The application of encapsulation material stability data to photovoltaic module life assessment

NASA Technical Reports Server (NTRS)

Coulbert, C. D.

1983-01-01

For any piece of hardware that degrades when subject to environmental and application stresses, the route or sequence that describes the degradation process may be summarized in terms of six key words: LOADS, RESPONSE, CHANGE, DAMAGE, FAILURE, and PENALTY. Applied to photovoltaic modules, these six factors form the core outline of an expanded failure analysis matrix for unifying and integrating relevant material degradation data and analyses. An important feature of this approach is the deliberate differentiation between factors such as CHANGE, DAMAGE, and FAILURE. The application of this outline to materials degradation research facilitates the distinction between quantifying material property changes and quantifying module damage or power loss with their economic consequences. The approach recommended for relating material stability data to photovoltaic module life is to use the degree of DAMAGE to (1) optical coupling, (2) encapsulant package integrity, (3) PV circuit integrity or (4) electrical isolation as the quantitative criterion for assessing module potential service life rather than simply using module power loss.

Functional modules of sigma factor regulons guarantee adaptability and evolvability

PubMed Central

Binder, Sebastian C.; Eckweiler, Denitsa; Schulz, Sebastian; Bielecka, Agata; Nicolai, Tanja; Franke, Raimo; Häussler, Susanne; Meyer-Hermann, Michael

2016-01-01

The focus of modern molecular biology turns from assigning functions to individual genes towards understanding the expression and regulation of complex sets of molecules. Here, we provide evidence that alternative sigma factor regulons in the pathogen Pseudomonas aeruginosa largely represent insulated functional modules which provide a critical level of biological organization involved in general adaptation and survival processes. Analysis of the operational state of the sigma factor network revealed that transcription factors functionally couple the sigma factor regulons and significantly modulate the transcription levels in the face of challenging environments. The threshold quality of newly evolved transcription factors was reached faster and more robustly in in silico testing when the structural organization of sigma factor networks was taken into account. These results indicate that the modular structures of alternative sigma factor regulons provide P. aeruginosa with a robust framework to function adequately in its environment and at the same time facilitate evolutionary change. Our data support the view that widespread modularity guarantees robustness of biological networks and is a key driver of evolvability. PMID:26915971

Integrating Information Systems in a Major Decentralized International Organization. Volume 7.

DTIC Science & Technology

1987-12-01

deployment of information technology. Three key conflicting organizational forces were found to significantly impact the technical strategies : 1... strategy was modulated by three key conflicting organizational forces - autonomy, integration and evolution. A conceptual system architecture has been... organizational needs. The second part, "Gaining Strategic Advantage Through Composite Tnformation Systems," identifies critical success factors for the

A modular modulation method for achieving increases in metabolite production.

PubMed

Acerenza, Luis; Monzon, Pablo; Ortega, Fernando

2015-01-01

Increasing the production of overproducing strains represents a great challenge. Here, we develop a modular modulation method to determine the key steps for genetic manipulation to increase metabolite production. The method consists of three steps: (i) modularization of the metabolic network into two modules connected by linking metabolites, (ii) change in the activity of the modules using auxiliary rates producing or consuming the linking metabolites in appropriate proportions and (iii) determination of the key modules and steps to increase production. The mathematical formulation of the method in matrix form shows that it may be applied to metabolic networks of any structure and size, with reactions showing any kind of rate laws. The results are valid for any type of conservation relationships in the metabolite concentrations or interactions between modules. The activity of the module may, in principle, be changed by any large factor. The method may be applied recursively or combined with other methods devised to perform fine searches in smaller regions. In practice, it is implemented by integrating to the producer strain heterologous reactions or synthetic pathways producing or consuming the linking metabolites. The new procedure may contribute to develop metabolic engineering into a more systematic practice. © 2015 American Institute of Chemical Engineers.

Identification of gene expression profiles and key genes in subchondral bone of osteoarthritis using weighted gene coexpression network analysis.

PubMed

Guo, Sheng-Min; Wang, Jian-Xiong; Li, Jin; Xu, Fang-Yuan; Wei, Quan; Wang, Hai-Ming; Huang, Hou-Qiang; Zheng, Si-Lin; Xie, Yu-Jie; Zhang, Chi

2018-06-15

Osteoarthritis (OA) significantly influences the quality life of people around the world. It is urgent to find an effective way to understand the genetic etiology of OA. We used weighted gene coexpression network analysis (WGCNA) to explore the key genes involved in the subchondral bone pathological process of OA. Fifty gene expression profiles of GSE51588 were downloaded from the Gene Expression Omnibus database. The OA-associated genes and gene ontologies were acquired from JuniorDoc. Weighted gene coexpression network analysis was used to find disease-related networks based on 21756 gene expression correlation coefficients, hub-genes with the highest connectivity in each module were selected, and the correlation between module eigengene and clinical traits was calculated. The genes in the traits-related gene coexpression modules were subject to functional annotation and pathway enrichment analysis using ClusterProfiler. A total of 73 gene modules were identified, of which, 12 modules were found with high connectivity with clinical traits. Five modules were found with enriched OA-associated genes. Moreover, 310 OA-associated genes were found, and 34 of them were among hub-genes in each module. Consequently, enrichment results indicated some key metabolic pathways, such as extracellular matrix (ECM)-receptor interaction (hsa04512), focal adhesion (hsa04510), the phosphatidylinositol 3'-kinase (PI3K)-Akt signaling pathway (PI3K-AKT) (hsa04151), transforming growth factor beta pathway, and Wnt pathway. We intended to identify some core genes, collagen (COL)6A3, COL6A1, ITGA11, BAMBI, and HCK, which could influence downstream signaling pathways once they were activated. In this study, we identified important genes within key coexpression modules, which associate with a pathological process of subchondral bone in OA. Functional analysis results could provide important information to understand the mechanism of OA. © 2018 Wiley Periodicals, Inc.

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

PubMed

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

2017-07-14

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

Bovine somatotropin and lactation: from basic science to commercial application.

PubMed

Bauman, D E

1999-10-01

Bovine somatotropin (bST) results in increased milk yield and an unprecedented improvement in efficiency. Beginning in the 1930s to present day, investigations have examined animal-related factors such as nutrition, bioenergetics, metabolism, health and well being and consumer-related factors such as milk quality, manufacturing characteristics, and product safety. Overall, bST is a homeorhetic control involved in orchestrating many physiological processes. Direct effects involve adaptations in many tissues and the metabolism of all nutrient classes--carbohydrates, lipids, protein, and minerals. Mechanisms include alterations in key enzymes, intracellular signal transduction systems, and tissue response to homeostatic signals. Indirect effects involve the mammary gland and are thought to be mediated by the insulin-like growth factor (IGF) system. Specific changes include increased cellular rates of milk synthesis and enhanced maintenance of secretory cells. Indirect effects are modulated by environment and management factors, especially nutritional status. This modulation is a central component in allowing ST to play a key role in regulating nutrient utilization across a range of physiological situations. U.S. commercial use began in 1994, and adoption has been extensive. From a consumer perspective, bST was unique, and special interest groups loudly predicted dire consequences. However, introduction of bST had no impact on milk consumption, and milk labeled as recombinant bST-free occupies a minor niche market. From a producer perspective, commercial use verified scientific studies and enhanced net farm income. Overall, ST is a key homeorhetic control regulating nutrient partitioning, and the ST/IGF system plays a key role in animal performance and well being across a range of physiological situations.

Influence of Sun and Other Cosmic Factors on Environment of the Earth

DTIC Science & Technology

2010-01-07

of the secondary cosmic rays (mostly muons , electrons, neutrons and gammas) can provide highly cost-effective information on the key characteristics...Coronal mass ejection (CME) from the Sun the impact on the Galactic Cosmic rays (GCR) will be observed. Particle detector is vital for measuring the...modulation effects the sun poses on the ambient population of the Galactic Cosmic Rays (GCR). The known agents of these modulation effects are Solar Flares

The use of mode of action information in risk assessment: quantitative key events/dose-response framework for modeling the dose-response for key events.

PubMed

Simon, Ted W; Simons, S Stoney; Preston, R Julian; Boobis, Alan R; Cohen, Samuel M; Doerrer, Nancy G; Fenner-Crisp, Penelope A; McMullin, Tami S; McQueen, Charlene A; Rowlands, J Craig

2014-08-01

The HESI RISK21 project formed the Dose-Response/Mode-of-Action Subteam to develop strategies for using all available data (in vitro, in vivo, and in silico) to advance the next-generation of chemical risk assessments. A goal of the Subteam is to enhance the existing Mode of Action/Human Relevance Framework and Key Events/Dose Response Framework (KEDRF) to make the best use of quantitative dose-response and timing information for Key Events (KEs). The resulting Quantitative Key Events/Dose-Response Framework (Q-KEDRF) provides a structured quantitative approach for systematic examination of the dose-response and timing of KEs resulting from a dose of a bioactive agent that causes a potential adverse outcome. Two concepts are described as aids to increasing the understanding of mode of action-Associative Events and Modulating Factors. These concepts are illustrated in two case studies; 1) cholinesterase inhibition by the pesticide chlorpyrifos, which illustrates the necessity of considering quantitative dose-response information when assessing the effect of a Modulating Factor, that is, enzyme polymorphisms in humans, and 2) estrogen-induced uterotrophic responses in rodents, which demonstrate how quantitative dose-response modeling for KE, the understanding of temporal relationships between KEs and a counterfactual examination of hypothesized KEs can determine whether they are Associative Events or true KEs.

Gut Microbiota: A Key Modulator of Intestinal Healing in Inflammatory Bowel Disease.

PubMed

Lopetuso, L R; Petito, V; Zambrano, D; Orlando, D; Dal Lago, A; Serrichhio, L; Papa, A; Gasbarrini, A; Scaldaferri, F

2016-01-01

Mucosal healing (MH) represents a crucial factor for maintaining gut homeostasis. Indeed, in inflammatory bowel disease, MH has become the standard therapeutical target, because it is associated with more effective disease control, more frequent steroid-free remission, lower rates of hospitalization and surgery, and improved quality of life. In this scenario, gut microbiota is a crucial player in modulating intestinal repair and regeneration process. It can act on the tumor necrosis factor-α production, modulation of reactive oxygen and nitrogen species, activity of matrix metalloproteinases and on many other mechanisms strictly involved in restoring gut health. In this review, we analyze and review the literature on the role of gut microbiota in sustaining mucosal injury and achieving MH. © 2016 S. Karger AG, Basel.

Modulation of hippocampal neural plasticity by glucose-related signaling.

PubMed

Mainardi, Marco; Fusco, Salvatore; Grassi, Claudio

2015-01-01

Hormones and peptides involved in glucose homeostasis are emerging as important modulators of neural plasticity. In this regard, increasing evidence shows that molecules such as insulin, insulin-like growth factor-I, glucagon-like peptide-1, and ghrelin impact on the function of the hippocampus, which is a key area for learning and memory. Indeed, all these factors affect fundamental hippocampal properties including synaptic plasticity (i.e., synapse potentiation and depression), structural plasticity (i.e., dynamics of dendritic spines), and adult neurogenesis, thus leading to modifications in cognitive performance. Here, we review the main mechanisms underlying the effects of glucose metabolism on hippocampal physiology. In particular, we discuss the role of these signals in the modulation of cognitive functions and their potential implications in dysmetabolism-related cognitive decline.

Kis antitoxin couples plasmid R1 replication and parD (kis,kid) maintenance modules.

PubMed

López-Villarejo, Juan; Diago-Navarro, Elizabeth; Hernández-Arriaga, Ana María; Díaz-Orejas, Ramón

2012-03-01

The coupling between the replication and parD (kis, kid) maintenance modules of R1 has been revisited here by the isolation of a significant collection of conditional replication mutants in the pKN1562 mini-R1 plasmid, and in its derivative, pJLV01, specifically affected in the RNase activity of the Kid toxin. This new analysis aims to identify key factors in this coupling. For this purpose we have quantified and characterized the restriction introduced by parD to isolate conditional replication mutants of this plasmid, a signature of the modular coupling. This restriction depends on the RNase activity of the Kid toxin and it is relieved by either over-expression of the Kis antitoxin or by preventing its degradation by Lon and ClpAP proteases. Based on these data and on the correlation between copy numbers and parD transcriptional levels obtained in the different mutants, it is proposed that a reduction of Kis antitoxin levels in response to inefficient plasmid replication is the key factor for coupling plasmid replication and parD modules. Copyright © 2012 Elsevier Inc. All rights reserved.

[Coffee as hepatoprotective factor].

PubMed

Szántová, Mária; Ďurkovičová, Zuzana

The mind about the coffee did change upon the recent studies and metaanalysis of the last years. Consensual protective effect of coffee on the progression of chronic liver diseases (NASH, viral hepatitis, liver cirrhosis, hepatocelullar carcinoma) was detected in experimental, clinical and large population studies together with decrease of mortality. Antioxidant, antifibrotic, insulinsensitizing and anticarcinogenic effect of coffee were detected. Modulation of genetic expression of key enzymes of fatty acid synthesis, modulation of mRNA included in autophagia, reduction of stress of endoplasmatic reticulum together with decrease of proinflammatory cytokines and decrease of fibrogenesis are main mechanisms. Chlorogenic acids, diterpens (cafestol, kahweol), caffein, polyfenols and melanoidins are key protective components of coffee. Inverse dose-dependent correlation of coffee consumption with liver diseases was found in clinical and population studies. Coffee is non-pharmacological tool of primary and secondary prevention of chronic liver diseases. Review of published data together with supposed mechanisms of hepatoprotection are given.Key words: coffee - hepatoprotective effect - metaanalysis.

Signed weighted gene co-expression network analysis of transcriptional regulation in murine embryonic stem cells

PubMed Central

Mason, Mike J; Fan, Guoping; Plath, Kathrin; Zhou, Qing; Horvath, Steve

2009-01-01

Background Recent work has revealed that a core group of transcription factors (TFs) regulates the key characteristics of embryonic stem (ES) cells: pluripotency and self-renewal. Current efforts focus on identifying genes that play important roles in maintaining pluripotency and self-renewal in ES cells and aim to understand the interactions among these genes. To that end, we investigated the use of unsigned and signed network analysis to identify pluripotency and differentiation related genes. Results We show that signed networks provide a better systems level understanding of the regulatory mechanisms of ES cells than unsigned networks, using two independent murine ES cell expression data sets. Specifically, using signed weighted gene co-expression network analysis (WGCNA), we found a pluripotency module and a differentiation module, which are not identified in unsigned networks. We confirmed the importance of these modules by incorporating genome-wide TF binding data for key ES cell regulators. Interestingly, we find that the pluripotency module is enriched with genes related to DNA damage repair and mitochondrial function in addition to transcriptional regulation. Using a connectivity measure of module membership, we not only identify known regulators of ES cells but also show that Mrpl15, Msh6, Nrf1, Nup133, Ppif, Rbpj, Sh3gl2, and Zfp39, among other genes, have important roles in maintaining ES cell pluripotency and self-renewal. We also report highly significant relationships between module membership and epigenetic modifications (histone modifications and promoter CpG methylation status), which are known to play a role in controlling gene expression during ES cell self-renewal and differentiation. Conclusion Our systems biologic re-analysis of gene expression, transcription factor binding, epigenetic and gene ontology data provides a novel integrative view of ES cell biology. PMID:19619308

Sensory modulation in preterm children: Theoretical perspective and systematic review

PubMed Central

Oostrom, Kim J.; Lafeber, Harrie N.; Jansma, Elise P.; Oosterlaan, Jaap

2017-01-01

Background Neurodevelopmental sequelae in preterm born children are generally considered to result from cerebral white matter damage and noxious effects of environmental factors in the neonatal intensive care unit (NICU). Cerebral white matter damage is associated with sensory processing problems in terms of registration, integration and modulation. However, research into sensory processing problems and, in particular, sensory modulation problems, is scarce in preterm children. Aim This review aims to integrate available evidence on sensory modulation problems in preterm infants and children (<37 weeks of gestation) and their association with neurocognitive and behavioral problems. Method Relevant studies were extracted from PubMed, EMBASE.com and PsycINFO following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Selection criteria included assessment of sensory modulation in preterm born children (<37 weeks of gestation) or with prematurity as a risk factor. Results Eighteen studies were included. Results of this review support the presence of sensory modulation problems in preterm children. Although prematurity may distort various aspects of sensory modulation, the nature and severity of sensory modulation problems differ widely between studies. Conclusions Sensory modulation problems may play a key role in understanding neurocognitive and behavioral sequelae in preterm children. Some support is found for a dose-response relationship between both white matter brain injury and length of NICU stay and sensory modulation problems. PMID:28182680

Does the Host Contribute to Modulation of Mycotoxin Production by Fruit Pathogens?

PubMed Central

Kumar, Dilip; Barad, Shiri; Sionov, Edward; Prusky, Dov B.

2017-01-01

Storage of freshly harvested fruit is a key factor in modulating their supply for several months after harvest; however, their quality can be reduced by pathogen attack. Fruit pathogens may infect their host through damaged surfaces, such as mechanical injuries occurring during growing, harvesting, and packing, leading to increased colonization as the fruit ripens. Of particular concern are fungal pathogens that not only macerate the host tissue but also secrete significant amounts of mycotoxins. Many studies have described the importance of physiological factors, including stage of fruit development, biochemical factors (ripening, C and N content), and environmental factors (humidity, temperature, water deficit) on the occurrence of mycotoxins. However, those factors usually show a correlative effect on fungal growth and mycotoxin accumulation. Recent reports have suggested that host factors can induce fungal metabolism, leading to the synthesis and accumulation of mycotoxins. This review describes the new vision of host-factor impact on the regulation of mycotoxin biosynthetic gene clusters underlying the complex regulation of mycotoxin accumulation in ripening fruit. PMID:28895896

Lubricin: A Principal Modulator of the Psychoneuroendocrine - Osteoimmune Interactome - Implications for Novel Treatments of Osteoarthritic Pathologies.

PubMed

Khakshooy, Allen; Balenton, Nicole; Chiappelli, Francesco

2017-01-01

Lubricin is a synovial glycoprotein that contributes to joint lubrication. We propose the hypothesis that lubricin is a key modulator of the psychoneuroendocrine-osteoimmune interactome, with important clinical relevance for osteoarthritic pathologies. We consider a variety of neuroendocrine-immune factors, including inflammatory cytokines and chemokines that may contribute to the modulation of lubricin in rheumatic complications. Based on our preliminary immunocytochemistry and fractal analysis data, and in the context of translational research of modern healthcare, we propose that molecular lubricin gene expression modification by means of the novel CRISPR/Cas system be considered for osteoarthritic therapies.

Pulse Shaped Constant Envelope 8-PSK Modulation Study

NASA Technical Reports Server (NTRS)

Tao, Jianping; Horan, Sheila

1997-01-01

This report provides simulation results for constant envelope pulse shaped 8 Level Phase Shift Keying (8 PSK) modulation for end to end system performance. In order to increase bandwidth utilization, pulse shaping is applied to signals before they are modulated. This report provides simulation results of power spectra and measurement of bit errors produced by pulse shaping in a non-linear channel with Additive White Gaussian Noise (AWGN). The pulse shaping filters can placed before (Type B) or after (Type A) signals are modulated. Three kinds of baseband filters, 5th order Butterworth, 3rd order Bessel and Square-Root Raised Cosine with different BTs or roll off factors, are utilized in the simulations. The simulations were performed on a Signal Processing Worksystem (SPW).

Stress modulation of cognitive and affective processes

PubMed Central

CAMPEAU, SERGE; LIBERZON, ISRAEL; MORILAK, DAVID; RESSLER, KERRY

2012-01-01

This review summarizes the major discussion points of a symposium on stress modulation of cognitive and affective processes, which was held during the 2010 workshop on the neurobiology of stress (Boulder, CO, USA). The four discussants addressed a number of specific cognitive and affective factors that are modulated by exposure to acute or repeated stress. Dr David Morilak discussed the effects of various repeated stress situations on cognitive flexibility, as assessed with a rodent model of attentional set-shifting task, and how performance on slightly different aspects of this test is modulated by different prefrontal regions through monoaminergic neurotransmission. Dr Serge Campeau summarized the findings of several studies exploring a number of factors and brain regions that regulate habituation of various autonomic and neuroendocrine responses to repeated audiogenic stress exposures. Dr Kerry Ressler discussed a body of work exploring the modulation and extinction of fear memories in rodents and humans, especially focusing on the role of key neurotransmitter systems including excitatory amino acids and brain-derived neurotrophic factor. Dr Israel Liberzon presented recent results on human decision-making processes in response to exogenous glucocorticoid hormone administration. Overall, these discussions are casting a wider framework on the cognitive/affective processes that are distinctly regulated by the experience of stress and some of the brain regions and neurotransmitter systems associated with these effects. PMID:21790481

Molecular targets for small-molecule modulators of circadian clocks

PubMed Central

He, Baokun; Chen, Zheng

2016-01-01

Background Circadian clocks are endogenous timing systems that regulate various aspects of mammalian metabolism, physiology and behavior. Traditional chronotherapy refers to the administration of drugs in a defined circadian time window to achieve optimal pharmacokinetic and therapeutic efficacies. In recent years, substantial efforts have been dedicated to developing novel small-molecule modulators of circadian clocks. Methods Here, we review the recent progress in the identification of molecular targets of small-molecule clock modulators and their efficacies in clock-related disorders. Specifically, we examine the clock components and regulatory factors as possible molecular targets of small molecules, and we review several key clock-related disorders as promising venues for testing the preventive/therapeutic efficacies of these small molecules. Finally, we also discuss circadian regulation of drug metabolism. Results Small molecules can modulate the period, phase and/or amplitude of the circadian cycle. Core clock proteins, nuclear hormone receptors, and clock-related kinases and other epigenetic regulators are promising molecular targets for small molecules. Through these targets small molecules exert protective effects against clock-related disorders including the metabolic syndrome, immune disorders, sleep disorders and cancer. Small molecules can also modulate circadian drug metabolism and response to existing therapeutics. Conclusion Small-molecule clock modulators target clock components or diverse cellular pathways that functionally impinge upon the clock. Target identification of new small-molecule modulators will deepen our understanding of key regulatory nodes in the circadian network. Studies of clock modulators will facilitate their therapeutic applications, alone or in combination, for clock-related diseases. PMID:26750111

A Hierarchical Modulation Coherent Communication Scheme for Simultaneous Four-State Continuous-Variable Quantum Key Distribution and Classical Communication

NASA Astrophysics Data System (ADS)

Yang, Can; Ma, Cheng; Hu, Linxi; He, Guangqiang

2018-06-01

We present a hierarchical modulation coherent communication protocol, which simultaneously achieves classical optical communication and continuous-variable quantum key distribution. Our hierarchical modulation scheme consists of a quadrature phase-shifting keying modulation for classical communication and a four-state discrete modulation for continuous-variable quantum key distribution. The simulation results based on practical parameters show that it is feasible to transmit both quantum information and classical information on a single carrier. We obtained a secure key rate of 10^{-3} bits/pulse to 10^{-1} bits/pulse within 40 kilometers, and in the meantime the maximum bit error rate for classical information is about 10^{-7}. Because continuous-variable quantum key distribution protocol is compatible with standard telecommunication technology, we think our hierarchical modulation scheme can be used to upgrade the digital communication systems to extend system function in the future.

Microarray analysis reveals key genes and pathways in Tetralogy of Fallot

PubMed Central

He, Yue-E; Qiu, Hui-Xian; Jiang, Jian-Bing; Wu, Rong-Zhou; Xiang, Ru-Lian; Zhang, Yuan-Hai

2017-01-01

The aim of the present study was to identify key genes that may be involved in the pathogenesis of Tetralogy of Fallot (TOF) using bioinformatics methods. The GSE26125 microarray dataset, which includes cardiovascular tissue samples derived from 16 children with TOF and five healthy age-matched control infants, was downloaded from the Gene Expression Omnibus database. Differential expression analysis was performed between TOF and control samples to identify differentially expressed genes (DEGs) using Student's t-test, and the R/limma package, with a log2 fold-change of >2 and a false discovery rate of <0.01 set as thresholds. The biological functions of DEGs were analyzed using the ToppGene database. The ReactomeFIViz application was used to construct functional interaction (FI) networks, and the genes in each module were subjected to pathway enrichment analysis. The iRegulon plugin was used to identify transcription factors predicted to regulate the DEGs in the FI network, and the gene-transcription factor pairs were then visualized using Cytoscape software. A total of 878 DEGs were identified, including 848 upregulated genes and 30 downregulated genes. The gene FI network contained seven function modules, which were all comprised of upregulated genes. Genes enriched in Module 1 were enriched in the following three neurological disorder-associated signaling pathways: Parkinson's disease, Alzheimer's disease and Huntington's disease. Genes in Modules 0, 3 and 5 were dominantly enriched in pathways associated with ribosomes and protein translation. The Xbox binding protein 1 transcription factor was demonstrated to be involved in the regulation of genes encoding the subunits of cytoplasmic and mitochondrial ribosomes, as well as genes involved in neurodegenerative disorders. Therefore, dysfunction of genes involved in signaling pathways associated with neurodegenerative disorders, ribosome function and protein translation may contribute to the pathogenesis of TOF. PMID:28713939

Heterogeneous microring and Mach-Zehnder modulators based on lithium niobate and chalcogenide glasses on silicon

DOE PAGES

Rao, Ashutosh; Patil, Aniket; Chiles, Jeff; ...

2015-08-20

In this study, thin films of lithium niobate are wafer bonded onto silicon substrates and rib-loaded with a chalcogenide glass, Ge 23Sb 7S 70, to demonstrate strongly confined single-mode submicron waveguides, microring modulators, and Mach-Zehnder modulators in the telecom C band. The 200 μm radii microring modulators present 1.2 dB/cm waveguide propagation loss, 1.2 × 10 5 quality factor, 0.4 GHz/V tuning rate, and 13 dB extinction ratio. The 6 mm long Mach-Zehnder modulators have a half-wave voltage-length product of 3.8 V.cm and an extinction ratio of 15 dB. The demonstrated work is a key step towards enabling wafer scalemore » dense on-chip integration of high performance lithium niobate electro-optical devices on silicon for short reach optical interconnects and higher order advanced modulation schemes.« less

Heterogeneous microring and Mach-Zehnder modulators based on lithium niobate and chalcogenide glasses on silicon

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

Rao, Ashutosh; Patil, Aniket; Chiles, Jeff

In this study, thin films of lithium niobate are wafer bonded onto silicon substrates and rib-loaded with a chalcogenide glass, Ge 23Sb 7S 70, to demonstrate strongly confined single-mode submicron waveguides, microring modulators, and Mach-Zehnder modulators in the telecom C band. The 200 μm radii microring modulators present 1.2 dB/cm waveguide propagation loss, 1.2 × 10 5 quality factor, 0.4 GHz/V tuning rate, and 13 dB extinction ratio. The 6 mm long Mach-Zehnder modulators have a half-wave voltage-length product of 3.8 V.cm and an extinction ratio of 15 dB. The demonstrated work is a key step towards enabling wafer scalemore » dense on-chip integration of high performance lithium niobate electro-optical devices on silicon for short reach optical interconnects and higher order advanced modulation schemes.« less

Low-Cost Thermocouple Signal-Conditioning Module

ERIC Educational Resources Information Center

Lenzi, Marcelo K.; Silva, Fabricio M.; Lima, Enrique L.; Pinto, Jose Carlos; Cunningham, Michael F.

2005-01-01

It is well known that reaction rates and physical properties of any substance depend on the temperature. Therefore, an accurate temperature measurement is a key factor for successful activities both in chemical laboratories and industrial plants. Although plenty of sensors can be adopted for temperature measurements, thermocouples are the most…

Reconstruction of the genome-scale co-expression network for the Hippo signaling pathway in colorectal cancer.

PubMed

Dehghanian, Fariba; Hojati, Zohreh; Hosseinkhan, Nazanin; Mousavian, Zaynab; Masoudi-Nejad, Ali

2018-05-26

The Hippo signaling pathway (HSP) has been identified as an essential and complex signaling pathway for tumor suppression that coordinates proliferation, differentiation, cell death, cell growth and stemness. In the present study, we conducted a genome-scale co-expression analysis to reconstruct the HSP in colorectal cancer (CRC). Five key modules were detected through network clustering, and a detailed discussion of two modules containing respectively 18 and 13 over and down-regulated members of HSP was provided. Our results suggest new potential regulatory factors in the HSP. The detected modules also suggest novel genes contributing to CRC. Moreover, differential expression analysis confirmed the differential expression pattern of HSP members and new suggested regulatory factors between tumor and normal samples. These findings can further reveal the importance of HSP in CRC. Copyright © 2018 Elsevier Ltd. All rights reserved.

Immunopathology in Taenia solium neurocysticercosis.

PubMed

Fleury, A; Cardenas, G; Adalid-Peralta, L; Fragoso, G; Sciutto, E

2016-03-01

Neurocysticercosis is a clinically and radiologically heterogeneous disease, ranging from asymptomatic infection to a severe, potentially fatal clinical picture. The intensity and extension of the parasite-elicited inflammatory reaction is a key factor for such variability. The main features of the inflammatory process found in the brain and in the peripheral blood of neurocysticercosis patients will be discussed in this review, and the factors involved in its modulation will be herein presented. © 2015 John Wiley & Sons Ltd.

Periosteum mechanobiology and mechanistic insights for regenerative medicine

PubMed Central

Knothe Tate, Melissa L; Yu, Nicole Y C; Jalilian, Iman; Pereira, André F; Knothe, Ulf R

2016-01-01

Periosteum is a smart mechanobiological material that serves as a habitat and delivery vehicle for stem cells as well as biological factors that modulate tissue genesis and healing. Periosteum's remarkable regenerative capacity has been harnessed clinically for over two hundred years. Scientific studies over the past decade have begun to decipher the mechanobiology of periosteum, which has a significant role in its regenerative capacity. This integrative review outlines recent mechanobiological insights that are key to modulating and translating periosteum and its resident stem cells in a regenerative medicine context. PMID:27974968

Flexible digital modulation and coding synthesis for satellite communications

NASA Technical Reports Server (NTRS)

Vanderaar, Mark; Budinger, James; Hoerig, Craig; Tague, John

1991-01-01

An architecture and a hardware prototype of a flexible trellis modem/codec (FTMC) transmitter are presented. The theory of operation is built upon a pragmatic approach to trellis-coded modulation that emphasizes power and spectral efficiency. The system incorporates programmable modulation formats, variations of trellis-coding, digital baseband pulse-shaping, and digital channel precompensation. The modulation formats examined include (uncoded and coded) binary phase shift keying (BPSK), quatenary phase shift keying (QPSK), octal phase shift keying (8PSK), 16-ary quadrature amplitude modulation (16-QAM), and quadrature quadrature phase shift keying (Q squared PSK) at programmable rates up to 20 megabits per second (Mbps). The FTMC is part of the developing test bed to quantify modulation and coding concepts.

The effect of 17 beta-estradiol on cholesterol in human macrophages is influenced by the lipoprotein milieu

USDA-ARS?s Scientific Manuscript database

Estrogen and testosterone are thought to modulate coronary heart disease (CHD) risk. To examine how these hormones affect human macrophage cholesterol transport, a key factor in atherogenesis, we obtained monocytes from healthy male and postmenopausal female donors (age 50-70 y). Cells were allowe...

Signalling properties and pharmacological analysis of two sulfakinin receptors from the red flour beetle, Tribolium castaneum

USDA-ARS?s Scientific Manuscript database

Sulfakinin is an insect neuropeptide that constitutes an important component of the complex network of hormonal and neural factors that regulate feeding and digestion. The key modulating functions of sulfakinin are mediated by binding and signaling via G-protein coupled receptors. Although a subst...

SPF45-related SPLICING FACTOR FOR PHYTOCHROME SIGNALING promotes photomorphogensis by regulating pre-mRNA splicing in arabidopsis

USDA-ARS?s Scientific Manuscript database

Light signals regulate plant growth and development by controlling a plethora of gene expression changes. Post-transcriptional regulation, especially pre-mRNA processing, is a key modulator of gene expression; however, the molecular mechanisms linking pre-mRNA processing and light signaling are not ...

Structural modulation of factor VIIa by full-length tissue factor (TF1-263): implication of novel interactions between EGF2 domain and TF.

PubMed

Prasad, Ramesh; Sen, Prosenjit

2018-02-01

Tissue factor (TF)-mediated factor VII (FVII) activation and a subsequent proteolytic TF-FVIIa binary complex formation is the key step initiating the coagulation cascade, with implications in various homeostatic and pathologic scenarios. TF binding allosterically modifies zymogen-like free FVIIa to its highly catalytically active form. As a result of unresolved crystal structure of the full-length TF 1-263 -FVIIa binary complex and free FVIIa, allosteric alterations in FVIIa following its binding to full-length TF and the consequences of these on function are not entirely clear. The present study aims to map and identify structural alterations in FVIIa and TF resulting from full-length TF binding to FVIIa and the key events responsible for enhanced FVIIa activity in coagulation. We constructed the full-length TF 1-263 -FVIIa membrane bound complex using computational modeling and subjected it to molecular dynamics (MD) simulations. MD simulations showed that TF alters the structure of each domain of FVIIa and these combined alterations contribute to enhanced TF-FVIIa activity. Detailed, domain-wise investigation revealed several new non-covalent interactions between TF and FVIIa that were not found in the truncated soluble TF-FVIIa crystal structure. The structural modulation of each FVIIa domain imparted by TF indicated that both inter and intra-domain communication is crucial for allosteric modulation of FVIIa. Our results suggest that these newly formed interactions can provide additional stability to the protease domain and regulate its activity profile by governing catalytic triad (CT) orientation and localization. The unexplored newly formed interactions between EGF2 and TF provides a possible explanation for TF-induced allosteric activation of FVIIa.

Stable, low cost SAW microwave transmitter

NASA Astrophysics Data System (ADS)

Lau, K. F.; Yen, K. H.

1986-06-01

The design flexibility and application possibilities of surface acoustic wave (SAW) technology is discussed. When a highly stable, AM-modulated transmitter is required, a SAW resonator can provide an oscillator Q of up to 20,000 at 1 GHz. When FM modulation is required, the SAW delay line can provide a lower oscillator Q, which represents the optimum tradeoff between frequency stability and FM modulability. The capabilities of SAW oscillators are reviewed, and two example transmitters are presented. One transmitter operates at 1680 MHz and provides an AM-modulated signal. The second operates at the 400 to 406 MHz range and provides an FM-modulated output at one of six frequencies. SAW transmitters are suitable for applications where moderately high stability and low cost are key factors. With direct generation of signals at microwave frequencies and the flexibility of SAW oscillator design, a wide range of performance characteristics can be achieved.

The NF-YC–RGL2 module integrates GA and ABA signalling to regulate seed germination in Arabidopsis

PubMed Central

Liu, Xu; Hu, Pengwei; Huang, Mingkun; Tang, Yang; Li, Yuge; Li, Ling; Hou, Xingliang

2016-01-01

The antagonistic crosstalk between gibberellic acid (GA) and abscisic acid (ABA) plays a pivotal role in the modulation of seed germination. However, the molecular mechanism of such phytohormone interaction remains largely elusive. Here we show that three Arabidopsis NUCLEAR FACTOR-Y C (NF-YC) homologues NF-YC3, NF-YC4 and NF-YC9 redundantly modulate GA- and ABA-mediated seed germination. These NF-YCs interact with the DELLA protein RGL2, a key repressor of GA signalling. The NF-YC–RGL2 module targets ABI5, a gene encoding a core component of ABA signalling, via specific CCAAT elements and collectively regulates a set of GA- and ABA-responsive genes, thus controlling germination. These results suggest that the NF-YC–RGL2–ABI5 module integrates GA and ABA signalling pathways during seed germination. PMID:27624486

Nicotinic modulation of hippocampal cell signaling and associated effects on learning and memory.

PubMed

Kutlu, Munir Gunes; Gould, Thomas J

2016-03-01

The hippocampus is a key brain structure involved in synaptic plasticity associated with long-term declarative memory formation. Importantly, nicotine and activation of nicotinic acetylcholine receptors (nAChRs) can alter hippocampal plasticity and these changes may occur through modulation of hippocampal kinases and transcription factors. Hippocampal kinases such as cAMP-dependent protein kinase (PKA), calcium/calmodulin-dependent protein kinases (CAMKs), extracellular signal-regulated kinases 1 and 2 (ERK1/2), and c-jun N-terminal kinase 1 (JNK1), and the transcription factor cAMP-response element-binding protein (CREB) that are activated either directly or indirectly by nicotine may modulate hippocampal plasticity and in parallel hippocampus-dependent learning and memory. Evidence suggests that nicotine may alter hippocampus-dependent learning by changing the time and magnitude of activation of kinases and transcription factors normally involved in learning and by recruiting additional cell signaling molecules. Understanding how nicotine alters learning and memory will advance basic understanding of the neural substrates of learning and aid in understanding mental disorders that involve cognitive and learning deficits. Copyright © 2015 Elsevier Inc. All rights reserved.

Fibroblast growth factors: key players in regeneration and tissue repair.

PubMed

Maddaluno, Luigi; Urwyler, Corinne; Werner, Sabine

2017-11-15

Tissue injury initiates a complex repair process, which in some organisms can lead to the complete regeneration of a tissue. In mammals, however, the repair of most organs is imperfect and results in scar formation. Both regeneration and repair are orchestrated by a highly coordinated interplay of different growth factors and cytokines. Among the key players are the fibroblast growth factors (FGFs), which control the migration, proliferation, differentiation and survival of different cell types. In addition, FGFs influence the expression of other factors involved in the regenerative response. Here, we summarize current knowledge on the roles of endogenous FGFs in regeneration and repair in different organisms and in different tissues and organs. Gaining a better understanding of these FGF activities is important for appropriate modulation of FGF signaling after injury to prevent impaired healing and to promote organ regeneration in humans. © 2017. Published by The Company of Biologists Ltd.

Systems Mechanobiology: Tension-Inhibited Protein Turnover Is Sufficient to Physically Control Gene Circuits

PubMed Central

Dingal, P.C. Dave P.; Discher, Dennis E.

2014-01-01

Mechanotransduction pathways convert forces that stress and strain structures within cells into gene expression levels that impact development, homeostasis, and disease. The levels of some key structural proteins in the nucleus, cytoskeleton, or extracellular matrix have been recently reported to scale with tissue- and cell-level forces or mechanical properties such as stiffness, and so the mathematics of mechanotransduction becomes important to understand. Here, we show that if a given structural protein positively regulates its own gene expression, then stresses need only inhibit degradation of that protein to achieve stable, mechanosensitive gene expression. This basic use-it-or-lose-it module is illustrated by application to meshworks of nuclear lamin A, minifilaments of myosin II, and extracellular matrix collagen fibers—all of which possess filamentous coiled-coil/supercoiled structures. Past experiments not only suggest that tension suppresses protein degradation mediated and/or initiated by various enzymes but also that transcript levels vary with protein levels because key transcription factors are regulated by these structural proteins. Coupling between modules occurs within single cells and between cells in tissue, as illustrated during embryonic heart development where cardiac fibroblasts make collagen that cardiomyocytes contract. With few additional assumptions, the basic module has sufficient physics to control key structural genes in both development and disease. PMID:25468352

Genome-wide RNAi Screening to Identify Host Factors That Modulate Oncolytic Virus Therapy.

PubMed

Allan, Kristina J; Mahoney, Douglas J; Baird, Stephen D; Lefebvre, Charles A; Stojdl, David F

2018-04-03

High-throughput genome-wide RNAi (RNA interference) screening technology has been widely used for discovering host factors that impact virus replication. Here we present the application of this technology to uncovering host targets that specifically modulate the replication of Maraba virus, an oncolytic rhabdovirus, and vaccinia virus with the goal of enhancing therapy. While the protocol has been tested for use with oncolytic Maraba virus and oncolytic vaccinia virus, this approach is applicable to other oncolytic viruses and can also be utilized for identifying host targets that modulate virus replication in mammalian cells in general. This protocol describes the development and validation of an assay for high-throughput RNAi screening in mammalian cells, the key considerations and preparation steps important for conducting a primary high-throughput RNAi screen, and a step-by-step guide for conducting a primary high-throughput RNAi screen; in addition, it broadly outlines the methods for conducting secondary screen validation and tertiary validation studies. The benefit of high-throughput RNAi screening is that it allows one to catalogue, in an extensive and unbiased fashion, host factors that modulate any aspect of virus replication for which one can develop an in vitro assay such as infectivity, burst size, and cytotoxicity. It has the power to uncover biotherapeutic targets unforeseen based on current knowledge.

Huygens' optical vector wave field synthesis via in-plane electric dipole metasurface.

PubMed

Park, Hyeonsoo; Yun, Hansik; Choi, Chulsoo; Hong, Jongwoo; Kim, Hwi; Lee, Byoungho

2018-04-16

We investigate Huygens' optical vector wave field synthesis scheme for electric dipole metasurfaces with the capability of modulating in-plane polarization and complex amplitude and discuss the practical issues involved in realizing multi-modulation metasurfaces. The proposed Huygens' vector wave field synthesis scheme identifies the vector Airy disk as a synthetic unit element and creates a designed vector optical field by integrating polarization-controlled and complex-modulated Airy disks. The metasurface structure for the proposed vector field synthesis is analyzed in terms of the signal-to-noise ratio of the synthesized field distribution. The design of practical metasurface structures with true vector modulation capability is possible through the analysis of the light field modulation characteristics of various complex modulated geometric phase metasurfaces. It is shown that the regularization of meta-atoms is a key factor that needs to be considered in field synthesis, given that it is essential for a wide range of optical field synthetic applications, including holographic displays, microscopy, and optical lithography.

MAT1A variants are associated with hypertension, stroke, and DNA damage and are modulated by vlasma vitamin B6 and folate concentration

USDA-ARS?s Scientific Manuscript database

Elevated plasma homocysteine is a cardiovascular disease (CVD) risk factor. However, the mechanism underlying this relationship is not understood. S-adenosylmethionine synthetase isoform type-1 (MAT1A) is a key enzyme in the metabolism of homocysteine, converting dietary methionine into S-adenosyl m...

CrcZ and CrcX regulate carbon utilization in Pseudomonas syringae pathovar tomato strain DC3000

USDA-ARS?s Scientific Manuscript database

Small non-coding RNAs (ncRNAs) are important components of many regulatory pathways in bacteria and play key roles in regulating factors important for virulence. Carbon catabolite repression control is modulated by small RNAs (crcZ or crcZ and crcY) in Pseudomonas aeruginosa and Pseudomonas putida. ...

Modulation of Immune Function by Polyphenols: Possible Contribution of Epigenetic Factors

PubMed Central

Cuevas, Alejandro; Saavedra, Nicolás; Salazar, Luis A.; Abdalla, Dulcineia S. P.

2013-01-01

Several biological activities have been described for polyphenolic compounds, including a modulator effect on the immune system. The effects of these biologically active compounds on the immune system are associated to processes as differentiation and activation of immune cells. Among the mechanisms associated to immune regulation are epigenetic modifications as DNA methylation of regulatory sequences, histone modifications and posttranscriptional repression by microRNAs that influences the gene expression of key players involved in the immune response. Considering that polyphenols are able to regulate the immune function and has been also demonstrated an effect on epigenetic mechanisms, it is possible to hypothesize that there exists a mediator role of epigenetic mechanisms in the modulation of the immune response by polyphenols. PMID:23812304

2D materials in electro-optic modulation: energy efficiency, electrostatics, mode overlap, material transfer and integration

NASA Astrophysics Data System (ADS)

Ma, Zhizhen; Hemnani, Rohit; Bartels, Ludwig; Agarwal, Ritesh; Sorger, Volker J.

2018-02-01

Here we discuss the physics of electro-optic modulators deploying 2D materials. We include a scaling laws analysis and show how energy-efficiency and speed change for three underlying cavity systems as a function of critical device length scaling. A key result is that the energy-per-bit of the modulator is proportional to the volume of the device, thus making the case for submicron-scale modulators possible deploying a plasmonic optical mode. We then show how Graphene's Pauli-blocking modulation mechanism is sensitive to the device operation temperature, whereby a reduction of the temperature enables a 10× reduction in modulator energy efficiency. Furthermore, we show how the high-index tunability of graphene is able to compensate for the small optical overlap factor of 2D-based material modulators, which is unlike classical silicon-based dispersion devices. Lastly, we demonstrate a novel method towards a 2D material printer suitable for cross-contamination free and on-demand printing. The latter paves the way to integrate 2D materials seamlessly into taped-out photonic chips.

Performance Evaluation and Nonlinear Mitigation through DQPSK Modulation in 32 × 40 Gbps Long-Haul DWDM Systems

NASA Astrophysics Data System (ADS)

Sharan, Lucky; Agrawal, Vaibhav M.; Chaubey, V. K.

2017-08-01

Higher spectral efficiency and greater data rate per channel are the most cost-effective strategies to meet the exponential demand of data traffic in the optical core network. Multilevel modulation formats being spectrally efficient enhance the transmission capacity by coding information in the amplitude, phase, polarization or a combination of all. This paper presents the design architecture of a 32-channel dense wavelength division multiplexed (DWDM) system, where each channel operates with multi-level phase modulation formats at 40 Gbps. The proposed design has been simulated for 50 GHz channel spacing to numerically compute the performance of both differential phase-shift keying (DPSK) and differential quadrature phase-shift keying (DQPSK) modulation formats in such high-speed DWDM system. The transmission link is analyzed with perfect dispersion compensation and also with under-compensation scheme. The link performance in terms of quality factor (Q) for varying input powers with different dispersion compensation schemes has been evaluated. The simulation study shows significant nonlinear mitigation for both DPSK- and DQPSK-based DWDM systems up to 1,000 km and beyond. It is concluded that at higher power levels DQPSK format having a narrower spectrum shows better tolerance to dispersion and nonlinearities than DPSK format.

Using molecular functional networks to manifest connections between obesity and obesity-related diseases

PubMed Central

Yang, Jialiang; Qiu, Jing; Wang, Kejing; Zhu, Lijuan; Fan, Jingjing; Zheng, Deyin; Meng, Xiaodi; Yang, Jiasheng; Peng, Lihong; Fu, Yu; Zhang, Dahan; Peng, Shouneng; Huang, Haiyun; Zhang, Yi

2017-01-01

Obesity is a primary risk factor for many diseases such as certain cancers. In this study, we have developed three algorithms including a random-walk based method OBNet, a shortest-path based method OBsp and a direct-overlap method OBoverlap, to reveal obesity-disease connections at protein-interaction subnetworks corresponding to thousands of biological functions and pathways. Through literature mining, we also curated an obesity-associated disease list, by which we compared the methods. As a result, OBNet outperforms other two methods. OBNet can predict whether a disease is obesity-related based on its associated genes. Meanwhile, OBNet identifies extensive connections between obesity genes and genes associated with a few diseases at various functional modules and pathways. Using breast cancer and Type 2 diabetes as two examples, OBNet identifies meaningful genes that may play key roles in connecting obesity and the two diseases. For example, TGFB1 and VEGFA are inferred to be the top two key genes mediating obesity-breast cancer connection in modules associated with brain development. Finally, the top modules identified by OBNet in breast cancer significantly overlap with modules identified from TCGA breast cancer gene expression study, revealing the power of OBNet in identifying biological processes involved in the disease. PMID:29156709

76 FR 68260 - Petition for Exemption From the Federal Motor Vehicle Theft Prevention Standard; Chrysler

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-03

...), Ignition Node Module (IGNM), Engine Control Module (ECM), Body Controller Module (BCM), Sentry Key..., Chrysler stated that the RFHM sends an invalid key message to the ECM, which will disable engine operation...

Multi-Modulator for Bandwidth-Efficient Communication

NASA Technical Reports Server (NTRS)

Gray, Andrew; Lee, Dennis; Lay, Norman; Cheetham, Craig; Fong, Wai; Yeh, Pen-Shu; King, Robin; Ghuman, Parminder; Hoy, Scott; Fisher, Dave

2009-01-01

A modulator circuit board has recently been developed to be used in conjunction with a vector modulator to generate any of a large number of modulations for bandwidth-efficient radio transmission of digital data signals at rates than can exceed 100 Mb/s. The modulations include quadrature phaseshift keying (QPSK), offset quadrature phase-shift keying (OQPSK), Gaussian minimum-shift keying (GMSK), and octonary phase-shift keying (8PSK) with square-root raised-cosine pulse shaping. The figure is a greatly simplified block diagram showing the relationship between the modulator board and the rest of the transmitter. The role of the modulator board is to encode the incoming data stream and to shape the resulting pulses, which are fed as inputs to the vector modulator. The combination of encoding and pulse shaping in a given application is chosen to maximize the bandwidth efficiency. The modulator board includes gallium arsenide serial-to-parallel converters at its input end. A complementary metal oxide/semiconductor (CMOS) field-programmable gate array (FPGA) performs the coding and modulation computations and utilizes parallel processing in doing so. The results of the parallel computation are combined and converted to pulse waveforms by use of gallium arsenide parallel-to-serial converters integrated with digital-to-analog converters. Without changing the hardware, one can configure the modulator to produce any of the designed combinations of coding and modulation by loading the appropriate bit configuration file into the FPGA.

Research into experiential learning in nurse education.

PubMed

Hill, Barry

2017-09-07

This research is founded on an innovative pedagogical project as part of a higher education lecturer teaching qualification. This project involved redesigning the module 'advanced history taking and physical examination with clinical reasoning', a continuing professional development at a higher education institution. The author undertook an exploration of the literature, considering evidence on teaching styles and the way in which students learn and gain knowledge. The module was redesigned, impelemented and then evaluated by the student participants. Key themes in the evaluation centred on the experiential learning style and experiential teaching style. There are numerous internal and external factors that affect teaching, and student learning. Experiential learning has provided a successful teaching pedagogy when applied to clinical skill acquisition, and has positively benefited the module delivery and pass rate, suggesting it has embedded 'deep learning'. Student feedback was positive, and the redesigned module has had a positive impact on student engagement and the teacher-student interaction.

Indoor modeling of the wind pressure in solar installations with flat and step-like frames for HCPV modules

NASA Astrophysics Data System (ADS)

Rumyantsev, Valery D.; Ashcheulov, Yury V.; Chekalin, Alexander V.; Chumakov, Yury S.; Shvarts, Maxim Z.; Timofeev, Vladimir V.

2014-09-01

As a rule, the HCPV modules are mounted on solar trackers in a form of a flat panel. Wind pressure is one of the key factors limiting the operation capabilities of such type solar installations. At the PV Lab of the Ioffe Institute, the sun-trackers with step-like frame for modules have been proposed and developed, which have a potential for significant reduction of wind pressure. Such a reduction is realized in a wide range of the frame tilt angles the most typical for day-light operation of solar installations. In the present work, theoretical consideration and indoor experiments with mechanical models of installation frames have been carried out. A wind tunnel has been used as an experimental instrument for quantitative comparison in conventional units of expected wind loads on module frames of different designs.

Interplay between TGF-β signaling and receptor tyrosine kinases in tumor development.

PubMed

Shi, Qiaoni; Chen, Ye-Guang

2017-10-01

Transforming growth factor-β (TGF-β) signaling regulates cell proliferation, differentiation, migration and death, and plays a critical role in embryogenesis and tissue homeostasis. Its deregulation results in various diseases including tumor formation. Receptor tyrosine kinases (RTKs), such as epidermal growth factor receptor (EGFR), fibroblast growth factor receptor (FGFR), vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR), also play key roles in the development and progression of many types of tumors. It has been realized that TGF-β signaling and RTK pathways interact with each other and their interplay is important for cancer development. They are mutually regulated and cooperatively modulate cell survival and migration, epithelial-mesenchymal transition, and tumor microenvironment to accelerate tumorigenesis and tumor metastasis. RTKs can modulate Smad-dependent transcription or cooperate with TGF-β to potentiate its oncogenic activity, while TGF-β signaling can in turn control RTK signaling by regulating their activities or expression. This review summarizes current understandings of the interplay between TGF-β signaling and RTKs and its influence on tumor development.

Towards the Improvement of the Student Experience of Assessment and Feedback in Construction Management Education

ERIC Educational Resources Information Center

Scott, Lloyd; Fortune, Chris

2013-01-01

It is widely accepted across Higher Education that assessment practices have a link with learning and a key factor in this link is formative assessment. Formative assessment is generally defined as taking place during a module/programme with the express purpose of improving and enhancing student learning. It is important to understand how…

Computational Re-design of Synthetic Genetic Oscillators for Independent Amplitude and Frequency Modulation.

PubMed

Tomazou, Marios; Barahona, Mauricio; Polizzi, Karen M; Stan, Guy-Bart

2018-04-25

To perform well in biotechnology applications, synthetic genetic oscillators must be engineered to allow independent modulation of amplitude and period. This need is currently unmet. Here, we demonstrate computationally how two classic genetic oscillators, the dual-feedback oscillator and the repressilator, can be re-designed to provide independent control of amplitude and period and improve tunability-that is, a broad dynamic range of periods and amplitudes accessible through the input "dials." Our approach decouples frequency and amplitude modulation by incorporating an orthogonal "sink module" where the key molecular species are channeled for enzymatic degradation. This sink module maintains fast oscillation cycles while alleviating the translational coupling between the oscillator's transcription factors and output. We characterize the behavior of our re-designed oscillators over a broad range of physiologically reasonable parameters, explain why this facilitates broader function and control, and provide general design principles for building synthetic genetic oscillators that are more precisely controllable. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Multi-Omics and Integrated Network Analyses Reveal New Insights into the Systems Relationships between Metabolites, Structural Genes, and Transcriptional Regulators in Developing Grape Berries (Vitis vinifera L.) Exposed to Water Deficit.

PubMed

Savoi, Stefania; Wong, Darren C J; Degu, Asfaw; Herrera, Jose C; Bucchetti, Barbara; Peterlunger, Enrico; Fait, Aaron; Mattivi, Fulvio; Castellarin, Simone D

2017-01-01

Grapes are one of the major fruit crops and they are cultivated in many dry environments. This study comprehensively characterizes the metabolic response of grape berries exposed to water deficit at different developmental stages. Increases of proline, branched-chain amino acids, phenylpropanoids, anthocyanins, and free volatile organic compounds have been previously observed in grape berries exposed to water deficit. Integrating RNA-sequencing analysis of the transcriptome with large-scale analysis of central and specialized metabolites, we reveal that these increases occur via a coordinated regulation of key structural pathway genes. Water deficit-induced up-regulation of flavonoid genes is also coordinated with the down-regulation of many stilbene synthases and a consistent decrease in stilbenoid concentration. Water deficit activated both ABA-dependent and ABA-independent signal transduction pathways by modulating the expression of several transcription factors. Gene-gene and gene-metabolite network analyses showed that water deficit-responsive transcription factors such as bZIPs, AP2/ERFs, MYBs, and NACs are implicated in the regulation of stress-responsive metabolites. Enrichment of known and novel cis -regulatory elements in the promoters of several ripening-specific/water deficit-induced modules further affirms the involvement of a transcription factor cross-talk in the berry response to water deficit. Together, our integrated approaches show that water deficit-regulated gene modules are strongly linked to key fruit-quality metabolites and multiple signal transduction pathways may be critical to achieve a balance between the regulation of the stress-response and the berry ripening program. This study constitutes an invaluable resource for future discoveries and comparative studies, in grapes and other fruits, centered on reproductive tissue metabolism under abiotic stress.

Ribosome Synthesis and MAPK Activity Modulate Ionizing Radiation-Induced Germ Cell Apoptosis in Caenorhabditis elegans

PubMed Central

Eberhard, Ralf; Stergiou, Lilli; Hofmann, E. Randal; Hofmann, Jen; Haenni, Simon; Teo, Youjin; Furger, André; Hengartner, Michael O.

2013-01-01

Synthesis of ribosomal RNA by RNA polymerase I (RNA pol I) is an elemental biological process and is key for cellular homeostasis. In a forward genetic screen in C. elegans designed to identify DNA damage-response factors, we isolated a point mutation of RNA pol I, rpoa-2(op259), that leads to altered rRNA synthesis and a concomitant resistance to ionizing radiation (IR)-induced germ cell apoptosis. This weak apoptotic IR response could be phenocopied when interfering with other factors of ribosome synthesis. Surprisingly, despite their resistance to DNA damage, rpoa-2(op259) mutants present a normal CEP-1/p53 response to IR and increased basal CEP-1 activity under normal growth conditions. In parallel, rpoa-2(op259) leads to reduced Ras/MAPK pathway activity, which is required for germ cell progression and physiological germ cell death. Ras/MAPK gain-of-function conditions could rescue the IR response defect in rpoa-2(op259), pointing to a function for Ras/MAPK in modulating DNA damage-induced apoptosis downstream of CEP-1. Our data demonstrate that a single point mutation in an RNA pol I subunit can interfere with multiple key signalling pathways. Ribosome synthesis and growth-factor signalling are perturbed in many cancer cells; such an interplay between basic cellular processes and signalling might be critical for how tumours evolve or respond to treatment. PMID:24278030

Surface temperature-modulating factors in the Sonoran Desert, Mexico

NASA Astrophysics Data System (ADS)

Tereshchenko, I.; Zolotokryin, A.; Titkova, T.; Brito-Castillo, L.; Monzon, C.

2013-05-01

This study is focused on seasonal cycle of parameters, which modulate surface temperature in the Sonora desert (North-West Mexico). The understanding of this process is important for monitoring of desertification. In this paper, a new approach to the monitoring of desertification based on the use of the albedo mechanism is proposed. It is known that the positive albedo-precipitation feedback plays a significant role in the desertification process. The originality of the work rest on considering the albedo mechanism not in isolation but as a joint effect of two temperature-modulating factors: radiation and evapotranspiration. It is assumed that the prevalence of the radiation factor is a manifestation of the albedo mechanism. One indirect characteristic of prevalence of the radiation factor is Normalized Difference Vegetation Index (NDVI), which is an indicator of green phytomass. We define and substantiate the criterion of predominance of the radiation factor by using the threshold value of NDVI AVHRR. The area, within which the threshold value is achieved, is a key factor; the data on the variability of this area becomes useful and essential in the process of monitoring of desertification. This is true because in a certain year, the time span of the period, during which the radiation factor is predominant, is an important factor in the desertification process. The main features of the ratio between albedo and surface temperature are discussed in terms of analysis of monthly means (albedo, temperature, NDVI) in the state of Sonora (29-32N, 111-115W), in particular, within the box 30-31N, 112-113W.

Long-distance continuous-variable quantum key distribution with a Gaussian modulation

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

Jouguet, Paul; SeQureNet, 23 avenue d'Italie, F-75013 Paris; Kunz-Jacques, Sebastien

2011-12-15

We designed high-efficiency error correcting codes allowing us to extract an errorless secret key in a continuous-variable quantum key distribution (CVQKD) protocol using a Gaussian modulation of coherent states and a homodyne detection. These codes are available for a wide range of signal-to-noise ratios on an additive white Gaussian noise channel with a binary modulation and can be combined with a multidimensional reconciliation method proven secure against arbitrary collective attacks. This improved reconciliation procedure considerably extends the secure range of a CVQKD with a Gaussian modulation, giving a secret key rate of about 10{sup -3} bit per pulse at amore » distance of 120 km for reasonable physical parameters.« less

Identifying key genes associated with acute myocardial infarction.

PubMed

Cheng, Ming; An, Shoukuan; Li, Junquan

2017-10-01

This study aimed to identify key genes associated with acute myocardial infarction (AMI) by reanalyzing microarray data. Three gene expression profile datasets GSE66360, GSE34198, and GSE48060 were downloaded from GEO database. After data preprocessing, genes without heterogeneity across different platforms were subjected to differential expression analysis between the AMI group and the control group using metaDE package. P < .05 was used as the cutoff for a differentially expressed gene (DEG). The expression data matrices of DEGs were imported in ReactomeFIViz to construct a gene functional interaction (FI) network. Then, DEGs in each module were subjected to pathway enrichment analysis using DAVID. MiRNAs and transcription factors predicted to regulate target DEGs were identified. Quantitative real-time polymerase chain reaction (RT-PCR) was applied to verify the expression of genes. A total of 913 upregulated genes and 1060 downregulated genes were identified in the AMI group. A FI network consists of 21 modules and DEGs in 12 modules were significantly enriched in pathways. The transcription factor-miRNA-gene network contains 2 transcription factors FOXO3 and MYBL2, and 2 miRNAs hsa-miR-21-5p and hsa-miR-30c-5p. RT-PCR validations showed that expression levels of FOXO3 and MYBL2 were significantly increased in AMI, and expression levels of hsa-miR-21-5p and hsa-miR-30c-5p were obviously decreased in AMI. A total of 41 DEGs, such as SOCS3, VAPA, and COL5A2, are speculated to have roles in the pathogenesis of AMI; 2 transcription factors FOXO3 and MYBL2, and 2 miRNAs hsa-miR-21-5p and hsa-miR-30c-5p may be involved in the regulation of the expression of these DEGs.

Identifying key genes associated with acute myocardial infarction

PubMed Central

Cheng, Ming; An, Shoukuan; Li, Junquan

2017-01-01

Abstract Background: This study aimed to identify key genes associated with acute myocardial infarction (AMI) by reanalyzing microarray data. Methods: Three gene expression profile datasets GSE66360, GSE34198, and GSE48060 were downloaded from GEO database. After data preprocessing, genes without heterogeneity across different platforms were subjected to differential expression analysis between the AMI group and the control group using metaDE package. P < .05 was used as the cutoff for a differentially expressed gene (DEG). The expression data matrices of DEGs were imported in ReactomeFIViz to construct a gene functional interaction (FI) network. Then, DEGs in each module were subjected to pathway enrichment analysis using DAVID. MiRNAs and transcription factors predicted to regulate target DEGs were identified. Quantitative real-time polymerase chain reaction (RT-PCR) was applied to verify the expression of genes. Result: A total of 913 upregulated genes and 1060 downregulated genes were identified in the AMI group. A FI network consists of 21 modules and DEGs in 12 modules were significantly enriched in pathways. The transcription factor-miRNA-gene network contains 2 transcription factors FOXO3 and MYBL2, and 2 miRNAs hsa-miR-21-5p and hsa-miR-30c-5p. RT-PCR validations showed that expression levels of FOXO3 and MYBL2 were significantly increased in AMI, and expression levels of hsa-miR-21–5p and hsa-miR-30c-5p were obviously decreased in AMI. Conclusion: A total of 41 DEGs, such as SOCS3, VAPA, and COL5A2, are speculated to have roles in the pathogenesis of AMI; 2 transcription factors FOXO3 and MYBL2, and 2 miRNAs hsa-miR-21-5p and hsa-miR-30c-5p may be involved in the regulation of the expression of these DEGs. PMID:29049183

A Teaching Module about Stellar Structure and Evolution

ERIC Educational Resources Information Center

Colantonio, Arturo; Galano, Silvia; Leccia, Silvio; Puddu, Emanuella; Testa, Italo

2017-01-01

In this paper, we present a teaching module about stellar structure, functioning and evolution. Drawing from literature in astronomy education, we designed the activities around three key ideas: spectral analysis, mechanical and thermal equilibrium, energy and nuclear reactions. The module is divided into four phases, in which the key ideas for…

Direct transcriptional activation of BT genes by NLP transcription factors is a key component of the nitrate response in Arabidopsis.

PubMed

Sato, Takeo; Maekawa, Shugo; Konishi, Mineko; Yoshioka, Nozomi; Sasaki, Yuki; Maeda, Haruna; Ishida, Tetsuya; Kato, Yuki; Yamaguchi, Junji; Yanagisawa, Shuichi

2017-01-29

Nitrate modulates growth and development, functioning as a nutrient signal in plants. Although many changes in physiological processes in response to nitrate have been well characterized as nitrate responses, the molecular mechanisms underlying the nitrate response are not yet fully understood. Here, we show that NLP transcription factors, which are key regulators of the nitrate response, directly activate the nitrate-inducible expression of BT1 and BT2 encoding putative scaffold proteins with a plant-specific domain structure in Arabidopsis. Interestingly, the 35S promoter-driven expression of BT2 partially rescued growth inhibition caused by reductions in NLP activity in Arabidopsis. Furthermore, simultaneous disruption of BT1 and BT2 affected nitrate-dependent lateral root development. These results suggest that direct activation of BT1 and BT2 by NLP transcriptional activators is a key component of the molecular mechanism underlying the nitrate response in Arabidopsis. Copyright © 2016 Elsevier Inc. All rights reserved.

What Are the Predictors of Altered Central Pain Modulation in Chronic Musculoskeletal Pain Populations? A Systematic Review.

