) focused on breast cancer alone, 14.3% (n=2) explored colorectal cancer or multiple cancers simultaneously, and 7.1% (n=1) only prostate cancer. More than half of the studies included multiple ethnicities in the sample, while one study included only low-income subjects. Despite findings of associations between social networks and cancer survival, risk, and screening, none of the studies utilized social networks as a mechanism for reducing health disparities; however, such an approach has been utilized for infectious disease control. Social networks and the support provided within these networks have important implications for health behaviors and ultimately cancer disparities. This review serves as the first step toward dialog on social networks as a missing component in the social determinants of cancer disparities literature that could move the needle upstream to target adverse cancer outcomes among vulnerable populations. © 2017 Elsevier Inc. All rights reserved.

BCM Search Launcher--an integrated interface to molecular biology data base search and analysis services available on the World Wide Web.

PubMed

Smith, R F; Wiese, B A; Wojzynski, M K; Davison, D B; Worley, K C

1996-05-01

The BCM Search Launcher is an integrated set of World Wide Web (WWW) pages that organize molecular biology-related search and analysis services available on the WWW by function, and provide a single point of entry for related searches. The Protein Sequence Search Page, for example, provides a single sequence entry form for submitting sequences to WWW servers that offer remote access to a variety of different protein sequence search tools, including BLAST, FASTA, Smith-Waterman, BEAUTY, PROSITE, and BLOCKS searches. Other Launch pages provide access to (1) nucleic acid sequence searches, (2) multiple and pair-wise sequence alignments, (3) gene feature searches, (4) protein secondary structure prediction, and (5) miscellaneous sequence utilities (e.g., six-frame translation). The BCM Search Launcher also provides a mechanism to extend the utility of other WWW services by adding supplementary hypertext links to results returned by remote servers. For example, links to the NCBI's Entrez data base and to the Sequence Retrieval System (SRS) are added to search results returned by the NCBI's WWW BLAST server. These links provide easy access to auxiliary information, such as Medline abstracts, that can be extremely helpful when analyzing BLAST data base hits. For new or infrequent users of sequence data base search tools, we have preset the default search parameters to provide the most informative first-pass sequence analysis possible. We have also developed a batch client interface for Unix and Macintosh computers that allows multiple input sequences to be searched automatically as a background task, with the results returned as individual HTML documents directly to the user's system. The BCM Search Launcher and batch client are available on the WWW at URL http:@gc.bcm.tmc.edu:8088/search-launcher.html.

Toward multimodal signal detection of adverse drug reactions.

PubMed

Harpaz, Rave; DuMouchel, William; Schuemie, Martijn; Bodenreider, Olivier; Friedman, Carol; Horvitz, Eric; Ripple, Anna; Sorbello, Alfred; White, Ryen W; Winnenburg, Rainer; Shah, Nigam H

2017-12-01

Improving mechanisms to detect adverse drug reactions (ADRs) is key to strengthening post-marketing drug safety surveillance. Signal detection is presently unimodal, relying on a single information source. Multimodal signal detection is based on jointly analyzing multiple information sources. Building on, and expanding the work done in prior studies, the aim of the article is to further research on multimodal signal detection, explore its potential benefits, and propose methods for its construction and evaluation. Four data sources are investigated; FDA's adverse event reporting system, insurance claims, the MEDLINE citation database, and the logs of major Web search engines. Published methods are used to generate and combine signals from each data source. Two distinct reference benchmarks corresponding to well-established and recently labeled ADRs respectively are used to evaluate the performance of multimodal signal detection in terms of area under the ROC curve (AUC) and lead-time-to-detection, with the latter relative to labeling revision dates. Limited to our reference benchmarks, multimodal signal detection provides AUC improvements ranging from 0.04 to 0.09 based on a widely used evaluation benchmark, and a comparative added lead-time of 7-22 months relative to labeling revision dates from a time-indexed benchmark. The results support the notion that utilizing and jointly analyzing multiple data sources may lead to improved signal detection. Given certain data and benchmark limitations, the early stage of development, and the complexity of ADRs, it is currently not possible to make definitive statements about the ultimate utility of the concept. Continued development of multimodal signal detection requires a deeper understanding the data sources used, additional benchmarks, and further research on methods to generate and synthesize signals. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of Personality on the Use and Perceived Utility of Web-Based Health Resources

ERIC Educational Resources Information Center

Hruska, Natalie

2012-01-01

Studies document numerous threats to human health exacerbated by multiple factors, including inadequate access to health-related information. The Internet has developed as one resource to provide health information; however, there remains a significant gap in understanding how personality differences influence the use and perceived utility of the…

Using Faculty Characteristics to Predict Attitudes toward Developmental Education

ERIC Educational Resources Information Center

Sides, Meredith Louise Carr

2017-01-01

The study adapted Astin's I-E-O model and utilized multiple regression analyses to predict faculty attitudes toward developmental education. The study utilized a cross-sectional survey design to survey faculty members at 27 different higher education institutions in the state of Alabama. The survey instrument was a self-designed questionnaire that…

Degradation and damages from utilizing ecosystem services in a river basin

Treesearch

Travis W. Warziniack

2012-01-01

We examine the tradeoffs between utilizing multiple ecosystem services in an economic model of the Lower Mississippi-Atchafalaya River Basin. We show how economic development in the basin degraded the ecosystem, but diversified the economy. A degraded ecosystem and more employment opportunities elsewhere reduced the region's reliance on agriculture and other...