PubMed

Clark, Jacqui; Nijs, Jo; Yeowell, Gillian; Goodwin, Peter Charles

2017-09-01

Altered central pain modulation is the predominant pain mechanism in a proportion of chronic musculoskeletal pain disorders and is associated with poor outcomes. Although existing studies predict poor outcomes such as persistent pain and disability, to date there is little consensus on what factors specifically predict altered central pain modulation. To review the existing literature on the predictive factors specifically for altered central pain modulation in musculoskeletal pain populations. This is a systematic review in accordance with supplemented PRISMA guidelines. A systematic search was performed by 2 mutually blinded reviewers. Relevant articles were screened by title and abstract from Medline, Embase, PubMed, CINAHL, and Web of Science electronic databases. Alternative sources were also sought to locate missed potential articles. Eligibility included studies published in English, adults aged 18 to 65, musculoskeletal pain, baseline measurements taken at the pre-morbid or acute stage, > 3-month follow-up time after pain onset, and primary outcome measures specific to altered central pain modulation. Studies were excluded where there were concurrent diseases or they were non-predictive studies. Risk of bias was assessed using the quality in prognostic studies (QUIPS) tool. Study design, demographics, musculoskeletal region, inclusion/exclusion criteria, measurement timelines, predictor and primary outcome measures, and results were extracted. Data were synthesized qualitatively and strength of evidence was scored using the grading of recommendations, assessment, development, and evaluations (GRADE) scoring system. Nine eligible articles were located, in various musculoskeletal populations (whiplash, n = 2; widespread pain, n = 5; temporomandibular disorder, n = 2). Moderate evidence was found for 2 predictive factors of altered central pain modulation: 1) high sensory sensitivity (using genetic testing or quantitative sensory tests), and 2) psychological factors (somatization and poor self-expectation of recovery), at a pre-morbid or acute stage baseline. At the times of the article publications, the current definitions and clinical guidelines for identifying altered central pain modulation were not yet available. Careful interpretation of the information provided using current knowledge and published guidelines was necessary to extract information specific to altered central pain modulation in some of the studies, avoiding unwarranted assumptions. Premorbid and acute stage high sensory sensitivity and/or somatization are the strongest predictors of altered central pain modulation in chronic musculoskeletal pain to date. This is the first systematic review specifically targeting altered central pain modulation as the primary outcome in musculoskeletal pain populations. Early identification of people at risk of developing chronic pain with altered central pain modulation may guide clinicians in appropriate management, diminishing the burden of persistent pain on patients and heath care providers alike. Systematic Review Registration no.: PROSPERO 2015:CRD42015032394.Key words: Predictive factors, pre-morbid and acute stage baselines, altered central pain modulation, chronic musculoskeletal pain, sensory processing, somatization.

Cyclooxygenase-2 inhibitors modulate skin aging in a catalytic activity-independent manner

PubMed Central

Lee, Mi Eun; Kim, So Ra; Lee, Seungkoo; Jung, Yu-Jin; Choi, Sun Shim; Kim, Woo Jin

2012-01-01

It has been proposed that the pro-inflammatory catalytic activity of cyclooxygenase-2 (COX-2) plays a key role in the aging process. However, it remains unclear whether the COX-2 activity is a causal factor for aging and whether COX-2 inhibitors could prevent aging. We here examined the effect of COX-2 inhibitors on aging in the intrinsic skin aging model of hairless mice. We observed that among two selective COX-2 inhibitors and one non-selective COX inhibitor studied, only NS-398 inhibited skin aging, while celecoxib and aspirin accelerated skin aging. In addition, NS-398 reduced the expression of p53 and p16, whereas celecoxib and aspirin enhanced their expression. We also found that the aging-modulating effect of the inhibitors is closely associated with the expression of type I procollagen and caveolin-1. These results suggest that pro-inflammatory catalytic activity of COX-2 is not a causal factor for aging at least in skin and that COX-2 inhibitors might modulate skin aging by regulating the expression of type I procollagen and caveolin-1. PMID:22771771

The Rts1 Regulatory Subunit of Protein Phosphatase 2A Is Required for Control of G1 Cyclin Transcription and Nutrient Modulation of Cell Size

PubMed Central

Artiles, Karen; Anastasia, Stephanie; McCusker, Derek; Kellogg, Douglas R.

2009-01-01

The key molecular event that marks entry into the cell cycle is transcription of G1 cyclins, which bind and activate cyclin-dependent kinases. In yeast cells, initiation of G1 cyclin transcription is linked to achievement of a critical cell size, which contributes to cell-size homeostasis. The critical cell size is modulated by nutrients, such that cells growing in poor nutrients are smaller than cells growing in rich nutrients. Nutrient modulation of cell size does not work through known critical regulators of G1 cyclin transcription and is therefore thought to work through a distinct pathway. Here, we report that Rts1, a highly conserved regulatory subunit of protein phosphatase 2A (PP2A), is required for normal control of G1 cyclin transcription. Loss of Rts1 caused delayed initiation of bud growth and delayed and reduced accumulation of G1 cyclins. Expression of the G1 cyclin CLN2 from an inducible promoter rescued the delayed bud growth in rts1Δ cells, indicating that Rts1 acts at the level of transcription. Moreover, loss of Rts1 caused altered regulation of Swi6, a key component of the SBF transcription factor that controls G1 cyclin transcription. Epistasis analysis revealed that Rts1 does not work solely through several known critical upstream regulators of G1 cyclin transcription. Cells lacking Rts1 failed to undergo nutrient modulation of cell size. Together, these observations demonstrate that Rts1 is a key player in pathways that link nutrient availability, cell size, and G1 cyclin transcription. Since Rts1 is highly conserved, it may function in similar pathways in vertebrates. PMID:19911052

Cabin Air Quality Dynamics On Board the International Space Station

NASA Technical Reports Server (NTRS)

Perry, J. L.; Peterson, B. V.

2003-01-01

Spacecraft cabin air quality is influenced by a variety of factors. Beyond normal equipment offgassing and crew metabolic loads, the vehicle s operational configuration contributes significantly to overall air quality. Leaks from system equipment and payload facilities, operational status of the atmospheric scrubbing systems, and the introduction of new equipment and modules to the vehicle all influence air quality. The dynamics associated with changes in the International Space Station's (ISS) configuration since the launch of the U.S. Segment s laboratory module, Destiny, is summarized. Key classes of trace chemical contaminants that are important to crew health and equipment performance are emphasized. The temporary effects associated with attaching each multi-purpose logistics module (MPLM) to the ISS and influence of in-flight air quality on the post-flight ground processing of the MPLM are explored.

Modulation of transcription factors by curcumin.

PubMed

Shishodia, Shishir; Singh, Tulika; Chaturvedi, Madan M

2007-01-01

Curcumin is the active ingredient of turmeric that has been consumed as a dietary spice for ages. Turmeric is widely used in traditional Indian medicine to cure biliary disorders, anorexia, cough, diabetic wounds, hepatic disorders, rheumatism, and sinusitis. Extensive investigation over the last five decades has indicated that curcumin reduces blood cholesterol, prevents low-density lipoprotein oxidation, inhibits platelet aggregation, suppresses thrombosis and myocardial infarction, suppresses symptoms associated with type II diabetes, rheumatoid arthritis, multiple sclerosis, and Alzheimer's disease, inhibits HIV replication, enhances wound healing, protects from liver injury, increases bile secretion, protects from cataract formation, and protects from pulmonary toxicity and fibrosis. Evidence indicates that the divergent effects of curcumin are dependent on its pleiotropic molecular effects. These include the regulation of signal transduction pathways and direct modulation of several enzymatic activities. Most of these signaling cascades lead to the activation of transcription factors. Curcumin has been found to modulate the activity of several key transcription factors and, in turn, the cellular expression profiles. Curcumin has been shown to elicit vital cellular responses such as cell cycle arrest, apoptosis, and differentiation by activating a cascade of molecular events. In this chapter, we briefly review the effects of curcumin on transcription factors NF-KB, AP-1, Egr-1, STATs, PPAR-gamma, beta-catenin, nrf2, EpRE, p53, CBP, and androgen receptor (AR) and AR-related cofactors giving major emphasis to the molecular mechanisms of its action.

Superoxide dismutase 1 expression is modulated by the core pluripotency transcription factors Oct4, Sox2 and Nanog in embryonic stem cells.

PubMed

Solari, Claudia; Petrone, María Victoria; Echegaray, Camila Vázquez; Cosentino, María Soledad; Waisman, Ariel; Francia, Marcos; Barañao, Lino; Miriuka, Santiago; Guberman, Alejandra

2018-06-19

Redox homeostasis is vital for cellular functions and to prevent the detrimental consequences of oxidative stress. Pluripotent stem cells (PSCs) have an enhanced antioxidant system which supports the preservation of their genome. Besides, reactive oxygen species (ROS) are proposed to be involved in both self-renewal maintenance and in differentiation in embryonic stem cells (ESCs). Increasing evidence shows that cellular systems related to the oxidative stress defense decline along differentiation of PSCs. Although redox homeostasis has been extensively studied for many years, the knowledge about the transcriptional regulation of the genes involved in these systems is still limited. In this work, we studied Sod1 gene modulation by the PSCs fundamental transcription factors Oct4, Sox2 and Nanog. We found that this gene, which is expressed in mouse ESCs (mESCs), was repressed when they were induced to differentiate. Accordingly, these factors induced Sod1 promoter activity in a trans-activation assay. Finally, Sod1 mRNA levels were reduced when Oct4, Sox2 and Nanog were down-regulated by a shRNA approach in mESCs. Taken together, we found that PSCs' key transcription factors are involved in the modulation of Sod1 gene, suggesting a relationship between the pluripotency core and redox homeostasis in these cells. Copyright © 2018. Published by Elsevier B.V.

Neurodevelopmental origin and adult neurogenesis of the neuroendocrine hypothalamus

PubMed Central

Maggi, Roberto; Zasso, Jacopo; Conti, Luciano

2015-01-01

The adult hypothalamus regulates many physiological functions and homeostatic loops, including growth, feeding and reproduction. In mammals, the hypothalamus derives from the ventral diencephalon where two distinct ventricular proliferative zones have been described. Although a set of transcription factors regulating the hypothalamic development has been identified, the exact molecular mechanisms that drive the differentiation of hypothalamic neural precursor cells (NPCs) toward specific neuroendocrine neuronal subtypes is yet not fully disclosed. Neurogenesis has been also reported in the adult hypothalamus at the level of specific niches located in the ventrolateral region of ventricle wall, where NPCs have been identified as radial glia-like tanycytes. Here we review the molecular and cellular systems proposed to support the neurogenic potential of developing and adult hypothalamic NPCs. We also report new insights on the mechanisms by which adult hypothalamic neurogenesis modulates key functions of this brain region. Finally, we discuss how environmental factors may modulate the adult hypothalamic neurogenic cascade. PMID:25610370

Redox sensitivity of the MyD88 immune signaling adapter.

PubMed

Stottmeier, Benjamin; Dick, Tobias P

2016-12-01

The transcription factor nuclear factor-κB (NF-κB) mediates expression of key genes involved in innate immunity and inflammation. NF-κB activation has been repeatedly reported to be modulated by hydrogen peroxide (H 2 O 2 ). Here, we show that the NF-κB-activating signaling adapter myeloid differentiation primary response gene 88 (MyD88) is highly sensitive to oxidation by H 2 O 2 and may be redox-regulated in its function, thus facilitating an influence of H 2 O 2 on the NF-κB signaling pathway. Upon oxidation, MyD88 forms distinct disulfide-linked conjugates which are reduced by the MyD88-interacting oxidoreductase nucleoredoxin (Nrx). MyD88 cysteine residues functionally modulate MyD88-dependent NF-κB activation, suggesting a link between MyD88 thiol oxidation state and immune signaling. Copyright © 2016 Elsevier Inc. All rights reserved.

Mixed coherent states in coupled chaotic systems: Design of secure wireless communication

NASA Astrophysics Data System (ADS)

Vigneshwaran, M.; Dana, S. K.; Padmanaban, E.

2016-12-01

A general coupling design is proposed to realize a mixed coherent (MC) state: coexistence of complete synchronization, antisynchronization, and amplitude death in different pairs of similar state variables of the coupled chaotic system. The stability of coupled system is ensured by the Lyapunov function and a scaling of each variable is also separately taken care of. When heterogeneity as a parameter mismatch is introduced in the coupled system, the coupling function facilitates to retain its coherence and displays the global stability with renewed scaling factor. Robust synchronization features facilitated by a MC state enable to design a dual modulation scheme: binary phase shift key (BPSK) and parameter mismatch shift key (PMSK), for secure data transmission. Two classes of decoders (coherent and noncoherent) are discussed, the noncoherent decoder shows better performance over the coherent decoder, mostly a noncoherent demodulator is preferred in biological implant applications. Both the modulation schemes are demonstrated numerically by using the Lorenz oscillator and the BPSK scheme is demonstrated experimentally using radio signals.

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

Horowitz, Kelsey A; Bench Reese, Samantha R; Remo, Timothy W

This brochure, published as an annual research highlight of the Clean Energy Manufacturing Analysis Center (CEMAC), summarizes CEMAC analysis of silicon carbide (SiC) power electronics for variable frequency motor drives. The key finding presented is that variations in manufacturing expertise, yields, and access to existing facilities impact regional costs and manufacturing location decisions for SiC ingots, wafers, chips, and power modules more than do core country-specific factors such as labor and electricity costs.

Information systems for material flow management in construction processes

NASA Astrophysics Data System (ADS)

Mesároš, P.; Mandičák, T.

2015-01-01

The article describes the options for the management of material flows in the construction process. Management and resource planning is one of the key factors influencing the effectiveness of construction project. It is very difficult to set these flows correctly. The current period offers several options and tools to do this. Information systems and their modules can be used just for the management of materials in the construction process.

Impact of transient soil water simulation to estimated nitrogen leaching and emission at high- and low-deposition forest sites in southern California

Treesearch

Yuan Yuan; Thomas Meixner; Mark E. Fenn; Jirka Simunek

2011-01-01

Soil water dynamics and drainage are key abiotic factors controlling losses of atmospherically deposited N in Southern California. In this paper soil N leaching and trace gaseous emissions simulated by the DAYCENT biogeochemical model using its original semi‐dynamic water flow module were compared to that coupled with a finite element transient water flow...

Redox Stimulation of Human THP-1 Monocytes in Response to Cold Physical Plasma.

PubMed

Bekeschus, Sander; Schmidt, Anke; Bethge, Lydia; Masur, Kai; von Woedtke, Thomas; Hasse, Sybille; Wende, Kristian

2016-01-01

In plasma medicine, cold physical plasma delivers a delicate mixture of reactive components to cells and tissues. Recent studies suggested a beneficial role of cold plasma in wound healing. Yet, the biological processes related to the redox modulation via plasma are not fully understood. We here used the monocytic cell line THP-1 as a model to test their response to cold plasma in vitro. Intriguingly, short term plasma treatment stimulated cell growth. Longer exposure only modestly compromised cell viability but apparently supported the growth of cells that were enlarged in size and that showed enhanced metabolic activity. A significantly increased mitochondrial content in plasma treated cells supported this notion. On THP-1 cell proteome level, we identified an increase of protein translation with key regulatory proteins being involved in redox regulation (hypoxia inducible factor 2α), differentiation (retinoic acid signaling and interferon inducible factors), and cell growth (Yin Yang 1). Regulation of inflammation is a key element in many chronic diseases, and we found a significantly increased expression of the anti-inflammatory heme oxygenase 1 (HMOX1) and of the neutrophil attractant chemokine interleukin-8 (IL-8). Together, these results foster the view that cold physical plasma modulates the redox balance and inflammatory processes in wound related cells.

Unconditional security proof of long-distance continuous-variable quantum key distribution with discrete modulation.

PubMed

Leverrier, Anthony; Grangier, Philippe

2009-05-08

We present a continuous-variable quantum key distribution protocol combining a discrete modulation and reverse reconciliation. This protocol is proven unconditionally secure and allows the distribution of secret keys over long distances, thanks to a reverse reconciliation scheme efficient at very low signal-to-noise ratio.

Generation and detection of 80-Gbit/s return-to-zero differential phase-shift keying signals

NASA Astrophysics Data System (ADS)

Möller, Lothar; Su, Yikai; Xie, Chongjin; Liu, Xiang; Leuthold, Juerg; Gill, Douglas; Wei, Xing

2003-12-01

Nonlinear polarization rotation between a pump and a probe signal in a highly nonlinear fiber is used as a modulation process to generate 80-Gbit/s return-to-zero differential phase-shift keying signals. Its performance is analyzed and compared with a conventional on-off keying modulated signal.

Transceivers and receivers for quantum key distribution and methods pertaining thereto

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

DeRose, Christopher; Sarovar, Mohan; Soh, Daniel B.S.

Various technologies for performing continuous-variable (CV) and discrete-variable (DV) quantum key distribution (QKD) with integrated electro-optical circuits are described herein. An integrated DV-QKD system uses Mach-Zehnder modulators to modulate a polarization of photons at a transmitter and select a photon polarization measurement basis at a receiver. An integrated CV-QKD system uses wavelength division multiplexing to send and receive amplitude-modulated and phase-modulated optical signals with a local oscillator signal while maintaining phase coherence between the modulated signals and the local oscillator signal.

Selective Modulation of K+ Channel Kv7.4 Significantly Affects the Excitability of DRN 5-HT Neurons.

PubMed

Zhao, Chen; Su, Min; Wang, Yingzi; Li, Xinmeng; Zhang, Yongxue; Du, Xiaona; Zhang, Hailin

2017-01-01

The serotonin (5-HT) system originating in the dorsal raphe nucleus (DRN) is implicated in various mood- and emotion-related disorders, such as anxiety, fear and stress. Abnormal activity of DRN 5-HT neurons is the key factor in the development of these disorders. Here, we describe a crucial role for the Kv7.4 potassium channel in modulating DRN 5-HT neuronal excitability. We demonstrate that Kv7.4 is selectively expressed in 5-HT neurons of the DRN. Using selective Kv7.4 opener fasudil and Kv7.4 knock-out mice, we demonstrate that Kv7.4 is a potent modulator of DRN 5-HT neuronal excitability. Furthermore, we demonstrate that the cellular redox signaling mechanism is involved in this 5-HT activation of Kv7.4. The current study suggests a new strategy for treating psychiatric disorders related to altered activity of DRN 5-HT neurons using K + channel modulators.

Selective Modulation of K+ Channel Kv7.4 Significantly Affects the Excitability of DRN 5-HT Neurons

PubMed Central

Zhao, Chen; Su, Min; Wang, Yingzi; Li, Xinmeng; Zhang, Yongxue; Du, Xiaona; Zhang, Hailin

2017-01-01

The serotonin (5-HT) system originating in the dorsal raphe nucleus (DRN) is implicated in various mood- and emotion-related disorders, such as anxiety, fear and stress. Abnormal activity of DRN 5-HT neurons is the key factor in the development of these disorders. Here, we describe a crucial role for the Kv7.4 potassium channel in modulating DRN 5-HT neuronal excitability. We demonstrate that Kv7.4 is selectively expressed in 5-HT neurons of the DRN. Using selective Kv7.4 opener fasudil and Kv7.4 knock-out mice, we demonstrate that Kv7.4 is a potent modulator of DRN 5-HT neuronal excitability. Furthermore, we demonstrate that the cellular redox signaling mechanism is involved in this 5-HT activation of Kv7.4. The current study suggests a new strategy for treating psychiatric disorders related to altered activity of DRN 5-HT neurons using K+ channel modulators. PMID:29311835

Arctigenin induced gallbladder cancer senescence through modulating epidermal growth factor receptor pathway.

PubMed

Zhang, Mingdi; Cai, Shizhong; Zuo, Bin; Gong, Wei; Tang, Zhaohui; Zhou, Di; Weng, Mingzhe; Qin, Yiyu; Wang, Shouhua; Liu, Jun; Ma, Fei; Quan, Zhiwei

2017-05-01

Gallbladder cancer has poor prognosis and limited therapeutic options. Arctigenin, a representative dibenzylbutyrolactone lignan, occurs in a variety of plants. However, the molecular mechanisms involved in the antitumor effect of arctigenin on gallbladder cancer have not been fully elucidated. The expression levels of epidermal growth factor receptor were examined in 100 matched pairs of gallbladder cancer tissues. A positive correlation between high epidermal growth factor receptor expression levels and poor prognosis was observed in gallbladder cancer tissues. Pharmacological inhibition or inhibition via RNA interference of epidermal growth factor receptor induced cellular senescence in gallbladder cancer cells. The antitumor effect of arctigenin on gallbladder cancer cells was primarily achieved by inducing cellular senescence. In gallbladder cancer cells treated with arctigenin, the expression level of epidermal growth factor receptor significantly decreased. The analysis of the activity of the kinases downstream of epidermal growth factor receptor revealed that the RAF-MEK-ERK signaling pathway was significantly inhibited. Furthermore, the cellular senescence induced by arctigenin could be reverted by pcDNA-epidermal growth factor receptor. Arctigenin also potently inhibited the growth of tumor xenografts, which was accompanied by the downregulation of epidermal growth factor receptor and induction of senescence. This study demonstrates arctigenin could induce cellular senescence in gallbladder cancer through the modulation of epidermal growth factor receptor pathway. These data identify epidermal growth factor receptor as a key regulator in arctigenin-induced gallbladder cancer senescence.

Cytokine modulation by glucocorticoids: mechanisms and actions in cellular studies.

PubMed

Brattsand, R; Linden, M

1996-01-01

Glucocorticoids inhibit the expression and action of most cytokines. This is part of the in vivo feed-back system between inflammation-derived cytokines and CNS-adrenal produced corticosteroids with the probable physiological relevance to balance parts of the host defence and anti-inflammatory systems of the body. Glucocorticoids modulate cytokine expression by a combination of genomic mechanisms. The activated glucocorticoid-receptor complex can (i) bind to and inactivate key proinflammatory transcription factors (e.g. AP-1, NF kappa B). This takes place at the promotor responsive elements of these factors, but has also been reported without the presence of DNA; (ii) via glucocorticoid responsive elements (GRE), upregulate the expression of cytokine inhibitory proteins, e.g. I kappa B, which inactivates the transcription factor NF kappa B and thereby the secondary expression of a series of cytokines; (iii) reduce the half-life time and utility of cytokine mRNAs. In studies with triggered human blood mononuclear cells in culture, glucocorticoids strongly diminish the production of the 'initial phase' cytokines IL-1 beta and TNF-alpha and the 'immunomodulatory' cytokines IL-2, IL-3, IL-4, IL-5, IL-10, IL-12 and IFN-gamma, as well as of IL-6, IL-8 and the growth factor GM-CSF. While steroid treatment broadly attenuates cytokine production, it cannot modulate it selectively, e.g. just the TH0, the TH1 or the TH2 pathways. The production of the 'anti-inflammatory' IL-10 is also inhibited. The exceptions of steroid down-regulatory activity on cytokine expression seem to affect 'repair phase' cytokines like TGF-beta and PDGF. These are even reported to be upregulated, which may explain the rather weak steroid dampening action on healing and fibrotic processes. Some growth factors, e.g. G-CSF and M-CSF, are only weakly affected. In addition to diminishing the production of a cytokine, steroids can also often inhibit its subsequent actions. Because cytokines work in cascades, this means that steroid treatment can block expression of the subsequent cytokines. The blocked cytokine activity does not depend on a reduced cytokine receptor expression; in fact available in vitro investigations show that while the cytokine expression is blunted, its receptor is upregulated. The cellular studies presented here may represent the maximum potential of steroids to modulate cytokine expression in human mononuclear cells. It remains to be determined by clinical-experimental studies how effective cytokine modulation can be achieved in situ in inflamed bowel by systemic or by topical steroid therapy. Such studies may also answer whether a blocked cytokine production/action is the key or just a secondary mechanism behind the unique efficacy of steroids in active inflammatory bowel disease.

Magnetic measurement of soft magnetic composites material under 3D SVPWM excitation

NASA Astrophysics Data System (ADS)

Zhang, Changgeng; Jiang, Baolin; Li, Yongjian; Yang, Qingxin

2018-05-01

The magnetic properties measurement and analysis of soft magnetic material under the rotational space-vector pulse width modulation (SVPWM) excitation are key factors in design and optimization of the adjustable speed motor. In this paper, a three-dimensional (3D) magnetic properties testing system fit for SVPWM excitation is built, which includes symmetrical orthogonal excitation magnetic circuit and cubic field-metric sensor. Base on the testing system, the vector B and H loci of soft magnetic composite (SMC) material under SVPWM excitation are measured and analyzed by proposed 3D SVPWM control method. Alternating and rotating core losses under various complex excitation with different magnitude modulation ratio are calculated and compared.

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

Yazawa, Kazuaki; Shakouri, Ali

The energy conversion efficiency of today’s thermoelectric generators is significantly lower than that of conventional mechanical engines. Almost all of the existing research is focused on materials to improve the conversion efficiency. Here we propose a general framework to study the cost-efficiency trade-off for thermoelectric power generation. A key factor is the optimization of thermoelectric modules together with their heat source and heat sinks. Full electrical and thermal co-optimization yield a simple analytical expression for optimum design. Based on this model, power output per unit mass can be maximized. We show that the fractional area coverage of thermoelectric elements inmore » a module could play a significant role in reducing the cost of power generation systems.« less

IGF1R as a Key Target in High Risk, Metastatic Medulloblastoma

PubMed Central

Svalina, Matthew N.; Kikuchi, Ken; Abraham, Jinu; Lal, Sangeet; Davare, Monika A.; Settelmeyer, Teagan P.; Young, Michael C.; Peckham, Jennifer L.; Cho, Yoon-Jae; Michalek, Joel E.; Hernandez, Brian S.; Berlow, Noah E.; Jackson, Melanie; Guillaume, Daniel J.; Selden, Nathan R.; Bigner, Darell D.; Nazemi, Kellie J.; Green, Sarah C.; Corless, Christopher L.; Gultekin, Sakir; Mansoor, Atiya; Rubin, Brian P.; Woltjer, Randall; Keller, Charles

2016-01-01

Risk or presence of metastasis in medulloblastoma causes substantial treatment-related morbidity and overall mortality. Through the comparison of cytokines and growth factors in the cerebrospinal fluid (CSF) of metastatic medulloblastoma patients with factors also in conditioned media of metastatic MYC amplified medulloblastoma or leptomeningeal cells, we were led to explore the bioactivity of IGF1 in medulloblastoma by elevated CSF levels of IGF1, IGF-sequestering IGFBP3, IGFBP3-cleaving proteases (MMP and tPA), and protease modulators (TIMP1 and PAI-1). IGF1 led not only to receptor phosphorylation but also accelerated migration/adhesion in MYC amplified medulloblastoma cells in the context of appropriate matrix or meningothelial cells. Clinical correlation suggests a peri-/sub-meningothelial source of IGF-liberating proteases that could facilitate leptomeningeal metastasis. In parallel, studies of key factors responsible for cell autonomous growth in MYC amplified medulloblastoma prioritized IGF1R inhibitors. Together, our studies identify IGF1R as a high value target for clinical trials in high risk medulloblastoma. PMID:27255663

Spatial Variability of Cyanobacteria and Heterotrophic Bacteria in Lake Taihu (China).

PubMed

Qian, Haifeng; Lu, Tao; Song, Hao; Lavoie, Michel; Xu, Jiahui; Fan, Xiaoji; Pan, Xiangliang

2017-09-01

Cyanobacterial blooms frequently occur in Lake Taihu (China), but the intertwined relationships between biotic and abiotic factors modulating the frequency and duration of the blooms remain enigmatic. To better understand the relationships between the key abiotic and biotic factors and cyanobacterial blooms, we measured the abundance and diversity of prokaryotic organisms by high-throughput sequencing, the abundance of key genes involved in microcystin production and nitrogen fixation or loss as well as several physicochemical parameters at several stations in Lake Taihu during a cyanobacterial bloom of Microcystis sp.. Measurements of the copy number of denitrification-related genes and 16S rRNA analyses show that denitrification potential and denitrifying bacteria abundance increased in concert with non-diazotrophic cyanobacteria (Microcystis sp.), suggesting limited competition between cyanobacteria and heterotrophic denitrifiers for nutrients, although potential bacteria-mediated N loss may hamper Microcystis growth. The present study provides insight into the importance of different abiotic and biotic factors in controlling cyanobacteria and heterotrophic bacteria spatial variability in Lake Taihu.

IGF1R as a Key Target in High Risk, Metastatic Medulloblastoma.

PubMed

Svalina, Matthew N; Kikuchi, Ken; Abraham, Jinu; Lal, Sangeet; Davare, Monika A; Settelmeyer, Teagan P; Young, Michael C; Peckham, Jennifer L; Cho, Yoon-Jae; Michalek, Joel E; Hernandez, Brian S; Berlow, Noah E; Jackson, Melanie; Guillaume, Daniel J; Selden, Nathan R; Bigner, Darell D; Nazemi, Kellie J; Green, Sarah C; Corless, Christopher L; Gultekin, Sakir; Mansoor, Atiya; Rubin, Brian P; Woltjer, Randall; Keller, Charles

2016-06-03

Risk or presence of metastasis in medulloblastoma causes substantial treatment-related morbidity and overall mortality. Through the comparison of cytokines and growth factors in the cerebrospinal fluid (CSF) of metastatic medulloblastoma patients with factors also in conditioned media of metastatic MYC amplified medulloblastoma or leptomeningeal cells, we were led to explore the bioactivity of IGF1 in medulloblastoma by elevated CSF levels of IGF1, IGF-sequestering IGFBP3, IGFBP3-cleaving proteases (MMP and tPA), and protease modulators (TIMP1 and PAI-1). IGF1 led not only to receptor phosphorylation but also accelerated migration/adhesion in MYC amplified medulloblastoma cells in the context of appropriate matrix or meningothelial cells. Clinical correlation suggests a peri-/sub-meningothelial source of IGF-liberating proteases that could facilitate leptomeningeal metastasis. In parallel, studies of key factors responsible for cell autonomous growth in MYC amplified medulloblastoma prioritized IGF1R inhibitors. Together, our studies identify IGF1R as a high value target for clinical trials in high risk medulloblastoma.

Asymmetry of perceived key movement in chorale sequences: converging evidence from a probe-tone analysis.

PubMed

Cuddy, L L; Thompson, W F

1992-01-01

In a probe-tone experiment, two groups of listeners--one trained, the other untrained, in traditional music theory--rated the goodness of fit of each of the 12 notes of the chromatic scale to four-voice harmonic sequences. Sequences were 12 simplified excerpts from Bach chorales, 4 nonmodulating, and 8 modulating. Modulations occurred either one or two steps in either the clockwise or the counterclockwise direction on the cycle of fifths. A consistent pattern of probe-tone ratings was obtained for each sequence, with no significant differences between listener groups. Two methods of analysis (Fourier analysis and regression analysis) revealed a directional asymmetry in the perceived key movement conveyed by modulating sequences. For a given modulation distance, modulations in the counterclockwise direction effected a clearer shift in tonal organization toward the final key than did clockwise modulations. The nature of the directional asymmetry was consistent with results reported for identification and rating of key change in the sequences (Thompson & Cuddy, 1989a). Further, according to the multiple-regression analysis, probe-tone ratings did not merely reflect the distribution of tones in the sequence. Rather, ratings were sensitive to the temporal structure of the tonal organization in the sequence.

System design of the Pioneer Venus spacecraft. Volume 5: Probe vehicle studies

NASA Technical Reports Server (NTRS)

Nolte, L. J.; Stephenson, D. S.

1973-01-01

A summary of the key issues and studies conducted for the Pioneer Venus spacecraft and the resulting probe designs are presented. The key deceleration module issues are aerodynamic configuration and heat shield material selection. The design and development of the pressure vessel module are explained. Thermal control and science integration of the pressure vessel module are explained. The deceleration module heat shield, parachute and separation/despin are reported. The Thor/Delta and Atlas/Centaur baseline descriptions are provided.

Mechanical Amplifier for a Piezoelectric Transducer

NASA Technical Reports Server (NTRS)

Moore, James; Swain, Mark; Lawson, Peter; Calvet, Robert

2003-01-01

A mechanical amplifier has been devised to multiply the stroke of a piezoelectric transducer (PZT) intended for use at liquid helium temperatures. Interferometry holds the key to high angular resolution imaging and astrometry in space. Future space missions that will detect planets around other solar systems and perform detailed studies of the evolution of stars and galaxies will use new interferometers that observe at mid- and far-infrared wavelengths. Phase-measurement interferometry is key to many aspects of astronomical interferometry, and PZTs are ideal modulators for most methods of phase measurement, but primarily at visible wavelengths. At far infrared wavelengths of 150 to 300 m, background noise is a severe problem and all optics must be cooled to about 4 K. Under these conditions, piezos are ill-suited as modulators, because their throw is reduced by as much as a factor of 2, and even a wavelength or two of modulation is beyond their capability. The largest commercially available piezo stacks are about 5 in. (12.7 cm) long and have a throw of about 180 m at room temperature and only 90 m at 4 K. It would seem difficult or impossible to use PZTs for phase measurements in the far infrared were it not for the new mechanical amplifier that was designed and built.

Evaluation of Information Leakage from Cryptographic Hardware via Common-Mode Current

NASA Astrophysics Data System (ADS)

Hayashi, Yu-Ichi; Homma, Naofumi; Mizuki, Takaaki; Sugawara, Takeshi; Kayano, Yoshiki; Aoki, Takafumi; Minegishi, Shigeki; Satoh, Akashi; Sone, Hideaki; Inoue, Hiroshi

This paper presents a possibility of Electromagnetic (EM) analysis against cryptographic modules outside their security boundaries. The mechanism behind the information leakage is explained from the view point of Electromagnetic Compatibility: electric fluctuation released from cryptographic modules can conduct to peripheral circuits based on ground bounce, resulting in radiation. We demonstrate the consequence of the mechanism through experiments where the ISO/IEC standard block cipher AES (Advanced Encryption Standard) is implemented on an FPGA board and EM radiations from power and communication cables are measured. Correlation Electromagnetic Analysis (CEMA) is conducted in order to evaluate the information leakage. The experimental results show that secret keys are revealed even though there are various disturbing factors such as voltage regulators and AC/DC converters between the target module and the measurement points. We also discuss information-suppression techniques as electrical-level countermeasures against such CEMAs.

Relative phase noise induced impairment in CO-OFDM optical communication system with distributed fiber Raman amplifier.

PubMed

Wu, Jiadi; Cheng, Jingchi; Tang, Ming; Deng, Lei; Songnian, Fu; Shum, Perry Ping; Liu, Deming

2014-05-15

In this Letter, we demonstrate that the interplay between Raman pump relative intensity noise and cross-phase modulation leads to a relative phase noise (RPN) that brings non-negligible performance degradation to coherent optical orthogonal frequency-division multiplexing (CO-OFDM) transmission systems with co-pumped Raman amplification. By theoretical analysis and numerical simulation, we proved that RPN brings more system impairment in terms of Q-factor penalty than the single carrier system, and relatively larger walk-off between pump and signal helps to suppress the RPN induced impairment. A higher-order modulated signal is less tolerant to RPN than a lower-order signal. With the same spectral efficiency, the quadrature-amplitude modulation format shows better tolerance to RPN than phase-shift keying. The reported findings will be useful for the design and optimization of Raman amplified CO-OFDM multi-carrier transmission systems.

The cerebral signature for pain perception and its modulation.

PubMed

Tracey, Irene; Mantyh, Patrick W

2007-08-02

Our understanding of the neural correlates of pain perception in humans has increased significantly since the advent of neuroimaging. Relating neural activity changes to the varied pain experiences has led to an increased awareness of how factors (e.g., cognition, emotion, context, injury) can separately influence pain perception. Tying this body of knowledge in humans to work in animal models of pain provides an opportunity to determine common features that reliably contribute to pain perception and its modulation. One key system that underpins the ability to change pain intensity is the brainstem's descending modulatory network with its pro- and antinociceptive components. We discuss not only the latest data describing the cerebral signature of pain and its modulation in humans, but also suggest that the brainstem plays a pivotal role in gating the degree of nociceptive transmission so that the resultant pain experienced is appropriate for the particular situation of the individual.

INFORMAS (International Network for Food and Obesity/non-communicable diseases Research, Monitoring and Action Support): overview and key principles.

PubMed

Swinburn, B; Sacks, G; Vandevijvere, S; Kumanyika, S; Lobstein, T; Neal, B; Barquera, S; Friel, S; Hawkes, C; Kelly, B; L'abbé, M; Lee, A; Ma, J; Macmullan, J; Mohan, S; Monteiro, C; Rayner, M; Sanders, D; Snowdon, W; Walker, C

2013-10-01

Non-communicable diseases (NCDs) dominate disease burdens globally and poor nutrition increasingly contributes to this global burden. Comprehensive monitoring of food environments, and evaluation of the impact of public and private sector policies on food environments is needed to strengthen accountability systems to reduce NCDs. The International Network for Food and Obesity/NCDs Research, Monitoring and Action Support (INFORMAS) is a global network of public-interest organizations and researchers that aims to monitor, benchmark and support public and private sector actions to create healthy food environments and reduce obesity, NCDs and their related inequalities. The INFORMAS framework includes two 'process' modules, that monitor the policies and actions of the public and private sectors, seven 'impact' modules that monitor the key characteristics of food environments and three 'outcome' modules that monitor dietary quality, risk factors and NCD morbidity and mortality. Monitoring frameworks and indicators have been developed for 10 modules to provide consistency, but allowing for stepwise approaches ('minimal', 'expanded', 'optimal') to data collection and analysis. INFORMAS data will enable benchmarking of food environments between countries, and monitoring of progress over time within countries. Through monitoring and benchmarking, INFORMAS will strengthen the accountability systems needed to help reduce the burden of obesity, NCDs and their related inequalities. © 2013 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of the International Association for the Study of Obesity.

Key-value store with internal key-value storage interface

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

Bent, John M.; Faibish, Sorin; Ting, Dennis P. J.

A key-value store is provided having one or more key-value storage interfaces. A key-value store on at least one compute node comprises a memory for storing a plurality of key-value pairs; and an abstract storage interface comprising a software interface module that communicates with at least one persistent storage device providing a key-value interface for persistent storage of one or more of the plurality of key-value pairs, wherein the software interface module provides the one or more key-value pairs to the at least one persistent storage device in a key-value format. The abstract storage interface optionally processes one or moremore » batch operations on the plurality of key-value pairs. A distributed embodiment for a partitioned key-value store is also provided.« less

An 8-PSK TDMA uplink modulation and coding system

NASA Technical Reports Server (NTRS)

Ames, S. A.

1992-01-01

The combination of 8-phase shift keying (8PSK) modulation and greater than 2 bits/sec/Hz drove the design of the Nyquist filter to one specified to have a rolloff factor of 0.2. This filter when built and tested was found to produce too much intersymbol interference and was abandoned for a design with a rolloff factor of 0.4. The preamble is limited to 100 bit periods of the uncoded bit period of 5 ns for a maximum preamble length of 500 ns or 40 8PSK symbol times at 12.5 ns per symbol. For 8PSK modulation, the required maximum degradation of 1 dB in -20 dB cochannel interference (CCI) drove the requirement for forward error correction coding. In this contract, the funding was not sufficient to develop the proposed codec so the codec was limited to a paper design during the preliminary design phase. The mechanization of the demodulator is digital, starting from the output of the analog to digital converters which quantize the outputs of the quadrature phase detectors. This approach is amenable to an application specific integrated circuit (ASIC) replacement in the next phase of development.

Tumor microenvironment: Modulation by decorin and related molecules harboring leucine-rich tandem motifs.

PubMed

Goldoni, Silvia; Iozzo, Renato V

2008-12-01

Decorin, the prototype member of the small leucine-rich proteoglycans, resides in the tumor microenvironment and affects the biology of various types of cancer by downregulating the activity of several receptors involved in cell growth and survival. Decorin binds to and modulates the signaling of the epidermal growth factor receptor and other members of the ErbB family of receptor tyrosine kinases. It exerts its antitumor activity by a dual mechanism: via inhibition of these key receptors through their physical downregulation coupled with attenuation of their signaling, and by binding to and sequestering TGFbeta. Decorin also modulates the insulin-like growth factor receptor and the low-density lipoprotein receptor-related protein 1, which indirectly affects the TGFbeta receptor pathway. When expressed in tumor xenograft-bearing mice or injected systemically, decorin inhibits both primary tumor growth and metastatic spreading. In this review, we summarize the latest reports on decorin and related molecules that are relevant to cancer and bring forward the idea of decorin as an anticancer therapeutic and possible prognostic marker for patients affected by various types of tumors. We also discuss the role of lumican and LRIG1, a novel cell growth inhibitor homologous to decorin. (c) 2008 Wiley-Liss, Inc.

Rapid Modulation of Protein Expression in the Rat Hippocampus Following Deep Brain Stimulation of the Fornix.

PubMed

Gondard, Elise; Chau, Hien N; Mann, Amandeep; Tierney, Travis S; Hamani, Clement; Kalia, Suneil K; Lozano, Andres M

2015-01-01

The forniceal area is currently being evaluated as a target for deep brain stimulation (DBS) to improve cognitive function in patients with Alzheimer's disease. The molecular changes at downstream targets within the stimulated circuit are unknown. To analyze the modulation of hippocampal protein expression following 1 h of fornix DBS in the rat. Animals underwent bilateral forniceal DBS for 1 h and sacrificed at different time-points after the initiation of the stimulation (1 h, 2.5 h, 5 h, 25 h). Bilateral hippocampi were isolated for western blot analyses. Forniceal DBS led to a dramatic elevation of cFos post-stimulation, suggesting that forniceal DBS activates the hippocampus. There was also a significant increase in candidate proteins including several trophic factors, such as brain derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) but not glial cell-derived neurotrophic factor (GDNF). There was in addition, increased expression of the synaptic markers growth associated protein 43 (GAP-43), synaptophysin and α-synuclein. No changes were observed at the studied time-points in Alzheimer's-related proteins including amyloid precursor protein (APP), tau, phosphorylated tau (ptau), or selected chaperone proteins (HSP40, HSP70 and CHIP). Forniceal DBS triggers hippocampal activity and rapidly modulate the expression of neurotrophic factors and markers of synaptic plasticity known to play key roles in memory processing. The clinical effects of DBS of the fornix may, in part, be mediated by producing changes in the expression of these proteins. Copyright © 2015 Elsevier Inc. All rights reserved.

Attitudes of health care students about computer-aided neuroanatomy instruction.

PubMed

McKeough, D Michael; Bagatell, Nancy

2009-01-01

This study examined students' attitudes toward computer-aided instruction (CAI), specifically neuroanatomy learning modules, to assess which components were primary in establishing these attitudes and to discuss the implications of these attitudes for successfully incorporating CAI in the preparation of health care providers. Seventy-seven masters degree, entry-level, health care professional students matriculated in an introductory neuroanatomy course volunteered as subjects for this study. Students independently reviewed the modules as supplements to lecture and completed a survey to evaluate teaching effectiveness. Responses to survey statements were compared across the learning modules to determine if students viewed the modules differently. Responses to individual survey statements were averaged to measure the strength of agreement or disagreement with the statement. Responses to open-ended questions were theme coded, and frequencies and percentages were calculated for each. Students saw no differences between the learning modules. Students perceived the learning modules as valuable; they enjoyed using the modules but did not prefer CAI over traditional lecture format. The modules were useful in learning or reinforcing neuroanatomical concepts and improving clinical problem-solving skills. Students reported that the visual representation of the neuroanatomical systems, computer animation, ability to control the use of the modules, and navigational fidelity were key factors in determining attitudes. The computer-based learning modules examined in this study were effective as adjuncts to lecture in helping entry-level health care students learn and make clinical applications of neuroanatomy information.

Experimental study on discretely modulated continuous-variable quantum key distribution

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

Shen Yong; Zou Hongxin; Chen Pingxing

2010-08-15

We present a discretely modulated continuous-variable quantum key distribution system in free space by using strong coherent states. The amplitude noise in the laser source is suppressed to the shot-noise limit by using a mode cleaner combined with a frequency shift technique. Also, it is proven that the phase noise in the source has no impact on the final secret key rate. In order to increase the encoding rate, we use broadband homodyne detectors and the no-switching protocol. In a realistic model, we establish a secret key rate of 46.8 kbits/s against collective attacks at an encoding rate of 10more » MHz for a 90% channel loss when the modulation variance is optimal.« less

Improved performance of analog and digital acousto-optic modulation with feedback under profiled beam propagation for secure communication using chaos

NASA Astrophysics Data System (ADS)

Almehmadi, Fares S.; Chatterjee, Monish R.

2014-12-01

Using intensity feedback, the closed-loop behavior of an acousto-optic hybrid device under profiled beam propagation has been recently shown to exhibit wider chaotic bands potentially leading to an increase in both the dynamic range and sensitivity to key parameters that characterize the encryption. In this work, a detailed examination is carried out vis-à-vis the robustness of the encryption/decryption process relative to parameter mismatch for both analog and pulse code modulation signals, and bit error rate (BER) curves are used to examine the impact of additive white noise. The simulations with profiled input beams are shown to produce a stronger encryption key (i.e., much lower parametric tolerance thresholds) relative to simulations with uniform plane wave input beams. In each case, it is shown that the tolerance for key parameters drops by factors ranging from 10 to 20 times below those for uniform plane wave propagation. Results are shown to be at consistently lower tolerances for secure transmission of analog and digital signals using parameter tolerance measures, as well as BER performance measures for digital signals. These results hold out the promise for considerably greater information transmission security for such a system.

Functional architecture of Escherichia coli: new insights provided by a natural decomposition approach.

PubMed

Freyre-González, Julio A; Alonso-Pavón, José A; Treviño-Quintanilla, Luis G; Collado-Vides, Julio

2008-10-27

Previous studies have used different methods in an effort to extract the modular organization of transcriptional regulatory networks. However, these approaches are not natural, as they try to cluster strongly connected genes into a module or locate known pleiotropic transcription factors in lower hierarchical layers. Here, we unravel the transcriptional regulatory network of Escherichia coli by separating it into its key elements, thus revealing its natural organization. We also present a mathematical criterion, based on the topological features of the transcriptional regulatory network, to classify the network elements into one of two possible classes: hierarchical or modular genes. We found that modular genes are clustered into physiologically correlated groups validated by a statistical analysis of the enrichment of the functional classes. Hierarchical genes encode transcription factors responsible for coordinating module responses based on general interest signals. Hierarchical elements correlate highly with the previously studied global regulators, suggesting that this could be the first mathematical method to identify global regulators. We identified a new element in transcriptional regulatory networks never described before: intermodular genes. These are structural genes that integrate, at the promoter level, signals coming from different modules, and therefore from different physiological responses. Using the concept of pleiotropy, we have reconstructed the hierarchy of the network and discuss the role of feedforward motifs in shaping the hierarchical backbone of the transcriptional regulatory network. This study sheds new light on the design principles underpinning the organization of transcriptional regulatory networks, showing a novel nonpyramidal architecture composed of independent modules globally governed by hierarchical transcription factors, whose responses are integrated by intermodular genes.

SC1 Promotes MiR124-3p Expression to Maintain the Self-Renewal of Mouse Embryonic Stem Cells by Inhibiting the MEK/ERK Pathway.

PubMed

Wei, Qing; Liu, Hongliang; Ai, Zhiying; Wu, Yongyan; Liu, Yingxiang; Shi, Zhaopeng; Ren, Xuexue; Guo, Zekun

2017-01-01

Self-renewal is one of the most important features of embryonic stem (ES) cells. SC1 is a small molecule modulator that effectively maintains the self-renewal of mouse ES cells in the absence of leukemia inhibitory factor (LIF), serum and feeder cells. However, the mechanism by which SC1 maintains the undifferentiated state of mouse ES cells remains unclear. In this study, microarray and small RNA deep-sequencing experiments were performed on mouse ES cells treated with or without SC1 to identify the key genes and microRNAs that contributed to self-renewal. SC1 regulates the expressions of pluripotency and differentiation factors, and antagonizes the retinoic acid (RA)-induced differentiation in the presence or absence of LIF. SC1 inhibits the MEK/ERK pathway through Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and pathway reporting experiments. Small RNA deep-sequencing revealed that SC1 significantly modulates the expression of multiple microRNAs with crucial functions in ES cells. The expression of miR124-3p is upregulated in SC1-treated ES cells, which significantly inhibits the MEK/ERK pathway by targeting Grb2, Sos2 and Egr1. SC1 enhances the self-renewal capacity of mouse ES cells by modulating the expression of key regulatory genes and pluripotency-associated microRNAs. SC1 significantly upregulates miR124-3p expression to further inhibit the MEK/ ERK pathway by targeting Grb2, Sos2 and Egr1. © 2017 The Author(s). Published by S. Karger AG, Basel.

Attention Induced Gain Stabilization in Broad and Narrow-Spiking Cells in the Frontal Eye-Field of Macaque Monkeys

PubMed Central

Brandt, Christian; Dasilva, Miguel; Gotthardt, Sascha; Chicharro, Daniel; Panzeri, Stefano; Distler, Claudia

2016-01-01

Top-down attention increases coding abilities by altering firing rates and rate variability. In the frontal eye field (FEF), a key area enabling top-down attention, attention induced firing rate changes are profound, but its effect on different cell types is unknown. Moreover, FEF is the only cortical area investigated in which attention does not affect rate variability, as assessed by the Fano factor, suggesting that task engagement affects cortical state nonuniformly. We show that putative interneurons in FEF of Macaca mulatta show stronger attentional rate modulation than putative pyramidal cells. Partitioning rate variability reveals that both cell types reduce rate variability with attention, but more strongly so in narrow-spiking cells. The effects are captured by a model in which attention stabilizes neuronal excitability, thereby reducing the expansive nonlinearity that links firing rate and variance. These results show that the effect of attention on different cell classes and different coding properties are consistent across the cortical hierarchy, acting through increased and stabilized neuronal excitability. SIGNIFICANCE STATEMENT Cortical processing is critically modulated by attention. A key feature of this influence is a modulation of “cortical state,” resulting in increased neuronal excitability and resilience of the network against perturbations, lower rate variability, and an increased signal-to-noise ratio. In the frontal eye field (FEF), an area assumed to control spatial attention in human and nonhuman primates, firing rate changes with attention occur, but rate variability, quantified by the Fano factor, appears to be unaffected by attention. Using recently developed analysis tools and models to quantify attention effects on narrow- and broad-spiking cell activity, we show that attention alters cortical state strongly in the FEF, demonstrating that its effect on the neuronal network is consistent across the cortical hierarchy. PMID:27445139

N-linked glycan truncation causes enhanced clearance of plasma-derived von Willebrand factor.

PubMed

O'Sullivan, J M; Aguila, S; McRae, E; Ward, S E; Rawley, O; Fallon, P G; Brophy, T M; Preston, R J S; Brady, L; Sheils, O; Chion, A; O'Donnell, J S

2016-12-01

Essentials von Willebrands factor (VWF) glycosylation plays a key role in modulating in vivo clearance. VWF glycoforms were used to examine the role of specific glycan moieties in regulating clearance. Reduction in sialylation resulted in enhanced VWF clearance through asialoglycoprotein receptor. Progressive VWF N-linked glycan trimming resulted in increased macrophage-mediated clearance. Click to hear Dr Denis discuss clearance of von Willebrand factor in a free presentation from the ISTH Academy SUMMARY: Background Enhanced von Willebrand factor (VWF) clearance is important in the etiology of both type 1 and type 2 von Willebrand disease (VWD). In addition, previous studies have demonstrated that VWF glycans play a key role in regulating in vivo clearance. However, the molecular mechanisms underlying VWF clearance remain poorly understood. Objective To define the molecular mechanisms through which VWF N-linked glycan structures influence in vivo clearance. Methods By use of a series of exoglycosidases, different plasma-derived VWF (pd-VWF) glycoforms were generated. In vivo clearance of these glycoforms was then assessed in VWF -/- mice in the presence or absence of inhibitors of asialoglycoprotein receptor (ASGPR), or following clodronate-induced macrophage depletion. Results Reduced amounts of N-linked and O-linked sialylation resulted in enhanced pd-VWF clearance modulated via ASGPR. In addition to this role of terminal sialylation, we further observed that progressive N-linked glycan trimming also resulted in markedly enhanced VWF clearance. Furthermore, these additional N-linked glycan effects on clearance were ASGPR-independent, and instead involved enhanced macrophage clearance that was mediated, at least in part, through LDL receptor-related protein 1. Conclusion The carbohydrate determinants expressed on VWF regulate susceptibility to proteolysis by ADAMTS-13. In addition, our findings now further demonstrate that non-sialic acid carbohydrate determinants expressed on VWF also play an unexpectedly important role in modulating in vivo clearance through both hepatic ASGPR-dependent and macrophage-dependent pathways. In addition, these data further support the hypothesis that variation in VWF glycosylation may be important in the pathophysiology underlying type 1C VWD. © 2016 International Society on Thrombosis and Haemostasis.

Analyzing the Energy Performance, Wind Loading, and Costs of Photovoltaic Slat Modules on Commercial Rooftops

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

Van Geet, Otto D.; Fu, Ran; Horowitz, Kelsey A.

NREL studied a new type of photovoltaic (PV) module configuration wherein multiple narrow, tilted slats are mounted in a single frame. Each slat of the PV slat module contains a single row of cells and is made using ordinary crystalline silicon PV module materials and processes, including a glass front sheet and weatherproof polymer encapsulation. Compared to a conventional ballasted system, a system using slat modules offer higher energy production and lower weight at lower LCOE. The key benefits of slat modules are reduced wind loading, improved capacity factor and reduced installation cost. First, the individual slats allow air tomore » flow through, which reduce wind loading. Using PV performance modeling software, we compared the performance of an optimized installation of slats modules to a typical installation of conventional modules in a ballasted rack mounting system. Based on the results of the performance modeling two different row tilt and spacing were tested in a wind tunnel. Scaled models of the PV Slat modules were wind tunnel tested to quantify the wind loading of a slat module system on a commercial rooftop, comparing the results to conventional ballasted rack mounted PV modules. Some commercial roofs do not have sufficient reserve dead load capacity to accommodate a ballasted system. A reduced ballast system design could make PV system installation on these roofs feasible for the first time without accepting the disadvantages of penetrating mounts. Finally, technoeconomic analysis was conducted to enable an economic comparison between a conventional commercial rooftop system and a reduced-ballast slat module installation.« less

Cost-efficiency trade-off and the design of thermoelectric power generators.

PubMed

Yazawa, Kazuaki; Shakouri, Ali

2011-09-01

The energy conversion efficiency of today's thermoelectric generators is significantly lower than that of conventional mechanical engines. Almost all of the existing research is focused on materials to improve the conversion efficiency. Here we propose a general framework to study the cost-efficiency trade-off for thermoelectric power generation. A key factor is the optimization of thermoelectric modules together with their heat source and heat sinks. Full electrical and thermal co-optimization yield a simple analytical expression for optimum design. Based on this model, power output per unit mass can be maximized. We show that the fractional area coverage of thermoelectric elements in a module could play a significant role in reducing the cost of power generation systems.

A simultaneous all-optical half/full-subtraction strategy using cascaded highly nonlinear fibers

NASA Astrophysics Data System (ADS)

Singh, Karamdeep; Kaur, Gurmeet; Singh, Maninder Lal

2018-02-01

Using non-linear effects such as cross-gain modulation (XGM) and cross-phase modulation (XPM) inside two highly non-linear fibres (HNLF) arranged in cascaded configuration, a simultaneous half/full-subtracter is proposed. The proposed simultaneous half/full-subtracter design is attractive due to several features such as input data pattern independence and usage of minimal number of non-linear elements i.e. HNLFs. Proof of concept simulations have been conducted at 100 Gbps rate, indicating fine performance, as extinction ratio (dB) > 6.28 dB and eye opening factors (EO) > 77.1072% are recorded for each implemented output. The proposed simultaneous half/full-subtracter can be used as a key component in all-optical information processing circuits.

Microglia recapitulate a hematopoietic master regulator network in the aging human frontal cortex

PubMed Central

Wehrspaun, Claudia C.; Haerty, Wilfried; Ponting, Chris P.

2015-01-01

Microglia form the immune system of the brain. Previous studies in cell cultures and animal models suggest altered activation states and cellular senescence in the aged brain. Instead, we analyzed 3 transcriptome data sets from the postmortem frontal cortex of 381 control individuals to show that microglia gene markers assemble into a transcriptional module in a gene coexpression network. These markers predominantly represented M1 and M1/M2b activation phenotypes. Expression of genes in this module generally declines over the adult life span. This decrease was more pronounced in microglia surface receptors for microglia and/or neuron crosstalk than in markers for activation state phenotypes. In addition to these receptors for exogenous signals, microglia are controlled by brain-expressed regulatory factors. We identified a subnetwork of transcription factors, including RUNX1, IRF8, PU.1, and TAL1, which are master regulators (MRs) for the age-dependent microglia module. The causal contributions of these MRs on the microglia module were verified using publicly available ChIP-Seq data. Interactions of these key MRs were preserved in a protein-protein interaction network. Importantly, these MRs appear to be essential for regulating microglia homeostasis in the adult human frontal cortex in addition to their crucial roles in hematopoiesis and myeloid cell-fate decisions during embryogenesis. PMID:26002684

Translational Mini-Review Series on Complement Factor H: Structural and functional correlations for factor H

PubMed Central

Schmidt, C Q; Herbert, A P; Hocking, H G; Uhrín, D; Barlow, P N

2008-01-01

The 155-kDa glycoprotein, complement factor H (CFH), is a regulator of complement activation that is abundant in human plasma. Three-dimensional structures of over half the 20 complement control protein (CCP) modules in CFH have been solved in the context of single-, double- and triple-module segments. Proven binding sites for C3b occupy the N and C termini of this elongated molecule and may be brought together by a bend in CFH mediated by its central CCP modules. The C-terminal CCP 20 is key to the ability of the molecule to adhere to polyanionic markers on self-surfaces where CFH acts to regulate amplification of the alternative pathway of complement. The surface patch on CCP 20 that binds to model glycosaminoglycans has been mapped using nuclear magnetic resonance (NMR), as has a second glycosaminoglycan-binding patch on CCP 7. These patches include many of the residue positions at which sequence variations have been linked to three complement-mediated disorders: dense deposit disease, age-related macular degeneration and atypical haemolytic uraemic syndrome. In one plausible model, CCP 20 anchors CFH to self-surfaces via a C3b/polyanion composite binding site, CCP 7 acts as a ‘proof-reader’ to help discriminate self- from non-self patterns of sulphation, and CCPs 1–4 disrupt C3/C5 convertase formation and stability. PMID:18081691

Splicing Factor 1 Modulates Dietary Restriction and TORC1 Pathway Longevity in C. elegans

PubMed Central

Heintz, Caroline; Escoubas, Caroline; Zhang, Yue; Weir, Heather J.; Dutta, Sneha; Silva-García, Carlos Giovanni; Bruun, Gitte Hoffmann; Morantte, Ianessa; Hoxhaj, Gerta; Manning, Brendan D.; Andresen, Brage S.; Mair, William B.

2016-01-01

Ageing is driven by a loss of transcriptional and protein homeostasis1–3 and is the key risk factor for multiple chronic diseases. Interventions that attenuate or reverse systemic dysfunction seen with age therefore have potential to reduce overall disease risk in the elderly. Pre-mRNA splicing is a fundamental link between gene expression and the proteome, and deregulation of the splicing machinery is linked to multiple age-related chronic diseases4,5. However, the role of splicing homeostasis in healthy ageing remains unclear. Here we demonstrate that pre-mRNA splicing homeostasis is a biomarker and predictor of life expectancy in Caenorhabditis elegans. Using transcriptomics and in-depth splicing analysis in young and old animals fed ad libitum or on dietary restriction (DR), we find defects in global pre-mRNA splicing with age that are reduced by DR via the branch point binding protein (BBP)/splicing factor 1 (SFA-1). We show that SFA-1 is specifically required for lifespan extension both by DR, and modulation of TORC1 pathway components AMPK, RAGA-1 and RSKS-1/S6 Kinase. Lastly, we demonstrate that overexpression of SFA-1 is sufficient to extend lifespan. Together, these data demonstrate a role for RNA splicing homeostasis in DR longevity and suggest modulation of specific spliceosome components can prolong healthy ageing. PMID:27919065

Passive measurement-device-independent quantum key distribution with orbital angular momentum and pulse position modulation

NASA Astrophysics Data System (ADS)

Wang, Lian; Zhou, Yuan-yuan; Zhou, Xue-jun; Chen, Xiao

2018-03-01

Based on the orbital angular momentum and pulse position modulation, we present a novel passive measurement-device-independent quantum key distribution (MDI-QKD) scheme with the two-mode source. Combining with the tight bounds of the yield and error rate of single-photon pairs given in our paper, we conduct performance analysis on the scheme with heralded single-photon source. The numerical simulations show that the performance of our scheme is significantly superior to the traditional MDI-QKD in the error rate, key generation rate and secure transmission distance, since the application of orbital angular momentum and pulse position modulation can exclude the basis-dependent flaw and increase the information content for each single photon. Moreover, the performance is improved with the rise of the frame length. Therefore, our scheme, without intensity modulation, avoids the source side channels and enhances the key generation rate. It has greatly utility value in the MDI-QKD setups.

User interface techniques in the counseling module of TOPS (Transportation Operational Personal Property Standard)

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

Yow, T.G.

The Transportation Operational Personal Property Standard System (TOPS) is an automated information management system to help administer the personal property transporation program for the Department of Defense (DOD). TOPS was fielded at four prototype sites in the late summer of 1988. Prototype testing is currently underway, with system deployment scheduled for 1989. When fully deployed, TOPS will save DOD both time and money and help ensure that all shipments made by armed services personnel are handled quickly and efficiently. The success of the TOPS system depends upon several key factors. Of course, TOPS must give transportation clerks at military personalmore » property shipping offices a tool with which they can perform their jobs with greater ease, speed, and correctness. However, before TOPS can achieve success in the field, it must first find acceptance from the transportation clerks themselves. The purpose of this document is to examine the user interface techniques used in the Counseling module of TOPS to ensure user acceptance and data base integrity, both key elements in the ultimate success of TOPS. 6 refs., 12 figs.« less

Re-modulated technology of WDM-PON employing different DQPSK downstream signals

NASA Astrophysics Data System (ADS)

Gao, Chao; Xin, Xiang-jun; Yu, Chong-xiu

2012-11-01

This paper proposes a kind of modulation architecture for wavelength-division-multiplexing passive optical network (WDMPON) employing optical differential quadrature phase shift keying (DQPSK) downstream signals and two different modulation formats of re-modulated upstream signals. At the optical line terminal (OLT), 10 Gbit/s signal is modulated with DQPSK. At the optical network unit (ONU), part of the downstream signal is re-modulated with on-off keying (OOK) or inverse-return-to-zero (IRZ). Simulation results show the impact on the system employing NRZ, RZ and carrier-suppressed return-to-zero (CSRZ). The analyses also reflect that the architecture can restrain chromatic dispersion and channel crosstalk, which makes it the best architecture of access network in the future.

α-Fetoprotein as a modulator of the pro-inflammatory response of human keratinocytes

PubMed Central

Potapovich, AI; Pastore, S; Kostyuk, VA; Lulli, D; Mariani, V; De Luca, C; Dudich, EI; Korkina, LG

2009-01-01

Background and purpose: The immunomodulatory effects of α-fetoprotein (AFP) on lymphocytes and macrophages have been described in vitro and in vivo. Recombinant forms of human AFP have been proposed as potential therapeutic entities for the treatment of autoimmune diseases. We examined the effects of embryonic and recombinant human AFP on the spontaneous, UVA- and cytokine-induced pro-inflammatory responses of human keratinocytes. Experimental approach: Cultures of primary and immortalized human keratinocytes (HaCaT) and human blood T lymphocytes were used. The effects of AFP on cytokine expression were studied by bioplexed elisa and quantitative reverse transcriptase polymerase chain reaction assay. Kinase and nuclear factor kappa B (NFκB) phosphorylation were quantified by intracellular elisa. Nuclear activator protein 1 and NFκB DNA binding activity was measured by specific assays. Nitric oxide and H2O2 production and redox status were assessed by fluorescent probe and biochemical methods. Key results: All forms of AFP enhanced baseline expression of cytokines, chemokines and growth factors. AFP dose-dependently increased tumour necrosis factor alpha-stimulated granulocyte macrophage colony stimulating factor and interleukin 8 expression and decreased tumour necrosis factor alpha-induced monocyte chemotactic protein 1 and IP-10 (interferon gamma-produced protein of 10 kDa) expression. AFP induced a marked activator protein 1 activation in human keratinocytes. AFP also increased H2O2 and modulated nitrite/nitrate levels in non-stimulated keratinocytes whereas it did not affect these parameters or cytokine release from UVA-stimulated cells. Phosphorylation of extracellular signal-regulated kinase (ERK1/2) and Akt1 but not NFκB was activated by AFP alone or by its combination with UVA. Conclusions and implications: Exogenous AFP induces activation of human keratinocytes, with de novo expression of a number of pro-inflammatory mediators and modulation of their pro-inflammatory response to cytokines or UVA. AFP may modulate inflammatory events in human skin. PMID:19785658

High-Fluence Light-Emitting Diode-Generated Red Light Modulates the Transforming Growth Factor-Beta Pathway in Human Skin Fibroblasts.

PubMed

Mamalis, Andrew; Jagdeo, Jared

2018-05-24

Skin fibrosis is a significant medical problem with limited available treatment modalities. The key cellular characteristics include increased fibroblast proliferation, collagen production, and transforming growth factor-beta (TGF-B)/SMAD pathway signaling. The authors have previously shown that high-fluence light-emitting diode red light (HF-LED-RL) decreases cellular proliferation and collagen production. Herein, the authors investigate the ability of HF-LED-RL to modulate the TGF-B/SMAD pathway. Normal human dermal fibroblasts were cultured and irradiated with a commercially available hand-held LED array. After irradiation, cell lysates were collected and levels of pSMAD2, TGF-Beta 1, and TGF-Beta I receptor were measured using Western blot. High-fluence light-emitting diode red light decreased TGF-Beta 1 ligand (TGF-B1) levels after irradiation. 320 J/cm HF-LED-RL resulted in 59% TGF-B1 and 640 J/cm HF-LED-RL resulted in 54% TGF-B1, relative to controls. 640 J/cm HF-LED-RL resulted in 62% pSMAD2 0 hours after irradiation, 65% pSMAD2 2 hours after irradiation, and 95% 4 hours after irradiation, compared with matched controls. High-fluence light-emitting diode red light resulted in no significant difference in transforming growth factor-beta receptor I levels compared with matched controls. Skin fibrosis is a significant medical problem with limited available treatment modalities. Light-emitting diode-generated red light is a safe, economic, and noninvasive modality that has a body of in vitro evidence supporting the reduction of key cellular characteristics associated with skin fibrosis.

The intracellular portion of GITR enhances NGF-promoted neurite growth through an inverse modulation of Erk and NF-κB signalling

PubMed Central

McKelvey, Laura; Gutierrez, Humberto; Nocentini, Giuseppe; Crampton, Sean J.; Davies, Alun M.; Riccardi, Carlo R.; O’keeffe, Gerard W.

2012-01-01

Summary NF-κB transcription factors play a key role in regulating the growth of neural processes in the developing PNS. Although several secreted proteins have been shown to activate NF-κB to inhibit the growth of developing sympathetic neurons, it is unknown how the endogenous level of NF-κB activity present in these neurons is restricted to allow neurite growth to occur during their normal development. Here we show that activation of the glucocorticoid-induced tumour necrosis factor receptor (GITR) inhibits NF-κB activation while promoting the activation of Erk in developing sympathetic neurons. Conversely, inhibition of GITR results in an increase in NF-κB dependent gene transcription and a decrease in Erk activation leading to a reduction in neurite growth. These findings show that GITR signalling can regulate the extent of sympathetic neurite growth through an inverse modulation of Erk and NF-κB signalling, which provides an optimal environment for NGF-promoted growth. PMID:23213379

The role of probiotics on each component of the metabolic syndrome and other cardiovascular risks.

PubMed

Miglioranza Scavuzzi, Bruna; Miglioranza, Lucia Helena da Silva; Henrique, Fernanda Carla; Pitelli Paroschi, Thanise; Lozovoy, Marcell Alysson Batisti; Simão, Andréa Name Colado; Dichi, Isaias

2015-01-01

Probiotics are defined as live microorganisms that when administered in adequate amounts confer health benefits to the host. The consumption of probiotics has gained increasing recognition from the scientific community due to the promising effects on metabolic health through gut microbiota modulation. This article presents a review of scientific studies investigating probiotic species and their effects on different risk factors of the metabolic syndrome (MetS). This article also presents a summary of the major mechanisms involved with gut microbiota and the components of the MetS and raises the key issues to be considered by scientists in search of probiotics species for treatment of patients suffering from this metabolic disorder. Probiotics may confer numerous health benefits to the host through positive gut microbiota modulation. The strain selection is the most important factor for determining health effects. Further studies may consider gut microbiota as a novel target for prevention and management of MetS components and other cardiovascular risks.

Butyrate modulating effects on pro-inflammatory pathways in human intestinal epithelial cells.

PubMed

Elce, A; Amato, F; Zarrilli, F; Calignano, A; Troncone, R; Castaldo, G; Canani, R B

2017-10-13

Butyrate acts as energy source for intestinal epithelial cells and as key mediator of several immune processes, modulating gene expression mainly through histone deacetylation inhibition. Thanks to these effects, butyrate has been proposed for the treatment of many intestinal diseases. Aim of this study was to investigate the effect of butyrate on the expression of a large series of target genes encoding proteins involved in pro-inflammatory pathways. We performed quantitative real-time-PCR analysis of the expression of 86 genes encoding proteins bearing to pro-inflammatory pathways, before and after butyrate exposure, in primary epithelial cells derived from human small intestine and colon. Butyrate significantly down-regulated the expression of genes involved in inflammatory response, among which nuclear factor kappa beta, interferon-gamma, Toll like 2 receptor and tumour necrosis factor-alpha. Further confirmations of these data, including studies at protein level, would support the use of butyrate as effective therapeutic strategy in intestinal inflammatory disorders.

Silicon Photonics Transmitter with SOA and Semiconductor Mode-Locked Laser.

PubMed

Moscoso-Mártir, Alvaro; Müller, Juliana; Hauck, Johannes; Chimot, Nicolas; Setter, Rony; Badihi, Avner; Rasmussen, Daniel E; Garreau, Alexandre; Nielsen, Mads; Islamova, Elmira; Romero-García, Sebastián; Shen, Bin; Sandomirsky, Anna; Rockman, Sylvie; Li, Chao; Sharif Azadeh, Saeed; Lo, Guo-Qiang; Mentovich, Elad; Merget, Florian; Lelarge, François; Witzens, Jeremy

2017-10-24

We experimentally investigate an optical link relying on silicon photonics transmitter and receiver components as well as a single section semiconductor mode-locked laser as a light source and a semiconductor optical amplifier for signal amplification. A transmitter based on a silicon photonics resonant ring modulator, an external single section mode-locked laser and an external semiconductor optical amplifier operated together with a standard receiver reliably supports 14 Gbps on-off keying signaling with a signal quality factor better than 7 for 8 consecutive comb lines, as well as 25 Gbps signaling with a signal quality factor better than 7 for one isolated comb line, both without forward error correction. Resonant ring modulators and Germanium waveguide photodetectors are further hybridly integrated with chip scale driver and receiver electronics, and their co-operability tested. These experiments will serve as the basis for assessing the feasibility of a silicon photonics wavelength division multiplexed link relying on a single section mode-locked laser as a multi-carrier light source.

Blood coagulation factor XII drives adaptive immunity during neuroinflammation via CD87-mediated modulation of dendritic cells

PubMed Central

Göbel, Kerstin; Pankratz, Susann; Asaridou, Chloi-Magdalini; Herrmann, Alexander M.; Bittner, Stefan; Merker, Monika; Ruck, Tobias; Glumm, Sarah; Langhauser, Friederike; Kraft, Peter; Krug, Thorsten F.; Breuer, Johanna; Herold, Martin; Gross, Catharina C.; Beckmann, Denise; Korb-Pap, Adelheid; Schuhmann, Michael K.; Kuerten, Stefanie; Mitroulis, Ioannis; Ruppert, Clemens; Nolte, Marc W.; Panousis, Con; Klotz, Luisa; Kehrel, Beate; Korn, Thomas; Langer, Harald F.; Pap, Thomas; Nieswandt, Bernhard; Wiendl, Heinz; Chavakis, Triantafyllos; Kleinschnitz, Christoph; Meuth, Sven G.

2016-01-01

Aberrant immune responses represent the underlying cause of central nervous system (CNS) autoimmunity, including multiple sclerosis (MS). Recent evidence implicated the crosstalk between coagulation and immunity in CNS autoimmunity. Here we identify coagulation factor XII (FXII), the initiator of the intrinsic coagulation cascade and the kallikrein–kinin system, as a specific immune cell modulator. High levels of FXII activity are present in the plasma of MS patients during relapse. Deficiency or pharmacologic blockade of FXII renders mice less susceptible to experimental autoimmune encephalomyelitis (a model of MS) and is accompanied by reduced numbers of interleukin-17A-producing T cells. Immune activation by FXII is mediated by dendritic cells in a CD87-dependent manner and involves alterations in intracellular cyclic AMP formation. Our study demonstrates that a member of the plasmatic coagulation cascade is a key mediator of autoimmunity. FXII inhibition may provide a strategy to combat MS and other immune-related disorders. PMID:27188843

Simple proof that Gaussian attacks are optimal among collective attacks against continuous-variable quantum key distribution with a Gaussian modulation

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

Leverrier, Anthony; Grangier, Philippe; Laboratoire Charles Fabry, Institut d'Optique, CNRS, University Paris-Sud, Campus Polytechnique, RD 128, F-91127 Palaiseau Cedex

2010-06-15

In this article, we give a simple proof of the fact that the optimal collective attacks against continuous-variable quantum key distribution with a Gaussian modulation are Gaussian attacks. Our proof, which makes use of symmetry properties of the protocol in phase space, is particularly relevant for the finite-key analysis of the protocol and therefore for practical applications.

The Development of a Portable Hard Disk Encryption/Decryption System with a MEMS Coded Lock.

PubMed

Zhang, Weiping; Chen, Wenyuan; Tang, Jian; Xu, Peng; Li, Yibin; Li, Shengyong

2009-01-01

In this paper, a novel portable hard-disk encryption/decryption system with a MEMS coded lock is presented, which can authenticate the user and provide the key for the AES encryption/decryption module. The portable hard-disk encryption/decryption system is composed of the authentication module, the USB portable hard-disk interface card, the ATA protocol command decoder module, the data encryption/decryption module, the cipher key management module, the MEMS coded lock controlling circuit module, the MEMS coded lock and the hard disk. The ATA protocol circuit, the MEMS control circuit and AES encryption/decryption circuit are designed and realized by FPGA(Field Programmable Gate Array). The MEMS coded lock with two couplers and two groups of counter-meshing-gears (CMGs) are fabricated by a LIGA-like process and precision engineering method. The whole prototype was fabricated and tested. The test results show that the user's password could be correctly discriminated by the MEMS coded lock, and the AES encryption module could get the key from the MEMS coded lock. Moreover, the data in the hard-disk could be encrypted or decrypted, and the read-write speed of the dataflow could reach 17 MB/s in Ultra DMA mode.

Role of RANKL in bone diseases.

PubMed

Anandarajah, Allen P

2009-03-01

Bone remodeling is a tightly regulated process of osteoclast-mediated bone resorption, balanced by osteoblast-mediated bone formation. Disruption of this balance can lead to increased bone turnover, resulting in excessive bone loss or extra bone formation and consequent skeletal disease. The receptor activator of nuclear factor kappaB ligand (RANKL) (along with its receptor), the receptor activator of nuclear factor kappaB and its natural decoy receptor, osteoprotegerin, are the final effector proteins of osteoclastic bone resorption. Here, I provide an overview of recent studies that highlight the key role of RANKL in the pathophysiology of several bone diseases and discuss the novel therapeutic approaches afforded by the modulation of RANKL.

A pathway to bone: signaling molecules and transcription factors involved in chondrocyte development and maturation

PubMed Central

Kozhemyakina, Elena; Lassar, Andrew B.; Zelzer, Elazar

2015-01-01

Decades of work have identified the signaling pathways that regulate the differentiation of chondrocytes during bone formation, from their initial induction from mesenchymal progenitor cells to their terminal maturation into hypertrophic chondrocytes. Here, we review how multiple signaling molecules, mechanical signals and morphological cell features are integrated to activate a set of key transcription factors that determine and regulate the genetic program that induces chondrogenesis and chondrocyte differentiation. Moreover, we describe recent findings regarding the roles of several signaling pathways in modulating the proliferation and maturation of chondrocytes in the growth plate, which is the ‘engine’ of bone elongation. PMID:25715393

Advanced technologies for encryption of satellite links

NASA Astrophysics Data System (ADS)

McMahan, Sherry S.

The use of encryption on satellite links is discussed. Advanced technology exists to provide transmission security for large earth station with data rates up to 50 megabits per second. One of the major concerns in the use of encryption equipment with very small aperture terminals (VSAT) is the key management issue and the related operational costs. The low cost requirement and the lack of physical protection of remote VSATs place severe constraints on the design of encryption equipment. Encryption may be accomplished by embedding a tamper proof encryption module into the baseband unit of each VSAT. VSAT networks are usually star networks where there is a single large earth station that serves as a hub and all satellite communications takes place between each VSAT and the hub earth station. The hub earth station has the secret master key of each VSAT. These master keys are used to downline load encrypted session keys to each VSAT. A more secure alternative is to use public key techniques where each embedded VSAT encryption module internally generates its own secret and public numbers. The secret number never leaves the module while the public number is sent to the hub at the time of initialization of the encryption module into the VSAT. Physical access control to encryption modules of VSAT systems can be implemented using passwords, smart cards or biometrics.

An adaptive grid algorithm for 3-D GIS landform optimization based on improved ant algorithm

NASA Astrophysics Data System (ADS)

Wu, Chenhan; Meng, Lingkui; Deng, Shijun

2005-07-01

The key technique of 3-D GIS is to realize quick and high-quality 3-D visualization, in which 3-D roaming system based on landform plays an important role. However how to increase efficiency of 3-D roaming engine and process a large amount of landform data is a key problem in 3-D landform roaming system and improper process of the problem would result in tremendous consumption of system resources. Therefore it has become the key of 3-D roaming system design that how to realize high-speed process of distributed data for landform DEM (Digital Elevation Model) and high-speed distributed modulation of various 3-D landform data resources. In the paper we improved the basic ant algorithm and designed the modulation strategy of 3-D GIS landform resources based on the improved ant algorithm. By initially hypothetic road weights σi , the change of the information factors in the original algorithm would transform from ˜τj to ∆τj+σi and the weights was decided by 3-D computative capacity of various nodes in network environment. So during the course of initial phase of task assignment, increasing the resource information factors of high task-accomplishing rate and decreasing ones of low accomplishing rate would make load accomplishing rate approach the same value as quickly as possible, then in the later process of task assignment, the load balanced ability of the system was further improved. Experimental results show by improving ant algorithm, our system not only decreases many disadvantage of the traditional ant algorithm, but also like ants looking for food effectively distributes the complicated landform algorithm to many computers to process cooperatively and gains a satisfying search result.

Curcumin ameliorates autoimmune diabetes. Evidence in accelerated murine models of type 1 diabetes

PubMed Central

Castro, C N; Barcala Tabarrozzi, A E; Winnewisser, J; Gimeno, M L; Antunica Noguerol, M; Liberman, A C; Paz, D A; Dewey, R A; Perone, M J

2014-01-01

Type 1 diabetes (T1DM) is a T cell-mediated autoimmune disease that selectively destroys pancreatic β cells. The only possible cure for T1DM is to control autoimmunity against β cell-specific antigens. We explored whether the natural compound curcumin, with anti-oxidant and anti-inflammatory activities, might down-regulate the T cell response that destroys pancreatic β cells to improve disease outcome in autoimmune diabetes. We employed two accelerated autoimmune diabetes models: (i) cyclophosphamide (CYP) administration to non-obese diabetic (NOD) mice and (ii) adoptive transfer of diabetogenic splenocytes into NODscid mice. Curcumin treatment led to significant delay of disease onset, and in some instances prevented autoimmune diabetes by inhibiting pancreatic leucocyte infiltration and preserving insulin-expressing cells. To investigate the mechanisms of protection we studied the effect of curcumin on key immune cell populations involved in the pathogenesis of the disease. Curcumin modulates the T lymphocyte response impairing proliferation and interferon (IFN)-γ production through modulation of T-box expressed in T cells (T-bet), a key transcription factor for proinflammatory T helper type 1 (Th1) lymphocyte differentiation, both at the transcriptional and translational levels. Also, curcumin reduces nuclear factor (NF)-κB activation in T cell receptor (TCR)-stimulated NOD lymphocytes. In addition, curcumin impairs the T cell stimulatory function of dendritic cells with reduced secretion of proinflammatory cytokines and nitric oxide (NO) and low surface expression of co-stimulatory molecules, leading to an overall diminished antigen-presenting cell activity. These in-vitro effects correlated with ex-vivo analysis of cells obtained from curcumin-treated mice during the course of autoimmune diabetes. These findings reveal an effective therapeutic effect of curcumin in autoimmune diabetes by its actions on key immune cells responsible for β cell death. PMID:24628444

Liver-derived systemic factors drive β-cell hyperplasia in insulin resistant states

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

El Ouaamari, Abdelfattah; Kawamori, Dan; Dirice, Ercument

2013-02-21

Integrative organ cross-talk regulates key aspects of energy homeostasis and its dysregulation may underlie metabolic disorders such as obesity and diabetes. To test the hypothesis that cross-talk between the liver and pancreatic islets modulates β-cell growth in response to insulin resistance, we used the Liver-specific Insulin Receptor Knockout (LIRKO) mouse, a unique model that exhibits dramatic islet hyperplasia. Using complementary in vivo parabiosis and transplantation assays, and in vitro islet culture approaches, we demonstrate that humoral, non-neural, non-cell autonomous factor(s) induce β-cell proliferation in LIRKO mice. Furthermore, we report that a hepatocyte-derived factor(s) stimulates mouse and human β-cell proliferation inmore » ex vivo assays, independent of ambient glucose and insulin levels. These data implicate the liver as a critical source of β-cell growth factors in insulin resistant states.« less

Teller Training Module: Off-Line Banking System. High-Technology Training Module.

ERIC Educational Resources Information Center

Lund, Candyce J.

This teller training module on offline banking systems is intended to be part of a postsecondary financial applications course. The module contains the following sections: module objective; specific objective; content--electronic audit machine key functions, practice packet--sample bank transactions and practicing procedures, and…

Fatty Acids Regulate Germline Sex Determination through ACS-4-Dependent Myristoylation.

PubMed

Tang, Hongyun; Han, Min

2017-04-20

Fat metabolism has been linked to fertility and reproductive adaptation in animals and humans, and environmental sex determination potentially plays a role in the process. To investigate the impact of fatty acids (FA) on sex determination and reproductive development, we examined and observed an impact of FA synthesis and mobilization by lipolysis in somatic tissues on oocyte fate in Caenorhabditis elegans. The subsequent genetic analysis identified ACS-4, an acyl-CoA synthetase and its FA-CoA product, as key germline factors that mediate the role of FA in promoting oocyte fate through protein myristoylation. Further tests indicated that ACS-4-dependent protein myristoylation perceives and translates the FA level into regulatory cues that modulate the activities of MPK-1/MAPK and key factors in the germline sex-determination pathway. These findings, including a similar role of ACS-4 in a male/female species, uncover a likely conserved mechanism by which FA, an environmental factor, regulates sex determination and reproductive development. Copyright © 2017 Elsevier Inc. All rights reserved.

Screening with an NMNAT2-MSD platform identifies small molecules that modulate NMNAT2 levels in cortical neurons.

PubMed

Ali, Yousuf O; Bradley, Gillian; Lu, Hui-Chen

2017-03-07

Nicotinamide mononucleotide adenylyl transferase 2 (NMNAT2) is a key neuronal maintenance factor and provides potent neuroprotection in numerous preclinical models of neurological disorders. NMNAT2 is significantly reduced in Alzheimer's, Huntington's, Parkinson's diseases. Here we developed a Meso Scale Discovery (MSD)-based screening platform to quantify endogenous NMNAT2 in cortical neurons. The high sensitivity and large dynamic range of this NMNAT2-MSD platform allowed us to screen the Sigma LOPAC library consisting of 1280 compounds. This library had a 2.89% hit rate, with 24 NMNAT2 positive and 13 negative modulators identified. Western analysis was conducted to validate and determine the dose-dependency of identified modulators. Caffeine, one identified NMNAT2 positive-modulator, when systemically administered restored NMNAT2 expression in rTg4510 tauopathy mice to normal levels. We confirmed in a cell culture model that four selected positive-modulators exerted NMNAT2-specific neuroprotection against vincristine-induced cell death while four selected NMNAT2 negative modulators reduced neuronal viability in an NMNAT2-dependent manner. Many of the identified NMNAT2 positive modulators are predicted to increase cAMP concentration, suggesting that neuronal NMNAT2 levels are tightly regulated by cAMP signaling. Taken together, our findings indicate that the NMNAT2-MSD platform provides a sensitive phenotypic screen to detect NMNAT2 in neurons.

Screening with an NMNAT2-MSD platform identifies small molecules that modulate NMNAT2 levels in cortical neurons

PubMed Central

Ali, Yousuf O.; Bradley, Gillian; Lu, Hui-Chen

2017-01-01

Nicotinamide mononucleotide adenylyl transferase 2 (NMNAT2) is a key neuronal maintenance factor and provides potent neuroprotection in numerous preclinical models of neurological disorders. NMNAT2 is significantly reduced in Alzheimer’s, Huntington’s, Parkinson’s diseases. Here we developed a Meso Scale Discovery (MSD)-based screening platform to quantify endogenous NMNAT2 in cortical neurons. The high sensitivity and large dynamic range of this NMNAT2-MSD platform allowed us to screen the Sigma LOPAC library consisting of 1280 compounds. This library had a 2.89% hit rate, with 24 NMNAT2 positive and 13 negative modulators identified. Western analysis was conducted to validate and determine the dose-dependency of identified modulators. Caffeine, one identified NMNAT2 positive-modulator, when systemically administered restored NMNAT2 expression in rTg4510 tauopathy mice to normal levels. We confirmed in a cell culture model that four selected positive-modulators exerted NMNAT2-specific neuroprotection against vincristine-induced cell death while four selected NMNAT2 negative modulators reduced neuronal viability in an NMNAT2-dependent manner. Many of the identified NMNAT2 positive modulators are predicted to increase cAMP concentration, suggesting that neuronal NMNAT2 levels are tightly regulated by cAMP signaling. Taken together, our findings indicate that the NMNAT2-MSD platform provides a sensitive phenotypic screen to detect NMNAT2 in neurons. PMID:28266613

The AMPA receptor potentiator Org 26576 modulates stress-induced transcription of BDNF isoforms in rat hippocampus.

PubMed

Fumagalli, Fabio; Calabrese, Francesca; Luoni, Alessia; Shahid, Mohammed; Racagni, Giorgio; Riva, Marco A

2012-02-01

Brain derived neurotrophic factor (BDNF) is a key mediator of brain plasticity. The modulation of its expression and function is important for cognition and represents a key strategy to enhance neuronal resilience. Within this context, there exists a close interaction between glutamatergic neurotransmission and BDNF activity towards regulating cellular homeostasis and plasticity. The aim of the current study was to investigate the ability of the AMPA receptor potentiator Org 26576 to modulate BDNF expression in selected brain regions under basal conditions or in response to an acute swim stress. Rats subjected to a single intraperitoneal injection with Org 26576 (10mg/kg) or saline were exposed to a swim stress session (5 min) and sacrificed 15 min after the end of stress. Real-time PCR assay was used to determine changes in BDNF transcription in different brain regions. Total BDNF mRNA levels were significantly increased in the hippocampus of animals exposed to the combination of Org 26576 and stress whereas, in prefrontal and frontal cortices, BDNF mRNA levels were modulated by the acute stress, independently from drug treatment. The analysis of BDNF transcripts in the hippocampus revealed a major contribution of exons I and IV. Our results suggest that AMPA receptor potentiation by Org 26576 exerts a positive modulatory influence on BDNF expression during ongoing neuronal activity. Given that these mechanisms are critical for neuronal plasticity, we hypothesized that such changes may facilitate learning/coping mechanisms associated with a mild stressful experience. Copyright © 2011 Elsevier Ltd. All rights reserved.

The basic helix-loop-helix transcription factor Nex-1/Math-2 promotes neuronal survival of PC12 cells by modulating the dynamic expression of anti-apoptotic and cell cycle regulators

PubMed Central

Uittenbogaard, Martine; Chiaramello, Anne

2006-01-01

The basic helix-loop-helix transcription factor Nex1/Math-2 belongs to the NeuroD subfamily, which plays a critical role during neuronal differentiation and maintenance of the differentiated state. Previously, we demonstrated that Nex1 is a key regulatory component of the nerve growth factor (NGF) pathway. Further supporting this hypothesis, this study shows that Nex1 has survival-inducing properties similar to NGF, as Nex1-overexpressing PC12 cells survive in the absence of trophic factors. We dissected the molecular mechanism by which Nex1 confers neuroprotection upon serum removal and found that constitutive expression of Nex1 maintained the expression of specific G1 phase cyclin-dependent kinase inhibitors and concomitantly induced a dynamic expression profile of key anti-apoptotic regulators. This study provides the first evidence of the underlying mechanism by which a member of the NeuroD-subfamily promotes an active anti-apoptotic program essential to the survival of neurons. Our results suggest that the survival program may be viewed as an integral component of the intrinsic programming of the differ entiated state. PMID:15659228

Understanding the Link Between Pregnancy and Breast Cancer

DTIC Science & Technology

2014-06-01

injected in the mammary glands of nude mice females and 2 groups were generated virgin group and the pregnant group, in which a male was added for mating...to modulate the effect of collagen. A key mediator of involution is the insulin -like growth factor binding protein 5 (IGFBP-5) 6-9. IGFBP-5 is...expressing PAPP-A were used. We found that rIGFBP-5 is resistant to cleavage by PAPP-A in the absence of collagen (Fig. 2f). Upon addition of

Inhibiting heat shock protein 90 and the ubiquitin-proteasome pathway impairs metabolic homeostasis and leads to cell death in human pancreatic cancer cells.

PubMed

Belalcazar, Astrid; Shaib, Walid L; Farren, Matthew R; Zhang, Chao; Chen, Zhengjia; Yang, Lily; Lesinski, Gregory B; El-Rayes, Bassel F; Nagaraju, Ganji Purnachandra

2017-12-15

Heat shock protein 90 (HSP90) and the ubiquitin-proteasome pathway play crucial roles in the homeostasis of pancreatic cancer cells. This study combined for the first time the HSP90 inhibitor ganetespib (Gan) and the proteasome inhibitor carfilzomib (Carf) to target key mechanisms of homeostasis in pancreatic cancer. It was hypothesized that Gan plus Carf would elicit potent antitumor activity by modulating complementary homeostatic processes. In vitro and in vivo effects of this combination on mechanisms of cell growth and viability were evaluated with human pancreatic cancer cell lines (MIA PaCa-2 and HPAC). Combined treatment with Gan and Carf significantly decreased cell viability. The mechanism varied by cell line and involved G 2 -M cell-cycle arrest accompanied by a consistent reduction in key cell-cycle regulatory proteins and concomitant upregulation of p27. Further studies revealed increased autophagy markers, including the upregulation of autophagy related 7 and light chain 3 cleavage, and evidence of apoptosis (increased Bax expression and processing of caspase 3). Immunoblot analyses confirmed the modulation of other pathways that influence cell viability, including phosphoinositide 3-kinase/Akt and nuclear factor κB. Finally, the treatment of athymic mice bearing HPAC tumors with Gan and Carf significantly reduced tumor growth in vivo. An immunoblot analysis of freshly isolated tumors from animals at the end of the study confirmed in vivo modulation of key signaling pathways. The results reveal Gan plus Carf to be a promising combination with synergistic antiproliferative, apoptotic, and pro-autophagy effects in preclinical studies of pancreatic cancer and will further the exploration of the utility of this treatment combination in clinical trials. Cancer 2017;123:4924-33. © 2017 American Cancer Society. © 2017 American Cancer Society.

Quantum hacking of two-way continuous-variable quantum key distribution using Trojan-horse attack

NASA Astrophysics Data System (ADS)

Ma, Hong-Xin; Bao, Wan-Su; Li, Hong-Wei; Chou, Chun

2016-08-01

We present a Trojan-horse attack on the practical two-way continuous-variable quantum key distribution system. Our attack mainly focuses on the imperfection of the practical system that the modulator has a redundancy of modulation pulse-width, which leaves a loophole for the eavesdropper inserting a Trojan-horse pulse. Utilizing the unique characteristics of two-way continuous-variable quantum key distribution that Alice only takes modulation operation on the received mode without any measurement, this attack allows the eavesdropper to render all of the final keys shared between the legitimate parties insecure without being detected. After analyzing the feasibility of the attack, the corresponding countermeasures are put forward. Project supported by the National Basic Research Program of China (Grant No. 2013CB338002) and the National Natural Science Foundation of China (Grant Nos. 11304397 and 61505261).

DiME: A Scalable Disease Module Identification Algorithm with Application to Glioma Progression

PubMed Central

Liu, Yunpeng; Tennant, Daniel A.; Zhu, Zexuan; Heath, John K.; Yao, Xin; He, Shan

2014-01-01

Disease module is a group of molecular components that interact intensively in the disease specific biological network. Since the connectivity and activity of disease modules may shed light on the molecular mechanisms of pathogenesis and disease progression, their identification becomes one of the most important challenges in network medicine, an emerging paradigm to study complex human disease. This paper proposes a novel algorithm, DiME (Disease Module Extraction), to identify putative disease modules from biological networks. We have developed novel heuristics to optimise Community Extraction, a module criterion originally proposed for social network analysis, to extract topological core modules from biological networks as putative disease modules. In addition, we have incorporated a statistical significance measure, B-score, to evaluate the quality of extracted modules. As an application to complex diseases, we have employed DiME to investigate the molecular mechanisms that underpin the progression of glioma, the most common type of brain tumour. We have built low (grade II) - and high (GBM) - grade glioma co-expression networks from three independent datasets and then applied DiME to extract potential disease modules from both networks for comparison. Examination of the interconnectivity of the identified modules have revealed changes in topology and module activity (expression) between low- and high- grade tumours, which are characteristic of the major shifts in the constitution and physiology of tumour cells during glioma progression. Our results suggest that transcription factors E2F4, AR and ETS1 are potential key regulators in tumour progression. Our DiME compiled software, R/C++ source code, sample data and a tutorial are available at http://www.cs.bham.ac.uk/~szh/DiME. PMID:24523864

Vascular Endothelial Growth Factor (VEGF) and Platelet (PF-4) Factor 4 Inputs Modulate Human Microvascular Endothelial Signaling in a Three-Dimensional Matrix Migration Context*

PubMed Central

Hang, Ta-Chun; Tedford, Nathan C.; Reddy, Raven J.; Rimchala, Tharathorn; Wells, Alan; White, Forest M.; Kamm, Roger D.; Lauffenburger, Douglas A.

2013-01-01

The process of angiogenesis is under complex regulation in adult organisms, particularly as it often occurs in an inflammatory post-wound environment. As such, there are many impacting factors that will regulate the generation of new blood vessels which include not only pro-angiogenic growth factors such as vascular endothelial growth factor, but also angiostatic factors. During initial postwound hemostasis, a large initial bolus of platelet factor 4 is released into localized areas of damage before progression of wound healing toward tissue homeostasis. Because of its early presence and high concentration, the angiostatic chemokine platelet factor 4, which can induce endothelial anoikis, can strongly affect angiogenesis. In our work, we explored signaling crosstalk interactions between vascular endothelial growth factor and platelet factor 4 using phosphotyrosine-enriched mass spectrometry methods on human dermal microvascular endothelial cells cultured under conditions facilitating migratory sprouting into collagen gel matrices. We developed new methods to enable mass spectrometry-based phosphorylation analysis of primary cells cultured on collagen gels, and quantified signaling pathways over the first 48 h of treatment with vascular endothelial growth factor in the presence or absence of platelet factor 4. By observing early and late signaling dynamics in tandem with correlation network modeling, we found that platelet factor 4 has significant crosstalk with vascular endothelial growth factor by modulating cell migration and polarization pathways, centered around P38α MAPK, Src family kinases Fyn and Lyn, along with FAK. Interestingly, we found EphA2 correlational topology to strongly involve key migration-related signaling nodes after introduction of platelet factor 4, indicating an influence of the angiostatic factor on this ambiguous but generally angiogenic signal in this complex environment. PMID:24023389

Mutations in IRX5 impair craniofacial development and germ cell migration via SDF1.

PubMed

Bonnard, Carine; Strobl, Anna C; Shboul, Mohammad; Lee, Hane; Merriman, Barry; Nelson, Stanley F; Ababneh, Osama H; Uz, Elif; Güran, Tülay; Kayserili, Hülya; Hamamy, Hanan; Reversade, Bruno

2012-05-13

Using homozygosity mapping and locus resequencing, we found that alterations in the homeodomain of the IRX5 transcription factor cause a recessive congenital disorder affecting face, brain, blood, heart, bone and gonad development. We found through in vivo modeling in Xenopus laevis embryos that Irx5 modulates the migration of progenitor cell populations in branchial arches and gonads by repressing Sdf1. We further found that transcriptional control by Irx5 is modulated by direct protein-protein interaction with two GATA zinc-finger proteins, GATA3 and TRPS1; disruptions of these proteins also cause craniofacial dysmorphisms. Our findings suggest that IRX proteins integrate combinatorial transcriptional inputs to regulate key signaling molecules involved in the ontogeny of multiple organs during embryogenesis and homeostasis.

Cations Modulate Actin Bundle Mechanics, Assembly Dynamics, and Structure.

PubMed

Castaneda, Nicholas; Zheng, Tianyu; Rivera-Jacquez, Hector J; Lee, Hyun-Ju; Hyun, Jaekyung; Balaeff, Alexander; Huo, Qun; Kang, Hyeran

2018-04-12

Actin bundles are key factors in the mechanical support and dynamic reorganization of the cytoskeleton. High concentrations of multivalent counterions promote bundle formation through electrostatic attraction between actin filaments that are negatively charged polyelectrolytes. In this study, we evaluate how physiologically relevant divalent cations affect the mechanical, dynamic, and structural properties of actin bundles. Using a combination of total internal reflection fluorescence microscopy, transmission electron microscopy, and dynamic light scattering, we demonstrate that divalent cations modulate bundle stiffness, length distribution, and lateral growth. Molecular dynamics simulations of an all-atom model of the actin bundle reveal specific actin residues coordinate cation-binding sites that promote the bundle formation. Our work suggests that specific cation interactions may play a fundamental role in the assembly, structure, and mechanical properties of actin bundles.

Growth and development of the root apical meristem.

PubMed

Perilli, Serena; Di Mambro, Riccardo; Sabatini, Sabrina

2012-02-01

A key question in plant developmental biology is how cell division and cell differentiation are balanced to modulate organ growth and shape organ size. In recent years, several advances have been made in understanding how this balance is achieved during root development. In the Arabidopsis root meristem, stem cells in the apical region of the meristem self-renew and produce daughter cells that differentiate in the distal meristem transition zone. Several factors have been implicated in controlling the different functional zones of the root meristem to modulate root growth; among these, plant hormones have been shown to play a main role. In this review, we summarize recent findings regarding the role of hormone signaling and transcriptional networks in regulating root development. Copyright © 2011 Elsevier Ltd. All rights reserved.

Design and Performance Investigation for the Optical Combinational Networks at High Data Rate

NASA Astrophysics Data System (ADS)

Tripathi, Devendra Kr.

2017-05-01

This article explores performance study for optical combinational designs based on nonlinear characteristics with semiconductor optical amplifier (SOA). Two configurations for optical half-adder with non-return-to-zero modulation pattern altogether with Mach-Zehnder modulator, interferometer at 50-Gbps data rate have been successfully realized. Accordingly, SUM and CARRY outputs have been concurrently executed and verified for their output waveforms. Numerical simulations for variation of data rate and key design parameters have been effectively executed outcome with optimum performance. Investigations depict overall good performance of the design in terms of the extinction factor. It also inferred that all-optical realization based on SOA is competent scheme, as it circumvents costly optoelectronic translation. This could be well supportive to erect larger complex optical combinational circuits.

Diverse Physiological Roles of Calcitonin Gene-Related Peptide in Migraine Pathology: Modulation of Neuronal-Glial-Immune Cells to Promote Peripheral and Central Sensitization

PubMed Central

Durham, Paul L.

2018-01-01

The neuropeptide calcitonin gene-related peptide (CGRP) is implicated in the underlying pathology of migraine by promoting the development of a sensitized state of primary and secondary nociceptive neurons. The ability of CGRP to initiate and maintain peripheral and central sensitization is mediated by modulation of neuronal, glial, and immune cells in the trigeminal nociceptive signaling pathway. There is accumulating evidence to support a key role of CGRP in promoting cross excitation within the trigeminal ganglion that may help to explain the high co-morbidity of migraine with rhinosinusitis and temporomandibular joint disorder. In addition, there is emerging evidence that CGRP facilitates and sustains a hyperresponsive neuronal state in migraineurs mediated by reported risk factors such as stress and anxiety. In this review, the significant role of CGRP as a modulator of the trigeminal system will be discussed to provide a better understanding of the underlying pathology associated with the migraine phenotype. PMID:27334137

On Approaching the Ultimate Limits of Communication Using a Photon-Counting Detector

NASA Technical Reports Server (NTRS)

Erkmen, Baris I.; Moision, Bruce E.; Dolinar, Samuel J.; Birnbaum, Kevin M.; Divsalar, Dariush

2012-01-01

Coherent states achieve the Holevo capacity of a pure-loss channel when paired with an optimal measurement, but a physical realization of this measurement scheme is as of yet unknown, and it is also likely to be of high complexity. In this paper, we focus on the photon-counting measurement and study the photon and dimensional efficiencies attainable with modulations over classical- and nonclassical-state alphabets. We analyze two binary modulation architectures that improve upon the dimensional versus photon efficiency tradeoff achievable with the state-of-the-art coherent-state on-off keying modulation. We show that at high photon efficiency these architectures achieve an efficiency tradeoff that differs from the best possible tradeoff--determined by the Holevo capacity--by only a constant factor. The first architecture we analyze is a coherent-state transmitter that relies on feedback from the receiver to control the transmitted energy. The second architecture uses a single-photon number-state source.

Caveolae: a regulatory platform for nutritional modulation of inflammatory diseases

PubMed Central

Layne, Joseph; Majkova, Zuzana; Smart, Eric J.; Toborek, Michal; Hennig, Bernhard

2010-01-01

Dietary intervention strategies have proven to be an effective means of decreasing several risk factors associated with the development of atherosclerosis. Endothelial cell dysfunction influences vascular inflammation and is involved in promoting the earliest stages of lesion formation. Caveolae are lipid raft microdomains abundant within the plasma membrane of endothelial cells and are responsible for mediating receptor-mediated signal transduction. Caveolae have been implicated in the regulation of enzymes associated with several key signaling pathways capable of determining intracellular redox status. Diet and plasma-derived nutrients may modulate an inflammatory outcome by interacting with and altering caveolae-associated cellular signaling. For example, omega-3 fatty acids and several polyphenolics have been shown to improve endothelial cell function by decreasing the formation of ROS and increasing NO bioavailability, events associated with altered caveolae composition. Thus, nutritional modulation of caveolae-mediated signaling events may provide an opportunity to ameliorate inflammatory signaling pathways capable of promoting the formation of vascular diseases, including atherosclerosis. PMID:21292468

Zinc in Infection and Inflammation

PubMed Central

Gammoh, Nour Zahi; Rink, Lothar

2017-01-01

Micronutrient homeostasis is a key factor in maintaining a healthy immune system. Zinc is an essential micronutrient that is involved in the regulation of the innate and adaptive immune responses. The main cause of zinc deficiency is malnutrition. Zinc deficiency leads to cell-mediated immune dysfunctions among other manifestations. Consequently, such dysfunctions lead to a worse outcome in the response towards bacterial infection and sepsis. For instance, zinc is an essential component of the pathogen-eliminating signal transduction pathways leading to neutrophil extracellular traps (NET) formation, as well as inducing cell-mediated immunity over humoral immunity by regulating specific factors of differentiation. Additionally, zinc deficiency plays a role in inflammation, mainly elevating inflammatory response as well as damage to host tissue. Zinc is involved in the modulation of the proinflammatory response by targeting Nuclear Factor Kappa B (NF-κB), a transcription factor that is the master regulator of proinflammatory responses. It is also involved in controlling oxidative stress and regulating inflammatory cytokines. Zinc plays an intricate function during an immune response and its homeostasis is critical for sustaining proper immune function. This review will summarize the latest findings concerning the role of this micronutrient during the course of infections and inflammatory response and how the immune system modulates zinc depending on different stimuli. PMID:28629136

pH Modulates the Binding of EGR1 Transcription Factor to DNA

PubMed Central

Mikles, David C.; Bhat, Vikas; Schuchardt, Brett J.; Deegan, Brian J.; Seldeen, Kenneth L.; McDonald, Caleb B.; Farooq, Amjad

2013-01-01

EGR1 transcription factor orchestrates a plethora of signaling cascades involved in cellular homeostasis and its down-regulation has been implicated in the development of prostate cancer. Herein, using a battery of biophysical tools, we show that the binding of EGR1 to DNA is tightly regulated by solution pH. Importantly, the binding affinity undergoes an enhancement of more than an order of magnitude with increasing pH from 5 to 8, implying that the deprotonation of an ionizable residue accounts for such behavior. This ionizable residue is identified as H382 by virtue of the fact that its substitution to non-ionizable residues abolishes pH-dependence of the binding of EGR1 to DNA. Notably, H382 inserts into the major groove of DNA and stabilizes the EGR1-DNA interaction via both hydrogen bonding and van der Waals contacts. Remarkably, H382 is predominantly conserved across other members of EGR1 family, implying that histidine protonation-deprotonation may serve as a molecular switch for modulating protein-DNA interactions central to this family of transcription factors. Collectively, our findings uncover an unexpected but a key step in the molecular recognition of EGR1 family of transcription factors and suggest that they may act as sensors of pH within the intracellular environment. PMID:23718776

Zinc in Infection and Inflammation.

PubMed

Gammoh, Nour Zahi; Rink, Lothar

2017-06-17

Micronutrient homeostasis is a key factor in maintaining a healthy immune system. Zinc is an essential micronutrient that is involved in the regulation of the innate and adaptive immune responses. The main cause of zinc deficiency is malnutrition. Zinc deficiency leads to cell-mediated immune dysfunctions among other manifestations. Consequently, such dysfunctions lead to a worse outcome in the response towards bacterial infection and sepsis. For instance, zinc is an essential component of the pathogen-eliminating signal transduction pathways leading to neutrophil extracellular traps (NET) formation, as well as inducing cell-mediated immunity over humoral immunity by regulating specific factors of differentiation. Additionally, zinc deficiency plays a role in inflammation, mainly elevating inflammatory response as well as damage to host tissue. Zinc is involved in the modulation of the proinflammatory response by targeting Nuclear Factor Kappa B (NF-κB), a transcription factor that is the master regulator of proinflammatory responses. It is also involved in controlling oxidative stress and regulating inflammatory cytokines. Zinc plays an intricate function during an immune response and its homeostasis is critical for sustaining proper immune function. This review will summarize the latest findings concerning the role of this micronutrient during the course of infections and inflammatory response and how the immune system modulates zinc depending on different stimuli.

The Development of a Portable Hard Disk Encryption/Decryption System with a MEMS Coded Lock

PubMed Central

Zhang, Weiping; Chen, Wenyuan; Tang, Jian; Xu, Peng; Li, Yibin; Li, Shengyong

2009-01-01

In this paper, a novel portable hard-disk encryption/decryption system with a MEMS coded lock is presented, which can authenticate the user and provide the key for the AES encryption/decryption module. The portable hard-disk encryption/decryption system is composed of the authentication module, the USB portable hard-disk interface card, the ATA protocol command decoder module, the data encryption/decryption module, the cipher key management module, the MEMS coded lock controlling circuit module, the MEMS coded lock and the hard disk. The ATA protocol circuit, the MEMS control circuit and AES encryption/decryption circuit are designed and realized by FPGA(Field Programmable Gate Array). The MEMS coded lock with two couplers and two groups of counter-meshing-gears (CMGs) are fabricated by a LIGA-like process and precision engineering method. The whole prototype was fabricated and tested. The test results show that the user's password could be correctly discriminated by the MEMS coded lock, and the AES encryption module could get the key from the MEMS coded lock. Moreover, the data in the hard-disk could be encrypted or decrypted, and the read-write speed of the dataflow could reach 17 MB/s in Ultra DMA mode. PMID:22291566

Nutrigenomics and Beef Quality: A Review about Lipogenesis.

PubMed

Ladeira, Marcio M; Schoonmaker, Jon P; Gionbelli, Mateus P; Dias, Júlio C O; Gionbelli, Tathyane R S; Carvalho, José Rodolfo R; Teixeira, Priscilla D

2016-06-10

The objective of the present review is to discuss the results of published studies that show how nutrition affects the expression of genes involved in lipid metabolism and how diet manipulation might change marbling and composition of fat in beef. Several key points in the synthesis of fat in cattle take place at the molecular level, and the association of nutritional factors with the modulation of this metabolism is one of the recent targets of nutrigenomic research. Within this context, special attention has been paid to the study of nuclear receptors associated with fatty acid metabolism. Among the transcription factors involved in lipid metabolism, the peroxisome proliferator-activated receptors (PPARs) and sterol regulatory element-binding proteins (SREBPs) stand out. The mRNA synthesis of these transcription factors is regulated by nutrients, and their metabolic action might be potentiated by diet components and change lipogenesis in muscle. Among the options for dietary manipulation with the objective to modulate lipogenesis, the use of different sources of polyunsaturated fatty acids, starch concentrations, forage ratios and vitamins stand out. Therefore, special care must be exercised in feedlot feed management, mainly when the goal is to produce high marbling beef.

Genetics of regular exercise and sedentary behaviors.

PubMed

de Geus, Eco J C; Bartels, Meike; Kaprio, Jaakko; Lightfoot, J Timothy; Thomis, Martine

2014-08-01

Studies on the determinants of physical activity have traditionally focused on social factors and environmental barriers, but recent research has shown the additional importance of biological factors, including genetic variation. Here we review the major tenets of this research to arrive at three major conclusions: First, individual differences in physical activity traits are significantly influenced by genetic factors, but genetic contribution varies strongly over age, with heritability of leisure time exercise behavior ranging from 27% to 84% and heritability of sedentary behaviors ranging from 9% to 48%. Second, candidate gene approaches based on animal or human QTLs or on biological relevance (e.g., dopaminergic or cannabinoid activity in the brain, or exercise performance influencing muscle physiology) have not yet yielded the necessary evidence to specify the genetic mechanisms underlying the heritability of physical activity traits. Third, there is significant genetic modulation of the beneficial effects of daily physical activity patterns on strength and endurance improvements and on health-related parameters like body mass index. Further increases in our understanding of the genetic determinants of sedentary and exercise behaviors as well as the genetic modulation of their effects on fitness and health will be key to meaningful future intervention on these behaviors.

The Arabidopsis transcription factor AtTCP15 regulates endoreduplication by modulating expression of key cell-cycle genes.

PubMed

Li, Zi-Yu; Li, Bin; Dong, Ai-Wu

2012-01-01

Plant cells frequently undergo endoreduplication, a modified cell cycle in which genome is repeatedly replicated without cytokinesis. As the key step to achieve final size and function for cells, endoreduplication is prevalent during plant development. However, mechanisms to control the balance between endoreduplication and mitotic cell division are still poorly understood. Here, we show that the Arabidopsis TCP (CINCINNATA-like TEOSINTE BRANCHED1-CYCLOIDEA-PCF)-family transcription factor gene AtTCP15 is expressed in trichomes, as well as in rapidly dividing and vascular tissues. Expression of AtTCP15SRDX, AtTCP15 fused with a SRDX repressor domain, induces extra endoreduplication in trichomes and cotyledon cells in transgenic Arabidopsis. On the contrary, overexpression of AtTCP15 suppresses endoreduplication in trichomes and other examined cells. Misregulation of AtTCP15 affects the expression of several important genes involved in cell-cycle regulation. AtTCP15 protein binds directly to the promoter regions of CYCA2;3 and RETINOBLASTOMA-RELATED (RBR) genes, which play key roles in endoreduplication. Taken together, AtTCP15 plays an important role in regulating endoreduplication during Arabidopsis development.

Cooperative DNA Recognition Modulated by an Interplay between Protein-Protein Interactions and DNA-Mediated Allostery

PubMed Central

Merino, Felipe; Bouvier, Benjamin; Cojocaru, Vlad

2015-01-01

Highly specific transcriptional regulation depends on the cooperative association of transcription factors into enhanceosomes. Usually, their DNA-binding cooperativity originates from either direct interactions or DNA-mediated allostery. Here, we performed unbiased molecular simulations followed by simulations of protein-DNA unbinding and free energy profiling to study the cooperative DNA recognition by OCT4 and SOX2, key components of enhanceosomes in pluripotent cells. We found that SOX2 influences the orientation and dynamics of the DNA-bound configuration of OCT4. In addition SOX2 modifies the unbinding free energy profiles of both DNA-binding domains of OCT4, the POU specific and POU homeodomain, despite interacting directly only with the first. Thus, we demonstrate that the OCT4-SOX2 cooperativity is modulated by an interplay between protein-protein interactions and DNA-mediated allostery. Further, we estimated the change in OCT4-DNA binding free energy due to the cooperativity with SOX2, observed a good agreement with experimental measurements, and found that SOX2 affects the relative DNA-binding strength of the two OCT4 domains. Based on these findings, we propose that available interaction partners in different biological contexts modulate the DNA exploration routes of multi-domain transcription factors such as OCT4. We consider the OCT4-SOX2 cooperativity as a paradigm of how specificity of transcriptional regulation is achieved through concerted modulation of protein-DNA recognition by different types of interactions. PMID:26067358

Cooperative DNA Recognition Modulated by an Interplay between Protein-Protein Interactions and DNA-Mediated Allostery.

PubMed

Merino, Felipe; Bouvier, Benjamin; Cojocaru, Vlad

2015-06-01

Highly specific transcriptional regulation depends on the cooperative association of transcription factors into enhanceosomes. Usually, their DNA-binding cooperativity originates from either direct interactions or DNA-mediated allostery. Here, we performed unbiased molecular simulations followed by simulations of protein-DNA unbinding and free energy profiling to study the cooperative DNA recognition by OCT4 and SOX2, key components of enhanceosomes in pluripotent cells. We found that SOX2 influences the orientation and dynamics of the DNA-bound configuration of OCT4. In addition SOX2 modifies the unbinding free energy profiles of both DNA-binding domains of OCT4, the POU specific and POU homeodomain, despite interacting directly only with the first. Thus, we demonstrate that the OCT4-SOX2 cooperativity is modulated by an interplay between protein-protein interactions and DNA-mediated allostery. Further, we estimated the change in OCT4-DNA binding free energy due to the cooperativity with SOX2, observed a good agreement with experimental measurements, and found that SOX2 affects the relative DNA-binding strength of the two OCT4 domains. Based on these findings, we propose that available interaction partners in different biological contexts modulate the DNA exploration routes of multi-domain transcription factors such as OCT4. We consider the OCT4-SOX2 cooperativity as a paradigm of how specificity of transcriptional regulation is achieved through concerted modulation of protein-DNA recognition by different types of interactions.

Insulin resistance, glycemic control and adiposity: key determinants of healthy lifespan.

PubMed

DiStefano, Peter S; Curtis, Rory; Geddes, Bradley J

2007-04-01

Identification of genes and pathways that alter lifespan has allowed for new insights into factors that control the aging process as well as disease. While strong molecular links exist between aging and metabolism, we hypothesize that targeting the mechanisms involved in aging will also give rise to therapeutics that treat other devastating age-related diseases, such as neurodegeneration, cancer, inflammation and cardiovascular disease. Insulin sensitivity, glycemic control and adiposity are not only hallmarks of the major metabolic diseases, type 2 diabetes and obesity, but they also represent significant risk factors for the development of Alzheimer's Disease and cognitive impairment. Insulin/IGF-1 signaling is an important pathway regulating aging and disease in a variety of species, including mammals. Here we describe an important role for the gut-derived peptide ghrelin in upstream signaling through the insulin/IGF-1 pathway and exemplify modulation of ghrelin signaling as an approach to mechanistic treatment of multiple age-related diseases by virtue of its ability to regulate key metabolic functions.

[Modulating expression of key genes within β-carotene synthetic pathway in recombinant Escherichia coli with RBS library to improve β-carotene production].

PubMed

Dai, Guanping; Sun, Tao; Miao, Liangtian; Li, Qingyan; Xiao, Dongguang; Zhang, Xueli

2014-08-01

β-carotene belongs to carotenoids family, widely applied in pharmaceuticals, neutraceuticals, cosmetics and food industries. In this study, three key genes (dxs, idi, and crt operon) within β-carotene synthetic pathway in recombinant Escherichia coli strain CAR005 were modulated with RBS Library to improve β-carotene production. There were 7%, 11% and 17% increase of β-carotene yield respectively after modulating dxs, idi and crt operon genes with RBS Library, demonstrating that modulating gene expression with regulatory parts libraries would have more opportunities to obtain optimal production of target compound. Combined modulation of crt operon, dxs and idi genes led to 35% increase of β-carotene yield compared to parent strain CAR005. The optimal gene expression strength identified in single gene modulation would not be the optimal strength when used in combined modulation. Our study provides a new strategy for improving production of target compound through modulation of gene expression.

Sulforaphane Protects Pancreatic Acinar Cell Injury by Modulating Nrf2-Mediated Oxidative Stress and NLRP3 Inflammatory Pathway

PubMed Central

Dong, Zhaojun; Shang, Haixiao; Chen, Yong Q.; Pan, Li-Long

2016-01-01

Acute pancreatitis (AP) is characterized by early activation of intra-acinar proteases followed by acinar cell death and inflammation. Cellular oxidative stress is a key mechanism underlying these pathological events. Sulforaphane (SFN) is a natural organosulfur antioxidant with undescribed effects on AP. Here we investigated modulatory effects of SFN on cellular oxidation and inflammation in AP. AP was induced by cerulean hyperstimulation in BALB/c mice. Treatment group received a single dose of 5 mg/kg SFN for 3 consecutive days before AP. We found that SFN administration attenuated pancreatic injury as evidenced by serum amylase, pancreatic edema, and myeloperoxidase, as well as by histological examination. SFN administration reverted AP-associated dysregulation of oxidative stress markers including pancreatic malondialdehyde and redox enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx). In acinar cells, SFN treatment upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) expression and Nrf2-regulated redox genes including quinoneoxidoreductase-1, heme oxidase-1, SOD1, and GPx1. In addition, SFN selectively suppressed cerulein-induced activation of the nucleotide-binding domain leucine-rich repeat containing family, pyrin domain-containing 3 (NLRP3) inflammasome, in parallel with reduced nuclear factor- (NF-) κB activation and modulated NF-κB-responsive cytokine expression. Together, our data suggested that SFN modulates Nrf2-mediated oxidative stress and NLRP3/NF-κB inflammatory pathways in acinar cells, thereby protecting against AP. PMID:27847555

Sulforaphane Protects Pancreatic Acinar Cell Injury by Modulating Nrf2-Mediated Oxidative Stress and NLRP3 Inflammatory Pathway.

PubMed

Dong, Zhaojun; Shang, Haixiao; Chen, Yong Q; Pan, Li-Long; Bhatia, Madhav; Sun, Jia

2016-01-01

Acute pancreatitis (AP) is characterized by early activation of intra-acinar proteases followed by acinar cell death and inflammation. Cellular oxidative stress is a key mechanism underlying these pathological events. Sulforaphane (SFN) is a natural organosulfur antioxidant with undescribed effects on AP. Here we investigated modulatory effects of SFN on cellular oxidation and inflammation in AP. AP was induced by cerulean hyperstimulation in BALB/c mice. Treatment group received a single dose of 5 mg/kg SFN for 3 consecutive days before AP. We found that SFN administration attenuated pancreatic injury as evidenced by serum amylase, pancreatic edema, and myeloperoxidase, as well as by histological examination. SFN administration reverted AP-associated dysregulation of oxidative stress markers including pancreatic malondialdehyde and redox enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx). In acinar cells, SFN treatment upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) expression and Nrf2-regulated redox genes including quinoneoxidoreductase-1, heme oxidase-1, SOD1, and GPx1. In addition, SFN selectively suppressed cerulein-induced activation of the nucleotide-binding domain leucine-rich repeat containing family, pyrin domain-containing 3 (NLRP3) inflammasome, in parallel with reduced nuclear factor- (NF-) κ B activation and modulated NF- κ B-responsive cytokine expression. Together, our data suggested that SFN modulates Nrf2-mediated oxidative stress and NLRP3/NF- κ B inflammatory pathways in acinar cells, thereby protecting against AP.

Evidence for a crucial modulating role of the sodium channel in the QTc prolongation related to antipsychotics.

PubMed

Silvestre, Jordi S; O'Neill, Michael F; Prous, Josep R

2014-04-01

Blockade of the cardiac hERG channel is recognized as the main mechanism underlying the QT prolongation induced by many classes of drugs, including antipsychotics. However, antipsychotics interact with a variety of other pharmacological targets that could also modulate cardiac function. The present study aims to identify those key factors involved in the QT prolongation induced by antipsychotics. The interactions of 28 antipsychotics were measured on a variety of pharmacological targets. Binding affinity (K(i)), functional channel blockade (IC₅₀), and the corresponding ratios to total and free plasma drug concentration were compared with the corrected QT changes (QTc) associated with the therapeutic use of these drugs by multivariable linear regression analysis to determine the best predictors of QTc. Besides confirming hERG as the primary predictor of QTc, all analyses consistently show the concomitant involvement of Na(V)1.5 channel as modulating factor of the QTc related to hERG blockade. In particular, the hERG/Na(V)1.5 ratio explains the 57% of the overall QTc variability associated with antipsychotics. Since it is known that inhibition of late I Na could offset the dysfunctional effects of hERG blockade, we hypothesize the inhibition of late I(Na) as a crucial compensatory mechanism of the QTc associated with antipsychotics and hence an important factor to consider concomitantly with hERG blockade to appraise the arrhythmogenic risk of these drugs more accurately.

A Conserved PHD Finger Protein and Endogenous RNAi Modulate Insulin Signaling in Caenorhabditis elegans

PubMed Central

Hoersch, Sebastian; Jensen, Morten B.; Kawli, Trupti; Kennedy, Lisa M.; Chavez, Violeta; Tan, Man-Wah; Lieb, Jason D.; Grishok, Alla

2011-01-01

Insulin signaling has a profound effect on longevity and the oxidative stress resistance of animals. Inhibition of insulin signaling results in the activation of DAF-16/FOXO and SKN-1/Nrf transcription factors and increased animal fitness. By studying the biological functions of the endogenous RNA interference factor RDE-4 and conserved PHD zinc finger protein ZFP-1 (AF10), which regulate overlapping sets of genes in Caenorhabditis elegans, we identified an important role for these factors in the negative modulation of transcription of the insulin/PI3 signaling-dependent kinase PDK-1. Consistently, increased expression of pdk-1 in zfp-1 and rde-4 mutants contributed to their reduced lifespan and sensitivity to oxidative stress and pathogens due to the reduction in the expression of DAF-16 and SKN-1 targets. We found that the function of ZFP-1 in modulating pdk-1 transcription was important for the extended lifespan of the age-1(hx546) reduction-of-function PI3 kinase mutant, since the lifespan of the age-1; zfp-1 double mutant strain was significantly shorter compared to age-1(hx546). We further demonstrate that overexpression of ZFP-1 caused an increased resistance to oxidative stress in a DAF-16–dependent manner. Our findings suggest that epigenetic regulation of key upstream signaling components in signal transduction pathways through chromatin and RNAi may have a large impact on the outcome of signaling and expression of numerous downstream genes. PMID:21980302

A conserved PHD finger protein and endogenous RNAi modulate insulin signaling in Caenorhabditis elegans.

PubMed

Mansisidor, Andres R; Cecere, Germano; Hoersch, Sebastian; Jensen, Morten B; Kawli, Trupti; Kennedy, Lisa M; Chavez, Violeta; Tan, Man-Wah; Lieb, Jason D; Grishok, Alla

2011-09-01

Insulin signaling has a profound effect on longevity and the oxidative stress resistance of animals. Inhibition of insulin signaling results in the activation of DAF-16/FOXO and SKN-1/Nrf transcription factors and increased animal fitness. By studying the biological functions of the endogenous RNA interference factor RDE-4 and conserved PHD zinc finger protein ZFP-1 (AF10), which regulate overlapping sets of genes in Caenorhabditis elegans, we identified an important role for these factors in the negative modulation of transcription of the insulin/PI3 signaling-dependent kinase PDK-1. Consistently, increased expression of pdk-1 in zfp-1 and rde-4 mutants contributed to their reduced lifespan and sensitivity to oxidative stress and pathogens due to the reduction in the expression of DAF-16 and SKN-1 targets. We found that the function of ZFP-1 in modulating pdk-1 transcription was important for the extended lifespan of the age-1(hx546) reduction-of-function PI3 kinase mutant, since the lifespan of the age-1; zfp-1 double mutant strain was significantly shorter compared to age-1(hx546). We further demonstrate that overexpression of ZFP-1 caused an increased resistance to oxidative stress in a DAF-16-dependent manner. Our findings suggest that epigenetic regulation of key upstream signaling components in signal transduction pathways through chromatin and RNAi may have a large impact on the outcome of signaling and expression of numerous downstream genes.

Transforming growth factor-beta inhibits human antigen-specific CD4+ T cell proliferation without modulating the cytokine response.

PubMed

Tiemessen, Machteld M; Kunzmann, Steffen; Schmidt-Weber, Carsten B; Garssen, Johan; Bruijnzeel-Koomen, Carla A F M; Knol, Edward F; van Hoffen, Els

2003-12-01

Transforming growth factor (TGF)-beta has been demonstrated to play a key role in the regulation of the immune response, mainly by its suppressive function towards cells of the immune system. In humans, the effect of TGF-beta on antigen-specific established memory T cells has not been investigated yet. In this study antigen-specific CD4(+) T cell clones (TCC) were used to determine the effect of TGF-beta on antigen-specific proliferation, the activation status of the T cells and their cytokine production. This study demonstrates that TGF-beta is an adequate suppressor of antigen-specific T cell proliferation, by reducing the cell-cycle rate rather than induction of apoptosis. Addition of TGF-beta resulted in increased CD69 expression and decreased CD25 expression on T cells, indicating that TGF-beta is able to modulate the activation status of in vivo differentiated T cells. On the contrary, the antigen-specific cytokine production was not affected by TGF-beta. Although TGF-beta was suppressive towards the majority of the T cells, insensitivity of a few TCC towards TGF-beta was also observed. This could not be correlated to differential expression of TGF-beta signaling molecules such as Smad3, Smad7, SARA (Smad anchor for receptor activation) and Hgs (hepatocyte growth factor-regulated tyrosine kinase substrate). In summary, TGF-beta has a pronounced inhibitory effect on antigen-specific T cell proliferation without modulating their cytokine production.

A Simple Snap Oscillator with Coexisting Attractors, Its Time-Delayed Form, Physical Realization, and Communication Designs

NASA Astrophysics Data System (ADS)

Rajagopal, Karthikeyan; Jafari, Sajad; Akgul, Akif; Karthikeyan, Anitha; Çiçek, Serdar; Shekofteh, Yasser

2018-05-01

In this paper, we report a novel chaotic snap oscillator with one nonlinear function. Dynamic analysis of the system shows the existence of bistability. To study the time delay effects on the proposed snap oscillator, we introduce multiple time delay in the fourth state equation. Investigation of dynamical properties of the time-delayed system shows that the snap oscillator exhibits the same multistable properties as the nondelayed system. The new multistable hyperjerk chaotic system has been tested in chaos shift keying and symmetric choc shift keying modulated communication designs for engineering applications. It has been determined that the symmetric chaos shift keying modulated communication system implemented with the new chaotic system is more successful than the chaos shift keying modulation for secure communication. Also, circuit implementation of the chaotic snap oscillator with tangent function is carried out showing its feasibility.

Security analysis of orthogonal-frequency-division-multiplexing-based continuous-variable quantum key distribution with imperfect modulation

NASA Astrophysics Data System (ADS)

Zhang, Hang; Mao, Yu; Huang, Duan; Li, Jiawei; Zhang, Ling; Guo, Ying

2018-05-01

We introduce a reliable scheme for continuous-variable quantum key distribution (CV-QKD) by using orthogonal frequency division multiplexing (OFDM). As a spectrally efficient multiplexing technique, OFDM allows a large number of closely spaced orthogonal subcarrier signals used to carry data on several parallel data streams or channels. We place emphasis on modulator impairments which would inevitably arise in the OFDM system and analyze how these impairments affect the OFDM-based CV-QKD system. Moreover, we also evaluate the security in the asymptotic limit and the Pirandola-Laurenza-Ottaviani-Banchi upper bound. Results indicate that although the emergence of imperfect modulation would bring about a slight decrease in the secret key bit rate of each subcarrier, the multiplexing technique combined with CV-QKD results in a desirable improvement on the total secret key bit rate which can raise the numerical value about an order of magnitude.

Nucleotide, c-di-GMP, c-di-AMP, cGMP, cAMP, (p)ppGpp signaling in bacteria and implications in pathogenesis.