Utilizing Ayurvedic literature for the identification of novel phytochemical inhibitors of botulinum neurotoxin A

USDA-ARS?s Scientific Manuscript database

Ethnopharmacological relevance: Ayurveda, an ancient holistic system of health care practiced on the Indian subcontinent, utilizes a number of multi-plant formulations and is considered by many as a potential source for novel treatments, as well as the identification of new drugs. Our aim is to iden...

Knowledge-for-Action Theories in Evaluation: Knowledge Utilization, Diffusion, Implementation, Transfer, and Translation

ERIC Educational Resources Information Center

Ottoson, Judith M.

2009-01-01

Five knowledge-for-action theories are summarized and compared in this chapter for their evaluation implications: knowledge utilization, diffusion, implementation, transfer, and translation. Usually dispersed across multiple fields and disciplines, these theories are gathered here for a common focus on knowledge and change. Knowledge in some form…

Do sampling methods differ in their utility for ecological monitoring? Comparison of line-point intercept, grid-point intercept, and ocular estimate methods

USDA-ARS?s Scientific Manuscript database

This study compared the utility of three sampling methods for ecological monitoring based on: interchangeability of data (rank correlations), precision (coefficient of variation), cost (minutes/transect), and potential of each method to generate multiple indicators. Species richness and foliar cover...

High speed multiwire photon camera

NASA Technical Reports Server (NTRS)

Lacy, Jeffrey L. (Inventor)

1991-01-01

An improved multiwire proportional counter camera having particular utility in the field of clinical nuclear medicine imaging. The detector utilizes direct coupled, low impedance, high speed delay lines, the segments of which are capacitor-inductor networks. A pile-up rejection test is provided to reject confused events otherwise caused by multiple ionization events occuring during the readout window.

High speed multiwire photon camera

NASA Technical Reports Server (NTRS)

Lacy, Jeffrey L. (Inventor)

1989-01-01

An improved multiwire proportional counter camera having particular utility in the field of clinical nuclear medicine imaging. The detector utilizes direct coupled, low impedance, high speed delay lines, the segments of which are capacitor-inductor networks. A pile-up rejection test is provided to reject confused events otherwise caused by multiple ionization events occurring during the readout window.

The Utility of the MAPI in Predicting Urban Middle School Competence.

ERIC Educational Resources Information Center

Paulus, John A.; Perosa, Linda M.

A sample of 107 eighth graders from a large urban middle school in the Midwest was administered the Millon Adolescent Personality Inventory (MAPI) to determine its utility in predicting grades earned, attendance, and social competence. The results of hierarchical multiple regression analysis indicated that the MAPI coping patterns significantly…

How Perceptions of Mental Illness Impact EAP Utilization.

PubMed

McRee, Jayme

2017-01-01

Studies of employee assistance program (EAP) clinical use across multiple industries and multiple EAP delivery models range from highs greater than 5% to lows of less than 1 %. Despite the range in utilization, the rates of employee behaviors that indicate a behavioral health issue are significantly higher, suggesting far too little use of EAPs overall. Studies of the costs to an employer for an employee with a mental health issue are as high as 37% lost annual productivity. EAPs have attempted to raise utilization through a variety of efforts, with mixed results. Most EAP utilization initiatives fail to address the impact of stigma, misunderstandings about mental illness and the reluctance of many employees to seek counseling as an option for better management of stress, work-life balance and overall mental wellness. For both employers and EAPs, addressing the impact of stigma and perceptions of mental illness is costly, requiring greater direct employee engagement and education. However, it is a more effective means of increasing EAP use than current practices and, ultimately, can result in significantly higher net gains in productivity while reducing employers' direct costs.

Optimization of Multiple Related Negotiation through Multi-Negotiation Network

NASA Astrophysics Data System (ADS)

Ren, Fenghui; Zhang, Minjie; Miao, Chunyan; Shen, Zhiqi

In this paper, a Multi-Negotiation Network (MNN) and a Multi- Negotiation Influence Diagram (MNID) are proposed to optimally handle Multiple Related Negotiations (MRN) in a multi-agent system. Most popular, state-of-the-art approaches perform MRN sequentially. However, a sequential procedure may not optimally execute MRN in terms of maximizing the global outcome, and may even lead to unnecessary losses in some situations. The motivation of this research is to use a MNN to handle MRN concurrently so as to maximize the expected utility of MRN. Firstly, both the joint success rate and the joint utility by considering all related negotiations are dynamically calculated based on a MNN. Secondly, by employing a MNID, an agent's possible decision on each related negotiation is reflected by the value of expected utility. Lastly, through comparing expected utilities between all possible policies to conduct MRN, an optimal policy is generated to optimize the global outcome of MRN. The experimental results indicate that the proposed approach can improve the global outcome of MRN in a successful end scenario, and avoid unnecessary losses in an unsuccessful end scenario.