PubMed

Kalia, Dimpy; Merey, Gökçe; Nakayama, Shizuka; Zheng, Yue; Zhou, Jie; Luo, Yiling; Guo, Min; Roembke, Benjamin T; Sintim, Herman O

2013-01-07

For an organism to survive, it must be able to sense its environment and regulate physiological processes accordingly. Understanding how bacteria integrate signals from various environmental factors and quorum sensing autoinducers to regulate the metabolism of various nucleotide second messengers c-di-GMP, c-di-AMP, cGMP, cAMP and ppGpp, which control several key processes required for adaptation is key for efforts to develop agents to curb bacterial infections. In this review, we provide an update of nucleotide signaling in bacteria and show how these signals intersect or integrate to regulate the bacterial phenotype. The intracellular concentrations of nucleotide second messengers in bacteria are regulated by synthases and phosphodiesterases and a significant number of these metabolism enzymes had been biochemically characterized but it is only in the last few years that the effector proteins and RNA riboswitches, which regulate bacterial physiology upon binding to nucleotides, have been identified and characterized by biochemical and structural methods. C-di-GMP, in particular, has attracted immense interest because it is found in many bacteria and regulate both biofilm formation and virulence factors production. In this review, we discuss how the activities of various c-di-GMP effector proteins and riboswitches are modulated upon c-di-GMP binding. Using V. cholerae, E. coli and B. subtilis as models, we discuss how both environmental factors and quorum sensing autoinducers regulate the metabolism and/or processing of nucleotide second messengers. The chemical syntheses of the various nucleotide second messengers and the use of analogs thereof as antibiofilm or immune modulators are also discussed.

Mlc Is a Transcriptional Activator with a Key Role in Integrating Cyclic AMP Receptor Protein and Integration Host Factor Regulation of Leukotoxin RNA Synthesis in Aggregatibacter actinomycetemcomitans

PubMed Central

Childress, Catherine; Feuerbacher, Leigh A.; Phillips, Linda; Burgum, Alex

2013-01-01

Aggregatibacter actinomycetemcomitans, a periodontal pathogen, synthesizes leukotoxin (LtxA), a protein that helps the bacterium evade the host immune response. Transcription of the ltxA operon is induced during anaerobic growth. The cyclic AMP (cAMP) receptor protein (CRP) indirectly increases ltxA expression, but the intermediary regulator is unknown. Integration host factor (IHF) binds to and represses the leukotoxin promoter, but neither CRP nor IHF is responsible for the anaerobic induction of ltxA RNA synthesis. Thus, we have undertaken studies to identify other regulators of leukotoxin transcription and to demonstrate how these proteins work together to modulate leukotoxin synthesis. First, analyses of ltxA RNA expression from defined leukotoxin promoter mutations in the chromosome identify positions −69 to −35 as the key control region and indicate that an activator protein modulates leukotoxin transcription. We show that Mlc, which is a repressor in Escherichia coli, functions as a direct transcriptional activator in A. actinomycetemcomitans; an mlc deletion mutant reduces leukotoxin RNA synthesis, and recombinant Mlc protein binds specifically at the −68 to −40 region of the leukotoxin promoter. Furthermore, we show that CRP activates ltxA expression indirectly by increasing the levels of Mlc. Analyses of Δmlc, Δihf, and Δihf Δmlc strains demonstrate that Mlc can increase RNA polymerase (RNAP) activity directly and that IHF represses ltxA RNA synthesis mainly by blocking Mlc binding. Finally, a Δihf Δmlc mutant still induces ltxA during anaerobic growth, indicating that there are additional factors involved in leukotoxin transcriptional regulation. A model for the coordinated regulation of leukotoxin transcription is presented. PMID:23475968

Rescue Manual. Module 5.

ERIC Educational Resources Information Center

Ohio State Univ., Columbus. Instructional Materials Lab.

This learner manual for rescuers covers the current techniques or practices required in the rescue service. The fifth of 10 modules contains information on hazardous materials. Key points, an introduction, and conclusion accompany substantive material in this module. In addition, the module contains a Department of Transportation guide chart on…

Identification of HDA15-PIF1 as a key repression module directing the transcriptional network of seed germination in the dark.

PubMed

Gu, Dachuan; Chen, Chia-Yang; Zhao, Minglei; Zhao, Linmao; Duan, Xuewu; Duan, Jun; Wu, Keqiang; Liu, Xuncheng

2017-07-07

Light is a major external factor in regulating seed germination. Photoreceptor phytochrome B (PHYB) plays a predominant role in promoting seed germination in the initial phase after imbibition, partially by repressing phytochrome-interacting factor1 (PIF1). However, the mechanism underlying the PHYB-PIF1-mediated transcription regulation remains largely unclear. Here, we identified that histone deacetylase15 (HDA15) is a negative component of PHYB-dependent seed germination. Overexpression of HDA15 in Arabidopsis inhibits PHYB-dependent seed germination, whereas loss of function of HDA15 increases PHYB-dependent seed germination. Genetic evidence indicated that HDA15 acts downstream of PHYB and represses seed germination dependent on PIF1. Furthermore, HDA15 interacts with PIF1 both in vitro and in vivo. Genome-wide transcriptome analysis revealed that HDA15 and PIF1 co-regulate the transcription of the light-responsive genes involved in multiple hormonal signaling pathways and cellular processes in germinating seeds in the dark. In addition, PIF1 recruits HDA15 to the promoter regions of target genes and represses their expression by decreasing the histone H3 acetylation levels in the dark. Taken together, our analysis uncovered the role of histone deacetylation in the light-regulated seed germination process and identified that HDA15-PIF1 acts as a key repression module directing the transcription network of seed germination. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Identification of HDA15-PIF1 as a key repression module directing the transcriptional network of seed germination in the dark

PubMed Central

Gu, Dachuan; Chen, Chia-Yang; Zhao, Minglei; Zhao, Linmao; Duan, Xuewu

2017-01-01

Abstract Light is a major external factor in regulating seed germination. Photoreceptor phytochrome B (PHYB) plays a predominant role in promoting seed germination in the initial phase after imbibition, partially by repressing phytochrome-interacting factor1 (PIF1). However, the mechanism underlying the PHYB-PIF1-mediated transcription regulation remains largely unclear. Here, we identified that histone deacetylase15 (HDA15) is a negative component of PHYB-dependent seed germination. Overexpression of HDA15 in Arabidopsis inhibits PHYB-dependent seed germination, whereas loss of function of HDA15 increases PHYB-dependent seed germination. Genetic evidence indicated that HDA15 acts downstream of PHYB and represses seed germination dependent on PIF1. Furthermore, HDA15 interacts with PIF1 both in vitro and in vivo. Genome-wide transcriptome analysis revealed that HDA15 and PIF1 co-regulate the transcription of the light-responsive genes involved in multiple hormonal signaling pathways and cellular processes in germinating seeds in the dark. In addition, PIF1 recruits HDA15 to the promoter regions of target genes and represses their expression by decreasing the histone H3 acetylation levels in the dark. Taken together, our analysis uncovered the role of histone deacetylation in the light-regulated seed germination process and identified that HDA15-PIF1 acts as a key repression module directing the transcription network of seed germination. PMID:28444370

The Arabidopsis MYB96 Transcription Factor Is a Positive Regulator of ABSCISIC ACID-INSENSITIVE4 in the Control of Seed Germination1

PubMed Central

Lee, Kyounghee; Lee, Hong Gil; Kim, Hyun Uk; Seo, Pil Joon

2015-01-01

Seed germination is a key developmental transition that initiates the plant life cycle. The timing of germination is determined by the coordinated action of two phytohormones, gibberellin and abscisic acid (ABA). In particular, ABA plays a key role in integrating environmental information and inhibiting the germination process. The utilization of embryonic lipid reserves contributes to seed germination by acting as an energy source, and ABA suppresses lipid degradation to modulate the germination process. Here, we report that the ABA-responsive R2R3-type MYB transcription factor MYB96, which is highly expressed in embryo, regulates seed germination by controlling the expression of ABSCISIC ACID-INSENSITIVE4 (ABI4) in Arabidopsis (Arabidopsis thaliana). In the presence of ABA, germination was accelerated in MYB96-deficient myb96-1 seeds, whereas the process was significantly delayed in MYB96-overexpressing activation-tagging myb96-ox seeds. Consistently, myb96-1 seeds degraded a larger extent of lipid reserves even in the presence of ABA, while reduced lipid mobilization was observed in myb96-ox seeds. MYB96 directly regulates ABI4, which acts as a repressor of lipid breakdown, to define its spatial and temporal expression. Genetic analysis further demonstrated that ABI4 is epistatic to MYB96 in the control of seed germination. Taken together, the MYB96-ABI4 module regulates lipid mobilization specifically in the embryo to ensure proper seed germination under suboptimal conditions. PMID:25869652

Critical review on the physical and mechanical factors involved in tissue engineering of cartilage.

PubMed

Gaut, Carrie; Sugaya, Kiminobu

2015-01-01

Articular cartilage defects often progress to osteoarthritis, which negatively impacts quality of life for millions of people worldwide and leads to high healthcare expenditures. Tissue engineering approaches to osteoarthritis have concentrated on proliferation and differentiation of stem cells by activation and suppression of signaling pathways, and by using a variety of scaffolding techniques. Recent studies indicate a key role of environmental factors in the differentiation of mesenchymal stem cells to mature cartilage-producing chondrocytes. Therapeutic approaches that consider environmental regulation could optimize chondrogenesis protocols for regeneration of articular cartilage. This review focuses on the effect of scaffold structure and composition, mechanical stress and hypoxia in modulating mesenchymal stem cell fate and the current use of these environmental factors in tissue engineering research.

Mammalian follicular development and atresia: role of apoptosis.

PubMed

Asselin, E; Xiao, C W; Wang, Y F; Tsang, B K

2000-01-01

The regulation of follicular development and atresia is a complex process and involves interactions between endocrine factors (gonadotropins) and intraovarian regulators (sex steroids, growth factors and cytokines) in the control of follicular cell fate (i.e. proliferation, differentiation and programmed cell death). Granulosa and theca cells are key players in this fascinating process. As atresia is the fate of most follicles, understanding of how these physiological regulators participate in determining the destiny of the follicle (to degenerate or to ovulate) at cellular and subcellular levels is fundamental. This short review summarizes the role of intraovarian modulators of programmed cell death in the induction of atresia during follicular development. Copyright 2000 S. Karger AG, Basel

Continuous-variable quantum key distribution with a leakage from state preparation

NASA Astrophysics Data System (ADS)

Derkach, Ivan; Usenko, Vladyslav C.; Filip, Radim

2017-12-01

We address side-channel leakage in a trusted preparation station of continuous-variable quantum key distribution with coherent and squeezed states. We consider two different scenarios: multimode Gaussian modulation, directly accessible to an eavesdropper, or side-channel loss of the signal states prior to the modulation stage. We show the negative impact of excessive modulation on both the coherent- and squeezed-state protocols. The impact is more pronounced for squeezed-state protocols and may require optimization of squeezing in the case of noisy quantum channels. Further, we demonstrate that the coherent-state protocol is immune to side-channel signal state leakage prior to modulation, while the squeezed-state protocol is vulnerable to such attacks, becoming more sensitive to the noise in the channel. In the general case of noisy quantum channels the signal squeezing can be optimized to provide best performance of the protocol in the presence of side-channel leakage prior to modulation. Our results demonstrate that leakage from the trusted source in continuous-variable quantum key distribution should not be underestimated and squeezing optimization is needed to overcome coherent state protocols.

76 FR 4991 - Petition for Exemption From the Vehicle Theft Prevention Standard; Suzuki

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-27

... include an electronically coded key fob, Body Control Module (BCM), Engine Control Module (ECM) and a... results are identical, the BCM will send data to the ECM allowing the vehicle to start. If either the key..., Suzuki stated that the ECM will prohibit operation of the vehicle. In addressing the specific content...

Optical multiple-image hiding based on interference and grating modulation

NASA Astrophysics Data System (ADS)

He, Wenqi; Peng, Xiang; Meng, Xiangfeng

2012-07-01

We present a method for multiple-image hiding on the basis of interference-based encryption architecture and grating modulation. By using a modified phase retrieval algorithm, we can separately hide a number of secret images into one arbitrarily preselected host image associated with a set of phase-only masks (POMs), which are regarded as secret keys. Thereafter, a grating modulation operation is introduced to multiplex and store the different POMs into a single key mask, which is then assigned to the authorized users in privacy. For recovery, after an appropriate demultiplexing process, one can reconstruct the distributions of all the secret keys and then recover the corresponding hidden images with suppressed crosstalk. Computer simulation results are presented to validate the feasibility of our approach.

The hedgehog system machinery controls transforming growth factor-β-dependent myofibroblastic differentiation in humans: involvement in idiopathic pulmonary fibrosis.

PubMed

Cigna, Natacha; Farrokhi Moshai, Elika; Brayer, Stéphanie; Marchal-Somme, Joëlle; Wémeau-Stervinou, Lidwine; Fabre, Aurélie; Mal, Hervé; Lesèche, Guy; Dehoux, Monique; Soler, Paul; Crestani, Bruno; Mailleux, Arnaud A

2012-12-01

Idiopathic pulmonary fibrosis (IPF) is a devastating disease of unknown cause. Key signaling developmental pathways are aberrantly expressed in IPF. The hedgehog pathway plays a key role during fetal lung development and may be involved in lung fibrogenesis. We determined the expression pattern of several Sonic hedgehog (SHH) pathway members in normal and IPF human lung biopsies and primary fibroblasts. The effect of hedgehog pathway inhibition was assayed by lung fibroblast proliferation and differentiation with and without transforming growth factor (TGF)-β1. We showed that the hedgehog pathway was reactivated in the IPF lung. Importantly, we deciphered the cross talk between the hedgehog and TGF-β pathway in human lung fibroblasts. TGF-β1 modulated the expression of key components of the hedgehog pathway independent of Smoothened, the obligatory signal transducer of the pathway. Smoothened was required for TGF-β1-induced myofibroblastic differentiation of control fibroblasts, but differentiation of IPF fibroblasts was partially resistant to Smoothened inhibition. Furthermore, functional hedgehog pathway machinery from the primary cilium, as well as GLI-dependent transcription in the nucleus, was required for the TGF-β1 effects on normal and IPF fibroblasts during myofibroblastic differentiation. These data identify the GLI transcription factors as potential therapeutic targets in lung fibrosis. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Microchip Module for Blood Sample Preparation and Nucleic Acid Amplification Reactions

PubMed Central

Yuen, Po Ki; Kricka, Larry J.; Fortina, Paolo; Panaro, Nicholas J.; Sakazume, Taku; Wilding, Peter

2001-01-01

A computer numerical control-machined plexiglas-based microchip module was designed and constructed for the integration of blood sample preparation and nucleic acid amplification reactions. The microchip module is comprised of a custom-made heater-cooler for thermal cycling, a series of 254 μm × 254 μm microchannels for transporting human whole blood and reagents in and out of an 8–9 μL dual-purpose (cell isolation and PCR) glass-silicon microchip. White blood cells were first isolated from a small volume of human whole blood (<3 μL) in an integrated cell isolation–PCR microchip containing a series of 3.5-μm feature-sized “weir-type” filters, formed by an etched silicon dam spanning the flow chamber. A genomic target, a region in the human coagulation Factor V gene (226-bp), was subsequently directly amplified by microchip-based PCR on DNA released from white blood cells isolated on the filter section of the microchip mounted onto the microchip module. The microchip module provides a convenient means to simplify nucleic acid analyses by integrating two key steps in genetic testing procedures, cell isolation and PCR and promises to be adaptable for additional types of integrated assays. PMID:11230164

A Multi-Cycle Q-Modulation for Dynamic Optimization of Inductive Links.

PubMed

Lee, Byunghun; Yeon, Pyungwoo; Ghovanloo, Maysam

2016-08-01

This paper presents a new method, called multi-cycle Q-modulation, which can be used in wireless power transmission (WPT) to modulate the quality factor (Q) of the receiver (Rx) coil and dynamically optimize the load impedance to maximize the power transfer efficiency (PTE) in two-coil links. A key advantage of the proposed method is that it can be easily implemented using off-the-shelf components without requiring fast switching at or above the carrier frequency, which is more suitable for integrated circuit design. Moreover, the proposed technique does not need any sophisticated synchronization between the power carrier and Q-modulation switching pulses. The multi-cycle Q-modulation is analyzed theoretically by a lumped circuit model, and verified in simulation and measurement using an off-the-shelf prototype. Automatic resonance tuning (ART) in the Rx, combined with multi-cycle Q-modulation helped maximizing PTE of the inductive link dynamically in the presence of environmental and loading variations, which can otherwise significantly degrade the PTE in multi-coil settings. In the prototype conventional 2-coil link, the proposed method increased the power amplifier (PA) plus inductive link efficiency from 4.8% to 16.5% at ( R L = 1 kΩ, d 23 = 3 cm), and from 23% to 28.2% at ( R L = 100 Ω, d 23 = 3 cm) after 11% change in the resonance capacitance, while delivering 168.1 mW to the load (PDL).

Simultaneous Modeling of the Thermophysical and Dynamical Evolution of Saturn's Icy Satellites

NASA Astrophysics Data System (ADS)

Johnson, Torrence V.; Castillo-Rogez, J. C.; Matson, D. L.; Sotin, C.; Lunine, J. I.

2007-10-01

This poster describes the methodology we use in modeling the geophysical and dynamical evolution of the icy satellites of Saturn. For each of the model's modules we identify the relevant physical, chemical, mineralogical, and material science principals that are used. Then we present the logic of the modeling approach and its implementation. The main modules handle thermal, geological, and dynamical processes. Key parameters such as temperature, thermal conductivity, rigidity, viscosity, Young's modulus, dynamic Love number k2, and frequency-dependent dissipation factor Q(ω) are transmitted between the modules in the course of calculating an evolutionary sequence. Important initial conditions include volatile and nonvolatile compositions, formation time, rotation period and shape, orbital eccentricity and semimajor axis, and temperature and porosity profiles. The thermal module treats the thermal effects of accretion, melting of ice, differentiation and tidal dissipation. Heat transfer is by conduction only because in the cases thus far studied the criterion for convection is not met. The geological module handles the evolution of porosity, shape, and lithospheric strength. The dynamical module calculates despinning and orbital evolution. Chief outputs include the orbital evolution, the interior temperatures as a function of time and depth, and other parameters of interest such as k2, and Q(ω) as a function of time. This work was carried out at the Jet Propulsion Laboratory-California Institute of Technology, under contract to NASA.

A cytokine axis regulates elastin formation and degradation

PubMed Central

Sproul, Erin P.; Argraves, W. Scott

2013-01-01

Underlying the dynamic regulation of tropoelastin expression and elastin formation in development and disease are transcriptional and post-transcriptional mechanisms that have been the focus of much research. Of particular importance is the cytokine–governed elastin regulatory axis in which the pro-elastogenic activities of transforming growth factor β-1 (TGFβ1) and insulin-like growth factor-I (IGF-I) are opposed by anti-elastogenic activities of basic fibroblast growth factor (bFGF/FGF-2), heparin-binding epidermal growth factor-like growth factor (HB-EGF), EGF, PDGF-BB, TGFα, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β and noncanonical TGFβ1 signaling. A key mechanistic feature of the regulatory axis is that cytokines influence elastin formation through effects on the cell cycle involving control of cyclin–cyclin dependent kinase complexes and activation of the Ras/MEK/ERK signaling pathway. In this article we provide an overview of the major cytokines/growth factors that modulate elastogenesis and describe the underlying molecular mechanisms for their action on elastin production. PMID:23160093

77 FR 65767 - Petition for Exemption From the Federal Motor Vehicle Theft Prevention Standard; Chrysler

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-30

... (RFHM), Ignition Node Module (IGNM), Engine Control Module, Body Controller Module, Sentry Key... disable engine operation and immobilize the vehicle after two seconds of running. This process is also...

Investigation of Stimulation-Response Relationships for Complex Fracture Systems in Enhanced Geothermal Reservoirs

DOE Data Explorer

Fu, Pengcheng; Johnson, Scott M.; Carrigan, Charles R.

2011-01-01

Hydraulic fracturing is currently the primary method for stimulating low-permeability geothermal reservoirs and creating Enhanced (or Engineered) Geothermal Systems (EGS) with improved permeability and heat production efficiency. Complex natural fracture systems usually exist in the formations to be stimulated and it is therefore critical to understand the interactions between existing fractures and newly created fractures before optimal stimulation strategies can be developed. Our study aims to improve the understanding of EGS stimulation-response relationships by developing and applying computer-based models that can effectively reflect the key mechanisms governing interactions between complex existing fracture networks and newly created hydraulic fractures. In this paper, we first briefly describe the key modules of our methodology, namely a geomechanics solver, a discrete fracture flow solver, a rock joint response model, an adaptive remeshing module, and most importantly their effective coupling. After verifying the numerical model against classical closed-form solutions, we investigate responses of reservoirs with different preexisting natural fractures to a variety of stimulation strategies. The factors investigated include: the in situ stress states (orientation of the principal stresses and the degree of stress anisotropy), pumping pressure, and stimulation sequences of multiple wells.

Continuous-variable quantum-key-distribution protocols with a non-Gaussian modulation

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

Leverrier, Anthony; Grangier, Philippe; Laboratoire Charles Fabry, Institut d'Optique, CNRS, Univ. Paris-Sud, Campus Polytechnique, RD 128, F-91127 Palaiseau Cedex

2011-04-15

In this paper, we consider continuous-variable quantum-key-distribution (QKD) protocols which use non-Gaussian modulations. These specific modulation schemes are compatible with very efficient error-correction procedures, hence allowing the protocols to outperform previous protocols in terms of achievable range. In their simplest implementation, these protocols are secure for any linear quantum channels (hence against Gaussian attacks). We also show how the use of decoy states makes the protocols secure against arbitrary collective attacks, which implies their unconditional security in the asymptotic limit.

Quantifying Hydro-biogeochemical Model Sensitivity in Assessment of Climate Change Effect on Hyporheic Zone Processes

NASA Astrophysics Data System (ADS)

Song, X.; Chen, X.; Dai, H.; Hammond, G. E.; Song, H. S.; Stegen, J.

2016-12-01

The hyporheic zone is an active region for biogeochemical processes such as carbon and nitrogen cycling, where the groundwater and surface water mix and interact with each other with distinct biogeochemical and thermal properties. The biogeochemical dynamics within the hyporheic zone are driven by both river water and groundwater hydraulic dynamics, which are directly affected by climate change scenarios. Besides that, the hydraulic and thermal properties of local sediments and microbial and chemical processes also play important roles in biogeochemical dynamics. Thus for a comprehensive understanding of the biogeochemical processes in the hyporheic zone, a coupled thermo-hydro-biogeochemical model is needed. As multiple uncertainty sources are involved in the integrated model, it is important to identify its key modules/parameters through sensitivity analysis. In this study, we develop a 2D cross-section model in the hyporheic zone at the DOE Hanford site adjacent to Columbia River and use this model to quantify module and parametric sensitivity on assessment of climate change. To achieve this purpose, We 1) develop a facies-based groundwater flow and heat transfer model that incorporates facies geometry and heterogeneity characterized from a field data set, 2) derive multiple reaction networks/pathways from batch experiments with in-situ samples and integrate temperate dependent reactive transport modules to the flow model, 3) assign multiple climate change scenarios to the coupled model by analyzing historical river stage data, 4) apply a variance-based global sensitivity analysis to quantify scenario/module/parameter uncertainty in hierarchy level. The objectives of the research include: 1) identifing the key control factors of the coupled thermo-hydro-biogeochemical model in the assessment of climate change, and 2) quantify the carbon consumption in different climate change scenarios in the hyporheic zone.

Hands-on lessons in ergonomics for youth

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

Bennett, C; Alexandre, M; Jacobs, K

Ergonomics risk factors apply to everybody. Numerous adults have experienced disabling injuries related to use of computers and other forms of technology. Now children are using technology even more than adults. Increasingly ergonomics risk factors are being recognized as present in the world of children. Outreach to schools and the surrounding community by employers may help protect the future work force. A growing body of researchers believe that children can benefit from the early introduction of ergonomics awareness and preventative measures. While individual representatives of the educational system may embrace the concept of introducing ergonomics into the classroom, a numbermore » of barriers can prevent implementation of integrated programs. Some of the barriers to introducing ergonomics in schools have been absence of a tie to educational standards, the existing demands on teaching hours, and the absence of easily executable lesson plans. Ergonomics is rarely included in teacher training and professional ergonomics expertise is needed for the development of a class-based program. As part of Strategic Vision plan for 2025, a National Laboratory identified community outreach and the future workforces as key areas for initiatives. A series of hands-on interactive modules have been developed by professional ergonomics specialists. They are being tested with elementary, middle and high school students. Where possible, the content has been tied to the educational standards in the State of California in the USA. Currently the modules include grip strength, effective breathing, optimal keyboard and mouse positions, optimizing chairs, posture and movement, backpack safety and safe lifting. Each module takes the students through a related activity or experience. An individual worksheet asks them questions about the experience and guides them to consider implications in their activities of daily living. A module on hearing is under development. The goal is to have a toolkit that teachers can use in classrooms with minimal training. The kit will come with lesson plans, including background material, key points, questions and answers, possible homework assignments and references. It will include instructions and worksheets for students as well as the materials needed for each module. A pre- and posttest will be administered to test the awareness and understanding of the principles introduced in through the modules. This interactive session will offer the opportunity to for attendees to participate in some of the modules that have been developed to provide experiential demonstration of ergonomics principles. Attendees will experience ergonomics in action and be able to evaluate the applicability of the process in their own area in the world of ergonomics. The session will consist of 20 minutes introduction, 40 minutes working with the toolkit, finally another 30 minutes for questions or discussion for a total time of 90 minutes.« less

Distributed metadata servers for cluster file systems using shared low latency persistent key-value metadata store

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

Bent, John M.; Faibish, Sorin; Pedone, Jr., James M.

A cluster file system is provided having a plurality of distributed metadata servers with shared access to one or more shared low latency persistent key-value metadata stores. A metadata server comprises an abstract storage interface comprising a software interface module that communicates with at least one shared persistent key-value metadata store providing a key-value interface for persistent storage of key-value metadata. The software interface module provides the key-value metadata to the at least one shared persistent key-value metadata store in a key-value format. The shared persistent key-value metadata store is accessed by a plurality of metadata servers. A metadata requestmore » can be processed by a given metadata server independently of other metadata servers in the cluster file system. A distributed metadata storage environment is also disclosed that comprises a plurality of metadata servers having an abstract storage interface to at least one shared persistent key-value metadata store.« less

Graphene-silicon phase modulators with gigahertz bandwidth

NASA Astrophysics Data System (ADS)

Sorianello, V.; Midrio, M.; Contestabile, G.; Asselberghs, I.; Van Campenhout, J.; Huyghebaert, C.; Goykhman, I.; Ott, A. K.; Ferrari, A. C.; Romagnoli, M.

2018-01-01

The modulator is a key component in optical communications. Several graphene-based amplitude modulators have been reported based on electro-absorption. However, graphene phase modulators (GPMs) are necessary for functions such as applying complex modulation formats or making switches or phased arrays. Here, we present a 10 Gb s-1 GPM integrated in a Mach-Zehnder interferometer configuration. This is a compact device based on a graphene-insulator-silicon capacitor, with a phase-shifter length of 300 μm and extinction ratio of 35 dB. The GPM has a modulation efficiency of 0.28 V cm at 1,550 nm. It has 5 GHz electro-optical bandwidth and operates at 10 Gb s-1 with 2 V peak-to-peak driving voltage in a push-pull configuration for binary transmission of a non-return-to-zero data stream over 50 km of single-mode fibre. This device is the key building block for graphene-based integrated photonics, enabling compact and energy-efficient hybrid graphene-silicon modulators for telecom, datacom and other applications.

Amplification of a bi-phase shift-key modulated signal by a mm-wave FEL

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

Prosnitz, D.; Scharlemann, E.T.; Sheaffer, M.K.

Bi-phase shift keying (BPSK) is a modulation scheme used in communications and radar in which the phase of a transmitted rf signal is switched in a coded pattern between discrete values differing by {pi} radians. The transmitted information rate (in communications) or resolution (in imaging radar) depends on the rate at which the transmitted signal can be modulated. Modulation rates of greater than 1 GHz are generally desired. Although the instantaneous gain bandwidth of a mm-wave FEL amplifier can be much greater than 10 GHz, slippage may limit the BPSK modulation rate that can be amplified. Qualitative slippage arguments wouldmore » limit the modulation rate to relatively low values; nevertheless, simulations with a time-dependent FEL code (GINGER) indicate that rates of 2 GHz or more are amplified without much loss in modulation integrity. In this paper we describe the effects of slippage in the simulations and discuss the limits of simple arguments.« less

The TIE1 Transcriptional Repressor Links TCP Transcription Factors with TOPLESS/TOPLESS-RELATED Corepressors and Modulates Leaf Development in Arabidopsis[W

PubMed Central

Tao, Qing; Guo, Dongshu; Wei, Baoye; Zhang, Fan; Pang, Changxu; Jiang, Hao; Zhang, Jinzhe; Wei, Tong; Gu, Hongya; Qu, Li-Jia; Qin, Genji

2013-01-01

Leaf size and shape are mainly determined by coordinated cell division and differentiation in lamina. The CINCINNATA (CIN)-like TEOSINTE BRANCHED1/CYCLOIDEA/PCF (TCP) transcription factors are key regulators of leaf development. However, the mechanisms that control TCP activities during leaf development are largely unknown. We identified the TCP Interactor containing EAR motif protein1 (TIE1), a novel transcriptional repressor, as a major modulator of TCP activities during leaf development. Overexpression of TIE1 leads to hyponastic and serrated leaves, whereas disruption of TIE1 causes epinastic leaves. TIE1 is expressed in young leaves and encodes a transcriptional repressor containing a C-terminal EAR motif, which mediates interactions with the TOPLESS (TPL)/TOPLESS-RELATED (TPR) corepressors. In addition, TIE1 physically interacts with CIN-like TCPs. We propose that TIE1 regulates leaf size and morphology by inhibiting the activities of TCPs through recruiting the TPL/TPR corepressors to form a tertiary complex at early stages of leaf development. PMID:23444332

Pyrrolidine Dithiocarbamate Prevents Neuroinflammation and Cognitive Dysfunction after Endotoxemia in Rats

PubMed Central

Kan, Min Hui; Yang, Ting; Fu, Hui Qun; Fan, Long; Wu, Yan; Terrando, Niccolò; Wang, Tian-Long

2016-01-01

Systemic inflammation, for example as a result of infection, often contributes to long-term complications. Neuroinflammation and cognitive decline are key hallmarks of several neurological conditions, including advance age. The contribution of systemic inflammation to the central nervous system (CNS) remains not fully understood. Using a model of peripheral endotoxemia with lipopolysaccharide (LPS) we investigated the role of nuclear factor-κB (NF-κB) activity in mediating long-term neuroinflammation and cognitive dysfunction in aged rats. Herein we describe the anti-inflammatory effects of pyrrolidine dithiocarbamate (PDTC), a selective NF-κB inhibitor, in modulating systemic cytokines including tumor necrosis factor (TNF)-α and interleukin-1β (IL-1β) and CNS markers after LPS exposure in aged rats. In the hippocampus, PDTC not only reduced neuroinflammation by modulating canonical NF-κB activity but also affected IL-1β expression in astrocytes. Parallel effects were observed on behavior and postsynaptic density-95 (PSD95), a marker of synaptic function. Taken together these changes improved acute and long-term cognitive function in aged rats after LPS exposure. PMID:27493629

Evidence that Meningeal Mast Cells Can Worsen Stroke Pathology in Mice

PubMed Central

Arac, Ahmet; Grimbaldeston, Michele A.; Nepomuceno, Andrew R.B.; Olayiwola, Oluwatobi; Pereira, Marta P.; Nishiyama, Yasuhiro; Tsykin, Anna; Goodall, Gregory J.; Schlecht, Ulrich; Vogel, Hannes; Tsai, Mindy; Galli, Stephen J.; Bliss, Tonya M.; Steinberg, Gary K.

2015-01-01

Stroke is the leading cause of adult disability and the fourth most common cause of death in the United States. Inflammation is thought to play an important role in stroke pathology, but the factors that promote inflammation in this setting remain to be fully defined. An understudied but important factor is the role of meningeal-located immune cells in modulating brain pathology. Although different immune cells traffic through meningeal vessels en route to the brain, mature mast cells do not circulate but are resident in the meninges. With the use of genetic and cell transfer approaches in mice, we identified evidence that meningeal mast cells can importantly contribute to the key features of stroke pathology, including infiltration of granulocytes and activated macrophages, brain swelling, and infarct size. We also obtained evidence that two mast cell-derived products, interleukin-6 and, to a lesser extent, chemokine (C-C motif) ligand 7, can contribute to stroke pathology. These findings indicate a novel role for mast cells in the meninges, the membranes that envelop the brain, as potential gatekeepers for modulating brain inflammation and pathology after stroke. PMID:25134760

Bandwidth scalable, coherent transmitter based on the parallel synthesis of multiple spectral slices using optical arbitrary waveform generation.

PubMed

Geisler, David J; Fontaine, Nicolas K; Scott, Ryan P; He, Tingting; Paraschis, Loukas; Gerstel, Ori; Heritage, Jonathan P; Yoo, S J B

2011-04-25

We demonstrate an optical transmitter based on dynamic optical arbitrary waveform generation (OAWG) which is capable of creating high-bandwidth (THz) data waveforms in any modulation format using the parallel synthesis of multiple coherent spectral slices. As an initial demonstration, the transmitter uses only 5.5 GHz of electrical bandwidth and two 10-GHz-wide spectral slices to create 100-ns duration, 20-GHz optical waveforms in various modulation formats including differential phase-shift keying (DPSK), quaternary phase-shift keying (QPSK), and eight phase-shift keying (8PSK) with only changes in software. The experimentally generated waveforms showed clear eye openings and separated constellation points when measured using a real-time digital coherent receiver. Bit-error-rate (BER) performance analysis resulted in a BER < 9.8 × 10(-6) for DPSK and QPSK waveforms. Additionally, we experimentally demonstrate three-slice, 4-ns long waveforms that highlight the bandwidth scalable nature of the optical transmitter. The various generated waveforms show that the key transmitter properties (i.e., packet length, modulation format, data rate, and modulation filter shape) are software definable, and that the optical transmitter is capable of acting as a flexible bandwidth transmitter.

Intestinal barrier: A gentlemen’s agreement between microbiota and immunity

PubMed Central

Caricilli, Andrea Moro; Castoldi, Angela; Câmara, Niels Olsen Saraiva

2014-01-01

Our body is colonized by more than a hundred trillion commensals, represented by viruses, bacteria and fungi. This complex interaction has shown that the microbiome system contributes to the host’s adaptation to its environment, providing genes and functionality that give flexibility of diet and modulate the immune system in order not to reject these symbionts. In the intestine, specifically, the microbiota helps developing organ structures, participates of the metabolism of nutrients and induces immunity. Certain components of the microbiota have been shown to trigger inflammatory responses, whereas others, anti-inflammatory responses. The diversity and the composition of the microbiota, thus, play a key role in the maintenance of intestinal homeostasis and explain partially the link between intestinal microbiota changes and gut-related disorders in humans. Tight junction proteins are key molecules for determination of the paracellular permeability. In the context of intestinal inflammatory diseases, the intestinal barrier is compromised, and decreased expression and differential distribution of tight junction proteins is observed. It is still unclear what is the nature of the luminal or mucosal factors that affect the tight junction proteins function, but the modulation of the immune cells found in the intestinal lamina propria is hypothesized as having a role in this modulation. In this review, we provide an overview of the current understanding of the interaction of the gut microbiota with the immune system in the development and maintenance of the intestinal barrier. PMID:24891972

SPOC1 modulates DNA repair by regulating key determinants of chromatin compaction and DNA damage response

PubMed Central

Mund, Andreas; Schubert, Tobias; Staege, Hannah; Kinkley, Sarah; Reumann, Kerstin; Kriegs, Malte; Fritsch, Lauriane; Battisti, Valentine; Ait-Si-Ali, Slimane; Hoffbeck, Anne-Sophie; Soutoglou, Evi; Will, Hans

2012-01-01

Survival time-associated plant homeodomain (PHD) finger protein in Ovarian Cancer 1 (SPOC1, also known as PHF13) is known to modulate chromatin structure and is essential for testicular stem-cell differentiation. Here we show that SPOC1 is recruited to DNA double-strand breaks (DSBs) in an ATM-dependent manner. Moreover, SPOC1 localizes at endogenous repair foci, including OPT domains and accumulates at large DSB repair foci characteristic for delayed repair at heterochromatic sites. SPOC1 depletion enhances the kinetics of ionizing radiation-induced foci (IRIF) formation after γ-irradiation (γ-IR), non-homologous end-joining (NHEJ) repair activity, and cellular radioresistance, but impairs homologous recombination (HR) repair. Conversely, SPOC1 overexpression delays IRIF formation and γH2AX expansion, reduces NHEJ repair activity and enhances cellular radiosensitivity. SPOC1 mediates dose-dependent changes in chromatin association of DNA compaction factors KAP-1, HP1-α and H3K9 methyltransferases (KMT) GLP, G9A and SETDB1. In addition, SPOC1 interacts with KAP-1 and H3K9 KMTs, inhibits KAP-1 phosphorylation and enhances H3K9 trimethylation. These findings provide the first evidence for a function of SPOC1 in DNA damage response (DDR) and repair. SPOC1 acts as a modulator of repair kinetics and choice of pathways. This involves its dose-dependent effects on DNA damage sensors, repair mediators and key regulators of chromatin structure. PMID:23034801

Cancer associated fibroblasts promote tumor growth and metastasis by modulating the tumor immune microenvironment in a 4T1 murine breast cancer model.

PubMed

Liao, Debbie; Luo, Yunping; Markowitz, Dorothy; Xiang, Rong; Reisfeld, Ralph A

2009-11-23

Local inflammation associated with solid tumors commonly results from factors released by tumor cells and the tumor stroma, and promotes tumor progression. Cancer associated fibroblasts comprise a majority of the cells found in tumor stroma and are appealing targets for cancer therapy. Here, our aim was to determine the efficacy of targeting cancer associated fibroblasts for the treatment of metastatic breast cancer. We demonstrate that cancer associated fibroblasts are key modulators of immune polarization in the tumor microenvironment of a 4T1 murine model of metastatic breast cancer. Elimination of cancer associated fibroblasts in vivo by a DNA vaccine targeted to fibroblast activation protein results in a shift of the immune microenvironment from a Th2 to Th1 polarization. This shift is characterized by increased protein expression of IL-2 and IL-7, suppressed recruitment of tumor-associated macrophages, myeloid derived suppressor cells, T regulatory cells, and decreased tumor angiogenesis and lymphangiogenesis. Additionally, the vaccine improved anti-metastatic effects of doxorubicin chemotherapy and enhanced suppression of IL-6 and IL-4 protein expression while increasing recruitment of dendritic cells and CD8(+) T cells. Treatment with the combination therapy also reduced tumor-associated Vegf, Pdgfc, and GM-CSF mRNA and protein expression. Our findings demonstrate that cancer associated fibroblasts promote tumor growth and metastasis through their role as key modulators of immune polarization in the tumor microenvironment and are valid targets for therapy of metastatic breast cancer.

Dynamic Modulation of Expression of Lentiviral Restriction Factors in Primary CD4+ T Cells following Simian Immunodeficiency Virus Infection.

PubMed

Rahmberg, Andrew R; Rajakumar, Premeela A; Billingsley, James M; Johnson, R Paul

2017-04-01

Although multiple restriction factors have been shown to inhibit HIV/SIV replication, little is known about their expression in vivo Expression of 45 confirmed and putative HIV/SIV restriction factors was analyzed in CD4 + T cells from peripheral blood and the jejunum in rhesus macaques, revealing distinct expression patterns in naive and memory subsets. In both peripheral blood and the jejunum, memory CD4 + T cells expressed higher levels of multiple restriction factors compared to naive cells. However, relative to their expression in peripheral blood CD4 + T cells, jejunal CCR5 + CD4 + T cells exhibited significantly lower expression of multiple restriction factors, including APOBEC3G , MX2 , and TRIM25 , which may contribute to the exquisite susceptibility of these cells to SIV infection. In vitro stimulation with anti-CD3/CD28 antibodies or type I interferon resulted in upregulation of distinct subsets of multiple restriction factors. After infection of rhesus macaques with SIVmac239, the expression of most confirmed and putative restriction factors substantially increased in all CD4 + T cell memory subsets at the peak of acute infection. Jejunal CCR5 + CD4 + T cells exhibited the highest levels of SIV RNA, corresponding to the lower restriction factor expression in this subset relative to peripheral blood prior to infection. These results illustrate the dynamic modulation of confirmed and putative restriction factor expression by memory differentiation, stimulation, tissue microenvironment and SIV infection and suggest that differential expression of restriction factors may play a key role in modulating the susceptibility of different populations of CD4 + T cells to lentiviral infection. IMPORTANCE Restriction factors are genes that have evolved to provide intrinsic defense against viruses. HIV and simian immunodeficiency virus (SIV) target CD4 + T cells. The baseline level of expression in vivo and degree to which expression of restriction factors is modulated by conditions such as CD4 + T cell differentiation, stimulation, tissue location, or SIV infection are currently poorly understood. We measured the expression of 45 confirmed and putative restriction factors in primary CD4 + T cells from rhesus macaques under various conditions, finding dynamic changes in each state. Most dramatically, in acute SIV infection, the expression of almost all target genes analyzed increased. These are the first measurements of many of these confirmed and putative restriction factors in primary cells or during the early events after SIV infection and suggest that the level of expression of restriction factors may contribute to the differential susceptibility of CD4 + T cells to SIV infection. Copyright © 2017 American Society for Microbiology.

Teaching patient safety and human factors in undergraduate nursing curricula in England: a pilot survey.

PubMed

Robson, Wayne; Clark, Debbie; Pinnock, David; White, Nick; Baxendale, Bryn

Patient safety is a key priority for all healthcare systems, and there is growing recognition for the need to educate tomorrow's nurses about the role of human factors in reducing avoidable harm to patients. A pilot survey was sent to 20 schools of nursing in England to explore the teaching of patient safety and human factors. All 13 schools that responded (65% response rate) stated that patient safety was covered in their curricula and was allocated more than 4 hours; all the classes included human factors. Only two respondents indicated their teaching to be multi-professional. Awareness of the World Health Organization's multiprofessional patient safety curriculum guide was poor. Faculties also seemed unaware that the Institute for Healthcare Improvement provides free online patient safety modules for students and that there is a global network of student patient safety chapters.

Identification of a Novel Pathway That Selectively Modulates Apoptosis of Breast Cancer Cells

PubMed Central

Tinnikov, Alexander A.; Yeung, Kay T.; Das, Sharmistha; Samuels, Herbert H.

2014-01-01

Expression of the nuclear receptor interacting factor 3 (NRIF3) coregulator in a wide variety of breast cancer cells selectively leads to rapid caspase-2–dependent apoptotic cell death. A novel death domain (DD1) was mapped to a 30– amino acid region of NRIF3. Because the cytotoxicity of NRIF3 and DD1 seems to be cell type–specific, these studies suggest that breast cancer cells contain a novel “death switch” that can be specifically modulated by NRIF3 or DD1. Using an MCF-7 cell cDNA library in a yeast two-hybrid screen, we cloned a factor that mediates apoptosis by DD1 and refer to this factor as DD1-interacting factor-1 (DIF-1). DIF-1 is a transcriptional repressor that mediates its effect through SirT1, and this repression is attenuated by the binding of NRIF3/DD1. DIF-1 expression rescues breast cancer cells from NRIF3/DD1-induced apoptosis. Small interfering RNA (siRNA) knockdown of DIF-1 selectively leads to apoptosis of breast cancer cells, further suggesting that DIF-1 plays a key role in NRIF3/DD1-mediated apoptosis. A protein kinase A inhibitor (H89) also elicits apoptosis of breast cancer cells but not of the other cell types examined, and DIF-1 also protects these cells from H89-mediated apoptosis. In addition, H89 incubation results in a rapid increase in NRIF3 levels and siRNA knockdown of NRIF3 protects breast cancer cells from H89-mediated apoptosis. Our results indicate that DIF-1 plays a key role in breast cancer cell survival and further characterizing this pathway may provide important insights into developing novel therapies to selec tively target breast cancer cells for apoptosis. PMID:19190336

Uncontrolled eating in adolescents: The role of impulsivity and automatic approach bias for food.

PubMed

Booth, Charlotte; Spronk, Desiree; Grol, Maud; Fox, Elaine

2018-01-01

Obesity is a global problem reaching epidemic proportions and can be explained by unhealthy eating and sedentary lifestyles. Understanding the psychological processes underlying unhealthy eating behaviour is crucial for the development of effective obesity prevention programmes. Dual-process models implicate the interplay between impaired cognitive control and enhanced automatic responsivity to rewarding food cues as key risk factors. The current study assessed the influence of four different components of trait impulsivity (reflecting impaired cognitive control) and automatic approach bias for food (reflecting automatic responsivity to food) on uncontrolled eating in a large sample (N = 504) of young adolescents. Of the four impulsivity factors, negative urgency was found to be the strongest predictor of uncontrolled eating. Interestingly, we found that lack of premeditation was a key risk factor for uncontrolled eating, but only when approach bias for food was high, supporting a dual-process model. Lack of perseverance showed a similar interactive pattern to a lesser degree and sensation-seeking did not predict uncontrolled eating. Together, our results show that distinct components of trait impulsivity are differentially associated with uncontrolled eating behaviour in adolescents, and that automatic processing of food cues may be an important factor in modulating this relationship. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Low-Complexity, Digital Encoder/Modulator Developed for High-Data-Rate Satellite B-ISDN Applications

NASA Technical Reports Server (NTRS)

1996-01-01

The Space Electronics Division at the NASA Lewis Research Center is developing advanced electronic technologies for the space communications and remote sensing systems of tomorrow. As part of the continuing effort to advance the state-of-the-art in satellite communications and remote sensing systems, Lewis developed a low-cost, modular, programmable, and reconfigurable all-digital encoder-modulator (DEM) for medium- to high-data-rate radiofrequency communication links. The DEM is particularly well suited to high-data-rate downlinks to ground terminals or direct data downlinks from near-Earth science platforms. It can support data rates up to 250 megabits per second (Mbps) and several modulation schemes, including the traditional binary phase-shift keying (BPSK) and quadrature phase-shift keying (QPSK) modes, as well as higher order schemes such as 8 phase-shift keying (8PSK) and 16 quadrature amplitude modulation (16QAM). The DEM architecture also can precompensate for channel disturbances and alleviate amplitude degradations caused by nonlinear transponder characteristics.

FPGA based digital phase-coding quantum key distribution system

NASA Astrophysics Data System (ADS)

Lu, XiaoMing; Zhang, LiJun; Wang, YongGang; Chen, Wei; Huang, DaJun; Li, Deng; Wang, Shuang; He, DeYong; Yin, ZhenQiang; Zhou, Yu; Hui, Cong; Han, ZhengFu

2015-12-01

Quantum key distribution (QKD) is a technology with the potential capability to achieve information-theoretic security. Phasecoding is an important approach to develop practical QKD systems in fiber channel. In order to improve the phase-coding modulation rate, we proposed a new digital-modulation method in this paper and constructed a compact and robust prototype of QKD system using currently available components in our lab to demonstrate the effectiveness of the method. The system was deployed in laboratory environment over a 50 km fiber and continuously operated during 87 h without manual interaction. The quantum bit error rate (QBER) of the system was stable with an average value of 3.22% and the secure key generation rate is 8.91 kbps. Although the modulation rate of the photon in the demo system was only 200 MHz, which was limited by the Faraday-Michelson interferometer (FMI) structure, the proposed method and the field programmable gate array (FPGA) based electronics scheme have a great potential for high speed QKD systems with Giga-bits/second modulation rate.

The Challenges in Meeting OSD’s Obligation and Expenditure Rate Goals: A Closer Look at Potential Causal Factors, Their Groupings, and How They Modulate

DTIC Science & Technology

2013-10-01

F22 Defense Contract Audit Agency (DCAA) administrative actions 44% 3.92 2.61 F23 Unplanned Congressional adds to Program Baseline (PB) request 43...materialized F21 Program delays from prerequisite events F22 DCAA administrative actions F23 Unplanned Congressional adds to PB request F24...functional areas (F27) and Tenure of PM and others in key positions (F46); and DCMA administrative actions (F36) and DCAA administrative actions ( F22

[Autism and Autism-associated Metabolites].

PubMed

Watanabe, Kunitomo

2016-06-01

Gene-microbiota interactions are now proposed to be a special case of gene-environmental interaction. Preclinical and clinical data summarized in this article reveal that a specific serum metabolite, associated with alterations in gut microbiome composition, might have an emerging role in the onset and pathogenesis of autism. Altered level of this specified metabolite may induce perturbations in the epigenome and modulate the expression of key disease susceptible genes in neurons and their associated cells during critical periods of neurodevelopment. The gut microbiota itself is now regarded as a reservoir for environmental epigenetic factors.

Evidence for the Involvement of Lfc and Tctex-1 in Axon Formation

PubMed Central

Conde, Cecilia; Arias, Cristina; Robin, Maria; Li, Aiqun; Saito, Masaki; Chuang, Jen-Zen; Nairn, Angus C.; Sung, Ching-Hwa; Cáceres, Alfredo

2013-01-01

RhoA and Rac play key and opposite roles during neuronal polarization. We now show that Lfc, a guanosine nucleotide exchange factor (GEF), localizes to the Golgi apparatus and growth cones of developing neurons and negatively regulates neurite sprouting and axon formation through a Rho signaling pathway. Tctex-1, a dynein light chain implicated in axon outgrowth by modulating actin dynamics and Rac activity, colocalizes and physically interacts with Lfc, thus inhibiting its GEF activity, decreasing Rho-GTP levels, and functionally antagonizing Lfc during neurite formation. PMID:20463241

Ionizing and Nonionizing Radiation Protection. Module SH-35. Safety and Health.

ERIC Educational Resources Information Center

Center for Occupational Research and Development, Inc., Waco, TX.

This student module on ionizing and nonionizing radiation protection is one of 50 modules concerned with job safety and health. This module describes various types of ionizing and nonionizing radiation, and the situations in the workplace where potential hazards from radiation may exist. Following the introduction, 13 objectives (each keyed to a…

Automatic Layout Design for Power Module

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

Ning, Puqi; Wang, Fei; Ngo, Khai

The layout of power modules is one of the key points in power module design, especially for high power densities, where couplings are increased. In this paper, along with the design example, an automatic design processes by using a genetic algorithm are presented. Some practical considerations and implementations are introduced in the optimization of module layout design.

Recognizing Job Health Hazards. Module SH-08. Safety and Health.

ERIC Educational Resources Information Center

Center for Occupational Research and Development, Inc., Waco, TX.

This student module on recognizing job health hazards is one of 50 modules concerned with job safety and health. This module presents the four general categories of environmental conditions or stresses: chemical, physical, biological, and ergonomic. Following the introduction, 14 objectives (each keyed to a page in the text) the student is…

OSHA Training Programs. Module SH-48. Safety and Health.

ERIC Educational Resources Information Center

Center for Occupational Research and Development, Inc., Waco, TX.

This student module on OSHA (Occupational Safety and Health Act) training programs is one of 50 modules concerned with job safety and health. This module provides a list of OSHA training requirements and describes OSHA training programs and other safety organizations' programs. Following the introduction, 11 objectives (each keyed to a page in the…

Design and implementation of ATCA-based 100Gbps DP-QPSK optical signal test instrument

NASA Astrophysics Data System (ADS)

Su, Shaojing; Qin, Jiangyi; Huang, Zhiping; Liu, Chenwu

2014-11-01

In order to achieve the receiving task of 100Gbps Dual Polarization-Quadrature Phase Shift Keying (DP-QPSK) optical signal acquisition instrument, improve acquisition performance of the instrument, this paper has deeply researched DP-QPSK modulation principles, demodulation techniques and the key technologies of optical signal acquisition. The theories of DP-QPSK optical signal transmission are researched. The DP-QPSK optical signal transmission model is deduced. And the clock and data recovery in high-speed data acquisition and offset correction of multi-channel data are researched. By reasonable hardware circuit design and software system construction, the utilization of high performance Advanced Telecom Computing Architecture (ATCA), this paper proposes a 100Gbps DP-QPSK optical signal acquisition instrument which is based on ATCA. The implementations of key modules are presented by comparison and argumentation. According to the modularization idea, the instrument can be divided into eight modules. Each module performs the following functions. (1) DP-QPSK coherent detection demodulation module; (2) deceleration module; (3) FPGA (Field Programmable Gate Array); (4) storage module; (5) data transmission module; (6) clock module; (7) power module; (8) JTAG debugging, configuration module; What is more, this paper has put forward two solutions to test optical signal acquisition instrument performance. The first scenario is based on a standard STM-256 optical signal format and exploits the SignalTap of QuartusII software to monitor the optical signal data. Another scenario is to use a pseudo-random signal series to generate data, acquisition module acquires a certain amount of data signals, and then the signals are transferred to a computer by the Gigabit Ethernet to analyze. Two testing results show that the bit error rate of optical signal acquisition instrument is low. And the instrument fully meets the requirements of signal receiving system. At the same time this design has an important significance in practical applications.

Calcitonin protects chondrocytes from lipopolysaccharide-induced apoptosis and inflammatory response through MAPK/Wnt/NF-κB pathways.

PubMed

Zhang, Lai-Bo; Man, Zhen-Tao; Li, Wei; Zhang, Wei; Wang, Xian-Quan; Sun, Shui

2017-07-01

Calcitonin (CT) is an anti-absorbent, which has long been used for treatment of osteoporosis. However, little information is available about the effects of CT on osteoarthritis (OA). This study was mainly aimed to explore the effects of CT on the treatment of OA, as well as the underlying mechanisms. Chondrocytes were isolated from immature mice and then were incubated with lipopolysaccharide (LPS), CT, small interfering (si) RNA against bone morphogenetic protein (BMP)-2, and/or the inhibitors of MAPK/Wnt/NF-κB pathway. Thereafter, cell viability, apoptosis, nitric oxide (NO) and inflammatory factors productions, and expression levels of cartilage synthesis protein key factors, cartilage-derived morphogenetic protein (CDMP) 1, SRY (sex-determining region Y)-box 9 protein (SOX9), and MAPK/Wnt/NF-κB pathways key factors were determined. CT significantly reversed LPS-induced cell viability decrease, apoptosis increase, the inflammatory factors and NO secretion, the abnormally expression of cartilage synthesis proteins and the activation of MAPK/Wnt/NF-κB pathways (P<0.05). In addition, we observed that administration of the inhibitors of MAPK/Wnt/NF-κB pathways statistically further increased the levels of CDMP1 and SOX9 (P<0.05). Suppression of BMP-2 decreased the levels of CDMP1 and SOX9 and activated MAPK/Wnt/NF-κB pathways, and could partially abolish CT-modulated the expression changes in CDMP1 and SOX9, and MAPK/Wnt/NF-κB pathways key factors (P<0.05). The results showed that CT protects chondrocytes from LPS-induced apoptosis and inflammatory response by regulating BMP-2 and thus blocking MAPK/Wnt/NF-κB pathways. Copyright © 2017 Elsevier Ltd. All rights reserved.

Rectangular QPSK for generation of optical eight-ary phase-shift keying.

PubMed

Lu, Guo-Wei; Sakamoto, Takahide; Kawanishi, Tetsuya

2011-09-12

Quadrature phase-shift keying (QPSK) is usually generated using an in-phase/quadrature (IQ) modulator in a balanced driving-condition, showing a square-shape constellation in complex plane. This conventional QPSK is referred to as square QPSK (S-QPSK) in this paper. On the other hand, when an IQ modulator is driven in an un-balanced manner with different amplitudes in in-phase (I) and quadrature (Q) branches, a rectangular QPSK (R-QPSK) could be synthesized. The concept of R-QPSK is proposed for the first time and applied to optical eight-ary phase-shift keying (8PSK) transmitter. By cascading an S-QPSK and an R-QPSK, an optical 8PSK could be synthesized. The transmitter configuration is based on two cascaded IQ modulators, which also could be used to generate other advanced multi-level formats like quadrature amplitude modulation (QAM) when different driving and bias conditions are applied. Therefore, the proposed transmitter structure has potential to be deployed as a versatile transmitter for synthesis of several different multi-level modulation formats for the future dynamic optical networks. A 30-Gb/s optical 8PSK is experimentally demonstrated using the proposed solution.

On the role of sparseness in the evolution of modularity in gene regulatory networks

PubMed Central

2018-01-01

Modularity is a widespread property in biological systems. It implies that interactions occur mainly within groups of system elements. A modular arrangement facilitates adjustment of one module without perturbing the rest of the system. Therefore, modularity of developmental mechanisms is a major factor for evolvability, the potential to produce beneficial variation from random genetic change. Understanding how modularity evolves in gene regulatory networks, that create the distinct gene activity patterns that characterize different parts of an organism, is key to developmental and evolutionary biology. One hypothesis for the evolution of modules suggests that interactions between some sets of genes become maladaptive when selection favours additional gene activity patterns. The removal of such interactions by selection would result in the formation of modules. A second hypothesis suggests that modularity evolves in response to sparseness, the scarcity of interactions within a system. Here I simulate the evolution of gene regulatory networks and analyse diverse experimentally sustained networks to study the relationship between sparseness and modularity. My results suggest that sparseness alone is neither sufficient nor necessary to explain modularity in gene regulatory networks. However, sparseness amplifies the effects of forms of selection that, like selection for additional gene activity patterns, already produce an increase in modularity. That evolution of new gene activity patterns is frequent across evolution also supports that it is a major factor in the evolution of modularity. That sparseness is widespread across gene regulatory networks indicates that it may have facilitated the evolution of modules in a wide variety of cases. PMID:29775459

On the role of sparseness in the evolution of modularity in gene regulatory networks.

PubMed

Espinosa-Soto, Carlos

2018-05-01

Modularity is a widespread property in biological systems. It implies that interactions occur mainly within groups of system elements. A modular arrangement facilitates adjustment of one module without perturbing the rest of the system. Therefore, modularity of developmental mechanisms is a major factor for evolvability, the potential to produce beneficial variation from random genetic change. Understanding how modularity evolves in gene regulatory networks, that create the distinct gene activity patterns that characterize different parts of an organism, is key to developmental and evolutionary biology. One hypothesis for the evolution of modules suggests that interactions between some sets of genes become maladaptive when selection favours additional gene activity patterns. The removal of such interactions by selection would result in the formation of modules. A second hypothesis suggests that modularity evolves in response to sparseness, the scarcity of interactions within a system. Here I simulate the evolution of gene regulatory networks and analyse diverse experimentally sustained networks to study the relationship between sparseness and modularity. My results suggest that sparseness alone is neither sufficient nor necessary to explain modularity in gene regulatory networks. However, sparseness amplifies the effects of forms of selection that, like selection for additional gene activity patterns, already produce an increase in modularity. That evolution of new gene activity patterns is frequent across evolution also supports that it is a major factor in the evolution of modularity. That sparseness is widespread across gene regulatory networks indicates that it may have facilitated the evolution of modules in a wide variety of cases.

The Dynamics of Transcript Abundance during Cellularization of Developing Barley Endosperm1[OPEN

PubMed Central

Zhang, Runxuan; Burton, Rachel A; Shirley, Neil J.; Little, Alan; Morris, Jenny; Milne, Linda

2016-01-01

Within the cereal grain, the endosperm and its nutrient reserves are critical for successful germination and in the context of grain utilization. The identification of molecular determinants of early endosperm development, particularly regulators of cell division and cell wall deposition, would help predict end-use properties such as yield, quality, and nutritional value. Custom microarray data have been generated using RNA isolated from developing barley grain endosperm 3 d to 8 d after pollination (DAP). Comparisons of transcript abundance over time revealed 47 gene expression modules that can be clustered into 10 broad groups. Superimposing these modules upon cytological data allowed patterns of transcript abundance to be linked with key stages of early grain development. Here, attention was focused on how the datasets could be mined to explore and define the processes of cell wall biosynthesis, remodeling, and degradation. Using a combination of spatial molecular network and gene ontology enrichment analyses, it is shown that genes involved in cell wall metabolism are found in multiple modules, but cluster into two main groups that exhibit peak expression at 3 DAP to 4 DAP and 5 DAP to 8 DAP. The presence of transcription factor genes in these modules allowed candidate genes for the control of wall metabolism during early barley grain development to be identified. The data are publicly available through a dedicated web interface (https://ics.hutton.ac.uk/barseed/), where they can be used to interrogate co- and differential expression for any other genes, groups of genes, or transcription factors expressed during early endosperm development. PMID:26754666

pH modulates the binding of early growth response protein 1 transcription factor to DNA.

PubMed

Mikles, David C; Bhat, Vikas; Schuchardt, Brett J; Deegan, Brian J; Seldeen, Kenneth L; McDonald, Caleb B; Farooq, Amjad

2013-08-01

The transcription factor early growth response protein (EGR)1 orchestrates a plethora of signaling cascades involved in cellular homeostasis, and its downregulation has been implicated in the development of prostate cancer. Herein, using a battery of biophysical tools, we show that the binding of EGR1 to DNA is tightly regulated by solution pH. Importantly, the binding affinity undergoes an enhancement of more than an order of magnitude with an increase in pH from 5 to 8, implying that the deprotonation of an ionizable residue accounts for such behavior. This ionizable residue is identified as His382 by virtue of the fact that its replacement by nonionizable residues abolishes the pH dependence of the binding of EGR1 to DNA. Notably, His382 inserts into the major groove of DNA, and stabilizes the EGR1-DNA interaction via both hydrogen bonding and van der Waals contacts. Remarkably, His382 is mainly conserved across other members of the EGR family, implying that histidine protonation-deprotonation may serve as a molecular switch for modulating the protein-DNA interactions that are central to this family of transcription factors. Collectively, our findings reveal an unexpected but a key step in the molecular recognition of the EGR family of transcription factors, and suggest that they may act as sensors of pH within the intracellular environment. © 2013 FEBS.

Chromatin reorganisation in Epstein-Barr virus-infected cells and its role in cancer development.

PubMed

West, Michelle J

2017-10-01

The oncogenic Epstein-Barr virus (EBV) growth transforms B cells and drives lymphoma and carcinoma development. The virus encodes four key transcription factors (EBNA2, EBNA3A, EBNA3B and EBNA3C) that hijack host cell factors to bind gene control elements and reprogramme infected B cells. These viral factors predominantly target long-range enhancers to alter the expression of host cell genes that control B cell growth and survival and facilitate virus persistence. Enhancer and super-enhancer binding by these EBNAs results in large-scale reorganisation of three-dimensional enhancer-promoter architecture to drive the overexpression of oncogenes, the silencing of tumour suppressors and the modulation of transcription, cell-cycle progression, migration and adhesion. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Scaffold Composition Determines the Angiogenic Outcome of Cell-Based Vascular Endothelial Growth Factor Expression by Modulating Its Microenvironmental Distribution.

PubMed

Gaudiello, Emanuele; Melly, Ludovic; Cerino, Giulia; Boccardo, Stefano; Jalili-Firoozinezhad, Sasan; Xu, Lifen; Eckstein, Friedrich; Martin, Ivan; Kaufmann, Beat A; Banfi, Andrea; Marsano, Anna

2017-12-01

Delivery of genetically modified cells overexpressing Vascular Endothelial Growth Factor (VEGF) is a promising approach to induce therapeutic angiogenesis in ischemic tissues. The effect of the protein is strictly modulated by its interaction with the components of the extracellular matrix. Its therapeutic potential depends on a sustained but controlled release at the microenvironmental level in order to avoid the formation of abnormal blood vessels. In this study, it is hypothesized that the composition of the scaffold plays a key role in modulating the binding, hence the therapeutic effect, of the VEGF released by 3D-cell constructs. It is found that collagen sponges, which poorly bind VEGF, prevent the formation of localized hot spots of excessive concentration, therefore, precluding the development of aberrant angiogenesis despite uncontrolled expression by a genetically engineered population of adipose tissue-derived stromal cells. On the contrary, after seeding on VEGF-binding egg-white scaffolds, the same cell population caused aberrantly enlarged vascular structures after 14 d. Collagen-based engineered tissues also induced a safe and efficient angiogenesis in both the patch itself and the underlying myocardium in rat models. These findings open new perspectives on the control and the delivery of proangiogenic stimuli, and are fundamental for the vascularization of engineered tissues/organs. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

78 FR 3081 - Petition for Exemption From the Federal Motor Vehicle Motor Theft Prevention Standard; Toyota

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-15

... receiver, electrical key and an electronic control module (ECM). The conventional key components consist of a transponder key ECU assembly, transponder key coil, security indicator, ignition key and an ECM... certification ECU and steering lock ECU receive confirmation of the valid key, allowing the ECM to start the...

Muscle RANK is a key regulator of Ca2+ storage, SERCA activity, and function of fast-twitch skeletal muscles.

PubMed

Dufresne, Sébastien S; Dumont, Nicolas A; Boulanger-Piette, Antoine; Fajardo, Val A; Gamu, Daniel; Kake-Guena, Sandrine-Aurélie; David, Rares Ovidiu; Bouchard, Patrice; Lavergne, Éliane; Penninger, Josef M; Pape, Paul C; Tupling, A Russell; Frenette, Jérôme

2016-04-15

Receptor-activator of nuclear factor-κB (RANK), its ligand RANKL, and the soluble decoy receptor osteoprotegerin are the key regulators of osteoclast differentiation and bone remodeling. Here we show that RANK is also expressed in fully differentiated myotubes and skeletal muscle. Muscle RANK deletion has inotropic effects in denervated, but not in sham, extensor digitorum longus (EDL) muscles preventing the loss of maximum specific force while promoting muscle atrophy, fatigability, and increased proportion of fast-twitch fibers. In denervated EDL muscles, RANK deletion markedly increased stromal interaction molecule 1 content, a Ca(2+)sensor, and altered activity of the sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) modulating Ca(2+)storage. Muscle RANK deletion had no significant effects on the sham or denervated slow-twitch soleus muscles. These data identify a novel role for RANK as a key regulator of Ca(2+)storage and SERCA activity, ultimately affecting denervated skeletal muscle function. Copyright © 2016 the American Physiological Society.

Muscle RANK is a key regulator of Ca2+ storage, SERCA activity, and function of fast-twitch skeletal muscles

PubMed Central

Dufresne, Sébastien S.; Dumont, Nicolas A.; Boulanger-Piette, Antoine; Fajardo, Val A.; Gamu, Daniel; Kake-Guena, Sandrine-Aurélie; David, Rares Ovidiu; Bouchard, Patrice; Lavergne, Éliane; Penninger, Josef M.; Pape, Paul C.; Tupling, A. Russell

2016-01-01

Receptor-activator of nuclear factor-κB (RANK), its ligand RANKL, and the soluble decoy receptor osteoprotegerin are the key regulators of osteoclast differentiation and bone remodeling. Here we show that RANK is also expressed in fully differentiated myotubes and skeletal muscle. Muscle RANK deletion has inotropic effects in denervated, but not in sham, extensor digitorum longus (EDL) muscles preventing the loss of maximum specific force while promoting muscle atrophy, fatigability, and increased proportion of fast-twitch fibers. In denervated EDL muscles, RANK deletion markedly increased stromal interaction molecule 1 content, a Ca2+ sensor, and altered activity of the sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) modulating Ca2+ storage. Muscle RANK deletion had no significant effects on the sham or denervated slow-twitch soleus muscles. These data identify a novel role for RANK as a key regulator of Ca2+ storage and SERCA activity, ultimately affecting denervated skeletal muscle function. PMID:26825123

Relative phase noise induced impairment in M-ary phase-shift-keying coherent optical communication system using distributed fiber Raman amplifier.

PubMed

Cheng, Jingchi; Tang, Ming; Fu, Songnian; Shum, Perry Ping; Liu, Deming

2013-04-01

We show for the first time, to the best of our knowledge, that, in a coherent communication system that employs a phase-shift-keying signal and Raman amplification, besides the pump relative intensity noise (RIN) transfer to the amplitude, the signal's phase will also be affected by pump RIN through the pump-signal cross-phase modulation. Although the average pump power induced linear phase change can be compensated for by the phase-correction algorithm, a relative phase noise (RPN) parameter has been found to characterize pump RIN induced stochastic phase noise. This extra phase noise brings non-negligible system impairments in terms of the Q-factor penalty. The calculation shows that copumping leads to much more stringent requirements to pump RIN, and relatively larger fiber dispersion helps to suppress the RPN induced impairment. A higher-order phase-shift keying (PSK) signal is less tolerant to noise than a lower-order PSK.

Identification and functional analysis of a core gene module associated with hepatitis C virus-induced human hepatocellular carcinoma progression.

PubMed

Bai, Gaobo; Zheng, Wenling; Ma, Wenli

2018-05-01

Hepatitis C virus (HCV)-induced human hepatocellular carcinoma (HCC) progression may be due to a complex multi-step processes. The developmental mechanism of these processes is worth investigating for the prevention, diagnosis and therapy of HCC. The aim of the present study was to investigate the molecular mechanism underlying the progression of HCV-induced hepatocarcinogenesis. First, the dynamic gene module, consisting of key genes associated with progression between the normal stage and HCC, was identified using the Weighted Gene Co-expression Network Analysis tool from R language. By defining those genes in the module as seeds, the change of co-expression in differentially expressed gene sets in two consecutive stages of pathological progression was examined. Finally, interaction pairs of HCV viral proteins and their directly targeted proteins in the identified module were extracted from the literature and a comprehensive interaction dataset from yeast two-hybrid experiments. By combining the interactions between HCV and their targets, and protein-protein interactions in the Search Tool for the Retrieval of Interacting Genes database (STRING), the HCV-key genes interaction network was constructed and visualized using Cytoscape software 3.2. As a result, a module containing 44 key genes was identified to be associated with HCC progression, due to the dynamic features and functions of those genes in the module. Several important differentially co-expressed gene pairs were identified between non-HCC and HCC stages. In the key genes, cyclin dependent kinase 1 (CDK1), NDC80, cyclin A2 (CCNA2) and rac GTPase activating protein 1 (RACGAP1) were shown to be targeted by the HCV nonstructural proteins NS5A, NS3 and NS5B, respectively. The four genes perform an intermediary role between the HCV viral proteins and the dysfunctional module in the HCV key genes interaction network. These findings provided valuable information for understanding the mechanism of HCV-induced HCC progression and for seeking drug targets for the therapy and prevention of HCC.

Screening key candidate genes and pathways involved in insulinoma by microarray analysis.

PubMed

Zhou, Wuhua; Gong, Li; Li, Xuefeng; Wan, Yunyan; Wang, Xiangfei; Li, Huili; Jiang, Bin

2018-06-01

Insulinoma is a rare type tumor and its genetic features remain largely unknown. This study aimed to search for potential key genes and relevant enriched pathways of insulinoma.The gene expression data from GSE73338 were downloaded from Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified between insulinoma tissues and normal pancreas tissues, followed by pathway enrichment analysis, protein-protein interaction (PPI) network construction, and module analysis. The expressions of candidate key genes were validated by quantitative real-time polymerase chain reaction (RT-PCR) in insulinoma tissues.A total of 1632 DEGs were obtained, including 1117 upregulated genes and 514 downregulated genes. Pathway enrichment results showed that upregulated DEGs were significantly implicated in insulin secretion, and downregulated DEGs were mainly enriched in pancreatic secretion. PPI network analysis revealed 7 hub genes with degrees more than 10, including GCG (glucagon), GCGR (glucagon receptor), PLCB1 (phospholipase C, beta 1), CASR (calcium sensing receptor), F2R (coagulation factor II thrombin receptor), GRM1 (glutamate metabotropic receptor 1), and GRM5 (glutamate metabotropic receptor 5). DEGs involved in the significant modules were enriched in calcium signaling pathway, protein ubiquitination, and platelet degranulation. Quantitative RT-PCR data confirmed that the expression trends of these hub genes were similar to the results of bioinformatic analysis.The present study demonstrated that candidate DEGs and enriched pathways were the potential critical molecule events involved in the development of insulinoma, and these findings were useful for better understanding of insulinoma genesis.

Continuous variable quantum key distribution with a real local oscillator using simultaneous pilot signals.

PubMed

Kleis, Sebastian; Rueckmann, Max; Schaeffer, Christian G

2017-04-15

In this Letter, we propose a novel implementation of continuous variable quantum key distribution that operates with a real local oscillator placed at the receiver site. In addition, pulsing of the continuous wave laser sources is not required, leading to an extraordinary practical and secure setup. It is suitable for arbitrary schemes based on modulated coherent states and heterodyne detection. The shown results include transmission experiments, as well as an excess noise analysis applying a discrete 8-state phase modulation. Achievable key rates under collective attacks are estimated. The results demonstrate the high potential of the approach to achieve high secret key rates at relatively low effort and cost.

Coast Guard Regulations Applied to Offshore Drilling. Module SH-45. Safety and Health.

ERIC Educational Resources Information Center

Center for Occupational Research and Development, Inc., Waco, TX.

This student module on Coast Guard regulations applied to offshore drilling is one of 50 modules concerned with job safety and health. This module presents requirements that apply to the design, construction, equipment, inspection, and operation of offshore drilling units. Following the introduction, 10 objectives (each keyed to a page in the…

A Firefly Learning Module for Environmental Sustainable Development in Samutsongkhram Province, Thailand

ERIC Educational Resources Information Center

To-Im, Jongdee; Klunklueng, Arunwan

2012-01-01

A firefly learning module for the sustainable development was developed for Thai secondary school students in the study province. A deeper connection between environment, social and economic dimensions, which lies at the core of sustainability, became the key issue for this learning module. Also an important dimension of the module was the…

Agricultural Chemical and Pesticide Hazards. Module SH-50. Safety and Health.

ERIC Educational Resources Information Center

Center for Occupational Research and Development, Inc., Waco, TX.

This student module on agricultural chemical and pesticide hazards is one of 50 modules concerned with job safety and health. This module contains information concerning the safe handling, use, and storage of many chemicals that are frequently used in the control of pests. Following the introduction, 10 objectives (each keyed to a page in the…

Recognizing Job Safety Hazards. Module SH-09. Safety and Health.

ERIC Educational Resources Information Center

Center for Occupational Research and Development, Inc., Waco, TX.

This student module on recognizing job safety hazards is one of 50 modules concerned with job safety and health. This module details employee and employer responsibilities in correcting and monitoring safety hazards. Following the introduction, 10 objectives (each keyed to a page in the text) the student is expected to accomplish are listed (e.g.,…

Steel Erection Safety. Module SH-39. Safety and Health.

ERIC Educational Resources Information Center

Center for Occupational Research and Development, Inc., Waco, TX.

This student module on steel erection safety is one of 50 modules concerned with job safety and health. This module identifies typical jobsite hazards encountered by steel erectors, as well as providing safe job procedures for general and specific construction activities. Following the introduction, 11 objectives (each keyed to a page in the text)…

Industrial Sanitation and Personal Facilities. Module SH-13. Safety and Health.

ERIC Educational Resources Information Center

Center for Occupational Research and Development, Inc., Waco, TX.

This student module on industrial sanitation and personal facilities is one of 50 modules concerned with job safety and health. This module deals wth many facets of industrial sanitation and the facilities industries should provide so that proper health procedures may be followed. Following the introduction, 14 objectives (each keyed to a page in…

Personal Protective Equipment. Module SH-12. Safety and Health.

ERIC Educational Resources Information Center

Center for Occupational Research and Development, Inc., Waco, TX.

This student module on personal protective equipment is one of 50 modules concerned with job safety and health. This module explains the need for personal protective equipment, how it is selected, and the way in which the equipment is supposed to work. Following the introduction, 13 objectives (each keyed to a page in the text) the student is…

Fire Prevention and Emergency Procedures. Module SH-05. Safety and Health.

ERIC Educational Resources Information Center

Center for Occupational Research and Development, Inc., Waco, TX.

This student module on fire prevention and emergency procedures is one of 50 modules concerned with job safety and health. This module discusses the chemistry of fire and the methods for extinguishment, along with the steps necessary for emergency action. Following the introduction, 10 objectives (each keyed to a page in the text) the student is…

Fundamentals of Electrical Safety. Module SH-03. Safety and Health.

ERIC Educational Resources Information Center

Center for Occupational Research and Development, Inc., Waco, TX.

This student module on fundamentals of electrical safety is one of 50 modules concerned with job safety and health. This module describes electricity and how it can affect the human body. Following the introduction, nine objectives (each keyed to a page in the text) the student is expected to accomplish are listed (e.g., Name five common…

Walking and Working Surfaces. Module SH-06. Safety and Health.

ERIC Educational Resources Information Center

Center for Occupational Research and Development, Inc., Waco, TX.

This student module on walking and working surfaces is one of 50 modules concerned with job safety and health. This module describes safety requirements for floors, stairways, ladders, and scaffolds, as well as OSHA standards for the construction, use, and maintenance of each of these. Following the introduction, nine objectives (each keyed to a…

Machine and Woodworking Tool Safety. Module SH-24. Safety and Health.

ERIC Educational Resources Information Center

Center for Occupational Research and Development, Inc., Waco, TX.

This student module on machine and woodworking tool safety is one of 50 modules concerned with job safety and health. This module discusses specific practices and precautions concerned with the efficient operation and use of most machine and woodworking tools in use today. Following the introduction, 13 objectives (each keyed to a page in the…

Estrogen receptor 1 (ESR1) regulates VEGFA in adipose tissue.

PubMed

Fatima, L A; Campello, R S; Santos, R de Souza; Freitas, H S; Frank, A P; Machado, U F; Clegg, D J

2017-12-01

Vascular endothelial growth factor A (VEGFA) is a key factor in the regulation of angiogenesis in adipose tissue. Poor vascularization during adipose tissue proliferation causes fibrosis and local inflammation, and is associated with insulin resistance. It is known that 17-beta estradiol (E2) regulates adipose tissue function and VEGFA expression in other tissues; however, the ability of E2 to regulate VEGFA in adipose tissue is currently unknown. In this study, we showed that, in 3T3-L1 cells, E2 and the estrogen receptor 1 (ESR1) agonist PPT induced VEGFA expression, while ESR1 antagonist (MPP), and selective knockdown of ESR1 using siRNA decreased VEGFA and prevented the ability of E2 to modulate its expression. Additionally, we found that E2 and PPT induced the binding of hypoxia inducible factor 1 alpha subunit (HIF1A) in the VEGFA gene promoter. We further found that VEGFA expression was lower in inguinal and gonadal white adipose tissues of ESR1 total body knockout female mice compared to wild type mice. In conclusion, our data provide evidence of an important role for E2/ESR1 in modulating adipose tissue VEGFA, which is potentially important to enhance angiogenesis, reduce inflammation and improve adipose tissue function.

The influence of Argonaute proteins on alternative RNA splicing.

PubMed

Batsché, Eric; Ameyar-Zazoua, Maya

2015-01-01

Alternative splicing of precursor RNAs is an important process in multicellular species because it impacts several aspects of gene expression: from the increase of protein repertoire to the level of expression. A large body of evidences demonstrates that factors regulating chromatin and transcription impact the outcomes of alternative splicing. Argonaute (AGO) proteins were known to play key roles in the regulation of gene expression at the post-transcriptional level. More recently, their role in the nucleus of human somatic cells has emerged. Here, we will discuss some of the nuclear functions of AGO, with special emphasis on alternative splicing. The AGO-mediated modulation of alternative splicing is based on several properties of these proteins: their binding to transcripts on chromatin and their interactions with many proteins, especially histone tail-modifying enzymes, HP1γ and splicing factors. AGO proteins may favor a decrease in the RNA-polymerase II kinetics at actively transcribed genes leading to the modulation of alternative splicing decisions. They could also influence alternative splicing through their interaction with core components of the splicing machinery and several splicing factors. We will discuss the modes of AGO recruitment on chromatin at active genes. We suggest that long intragenic antisense transcripts (lincRNA) might be an important feature of genes containing splicing events regulated by AGO. © 2014 John Wiley & Sons, Ltd.

Biochemical pharmacology of paradoxical sleep

PubMed Central

Gaillard, J. -M.

1983-01-01

1 The role of noradrenergic cells in the regulation of paradoxical sleep is still controversial, and experimental data have given rise to contradictory interpretations. 2 Early investigations focused primarily on chemical neurotransmissions. However, the process of information transmission between cells involves many other factors, and the cell surface is an important site for transduction of messages into modifications of the activity of postsynaptic cells. 3 α-adrenoceptors are believed to play an important role in the control of wakefulness and paradoxical sleep. Experimental evidence suggests that physiological modulation of receptor sensitivity, possibly by specific neuro-modulators, may be a key mechanism in synaptic transmission. 4 In the investigation of the mechanisms involved in paradoxical sleep regulation, lesions of the locus coeruleus have given equivocal results. Collateral inhibition, probably mediated by α2-adrenoceptors, appears to be a powerful mechanism. The exact temporal relationship between noradrenergic cell activation and paradoxical sleep production is not established, but 5-HT appears to be involved. Differences between paradoxical sleep and waking may be related to a physiological modulation of α2-adrenoceptor sensitivity. PMID:6140943

Healthcare students' experiences when integrating e-learning and flipped classroom instructional approaches.

PubMed

Telford, Mark; Senior, Emma

2017-06-08

This article describes the experiences of undergraduate healthcare students taking a module adopting a 'flipped classroom' approach. Evidence suggests that flipped classroom as a pedagogical tool has the potential to enhance student learning and to improve healthcare practice. This innovative approach was implemented within a healthcare curriculum and in a module looking at public health delivered at the beginning of year two of a 3-year programme. The focus of the evaluation study was on the e-learning resources used in the module and the student experiences of these; with a specific aim to evaluate this element of the flipped classroom approach. A mixed-methods approach was adopted and data collected using questionnaires, which were distributed across a whole cohort, and a focus group involving ten participants. Statistical analysis of the data showed the positive student experience of engaging with e-learning. The thematic analysis identified two key themes; factors influencing a positive learning experience and the challenges when developing e-learning within a flipped classroom approach. The study provides guidance for further developments and improvements when developing e-learning as part of the flipped classroom approach.

Performance analysis of cooperative virtual MIMO systems for wireless sensor networks.

PubMed

Rafique, Zimran; Seet, Boon-Chong; Al-Anbuky, Adnan

2013-05-28

Multi-Input Multi-Output (MIMO) techniques can be used to increase the data rate for a given bit error rate (BER) and transmission power. Due to the small form factor, energy and processing constraints of wireless sensor nodes, a cooperative Virtual MIMO as opposed to True MIMO system architecture is considered more feasible for wireless sensor network (WSN) applications. Virtual MIMO with Vertical-Bell Labs Layered Space-Time (V-BLAST) multiplexing architecture has been recently established to enhance WSN performance. In this paper, we further investigate the impact of different modulation techniques, and analyze for the first time, the performance of a cooperative Virtual MIMO system based on V-BLAST architecture with multi-carrier modulation techniques. Through analytical models and simulations using real hardware and environment settings, both communication and processing energy consumptions, BER, spectral efficiency, and total time delay of multiple cooperative nodes each with single antenna are evaluated. The results show that cooperative Virtual-MIMO with Binary Phase Shift Keying-Wavelet based Orthogonal Frequency Division Multiplexing (BPSK-WOFDM) modulation is a promising solution for future high data-rate and energy-efficient WSNs.

Performance Analysis of Cooperative Virtual MIMO Systems for Wireless Sensor Networks

PubMed Central

Rafique, Zimran; Seet, Boon-Chong; Al-Anbuky, Adnan

2013-01-01

Multi-Input Multi-Output (MIMO) techniques can be used to increase the data rate for a given bit error rate (BER) and transmission power. Due to the small form factor, energy and processing constraints of wireless sensor nodes, a cooperative Virtual MIMO as opposed to True MIMO system architecture is considered more feasible for wireless sensor network (WSN) applications. Virtual MIMO with Vertical-Bell Labs Layered Space-Time (V-BLAST) multiplexing architecture has been recently established to enhance WSN performance. In this paper, we further investigate the impact of different modulation techniques, and analyze for the first time, the performance of a cooperative Virtual MIMO system based on V-BLAST architecture with multi-carrier modulation techniques. Through analytical models and simulations using real hardware and environment settings, both communication and processing energy consumptions, BER, spectral efficiency, and total time delay of multiple cooperative nodes each with single antenna are evaluated. The results show that cooperative Virtual-MIMO with Binary Phase Shift Keying-Wavelet based Orthogonal Frequency Division Multiplexing (BPSK-WOFDM) modulation is a promising solution for future high data-rate and energy-efficient WSNs. PMID:23760087

Virtual k -Space Modulation Optical Microscopy

NASA Astrophysics Data System (ADS)

Kuang, Cuifang; Ma, Ye; Zhou, Renjie; Zheng, Guoan; Fang, Yue; Xu, Yingke; Liu, Xu; So, Peter T. C.

2016-07-01

We report a novel superresolution microscopy approach for imaging fluorescence samples. The reported approach, termed virtual k -space modulation optical microscopy (VIKMOM), is able to improve the lateral resolution by a factor of 2, reduce the background level, improve the optical sectioning effect and correct for unknown optical aberrations. In the acquisition process of VIKMOM, we used a scanning confocal microscope setup with a 2D detector array to capture sample information at each scanned x -y position. In the recovery process of VIKMOM, we first modulated the captured data by virtual k -space coding and then employed a ptychography-inspired procedure to recover the sample information and correct for unknown optical aberrations. We demonstrated the performance of the reported approach by imaging fluorescent beads, fixed bovine pulmonary artery endothelial (BPAE) cells, and living human astrocytes (HA). As the VIKMOM approach is fully compatible with conventional confocal microscope setups, it may provide a turn-key solution for imaging biological samples with ˜100 nm lateral resolution, in two or three dimensions, with improved optical sectioning capabilities and aberration correcting.

Amplitude-Phase Modulation, Topological Horseshoe and Scaling Attractor of a Dynamical System

NASA Astrophysics Data System (ADS)

Li, Chun-Lai; Li, Wen; Zhang, Jing; Xie, Yuan-Xi; Zhao, Yi-Bo

2016-09-01

A three-dimensional autonomous chaotic system is discussed in this paper. Some basic dynamical properties of the system, including phase portrait, Poincaré map, power spectrum, Kaplan-Yorke dimension, Lyapunov exponent spectra, signal amplitude and topological horseshoe are studied theoretically and numerically. The main finding by analysis is that the signal amplitude can be modulated via controlling the coefficients of the linear term, cross-product term and squared term simultaneously or respectively, and the phase of x3 can be modulated by the product of the coefficients of the linear term and cross-product term. Furthermore, scaling chaotic attractors of this system are achieved by modified projective synchronization with an optimization-based linear coupling method, which is safer for secure communications than the existed synchronization scheme since the scaling factors can be regarded as the security encoding key. Supported by Hunan Provincial Natural Science Foundation of China under Grant No. 2016JJ4036, University Natural Science Foundation of Jiangsu Province under Grant No. 14KJB120007 and the National Natural Science Foundation of China under Grant Nos. 11504176 and 11602084

GAP-43 is essential for the neurotrophic effects of BDNF and positive AMPA receptor modulator S18986.

PubMed

Gupta, S K; Mishra, R; Kusum, S; Spedding, M; Meiri, K F; Gressens, P; Mani, S

2009-04-01

Positive alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor modulators include benzamide compounds that allosterically modulate AMPA glutamate receptors. These small molecules that cross the blood-brain barrier have been shown to act as a neuroprotectant by increasing the levels of endogenous brain-derived neurotrophic factor (BDNF). Positive AMPA receptor modulators have also been shown to increase the levels of growth-associated protein-43 (GAP-43). GAP-43 plays a major role in many aspects of neuronal function in vertebrates. The goal of this study was to determine whether GAP-43 was important in mediating the actions of positive AMPA receptor modulator (S18986) and BDNF. Using cortical cultures from GAP-43 knockout and control mice, we show that (1) GAP-43 is upregulated in response to S18986 and BDNF in control cultures; (2) this upregulation of GAP-43 is essential for mediating the neuroprotective effects of S18986 and BDNF; (3) administration of S18986 and BDNF leads to an increase in the expression of the glutamate transporters GLT-1 and GLAST that are key to limiting excitotoxic cell death and this increase in GLT-1 and GLAST expression is completely blocked in the absence of GAP-43. Taken together this study concludes that GAP-43 is an important mediator of the neurotrophic effects of S18986 and BDNF on neuronal survival and plasticity, and is essential for the success of positive AMPA receptor modulator-BDNF-based neurotrophin therapy.

Linear Equations. [Student Worksheets for Vocational Agricultural Courses].

ERIC Educational Resources Information Center

Jewell, Larry R.

This learning module provides students with practice in applying algebraic operations to vocational agriculture. The module consists of unit objectives, definitions, information, problems to solve, worksheets suitable for various levels of vocational agriculture instruction, and answer keys for the problems and worksheets. This module, which…

Common Fractions. [Student Worksheets for Vocational Agricultural Courses].

ERIC Educational Resources Information Center

Jewell, Larry R.

This learning module provides students with practice in applying mathematical operations to vocational agriculture. The module consists of unit objectives, definitions, information, problems to solve, worksheets suitable for various levels of vocational agriculture instruction, and answer keys for the problems and worksheets. This module, which…

Evidence of variable bacterial colonization on coloured elastomeric ligatures during orthodontic treatment: An intermodular comparative study.

PubMed

Sharma, Ravish; Sharma, Kavita; Sawhney, Rajesh

2018-03-01

Besides, other factors, the choice of materials used as orthodontic ligatures could be one of the many tools to counter the effects of microbial adhesion, that culminates into dental ailments. Therefore, we assessed bacterial adhesion on elastomeric ligatures with special reference to coloured elastomeric rings during orthodontic treatment. A split mouth study, involving 240 samples of different elastomeric ligatures from forty orthodontic patients possessing good oral hygiene was carried out. The archwire was ligated to the brackets on both arches with elastomeric rings (superslick, clear transparent , blue and pink) at predetermined quadrants. After six weeks, ligatures from second premolars were removed and processed for bacterial enumeration using standard techniques. Bacterial counts were also determined for stimulated saliva samples taken at 0 and 6 weeks. A statistically significant difference in bacterial counts was obtained amongst different elastomeric modules used. Maximum bacterial counts were found on conventional pigmented elastomeric modules, followed by Superslick module and clear module. More number of bacteria associated with the conventional pink as compared to the conventional blue pigmented modules, however it was not statistically significant. The three bacterial genera Streptococcus Staphylococcus and Aerobic Lactobacilli adhered to elastomeric modules in following predominant pattern i.e. Conventional pink>Conventional Blue>Superslick>Clear. The studies evidenced colour and material dependent bacterial colonization on orthodontic modules and could be an indicator of bacterial biofilm forming potential based on surface chemistries and a clinically efficacious tool to redesign conventional and modified elastomeric rings as orthodontic ligation accessories. Key words: Bacterial colonization, biofilm, coloured elastomers, orthodontic ligatures.

Disulfide bridge regulates ligand-binding site selectivity in liver bile acid-binding proteins.

PubMed

Cogliati, Clelia; Tomaselli, Simona; Assfalg, Michael; Pedò, Massimo; Ferranti, Pasquale; Zetta, Lucia; Molinari, Henriette; Ragona, Laura

2009-10-01

Bile acid-binding proteins (BABPs) are cytosolic lipid chaperones that play central roles in driving bile flow, as well as in the adaptation to various pathological conditions, contributing to the maintenance of bile acid homeostasis and functional distribution within the cell. Understanding the mode of binding of bile acids with their cytoplasmic transporters is a key issue in providing a model for the mechanism of their transfer from the cytoplasm to the nucleus, for delivery to nuclear receptors. A number of factors have been shown to modulate bile salt selectivity, stoichiometry, and affinity of binding to BABPs, e.g. chemistry of the ligand, protein plasticity and, possibly, the formation of disulfide bridges. Here, the effects of the presence of a naturally occurring disulfide bridge on liver BABP ligand-binding properties and backbone dynamics have been investigated by NMR. Interestingly, the disulfide bridge does not modify the protein-binding stoichiometry, but has a key role in modulating recognition at both sites, inducing site selectivity for glycocholic and glycochenodeoxycholic acid. Protein conformational changes following the introduction of a disulfide bridge are small and located around the inner binding site, whereas significant changes in backbone motions are observed for several residues distributed over the entire protein, both in the apo form and in the holo form. Site selectivity appears, therefore, to be dependent on protein mobility rather than being governed by steric factors. The detected properties further establish a parallelism with the behaviour of human ileal BABP, substantiating the proposal that BABPs have parallel functions in hepatocytes and enterocytes.

An Unbiased Systems Genetics Approach to Mapping Genetic Loci Modulating Susceptibility to Severe Streptococcal Sepsis

PubMed Central

Abdeltawab, Nourtan F.; Aziz, Ramy K.; Kansal, Rita; Rowe, Sarah L.; Su, Yin; Gardner, Lidia; Brannen, Charity; Nooh, Mohammed M.; Attia, Ramy R.; Abdelsamed, Hossam A.; Taylor, William L.; Lu, Lu; Williams, Robert W.; Kotb, Malak

2008-01-01

Striking individual differences in severity of group A streptococcal (GAS) sepsis have been noted, even among patients infected with the same bacterial strain. We had provided evidence that HLA class II allelic variation contributes significantly to differences in systemic disease severity by modulating host responses to streptococcal superantigens. Inasmuch as the bacteria produce additional virulence factors that participate in the pathogenesis of this complex disease, we sought to identify additional gene networks modulating GAS sepsis. Accordingly, we applied a systems genetics approach using a panel of advanced recombinant inbred mice. By analyzing disease phenotypes in the context of mice genotypes we identified a highly significant quantitative trait locus (QTL) on Chromosome 2 between 22 and 34 Mb that strongly predicts disease severity, accounting for 25%–30% of variance. This QTL harbors several polymorphic genes known to regulate immune responses to bacterial infections. We evaluated candidate genes within this QTL using multiple parameters that included linkage, gene ontology, variation in gene expression, cocitation networks, and biological relevance, and identified interleukin1 alpha and prostaglandin E synthases pathways as key networks involved in modulating GAS sepsis severity. The association of GAS sepsis with multiple pathways underscores the complexity of traits modulating GAS sepsis and provides a powerful approach for analyzing interactive traits affecting outcomes of other infectious diseases. PMID:18421376

On the power spectral density of quadrature modulated signals. [satellite communication

NASA Technical Reports Server (NTRS)

Yan, T. Y.

1981-01-01

The conventional (no-offset) quadriphase modulation technique suffers from the fact that hardlimiting will restore the frequency sidelobes removed by proper filtering. Thus, offset keyed quadriphase modulation techniques are often proposed for satellite communication with bandpass hardlimiting. A unified theory is developed which is capable of describing the power spectral density before and after the hardlimiting process. Using the in-phase and the quadrature phase channel with arbitrary pulse shaping, analytical results are established for generalized quadriphase modulation. In particular MSK, OPSK or the recently introduced overlapped raised cosine keying all fall into this general category. It is shown that for a linear communication channel, the power spectral density of the modulated signal remains unchanged regardless of the offset delay. Furthermore, if the in phase and the quadrature phase channel have identical pulse shapes without offset, the spectrum after bandpass hardlimiting will be identical to that of the conventional QPSK modulation. Numerical examples are given for various modulation techniques. A case of different pulse shapes in the in phase and the quadrature phase channel is also considered.

Aerodynamics of the advanced launch system (ALS) propulsion and avionics (P/A) module

NASA Technical Reports Server (NTRS)

Ferguson, Stan; Savage, Dick

1992-01-01

This paper discusses the design and testing of candidate Advanced Launch System (ALS) Propulsion and Avionics (P/A) Module configurations. The P/A Module is a key element of future launch systems because it is essential to the recovery and reuse of high-value propulsion and avionics hardware. The ALS approach involves landing of first stage (booster) and/or second stage (core) P/A modules near the launch site to minimize logistics and refurbishment cost. The key issue addressed herein is the aerodynamic design of the P/A module, including the stability characteristics and the lift-to-drag (L/D) performance required to achieve the necessary landing guidance accuracy. The reference P/A module configuration was found to be statically stable for the desired flight regime, to provide adequate L/D for targeting, and to have effective modulation of the L/D performance using a body flap. The hypersonic aerodynamic trends for nose corner radius, boattail angle and body flap deflections were consistent with pretest predictions. However, the levels for the L/D and axial force for hypersonic Mach numbers were overpredicted by impact theories.

Programmable rate modem utilizing digital signal processing techniques

NASA Technical Reports Server (NTRS)

Naveh, Arad

1992-01-01

The need for a Programmable Rate Digital Satellite Modem capable of supporting both burst and continuous transmission modes with either Binary Phase Shift Keying (BPSK) or Quadrature Phase Shift Keying (QPSK) modulation is discussed. The preferred implementation technique is an all digital one which utilizes as much digital signal processing (DSP) as possible. The design trade-offs in each portion of the modulator and demodulator subsystem are outlined.

Continuous variable quantum key distribution with modulated entangled states.

PubMed

Madsen, Lars S; Usenko, Vladyslav C; Lassen, Mikael; Filip, Radim; Andersen, Ulrik L

2012-01-01

Quantum key distribution enables two remote parties to grow a shared key, which they can use for unconditionally secure communication over a certain distance. The maximal distance depends on the loss and the excess noise of the connecting quantum channel. Several quantum key distribution schemes based on coherent states and continuous variable measurements are resilient to high loss in the channel, but are strongly affected by small amounts of channel excess noise. Here we propose and experimentally address a continuous variable quantum key distribution protocol that uses modulated fragile entangled states of light to greatly enhance the robustness to channel noise. We experimentally demonstrate that the resulting quantum key distribution protocol can tolerate more noise than the benchmark set by the ideal continuous variable coherent state protocol. Our scheme represents a very promising avenue for extending the distance for which secure communication is possible.

Concatenated Coding Using Trellis-Coded Modulation

NASA Technical Reports Server (NTRS)

Thompson, Michael W.

1997-01-01

In the late seventies and early eighties a technique known as Trellis Coded Modulation (TCM) was developed for providing spectrally efficient error correction coding. Instead of adding redundant information in the form of parity bits, redundancy is added at the modulation stage thereby increasing bandwidth efficiency. A digital communications system can be designed to use bandwidth-efficient multilevel/phase modulation such as Amplitude Shift Keying (ASK), Phase Shift Keying (PSK), Differential Phase Shift Keying (DPSK) or Quadrature Amplitude Modulation (QAM). Performance gain can be achieved by increasing the number of signals over the corresponding uncoded system to compensate for the redundancy introduced by the code. A considerable amount of research and development has been devoted toward developing good TCM codes for severely bandlimited applications. More recently, the use of TCM for satellite and deep space communications applications has received increased attention. This report describes the general approach of using a concatenated coding scheme that features TCM and RS coding. Results have indicated that substantial (6-10 dB) performance gains can be achieved with this approach with comparatively little bandwidth expansion. Since all of the bandwidth expansion is due to the RS code we see that TCM based concatenated coding results in roughly 10-50% bandwidth expansion compared to 70-150% expansion for similar concatenated scheme which use convolution code. We stress that combined coding and modulation optimization is important for achieving performance gains while maintaining spectral efficiency.

Piezoelectric modulation of surface voltage in GaN and AlGaN/GaN: charge screening effects and 2DEG

NASA Astrophysics Data System (ADS)

Wilson, Marshall; Schrayer, Bret; Savtchouk, Alexandre; Hillard, Bob; Lagowski, Jacek

2017-02-01

Surface voltage response to pulses of piezoelectric polarization is measured with a Kelvin-probe providing a unique means for investigation of the dynamics of polarization induced sheet charge and 2DEG. Combined with biasing of the surface with a corona-deposited charge from accumulation to deep depletion and corresponding non-contact C-V type characterization, the technique identifies surface band bending and interface traps as key factors that affect the magnitude and time decay of piezoelectric polarization. For 2DEG structures, surface potential pinning is observed when the 2DEG is fully populated. Pinning is released by negative corona charging to fully deplete the 2DEG. These results are consistent with the role of surface states. Presently demonstrated polarization modulation and wafer scale measurements shall impact the in-depth characterization and fundamental understanding of AlGaN/GaN 2DEG structures.

White LEDs and modules in chip-on-board technology for general lighting

NASA Astrophysics Data System (ADS)

Hartmann, Paul; Wenzl, Franz P.; Sommer, Christian; Pachler, Peter; Hoschopf, Hans; Schweighart, Marko; Hartmann, Martin; Kuna, Ladislav; Jakopic, Georg; Leising, Guenther; Tasch, Stefan

2006-08-01

At present, light-emitting diode (LED) modules in various shapes are developed and designed for the general lighting, advertisement, emergency lighting, design and architectural markets. To compete with and to surpass the performance of traditional lighting systems, enhancement of Lumen output and the white light quality as well as the thermal management and the luminary integration are key factors for success. Regarding these issues, white LEDs based on the chip-on-board (COB) technology show pronounced advantages. State-of-the-art LEDs exploiting this technology are now ready to enter the general lighting segments. We introduce and discuss the specific properties of the Tridonic COB technology dedicated for general lighting. This technology, in combination with a comprehensive set of tools to improve and to enhance the Lumen output and the white light quality, including optical simulation, is the scaffolding for the application of white LEDs in emerging areas, for which an outlook will be given.

The Interplay between Magnesium and Testosterone in Modulating Physical Function in Men

PubMed Central

Maggio, Marcello; De Vita, Francesca; Lauretani, Fulvio; Meschi, Tiziana; Ticinesi, Andrea; Dominguez, Ligia J.; Barbagallo, Mario; Dall'Aglio, Elisabetta; Ceda, Gian Paolo

2014-01-01

The role of nutritional status as key factor of successful aging is very well recognized. Among the different mechanisms by which nutrients may exert their beneficial effects is the modulation of the hormonal anabolic milieu, which is significantly reduced with aging. Undernutrition and anabolic hormonal deficiency frequently coexist in older individuals determining an increased risk of mobility impairment and other adverse outcomes. Mineral assessment has received attention as an important determinant of physical performance. In particular, there is evidence that magnesium exerts a positive influence on anabolic hormonal status, including Testosterone, in men. In this review we summarize data from observational and intervention studies about the role of magnesium in Testosterone bioactivity and the potential underlying mechanisms of this relationship in male subjects. If larger studies will confirm these pivotal data, the combination of hormonal and mineral replacements might be adopted to prevent or delay the onset of disability in the elderly. PMID:24723948

The Interplay between Magnesium and Testosterone in Modulating Physical Function in Men.

PubMed

Maggio, Marcello; De Vita, Francesca; Lauretani, Fulvio; Nouvenne, Antonio; Meschi, Tiziana; Ticinesi, Andrea; Dominguez, Ligia J; Barbagallo, Mario; Dall'aglio, Elisabetta; Ceda, Gian Paolo

2014-01-01

The role of nutritional status as key factor of successful aging is very well recognized. Among the different mechanisms by which nutrients may exert their beneficial effects is the modulation of the hormonal anabolic milieu, which is significantly reduced with aging. Undernutrition and anabolic hormonal deficiency frequently coexist in older individuals determining an increased risk of mobility impairment and other adverse outcomes. Mineral assessment has received attention as an important determinant of physical performance. In particular, there is evidence that magnesium exerts a positive influence on anabolic hormonal status, including Testosterone, in men. In this review we summarize data from observational and intervention studies about the role of magnesium in Testosterone bioactivity and the potential underlying mechanisms of this relationship in male subjects. If larger studies will confirm these pivotal data, the combination of hormonal and mineral replacements might be adopted to prevent or delay the onset of disability in the elderly.

Defense system shortcuts and limits of scope.

PubMed

Rewald, E; Francischetti, M M

2000-10-01

Defense, as a key factor of life, shares the biological tendencies of simplicity and energy saving. We propose that, like the mind, defense tends to rely on shortcuts via immune memes. Also, response repetition may induce the formation of virtual 'modules' [toolkits] to simplify and perfect performance. Engaged modules may expand by proliferating or by capturing immune components from the 'dormant' and even perhaps from active ones. With regard to recovery and/or survival, complexity of the integrated defense system (IDS) (1) requires to be inside of what we call the 'functional window'. In contrast to the physiological and common disease repair, energy is squandered when IDS perceives real danger. Our concern is the uncertain transition to conditions that do not fit into the IDS routine and, even worse, that are outside the functional window where the system is lacking. Copyright 2000 Harcourt Publishers Ltd.

NEU3 sialidase strictly modulates GM3 levels in skeletal myoblasts C2C12 thus favoring their differentiation and protecting them from apoptosis.

PubMed

Anastasia, Luigi; Papini, Nadia; Colazzo, Francesca; Palazzolo, Giacomo; Tringali, Cristina; Dileo, Loredana; Piccoli, Marco; Conforti, Erika; Sitzia, Clementina; Monti, Eugenio; Sampaolesi, Maurilio; Tettamanti, Guido; Venerando, Bruno

2008-12-26

Membrane-bound sialidase NEU3, often referred to as the "ganglioside sialidase," has a critical regulatory function on the sialoglycosphingolipid pattern of the cell membrane, with an anti-apoptotic function, especially in cancer cells. Although other sialidases have been shown to be involved in skeletal muscle differentiation, the role of NEU3 had yet to be disclosed. Herein we report that NEU3 plays a key role in skeletal muscle differentiation by strictly modulating the ganglioside content of adjacent cells, with special regard to GM3. Induced down-regulation of NEU3 in murine C2C12 myoblasts, even when partial, totally inhibits their capability to differentiate by increasing the GM3 level above a critical point, which causes epidermal growth factor receptor inhibition (and ultimately its down-regulation) and an higher responsiveness of myoblasts to the apoptotic stimuli.

Light-induced effects-impacts to module performance measurements and reliability testing: An overview

NASA Technical Reports Server (NTRS)

Wronski, C. R.

1985-01-01

The stability of solar cells is a key factor in determining the reliability of photovoltaic modules and is of great interest in the case of solar cells having a new technology which has not yet been fully developed. In particular this question arises with hydrogenated amorphous silicon (a-Si) solar cells because a-Si exhibits reversible light induced changes in its electronic properties, commonly referred to as the Staebler-Wronski effect (SWE). Continuous progress is being made in the peak conversion efficiencies of a-Si solar cells and efficiencies in excess of 11% have been achieved. However, stability is still a problem. ARCO Solar reports results on solar cells which, after over a year's exposure to sunlight, under open circuit conditions, still have about 7% conversion efficiency. Other results show a region of fast degradation for about a month, after which the degradation diminishes rapidly.

miR-Let7A Modulates Autophagy Induction in LPS-Activated Microglia

PubMed Central

Song, Juhyun; Oh, Yumi

2015-01-01

Microglia regulate the secretion of various immunomediators in central nervous system diseases. Microglial autophagy is the crucial process for cell's survival and cytokine productions. Recent studies have reported that several microRNAs are involved in the autophagy system. miR-Let7A is such a microRNA that plays a role in various inflammation responses, and is magnified as a key modulator particularly in the autophagy system. In present study, we investigated whether miR-Let7A is involved in autophagy in activating microglia. Overexpression of miR-Let7A in LPS-stimulated BV2 microglial cells promoted the induction of the autophagy related factors such as LC3II, Beclin1, and ATG3. Our results suggest a potential role of miR-Let7A in the autophagy process of microglia during CNS inflammation. PMID:26113790

Modulation of Kv7 channels and excitability in the brain.

PubMed

Greene, Derek L; Hoshi, Naoto

2017-02-01

Neuronal Kv7 channels underlie a voltage-gated non-inactivating potassium current known as the M-current. Due to its particular characteristics, Kv7 channels show pronounced control over the excitability of neurons. We will discuss various factors that have been shown to drastically alter the activity of this channel such as protein and phospholipid interactions, phosphorylation, calcium, and numerous neurotransmitters. Kv7 channels locate to key areas for the control of action potential initiation and propagation. Moreover, we will explore the dynamic surface expression of the channel modulated by neurotransmitters and neural activity. We will also focus on known principle functions of neural Kv7 channels: control of resting membrane potential and spiking threshold, setting the firing frequency, afterhyperpolarization after burst firing, theta resonance, and transient hyperexcitability from neurotransmitter-induced suppression of the M-current. Finally, we will discuss the contribution of altered Kv7 activity to pathologies such as epilepsy and cognitive deficits.

Modulation of Kv7 channels and excitability in the brain

PubMed Central

Greene, Derek L; Hoshi, Naoto

2016-01-01

Neuronal Kv7 channels underlie a voltage-gated non-inactivating potassium current known as the M-current. Due to its particular characteristics, Kv7 channels show pronounced control over the excitability of neurons. We will discuss various factors that have been shown to drastically alter the activity of this channel such as protein and phospholipid interactions, phosphorylation, calcium, and numerous neurotransmitters. Kv7 channels locate to key areas for the control of action potential initiation and propagation. Moreover, we will explore the dynamic surface expression of the channel modulated by neurotransmitters and neural activity. We will also focus on known principle functions of neural Kv7 channels: control of resting membrane potential and spiking threshold, setting the firing frequency, afterhyperpolarization after burst firing, theta resonance, and transient hyperexcitability from neurotransmitter-induced suppression of the M-current. Finally, we will discuss the contribution of altered Kv7 activity to pathologies such as epilepsy and cognitive deficits. PMID:27645822

47 CFR 97.307 - Emission standards.

Code of Federal Regulations, 2013 CFR

2013-10-01

...-modulated emission may have a modulation index greater than 1 at the highest modulation frequency. (2) No..., or for frequency-shift keying, the frequency shift between mark and space must not exceed 1 kHz. (5... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES AMATEUR RADIO...

47 CFR 97.307 - Emission standards.

Code of Federal Regulations, 2011 CFR

2011-10-01

...-modulated emission may have a modulation index greater than 1 at the highest modulation frequency. (2) No..., or for frequency-shift keying, the frequency shift between mark and space must not exceed 1 kHz. (5... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES AMATEUR RADIO...

47 CFR 97.307 - Emission standards.

Code of Federal Regulations, 2012 CFR

2012-10-01

...-modulated emission may have a modulation index greater than 1 at the highest modulation frequency. (2) No..., or for frequency-shift keying, the frequency shift between mark and space must not exceed 1 kHz. (5... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES AMATEUR RADIO...

47 CFR 97.307 - Emission standards.

Code of Federal Regulations, 2014 CFR

2014-10-01

...-modulated emission may have a modulation index greater than 1 at the highest modulation frequency. (2) No..., or for frequency-shift keying, the frequency shift between mark and space must not exceed 1 kHz. (5... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES AMATEUR RADIO...

47 CFR 97.307 - Emission standards.

Code of Federal Regulations, 2010 CFR

2010-10-01

...-modulated emission may have a modulation index greater than 1 at the highest modulation frequency. (2) No..., or for frequency-shift keying, the frequency shift between mark and space must not exceed 1 kHz. (5... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES AMATEUR RADIO...

The Metric System. [Student Worksheets for Vocational Agricultural Courses].

ERIC Educational Resources Information Center

Jewell, Larry R.

This learning module provides students with practice in applying mathematical operations to vocational agriculture. The module consists of unit objectives, definitions, information, problems to solve, worksheets suitable for various levels of vocational agriculture instruction, and answer keys for the problems and worksheets. This module, which…

An Inexpensive Instrument for Demonstrating Automated Chemical Analysis.

ERIC Educational Resources Information Center

Paselk, Richard A.

1982-01-01

A technician auto analyzer (consisting of six modules: sampler, multichannel peristaltic pump, dialyser, heating/incubation bath, colorimeter, and recorder) was modified by using key modules and substituting standard equipment for others; spectronic 20 with homemade flow cell for colorimeter module. Descriptions and diagrams of the apparatus are…

Critical Role of Transforming Growth Factor Beta in Different Phases of Wound Healing

PubMed Central

Pakyari, Mohammadreza; Farrokhi, Ali; Maharlooei, Mohsen Khosravi; Ghahary, Aziz

2013-01-01

Significance This review highlights the critical role of transforming growth factor beta (TGF-β)1–3 within different phases of wound healing, in particular, late-stage wound healing. It is also very important to identify the TGF-β1–controlling factors involved in slowing down the healing process upon wound epithelialization. Recent Advances TGF-β1, as a growth factor, is a known proponent of dermal fibrosis. Several strategies to modulate or regulate TGF's actions have been thoroughly investigated in an effort to create successful therapies. This study reviews current discourse regarding the many roles of TGF-β1 in wound healing by modulating infiltrated immune cells and the extracellular matrix. Critical Issues It is well established that TGF-β1 functions as a wound-healing promoting factor, and thereby if in excess it may lead to overhealing outcomes, such as hypertrophic scarring and keloid. Thus, the regulation of TGF-β1 in the later stages of the healing process remains as critical issue of which to better understand. Future Directions One hypothesis is that cell communication is the key to regulate later stages of wound healing. To elucidate the role of keratinocyte/fibroblast cross talk in controlling the later stages of wound healing we need to: (1) identify those keratinocyte-released factors which would function as wound-healing stop signals, (2) evaluate the functionality of these factors in controlling the outcome of the healing process, and (3) formulate topical vehicles for these antifibrogenic factors to improve or even prevent the development of hypertrophic scarring and keloids as a result of deep trauma, burn injuries, and any type of surgical incision. PMID:24527344

A Western diet ecological module identified from the 'humanized' mouse microbiota predicts diet in adults and formula feeding in children.

PubMed

Siddharth, Jay; Holway, Nicholas; Parkinson, Scott J

2013-01-01

The interplay between diet and the microbiota has been implicated in the growing frequency of chronic diseases associated with the Western lifestyle. However, the complexity and variability of microbial ecology in humans and preclinical models has hampered identification of the molecular mechanisms underlying the association of the microbiota in this context. We sought to address two key questions. Can the microbial ecology of preclinical models predict human populations? And can we identify underlying principles that surpass the plasticity of microbial ecology in humans? To do this, we focused our study on diet; perhaps the most influential factor determining the composition of the gut microbiota. Beginning with a study in 'humanized' mice we identified an interactive module of 9 genera allied with Western diet intake. This module was applied to a controlled dietary study in humans. The abundance of the Western ecological module correctly predicted the dietary intake of 19/21 top and 21/21 of the bottom quartile samples inclusive of all 5 Western and 'low-fat' diet subjects, respectively. In 98 volunteers the abundance of the Western module correlated appropriately with dietary intake of saturated fatty acids, fat-soluble vitamins and fiber. Furthermore, it correlated with the geographical location and dietary habits of healthy adults from the Western, developing and third world. The module was also coupled to dietary intake in children (and piglets) correlating with formula (vs breast) feeding and associated with a precipitous development of the ecological module in young children. Our study provides a conceptual platform to translate microbial ecology from preclinical models to humans and identifies an ecological network module underlying the association of the gut microbiota with Western dietary habits.

A Western Diet Ecological Module Identified from the ‘Humanized’ Mouse Microbiota Predicts Diet in Adults and Formula Feeding in Children

PubMed Central

Siddharth, Jay; Holway, Nicholas; Parkinson, Scott J.

2013-01-01

The interplay between diet and the microbiota has been implicated in the growing frequency of chronic diseases associated with the Western lifestyle. However, the complexity and variability of microbial ecology in humans and preclinical models has hampered identification of the molecular mechanisms underlying the association of the microbiota in this context. We sought to address two key questions. Can the microbial ecology of preclinical models predict human populations? And can we identify underlying principles that surpass the plasticity of microbial ecology in humans? To do this, we focused our study on diet; perhaps the most influential factor determining the composition of the gut microbiota. Beginning with a study in ‘humanized’ mice we identified an interactive module of 9 genera allied with Western diet intake. This module was applied to a controlled dietary study in humans. The abundance of the Western ecological module correctly predicted the dietary intake of 19/21 top and 21/21 of the bottom quartile samples inclusive of all 5 Western and ‘low-fat’ diet subjects, respectively. In 98 volunteers the abundance of the Western module correlated appropriately with dietary intake of saturated fatty acids, fat-soluble vitamins and fiber. Furthermore, it correlated with the geographical location and dietary habits of healthy adults from the Western, developing and third world. The module was also coupled to dietary intake in children (and piglets) correlating with formula (vs breast) feeding and associated with a precipitous development of the ecological module in young children. Our study provides a conceptual platform to translate microbial ecology from preclinical models to humans and identifies an ecological network module underlying the association of the gut microbiota with Western dietary habits. PMID:24391809

Mechanized Off-Road Equipment Safety. Module SH-17. Safety and Health.

ERIC Educational Resources Information Center

Center for Occupational Research and Development, Inc., Waco, TX.

This student module on mechanized off-road equipment safety is one of 50 modules concerned with job safety and health. This module aims to encourage the development of a positive approach to safety as it concerns the heavy equipment industry. Following the introduction, 15 objectives (each keyed to a page in the text) the student is expected to…

Safety for Compressed Gas and Air Equipment. Module SH-26. Safety and Health.

ERIC Educational Resources Information Center

Center for Occupational Research and Development, Inc., Waco, TX.

This student module on safety for compressed gas and air equipment is one of 50 modules concerned with job safety and health. This module presents technical data about commonly used gases and stresses the procedures necessary for safe handling of compressed gases. Following the introduction, 14 objectives (each keyed to a page in the text) the…

Safe Handling and Use of Flammable and Combustible Materials. Module SH-30. Safety and Health.

ERIC Educational Resources Information Center

Center for Occupational Research and Development, Inc., Waco, TX.

This student module on safe handling and use of flammable and combustible materials is one of 50 modules concerned with job safety and health. This module introduces the student to the hazards of flammable and combustible materials and the measures necessary to control those hazards. Following the introduction, 14 objectives (each keyed to a page…

Nuclear Technology. Course 31: Quality Assurance Practices. Module 31-7, Auditing for Quality Assurance.

ERIC Educational Resources Information Center

Pritchard, Jim; Espy, John

This seventh in a series of eight modules for a course titled Quality Assurance Practices describes the key features of an audit system and offers practice in carrying out tasks of the technicians. The module follows a typical format that includes the following sections: (1) introduction, (2) module prerequisites, (3) objectives, (4) notes to…

Safety with Hand and Portable Power Tools. Module SH-14. Safety and Health.

ERIC Educational Resources Information Center

Center for Occupational Research and Development, Inc., Waco, TX.

This student module on safety with hand and portable power tools is one of 50 modules concerned with job safety and health. This module discusses the proper use and maintenance of tools, including the need for protective equipment for the worker. Following the introduction, 16 objectives (each keyed to a page in the text) the student is expected…

Working Safety in Confined Spaces. Module SH-32. Safety and Health.

ERIC Educational Resources Information Center

Center for Occupational Research and Development, Inc., Waco, TX.

This student module on working safely in confined spaces in one of 50 modules concerned with job safety and health. This module explains how to recognize potential hazards in confined spaces, how to deal with these hazards, and how planning can prevent accidents. Following the introduction, 17 objectives (each keyed to a page in the text) the…

Insight into the Intermolecular Recognition Mechanism between Keap1 and IKKβ Combining Homology Modelling, Protein-Protein Docking, Molecular Dynamics Simulations and Virtual Alanine Mutation

PubMed Central

Jiang, Zheng-Yu; Chu, Hong-Xi; Xi, Mei-Yang; Yang, Ting-Ting; Jia, Jian-Min; Huang, Jing-Jie; Guo, Xiao-Ke; Zhang, Xiao-Jin; You, Qi-Dong; Sun, Hao-Peng

2013-01-01

Degradation of certain proteins through the ubiquitin-proteasome pathway is a common strategy taken by the key modulators responsible for stress responses. Kelch-like ECH-associated protein-1(Keap1), a substrate adaptor component of the Cullin3 (Cul3)-based ubiquitin E3 ligase complex, mediates the ubiquitination of two key modulators, NF-E2-related factor 2 (Nrf2) and IκB kinase β (IKKβ), which are involved in the redox control of gene transcription. However, compared to the Keap1-Nrf2 protein-protein interaction (PPI), the intermolecular recognition mechanism of Keap1 and IKKβ has been poorly investigated. In order to explore the binding pattern between Keap1 and IKKβ, the PPI model of Keap1 and IKKβ was investigated. The structure of human IKKβ was constructed by means of the homology modeling method and using reported crystal structure of Xenopus laevis IKKβ as the template. A protein-protein docking method was applied to develop the Keap1-IKKβ complex model. After the refinement and visual analysis of docked proteins, the chosen pose was further optimized through molecular dynamics simulations. The resulting structure was utilized to conduct the virtual alanine mutation for the exploration of hot-spots significant for the intermolecular interaction. Overall, our results provided structural insights into the PPI model of Keap1-IKKβ and suggest that the substrate specificity of Keap1 depend on the interaction with the key tyrosines, namely Tyr525, Tyr574 and Tyr334. The study presented in the current project may be useful to design molecules that selectively modulate Keap1. The selective recognition mechanism of Keap1 with IKKβ or Nrf2 will be helpful to further know the crosstalk between NF-κB and Nrf2 signaling. PMID:24066166

Insight into the intermolecular recognition mechanism between Keap1 and IKKβ combining homology modelling, protein-protein docking, molecular dynamics simulations and virtual alanine mutation.

PubMed

Jiang, Zheng-Yu; Chu, Hong-Xi; Xi, Mei-Yang; Yang, Ting-Ting; Jia, Jian-Min; Huang, Jing-Jie; Guo, Xiao-Ke; Zhang, Xiao-Jin; You, Qi-Dong; Sun, Hao-Peng

2013-01-01

Degradation of certain proteins through the ubiquitin-proteasome pathway is a common strategy taken by the key modulators responsible for stress responses. Kelch-like ECH-associated protein-1(Keap1), a substrate adaptor component of the Cullin3 (Cul3)-based ubiquitin E3 ligase complex, mediates the ubiquitination of two key modulators, NF-E2-related factor 2 (Nrf2) and IκB kinase β (IKKβ), which are involved in the redox control of gene transcription. However, compared to the Keap1-Nrf2 protein-protein interaction (PPI), the intermolecular recognition mechanism of Keap1 and IKKβ has been poorly investigated. In order to explore the binding pattern between Keap1 and IKKβ, the PPI model of Keap1 and IKKβ was investigated. The structure of human IKKβ was constructed by means of the homology modeling method and using reported crystal structure of Xenopus laevis IKKβ as the template. A protein-protein docking method was applied to develop the Keap1-IKKβ complex model. After the refinement and visual analysis of docked proteins, the chosen pose was further optimized through molecular dynamics simulations. The resulting structure was utilized to conduct the virtual alanine mutation for the exploration of hot-spots significant for the intermolecular interaction. Overall, our results provided structural insights into the PPI model of Keap1-IKKβ and suggest that the substrate specificity of Keap1 depend on the interaction with the key tyrosines, namely Tyr525, Tyr574 and Tyr334. The study presented in the current project may be useful to design molecules that selectively modulate Keap1. The selective recognition mechanism of Keap1 with IKKβ or Nrf2 will be helpful to further know the crosstalk between NF-κB and Nrf2 signaling.

Exploring novel key regulators in breast cancer network.

PubMed

Ali, Shahnawaz; Malik, Md Zubbair; Singh, Soibam Shyamchand; Chirom, Keilash; Ishrat, Romana; Singh, R K Brojen

2018-01-01

The breast cancer network constructed from 70 experimentally verified genes is found to follow hierarchical scale free nature with heterogeneous modular organization and diverge leading hubs. The topological parameters (degree distributions, clustering co-efficient, connectivity and centralities) of this network obey fractal rules indicating absence of centrality lethality rule, and efficient communication among the components. From the network theoretical approach, we identified few key regulators out of large number of leading hubs, which are deeply rooted from top to down of the network, serve as backbone of the network, and possible target genes. However, p53, which is one of these key regulators, is found to be in low rank and keep itself at low profile but directly cross-talks with important genes BRCA2 and BRCA3. The popularity of these hubs gets changed in unpredictable way at various levels of organization thus showing disassortive nature. The local community paradigm approach in this network shows strong correlation of nodes in majority of modules/sub-modules (fast communication among nodes) and weak correlation of nodes only in few modules/sub-modules (slow communication among nodes) at various levels of network organization.

Motor modules during adaptation to walking in a powered ankle exoskeleton.

PubMed

Jacobs, Daniel A; Koller, Jeffrey R; Steele, Katherine M; Ferris, Daniel P

2018-01-03

Modules of muscle recruitment can be extracted from electromyography (EMG) during motions, such as walking, running, and swimming, to identify key features of muscle coordination. These features may provide insight into gait adaptation as a result of powered assistance. The aim of this study was to investigate the changes (module size, module timing and weighting patterns) of surface EMG data during assisted and unassisted walking in an powered, myoelectric, ankle-foot orthosis (ankle exoskeleton). Eight healthy subjects wore bilateral ankle exoskeletons and walked at 1.2 m/s on a treadmill. In three training sessions, subjects walked for 40 min in two conditions: unpowered (10 min) and powered (30 min). During each session, we extracted modules of muscle recruitment via nonnegative matrix factorization (NNMF) from the surface EMG signals of ten muscles in the lower limb. We evaluated reconstruction quality for each muscle individually using R 2 and normalized root mean squared error (NRMSE). We hypothesized that the number of modules needed to reconstruct muscle data would be the same between conditions and that there would be greater similarity in module timings than weightings. Across subjects, we found that six modules were sufficient to reconstruct the muscle data for both conditions, suggesting that the number of modules was preserved. The similarity of module timings and weightings between conditions was greater then random chance, indicating that muscle coordination was also preserved. Motor adaptation during walking in the exoskeleton was dominated by changes in the module timings rather than module weightings. The segment number and the session number were significant fixed effects in a linear mixed-effect model for the increase in R 2 with time. Our results show that subjects walking in a exoskeleton preserved the number of modules and the coordination of muscles within the modules across conditions. Training (motor adaptation within the session and motor skill consolidation across sessions) led to improved consistency of the muscle patterns. Subjects adapted primarily by changing the timing of their muscle patterns rather than the weightings of muscles in the modules. The results of this study give new insight into strategies for muscle recruitment during adaptation to a powered ankle exoskeleton.

Modulated Chlorophyll "a" Fluorescence: A Tool for Teaching Photosynthesis

ERIC Educational Resources Information Center

Marques da Silva, Jorge; Bernardes da Silva, Anabela; Padua, Mario

2007-01-01

"In vivo" chlorophyll "a" fluorescence is a key technique in photosynthesis research. The recent release of a low cost, commercial, modulated fluorometer enables this powerful technology to be used in education. Modulated chlorophyll a fluorescence measurement "in vivo" is here proposed as a tool to demonstrate basic…

The New Youth Entrepreneur: Money To Get Started. Module 5.

ERIC Educational Resources Information Center

Kourilsky, Marilyn; And Others

The New Youth Entrepreneur curriculum is a series of 12 youth-oriented educational modules containing instructional materials, learning activities, and checkup exercises designed to teach students key elements of entrepreneurship. This document is the fifth module, and introduces students to the financial issues involved in starting a business,…

ART CONCEPTS - APOLLO IX

NASA Image and Video Library

1969-02-20

S69-19798 (February 1969) --- Composite of three artist's concepts illustrating key events, tasks and activities on the tenth day of the Apollo 9 mission, including Command Module and Service Modules separation, re-entry, and Atlantic splashdown. The Apollo 9 mission will evaluate spacecraft lunar module systems performance during manned Earth-orbital flight.

The New Youth Entrepreneur: Types of Business Ownership. Module 7.

ERIC Educational Resources Information Center

Kourilsky, Marilyn; And Others

The New Youth Entrepreneur curriculum is a series of 12 youth-oriented educational modules containing instructional materials, learning activities, and checkup exercises designed to teach students key elements of entrepreneurship. This document is the seventh module, and examines the potential advantages and disadvantages of entering into four…

Modulation control over ultrasound-mediated gene delivery: evaluating the importance of standing waves.

PubMed

Hassan, Mariame A; Buldakov, Mikhail A; Ogawa, Ryohei; Zhao, Qing-Li; Furusawa, Yukihiro; Kudo, Nobuki; Kondo, Takashi; Riesz, Peter

2010-01-04

Low modulation frequencies from 0.5 to 100Hz were shown to alter the characteristics of the ultrasound field producing solution agitation (<5Hz; region of "ultrasound streaming" prevalence) or stagnancy (>5Hz; region of standing waves establishment) (Buldakov et al., Ultrason. Sonochem., 2009). In this study, the same conditions were used to depict the changes in exogenous DNA delivery in these regions. The luciferase expression data revealed that lower modulations were more capable of enhancing delivery at the expense of viability. On the contrary, the viability was conserved at higher modulations whereas delivery was found to be null. Cavitational activity and acoustic streaming were the effecters beyond the observed pattern and delivery enhancement was shown to be mediated mainly through sonopermeation. To promote transfection, the addition of calcium ions or an echo contrast agent (Levovist((R))) was proposed. Depending on the mechanism involved in each approach, differential enhancement was observed in both regions and at the interim zone (5Hz). In both cases, enhancement in standing waves field was significant reaching 16.0 and 3.3 folds increase, respectively. Therefore, it is concluded that although the establishment of standing waves is not the only prerequisite for high transfection rates, yet, it is a key element in optimization when other factors such as proximity and cavitation are considered.

Swiss national community survey on functioning after spinal cord injury: Protocol, characteristics of participants and determinants of non-response.

PubMed

Brinkhof, Martin W G; Fekete, Christine; Chamberlain, Jonviea D; Post, Marcel W M; Gemperli, Armin

2016-02-01

To detail the protocol, recruitment, study population, response, and data quality of the first population-based community survey of the Swiss Spinal Cord Injury (SwiSCI) Cohort Study. The survey consisted of 3 successive modules administered between September 2011 and March 2013. The first two modules queried demographics, lesion characteristics and key domains of functioning. The third module collected information on psychological personal factors and health behaviour; work integration; or health services and aging. Community-dwelling persons with chronic spinal cord injury in Switzerland. Descriptive analyses of the recruitment process, participant characteristics, and correspondence between self-reported and clinical data. Determinants for participation and the impact of non-response on survey results were assessed. Out of 3,144 eligible persons 1,549 participated in the first two modules (cumulative response rate 49.3%). Approximately three-quarters of participants were male, with a median age of 53 years, and 78% had traumatic spinal cord injury. Record-linkage with medical records demonstrated substantial agreement with self-reported demographic and lesion characteristics. A minimal non-response bias was found. The community survey was effective in recruiting an unbiased sample, thus providing valuable information to study functioning, health maintenance, and quality of life in the Swiss SCI community.

Experimental study on all-fiber-based unidimensional continuous-variable quantum key distribution

NASA Astrophysics Data System (ADS)

Wang, Xuyang; Liu, Wenyuan; Wang, Pu; Li, Yongmin

2017-06-01

We experimentally demonstrated an all-fiber-based unidimensional continuous-variable quantum key distribution (CV QKD) protocol and analyzed its security under collective attack in realistic conditions. A pulsed balanced homodyne detector, which could not be accessed by eavesdroppers, with phase-insensitive efficiency and electronic noise, was considered. Furthermore, a modulation method and an improved relative phase-locking technique with one amplitude modulator and one phase modulator were designed. The relative phase could be locked precisely with a standard deviation of 0.5° and a mean of almost zero. Secret key bit rates of 5.4 kbps and 700 bps were achieved for transmission fiber lengths of 30 and 50 km, respectively. The protocol, which simplified the CV QKD system and reduced the cost, displayed a performance comparable to that of a symmetrical counterpart under realistic conditions. It is expected that the developed protocol can facilitate the practical application of the CV QKD.

Soybean Roots Grown under Heat Stress Show Global Changes in Their Transcriptional and Proteomic Profiles

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

Valdés-López, Oswaldo; Batek, Josef; Gomez-Hernandez, Nicolas

2016-04-25

Heat stress is likely to be a key factor in the negative impact of climate change on crop production. Roots provide support, water and nutrients to other plant organs. Likewise, roots play an important role in the establishment of symbiotic associations with different microorganisms. Despite the physiological relevance of roots, few studies have examined the response of these plant organs to heat stress. In this study, we performed genome-wide transcriptomic and proteomic analyses on isolated root hairs, which are a single, epidermal cell type, and compared their response to whole roots. We identified 2,013 genes differentially regulated in root hairsmore » in response to heat stress. Our gene regulatory module analysis identified ten, key modules that controlled the majority of the transcriptional response to heat stress. We also conducted proteomic analysis on membrane fractions isolated from roots and root hairs. These experiments identified a variety of proteins whose expression changed within 3 hours of application of heat stress. Most of these proteins were predicted to play a role in thermotolerance, as well as in chromatin remodeling and post-transcriptional regulation. The data presented represent an in-depth analysis of the heat stress response of a single cell type in soybean.« less

Modulators of mercury risk to wildlife and humans in the context of rapid global change

USGS Publications Warehouse

Eagles-Smith, Collin A.; Silbergeld, Ellen K.; Basu, Niladri; Bustamante, Paco; Diaz-Barriga, Fernando; Hopkins, William A.; Kidd, Karen A.; Nyland, Jennifer F.

2018-01-01

Environmental mercury (Hg) contamination is an urgent global health threat. The complexity of Hg in the environment can hinder accurate determination of ecological and human health risks, particularly within the context of the rapid global changes that are altering many ecological processes, socioeconomic patterns, and other factors like infectious disease incidence, which can affect Hg exposures and health outcomes. However, the success of global Hg-reduction efforts depends on accurate assessments of their effectiveness in reducing health risks. In this paper, we examine the role that key extrinsic and intrinsic drivers play on several aspects of Hg risk to humans and organisms in the environment. We do so within three key domains of ecological and human health risk. First, we examine how extrinsic global change drivers influence pathways of Hg bioaccumulation and biomagnification through food webs. Next, we describe how extrinsic socioeconomic drivers at a global scale, and intrinsic individual-level drivers, influence human Hg exposure. Finally, we address how the adverse health effects of Hg in humans and wildlife are modulated by a range of extrinsic and intrinsic drivers within the context of rapid global change. Incorporating components of these three domains into research and monitoring will facilitate a more holistic understanding of how ecological and societal drivers interact to influence Hg health risks.

A large-alphabet three-party quantum key distribution protocol based on orbital and spin angular momenta hybrid entanglement

NASA Astrophysics Data System (ADS)

Lai, Hong; Luo, Mingxing; Zhang, Jun; Pieprzyk, Josef; Pan, Lei; Orgun, Mehmet A.

2018-07-01

The orthogonality of the orbital angular momentum (OAM) eigenstates enables a single photon carry an arbitrary number of bits. Moreover, additional degrees of freedom (DOFs) of OAM can span a high-dimensional Hilbert space, which could greatly increase information capacity and security. Moreover, the use of the spin angular momentum-OAM hybrid entangled state can increase Shannon dimensionality, because photons can be hybrid entangled in multiple DOFs. Based on these observations, we develop a hybrid entanglement quantum key distribution (QKD) protocol to achieve three-party quantum key distribution without classical message exchanges. In our proposed protocol, a communicating party uses a spatial light modulator (SLM) and a specific phase hologram to modulate photons' OAM state. Similarly, the other communicating parties use their SLMs and the fixed different phase holograms to modulate the OAM entangled photon pairs, producing the shared key among the parties Alice, Bob and Charlie without classical message exchanges. More importantly, when the same operation is repeated for every party, our protocol could be extended to a multiple-party QKD protocol.

Secure polarization-independent subcarrier quantum key distribution in optical fiber channel using BB84 protocol with a strong reference.

PubMed

Gleim, A V; Egorov, V I; Nazarov, Yu V; Smirnov, S V; Chistyakov, V V; Bannik, O I; Anisimov, A A; Kynev, S M; Ivanova, A E; Collins, R J; Kozlov, S A; Buller, G S

2016-02-08

A quantum key distribution system based on the subcarrier wave modulation method has been demonstrated which employs the BB84 protocol with a strong reference to generate secure bits at a rate of 16.5 kbit/s with an error of 0.5% over an optical channel of 10 dB loss, and 18 bits/s with an error of 0.75% over 25 dB of channel loss. To the best of our knowledge, these results represent the highest channel loss reported for secure quantum key distribution using the subcarrier wave approach. A passive unidirectional scheme has been used to compensate for the polarization dependence of the phase modulators in the receiver module, which resulted in a high visibility of 98.8%. The system is thus fully insensitive to polarization fluctuations and robust to environmental changes, making the approach promising for use in optical telecommunication networks. Further improvements in secure key rate and transmission distance can be achieved by implementing the decoy states protocol or by optimizing the mean photon number used in line with experimental parameters.

The Role of OSHA in Safety and Health. Module SH-02. Safety and Health.

ERIC Educational Resources Information Center

Center for Occupational Research and Development, Inc., Waco, TX.

This student module on the role of OSHA (Occupational Safety and Health Act) in Safety and Health is one of 50 modules concerned with job safety and health. This module looks at the OSHA Act, its aims, and the rights and responsibilities of employers and workers under the Act. Following the introduction, 16 objectives (each keyed to a page in the…

Case Study: The Role of eLearning in Midwifery Pre-Service Education in Ghana.

PubMed

Appiagyei, Martha; Trump, Alison; Danso, Evans; Yeboah, Alex; Searle, Sarah; Carr, Catherine

The issues and challenges of implementing eLearning in pre-service health education were explored through a pilot study conducted in six nurse-midwifery education programs in Ghana. Case-based, interactive computer mediated eLearning modules, targeted to basic emergency and obstetrical signal functions, were delivered both online and offline using a free-for-use eLearning platform, skoool HE(®). Key success factors included broad stakeholder support, an established curriculum and student and tutor interest. Challenges included infrastructure limitations, large class sizes and added workloads for tutors and information technology staff. National scale up is planned.

Saw palmetto ethanol extract inhibits adipocyte differentiation.

PubMed

Villaverde, Nicole; Galvis, Adriana; Marcano, Adriana; Priestap, Horacio A; Bennett, Bradley C; Barbieri, M Alejandro

2013-07-01

The fruits of saw palmetto have been used for the treatment of a variety of urinary and reproductive system problems. In this study we investigated whether the fruit extracts affect in vitro adipogenesis. Saw palmetto ethanol extract inhibited the lipid droplet accumulation by induction media in a dose-dependent manner, and it also attenuated the protein expressions of C-EBPα and PPARγ. Phosphorylation of Erk1/2 and Akt1 were also decreased by saw palmetto ethanol extract. This report suggests that saw palmetto extracts selectively affect the adipocyte differentiation through the modulation of several key factors that play a critical role during adipogenesis.

LRP1 protects the vasculature by regulating levels of connective tissue growth factor and HtrA1.

PubMed

Muratoglu, Selen C; Belgrave, Shani; Hampton, Brian; Migliorini, Mary; Coksaygan, Turhan; Chen, Ling; Mikhailenko, Irina; Strickland, Dudley K

2013-09-01

Low-density lipoprotein receptor-related protein 1 (LRP1) is a large endocytic and signaling receptor that is abundant in vascular smooth muscle cells. Mice in which the lrp1 gene is deleted in smooth muscle cells (smLRP1(-/-)) on a low-density lipoprotein receptor-deficient background display excessive platelet derived growth factor-signaling, smooth muscle cell proliferation, aneurysm formation, and increased susceptibility to atherosclerosis. The objectives of the current study were to examine the potential of LRP1 to modulate vascular physiology under nonatherogenic conditions. We found smLRP1(-/-) mice to have extensive in vivo aortic dilatation accompanied by disorganized and degraded elastic lamina along with medial thickening of the arterial vessels resulting from excess matrix deposition. Surprisingly, this was not attributable to excessive platelet derived growth factor-signaling. Rather, quantitative differential proteomic analysis revealed that smLRP1(-/-) vessels contain a 4-fold increase in protein levels of high-temperature requirement factor A1 (HtrA1), which is a secreted serine protease that is known to degrade matrix components and to impair elastogenesis, resulting in fragmentation of elastic fibers. Importantly, our study discovered that HtrA1 is a novel LRP1 ligand. Proteomics analysis also identified excessive accumulation of connective tissue growth factor, an LRP1 ligand and a key mediator of fibrosis. Our findings suggest a critical role for LRP1 in maintaining the integrity of vessels by regulating protease activity as well as matrix deposition by modulating HtrA1 and connective tissue growth factor protein levels. This study highlights 2 new molecules, connective tissue growth factor and HtrA1, which contribute to detrimental changes in the vasculature and, therefore, represent new target molecules for potential therapeutic intervention to maintain vessel wall homeostasis.

Systems analysis of transcriptome data provides new hypotheses about Arabidopsis root response to nitrate treatments

PubMed Central

Canales, Javier; Moyano, Tomás C.; Villarroel, Eva; Gutiérrez, Rodrigo A.

2014-01-01

Nitrogen (N) is an essential macronutrient for plant growth and development. Plants adapt to changes in N availability partly by changes in global gene expression. We integrated publicly available root microarray data under contrasting nitrate conditions to identify new genes and functions important for adaptive nitrate responses in Arabidopsis thaliana roots. Overall, more than 2000 genes exhibited changes in expression in response to nitrate treatments in Arabidopsis thaliana root organs. Global regulation of gene expression by nitrate depends largely on the experimental context. However, despite significant differences from experiment to experiment in the identity of regulated genes, there is a robust nitrate response of specific biological functions. Integrative gene network analysis uncovered relationships between nitrate-responsive genes and 11 highly co-expressed gene clusters (modules). Four of these gene network modules have robust nitrate responsive functions such as transport, signaling, and metabolism. Network analysis hypothesized G2-like transcription factors are key regulatory factors controlling transport and signaling functions. Our meta-analysis highlights the role of biological processes not studied before in the context of the nitrate response such as root hair development and provides testable hypothesis to advance our understanding of nitrate responses in plants. PMID:24570678

Monocyte/Macrophage-derived IGF-1 Orchestrates Murine Skeletal Muscle Regeneration and Modulates Autocrine Polarization

PubMed Central

Tonkin, Joanne; Temmerman, Lieve; Sampson, Robert D; Gallego-Colon, Enrique; Barberi, Laura; Bilbao, Daniel; Schneider, Michael D; Musarò, Antonio; Rosenthal, Nadia

2015-01-01

Insulin-like growth factor 1 (IGF-1) is a potent enhancer of tissue regeneration, and its overexpression in muscle injury leads to hastened resolution of the inflammatory phase. Here, we show that monocytes/macrophages constitute an important initial source of IGF-1 in muscle injury, as conditional deletion of the IGF-1 gene specifically in mouse myeloid cells (ϕIGF-1 CKO) blocked the normal surge of local IGF-1 in damaged muscle and significantly compromised regeneration. In injured muscle, Ly6C+ monocytes/macrophages and CD206+ macrophages expressed equivalent IGF-1 levels, which were transiently upregulated during transition from the inflammation to repair. In injured ϕIGF-1 CKO mouse muscle, accumulation of CD206+ macrophages was impaired, while an increase in Ly6C+ monocytes/macrophages was favored. Transcriptional profiling uncovered inflammatory skewing in ϕIGF-1 CKO macrophages, which failed to fully induce a reparative gene program in vitro or in vivo, revealing a novel autocrine role for IGF-1 in modulating murine macrophage phenotypes. These data establish local macrophage-derived IGF-1 as a key factor in inflammation resolution and macrophage polarization during muscle regeneration. PMID:25896247

O-GlcNAc Transferase/Host Cell Factor C1 Complex Regulates Gluconeogenesis by Modulating PGC-1α Stability

PubMed Central

Ruan, Hai-Bin; Han, Xuemei; Li, Min-Dian; Singh, Jay Prakash; Qian, Kevin; Azarhoush, Sascha; Zhao, Lin; Bennett, Anton M.; Samuel, Varman T.; Wu, Jing; Yates, John R.; Yang, Xiaoyong

2012-01-01

SUMMARY A major cause of hyperglycemia in diabetic patients is inappropriate hepatic gluconeogenesis. PGC-1α is a master regulator of gluconeogenesis, and its activity is controlled by various post-translational modifications. A small portion of glucose metabolizes through the hexosamine biosynthetic pathway, which leads to O-linked β-N-acetylglucosamine (O-GlcNAc) modification of cytoplasmic and nuclear proteins. Using a proteomic approach, we identified a broad variety of proteins associated with O-GlcNAc transferase (OGT), among which host cell factor C1 (HCF-1) is highly abundant. HCF-1 recruits OGT to O-GlcNAcylate PGC-1α and O-GlcNAcylation facilitates the binding of the deubiquitinase BAP1, thus protecting PGC-1α from degradation and promoting gluconeogenesis. Glucose availability modulates gluconeogenesis through the regulation of PGC-1α O-GlcNAcylation and stability by the OGT/HCF1 complex. Hepatic knockdown of OGT and HCF-1 improves glucose homeostasis in diabetic mice. These findings define the OGT/HCF-1 complex as a glucose sensor and key regulator of gluconeogenesis, shedding light on new strategies for treating diabetes. PMID:22883232

Exercise improves cardiac autonomic function in obesity and diabetes.

PubMed

Voulgari, Christina; Pagoni, Stamatina; Vinik, Aaron; Poirier, Paul

2013-05-01

Physical activity is a key element in the prevention and management of obesity and diabetes. Regular physical activity efficiently supports diet-induced weight loss, improves glycemic control, and can prevent or delay type 2 diabetes diagnosis. Furthermore, physical activity positively affects lipid profile, blood pressure, reduces the rate of cardiovascular events and associated mortality, and restores the quality of life in type 2 diabetes. However, recent studies have documented that a high percentage of the cardiovascular benefits of exercise cannot be attributed solely to enhanced cardiovascular risk factor modulation. Obesity in concert with diabetes is characterized by sympathetic overactivity and the progressive loss of cardiac parasympathetic influx. These are manifested via different pathogenetic mechanisms, including hyperinsulinemia, visceral obesity, subclinical inflammation and increased thrombosis. Cardiac autonomic neuropathy is an underestimated risk factor for the increased cardiovascular morbidity and mortality associated with obesity and diabetes. The same is true for the role of physical exercise in the restoration of the heart cardioprotective autonomic modulation in these individuals. This review addresses the interplay of cardiac autonomic function in obesity and diabetes, and focuses on the importance of exercise in improving cardiac autonomic dysfunction. Copyright © 2013 Elsevier Inc. All rights reserved.

Nuclear cereblon modulates transcriptional activity of Ikaros and regulates its downstream target, enkephalin, in human neuroblastoma cells

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

Wada, Takeyoshi; Asahi, Toru; Research Organization for Nano & Life Innovation, Waseda University #03C309, TWIns, 2-2 Wakamatsu, Shinjuku, Tokyo, 162-8480

2016-08-26

The gene coding cereblon (CRBN) was originally identified in genetic linkage analysis of mild autosomal recessive nonsyndromic intellectual disability. CRBN has broad localization in both the cytoplasm and nucleus. However, the significance of nuclear CRBN remains unknown. In the present study, we aimed to elucidate the role of CRBN in the nucleus. First, we generated a series of CRBN deletion mutants and determined the regions responsible for the nuclear localization. Only CRBN protein lacking the N-terminal region was localized outside of the nucleus, suggesting that the N-terminal region is important for its nuclear localization. CRBN was also identified as amore » thalidomide-binding protein and component of the cullin-4-containing E3 ubiquitin ligase complex. Thalidomide has been reported to be involved in the regulation of the transcription factor Ikaros by CRBN-mediated degradation. To investigate the nuclear functions of CRBN, we performed co-immunoprecipitation experiments and evaluated the binding of CRBN to Ikaros. As a result, we found that CRBN was associated with Ikaros protein, and the N-terminal region of CRBN was required for Ikaros binding. In luciferase reporter gene experiments, CRBN modulated transcriptional activity of Ikaros. Furthermore, we found that CRBN modulated Ikaros-mediated transcriptional repression of the proenkephalin gene by binding to its promoter region. These results suggest that CRBN binds to Ikaros via its N-terminal region and regulates transcriptional activities of Ikaros and its downstream target, enkephalin. - Highlights: • We found that CRBN is a nucleocytoplasmic shutting protein and identified the key domain for nucleocytoplasmic shuttling. • CRBN associates with the transcription factor Ikaros via the N-terminal domain. • CRBN modulates Ikaros-mediated transcriptional regulation and its downstream target, enkephalin.« less

Modulation of KCNQ1 alternative splicing regulates cardiac IKs and action potential repolarization.

PubMed

Lee, Hsiang-Chun; Rudy, Yoram; Po-Yuan, Phd; Sheu, Sheng-Hsiung; Chang, Jan-Gowth; Cui, Jianmin

2013-08-01

Slow delayed-rectifier potassium current (IKs) channels, made of the pore-forming KCNQ1 and auxiliary KCNE1 subunits, play a key role in determining action potential duration (APD) in cardiac myocytes. The consequences of drug-induced KCNQ1 splice alteration remain unknown. To study the modulation of KCNQ1 alternative splicing by amiloride and the consequent changes in IKs and action potentials (APs) in ventricular myocytes. Canine endocardial, midmyocardial, and epicardial ventricular myocytes were isolated. Levels of KCNQ1a and KCNQ1b as well as a series of splicing factors were quantified by using the reverse transcriptase-polymerase chain reaction and Western blot. The effect of amiloride-induced changes in the KCNQ1b/total KCNQ1 ratio on AP was measured by using whole-cell patch clamp with and without isoproterenol. With 50 μmol/L of amiloride for 6 hours, KCNQ1a at transcriptional and translational levels increased in midmyocardial myocytes but decreased in endo- and epicardial myocytes. Likewise, changes in splicing factors in midmyocardial were opposite to that in endo- and epicardial myocytes. In midmyocardial myocytes amiloride shortened APD and decreased isoproterenol-induced early afterdepolarizations significantly. The same amiloride-induced effects were demonstrated by using human ventricular myocyte model for AP simulations under beta-adrenergic stimulation. Moreover, amiloride reduced the transmural dispersion of repolarization in pseudo-electrocardiogram. Amiloride regulates IKs and APs with transmural differences and reduces arrhythmogenicity through the modulation of KCNQ1 splicing. We suggested that the modulation of KCNQ1 splicing may help prevent arrhythmia. Copyright © 2013 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

GIV/Girdin activates Gαi and inhibits Gαs via the same motif

PubMed Central

Gupta, Vijay; Bhandari, Deepali; Leyme, Anthony; Aznar, Nicolas; Midde, Krishna K.; Lo, I-Chung; Ear, Jason; Niesman, Ingrid; López-Sánchez, Inmaculada; Blanco-Canosa, Juan Bautista; von Zastrow, Mark; Garcia-Marcos, Mikel; Farquhar, Marilyn G.; Ghosh, Pradipta

2016-01-01

We previously showed that guanine nucleotide-binding (G) protein α subunit (Gα)-interacting vesicle-associated protein (GIV), a guanine-nucleotide exchange factor (GEF), transactivates Gα activity-inhibiting polypeptide 1 (Gαi) proteins in response to growth factors, such as EGF, using a short C-terminal motif. Subsequent work demonstrated that GIV also binds Gαs and that inactive Gαs promotes maturation of endosomes and shuts down mitogenic MAPK–ERK1/2 signals from endosomes. However, the mechanism and consequences of dual coupling of GIV to two G proteins, Gαi and Gαs, remained unknown. Here we report that GIV is a bifunctional modulator of G proteins; it serves as a guanine nucleotide dissociation inhibitor (GDI) for Gαs using the same motif that allows it to serve as a GEF for Gαi. Upon EGF stimulation, GIV modulates Gαi and Gαs sequentially: first, a key phosphomodification favors the assembly of GIV–Gαi complexes and activates GIV’s GEF function; then a second phosphomodification terminates GIV’s GEF function, triggers the assembly of GIV–Gαs complexes, and activates GIV’s GDI function. By comparing WT and GIV mutants, we demonstrate that GIV inhibits Gαs activity in cells responding to EGF. Consequently, the cAMP→PKA→cAMP response element-binding protein signaling axis is inhibited, the transit time of EGF receptor through early endosomes are accelerated, mitogenic MAPK–ERK1/2 signals are rapidly terminated, and proliferation is suppressed. These insights define a paradigm in G-protein signaling in which a pleiotropically acting modulator uses the same motif both to activate and to inhibit G proteins. Our findings also illuminate how such modulation of two opposing Gα proteins integrates downstream signals and cellular responses. PMID:27621449

Chroma key without color restrictions based on asynchronous amplitude modulation of background illumination on retroreflective screens

NASA Astrophysics Data System (ADS)

Vidal, Borja; Lafuente, Juan A.

2016-03-01

A simple technique to avoid color limitations in image capture systems based on chroma key video composition using retroreflective screens and light-emitting diodes (LED) rings is proposed and demonstrated. The combination of an asynchronous temporal modulation onto the background illumination and simple image processing removes the usual restrictions on foreground colors in the scene. The technique removes technical constraints in stage composition, allowing its design to be purely based on artistic grounds. Since it only requires adding a very simple electronic circuit to widely used chroma keying hardware based on retroreflective screens, the technique is easily applicable to TV and filming studios.

Gaussian-modulated coherent-state measurement-device-independent quantum key distribution

NASA Astrophysics Data System (ADS)

Ma, Xiang-Chun; Sun, Shi-Hai; Jiang, Mu-Sheng; Gui, Ming; Liang, Lin-Mei

2014-04-01

Measurement-device-independent quantum key distribution (MDI-QKD), leaving the detection procedure to the third partner and thus being immune to all detector side-channel attacks, is very promising for the construction of high-security quantum information networks. We propose a scheme to implement MDI-QKD, but with continuous variables instead of discrete ones, i.e., with the source of Gaussian-modulated coherent states, based on the principle of continuous-variable entanglement swapping. This protocol not only can be implemented with current telecom components but also has high key rates compared to its discrete counterpart; thus it will be highly compatible with quantum networks.

A Nasal Epithelial Receptor for Staphylococcus aureus WTA Governs Adhesion to Epithelial Cells and Modulates Nasal Colonization

PubMed Central

Faulstich, Manuela; Grau, Timo; Severin, Yannik; Unger, Clemens; Hoffmann, Wolfgang H.; Rudel, Thomas; Autenrieth, Ingo B.; Weidenmaier, Christopher

2014-01-01

Nasal colonization is a major risk factor for S. aureus infections. The mechanisms responsible for colonization are still not well understood and involve several factors on the host and the bacterial side. One key factor is the cell wall teichoic acid (WTA) of S. aureus, which governs direct interactions with nasal epithelial surfaces. We report here the first receptor for the cell wall glycopolymer WTA on nasal epithelial cells. In several assay systems this type F-scavenger receptor, termed SREC-I, bound WTA in a charge dependent manner and mediated adhesion to nasal epithelial cells in vitro. The impact of WTA and SREC-I interaction on epithelial adhesion was especially pronounced under shear stress, which resembles the conditions found in the nasal cavity. Most importantly, we demonstrate here a key role of the WTA-receptor interaction in a cotton rat model of nasal colonization. When we inhibited WTA mediated adhesion with a SREC-I antibody, nasal colonization in the animal model was strongly reduced at the early onset of colonization. More importantly, colonization stayed low over an extended period of 6 days. Therefore we propose targeting of this glycopolymer-receptor interaction as a novel strategy to prevent or control S. aureus nasal colonization. PMID:24788600

Translational models of tumor angiogenesis: A nexus of in silico and in vitro models.

PubMed

Soleimani, Shirin; Shamsi, Milad; Ghazani, Mehran Akbarpour; Modarres, Hassan Pezeshgi; Valente, Karolina Papera; Saghafian, Mohsen; Ashani, Mehdi Mohammadi; Akbari, Mohsen; Sanati-Nezhad, Amir

2018-03-05

Emerging evidence shows that endothelial cells are not only the building blocks of vascular networks that enable oxygen and nutrient delivery throughout a tissue but also serve as a rich resource of angiocrine factors. Endothelial cells play key roles in determining cancer progression and response to anti-cancer drugs. Furthermore, the endothelium-specific deposition of extracellular matrix is a key modulator of the availability of angiocrine factors to both stromal and cancer cells. Considering tumor vascular network as a decisive factor in cancer pathogenesis and treatment response, these networks need to be an inseparable component of cancer models. Both computational and in vitro experimental models have been extensively developed to model tumor-endothelium interactions. While informative, they have been developed in different communities and do not yet represent a comprehensive platform. In this review, we overview the necessity of incorporating vascular networks for both in vitro and in silico cancer models and discuss recent progresses and challenges of in vitro experimental microfluidic cancer vasculature-on-chip systems and their in silico counterparts. We further highlight how these two approaches can merge together with the aim of presenting a predictive combinatorial platform for studying cancer pathogenesis and testing the efficacy of single or multi-drug therapeutics for cancer treatment. Copyright © 2018. Published by Elsevier Inc.

Pathogenesis of Cognitive Dysfunction in Patients with Obstructive Sleep Apnea: A Hypothesis with Emphasis on the Nucleus Tractus Solitarius

PubMed Central

Daulatzai, Mak Adam

2012-01-01

OSA is characterized by the quintessential triad of intermittent apnea, hypoxia, and hypoxemia due to pharyngeal collapse. This paper highlights the upstream mechanisms that may trigger cognitive decline in OSA. Three interrelated steps underpin cognitive dysfunction in OSA patients. First, several risk factors upregulate peripheral inflammation; these crucial factors promote neuroinflammation, cerebrovascular endothelial dysfunction, and oxidative stress in OSA. Secondly, the neuroinflammation exerts negative impact globally on the CNS, and thirdly, important foci in the neocortex and brainstem are rendered inflamed and dysfunctional. A strong link is known to exist between neuroinflammation and neurodegeneration. A unique perspective delineated here underscores the importance of dysfunctional brainstem nuclei in etiopathogenesis of cognitive decline in OSA patients. Nucleus tractus solitarius (NTS) is the central integration hub for afferents from upper airway (somatosensory/gustatory), respiratory, gastrointestinal, cardiovascular (baroreceptor and chemoreceptor) and other systems. The NTS has an essential role in sympathetic and parasympathetic systems also; it projects to most key brain regions and modulates numerous physiological functions. Inflamed and dysfunctional NTS and other key brainstem nuclei may play a pivotal role in triggering memory and cognitive dysfunction in OSA. Attenuation of upstream factors and amelioration of the NTS dysfunction remain important challenges. PMID:23470865

Role of hydrogen sulfide in paramyxovirus infections.

PubMed

Li, Hui; Ma, Yinghong; Escaffre, Oliver; Ivanciuc, Teodora; Komaravelli, Narayana; Kelley, John P; Coletta, Ciro; Szabo, Csaba; Rockx, Barry; Garofalo, Roberto P; Casola, Antonella

2015-05-01

Hydrogen sulfide (H2S) is an endogenous gaseous mediator that has gained increasing recognition as an important player in modulating acute and chronic inflammatory diseases. However, its role in virus-induced lung inflammation is currently unknown. Respiratory syncytial virus (RSV) is a major cause of upper and lower respiratory tract infections in children for which no vaccine or effective treatment is available. Using the slow-releasing H2S donor GYY4137 and propargylglycin (PAG), an inhibitor of cystathionine-γ-lyase (CSE), a key enzyme that produces intracellular H2S, we found that RSV infection led to a reduced ability to generate and maintain intracellular H2S levels in airway epithelial cells (AECs). Inhibition of CSE with PAG resulted in increased viral replication and chemokine secretion. On the other hand, treatment of AECs with the H2S donor GYY4137 reduced proinflammatory mediator production and significantly reduced viral replication, even when administered several hours after viral absorption. GYY4137 also significantly reduced replication and inflammatory chemokine production induced by human metapneumovirus (hMPV) and Nipah virus (NiV), suggesting a broad inhibitory effect of H2S on paramyxovirus infections. GYY4137 treatment had no effect on RSV genome replication or viral mRNA and protein synthesis, but it inhibited syncytium formation and virus assembly/release. GYY4137 inhibition of proinflammatory gene expression occurred by modulation of the activation of the key transcription factors nuclear factor κB (NF-κB) and interferon regulatory factor 3 (IRF-3) at a step subsequent to their nuclear translocation. H2S antiviral and immunoregulatory properties could represent a novel treatment strategy for paramyxovirus infections. RSV is a global health concern, causing significant morbidity and economic losses as well as mortality in developing countries. After decades of intensive research, no vaccine or effective treatment, with the exception of immunoprophylaxis, is available for this infection as well as for other important respiratory mucosal viruses. This study identifies hydrogen sulfide as a novel cellular mediator that can modulate viral replication and proinflammatory gene expression, both important determinants of lung injury in respiratory viral infections, with potential for rapid translation of such findings into novel therapeutic approaches for viral bronchiolitis and pneumonia. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

PAR-1 and thrombin: the ties that bind the microenvironment to melanoma metastasis.

PubMed

Zigler, Maya; Kamiya, Takafumi; Brantley, Emily C; Villares, Gabriel J; Bar-Eli, Menashe

2011-11-01

Progression of melanoma is dependent on cross-talk between tumor cells and the adjacent microenvironment. The thrombin receptor, protease-activated receptor-1 (PAR-1), plays a key role in exerting this function during melanoma progression. PAR-1 and its activating factors, which are expressed on tumor cells and the surrounding stroma, induce not only coagulation but also cell signaling, which promotes the metastatic phenotype. Several adhesion molecules, cytokines, growth factors, and proteases have recently been identified as downstream targets of PAR-1 and have been shown to modulate interactions between tumor cells and the microenvironment in the process of melanoma growth and metastasis. Inhibiting such interactions by targeting PAR-1 could potentially be a useful therapeutic modality for melanoma patients. ©2011 AACR.

Understanding epigenetic architecture of suicide neurobiology: A critical perspective

PubMed Central

Roy, Bhaskar; Dwivedi, Yogesh

2016-01-01

Current understanding of environmental cross-talk with genetic makeup is found to be mediated through an epigenetic interface which is associated with prominent reversible and heritable changes at gene expression level. Recent emergence of epigenetic modulation in shaping the genetic information has become a key regulatory factor in answering the underlying complexities associated with several mental disorders. A comprehensive understanding of the pertinent changes in the epigenetic makeup of suicide phenotype exhibits a characteristic signature with the possibility of using it as a biomarker to help predict the risk factors associated with suicide. Within the scope of this current review, the most sought after epigenetic changes of DNA methylation and histone modification are thoroughly scrutinized to understand their close functional association with the broad spectrum of suicide phenotype. PMID:27836463

Analysis of the Image Quality of no Ground Controlled Positioning Precision about Surveying and Mapping Satellite

NASA Astrophysics Data System (ADS)

Wang, Y.; Hu, X.; Yang, X.; Xie, G.

2018-04-01

The image quality of the surveying camera will affect the stereoscopic positioning accuracy of the remote sensing satellite. The key factors closely related to the image quality are Modulation Transfer Function(MTF),Signal to Noise Ratio(SNR) and Quantization Bits(QB). In "Mapping Satellite-1" image as the background, research the effect of positioning precision about the image quality in no ground controlled conditions, and evaluate the quantitative relationship with the positioning precision. At last verify the validity of the experimental results by simulating three factors of the degraded data on orbit, and counting the number of matching points, the mismatch rate, and the matching residuals of the degraded data. The reason for the variety of the positioning precision was analyzed.

A bandwidth efficient coding scheme for the Hubble Space Telescope

NASA Technical Reports Server (NTRS)

Pietrobon, Steven S.; Costello, Daniel J., Jr.

1991-01-01

As a demonstration of the performance capabilities of trellis codes using multidimensional signal sets, a Viterbi decoder was designed. The choice of code was based on two factors. The first factor was its application as a possible replacement for the coding scheme currently used on the Hubble Space Telescope (HST). The HST at present uses the rate 1/3 nu = 6 (with 2 (exp nu) = 64 states) convolutional code with Binary Phase Shift Keying (BPSK) modulation. With the modulator restricted to a 3 Msym/s, this implies a data rate of only 1 Mbit/s, since the bandwidth efficiency K = 1/3 bit/sym. This is a very bandwidth inefficient scheme, although the system has the advantage of simplicity and large coding gain. The basic requirement from NASA was for a scheme that has as large a K as possible. Since a satellite channel was being used, 8PSK modulation was selected. This allows a K of between 2 and 3 bit/sym. The next influencing factor was INTELSAT's intention of transmitting the SONET 155.52 Mbit/s standard data rate over the 72 MHz transponders on its satellites. This requires a bandwidth efficiency of around 2.5 bit/sym. A Reed-Solomon block code is used as an outer code to give very low bit error rates (BER). A 16 state rate 5/6, 2.5 bit/sym, 4D-8PSK trellis code was selected. This code has reasonable complexity and has a coding gain of 4.8 dB compared to uncoded 8PSK (2). This trellis code also has the advantage that it is 45 deg rotationally invariant. This means that the decoder needs only to synchronize to one of the two naturally mapped 8PSK signals in the signal set.

The New Youth Entrepreneur: Records and Books. Did You Make Any Money? Module 9.

ERIC Educational Resources Information Center

Kourilsky, Marilyn; And Others

The New Youth Entrepreneur curriculum is a series of 12 youth-oriented educational modules containing instructional materials, learning activities, and checkup exercises designed to teach students key elements of entrepreneurship. This document is the ninth module, and introduces students to recordkeeping and bookkeeping strategies essential for…

Rapid Deposition Technology Holds the Key for the World's Largest Manufacturer of Thin-Film Solar Modules (Fact Sheet)

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

Not Available

2013-08-01

First Solar, Inc. has been collaborating with NREL since 1991, advancing its thin-film cadmium telluride solar technology to grow from a startup company to become one of the world's largest manufacturers of solar modules, and the world's largest manufacturer of thin-film solar modules.

Online Video Modules for Improvement in Student Learning

ERIC Educational Resources Information Center

Lancellotti, Matthew; Thomas, Sunil; Kohli, Chiranjeev

2016-01-01

The objective of this teaching innovation was to incorporate a comprehensive set of short online video modules covering key topics from the undergraduate principles of marketing class, and to evaluate its effectiveness in improving student learning. A quasiexperimental design was used to compare students who had access to video modules with a…

The New Youth Entrepreneur: How To Mind Your Own Business. Module 11.

ERIC Educational Resources Information Center

Kourilsky, Marilyn; And Others

The New Youth Entrepreneur curriculum is a series of 12 youth-oriented educational modules containing instructional materials, learning activities, and checkup exercises designed to teach students key elements of entrepreneurship. This document is the eleventh module, and focuses on issues related to managing the day-to-day affairs of a small…

Coherent detection of frequency-hopped quadrature modulations in the presence of jamming. II - QPR Class I modulation. [Quadrature Partial Response

NASA Technical Reports Server (NTRS)

Simon, M. K.

1981-01-01

This paper considers the performance of quadrature partial response (QPR) in the presence of jamming. Although a QPR system employs a single sample detector in its receiver, while quadrature amplitude shift keying (or quadrature phase shift keying) requires a matched-filter type of receiver, it is shown that the coherent detection performances of the two in the presence of the intentional jammer have definite similarities.

The hysteretic evapotranspiration—Vapor pressure deficit relation

NASA Astrophysics Data System (ADS)

Zhang, Quan; Manzoni, Stefano; Katul, Gabriel; Porporato, Amilcare; Yang, Dawen

2014-02-01

Diurnal hysteresis between evapotranspiration (ET) and vapor pressure deficit (VPD) was reported in many ecosystems, but justification for its onset and magnitude remains incomplete with biotic and abiotic factors invoked as possible explanations. To place these explanations within a holistic framework, the occurrence of hysteresis was theoretically assessed along a hierarchy of model systems where both abiotic and biotic components are sequentially added. Lysimeter evaporation (E) measurements and model calculations using the Penman equation were used to investigate the effect of the time lag between net radiation and VPD on the hysteresis in the absence of any biotic effects. Modulations from biotic effects on the ET-VPD hysteresis were then added using soil-plant-atmosphere models of different complexities applied to a grassland ecosystem. The results suggest that the hysteresis magnitude depends on the radiation-VPD lag, while the plant and soil water potentials are both key factors modulating the hysteretic ET-VPD relation as soil moisture declines. In particular, larger hysteresis magnitude is achieved at less negative leaf water potential, root water potential, and soil water potential. While plant hydraulic capacitance affects the leaf water potential-ET relation, it has negligible effects on the ET-VPD hysteresis. Therefore, the genesis and magnitude of the ET-VPD hysteresis are controlled directly by both abiotic factors such as soil water availability, biotic factors (leaf and root water potentials, which in turn depend on soil moisture), and the time lag between radiation and VPD.

PrPC Governs Susceptibility to Prion Strains in Bank Vole, While Other Host Factors Modulate Strain Features

PubMed Central

Espinosa, J. C.; Nonno, R.; Di Bari, M.; Aguilar-Calvo, P.; Pirisinu, L.; Fernández-Borges, N.; Vanni, I.; Vaccari, G.; Marín-Moreno, A.; Frassanito, P.; Lorenzo, P.; Agrimi, U.

2016-01-01

ABSTRACT Bank vole is a rodent species that shows differential susceptibility to the experimental transmission of different prion strains. In this work, the transmission features of a panel of diverse prions with distinct origins were assayed both in bank vole expressing methionine at codon 109 (Bv109M) and in transgenic mice expressing physiological levels of bank vole PrPC (the BvPrP-Tg407 mouse line). This work is the first systematic comparison of the transmission features of a collection of prion isolates, representing a panel of diverse prion strains, in a transgenic-mouse model and in its natural counterpart. The results showed very similar transmission properties in both the natural species and the transgenic-mouse model, demonstrating the key role of the PrP amino acid sequence in prion transmission susceptibility. However, differences in the PrPSc types propagated by Bv109M and BvPrP-Tg407 suggest that host factors other than PrPC modulate prion strain features. IMPORTANCE The differential susceptibility of bank voles to prion strains can be modeled in transgenic mice, suggesting that this selective susceptibility is controlled by the vole PrP sequence alone rather than by other species-specific factors. Differences in the phenotypes observed after prion transmissions in bank voles and in the transgenic mice suggest that host factors other than the PrPC sequence may affect the selection of the substrain replicating in the animal model. PMID:27654300

A kidney-specific genetic control module in mice governs endocrine regulation of the cytochrome P450 gene Cyp27b1 essential for vitamin D3 activation

PubMed Central

Meyer, Mark B.; Benkusky, Nancy A.; Kaufmann, Martin; Lee, Seong Min; Onal, Melda; Jones, Glenville; Pike, J. Wesley

2017-01-01

The vitamin D endocrine system regulates mineral homeostasis through its activities in the intestine, kidney, and bone. Terminal activation of vitamin D3 to its hormonal form, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3), occurs in the kidney via the cytochrome P450 enzyme CYP27B1. Despite its importance in vitamin D metabolism, the molecular mechanisms underlying the regulation of the gene for this enzyme, Cyp27b1, are unknown. Here, we identified a kidney-specific control module governed by a renal cell-specific chromatin structure located distal to Cyp27b1 that mediates unique basal and parathyroid hormone (PTH)-, fibroblast growth factor 23 (FGF23)-, and 1,25(OH)2D3-mediated regulation of Cyp27b1 expression. Selective genomic deletion of key components within this module in mice resulted in loss of either PTH induction or FGF23 and 1,25(OH)2D3 suppression of Cyp27b1 gene expression; the former loss caused a debilitating skeletal phenotype, whereas the latter conferred a quasi-normal bone mineral phenotype through compensatory homeostatic mechanisms involving Cyp24a1. We found that Cyp27b1 is also expressed at low levels in non-renal cells, in which transcription was modulated exclusively by inflammatory factors via a process that was unaffected by deletion of the kidney-specific module. These results reveal that differential regulation of Cyp27b1 expression represents a mechanism whereby 1,25(OH)2D3 can fulfill separate functional roles, first in the kidney to control mineral homeostasis and second in extra-renal cells to regulate target genes linked to specific biological responses. Furthermore, we conclude that these mouse models open new avenues for the study of vitamin D metabolism and its involvement in therapeutic strategies for human health and disease. PMID:28808057

Membrane Type 1–Matrix Metalloproteinase/Akt Signaling Axis Modulates TNF-α-Induced Procoagulant Activity and Apoptosis in Endothelial Cells

PubMed Central

Ohkawara, Hiroshi; Ishibashi, Toshiyuki; Sugimoto, Koichi; Ikeda, Kazuhiko; Ogawa, Kazuei; Takeishi, Yasuchika

2014-01-01

Membrane type 1–matrix metalloproteinase (MT1-MMP) functions as a signaling molecule in addition to a proteolytic enzyme. Our hypothesis was that MT1-MMP cooperates with protein kinase B (Akt) in tumor necrosis factor (TNF)-α-induced signaling pathways of vascular responses, including tissue factor (TF) procoagulant activity and endothelial apoptosis, in cultured human aortic endothelial cells (ECs). TNF-α (10 ng/mL) induced a decrease in Akt phosphorylation within 60 minutes in ECs. A chemical inhibitor of MMP, TIMP-2 and selective small interfering RNA (siRNA)-mediated suppression of MT1-MMP reversed TNF-α-triggered transient decrease of Akt phosphorylation within 60 minutes, suggesting that MT1-MMP may be a key regulator of Akt phosphorylation in TNF-α-stimulated ECs. In the downstream events, TNF-α increased TF antigen and activity, and suppressed the expression of thrombomodulin (TM) antigen. Inhibition of Akt markedly enhanced TNF-α-induced expression of TF antigen and activity, and further reduced the expression of TM antigen. Silencing of MT1-MMP by siRNA also reversed the changed expression of TF and TM induced by TNF-α. Moreover, TNF-α induced apoptosis of ECs through Akt- and forkhead box protein O1 (FoxO1)-dependent signaling pathway and nuclear factor-kB (NF-kB) activation. Knockdown of MT1-MMP by siRNA reversed apoptosis of ECs by inhibiting TNF-α-induced Akt-dependent regulation of FoxO1 in TNF-α-stimulated ECs. Immunoprecipitation demonstrated that TNF-α induced the changes in the associations between the cytoplasmic fraction of MT1-MMP and Akt in ECs. In conclusion, we show new evidence that MT1-MMP/Akt signaling axis is a key modifier for TNF-α-induced signaling pathways for modulation of procoagulant activity and apoptosis of ECs. PMID:25162582

Noise performance of frequency modulation Kelvin force microscopy

PubMed Central

Deresmes, Dominique; Mélin, Thierry

2014-01-01

Summary Noise performance of a phase-locked loop (PLL) based frequency modulation Kelvin force microscope (FM-KFM) is assessed. Noise propagation is modeled step by step throughout the setup using both exact closed loop noise gains and an approximation known as “noise gain” from operational amplifier (OpAmp) design that offers the advantage of decoupling the noise performance study from considerations of stability and ideal loop response. The bandwidth can be chosen depending on how much noise is acceptable and it is shown that stability is not an issue up to a limit that will be discussed. With thermal and detector noise as the only sources, both approaches yield PLL frequency noise expressions equal to the theoretical value for self-oscillating circuits and in agreement with measurement, demonstrating that the PLL components neither modify nor contribute noise. Kelvin output noise is then investigated by modeling the surrounding bias feedback loop. A design rule is proposed that allows choosing the AC modulation frequency for optimized sharing of the PLL bandwidth between Kelvin and topography loops. A crossover criterion determines as a function of bandwidth, temperature and probe parameters whether thermal or detector noise is the dominating noise source. Probe merit factors for both cases are then established, suggesting how to tackle noise performance by probe design. Typical merit factors of common probe types are compared. This comprehensive study is an encouraging step toward a more integral performance assessment and a remedy against focusing on single aspects and optimizing around randomly chosen key values. PMID:24455457

Low cost, small form factor, and integration as the key features for the optical component industry takeoff

NASA Astrophysics Data System (ADS)

Schiattone, Francesco; Bonino, Stefano; Gobbi, Luigi; Groppi, Angelamaria; Marazzi, Marco; Musio, Maurizio

2003-04-01

In the past the optical component market has been mainly driven by performances. Today, as the number of competitors has drastically increased, the system integrators have a wide range of possible suppliers and solutions giving them the possibility to be more focused on cost and also on footprint reduction. So, if performances are still essential, low cost and Small Form Factor issues are becoming more and more crucial in selecting components. Another evolution in the market is the current request of the optical system companies to simplify the supply chain in order to reduce the assembling and testing steps at system level. This corresponds to a growing demand in providing subassemblies, modules or hybrid integrated components: that means also Integration will be an issue in which all the optical component companies will compete to gain market shares. As we can see looking several examples offered by electronic market, to combine low cost and SFF is a very challenging task but Integration can help in achieving both features. In this work we present how these issues could be approached giving examples of some advanced solutions applied to LiNbO3 modulators. In particular we describe the progress made on automation, new materials and low cost fabrication methods for the parts. We also introduce an approach in integrating optical and electrical functionality on LiNbO3 modulators including RF driver, bias control loop, attenuator and photodiode integrated in a single device.

PrP(C) regulates epidermal growth factor receptor function and cell shape dynamics in Neuro2a cells.

PubMed

Llorens, Franc; Carulla, Patricia; Villa, Ana; Torres, Juan M; Fortes, Puri; Ferrer, Isidre; del Río, José A

2013-10-01

The prion protein (PrP) plays a key role in prion disease pathogenesis. Although the misfolded and pathologic variant of this protein (PrP(SC)) has been studied in depth, the physiological role of PrP(C) remains elusive and controversial. PrP(C) is a cell-surface glycoprotein involved in multiple cellular functions at the plasma membrane, where it interacts with a myriad of partners and regulates several intracellular signal transduction cascades. However, little is known about the gene expression changes modulated by PrP(C) in animals and in cellular models. In this article, we present PrP(C)-dependent gene expression signature in N2a cells and its implication in the most overrepresented functions: cell cycle, cell growth and proliferation, and maintenance of cell shape. PrP(C) over-expression enhances cell proliferation and cell cycle re-entrance after serum stimulation, while PrP(C) silencing slows down cell cycle progression. In addition, MAP kinase and protein kinase B (AKT) pathway activation are under the regulation of PrP(C) in asynchronous cells and following mitogenic stimulation. These effects are due in part to the modulation of epidermal growth factor receptor (EGFR) by PrP(C) in the plasma membrane, where the two proteins interact in a multimeric complex. We also describe how PrP(C) over-expression modulates filopodia formation by Rho GTPase regulation mainly in an AKT-Cdc42-N-WASP-dependent pathway. © 2013 International Society for Neurochemistry.

NF-κB Decoy Oligodeoxynucleotide Enhanced Osteogenesis in Mesenchymal Stem Cells Exposed to Polyethylene Particle

PubMed Central

Lin, Tzu-Hua; Sato, Taishi; Barcay, Katherine R.; Waters, Heather; Loi, Florence; Zhang, Ruth; Pajarinen, Jukka; Egashira, Kensuke; Yao, Zhenyu

2015-01-01

Excessive generation of wear particles after total joint replacement may lead to local inflammation and periprosthetic osteolysis. Modulation of the key transcription factor NF-κB in immune cells could potentially mitigate the osteolytic process. We previously showed that local delivery of ultrahigh-molecular-weight polyethylene (UHMWPE) particles recruited osteoprogenitor cells and reduced osteolysis. However, the biological effects of modulating the NF-κB signaling pathway on osteoprogenitor/mesenchymal stem cells (MSCs) remain unclear. Here we showed that decoy oligodeoxynucleotide (ODN) increased cell viability when primary murine MSCs were exposed to UHMWPE particles, but had no effects on cellular apoptosis. Decoy ODN increased transforming growth factor-beta 1 (TGF-β1) and osteoprotegerin (OPG) in MSCs exposed to UHMWPE particles. Mechanistic studies showed that decoy ODN upregulated OPG expression through a TGF-β1-dependent pathway. By measuring the alkaline phosphatase activity, osteocalcin levels, Runx2 and osteopontin expression, and performing a bone mineralization assay, we found that decoy ODN increased MSC osteogenic ability when the cells were exposed to UHMWPE particles. Furthermore, the cellular response to decoy ODN and UHMWPE particles with regard to cell phenotype, cell viability, and osteogenic ability was confirmed using primary human MSCs. Our results suggest that modulation of wear particle-induced inflammation by NF-κB decoy ODN had no adverse effects on MSCs and may potentially further mitigate periprosthetic osteolysis by protecting MSC viability and osteogenic ability. PMID:25518013

Ascending control of arousal and motivation: role of nucleus incertus and its peptide neuromodulators in behavioural responses to stress.

PubMed

Ma, S; Gundlach, A L

2015-06-01

Arousal is a process that involves the activation of ascending neural pathways originating in the rostral pons that project to the forebrain through the midbrain reticular formation to promote the activation of key cortical, thalamic, hypothalamic and limbic centres. Established modulators of arousal include the cholinergic, serotonergic, noradrenergic and dopaminergic networks originating in the pons and midbrain. Recent data indicate that a population of largely GABAergic projection neurones located in the nucleus incertus (NI) are also involved in arousal and motivational processes. The NI has prominent efferent connections with distinct hypothalamic, amygdalar and thalamic nuclei, in addition to dense projections to key brain regions associated with the generation and pacing of hippocampal activity. The NI receives strong inputs from the prefrontal cortex, lateral habenula and the interpeduncular and median raphe nuclei, suggesting it is highly integrated in circuits regulating higher cognitive behaviours (hippocampal theta rhythm) and emotion. Anatomical and functional studies have revealed that the NI is a rich source of multiple peptide neuromodulators, including relaxin-3, and may mediate extra-hypothalamic effects of the stress hormone corticotrophin-releasing factor, as well as other key modulators such as orexins and oxytocin. This review provides an overview of earlier studies and highlights more recent research that implicates this neural network in the integration of arousal and motivated behaviours and has begun to identify the associated mechanisms. Future research that should help to better clarify the connectivity and function of the NI in major experimental species and humans is also discussed. © 2015 British Society for Neuroendocrinology.

The effects of dynamical synapses on firing rate activity: a spiking neural network model.

PubMed

Khalil, Radwa; Moftah, Marie Z; Moustafa, Ahmed A

2017-11-01

Accumulating evidence relates the fine-tuning of synaptic maturation and regulation of neural network activity to several key factors, including GABA A signaling and a lateral spread length between neighboring neurons (i.e., local connectivity). Furthermore, a number of studies consider short-term synaptic plasticity (STP) as an essential element in the instant modification of synaptic efficacy in the neuronal network and in modulating responses to sustained ranges of external Poisson input frequency (IF). Nevertheless, evaluating the firing activity in response to the dynamical interaction between STP (triggered by ranges of IF) and these key parameters in vitro remains elusive. Therefore, we designed a spiking neural network (SNN) model in which we incorporated the following parameters: local density of arbor essences and a lateral spread length between neighboring neurons. We also created several network scenarios based on these key parameters. Then, we implemented two classes of STP: (1) short-term synaptic depression (STD) and (2) short-term synaptic facilitation (STF). Each class has two differential forms based on the parametric value of its synaptic time constant (either for depressing or facilitating synapses). Lastly, we compared the neural firing responses before and after the treatment with STP. We found that dynamical synapses (STP) have a critical differential role on evaluating and modulating the firing rate activity in each network scenario. Moreover, we investigated the impact of changing the balance between excitation (E) and inhibition (I) on stabilizing this firing activity. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Architecture of human translation initiation factor 3

PubMed Central

Querol-Audi, Jordi; Sun, Chaomin; Vogan, Jacob M.; Smith, Duane; Gu, Yu; Cate, Jamie; Nogales, Eva

2013-01-01

SUMMARY Eukaryotic translation initiation factor 3 (eIF3) plays a central role in protein synthesis by organizing the formation of the 43S preinitiation complex. Using genetic tag visualization by electron microscopy, we reveal the molecular organization of ten human eIF3 subunits, including an octameric core. The structure of eIF3 bears a close resemblance to that of the proteasome lid, with a conserved spatial organization of eight core subunits containing PCI and MPN domains that coordinate functional interactions in both complexes. We further show that eIF3 subunits a and c interact with initiation factors eIF1 and eIF1A, which control the stringency of start codon selection. Finally, we find that subunit j, which modulates messenger RNA interactions with the small ribosomal subunit, makes multiple independent interactions with the eIF3 octameric core. These results highlight the conserved architecture of eIF3 and how it scaffolds key factors that control translation initiation in higher eukaryotes, including humans. PMID:23623729

Direct-Sequence Spread Spectrum System

DTIC Science & Technology

1990-06-01

by directly modulating a conventional narrowband frequency-modulated (FM) carrier by a high rate digital code. The direct modulation is binary phase ...specification of the DSSS system will not be developed. The results of the evaluation phase of this research will be compared against theoretical...spread spectrum is called binary phase -shift keying 19 (BPSK). BPSK is a modulation in which a binary Ŕ" represents a 0-degree relative phase

60-GHz integrated-circuit high data rate quadriphase shift keying exciter and modulator

NASA Technical Reports Server (NTRS)

Grote, A.; Chang, K.

1984-01-01

An integrated-circuit quadriphase shift keying (QPSK) exciter and modulator have demonstrated excellent performance directly modulating a carrier frequency of 60 GHz with an output phase error of less than 3 degrees and maximum amplitude error of 0.5 dB. The circuit consists of a 60-GHz Gunn VCO phase-locked to a low-frequency reference source, a 4th subharmonic mixer, and a QPSK modlator packaged into a small volume of 1.8 x 2.5 x 0.35 in. The use of microstrip has the advantages of small size, light-weight, and low-cost fabrication. The unit has the potential for multigigabit data rate applications.

Combinatorial FSK modulation for power-efficient high-rate communications

NASA Technical Reports Server (NTRS)

Wagner, Paul K.; Budinger, James M.; Vanderaar, Mark J.

1991-01-01

Deep-space and satellite communications systems must be capable of conveying high-rate data accurately with low transmitter power, often through dispersive channels. A class of noncoherent Combinatorial Frequency Shift Keying (CFSK) modulation schemes is investigated which address these needs. The bit error rate performance of this class of modulation formats is analyzed and compared to the more traditional modulation types. Candidate modulator, demodulator, and digital signal processing (DSP) hardware structures are examined in detail. System-level issues are also discussed.

High extinction ratio integrated optical modulator for quantum telecommunication systems

NASA Astrophysics Data System (ADS)

Tronev, A.; Parfenov, M.; Agruzov, P.; Ilichev, I.; Shamray, A.

2018-01-01

A method for increasing the extinction ratio of integrated optical Mach-Zehnder modulators based on LiNbO3 via the photorefractive effect is proposed. The influence of the photorefractive effect on the X- and Y-splitters of intensity modulators is experimentally studied. An increase in the modulator extinction ratio by 17 dB (from 30 to 47 dB) is obtained. It is shown that fabricated modulators with a high extinction ratio are important for quantum key distribution systems.

High performance zeolite LTA pervaporation membranes on ceramic hollow fibers by dipcoating-wiping seed deposition.

PubMed

Wang, Zhengbao; Ge, Qinqin; Shao, Jia; Yan, Yushan

2009-05-27

We demonstrate for the first time that by one single hydrothermal synthesis a zeolite LTA membrane with a high flux of 9.0 kg/m(2) h and high water/ethanol separation factor of 10,000 could be formed on a ceramic hollow fiber that is known for its ability to form a compact module. The flux is the highest reported in the literatures. A novel seeding method, dipcoating-wiping, is key to obtaining zeolite membranes with high separation performance because it reproducibly produces a uniform and trace seed layer on the support. This new seeding method is expected to have serious implications for making defect-free zeolite films and membranes for many applications. The membranes reported here have the potential to solve the key problems that have prevented zeolite membranes from widespread use for biofuel production.

QM/PSK Voice/Data Modem

DOT National Transportation Integrated Search

1976-03-01

Two Quadrature Modulation/Phase Shift Keyed (QM/PSK) Voice/Data Modem systems have been developed as part of the satellite communications hardware for advanced air traffic control systems. These systems consist of a modulator and demodulator unti whi...

The Hands-On Optics Project: a demonstration of module 3-magnificent magnifications

NASA Astrophysics Data System (ADS)

Pompea, Stephen M.; Sparks, Robert T.; Walker, Constance E.

2014-07-01

The Hands-On Optics project offers an example of a set of instructional modules that foster active prolonged engagement. Developed by SPIE, OSA, and NOAO through funding from the U.S. National Science Foundation, the modules were originally designed for afterschool settings and museums. However, because they were based on national standards in mathematics, science, and technology, they were easily adapted for use in classrooms. The philosophy and implementation strategies of the six modules will be described as well as lessons learned in training educators. The modules were implementing with the help of optics industry professionals who served as expert volunteers to assist educators. A key element of the modules was that they were developed around an understanding of optics misconceptions and used culminating activities in each module as a form of authentic assessment. Thus student achievement could be measured by evaluating the actual product created by each student in applying key concepts, tools, and applications together at the end of each module. The program used a progression of disciplinary core concepts to build an integrated sequence and crosscutting ideas and practices to infuse the principles of the modern electro-optical field into the modules. Whenever possible, students were encouraged to experiment and to create, and to pursue inquiry-based approaches. The result was a program that had high appeal to regular as well as gifted students.

TGF-β/BMP signaling and other molecular events: regulation of osteoblastogenesis and bone formation

PubMed Central

Rahman, Md Shaifur; Akhtar, Naznin; Jamil, Hossen Mohammad; Banik, Rajat Suvra; Asaduzzaman, Sikder M

2015-01-01

Transforming growth factor-beta (TGF-β)/bone morphogenetic protein (BMP) plays a fundamental role in the regulation of bone organogenesis through the activation of receptor serine/threonine kinases. Perturbations of TGF-β/BMP activity are almost invariably linked to a wide variety of clinical outcomes, i.e., skeletal, extra skeletal anomalies, autoimmune, cancer, and cardiovascular diseases. Phosphorylation of TGF-β (I/II) or BMP receptors activates intracellular downstream Smads, the transducer of TGF-β/BMP signals. This signaling is modulated by various factors and pathways, including transcription factor Runx2. The signaling network in skeletal development and bone formation is overwhelmingly complex and highly time and space specific. Additive, positive, negative, or synergistic effects are observed when TGF-β/BMP interacts with the pathways of MAPK, Wnt, Hedgehog (Hh), Notch, Akt/mTOR, and miRNA to regulate the effects of BMP-induced signaling in bone dynamics. Accumulating evidence indicates that Runx2 is the key integrator, whereas Hh is a possible modulator, miRNAs are regulators, and β-catenin is a mediator/regulator within the extensive intracellular network. This review focuses on the activation of BMP signaling and interaction with other regulatory components and pathways highlighting the molecular mechanisms regarding TGF-β/BMP function and regulation that could allow understanding the complexity of bone tissue dynamics. PMID:26273537

Stress, food, and inflammation: psychoneuroimmunology and nutrition at the cutting edge.

PubMed

Kiecolt-Glaser, Janice K

2010-05-01

Inflammation is the common link among the leading causes of death. Mechanistic studies have shown how various dietary components can modulate key pathways to inflammation, including sympathetic activity, oxidative stress, transcription factor nuclear factor-kappaB activation, and proinflammatory cytokine production. Behavioral studies have demonstrated that stressful events and depression can also influence inflammation through these same processes. If the joint contributions of diet and behavior to inflammation were simply additive, they would be important. However, several far more intriguing interactive possibilities are discussed: stress influences food choices; stress can enhance maladaptive metabolic responses to unhealthy meals; and diet can affect mood as well as proinflammatory responses to stressors. Furthermore, because the vagus nerve innervates tissues involved in the digestion, absorption, and metabolism of nutrients, vagal activation can directly and profoundly influence metabolic responses to food, as well as inflammation; in turn, both depression and stress have well-documented negative effects on vagal activation, contributing to the lively interplay between the brain and the gut. As one example, omega-3 fatty acid intake can boost mood and vagal tone, dampen nuclear factor-kappaB activation and responses to endotoxin, and modulate the magnitude of inflammatory responses to stressors. A better understanding of how stressors, negative emotions, and unhealthy meals work together to enhance inflammation will benefit behavioral and nutritional research, as well as the broader biomedical community.

Lifestyle Modulators of Neuroplasticity: How Physical Activity, Mental Engagement, and Diet Promote Cognitive Health during Aging.

PubMed

Phillips, Cristy

2017-01-01

The number of the elderly across the globe will approximate 2.1 billion by 2050. Juxtaposed against this burgeoning segment of the population is evidence that nonpathological aging is associated with an increased risk for cognitive decline in a variety of domains, changes that can cause mild disability even before the onset of dementia. Given that pharmacological treatments that mitigate dementia are still outstanding, alternative therapeutic options are being investigated increasingly. The results from translational studies have shown that modifiable lifestyle factors-including physical activity, cognitive engagement, and diet-are a key strategy for maintaining brain health during aging. Indeed, a multiplicity of studies has demonstrated relationships between lifestyle factors, brain structure and function, and cognitive function in aging adults. For example, physical activity and diet modulate common neuroplasticity substrates (neurotrophic signaling, neurogenesis, inflammation, stress response, and antioxidant defense) in the brain whereas cognitive engagement enhances brain and cognitive reserve. The aims of this review are to evaluate the relationship between modifiable lifestyle factors, neuroplasticity, and optimal brain health during aging; to identify putative mechanisms that contribute positive brain aging; and to highlight future directions for scientists and clinicians. Undoubtedly, the translation of cutting-edge knowledge derived from the field of cognitive neuroscience will advance our understanding and enhance clinical treatment interventions as we endeavor to promote brain health during aging.

Key factors regulating protein carbonylation by α,β unsaturated carbonyls: A structural study based on a retrospective meta-analysis.

PubMed

Vistoli, Giulio; Mantovani, Chiara; Gervasoni, Silvia; Pedretti, Alessandro; Aldini, Giancarlo

2017-11-01

Protein carbonylation represents one of the most important oxidative-based modifications involving nucleophilic amino acids and affecting protein folding and function. Protein carbonylation is induced by electrophilic carbonyl species and is an highly selective process since few nucleophilic residues are carbonylated within each protein. While considering the great interest for protein carbonylation, few studies investigated the factors which render a nucleophilic residue susceptible to carbonylation. Hence, the present study is aimed to delve into the factors which modulate the reactivity of cysteine, histidine and lysine residues towards α,β unsaturated carbonyls by a retrospective analysis of the available studies which identified the adducted residues for proteins, the structure of which was resolved. Such an analysis involved different parameters including exposure, nucleophilicity, surrounding residues and capacity to attract carbonyl species (as derived by docking simulations). The obtained results allowed a meaningful clustering of the analyzed proteins suggesting that on average carbonylation selectivity increases with protein size. The comparison between adducted and unreactive residues revealed differences in all monitored parameters which are markedly more pronounced for cysteines compared to lysines and histidines. Overall, these results suggest that cysteine's carbonylation is a finely (and reasonably purposely) modulated process, while the carbonylation of lysines and histidines seems to be a fairly random event in which limited differences influence their reactivity. Copyright © 2017 Elsevier B.V. All rights reserved.

Inhibition of GSK3 differentially modulates NF-{kappa}B, CREB, AP-1 and {beta}-catenin signaling in hepatocytes, but fails to promote TNF-{alpha}-induced apoptosis

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

Goetschel, Frank; Kern, Claudia; Lang, Simona

2008-04-01

Glycogen synthase kinase-3 (GSK-3) is known to modulate cell survival and apoptosis through multiple intracellular signaling pathways. However, its hepatoprotective function and its role in activation of NF-{kappa}B and anti-apoptotic factors are poorly understood and remain controversial. Here we investigated whether inhibition of GSK-3 could induce apoptosis in the presence of TNF-{alpha} in primary mouse hepatocytes. We show that pharmacological inhibition of GSK-3 in primary mouse hepatocytes does not lead to TNF-{alpha}-induced apoptosis despite reduced NF-{kappa}B activity. Enhanced stability of I{kappa}B-{alpha} appears to be responsible for lower levels of nuclear NF-{kappa}B and hence reduced transactivation. Additionally, inhibition of GSK-3 wasmore » accompanied by marked upregulation of {beta}-catenin, AP-1, and CREB transcription factors. Stimulation of canonical Wnt signaling and CREB activity led to elevated levels of anti-apoptotic factors. Hence, survival of primary mouse hepatocytes may be caused by the activation and/or upregulation of other key regulators of liver homeostasis and regeneration. These signaling molecules may compensate for the compromised anti-apoptotic function of NF-{kappa}B and allow survival of hepatocytes in the presence of TNF-{alpha} and GSK-3 inhibition.« less

Mitochondrial and Chloroplast Stress Responses Are Modulated in Distinct Touch and Chemical Inhibition Phases1[OPEN

PubMed Central

Ivanova, Aneta; Millar, A. Harvey; Whelan, James

2016-01-01

Previous studies have identified a range of transcription factors that modulate retrograde regulation of mitochondrial and chloroplast functions in Arabidopsis (Arabidopsis thaliana). However, the relative importance of these regulators and whether they act downstream of separate or overlapping signaling cascades is still unclear. Here, we demonstrate that multiple stress-related signaling pathways, with distinct kinetic signatures, converge on overlapping gene sets involved in energy organelle function. The transcription factor ANAC017 is almost solely responsible for transcript induction of marker genes around 3 to 6 h after chemical inhibition of organelle function and is a key regulator of mitochondrial and specific types of chloroplast retrograde signaling. However, an independent and highly transient gene expression phase, initiated within 10 to 30 min after treatment, also targets energy organelle functions, and is related to touch and wounding responses. Metabolite analysis demonstrates that this early response is concurrent with rapid changes in tricarboxylic acid cycle intermediates and large changes in transcript abundance of genes encoding mitochondrial dicarboxylate carrier proteins. It was further demonstrated that transcription factors AtWRKY15 and AtWRKY40 have repressive regulatory roles in this touch-responsive gene expression. Together, our results show that several regulatory systems can independently affect energy organelle function in response to stress, providing different means to exert operational control. PMID:27208304

Design and Processing of a Novel Chaos-Based Stepped Frequency Synthesized Wideband Radar Signal.

PubMed

Zeng, Tao; Chang, Shaoqiang; Fan, Huayu; Liu, Quanhua

2018-03-26

The linear stepped frequency and linear frequency shift keying (FSK) signal has been widely used in radar systems. However, such linear modulation signals suffer from the range-Doppler coupling that degrades radar multi-target resolution. Moreover, the fixed frequency-hopping or frequency-coded sequence can be easily predicted by the interception receiver in the electronic countermeasures (ECM) environments, which limits radar anti-jamming performance. In addition, the single FSK modulation reduces the radar low probability of intercept (LPI) performance, for it cannot achieve a large time-bandwidth product. To solve such problems, we propose a novel chaos-based stepped frequency (CSF) synthesized wideband signal in this paper. The signal introduces chaotic frequency hopping between the coherent stepped frequency pulses, and adopts a chaotic frequency shift keying (CFSK) and phase shift keying (PSK) composited coded modulation in a subpulse, called CSF-CFSK/PSK. Correspondingly, the processing method for the signal has been proposed. According to our theoretical analyses and the simulations, the proposed signal and processing method achieve better multi-target resolution and LPI performance. Furthermore, flexible modulation is able to increase the robustness against identification of the interception receiver and improve the anti-jamming performance of the radar.

The New Youth Entrepreneur: Getting Ready for Entrepreneurship. Opportunities-They Are All Around You. Module 2.

ERIC Educational Resources Information Center

Kourilsky, Marilyn; And Others

The New Youth Entrepreneur curriculum is a series of 12 youth-oriented educational modules containing instructional materials, learning activities, and checkup exercises designed to teach students key elements of entrepreneurship. This document is the second module, designed to help students define the notion of opportunity, determine sources of…

Project VITA: Phototypesetting. Module III, Lessons 8, 9, and 10. Teacher Manual [and] Student Handbook.

ERIC Educational Resources Information Center

Mika, Michelle A.; Unsworth, Linda

This document is the third of five curriculum modules containing instructional units for disabled students who need assistance in mastering the function keys for the ExecuWriter II, a phototypesetter manufactured by Compugraphics of Wilmington, Massachusetts. The purpose of these modules is to provide supplementary instruction on an individualized…

The New Youth Entrepreneur: Getting Ready for Entrepreneurship. Business Ideas for All Communities. Module 3.

ERIC Educational Resources Information Center

Kourilsky, Marilyn; And Others

The New Youth Entrepreneur curriculum is a series of 12 youth-oriented educational modules containing instructional materials, learning activities, and checkup exercises designed to teach students key elements of entrepreneurship. This document is the third module, which focuses on issues related to starting a business and providing ideas for…

Nuclear Technology. Course 28: Welding Inspection. Module 28-2, Shielded Metal Arc and Oxyacetylene Welding.

ERIC Educational Resources Information Center

Espy, John; Selleck, Ben

This second in a series of ten modules for a course titled Welding Inspection describes the key features of the oxyacetylene and shielded metal arc welding process. The apparatus, process techniques, procedures, applications, associated defects, and inspections are presented. The module follows a typical format that includes the following…

Agribusiness Safety. Module SH-15. Safety and Health.

ERIC Educational Resources Information Center

Center for Occupational Research and Development, Inc., Waco, TX.

This student module on agribusiness safety is one of 50 modules concerned with job safety and health. Following the introduction, 11 objectives (each keyed to a page in the text) the student is expected to accomplish are listed (e.g., List at least two reasons for agribusiness safety standards). Then each objective is taught in detail, sometimes…

The New Youth Entrepreneur: You Can Make It Happen. YESS! You. The Business Plan. Module 12.

ERIC Educational Resources Information Center

Kourilsky, Marilyn; And Others

The New Youth Entrepreneur curriculum is a series of 12 youth-oriented educational modules containing instructional materials, learning activities, and checkup exercises designed to teach students key elements of entrepreneurship. This document is the twelfth module, and discusses the usefulness of a business plan for entrepreneurs starting small…

Vibration and Noise Control. Module SH-33. Safety and Health.

ERIC Educational Resources Information Center

Center for Occupational Research and Development, Inc., Waco, TX.

This student module on vibration and noise control is one of 50 modules concerned with job safety and health. Following the introduction, nine objectives (each keyed to a page in the text) the student is expected to accomplish are listed (e.g., Compare four strategies for vibration control). Then each objective is taught in detail, sometimes…

Modulation of Decidual Macrophage Polarization by Macrophage Colony-Stimulating Factor Derived from First-Trimester Decidual Cells

PubMed Central

Li, Min; Piao, Longzhu; Chen, Chie-Pein; Wu, Xianqing; Yeh, Chang-Ching; Masch, Rachel; Chang, Chi-Chang; Huang, S. Joseph

2017-01-01

During human pregnancy, immune tolerance of the fetal semiallograft occurs in the presence of abundant maternal leukocytes. At the implantation site, macrophages comprise approximately 20% of the leukocyte population and act as primary mediators of tissue remodeling. Decidual macrophages display a balance between anti-inflammatory and proinflammatory phenotypes. However, a shift to an M1 subtype is reported in preeclampsia. Granulocyte-macrophage colony-stimulating-factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) are major differentiating factors that mediate M1 and M2 polarization, respectively. Previously, we observed the following: i) the preeclamptic decidua contains an excess of both macrophages and GM-CSF, ii) the preeclampsia-associated proinflammatory cytokines, IL-1β and tumor necrosis factor-α, markedly enhance GM-CSF and M-CSF expression in cultured leukocyte-free first-trimester decidual cells (FTDCs), iii) FTDC-secreted GM-CSF polarizes macrophages toward an M1 subtype. The microenvironment is a key determinant of macrophage phenotype. Thus, we examined proinflammatory stimulation of FTDC-secreted M-CSF and its role in macrophage development. Immunofluorescence staining demonstrated elevated M-CSF–positive decidual cell numbers in preeclamptic decidua. In FTDCs, IL-1β and tumor necrosis factor-α signal through the NF-κB pathway to induce M-CSF production, which does the following: i) enhances differentiation of and elevates CD163 expression in macrophages, ii) increases macrophage phagocytic capacity, and iii) inhibits signal-regulatory protein α expression by macrophages. These findings suggest that FTDC-secreted M-CSF modulates the decidual immune balance by inducing M2 macrophage polarization and phagocytic capacity in response to proinflammatory stimuli. PMID:26970370

Pregnane and Xenobiotic Receptor gene expression in liver cells is modulated by Ets-1 in synchrony with transcription factors Pax5, LEF-1 and c-jun

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

Kumari, Sangeeta; Saradhi, Mallampati; Rana, Manjul

2015-01-15

Nuclear receptor PXR is predominantly expressed in liver and intestine. Expression of PXR is observed to be dysregulated in various metabolic disorders indicating its involvement in disease development. However, information available on mechanisms of PXR self-regulation is fragmentary. The present investigation identifies some of the regulatory elements responsible for its tight regulation and low cellular expression. Here, we report that the PXR-promoter is a target for some key transcription factors like PU.1/Ets-1, Pax5, LEF-1 and c-Jun. Interestingly, we observed that PXR-promoter responsiveness to Pax5, LEF-1 and c-Jun, is considerably enhanced by Ets transcription factors (PU.1 and Ets-1). Co-transfection of cellsmore » with Ets-1, LEF-1 and c-Jun increased PXR-promoter activity by 5-fold and also induced expression of endogenous human PXR. Site-directed mutagenesis and transfection studies revealed that two Ets binding sites and two of the three LEF binding sites in the PXR-promoter are functional and have a positive effect on PXR transcription. Results suggest that expression of Ets family members, in conjunction with Pax5, LEF-1 and c-Jun, lead to coordinated up-regulation of PXR gene transcription. Insights obtained on the regulation of PXR gene have relevance in offering important cues towards normal functioning as well as development of several metabolic disorders via PXR signaling. - Highlights: • The study identified cis-regulatory elements in the nuclear receptor PXR promoter. • Several trans-acting factors modulating the PXR-promoter have been identified. • PU.1/Ets-1, Pax5, LEF-1, c-Jun, LyF-VI and NF-1 act as modulators of the PXR-promoter. • Ets-1 in conjunction with LEF-1 and c-Jun exhibit 5-fold activation of the PXR-promoter. • Insights into PXR-regulation have relevance in normal and pathological conditions.« less

The trypanocidal benznidazole promotes adaptive response to oxidative injury: Involvement of the nuclear factor-erythroid 2-related factor-2 (Nrf2) and multidrug resistance associated protein 2 (MRP2)

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

Rigalli, Juan Pablo

Oxidative stress is a frequent cause underlying drug-induced hepatotoxicity. Benznidazole (BZL) is the only trypanocidal agent available for treatment of Chagas disease in endemic areas. Its use is associated with side effects, including increases in biomarkers of hepatotoxicity. However, BZL potential to cause oxidative stress has been poorly investigated. Here, we evaluated the effect of a pharmacologically relevant BZL concentration (200 μM) at different time points on redox status and the counteracting mechanisms in the human hepatic cell line HepG2. BZL increased reactive oxygen species (ROS) after 1 and 3 h of exposure, returning to normality at 24 h. Additionally,more » BZL increased glutathione peroxidase activity at 12 h and the oxidized glutathione/total glutathione (GSSG/GSSG + GSH) ratio that reached a peak at 24 h. Thus, an enhanced detoxification of peroxide and GSSG formation could account for ROS normalization. GSSG/GSSG + GSH returned to control values at 48 h. Expression of the multidrug resistance-associated protein 2 (MRP2) and GSSG efflux via MRP2 were induced by BZL at 24 and 48 h, explaining normalization of GSSG/GSSG + GSH. BZL activated the nuclear erythroid 2-related factor 2 (Nrf2), already shown to modulate MRP2 expression in response to oxidative stress. Nrf2 participation was confirmed using Nrf2-knockout mice in which MRP2 mRNA expression was not affected by BZL. In summary, we demonstrated a ROS increase by BZL in HepG2 cells and a glutathione peroxidase- and MRP2 driven counteracting mechanism, being Nrf2 a key modulator of this response. Our results could explain hepatic alterations associated with BZL therapy. - Highlights: • BZL triggers a redox imbalance in the human hepatic cell line HepG2. • Concomitantly BZL triggers compensatory mechanisms to alleviate the redox injury. • Response mechanisms comprise an enhanced glutathione peroxidase and MRP2 activity. • Transcription factor Nrf2 plays a key role orchestrating compensatory mechanisms.« less

Quadrature-quadrature phase-shift keying

NASA Astrophysics Data System (ADS)

Saha, Debabrata; Birdsall, Theodore G.

1989-05-01

Quadrature-quadrature phase-shift keying (Q2PSK) is a spectrally efficient modulation scheme which utilizes available signal space dimensions in a more efficient way than two-dimensional schemes such as QPSK and MSK (minimum-shift keying). It uses two data shaping pulses and two carriers, which are pairwise quadrature in phase, to create a four-dimensional signal space and increases the transmission rate by a factor of two over QPSK and MSK. However, the bit error rate performance depends on the choice of pulse pair. With simple sinusoidal and cosinusoidal data pulses, the Eb/N0 requirement for Pb(E) = 10 to the -5 is approximately 1.6 dB higher than that of MSK. Without additional constraints, Q2PSK does not maintain constant envelope. However, a simple block coding provides a constant envelope. This coded signal substantially outperforms MSKS and TFM (time-frequency multiplexing) in bandwidth efficiency. Like MSK, Q2PSK also has self-clocking and self-synchronizing ability. An optimum class of pulse shapes for use in Q2PSK-format is presented. One suboptimum realization achieves the Nyquist rate of 2 bits/s/Hz using binary detection.

Multiple Assembly Rules Drive the Co-occurrence of Orthopteran and Plant Species in Grasslands: Combining Network, Functional and Phylogenetic Approaches

PubMed Central

Fournier, Bertrand; Mouly, Arnaud; Gillet, François

2016-01-01

Understanding the factors underlying the co-occurrence of multiple species remains a challenge in ecology. Biotic interactions, environmental filtering and neutral processes are among the main mechanisms evoked to explain species co-occurrence. However, they are most often studied separately or even considered as mutually exclusive. This likely hampers a more global understanding of species assembly. Here, we investigate the general hypothesis that the structure of co-occurrence networks results from multiple assembly rules and its potential implications for grassland ecosystems. We surveyed orthopteran and plant communities in 48 permanent grasslands of the French Jura Mountains and gathered functional and phylogenetic data for all species. We constructed a network of plant and orthopteran species co-occurrences and verified whether its structure was modular or nested. We investigated the role of all species in the structure of the network (modularity and nestedness). We also investigated the assembly rules driving the structure of the plant-orthopteran co-occurrence network by using null models on species functional traits, phylogenetic relatedness and environmental conditions. We finally compared our results to abundance-based approaches. We found that the plant-orthopteran co-occurrence network had a modular organization. Community assembly rules differed among modules for plants while interactions with plants best explained the distribution of orthopterans into modules. Few species had a disproportionately high positive contribution to this modular organization and are likely to have a key importance to modulate future changes. The impact of agricultural practices was restricted to some modules (3 out of 5) suggesting that shifts in agricultural practices might not impact the entire plant-orthopteran co-occurrence network. These findings support our hypothesis that multiple assembly rules drive the modular structure of the plant-orthopteran network. This modular structure is likely to play a key role in the response of grassland ecosystems to future changes by limiting the impact of changes in agricultural practices such as intensification to some modules leaving species from other modules poorly impacted. The next step is to understand the importance of this modular structure for the long-term maintenance of grassland ecosystem structure and functions as well as to develop tools to integrate network structure into models to improve their capacity to predict future changes. PMID:27582754

A teaching module about stellar structure and evolution

NASA Astrophysics Data System (ADS)

Colantonio, Arturo; Galano, Silvia; Leccia, Silvio; Puddu, Emanuella; Testa, Italo

2017-01-01

In this paper, we present a teaching module about stellar structure, functioning and evolution. Drawing from literature in astronomy education, we designed the activities around three key ideas: spectral analysis, mechanical and thermal equilibrium, energy and nuclear reactions. The module is divided into four phases, in which the key ideas for describing stars' functioning and physical mechanisms are gradually introduced. The activities (20 hours) build on previously learned laws in mechanics, thermodynamics, and electromagnetism and help students combine them meaningfully in order to get a complete picture of processes that happens in stars. The module was piloted with two intact classes of secondary school students (N = 59 students, 17-18 years old), using a ten-question multiple-choice questionnaire as research instrument. Results support the effectiveness of the proposed activities. Implications for the teaching of advanced physics topics using stars as fruitful context are briefly discussed.

A WDM-PON with DPSK modulated downstream and OOK modulated upstream signals based on symmetric 10 Gbit/s wavelength reused bidirectional reflective SOA

NASA Astrophysics Data System (ADS)

El-Nahal, Fady I.

2017-01-01

We investigate a wavelength-division-multiplexing passive optical network (WDM-PON) with centralized lightwave and direct detection. The system is demonstrated for symmetric 10 Gbit/s differential phase-shift keying (DPSK) downstream signals and on-off keying (OOK) upstream signals, respectively. A wavelength reused scheme is employed to carry the upstream data by using a reflective semiconductor optical amplifier (RSOA) as an intensity modulator at the optical network unit (ONU). The constant-intensity property of the DPSK modulation format can keep high extinction ratio ( ER) of downstream signal and reduce the crosstalk to the upstream signal. The bit error rate ( BER) performance of our scheme shows that the proposed 10 Gbit/s symmetric WDM-PON can achieve error free transmission over 25-km-long fiber transmission with low power penalty.

Low-cost manufacturing of the point focus concentrating module and its key component, the Fresnel lens. Final subcontract report, 31 January 1991--6 May 1991

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

Saifee, T.; Konnerth, A. III

1991-11-01

Solar Kinetics, Inc. (SKI) has been developing point-focus concentrating PV modules since 1986. SKI is currently in position to manufacture between 200 to 600 kilowatts annually of the current design by a combination of manual and semi-automated methods. This report reviews the current status of module manufacture and specifies the required approach to achieve a high-volume manufacturing capability and low cost. The approach taken will include process development concurrent with module design for automated manufacturing. The current effort reviews the major manufacturing costs and identifies components and processes whose improvements would produce the greatest effect on manufacturability and cost reduction.more » The Fresnel lens is one such key component. Investigating specific alternative manufacturing methods and sources has substantially reduced the lens costs and has exceeded the DOE cost-reduction goals. 15 refs.« less

Wave-Coupled Millimeter-Wave Electro-Optic Techniques

DTIC Science & Technology

2001-03-01

This report details results on two antenna-coupled millimeter-wave electro - optic modulators, the slot-vee antenna-coupled modulator and a 94 GHz...study of the effects of velocity mismatch on linearized electro - optic modulators was made and the results published. A key result was that directional...drift in electro - optic modulators was made and protons were determined to be the cause. Several inventions were made to reduce or eliminate proton-caused bias drift.

V-band integrated quadriphase modulator

NASA Technical Reports Server (NTRS)

Grote, A.; Chang, K.

1983-01-01

A V-band integrated circuit quadriphase shift keyed modulator/exciter for space communications systems was developed. Intersatellite communications systems require direct modulation at 60 GHz to enhance signal processing capability. For most systems, particularly space applications, small and lightweight components are essential to alleviate severe system design constraints. Thus to achieve wideband, high data rate systems, direct modulation techniques at millimeter waves using solid state integrated circuit technology are an integral part of the overall technology developments.

Advancements in n-Type Base Crystalline Silicon Solar Cells and Their Emergence in the Photovoltaic Industry

PubMed Central

ur Rehman, Atteq; Lee, Soo Hong

2013-01-01

The p-type crystalline silicon wafers have occupied most of the solar cell market today. However, modules made with n-type crystalline silicon wafers are actually the most efficient modules up to date. This is because the material properties offered by n-type crystalline silicon substrates are suitable for higher efficiencies. Properties such as the absence of boron-oxygen related defects and a greater tolerance to key metal impurities by n-type crystalline silicon substrates are major factors that underline the efficiency of n-type crystalline silicon wafer modules. The bi-facial design of n-type cells with good rear-side electronic and optical properties on an industrial scale can be shaped as well. Furthermore, the development in the industrialization of solar cell designs based on n-type crystalline silicon substrates also highlights its boost in the contributions to the photovoltaic industry. In this paper, a review of various solar cell structures that can be realized on n-type crystalline silicon substrates will be given. Moreover, the current standing of solar cell technology based on n-type substrates and its contribution in photovoltaic industry will also be discussed. PMID:24459433

Real-time experimental demonstrations of software reconfigurable optical OFDM transceivers utilizing DSP-based digital orthogonal filters for SDN PONs.

PubMed

Duan, X; Giddings, R P; Bolea, M; Ling, Y; Cao, B; Mansoor, S; Tang, J M

2014-08-11

Real-time optical OFDM (OOFDM) transceivers with on-line software-controllable channel reconfigurability and transmission performance adaptability are experimentally demonstrated, for the first time, utilizing Hilbert-pair-based 32-tap digital orthogonal filters implemented in FPGAs. By making use of an 8-bit DAC/ADC operating at 2GS/s, an oversampling factor of 2 and an EML intensity modulator, the demonstrated RF conversion-free transceiver supports end-to-end real-time simultaneous adaptive transmissions, within a 1GHz signal spectrum region, of a 2.03Gb/s in-phase OOFDM channel and a 1.41Gb/s quadrature-phase OOFDM channel over a 25km SSMF IMDD system. In addition, detailed experimental explorations are also undertaken of key physical mechanisms limiting the maximum achievable transmission performance, impacts of transceiver's channel multiplexing/demultiplexing operations on the system BER performance, and the feasibility of utilizing adaptive modulation to combat impairments associated with low-complexity digital filter designs. Furthermore, experimental results indicate that the transceiver incorporating a fixed digital orthogonal filter DSP architecture can be made transparent to various signal modulation formats up to 64-QAM.

Pharmacologic approaches to cerebral aging and neuroplasticity: insights from the stroke model.

PubMed

Chollet, François

2013-03-01

Brain plasticity is an intrinsic characteristic of the nervous system that allows continuous remodeling of brain functions in pathophysiological conditions. Although normal aging is associated with morphological modifications and decline of cerebral functions, brain plasticity is at least partially preserved in elderly individuals. A growing body of evidence supports the notion that cognitive enrichment and aerobic training induce a dynamic reorganization of higher cerebral functions, thereby helping to maintain operational skills in the elderly and reducing the incidence of dementia. The stroke model clearly shows that spontaneous brain plasticity exists after a lesion, even in old patients, and that it can be modulated through external factors like rehabilitation and drugs. Whether drugs can be used with the aim of modulating the effects of physical training or cognitive stimulation in healthy aged people has not been addressed until now. The risk:benefit ratio will be the key question with regard to the ethical aspect of this challenge. We review in this article the main aspects of human brain plasticity as shown in patients with stroke, the drug modulation of brain plasticity and its consequences on recovery, and finally we address the question of the influence of aging on brain plasticity.

Advancements in n-type base crystalline silicon solar cells and their emergence in the photovoltaic industry.

PubMed

ur Rehman, Atteq; Lee, Soo Hong

2013-01-01

The p-type crystalline silicon wafers have occupied most of the solar cell market today. However, modules made with n-type crystalline silicon wafers are actually the most efficient modules up to date. This is because the material properties offered by n-type crystalline silicon substrates are suitable for higher efficiencies. Properties such as the absence of boron-oxygen related defects and a greater tolerance to key metal impurities by n-type crystalline silicon substrates are major factors that underline the efficiency of n-type crystalline silicon wafer modules. The bi-facial design of n-type cells with good rear-side electronic and optical properties on an industrial scale can be shaped as well. Furthermore, the development in the industrialization of solar cell designs based on n-type crystalline silicon substrates also highlights its boost in the contributions to the photovoltaic industry. In this paper, a review of various solar cell structures that can be realized on n-type crystalline silicon substrates will be given. Moreover, the current standing of solar cell technology based on n-type substrates and its contribution in photovoltaic industry will also be discussed.

TACE/ADAM17 is essential for oligodendrocyte development and CNS myelination.

PubMed

Palazuelos, Javier; Crawford, Howard C; Klingener, Michael; Sun, Bingru; Karelis, Jason; Raines, Elaine W; Aguirre, Adan

2014-09-03

Several studies have elucidated the significance of a disintegrin and metalloproteinase proteins (ADAMs) in PNS myelination, but there is no evidence if they also play a role in oligodendrogenesis and CNS myelination. Our study identifies ADAM17, also called tumor necrosis factor-α converting enzyme (TACE), as a novel key modulator of oligodendrocyte (OL) development and CNS myelination. Genetic deletion of TACE in oligodendrocyte progenitor cells (OPs) induces premature cell cycle exit and reduces OL cell survival during postnatal myelination of the subcortical white matter (SCWM). These cellular and molecular changes lead to deficits in SCWM myelination and motor behavior. Mechanistically, TACE regulates oligodendrogenesis by modulating the shedding of EGFR ligands TGFα and HB-EGF and, consequently, EGFR signaling activation in OL lineage cells. Constitutive TACE depletion in OPs in vivo leads to similar alterations in CNS myelination and motor behavior as to what is observed in the EGFR hypofunctional mouse line EgfrWa2. EGFR overexpression in TACE-deficient OPs restores OL survival and development. Our study reveals an essential function of TACE in oligodendrogenesis, and demonstrates how this molecule modulates EGFR signaling activation to regulate postnatal CNS myelination. Copyright © 2014 the authors 0270-6474/14/3411884-13$15.00/0.

High gain solar photovoltaics

NASA Astrophysics Data System (ADS)

MacDonald, B.; Finot, M.; Heiken, B.; Trowbridge, T.; Ackler, H.; Leonard, L.; Johnson, E.; Chang, B.; Keating, T.

2009-08-01

Skyline Solar Inc. has developed a novel silicon-based PV system to simultaneously reduce energy cost and improve scalability of solar energy. The system achieves high gain through a combination of high capacity factor and optical concentration. The design approach drives innovation not only into the details of the system hardware, but also into manufacturing and deployment-related costs and bottlenecks. The result of this philosophy is a modular PV system whose manufacturing strategy relies only on currently existing silicon solar cell, module, reflector and aluminum parts supply chains, as well as turnkey PV module production lines and metal fabrication industries that already exist at enormous scale. Furthermore, with a high gain system design, the generating capacity of all components is multiplied, leading to a rapidly scalable system. The product design and commercialization strategy cooperate synergistically to promise dramatically lower LCOE with substantially lower risk relative to materials-intensive innovations. In this paper, we will present the key design aspects of Skyline's system, including aspects of the optical, mechanical and thermal components, revealing the ease of scalability, low cost and high performance. Additionally, we will present performance and reliability results on modules and the system, using ASTM and UL/IEC methodologies.

Picosecond dynamics from lanthanide chloride melts

NASA Astrophysics Data System (ADS)

Kalampounias, Angelos G.

2012-12-01

The picosecond dynamics of molten lanthanide chlorides is studied by means of vibrational spectroscopy. Polarized Raman spectra of molten LaCl3, NdCl3, GdCl3, DyCl3, HoCl3 and YCl3 are fitted to a model enabling to obtain the times of vibrational dephasing, tν and vibrational frequency modulation tω. Our aim is to find possible sensitive indicators of short-time dynamics. It has been found that all lanthanide chlorides exhibit qualitative similarities in the vibrational relaxation and frequency modulation times in the molten state. It appears that the vibrational correlation functions of all melts comply with the Rothschild approach assuming that the environmental modulation is described by a stretched exponential decay. The evolution of the dispersion parameter α indicates the deviation of the melts from the model simple liquid and the similar local environment in which the oscillator is placed and with which it is coupled. The "packing" of the anions around central La3+ cation seems to be the key factor for the structure and the dynamics of the melts. The results are discussed in the framework of the current phenomenological status of the field.

Key Questions in Building Defect Prediction Models in Practice

NASA Astrophysics Data System (ADS)

Ramler, Rudolf; Wolfmaier, Klaus; Stauder, Erwin; Kossak, Felix; Natschläger, Thomas

The information about which modules of a future version of a software system are defect-prone is a valuable planning aid for quality managers and testers. Defect prediction promises to indicate these defect-prone modules. However, constructing effective defect prediction models in an industrial setting involves a number of key questions. In this paper we discuss ten key questions identified in context of establishing defect prediction in a large software development project. Seven consecutive versions of the software system have been used to construct and validate defect prediction models for system test planning. Furthermore, the paper presents initial empirical results from the studied project and, by this means, contributes answers to the identified questions.

An Iterative Information-Reduced Quadriphase-Shift-Keyed Carrier Synchronization Scheme Using Decision Feedback for Low Signal-to-Noise Ratio Applications

NASA Technical Reports Server (NTRS)

Simon, M.; Tkacenko, A.

2006-01-01

In a previous publication [1], an iterative closed-loop carrier synchronization scheme for binary phase-shift keyed (BPSK) modulation was proposed that was based on feeding back data decisions to the input of the loop, the purpose being to remove the modulation prior to carrier synchronization as opposed to the more conventional decision-feedback schemes that incorporate such feedback inside the loop. The idea there was that, with sufficient independence between the received data and the decisions on it that are fed back (as would occur in an error-correction coding environment with sufficient decoding delay), a pure tone in the presence of noise would ultimately be produced (after sufficient iteration and low enough error probability) and thus could be tracked without any squaring loss. This article demonstrates that, with some modification, the same idea of iterative information reduction through decision feedback can be applied to quadrature phase-shift keyed (QPSK) modulation, something that was mentioned in the previous publication but never pursued.

Auditing and Mapping Key Skills within University Curricula

ERIC Educational Resources Information Center

Tariq, Vicki N.; Scott, Eileen M.; Cochrane, A. Clive; Lee, Maria; Ryles, Linda

2004-01-01

Universities are encouraged to embed key skills in their undergraduate curricula, yet there is often little support on how to identify skills development and progression. This paper describes a tool that facilitates colleagues in auditing key skills and career/employability skills within individual modules and mapping these skills across degree…

Implementation of continuous-variable quantum key distribution with discrete modulation

NASA Astrophysics Data System (ADS)

Hirano, Takuya; Ichikawa, Tsubasa; Matsubara, Takuto; Ono, Motoharu; Oguri, Yusuke; Namiki, Ryo; Kasai, Kenta; Matsumoto, Ryutaroh; Tsurumaru, Toyohiro

2017-06-01

We have developed a continuous-variable quantum key distribution (CV-QKD) system that employs discrete quadrature-amplitude modulation and homodyne detection of coherent states of light. We experimentally demonstrated automated secure key generation with a rate of 50 kbps when a quantum channel is a 10 km optical fibre. The CV-QKD system utilises a four-state and post-selection protocol and generates a secure key against the entangling cloner attack. We used a pulsed light source of 1550 nm wavelength with a repetition rate of 10 MHz. A commercially available balanced receiver is used to realise shot-noise-limited pulsed homodyne detection. We used a non-binary LDPC code for error correction (reverse reconciliation) and the Toeplitz matrix multiplication for privacy amplification. A graphical processing unit card is used to accelerate the software-based post-processing.

Electromagnetic behavior of spatial terahertz wave modulators based on reconfigurable micromirror gratings in Littrow configuration.

PubMed

Kappa, Jan; Schmitt, Klemens M; Rahm, Marco

2017-08-21

Efficient, high speed spatial modulators with predictable performance are a key element in any coded aperture terahertz imaging system. For spectroscopy, the modulators must also provide a broad modulation frequency range. In this study, we numerically analyze the electromagnetic behavior of a dynamically reconfigurable spatial terahertz wave modulator based on a micromirror grating in Littrow configuration. We show that such a modulator can modulate terahertz radiation over a wide frequency range from 1.7 THz to beyond 3 THz at a modulation depth of more than 0.6. As a specific example, we numerically simulated coded aperture imaging of an object with binary transmissive properties and successfully reconstructed the image.

Quantum cryptography to satellites for global secure key distribution

NASA Astrophysics Data System (ADS)

Rarity, John G.; Gorman, Philip M.; Knight, Paul; Wallace, Kotska; Tapster, Paul R.

2017-11-01

We have designed and built a free space secure key exchange system using weak laser pulses with polarisation modulation by acousto-optic switching. We have used this system to exchange keys over a 1.2km ground range with absolute security. Building from this initial result we analyse the feasibility of exchanging keys to a low earth orbit satellite.

Optical key system

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

Hagans, K.G.; Clough, R.E.

2000-04-25

An optical key system comprises a battery-operated optical key and an isolated lock that derives both its operating power and unlock signals from the correct optical key. A light emitting diode or laser diode is included within the optical key and is connected to transmit a bit-serial password. The key user physically enters either the code-to-transmit directly, or an index to a pseudorandom number code, in the key. Such person identification numbers can be retained permanently, or ephemeral. When a send button is pressed, the key transmits a beam of light modulated with the password information. The modulated beam ofmore » light is received by a corresponding optical lock with a photovoltaic cell that produces enough power from the beam of light to operate a password-screen digital logic. In one application, an acceptable password allows a two watt power laser diode to pump ignition and timing information over a fiberoptic cable into a sealed engine compartment. The receipt of a good password allows the fuel pump, spark, and starter systems to each operate. Therefore, bypassing the lock mechanism as is now routine with automobile thieves is pointless because the engine is so thoroughly disabled.« less

Optical key system

DOEpatents

Hagans, Karla G.; Clough, Robert E.

2000-01-01

An optical key system comprises a battery-operated optical key and an isolated lock that derives both its operating power and unlock signals from the correct optical key. A light emitting diode or laser diode is included within the optical key and is connected to transmit a bit-serial password. The key user physically enters either the code-to-transmit directly, or an index to a pseudorandom number code, in the key. Such person identification numbers can be retained permanently, or ephemeral. When a send button is pressed, the key transmits a beam of light modulated with the password information. The modulated beam of light is received by a corresponding optical lock with a photovoltaic cell that produces enough power from the beam of light to operate a password-screen digital logic. In one application, an acceptable password allows a two watt power laser diode to pump ignition and timing information over a fiberoptic cable into a sealed engine compartment. The receipt of a good password allows the fuel pump, spark, and starter systems to each operate. Therefore, bypassing the lock mechanism as is now routine with automobile thieves is pointless because the engine is so thoroughly disabled.

Global analysis of gene expression in maize leaves treated with low temperature. II. Combined effect of severe cold (8 °C) and circadian rhythm.

PubMed

Jończyk, M; Sobkowiak, A; Trzcinska-Danielewicz, J; Skoneczny, M; Solecka, D; Fronk, J; Sowiński, P

2017-10-01

In maize seedlings, severe cold results in dysregulation of circadian pattern of gene expression causing profound modulation of transcription of genes related to photosynthesis and other key biological processes. Plants live highly cyclic life and their response to environmental stresses must allow for underlying biological rhythms. To study the interplay of a stress and a rhythmic cue we investigated transcriptomic response of maize seedlings to low temperature in the context of diurnal gene expression. Severe cold stress had pronounced effect on the circadian rhythm of a substantial proportion of genes. Their response was strikingly dual, comprising either flattening (partial or complete) of the diel amplitude or delay of expression maximum/minimum by several hours. Genes encoding central oscillator components behaved in the same dual manner, unlike their Arabidopsis counterparts reported earlier to cease cycling altogether upon cold treatment. Also numerous genes lacking circadian rhythm responded to the cold by undergoing up- or down-regulation. Notably, the transcriptome changes preceded major physiological manifestations of cold stress. In silico analysis of metabolic processes likely affected by observed gene expression changes indicated major down-regulation of photosynthesis, profound and multifarious modulation of plant hormone levels, and of chromatin structure, transcription, and translation. A role of trehalose and stachyose in cold stress signaling was also suggested. Meta-analysis of published transcriptomic data allowed discrimination between general stress response of maize and that unique to severe cold. Several cis- and trans-factors likely involved in the latter were predicted, albeit none of them seemed to have a major role. These results underscore a key role of modulation of diel gene expression in maize response to severe cold and the unique character of the cold-response of the maize circadian clock.

Tumor-associated macrophages, nanomedicine and imaging: the axis of success in the future of cancer immunotherapy.

PubMed

Zanganeh, Saeid; Spitler, Ryan; Hutter, Gregor; Ho, Jim Q; Pauliah, Mohan; Mahmoudi, Morteza

2017-09-01

The success of any given cancer immunotherapy relies on several key factors. In particular, success hinges on the ability to stimulate the immune system in a controlled and precise fashion, select the best treatment options and appropriate therapeutic agents, and use highly effective tools to accurately and efficiently assess the outcome of the immunotherapeutic intervention. Furthermore, a deep understanding and effective utilization of tumor-associated macrophages (TAMs), nanomedicine and biomedical imaging must be harmonized to improve treatment efficacy. Additionally, a keen appreciation of the dynamic interplay that occurs between immune cells and the tumor microenvironment (TME) is also essential. New advances toward the modulation of the immune TME have led to many novel translational research approaches focusing on the targeting of TAMs, enhanced drug and nucleic acid delivery, and the development of theranostic probes and nanoparticles for clinical trials. In this review, we discuss the key cogitations that influence TME, TAM modulations and immunotherapy in solid tumors as well as the methods and resources of tracking the tumor response. The vast array of current nanomedicine technologies can be readily modified to modulate immune function, target specific cell types, deliver therapeutic payloads and be monitored using several different imaging modalities. This allows for the development of more effective treatments, which can be specifically designed for particular types of cancer or on an individual basis. Our current capacities have allowed for greater use of theranostic probes and multimodal imaging strategies that have led to better image contrast, real-time imaging capabilities leveraging targeting moieties, tracer kinetics and enabling more detailed response profiles at the cellular and molecular levels. These novel capabilities along with new discoveries in cancer biology should drive innovation for improved biomarkers for efficient and individualized cancer therapy.

Development of an HTS-Compatible Assay for Discovery of Melanoma-Related Microphthalmia Transcription Factor Disruptors Using AlphaScreen Technology.

PubMed

Wang, Jing; Fang, Pengfei; Chase, Peter; Tshori, Sagi; Razin, Ehud; Spicer, Timothy P; Scampavia, Louis; Hodder, Peter; Guo, Min

2017-01-01

Microphthalmia transcription factor (MITF) is a master transcription factor expressed in melanocytes, essential for melanocyte survival, differentiation, and pigment formation, and is a key oncogenic factor in melanoma initiation, migration, and treatment resistance. Although identified as an important therapeutic target for melanoma, clinical inhibitors directly targeting the MITF protein are not available. Based on the functional state of MITF, we have designed an MITF dimerization-based AlphaScreen (MIDAS) assay that sensitively and specifically mirrors the dimerization of MITF in vitro. This assay is further exploited for identification of the MITF dimer disruptor for high-throughput screening. A pilot screen against a library of 1280 pharmacologically active compounds indicates that the MIDAS assay performance exhibits exceptional results with a Z' factor of 0.81 and a signal-to-background (S/B) ratio of 3.92 while identifying initial hit compounds that yield an ability to disrupt MITF-DNA interaction. The results presented demonstrate that the MIDAS assay is ready to screen large chemical libraries in order to discover novel modulators of MITF for potential melanoma treatment.

Colorless ONU implementation for WDM-PON using direct-detection optical OFDM

NASA Astrophysics Data System (ADS)

Feng, Min; Luo, Qing-long; Bai, Cheng-lin

2013-03-01

A novel architecture for the colorless optical network unit (ONU) is proposed and experimentally demonstrated with direct-detection optical orthogonal frequency division multiplexing (DDO-OFDM). In this architecture, polarization-division multiplexing is used to reduce the cost at ONU. In optical line terminal (OLT), quadrature amplitude modulation (QAM) intensity-modulated OFDM signal with x-polarization at 10 Gbit/s is transmitted as downstream. At each ONU, the optical OFDM signal is demodulated with direct detection, and γ-polarization signal is modulated for upstream on-off keying (OOK) data at 5 Gbit/s. Simulation results show that the power penalty is negligible for both optical OFDM downstream and the on-off keying upstream signals after over 50 km single-mode fiber (SMF) transmission.

In Vitro Studies on the Antimicrobial Peptide Human Beta-Defensin 9 (HBD9): Signalling Pathways and Pathogen-Related Response (An American Ophthalmological Society Thesis)

PubMed Central

Dua, Harminder S.; Otri, Ahmad Muneer; Hopkinson, Andrew; Mohammed, Imran

2014-01-01

Purpose: Human β-defensins (HBDs) are an important part of the innate immune host defense at the ocular surface. Unlike other defensins, expression of HBD9 at the ocular surface is reduced during microbial infection, but activation of toll-like receptor 2 (TLR2) in corneal epithelial cells has been shown to up-regulate HBD9. Our purpose was to test the hypothesis that TLR2 has a key role in the signalling pathway(s) involved in the overexpression or underexpression of HBD9, and accordingly, different pathogens would induce a different expression pattern of HBD9. Methods: The in vitro RNAi silencing method and response to dexamethasone were used to determine key molecules involved in signalling pathways of HBD9 in immortalized human corneal epithelial cells. The techniques included cell culture with exposure to specific transcription factor inhibitors and bacteria, RNA extraction and cDNA synthesis, quantitative real-time polymerase chain reaction, and immunohistology. Results: This study demonstrates that TLR2 induces HBD9 mRNA and protein expression in a time- and dose-dependent manner. Transforming growth factor-β–activated kinase 1 (TAK1) plays a central role in HBD9 induction by TLR2, and transcription factors c-JUN and activating transcription factor 2 are also involved. Dexamethasone reduces TLR2-mediated up-regulation of HBD9 mRNA and protein levels in mitogen-activated protein kinase phosphatase 1 (MKP1)-dependent and c-JUN-independent manner. HBD9 expression differs with gram-negative and gram-positive bacteria. Conclusions: TLR2-mediated MKPs and nuclear factor-κB signalling pathways are involved in HBD9 expression. TAK-1 is a key molecule. These molecules can be potentially targeted to modulate HBD9 expression. Differential expression of HBD9 with different bacteria could be related to differences in pathogen-associated molecular patterns of these organisms. PMID:25646028

Feeding the microbiota-gut-brain axis: diet, microbiome, and neuropsychiatry.

PubMed

Sandhu, Kiran V; Sherwin, Eoin; Schellekens, Harriët; Stanton, Catherine; Dinan, Timothy G; Cryan, John F

2017-01-01

The microbial population residing within the human gut represents one of the most densely populated microbial niche in the human body with growing evidence showing it playing a key role in the regulation of behavior and brain function. The bidirectional communication between the gut microbiota and the brain, the microbiota-gut-brain axis, occurs through various pathways including the vagus nerve, the immune system, neuroendocrine pathways, and bacteria-derived metabolites. This axis has been shown to influence neurotransmission and the behavior that are often associated with neuropsychiatric conditions. Therefore, research targeting the modulation of this gut microbiota as a novel therapy for the treatment of various neuropsychiatric conditions is gaining interest. Numerous factors have been highlighted to influence gut microbiota composition, including genetics, health status, mode of birth, and environment. However, it is diet composition and nutritional status that has repeatedly been shown to be one of the most critical modifiable factors regulating the gut microbiota at different time points across the lifespan and under various health conditions. Thus the microbiota is poised to play a key role in nutritional interventions for maintaining brain health. Copyright © 2016 Elsevier Inc. All rights reserved.

Drug-Like Protein–Protein Interaction Modulators: Challenges and Opportunities for Drug Discovery and Chemical Biology

PubMed Central

Villoutreix, Bruno O; Kuenemann, Melaine A; Poyet, Jean-Luc; Bruzzoni-Giovanelli, Heriberto; Labbé, Céline; Lagorce, David; Sperandio, Olivier; Miteva, Maria A

2014-01-01

Fundamental processes in living cells are largely controlled by macromolecular interactions and among them, protein–protein interactions (PPIs) have a critical role while their dysregulations can contribute to the pathogenesis of numerous diseases. Although PPIs were considered as attractive pharmaceutical targets already some years ago, they have been thus far largely unexploited for therapeutic interventions with low molecular weight compounds. Several limiting factors, from technological hurdles to conceptual barriers, are known, which, taken together, explain why research in this area has been relatively slow. However, this last decade, the scientific community has challenged the dogma and became more enthusiastic about the modulation of PPIs with small drug-like molecules. In fact, several success stories were reported both, at the preclinical and clinical stages. In this review article, written for the 2014 International Summer School in Chemoinformatics (Strasbourg, France), we discuss in silico tools (essentially post 2012) and databases that can assist the design of low molecular weight PPI modulators (these tools can be found at www.vls3d.com). We first introduce the field of protein–protein interaction research, discuss key challenges and comment recently reported in silico packages, protocols and databases dedicated to PPIs. Then, we illustrate how in silico methods can be used and combined with experimental work to identify PPI modulators. PMID:25254076

Oxygen-Dependent Globin Coupled Sensor Signaling Modulates Motility and Virulence of the Plant Pathogen Pectobacterium carotovorum.

PubMed

Burns, Justin L; Jariwala, Parth B; Rivera, Shannon; Fontaine, Benjamin M; Briggs, Laura; Weinert, Emily E

2017-08-18

Bacterial pathogens utilize numerous signals to identify the presence of their host and coordinate changes in gene expression that allow for infection. Within plant pathogens, these signals typically include small molecules and/or proteins from their plant hosts and bacterial quorum sensing molecules to ensure sufficient bacterial cell density for successful infection. In addition, bacteria use environmental signals to identify conditions when the host defenses are weakened and potentially to signal entry into an appropriate host/niche for infection. A globin coupled sensor protein (GCS), termed PccGCS, within the soft rot bacterium Pectobacterium carotovorum ssp. carotovorum WPP14 has been identified as an O 2 sensor and demonstrated to alter virulence factor excretion and control motility, with deletion of PccGCS resulting in decreased rotting of a potato host. Using small molecules that modulate bacterial growth and quorum sensing, PccGCS signaling also has been shown to modulate quorum sensing pathways, resulting in the PccGCS deletion strain being more sensitive to plant-derived phenolic acids, which can function as quorum sensing inhibitors, and exhibiting increased N-acylhomoserine lactone (AHL) production. These findings highlight a role for GCS proteins in controlling key O 2 -dependent phenotypes of pathogenic bacteria and suggest that modulating GCS signaling to limit P. carotovorum motility may provide a means to decrease rotting of plant hosts.

Programmable Modulation of Copper Nanoclusters Electrochemiluminescence via DNA Nanocranes for Ultrasensitive Detection of microRNA.

PubMed

Zhou, Ying; Wang, Haijun; Zhang, Han; Chai, Yaqin; Yuan, Ruo

2018-03-06

The DNA nanocrane with functionalized manipulator and fixed-size base offered a programmable approach to modulate the luminous efficiency of copper nanoclusters (Cu NCs) for achieving remarkable electrochemiluminescence (ECL) enhancement, further the Cu NCs as signal label was constructed in biosensor for ultrasensitive detection of microRNA-155. Herein, the DNA nanocrane was first constructed by combining binding-induced DNA assembly as manipulator and tetrahedral DNA nanostructure (TDN) as base, which harnessed a small quantity of specific target (microRNA (miRNA)-155) binding to trigger assembly of separate DNA components for producing numerous AT-rich double-stranded DNA (dsDNA) on the vertex of TDN. Upon the incubation of Cu 2+ on the AT-rich dsDNA, each DNA-stabilized Cu NCs probe could be in situ electrochemically generated on an individual TDN owing to the A-Cu 2+ -T bond. Thus, the generation of Cu NCs was highly regulated with AT-rich dsDNA as the template, and its lateral distance was tuned by the TDN size, which were two key factors to influence the luminous efficiency of Cu NCs. By coordinate modulation, the detection limit of the ultrasensitive biosensor for miRNA-155 down to 36 aM and the programmable modulation strategy paved the way for comprehensive applications of DNA nanomachines and metal nanoclusters in biosensing and clinical diagnosis.

Ultracompact electro-optic phase modulator based on III-V-on-silicon microdisk resonator.

PubMed

Lloret, J; Kumar, R; Sales, S; Ramos, F; Morthier, G; Mechet, P; Spuesens, T; Van Thourhout, D; Olivier, N; Fédéli, J-M; Capmany, J

2012-06-15

A novel ultracompact electro-optic phase modulator based on a single 9 μm-diameter III-V microdisk resonator heterogeneously integrated on and coupled to a nanophotonic waveguide is presented. Modulation is enabled by effective index modification through carrier injection. Proof-of-concept implementation involving binary phase shift keying modulation format is assembled. A power imbalance of ∼0.6  dB between both symbols and a modulation rate up to 1.8 Gbps are demonstrated without using any special driving technique.

Advanced modulation technology development for earth station demodulator applications

NASA Technical Reports Server (NTRS)

Davis, R. C.; Wernlund, J. V.; Gann, J. A.; Roesch, J. F.; Wright, T.; Crowley, R. D.

1989-01-01

The purpose of this contract was to develop a high rate (200 Mbps), bandwidth efficient, modulation format using low cost hardware, in 1990's technology. The modulation format chosen is 16-ary continuous phase frequency shift keying (CPFSK). The implementation of the modulation format uses a unique combination of a limiter/discriminator followed by an accumulator to determine transmitted phase. An important feature of the modulation scheme is the way coding is applied to efficiently gain back the performance lost by the close spacing of the phase points.

Safety in Elevators and Grain Handling Facilities. Module SH-27. Safety and Health.

ERIC Educational Resources Information Center

Center for Occupational Research and Development, Inc., Waco, TX.

This student module on safety in elevators and grain handling facilities is one of 50 modules concerned with job safety and health. Following the introduction, 15 objectives (each keyed to a page in the text) the student is expected to accomplish are listed (e.g., Explain how explosion suppression works). Then each objective is taught in detail,…

Music for Elementary Teachers; Self-Help Guide (MUS 370). Adams State College.

ERIC Educational Resources Information Center

Stokes, Cloyce

This self-help guide for the music teacher is one of a series of eight Teacher Education Modules developed by Adams State College Teacher Corps Program. The guide itself consists of 11 modules, the first five of which focus on the mathematical and scientific aspects of music--pitch, tempo, furation, time, and key. These five modules are…

An Evaluation of Training Modules for Part-Time Workers in Community Education. SCRE Project Report No. 19.

ERIC Educational Resources Information Center

Castelino, Celine; Munn, Pamela

This project evaluated three modules, which were developed to meet key basic training requirements common to part-time workers in different branches of community education (adult education, community development, and youth work). Draft modules were sent to about 40 individuals or organizations in the field for comment on their structure and…

ART CONCEPTS - APOLLO IX

NASA Image and Video Library

1969-02-20

S69-19796 (February 1969) --- Composite of six artist's concepts illustrating key events, tasks and activities on the fifth day of the Apollo 9 mission, including vehicles undocked, Lunar Module burns for rendezvous, maximum separation, ascent propulsion system burn, formation flying and docking, and Lunar Module jettison ascent burn. The Apollo 9 mission will evaluate spacecraft lunar module systems performance during manned Earth-orbital flight.

Resolving Conflicts: Getting along with Co-Workers. JobLink Winning at Work Instructor's Manual, Module 8.

ERIC Educational Resources Information Center

Coast Community Coll. District, Costa Mesa, CA.

This manual is a guide to an interactive training program designed to address key skills necessary in today's high performance workplace. The module is intended to meet the learning needs of production workers who may have limited basic skills or literacy. This module, which addresses conflict resolution, focuses on helping employees understand…

Frequency-doubled microwave waveforms generation using a dual-polarization quadrature phase shift keying modulator driven by a single frequency radio frequency signal

NASA Astrophysics Data System (ADS)

Zhu, Zihang; Zhao, Shanghong; Li, Xuan; Qu, Kun; Lin, Tao

2018-01-01

A photonic approach to generate frequency-doubled microwave waveforms using an integrated dual-polarization quadrature phase shift keying (DP-QPSK) modulator driven by a sinusoidal radio frequency (RF) signal is proposed. By adjusting the dc bias points of the DP-QPSK modulator, the obtained second-order and six-order harmonics are in phase while the fourth-order harmonics are complementary when the orthogonal polarized outputs of the modulator are photodetected. After properly setting the modulation indices of the modulator, the amplitude of the second-order harmonic is 9 times of that of the six-order harmonic, indicating a frequency-doubled triangular waveform is generated. If a broadband 90° microwave phase shifter is attached after the photodetector (PD) to introduce a 90° phase shift, a frequency-doubled square waveform can be obtained after adjusting the amplitude of the second-order harmonic 3 times of that of the six-order harmonic. The proposal is first theoretically analyzed and then validated by simulation. Simulation results show that a 10 GHz triangular and square waveform sequences are successfully generated from a 5 GHz sinusoidal RF drive signal.

Sensing Danger: Key to Activating Plant Immunity.

PubMed

Gust, Andrea A; Pruitt, Rory; Nürnberger, Thorsten

2017-09-01

In both plants and animals, defense against pathogens relies on a complex surveillance system for signs of danger. Danger signals may originate from the infectious agent or from the host itself. Immunogenic plant host factors can be roughly divided into two categories: molecules which are passively released upon cell damage ('classical' damage-associated molecular patterns, DAMPs), and peptides which are processed and/or secreted upon infection to modulate the immune response (phytocytokines). We highlight the ongoing challenge to understand how plants sense various danger signals and integrate this information to produce an appropriate immune response to diverse challenges. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cell Cycle Deregulation in Ewing's Sarcoma Pathogenesis

PubMed Central

Kowalewski, Ashley A.; Randall, R. Lor; Lessnick, Stephen L.

2011-01-01

Ewing's sarcoma is a highly aggressive pediatric tumor of bone that usually contains the characteristic chromosomal translocation t(11;22)(q24;q12). This translocation encodes the oncogenic fusion protein EWS/FLI, which acts as an aberrant transcription factor to deregulate target genes necessary for oncogenesis. One key feature of oncogenic transformation is dysregulation of cell cycle control. It is therefore likely that EWS/FLI and other cooperating mutations in Ewing's sarcoma modulate the cell cycle to facilitate tumorigenesis. This paper will summarize current published data associated with deregulation of the cell cycle in Ewing's sarcoma and highlight important questions that remain to be answered. PMID:21052502

The Influence of the Gut Microbiome on Cancer, Immunity, and Cancer Immunotherapy.

PubMed

Gopalakrishnan, Vancheswaran; Helmink, Beth A; Spencer, Christine N; Reuben, Alexandre; Wargo, Jennifer A

2018-04-09

The microbiome is receiving significant attention given its influence on a host of human diseases including cancer. Its role in response to cancer treatment is becoming increasingly apparent, with evidence suggesting that modulating the gut microbiome may affect responses to numerous forms of cancer therapy. A working knowledge of the microbiome is vital as we move forward in this age of precision medicine, and an understanding of the microbiome's influence on immune responses and cancer is key. It is also important to understand factors influencing the gut microbiome and strategies to manipulate the microbiome to augment therapeutic responses. Copyright © 2018 Elsevier Inc. All rights reserved.

Taurine and its neuroprotective role.

PubMed

Kumari, Neeta; Prentice, Howard; Wu, Jang-Yen

2013-01-01

Taurine plays multiple roles in the CNS including acting as a -neuro-modulator, an osmoregulator, a regulator of cytoplasmic calcium levels, a trophic factor in development, and a neuroprotectant. In neurons taurine has been shown to prevent mitochondrial dysfunction and to protect against endoplasmic reticulum (ER) stress associated with neurological disorders. In cortical neurons in culture taurine protects against excitotoxicity through reversing an increase in levels of key ER signaling components including eIF-2-alpha and cleaved ATF6. The role of communication between the ER and mitochondrion is also important and examples are presented of protection by taurine against ER stress together with prevention of subsequent mitochondrial initiated apoptosis.

Application of harmonic detection technology in methane telemetry

NASA Astrophysics Data System (ADS)

Huo, Yuehua; Fan, Weiqiang

2017-08-01

Methane telemetry plays a vital role in ensuring the safe production of coal mines and monitoring the leakage of natural gas pipelines. Harmonic detection is the key technology of methane telemetry accuracy and sensitivity, but the current telemetry distance is short, the relationship between different modulation parameters is complex, and the harmonic signal is affected by noise interference. These factors seriously affect the development of harmonic detection technology. In this paper, the principle of methane telemetry based on harmonic detection technology is introduced. The present situation and characteristics of harmonic detection technology are expounded. The problems existing in harmonic detection are analyzed. Finally, the future development trend is discussed.

Research on SOI-based micro-resonator devices

NASA Astrophysics Data System (ADS)

Xiao, Xi; Xu, Haihua; Hu, Yingtao; Zhou, Liang; Xiong, Kang; Li, Zhiyong; Li, Yuntao; Fan, Zhongchao; Han, Weihua; Yu, Yude; Yu, Jinzhong

2010-10-01

SOI (silicon-on-insulator)-based micro-resonator is the key building block of silicon photonics, which is considered as a promising solution to alleviate the bandwidth bottleneck of on-chip interconnects. Silicon-based sub-micron waveguide, microring and microdisk devices are investigated in Institute of Semiconductors, Chinese Academy of Sciences. The main progress in recent years is presented in this talk, such as high Q factor single mode microdisk filters, compact thirdorder microring filters with the through/drop port extinctions to be ~ 30/40 dB, fast microring electro-optical switches with the switch time of < 400 ps and crosstalk < -23 dB, and > 10 Gbit/s high speed microring modulators.

Unveiling combinatorial regulation through the combination of ChIP information and in silico cis-regulatory module detection

PubMed Central

Sun, Hong; Guns, Tias; Fierro, Ana Carolina; Thorrez, Lieven; Nijssen, Siegfried; Marchal, Kathleen

2012-01-01

Computationally retrieving biologically relevant cis-regulatory modules (CRMs) is not straightforward. Because of the large number of candidates and the imperfection of the screening methods, many spurious CRMs are detected that are as high scoring as the biologically true ones. Using ChIP-information allows not only to reduce the regions in which the binding sites of the assayed transcription factor (TF) should be located, but also allows restricting the valid CRMs to those that contain the assayed TF (here referred to as applying CRM detection in a query-based mode). In this study, we show that exploiting ChIP-information in a query-based way makes in silico CRM detection a much more feasible endeavor. To be able to handle the large datasets, the query-based setting and other specificities proper to CRM detection on ChIP-Seq based data, we developed a novel powerful CRM detection method ‘CPModule’. By applying it on a well-studied ChIP-Seq data set involved in self-renewal of mouse embryonic stem cells, we demonstrate how our tool can recover combinatorial regulation of five known TFs that are key in the self-renewal of mouse embryonic stem cells. Additionally, we make a number of new predictions on combinatorial regulation of these five key TFs with other TFs documented in TRANSFAC. PMID:22422841

Modulation of Haemophilus influenzae interaction with hydrophobic molecules by the VacJ/MlaA lipoprotein impacts strongly on its interplay with the airways.

PubMed

Fernández-Calvet, Ariadna; Rodríguez-Arce, Irene; Almagro, Goizeder; Moleres, Javier; Euba, Begoña; Caballero, Lucía; Martí, Sara; Ramos-Vivas, José; Bartholomew, Toby Leigh; Morales, Xabier; Ortíz-de-Solórzano, Carlos; Yuste, José Enrique; Bengoechea, José Antonio; Conde-Álvarez, Raquel; Garmendia, Junkal

2018-05-02

Airway infection by nontypeable Haemophilus influenzae (NTHi) associates to chronic obstructive pulmonary disease (COPD) exacerbation and asthma neutrophilic airway inflammation. Lipids are key inflammatory mediators in these disease conditions and consequently, NTHi may encounter free fatty acids during airway persistence. However, molecular information on the interplay NTHi-free fatty acids is limited, and we lack evidence on the importance of such interaction to infection. Maintenance of the outer membrane lipid asymmetry may play an essential role in NTHi barrier function and interaction with hydrophobic molecules. VacJ/MlaA-MlaBCDEF prevents phospholipid accumulation at the bacterial surface, being the only system involved in maintaining membrane asymmetry identified in NTHi. We assessed the relationship among the NTHi VacJ/MlaA outer membrane lipoprotein, bacterial and exogenous fatty acids, and respiratory infection. The vacJ/mlaA gene inactivation increased NTHi fatty acid and phospholipid global content and fatty acyl specific species, which in turn increased bacterial susceptibility to hydrophobic antimicrobials, decreased NTHi epithelial infection, and increased clearance during pulmonary infection in mice with both normal lung function and emphysema, maybe related to their shared lung fatty acid profiles. Altogether, we provide evidence for VacJ/MlaA as a key bacterial factor modulating NTHi survival at the human airway upon exposure to hydrophobic molecules.

Mitochondrial multifaceted dysfunction in schizophrenia; complex I as a possible pathological target.

PubMed

Ben-Shachar, Dorit

2017-09-01

Mitochondria are key players in various essential cellular processes beyond being the main energy supplier of the cell. Accordingly, they are involved in neuronal synaptic transmission, neuronal growth and sprouting and consequently neuronal plasticity and connectivity. In addition, mitochondria participate in the modulation of gene transcription and inflammation as well in physiological responses in health and disease. Schizophrenia is currently regarded as a neurodevelopmental disorder associated with impaired immune system, aberrant neuronal differentiation and abnormalities in various neurotransmitter systems mainly the dopaminergic, glutaminergic and GABAergic. Ample evidence has been accumulated over the last decade indicating a multifaceted dysfunction of mitochondria in schizophrenia. Indeed, mitochondrial deficit can be of relevance for the majority of the pathologies observed in this disease. In the present article, we overview specific deficits of the mitochondria in schizophrenia, with a focus on the first complex (complex I) of the mitochondrial electron transport chain (ETC). We argue that complex I, being a major factor in the regulation of mitochondrial ETC, is a possible key modulator of various functions of the mitochondria. We review biochemical, molecular, cellular and functional evidence for mitochondrial impairments and their possible convergence to impact in-vitro neuronal differentiation efficiency in schizophrenia. Mitochondrial function in schizophrenia may advance our knowledge of the disease pathophysiology and open the road for new treatment targets for the benefit of the patients. Copyright © 2016 Elsevier B.V. All rights reserved.

Soybean Roots Grown under Heat Stress Show Global Changes in Their Transcriptional and Proteomic Profiles

DOE PAGES

Valdés-López, Oswaldo; Batek, Josef; Gomez-Hernandez, Nicolas; ...

2016-04-25

Heat stress is likely to be a key factor in the negative impact of climate change on crop production. Heat stress significantly influences the functions of roots, which provide support, water, and nutrients to other plant organs. Likewise, roots play an important role in the establishment of symbiotic associations with different microorganisms. Despite the physiological relevance of roots, few studies have examined their response to heat stress. Here in this study, we performed genome-wide transcriptomic and proteomic analyses on isolated root hairs, which are a single, epidermal cell type, and compared their response to stripped roots. On average, we identifiedmore » 1849 and 3091 genes differentially regulated in root hairs and stripped roots, respectively, in response to heat stress. Our gene regulatory module analysis identified 10 key modules that might control the majority of the transcriptional response to heat stress. We also conducted proteomic analysis on membrane fractions isolated from root hairs and compared these responses to stripped roots. These experiments identified a variety of proteins whose expression changed within 3 h of application of heat stress. Most of these proteins were predicted to play a significant role in thermo-tolerance, as well as in chromatin remodeling and post-transcriptional regulation. In conclusion, the data presented represent an in-depth analysis of the heat stress response of a single cell type in soybean.« less

Involvement of neuron-derived orphan receptor-1 (NOR-1) in LDL-induced mitogenic stimulus in vascular smooth muscle cells: role of CREB.

PubMed

Rius, Jordi; Martínez-González, José; Crespo, Javier; Badimon, Lina

2004-04-01

Low density lipoproteins (LDLs) modulate the expression of key genes involved in atherogenesis. Recently, we have shown that the transcription factor neuron-derived orphan receptor-1 (NOR-1) is involved in vascular smooth muscle cell (VSMC) proliferation. Our aim was to analyze whether NOR-1 is involved in LDL-induced mitogenic effects in VSMC. LDL induced NOR-1 expression in a time- and dose-dependent manner. Antisense oligonucleotides against NOR-1 inhibit DNA synthesis induced by LDL in VSMCs as efficiently as antisense against the protooncogene c-fos. The upregulation of NOR-1 mRNA levels by LDL involves pertusis-sensitive G protein-coupled receptors, Ca2+ mobilization, protein kinases A (PKA) and C (PKC) activation, and mitogen-activated protein kinase pathways (MAPK) (p44/p42 and p38). LDL promotes cAMP response element binding protein (CREB) activation (phosphorylation in Ser133). In transfection assays a dominant-negative of CREB inhibits NOR-1 promoter activity, while mutation of specific (cAMP response element) CRE sites in the NOR-1 promoter abolishes LDL-induced NOR-1 promoter activity. In VSMCs, LDL-induced mitogenesis involves NOR-1 upregulation through a CREB-dependent mechanism. CREB could play a role in the modulation by LDL of key genes (containing CRE sites) involved in atherogenesis.

New insights into redox regulation of stem cell self-renewal and differentiation.

PubMed

Ren, Fenglian; Wang, Kui; Zhang, Tao; Jiang, Jingwen; Nice, Edouard Collins; Huang, Canhua

2015-08-01

Reactive oxygen species (ROS), the natural byproducts of aerobic metabolism, are precisely orchestrated to evoke diverse signaling pathways. To date, studies have focused mainly on the detrimental effects of ROS in stem cells. Recently, accumulating evidence has suggested that ROS also function as second messengers that modulate stem cell self-renewal and differentiation by regulating intricate signaling networks. Although many efforts have been made to clarify the general effects of ROS on signal transduction in stem cells, less is known about the initial and direct executors of ROS signaling, which are known as 'redox sensors'. Modifications of cysteine residues in redox sensors are of significant importance in the modulation of protein function in response to different redox conditions. Intriguingly, most key molecules in ROS signaling and cell cycle regulation (including transcriptional factors and kinases) that are crucial in the regulation of stem cell self-renewal and differentiation have the potential to be redox sensors. We highlight herein the importance of redox regulation of these key regulators in stem cell self-renewal and differentiation. Understanding the mechanisms of redox regulation in stem cell self-renewal and differentiation will open exciting new perspectives for stem cell biology. This article is part of a Special Issue entitled Redox regulation of differentiation and de-differentiation. Copyright © 2015 Elsevier B.V. All rights reserved.

Epigenetics and environmental exposures.

PubMed

Stein, Richard A

2012-01-01

It is becoming increasingly apparent that genetic factors are inadequate to fully explain many processes that shape development and disease. For example, monozygotic twin pairs, despite sharing identical DNA sequences, are often discordant for many traits and diseases, indicating that the same genotype can give rise to distinct phenotypes. This points towards the involvement of additional factors that cannot be explained solely by the sequence of the genome. Epigenetic modifications, defined as heritable changes that do not alter the nucleotide sequence, emerge as key factors that regulate chromatin structure and gene expression and, together with genetic factors, provide the mechanistic basis to understand the biological effects of various classes of environmental exposures. Epigenetic mechanisms explain the ability of certain chemical compounds to initiate biological perturbations that can lead to malignancy, despite being weak mutagens or lacking mutagenic activity altogether-a view that challenges old beliefs and opens new avenues in public health. The field of epigenetics also explains the causal link between certain infectious diseases and cancer, a relationship that was first observed over a century ago and was initially discounted, then fell into oblivion and more recently re-emerged as an important concept in biology. A key feature that distinguishes epigenetic modifications from genetic changes is their reversible nature. This provides exciting prophylactic and therapeutic perspectives, some of which already materialised with the approval of the first drugs that modulate the epigenetic machinery, reinforcing the idea that our genes are not our destiny.

Wnt3 and Gata4 regulate axon regeneration in adult mouse DRG neurons.

PubMed

Duan, Run-Shan; Liu, Pei-Pei; Xi, Feng; Wang, Wei-Hua; Tang, Gang-Bin; Wang, Rui-Ying; Saijilafu; Liu, Chang-Mei

2018-05-05

Neurons in the adult central nervous system (CNS) have a poor intrinsic axon growth potential after injury, but the underlying mechanisms are largely unknown. Wingless-related mouse mammary tumor virus integration site (WNT) family members regulate neural stem cell proliferation, axon tract and forebrain development in the nervous system. Here we report that Wnt3 is an important modulator of axon regeneration. Downregulation or overexpression of Wnt3 in adult dorsal root ganglion (DRG) neurons enhances or inhibits their axon regeneration ability respectively in vitro and in vivo. Especially, we show that Wnt3 modulates axon regeneration by repressing mRNA translation of the important transcription factor Gata4 via binding to the three prime untranslated region (3'UTR). Downregulation of Gata4 could restore the phenotype exhibited by Wnt3 downregulation in DRG neurons. Taken together, these data indicate that Wnt3 is a key intrinsic regulator of axon growth ability of the nervous system. Copyright © 2018 Elsevier Inc. All rights reserved.

A Nomographic Methodology for Use in Performance Trade-Off Studies of Parabolic Dish Solar Power Modules

NASA Technical Reports Server (NTRS)

Selcuk, M. K.; Fujita, T.

1984-01-01

A simple graphical method was developed to undertake technical design trade-off studies for individual parabolic dish models comprising a two-axis tracking parabolic dish with a cavity receiver and power conversion assembly at the focal point. The results of these technical studies are then used in performing the techno-economic analyses required for determining appropriate subsystem sizing. Selected graphs that characterize the performance of subsystems within the module were arranged in the form of a nomogram that would enable an investigator to carry out several design trade-off studies. Key performance parameters encompassed in the nomogram include receiver losses, intercept factor, engine rating, and engine efficiency. Design and operation parameters such as concentrator size, receiver type (open or windowed aperture), receiver aperture size, operating temperature of the receiver and engine, engine partial load characteristics, concentrator slope error, and the type of reflector surface, are also included in the graphical solution. Cost considerations are not included.

Beyond anorexia -cachexia. Nutrition and modulation of cancer patients' metabolism: supplementary, complementary or alternative anti-neoplastic therapy?

PubMed

Laviano, Alessandro; Seelaender, Marilia; Sanchez-Lara, Karla; Gioulbasanis, Ioannis; Molfino, Alessio; Rossi Fanelli, Filippo

2011-09-01

Anorexia and muscle wasting are frequently observed in cancer patients and influence their clinical outcome. The better understanding of the mechanisms underlying behavioral changes and altered metabolism yielded to the development of specialized nutritional support, which enhances utilization of provided calories and proteins by counteracting some of the metabolic derangements occurring during tumor growth. Inflammation appears to be a key factor determining the cancer-associated biochemical abnormalities eventually leading to anorexia and cachexia. Interestingly, inflammation is also involved in carcinogenesis, cancer progression and metastasis by impairing immune surveillance, among other mechanisms. Therefore, nutritional interventions aiming at modulating inflammation to restore nutritional status may also result in improved response to pharmacological anti-cancer therapies. Recent clinical data show that supplementation with nutrients targeting inflammation and immune system increases response rate and survival in cancer patients. This suggests that nutrition therapy should be considered as an important adjuvant strategy in the multidimensional approach to cancer patients. Copyright © 2011 Elsevier B.V. All rights reserved.

Intrafamily and intragenomic conflicts in human warfare

PubMed Central

2017-01-01

Recent years have seen an explosion of multidisciplinary interest in ancient human warfare. Theory has emphasized a key role for kin-selected cooperation, modulated by sex-specific demography, in explaining intergroup violence. However, conflicts of interest remain a relatively underexplored factor in the evolutionary-ecological study of warfare, with little consideration given to which parties influence the decision to go to war and how their motivations may differ. We develop a mathematical model to investigate the interplay between sex-specific demography and human warfare, showing that: the ecology of warfare drives the evolution of sex-biased dispersal; sex-biased dispersal modulates intrafamily and intragenomic conflicts in relation to warfare; intragenomic conflict drives parent-of-origin-specific patterns of gene expression—i.e. ‘genomic imprinting’—in relation to warfare phenotypes; and an ecological perspective of conflicts at the levels of the gene, individual, and social group yields novel predictions as to pathologies associated with mutations and epimutations at loci underpinning human violence. PMID:28228515

Intrafamily and intragenomic conflicts in human warfare.

PubMed

Micheletti, Alberto J C; Ruxton, Graeme D; Gardner, Andy

2017-02-22

Recent years have seen an explosion of multidisciplinary interest in ancient human warfare. Theory has emphasized a key role for kin-selected cooperation, modulated by sex-specific demography, in explaining intergroup violence. However, conflicts of interest remain a relatively underexplored factor in the evolutionary-ecological study of warfare, with little consideration given to which parties influence the decision to go to war and how their motivations may differ. We develop a mathematical model to investigate the interplay between sex-specific demography and human warfare, showing that: the ecology of warfare drives the evolution of sex-biased dispersal; sex-biased dispersal modulates intrafamily and intragenomic conflicts in relation to warfare; intragenomic conflict drives parent-of-origin-specific patterns of gene expression-i.e. 'genomic imprinting'-in relation to warfare phenotypes; and an ecological perspective of conflicts at the levels of the gene, individual, and social group yields novel predictions as to pathologies associated with mutations and epimutations at loci underpinning human violence. © 2017 The Authors.

Dopamine and serotonin interactions in the prefrontal cortex: insights on antipsychotic drugs and their mechanism of action.

PubMed

Di Pietro, N C; Seamans, J K

2007-12-01

Diminished activity within the prefrontal cortex (PFC) has been associated with many of the cognitive deficits that are observed in schizophrenia. It has been hypothesized that antipsychotic drugs (APDs) used to treat schizophrenia restore normal activity by antagonizing the dopamine (DA) D2 receptor, which is also known to modulate key ionic currents in the PFC. However, the hypothesis that an under-active cortical DA system is responsible for schizophrenic symptoms has been challenged by evidence that newer atypical APDs are weak antagonists at the D2 receptor but potent antagonists at the serotonin (5-HT) 2A receptor . This review examines how DA and 5-HT modulate cortical activity and how they may interact in ways that are relevant to schizophrenia. It is concluded that although D2 receptor antagonism remains a critical factor in restoring impaired cortical activity, effects on 5-HT receptors may act in a synergistic manner on NMDA and GABA currents to potentiate antipsychotic actions in the PFC.

Fife organizes synaptic vesicles and calcium channels for high-probability neurotransmitter release

PubMed Central

Rao, Monica; Ukken, Fiona

2017-01-01

The strength of synaptic connections varies significantly and is a key determinant of communication within neural circuits. Mechanistic insight into presynaptic factors that establish and modulate neurotransmitter release properties is crucial to understanding synapse strength, circuit function, and neural plasticity. We previously identified Drosophila Piccolo-RIM-related Fife, which regulates neurotransmission and motor behavior through an unknown mechanism. Here, we demonstrate that Fife localizes and interacts with RIM at the active zone cytomatrix to promote neurotransmitter release. Loss of Fife results in the severe disruption of active zone cytomatrix architecture and molecular organization. Through electron tomographic and electrophysiological studies, we find a decrease in the accumulation of release-ready synaptic vesicles and their release probability caused by impaired coupling to Ca2+ channels. Finally, we find that Fife is essential for the homeostatic modulation of neurotransmission. We propose that Fife organizes active zones to create synaptic vesicle release sites within nanometer distance of Ca2+ channel clusters for reliable and modifiable neurotransmitter release. PMID:27998991

Circular non-coding RNA ANRIL modulates ribosomal RNA maturation and atherosclerosis in humans

PubMed Central

Holdt, Lesca M.; Stahringer, Anika; Sass, Kristina; Pichler, Garwin; Kulak, Nils A.; Wilfert, Wolfgang; Kohlmaier, Alexander; Herbst, Andreas; Northoff, Bernd H.; Nicolaou, Alexandros; Gäbel, Gabor; Beutner, Frank; Scholz, Markus; Thiery, Joachim; Musunuru, Kiran; Krohn, Knut; Mann, Matthias; Teupser, Daniel

2016-01-01

Circular RNAs (circRNAs) are broadly expressed in eukaryotic cells, but their molecular mechanism in human disease remains obscure. Here we show that circular antisense non-coding RNA in the INK4 locus (circANRIL), which is transcribed at a locus of atherosclerotic cardiovascular disease on chromosome 9p21, confers atheroprotection by controlling ribosomal RNA (rRNA) maturation and modulating pathways of atherogenesis. CircANRIL binds to pescadillo homologue 1 (PES1), an essential 60S-preribosomal assembly factor, thereby impairing exonuclease-mediated pre-rRNA processing and ribosome biogenesis in vascular smooth muscle cells and macrophages. As a consequence, circANRIL induces nucleolar stress and p53 activation, resulting in the induction of apoptosis and inhibition of proliferation, which are key cell functions in atherosclerosis. Collectively, these findings identify circANRIL as a prototype of a circRNA regulating ribosome biogenesis and conferring atheroprotection, thereby showing that circularization of long non-coding RNAs may alter RNA function and protect from human disease. PMID:27539542

Peer mentoring: Enhancing the transition from student to professional.

PubMed

Fisher, Margaret; Stanyer, Rachel

2018-05-01

to share the experience of a model of peer mentoring in a pre-qualification midwifery programme DESIGN: description of the framework and benefits of the model SETTING: University and practice PARTICIPANTS: third year midwifery students INTERVENTIONS: practical activities meeting regulatory body requirements in a pre-qualification mentorship module MEASUREMENTS AND FINDINGS: informal evaluations by students of key activities undertaken during peer mentoring demonstrated a range of positive outcomes. These included enhanced confidence, self-awareness, interpersonal and teaching skills, team-working and leadership - factors also associated with emotional intelligence. Students developed an appreciation of the accountability of the mentor including making practice assessment decisions. They stated that the learning achieved had aided their professional development and enhanced employability. this module equips students with skills for their future role in facilitating learners and contributes to development of a 'professional persona', enhancing their transition to qualified midwives. The Peer Mentoring Model would be easily adapted to other programmes and professional contexts. Copyright © 2018 Elsevier Ltd. All rights reserved.

Modulation of lipoprotein metabolism by antisense technology: preclinical drug discovery methodology.

PubMed

Crooke, Rosanne M; Graham, Mark J

2013-01-01

Antisense oligonucleotides (ASOs) are a new class of specific therapeutic agents that alter the intermediary metabolism of mRNA, resulting in the suppression of disease-associated gene products. ASOs exert their pharmacological effects after hybridizing, via Watson-Crick base pairing, to a specific target RNA. If appropriately designed, this event results in the recruitment of RNase H, the degradation of targeted mRNA or pre-mRNA, and subsequent inhibition of the synthesis of a specific protein. A key advantage of the technology is the ability to selectively inhibit targets that cannot be modulated by traditional therapeutics such as structural proteins, transcription factors, and, of topical interest, lipoproteins. In this chapter, we will first provide an overview of antisense technology, then more specifically describe the status of lipoprotein-related genes that have been studied using the antisense platform, and finally, outline the general methodology required to design and evaluate the in vitro and in vivo efficacy of those drugs.

17 O MRS assesses the effect of mild hypothermia on oxygen consumption rate in tumors.

PubMed

Neveu, Marie-Aline; Joudiou, Nicolas; De Preter, Géraldine; Dehoux, Jean-Paul; Jordan, Bénédicte F; Gallez, Bernard

2017-08-01

Although oxygen consumption is a key factor in metabolic phenotyping, its assessment in tumors remains critical, as current technologies generally display poor specificity. The objectives of this study were to explore the feasibility of direct 17 O nuclear magnetic resonance (NMR) spectroscopy to assess oxygen metabolism in tumors and its modulations. To investigate the impact of hypometabolism induction in the murine fibrosarcoma FSAII tumor model, we monitored the oxygen consumption of normothermic (37°C) and hypothermic (32°C) tumor-bearing mice. Hypothermic animals showed an increase in tumor pO 2 (measured by electron paramagnetic resonance oximetry) contrary to normothermic animals. This was related to a decrease in oxygen consumption rate (assessed using 17 O magnetic resonance spectroscopy (MRS) after the inhalation of 17 O 2 -enriched gas). This study highlights the ability of direct 17 O MRS to measure oxygen metabolism in tumors and modulations of tumor oxygen consumption rate. Copyright © 2017 John Wiley & Sons, Ltd.

Performance improvement of eight-state continuous-variable quantum key distribution with an optical amplifier

NASA Astrophysics Data System (ADS)

Guo, Ying; Li, Renjie; Liao, Qin; Zhou, Jian; Huang, Duan

2018-02-01

Discrete modulation is proven to be beneficial to improving the performance of continuous-variable quantum key distribution (CVQKD) in long-distance transmission. In this paper, we suggest a construct to improve the maximal generated secret key rate of discretely modulated eight-state CVQKD using an optical amplifier (OA) with a slight cost of transmission distance. In the proposed scheme, an optical amplifier is exploited to compensate imperfection of Bob's apparatus, so that the generated secret key rate of eight-state protocol is enhanced. Specifically, we investigate two types of optical amplifiers, phase-insensitive amplifier (PIA) and phase-sensitive amplifier (PSA), and thereby obtain approximately equivalent improved performance for eight-state CVQKD system when applying these two different amplifiers. Numeric simulation shows that the proposed scheme can well improve the generated secret key rate of eight-state CVQKD in both asymptotic limit and finite-size regime. We also show that the proposed scheme can achieve the relatively high-rate transmission at long-distance communication system.

A direct link between carbohydrate utilization and virulence in the major human pathogen group A Streptococcus.

PubMed

Shelburne, Samuel A; Keith, David; Horstmann, Nicola; Sumby, Paul; Davenport, Michael T; Graviss, Edward A; Brennan, Richard G; Musser, James M

2008-02-05

Although central to pathogenesis, the molecular mechanisms used by microbes to regulate virulence factor production in specific environments during host-pathogen interaction are poorly defined. Several recent ex vivo and in vivo studies have found that the level of group A Streptococcus (GAS) virulence factor gene transcripts is temporally related to altered expression of genes encoding carbohydrate utilization proteins. These findings stimulated us to analyze the role in pathogenesis of catabolite control protein A (CcpA), a GAS ortholog of a key global regulator of carbohydrate metabolism in Bacillus subtilis. Inasmuch as the genomewide effects of CcpA in a human pathogen are unknown, we analyzed the transcriptome of a DeltaccpA isogenic mutant strain grown in nutrient-rich medium. CcpA influences the transcript levels of many carbohydrate utilization genes and several well characterized GAS virulence factors, including the potent cytolysin streptolysin S. Compared with the wild-type parental strain, the DeltaccpA isogenic mutant strain was significantly less virulent in a mouse model of invasive infection. Moreover, the isogenic mutant strain was significantly impaired in ability to colonize the mouse oropharynx. When grown in human saliva, a nutrient-limited environment, CcpA influenced production of several key virulence factors not influenced during growth in nutrient-rich medium. Purified recombinant CcpA bound to the promoter region of the gene encoding streptolysin S. Our discovery that GAS virulence and complex carbohydrate utilization are directly linked through CcpA provides enhanced understanding of a mechanism used by a Gram-positive pathogen to modulate virulence factor production in specific environments.

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

PubMed

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

2014-05-01

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

Quantum key distribution using gaussian-modulated coherent states

NASA Astrophysics Data System (ADS)

Grosshans, Frédéric; Van Assche, Gilles; Wenger, Jérôme; Brouri, Rosa; Cerf, Nicolas J.; Grangier, Philippe

2003-01-01

Quantum continuous variables are being explored as an alternative means to implement quantum key distribution, which is usually based on single photon counting. The former approach is potentially advantageous because it should enable higher key distribution rates. Here we propose and experimentally demonstrate a quantum key distribution protocol based on the transmission of gaussian-modulated coherent states (consisting of laser pulses containing a few hundred photons) and shot-noise-limited homodyne detection; squeezed or entangled beams are not required. Complete secret key extraction is achieved using a reverse reconciliation technique followed by privacy amplification. The reverse reconciliation technique is in principle secure for any value of the line transmission, against gaussian individual attacks based on entanglement and quantum memories. Our table-top experiment yields a net key transmission rate of about 1.7 megabits per second for a loss-free line, and 75 kilobits per second for a line with losses of 3.1dB. We anticipate that the scheme should remain effective for lines with higher losses, particularly because the present limitations are essentially technical, so that significant margin for improvement is available on both the hardware and software.

Simple 2.5 GHz time-bin quantum key distribution

NASA Astrophysics Data System (ADS)

Boaron, Alberto; Korzh, Boris; Houlmann, Raphael; Boso, Gianluca; Rusca, Davide; Gray, Stuart; Li, Ming-Jun; Nolan, Daniel; Martin, Anthony; Zbinden, Hugo

2018-04-01

We present a 2.5 GHz quantum key distribution setup with the emphasis on a simple experimental realization. It features a three-state time-bin protocol based on a pulsed diode laser and a single intensity modulator. Implementing an efficient one-decoy scheme and finite-key analysis, we achieve record breaking secret key rates of 1.5 kbps over 200 km of standard optical fibers.

Host modulation therapeutics in periodontics: role as an adjunctive periodontal therapy.

PubMed

Shinwari, Muhammad Saad; Tanwir, Farzeen; Hyder, Pakiza Raza; Bin Saeed, Muhammad Humza

2014-09-01

Host Modulation Therapy (HMT) is a treatment concept that reduces tissue destruction and stabilizes or even regenerates inflammatory tissue by modifying host response factors. It has been used for treating osteoporosis and arthritis for several decades. However, its use in dentistry has only been recently reported. The objective of this article is to present a review of the various literatures available on HMT and also its role as adjunct therapy in periodontics. For identifying studies for this review, a PUBMED search was carried out in 2013 for all articles published till December 2012. The search was restricted to English language publications only. Longitudinal prospective and retrospective studies were included in the search. The key words used were: Host Modulation Therapy; Sub antimicrobial dose doxycycline and Non-Surgical Periodontal Therapy. The main outcomes sought were host modulation therapeutics in periodontics. Exclusion criteria included cross sectional studies, short case series as well as studies with short follow-up periods. There is a paucity of literature on HMT in periodontics although the only drug approved by United States Food and Drug Administration (FDA) is a subantimicrobial dose of doxycycline (SDD) with highly predictable results as a host modulating agent in periodontal diseases and also an effective adjunctive therapy in various diseases of periodontium. However, more randomized controlled trials are needed to obtain clinical guidelines on the usage of other host modulating agents as adjunct as well as definite therapy for periodontal diseases. SDD is an effective adjunct therapy when used in dosage of 20mg twice daily for minimum 3 months duration in various periodontal diseases with predictable clinical outcomes. It is also recommended that future clinical research on anti cytokine drugs, chemically modified tetracycline and other HMT agents should be conducted so that new drugs are available with highly predictable results.

Passive state preparation in the Gaussian-modulated coherent-states quantum key distribution

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

Qi, Bing; Evans, Philip G.; Grice, Warren P.

In the Gaussian-modulated coherent-states (GMCS) quantum key distribution (QKD) protocol, Alice prepares quantum states actively: For each transmission, Alice generates a pair of Gaussian-distributed random numbers, encodes them on a weak coherent pulse using optical amplitude and phase modulators, and then transmits the Gaussian-modulated weak coherent pulse to Bob. Here we propose a passive state preparation scheme using a thermal source. In our scheme, Alice splits the output of a thermal source into two spatial modes using a beam splitter. She measures one mode locally using conjugate optical homodyne detectors, and transmits the other mode to Bob after applying appropriatemore » optical attenuation. Under normal conditions, Alice's measurement results are correlated to Bob's, and they can work out a secure key, as in the active state preparation scheme. Given the initial thermal state generated by the source is strong enough, this scheme can tolerate high detector noise at Alice's side. Furthermore, the output of the source does not need to be single mode, since an optical homodyne detector can selectively measure a single mode determined by the local oscillator. Preliminary experimental results suggest that the proposed scheme could be implemented using an off-the-shelf amplified spontaneous emission source.« less

Passive state preparation in the Gaussian-modulated coherent-states quantum key distribution

DOE PAGES

Qi, Bing; Evans, Philip G.; Grice, Warren P.

2018-01-01

In the Gaussian-modulated coherent-states (GMCS) quantum key distribution (QKD) protocol, Alice prepares quantum states actively: For each transmission, Alice generates a pair of Gaussian-distributed random numbers, encodes them on a weak coherent pulse using optical amplitude and phase modulators, and then transmits the Gaussian-modulated weak coherent pulse to Bob. Here we propose a passive state preparation scheme using a thermal source. In our scheme, Alice splits the output of a thermal source into two spatial modes using a beam splitter. She measures one mode locally using conjugate optical homodyne detectors, and transmits the other mode to Bob after applying appropriatemore » optical attenuation. Under normal conditions, Alice's measurement results are correlated to Bob's, and they can work out a secure key, as in the active state preparation scheme. Given the initial thermal state generated by the source is strong enough, this scheme can tolerate high detector noise at Alice's side. Furthermore, the output of the source does not need to be single mode, since an optical homodyne detector can selectively measure a single mode determined by the local oscillator. Preliminary experimental results suggest that the proposed scheme could be implemented using an off-the-shelf amplified spontaneous emission source.« less

PrPC Governs Susceptibility to Prion Strains in Bank Vole, While Other Host Factors Modulate Strain Features.

PubMed

Espinosa, J C; Nonno, R; Di Bari, M; Aguilar-Calvo, P; Pirisinu, L; Fernández-Borges, N; Vanni, I; Vaccari, G; Marín-Moreno, A; Frassanito, P; Lorenzo, P; Agrimi, U; Torres, J M

2016-12-01

Bank vole is a rodent species that shows differential susceptibility to the experimental transmission of different prion strains. In this work, the transmission features of a panel of diverse prions with distinct origins were assayed both in bank vole expressing methionine at codon 109 (Bv109M) and in transgenic mice expressing physiological levels of bank vole PrP C (the BvPrP-Tg407 mouse line). This work is the first systematic comparison of the transmission features of a collection of prion isolates, representing a panel of diverse prion strains, in a transgenic-mouse model and in its natural counterpart. The results showed very similar transmission properties in both the natural species and the transgenic-mouse model, demonstrating the key role of the PrP amino acid sequence in prion transmission susceptibility. However, differences in the PrP Sc types propagated by Bv109M and BvPrP-Tg407 suggest that host factors other than PrP C modulate prion strain features. The differential susceptibility of bank voles to prion strains can be modeled in transgenic mice, suggesting that this selective susceptibility is controlled by the vole PrP sequence alone rather than by other species-specific factors. Differences in the phenotypes observed after prion transmissions in bank voles and in the transgenic mice suggest that host factors other than the PrP C sequence may affect the selection of the substrain replicating in the animal model. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

78 FR 4195 - Petition for Exemption From the Vehicle Theft Prevention Standard; Mercedes-Benz

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-18

..., transmitter key, electronic ignition starter switch control unit (EIS), the engine control module (ECM) and... immobilizer function. The interlinked system includes the engine, EIS, transmitter key, TCM and ECM (including...

Quantum key distribution using basis encoding of Gaussian-modulated coherent states

NASA Astrophysics Data System (ADS)

Huang, Peng; Huang, Jingzheng; Zhang, Zheshen; Zeng, Guihua

2018-04-01

The continuous-variable quantum key distribution (CVQKD) has been demonstrated to be available in practical secure quantum cryptography. However, its performance is restricted strongly by the channel excess noise and the reconciliation efficiency. In this paper, we present a quantum key distribution (QKD) protocol by encoding the secret keys on the random choices of two measurement bases: the conjugate quadratures X and P . The employed encoding method can dramatically weaken the effects of channel excess noise and reconciliation efficiency on the performance of the QKD protocol. Subsequently, the proposed scheme exhibits the capability to tolerate much higher excess noise and enables us to reach a much longer secure transmission distance even at lower reconciliation efficiency. The proposal can work alternatively to strengthen significantly the performance of the known Gaussian-modulated CVQKD protocol and serve as a multiplier for practical secure quantum cryptography with continuous variables.

Performance Analysis of Direct-Sequence Code-Division Multiple-Access Communications with Asymmetric Quadrature Phase-Shift-Keying Modulation

NASA Technical Reports Server (NTRS)

Wang, C.-W.; Stark, W.

2005-01-01

This article considers a quaternary direct-sequence code-division multiple-access (DS-CDMA) communication system with asymmetric quadrature phase-shift-keying (AQPSK) modulation for unequal error protection (UEP) capability. Both time synchronous and asynchronous cases are investigated. An expression for the probability distribution of the multiple-access interference is derived. The exact bit-error performance and the approximate performance using a Gaussian approximation and random signature sequences are evaluated by extending the techniques used for uniform quadrature phase-shift-keying (QPSK) and binary phase-shift-keying (BPSK) DS-CDMA systems. Finally, a general system model with unequal user power and the near-far problem is considered and analyzed. The results show that, for a system with UEP capability, the less protected data bits are more sensitive to the near-far effect that occurs in a multiple-access environment than are the more protected bits.

The ANTARES optical module

NASA Astrophysics Data System (ADS)

ANTARES Collaboration; Amram, P.; Anghinolfi, M.; Anvar, S.; Ardellier-Desages, F. E.; Aslanides, E.; Aubert, J.-J.; Azoulay, R.; Bailey, D.; Basa, S.; Battaglieri, M.; Bellotti, R.; Benhammou, Y.; Bernard, F.; Berthier, R.; Bertin, V.; Billault, M.; Blaes, R.; Bland, R. W.; Blondeau, F.; de Botton, N.; Boulesteix, J.; Brooks, C. B.; Brunner, J.; Cafagna, F.; Calzas, A.; Capone, A.; Caponetto, L.; Cârloganu, C.; Carmona, E.; Carr, J.; Carton, P.-H.; Cartwright, S. L.; Cassol, F.; Cecchini, S.; Ciacio, F.; Circella, M.; Compère, C.; Cooper, S.; Coyle, P.; Croquette, J.; Cuneo, S.; Danilov, M.; van Dantzig, R.; De Marzo, C.; DeVita, R.; Deck, P.; Destelle, J.-J.; Dispau, G.; Drougou, J. F.; Druillole, F.; Engelen, J.; Feinstein, F.; Festy, D.; Fopma, J.; Gallone, J.-M.; Giacomelli, G.; Goret, P.; Gosset, L.; Gournay, J.-F.; Heijboer, A.; Hernández-Rey, J. J.; Herrouin, G.; Hubbard, J. R.; Jaquet, M.; de Jong, M.; Karolak, M.; Kooijman, P.; Kouchner, A.; Kudryavtsev, V. A.; Lachartre, D.; Lafoux, H.; Lamare, P.; Languillat, J.-C.; Laubier, L.; Laugier, J.-P.; Le Guen, Y.; Le Provost, H.; Le Van Suu, A.; Lemoine, L.; Lo Nigro, L.; Lo Presti, D.; Loucatos, S.; Louis, F.; Lyashuk, V.; Magnier, P.; Marcelin, M.; Margiotta, A.; Massol, A.; Masullo, R.; Mazéas, F.; Mazeau, B.; Mazure, A.; McMillan, J. E.; Michel, J. L.; Migneco, E.; Millot, C.; Mols, P.; Montanet, F.; Montaruli, T.; Morel, J. P.; Moscoso, L.; Musumeci, M.; Navas, S.; Nezri, E.; Nooren, G. J.; Oberski, J.; Olivetto, C.; Oppelt-Pohl, A.; Palanque-Delabrouille, N.; Papaleo, R.; Payre, P.; Perrin, P.; Petruccetti, M.; Petta, C.; Piattelli, P.; Poinsignon, J.; Potheau, R.; Queinec, Y.; Racca, C.; Raia, G.; Randazzo, N.; Rethore, F.; Riccobene, G.; Ricol, J.-S.; Ripani, M.; Roca-Blay, V.; Rolin, J. F.; Rostovstev, A.; Russo, G. V.; Sacquin, Y.; Salusti, E.; Schuller, J.-P.; Schuster, W.; Soirat, J.-P.; Souvorova, O.; Spooner, N. J. C.; Spurio, M.; Stolarczyk, T.; Stubert, D.; Taiuti, M.; Tao, C.; Tayalati, Y.; Thompson, L. F.; Tilav, S.; Triay, R.; Valente, V.; Varlamov, I.; Vaudaine, G.; Vernin, P.; de Witt Huberts, P.; de Wolf, E.; Zakharov, V.; Zavatarelli, S.; de D. Zornoza, J.; Zún~iga, J.

2002-05-01

The ANTARES collaboration is building a deep sea neutrino telescope in the Mediterranean Sea. This detector will cover a sensitive area of typically 0.1km2 and will be equipped with about 1000 optical modules. Each of these optical modules consists of a large area photomultiplier and its associated electronics housed in a pressure resistant glass sphere. The design of the ANTARES optical module, which is a key element of the detector, has been finalized following extensive R&D studies and is reviewed here in detail.

Modulation and coding for throughput-efficient optical free-space links

NASA Technical Reports Server (NTRS)

Georghiades, Costas N.

1993-01-01

Optical direct-detection systems are currently being considered for some high-speed inter-satellite links, where data-rates of a few hundred megabits per second are evisioned under power and pulsewidth constraints. In this paper we investigate the capacity, cutoff-rate and error-probability performance of uncoded and trellis-coded systems for various modulation schemes and under various throughput and power constraints. Modulation schemes considered are on-off keying (OOK), pulse-position modulation (PPM), overlapping PPM (OPPM) and multi-pulse (combinatorial) PPM (MPPM).

EWS-FLI1 inhibits TNF{alpha}-induced NF{kappa}B-dependent transcription in Ewing sarcoma cells

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

Lagirand-Cantaloube, Julie, E-mail: julie.cantaloube@crbm.cnrs.fr; Laud, Karine, E-mail: karine.laud@curie.fr; Institut Curie, Genetique et biologie des cancers, Paris

2010-09-03

Research highlights: {yields} EWS-FLI1 interferes with TNF-induced activation of NF{kappa}B in Ewing sarcoma cells. {yields} EWS-FLI1 knockdown in Ewing sarcoma cells increases TNF-induced NF{kappa}B binding to DNA. {yields} EWS-FLI1 reduces TNF-stimulated NF{kappa}B-dependent transcriptional activation. {yields} Constitutive NF{kappa}B activity is not affected by EWS-FLI1. {yields} EWS-FLI1 physically interacts with NF{kappa}B p65 in vivo. -- Abstract: Ewing sarcoma is primarily caused by a t(11;22) chromosomal translocation encoding the EWS-FLI1 fusion protein. To exert its oncogenic function, EWS-FLI1 acts as an aberrant transcription factor, broadly altering the gene expression profile of tumor cells. Nuclear factor-kappaB (NF{kappa}B) is a tightly regulated transcription factor controllingmore » cell survival, proliferation and differentiation, as well as tumorigenesis. NF{kappa}B activity is very low in unstimulated Ewing sarcoma cells, but can be induced in response to tumor necrosis factor (TNF). We wondered whether NF{kappa}B activity could be modulated by EWS-FLI1 in Ewing sarcoma. Using a knockdown approach in Ewing sarcoma cells, we demonstrated that EWS-FLI1 has no influence on NF{kappa}B basal activity, but impairs TNF-induced NF{kappa}B-driven transcription, at least in part through inhibition of NF{kappa}B binding to DNA. We detected an in vivo physical interaction between the fusion protein and NF{kappa}B p65, which could mediate these effects. Our findings suggest that, besides directly controlling the activity of its primary target promoters, EWS-FLI1 can also indirectly influence gene expression in tumor cells by modulating the activity of key transcription factors such as NF{kappa}B.« less

Development of a health promotion programme to improve awareness of factors that affect fertility, and evaluation of its reach in the first 5 years.

PubMed

Hammarberg, Karin; Norman, Robert J; Robertson, Sarah; McLachlan, Robert; Michelmore, Janet; Johnson, Louise

2017-06-01

Awareness among people of reproductive age about the factors that influence fertility and reproductive outcomes, including medically assisted reproduction outcomes, is generally low. To improve awareness about the potentially modifiable factors that affect fertility and reproductive outcomes, 'Your Fertility', a fertility health promotion programme funded by the Australian Government, was established in 2011. This paper describes the development and evaluation of the reach of the Your Fertility programme from its inception in 2011 to June 2016. Systematically recorded outcomes for the programme's key focus areas and Google Analytics data were collated. Key achievements include developing and maintaining an internationally renowned website that experiences high growth and demand for fertility-related information; by 2016, over 5 million users had viewed more than 10 million webpages, and over 96,000 users had engaged in programme messages across social media. Programme messages have reached more than 4 million Australian social media users, and a potential audience of 150 million through media coverage across more than 320 media features. More than 4200 education and health professionals have completed online learning modules, and external partnerships have been established with 14 separate organizations. Data collected over 5 years indicate that the Your Fertility programme meets a need for targeted, evidence-based, accessible fertility-related information.

Organization of Anti-Phase Synchronization Pattern in Neural Networks: What are the Key Factors?

PubMed Central

Li, Dong; Zhou, Changsong

2011-01-01

Anti-phase oscillation has been widely observed in cortical neural network. Elucidating the mechanism underlying the organization of anti-phase pattern is of significance for better understanding more complicated pattern formations in brain networks. In dynamical systems theory, the organization of anti-phase oscillation pattern has usually been considered to relate to time delay in coupling. This is consistent to conduction delays in real neural networks in the brain due to finite propagation velocity of action potentials. However, other structural factors in cortical neural network, such as modular organization (connection density) and the coupling types (excitatory or inhibitory), could also play an important role. In this work, we investigate the anti-phase oscillation pattern organized on a two-module network of either neuronal cell model or neural mass model, and analyze the impact of the conduction delay times, the connection densities, and coupling types. Our results show that delay times and coupling types can play key roles in this organization. The connection densities may have an influence on the stability if an anti-phase pattern exists due to the other factors. Furthermore, we show that anti-phase synchronization of slow oscillations can be achieved with small delay times if there is interaction between slow and fast oscillations. These results are significant for further understanding more realistic spatiotemporal dynamics of cortico-cortical communications. PMID:22232576

Achieving Success in Small Business: A Self-Instruction Program for Small Business Owner-Managers. Assessing the Health of Your Business.

ERIC Educational Resources Information Center

Virginia Polytechnic Inst. and State Univ., Blacksburg. Div. of Vocational-Technical Education.

This self-instructional module on assessing the health of your business is the eleventh in a set of twelve modules designed for small business owner-managers. The competency for this module is to assess the financial condition of your business. Provided are information sections (key business records, balance sheet and profit and loss statements,…

Compact transmission system using single-sideband modulation of light for quantum cryptography.

PubMed

Duraffourg, L; Merolla, J M; Goedgebuer, J P; Mazurenko, Y; Rhodes, W T

2001-09-15

We report a new transmission that can be used for quantum key distribution. The system uses single-sideband-modulated light in an implementation of the BB84 quantum cryptography protocol. The system is formed by two integrated unbalanced Mach-Zehnder interferometers and is based on interference between phase-modulated sidebands in the spectral domain. Experiments show that high interference visibility can be obtained.

A system view and analysis of essential hypertension.

PubMed

Botzer, Alon; Grossman, Ehud; Moult, John; Unger, Ron

2018-05-01

The goal of this study was to investigate genes associated with essential hypertension from a system perspective, making use of bioinformatic tools to gain insights that are not evident when focusing at a detail-based resolution. Using various databases (pathways, Genome Wide Association Studies, knockouts etc.), we compiled a set of about 200 genes that play a major role in hypertension and identified the interactions between them. This enabled us to create a protein-protein interaction network graph, from which we identified key elements, based on graph centrality analysis. Enriched gene regulatory elements (transcription factors and microRNAs) were extracted by motif finding techniques and knowledge-based tools. We found that the network is composed of modules associated with functions such as water retention, endothelial vasoconstriction, sympathetic activity and others. We identified the transcription factor SP1 and the two microRNAs miR27 (a and b) and miR548c-3p that seem to play a major role in regulating the network as they exert their control over several modules and are not restricted to specific functions. We also noticed that genes involved in metabolic diseases (e.g. insulin) are central to the network. We view the blood-pressure regulation mechanism as a system-of-systems, composed of several contributing subsystems and pathways rather than a single module. The system is regulated by distributed elements. Understanding this mode of action can lead to a more precise treatment and drug target discovery. Our analysis suggests that insulin plays a primary role in hypertension, highlighting the tight link between essential hypertension and diseases associated with the metabolic syndrome.

Characterizing the role benthos plays in large coastal seas and estuaries: A modular approach

USGS Publications Warehouse

Tenore, K.R.; Zajac, R.N.; Terwin, J.; Andrade, F.; Blanton, J.; Boynton, W.; Carey, D.; Diaz, R.; Holland, Austin F.; Lopez-Jamar, E.; Montagna, P.; Nichols, F.; Rosenberg, R.; Queiroga, H.; Sprung, M.; Whitlatch, R.B.

2006-01-01

Ecologists studying coastal and estuarine benthic communities have long taken a macroecological view, by relating benthic community patterns to environmental factors across several spatial scales. Although many general ecological patterns have been established, often a significant amount of the spatial and temporal variation in soft-sediment communities within and among systems remains unexplained. Here we propose a framework that may aid in unraveling the complex influence of environmental factors associated with the different components of coastal systems (i.e. the terrestrial and benthic landscapes, and the hydrological seascape) on benthic communities, and use this information to assess the role played by benthos in coastal ecosystems. A primary component of the approach is the recognition of system modules (e.g. marshes, dendritic systems, tidal rivers, enclosed basins, open bays, lagoons). The modules may differentially interact with key forcing functions (e.g. temperature, salinity, currents) that influence system processes and in turn benthic responses and functions. Modules may also constrain benthic characteristics and related processes within certain ecological boundaries and help explain their overall spatio-temporal variation. We present an example of how benthic community characteristics are related to the modular structure of 14 coastal seas and estuaries, and show that benthic functional group composition is significantly related to the modular structure of these systems. We also propose a framework for exploring the role of benthic communities in coastal systems using this modular approach and offer predictions of how benthic communities may vary depending on the modular composition and characteristics of a coastal system. ?? 2006 Elsevier B.V. All rights reserved.

Transcription factor assisted loading and enhancer dynamics dictate the hepatic fasting response

PubMed Central

Goldstein, Ido; Baek, Songjoon; Presman, Diego M.; Paakinaho, Ville; Swinstead, Erin E.; Hager, Gordon L.

2017-01-01

Fasting elicits transcriptional programs in hepatocytes leading to glucose and ketone production. This transcriptional program is regulated by many transcription factors (TFs). To understand how this complex network regulates the metabolic response to fasting, we aimed at isolating the enhancers and TFs dictating it. Measuring chromatin accessibility revealed that fasting massively reorganizes liver chromatin, exposing numerous fasting-induced enhancers. By utilizing computational methods in combination with dissecting enhancer features and TF cistromes, we implicated four key TFs regulating the fasting response: glucocorticoid receptor (GR), cAMP responsive element binding protein 1 (CREB1), peroxisome proliferator activated receptor alpha (PPARA), and CCAAT/enhancer binding protein beta (CEBPB). These TFs regulate fuel production by two distinctly operating modules, each controlling a separate metabolic pathway. The gluconeogenic module operates through assisted loading, whereby GR doubles the number of sites occupied by CREB1 as well as enhances CREB1 binding intensity and increases accessibility of CREB1 binding sites. Importantly, this GR-assisted CREB1 binding was enhancer-selective and did not affect all CREB1-bound enhancers. Single-molecule tracking revealed that GR increases the number and DNA residence time of a portion of chromatin-bound CREB1 molecules. These events collectively result in rapid synergistic gene expression and higher hepatic glucose production. Conversely, the ketogenic module operates via a GR-induced TF cascade, whereby PPARA levels are increased following GR activation, facilitating gradual enhancer maturation next to PPARA target genes and delayed ketogenic gene expression. Our findings reveal a complex network of enhancers and TFs that dynamically cooperate to restore homeostasis upon fasting. PMID:28031249

NutrimiRAging: Micromanaging Nutrient Sensing Pathways through Nutrition to Promote Healthy Aging.

PubMed

Micó, Víctor; Berninches, Laura; Tapia, Javier; Daimiel, Lidia

2017-04-26

Current sociodemographic predictions point to a demographic shift in developed and developing countries that will result in an unprecedented increase of the elderly population. This will be accompanied by an increase in age-related conditions that will strongly impair human health and quality of life. For this reason, aging is a major concern worldwide. Healthy aging depends on a combination of individual genetic factors and external environmental factors. Diet has been proved to be a powerful tool to modulate aging and caloric restriction has emerged as a valuable intervention in this regard. However, many questions about how a controlled caloric restriction intervention affects aging-related processes are still unanswered. Nutrient sensing pathways become deregulated with age and lose effectiveness with age. These pathways are a link between diet and aging. Thus, fully understanding this link is a mandatory step before bringing caloric restriction into practice. MicroRNAs have emerged as important regulators of cellular functions and can be modified by diet. Some microRNAs target genes encoding proteins and enzymes belonging to the nutrient sensing pathways and, therefore, may play key roles in the modulation of the aging process. In this review, we aimed to show the relationship between diet, nutrient sensing pathways and microRNAs in the context of aging.

A Light-Regulated Genetic Module Was Recruited to Carpel Development in Arabidopsis following a Structural Change to SPATULA[W

PubMed Central

Reymond, Mathieu C.; Brunoud, Géraldine; Chauvet, Aurélie; Martínez-Garcia, Jaime F.; Martin-Magniette, Marie-Laure; Monéger, Françoise; Scutt, Charles P.

2012-01-01

A key innovation of flowering plants is the female reproductive organ, the carpel. Here, we show that a mechanism that regulates carpel margin development in the model flowering plant Arabidopsis thaliana was recruited from light-regulated processes. This recruitment followed the loss from the basic helix-loop-helix transcription factor SPATULA (SPT) of a domain previously responsible for its negative regulation by phytochrome. We propose that the loss of this domain was a prerequisite for the light-independent expression in female reproductive tissues of a genetic module that also promotes shade avoidance responses in vegetative organs. Striking evidence for this proposition is provided by the restoration of wild-type carpel development to spt mutants by low red/far-red light ratios, simulating vegetation shade, which we show to occur via phytochrome B, PHYTOCHROME INTERACTING FACTOR4 (PIF4), and PIF5. Our data illustrate the potential of modular evolutionary events to generate rapid morphological change and thereby provide a molecular basis for neo-Darwinian theories that describe this nongradualist phenomenon. Furthermore, the effects shown here of light quality perception on carpel development lead us to speculate on the potential role of light-regulated mechanisms in plant organs that, like the carpel, form within the shade of surrounding tissues. PMID:22851763

Probabilistic Analysis of a Composite Crew Module

NASA Technical Reports Server (NTRS)

Mason, Brian H.; Krishnamurthy, Thiagarajan

2011-01-01

An approach for conducting reliability-based analysis (RBA) of a Composite Crew Module (CCM) is presented. The goal is to identify and quantify the benefits of probabilistic design methods for the CCM and future space vehicles. The coarse finite element model from a previous NASA Engineering and Safety Center (NESC) project is used as the baseline deterministic analysis model to evaluate the performance of the CCM using a strength-based failure index. The first step in the probabilistic analysis process is the determination of the uncertainty distributions for key parameters in the model. Analytical data from water landing simulations are used to develop an uncertainty distribution, but such data were unavailable for other load cases. The uncertainty distributions for the other load scale factors and the strength allowables are generated based on assumed coefficients of variation. Probability of first-ply failure is estimated using three methods: the first order reliability method (FORM), Monte Carlo simulation, and conditional sampling. Results for the three methods were consistent. The reliability is shown to be driven by first ply failure in one region of the CCM at the high altitude abort load set. The final predicted probability of failure is on the order of 10-11 due to the conservative nature of the factors of safety on the deterministic loads.

The MADS transcription factor XAL2/AGL14 modulates auxin transport during Arabidopsis root development by regulating PIN expression

PubMed Central

Garay-Arroyo, Adriana; Ortiz-Moreno, Enrique; de la Paz Sánchez, María; Murphy, Angus S; García-Ponce, Berenice; Marsch-Martínez, Nayelli; de Folter, Stefan; Corvera-Poiré, Adriana; Jaimes-Miranda, Fabiola; Pacheco-Escobedo, Mario A; Dubrovsky, Joseph G; Pelaz, Soraya; Álvarez-Buylla, Elena R

2013-01-01

Elucidating molecular links between cell-fate regulatory networks and dynamic patterning modules is a key for understanding development. Auxin is important for plant patterning, particularly in roots, where it establishes positional information for cell-fate decisions. PIN genes encode plasma membrane proteins that serve as auxin efflux transporters; mutations in members of this gene family exhibit smaller roots with altered root meristems and stem-cell patterning. Direct regulators of PIN transcription have remained elusive. Here, we establish that a MADS-box gene (XAANTAL2, XAL2/AGL14) controls auxin transport via PIN transcriptional regulation during Arabidopsis root development; mutations in this gene exhibit altered stem-cell patterning, root meristem size, and root growth. XAL2 is necessary for normal shootward and rootward auxin transport, as well as for maintaining normal auxin distribution within the root. Furthermore, this MADS-domain transcription factor upregulates PIN1 and PIN4 by direct binding to regulatory regions and it is required for PIN4-dependent auxin response. In turn, XAL2 expression is regulated by auxin levels thus establishing a positive feedback loop between auxin levels and PIN regulation that is likely to be important for robust root patterning. PMID:24121311

The regulatory network analysis of long noncoding RNAs in human colorectal cancer.

PubMed

Zhang, Yuwei; Tao, Yang; Li, Yang; Zhao, Jinshun; Zhang, Lina; Zhang, Xiaohong; Dong, Changzheng; Xie, Yangyang; Dai, Xiaoyu; Zhang, Xinjun; Liao, Qi

2018-05-01

Colorectal cancer (CRC) is among one of the most prevalent and lethiferous diseases worldwide. Long noncoding RNAs (lncRNAs) are commonly accepted to function as a key regulatory factor in human cancer, but the potential regulatory mechanisms of CRC-associated lncRNA are largely obscure. Here, we integrated several expression profiles to obtain 55 differentially expressed (DE) lncRNAs. We first detected lncRNA interactions with transcription factors, microRNAs, mRNAs, and RNA-binding proteins to construct a regulatory network and then create functional enrichment analyses for them using bioinformatics approaches. We found the upregulated genes in the regulatory network are enriched in cell cycle and DNA damage response, while the downregulated genes are enriched in cell differentiation, cellular response, and cell signaling. We then employed module-based methods to mine several intriguing modules from the overall network, which helps to classify the functions of genes more specifically. Next, we confirmed the validity of our network by comparisons with a randomized network using computational method. Finally, we attempted to annotate lncRNA functions based on the regulatory network, which indicated its potential application. Our study of the lncRNA regulatory network provided significant clues to unveil lncRNAs potential regulatory mechanisms in CRC and laid a foundation for further experimental investigation.

Promoting tissue regeneration by modulating the immune system.

PubMed

Julier, Ziad; Park, Anthony J; Briquez, Priscilla S; Martino, Mikaël M

2017-04-15

The immune system plays a central role in tissue repair and regeneration. Indeed, the immune response to tissue injury is crucial in determining the speed and the outcome of the healing process, including the extent of scarring and the restoration of organ function. Therefore, controlling immune components via biomaterials and drug delivery systems is becoming an attractive approach in regenerative medicine, since therapies based on stem cells and growth factors have not yet proven to be broadly effective in the clinic. To integrate the immune system into regenerative strategies, one of the first challenges is to understand the precise functions of the different immune components during the tissue healing process. While remarkable progress has been made, the immune mechanisms involved are still elusive, and there is indication for both negative and positive roles depending on the tissue type or organ and life stage. It is well recognized that the innate immune response comprising danger signals, neutrophils and macrophages modulates tissue healing. In addition, it is becoming evident that the adaptive immune response, in particular T cell subset activities, plays a critical role. In this review, we first present an overview of the basic immune mechanisms involved in tissue repair and regeneration. Then, we highlight various approaches based on biomaterials and drug delivery systems that aim at modulating these mechanisms to limit fibrosis and promote regeneration. We propose that the next generation of regenerative therapies may evolve from typical biomaterial-, stem cell-, or growth factor-centric approaches to an immune-centric approach. Most regenerative strategies have not yet proven to be safe or reasonably efficient in the clinic. In addition to stem cells and growth factors, the immune system plays a crucial role in the tissue healing process. Here, we propose that controlling the immune-mediated mechanisms of tissue repair and regeneration may support existing regenerative strategies or could be an alternative to using stem cells and growth factors. The first part of this review we highlight key immune mechanisms involved in the tissue healing process and marks them as potential target for designing regenerative strategies. In the second part, we discuss various approaches using biomaterials and drug delivery systems that aim at modulating the components of the immune system to promote tissue regeneration. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Influence of laser linewidth and polarization modulator length on polarization shift keying for free space optical communication.

PubMed

Han, Biao; Zhao, Wei; Xie, Xiaoping; Su, Yulong; Wang, Wei; Hu, Hui

2015-04-06

Modulating signal with polarization modulator (PolM) is the simplest method for polarization shift keying (PolSK) in free space optical communication. However, this method has an intrinsic drawback on degree of polarization (DOP) reduction for the existence of polarization mode dispersion (PMD) in PolM. In this work, we analyze this change of DOP and its influence on PolSK using coherency matrix. We demonstrate that the decrease of DOP after PolM will generate extra loss and bit error ratio (BER) for PolSK communication, while this loss and BER will aggravate with the increase of laser linewidth and PolM length. For a practical PolSK system, laser linewidth should be less than 0.008nm.

Metal-capped silicon organic micro-ring electro-optical modulator (Conference Presentation)

NASA Astrophysics Data System (ADS)

Zaki, Aya O.; Kirah, Khaled A.; Swillam, Mohamed A.

2017-02-01

An ultra-compact hybrid plasmonic waveguide ring electro-optical modulator is designed to be easily fabricated on silicon on insulator (SOI) substrates using standard silicon photonics technology. The proposed waveguide is based on a buried standard silicon waveguide of height 220 nm topped with polymer and metal. The key advantage of this novel design is that only the silicon layer of the waveguide is structured as a coupled ring resonator. Then, the device is covered with electro-optical polymer and metal in post processes with no need for lithography or accurate mask alignment techniques. The simple fabrication method imposes many design challenges to obtain a resonator of reasonable loaded quality factor and high extinction ratio. Here, the performance of the resonator is optimized in the telecom wavelength range around 1550 nm using 3D FDTD simulations. The design of the coupling junction between the access waveguide and the tightly bent ring is thoroughly studied. The extension of the metal over the coupling region is exploited to make the critical dimension of the design geometry at least 2.5 times larger than conventional plasmonic resonators and the design is thus more robust. In this paper, we demonstrate an electro-optical modulator that offers an insertion loss < 1 dB, a modulation depth of 12 dB for an applied peak to peak voltage of only 2 V and energy consumption of 1.74 fJ/bit. The performance is superior to previously reported hybrid plasmonic ring resonator based modulators while the design shows robustness and low fabrication cost.

Expression of AtWRKY33 encoding a pathogen- or PAMP-responsive WRKY transcription factor is regulated by a composite DNA motif containing W box elements.

PubMed

Lippok, Bernadette; Birkenbihl, Rainer P; Rivory, Gaelle; Brümmer, Janna; Schmelzer, Elmon; Logemann, Elke; Somssich, Imre E

2007-04-01

WRKY transcription factors regulate distinct parts of the plant defense transcriptome. Expression of many WRKY genes themselves is induced by pathogens or pathogen-mimicking molecules. Here, we demonstrate that Arabidopsis WRKY33 responds to various stimuli associated with plant defense as well as to different kinds of phytopathogens. Although rapid pathogen-induced AtWRKY33 expression does not require salicylic acid (SA) signaling, it is dependent on PAD4, a key regulator upstream of SA. Activation of AtWRKY33 is independent of de novo protein synthesis, suggesting that it is at least partly under negative regulatory control. We show that a set of three WRKY-specific cis-acting DNA elements (W boxes) within the AtWRKY33 promoter is required for efficient pathogen- or PAMP-triggered gene activation. This strongly indicates that WRKY transcription factors are major components of the regulatory machinery modulating immediate to early expression of this gene in response to pathogen attack.

PIF4 and PIF5 transcription factors link blue light and auxin to regulate the phototropic response in Arabidopsis.

PubMed

Sun, Jiaqiang; Qi, Linlin; Li, Yanan; Zhai, Qingzhe; Li, Chuanyou

2013-06-01

Both blue light (BL) and auxin are essential for phototropism in Arabidopsis thaliana. However, the mechanisms by which light is molecularly linked to auxin during phototropism remain elusive. Here, we report that phytochrome interacting factoR4 (PIF4) and PIF5 act downstream of the BL sensor phototropin1 (PHOT1) to negatively modulate phototropism in Arabidopsis. We also reveal that PIF4 and PIF5 negatively regulate auxin signaling. Furthermore, we demonstrate that PIF4 directly activates the expression of the auxin/indole-3-acetic acid (IAA) genes IAA19 and IAA29 by binding to the G-box (CACGTG) motifs in their promoters. Our genetic assays demonstrate that IAA19 and IAA29, which physically interact with auxin response factor7 (ARF7), are sufficient for PIF4 to negatively regulate auxin signaling and phototropism. This study identifies a key step of phototropic signaling in Arabidopsis by showing that PIF4 and PIF5 link light and auxin.

NRF2 Orchestrates the Metabolic Shift during Induced Pluripotent Stem Cell Reprogramming

PubMed Central

Hawkins, Kate E.; Joy, Shona; Delhove, Juliette M.K.M.; Kotiadis, Vassilios N.; Fernandez, Emilio; Fitzpatrick, Lorna M.; Whiteford, James R.; King, Peter J.; Bolanos, Juan P.; Duchen, Michael R.; Waddington, Simon N.; McKay, Tristan R.

2016-01-01

Summary The potential of induced pluripotent stem cells (iPSCs) in disease modeling and regenerative medicine is vast, but current methodologies remain inefficient. Understanding the cellular mechanisms underlying iPSC reprogramming, such as the metabolic shift from oxidative to glycolytic energy production, is key to improving its efficiency. We have developed a lentiviral reporter system to assay longitudinal changes in cell signaling and transcription factor activity in living cells throughout iPSC reprogramming of human dermal fibroblasts. We reveal early NF-κB, AP-1, and NRF2 transcription factor activation prior to a temporal peak in hypoxia inducible factor α (HIFα) activity. Mechanistically, we show that an early burst in oxidative phosphorylation and elevated reactive oxygen species generation mediates increased NRF2 activity, which in turn initiates the HIFα-mediated glycolytic shift and may modulate glucose redistribution to the pentose phosphate pathway. Critically, inhibition of NRF2 by KEAP1 overexpression compromises metabolic reprogramming and results in reduced efficiency of iPSC colony formation. PMID:26904936

RNA:RNA interaction can enhance RNA localization in Drosophila oocytes

PubMed Central

Hartswood, Eve; Brodie, Jim; Vendra, Georgia; Davis, Ilan; Finnegan, David J.

2012-01-01

RNA localization is a key mechanism for targeting proteins to particular subcellular domains. Sequences necessary and sufficient for localization have been identified, but little is known about factors that affect its kinetics. Transcripts of gurken and the I factor, a non-LTR retrotransposon, colocalize at the nucleus in the dorso–antero corner of the Drosophila oocyte directed by localization signals, the GLS and ILS. I factor RNA localizes faster than gurken after injection into oocytes, due to a difference in the intrinsic localization ability of the GLS and ILS. The kinetics of localization of RNA containing the ILS are enhanced by the presence of a stem–loop, the A loop. This acts as an RNA:RNA interaction element in vivo and in vitro, and stimulates localization of RNA containing other localization signals. RNA:RNA interaction may be a general mechanism for modulating RNA localization and could allow an mRNA that lacks a localization signal to hitchhike on another RNA that has one. PMID:22345148

76 FR 12221 - Petition for Exemption From the Federal Motor Vehicle Motor Theft Prevention Standard; Toyota

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-04

...), assembly, transponder key amplifier, security indicator, ignition key and Electronic control module (ECM... been verified, the immobilizer allows the ECM to start the engine. Toyota also stated that there will...

SU-E-T-97: Dependence Of Optically Stimulated Luminescent Dosimeter (OSLD) Out Of Field Response On Volumetric Modulated Arc Therapy (VMAT) Field Modulation

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

Ware, S; Clouser, E

2014-06-01

Purpose: To determine the out of field response of Microstar ii OSLDs as a function of field modulation and distance in VMAT plan delivery. This work has potential application in fetal dose monitoring or measurements on cardiac pacemakers Methods: VMAT plans were created in Eclipse and optimized to varying degrees of modulation. Three plans were chosen to represent low, medium and high degrees of modulation (modulation factors as defined by MU/cGy). Plans were delivered to slabs of solid water with dimensions 60cm length, 30cm width, and 10cm height. For each modulation factor, 2 OSLDs were placed at 1cm depth withmore » out of field distances of 1, 2, 3, 5, 8 and 10cm and the plan delivered isocentrically to a depth of 5cm. This technique was repeated for a Farmer Chamber by incrementing the table by the appropriate distance. The charge readings for the Farmer Chamber were converted to dose and the ratios taken as functions of modulation factors and distances out of field Results: Examination of the results as a function of out of field distance shows a trend of increasing OSLD/Farmer Chamber ratios for all modulation factors. The slopes appear to be roughly equivalent for all modulation factors investigated. Results as a function of modulation showed a downward trend for all out of field distances, with the greatest differences seen at 5cm and 8cm Conclusion: This study demonstrates that the response of OSLD dosimeters change as a function of out of field distance and modulation. The differences seen are within the stated accuracy of the system for the out of field distances and modulations investigated. Additional investigation is warranted to see if the OSLD response changes appreciably with longer out of field distances or wider ranges of modulation.« less

ART CONCEPTS - APOLLO IX

NASA Image and Video Library

1969-02-20

S69-19794 (February 1969) --- Composite of two artist's concepts illustrating key events, tasks and activities on the third day of the Apollo 9 mission, including crew transfer and Lunar Module system evaluation. The Apollo 9 mission will evaluate spacecraft lunar module systems performance during manned Earth-orbital flight.

Carpentry. Student Learning Guide.

ERIC Educational Resources Information Center

Palm Beach County Board of Public Instruction, West Palm Beach, FL.

This student learning guide contains 17 modules for completing a course in carpentry. It is designed especially for use in secondary schools in Palm Beach County, Florida. Each module covers one task, and consists of a purpose, performance objective, enabling objectives, learning activities keyed to resources, information sheets, student…

Masonry. Student Learning Guide.

ERIC Educational Resources Information Center

Palm Beach County Board of Public Instruction, West Palm Beach, FL.

This student learning guide contains nine modules for completing a course in masonry. It is designed especially for use in secondary schools in Palm Beach County, Florida. Each module covers one task, and consists of a purpose, performance objective, enabling objectives, learning activities keyed to resources, information sheets, student…

Summary and Synthesis: How to Present a Research Proposal.

PubMed

Setia, Maninder Singh; Panda, Saumya

2017-01-01

This concluding module attempts to synthesize the key learning points discussed during the course of the previous ten sets of modules on methodology and biostatistics. The objective of this module is to discuss how to present a model research proposal, based on whatever was discussed in the preceding modules. The lynchpin of a research proposal is the protocol, and the key component of a protocol is the study design. However, one must not neglect the other areas, be it the project summary through which one catches the eyes of the reviewer of the proposal, or the background and the literature review, or the aims and objectives of the study. Two critical areas in the "methods" section that cannot be emphasized more are the sampling strategy and a formal estimation of sample size. Without a legitimate sample size, none of the conclusions based on the statistical analysis would be valid. Finally, the ethical parameters of the study should be well understood by the researchers, and that should get reflected in the proposal.

High-security communication by coherence modulation at the photon-counting level.

PubMed

Rhodes, William T; Boughanmi, Abdellatif; Moreno, Yezid Torres

2016-05-20

We show that key-specified interferometer path-length difference modulation (often referred to as coherence modulation), operating in the photon-counting regime with a broadband source, can provide a quantifiably high level of physics-guaranteed security for binary signal transmission. Each signal bit is associated with many photocounts, perhaps numbering in the thousands. Of great importance, the presence of an eavesdropper can be quickly detected. We first review the operation of key-specified coherence modulation at high light levels, illustrating by means of an example its lack of security against attack. We then show, using the same example, that, through the reduction of light intensities to photon-counting levels, a high level of security can be attained. A particular attack on the system is analyzed to demonstrate the quantifiability of the scheme's security, and various remaining research issues are discussed. A potential weakness of the scheme lies in a possible vulnerability to light amplification by an attacker.

Summary and Synthesis: How to Present a Research Proposal

PubMed Central

Setia, Maninder Singh; Panda, Saumya

2017-01-01

This concluding module attempts to synthesize the key learning points discussed during the course of the previous ten sets of modules on methodology and biostatistics. The objective of this module is to discuss how to present a model research proposal, based on whatever was discussed in the preceding modules. The lynchpin of a research proposal is the protocol, and the key component of a protocol is the study design. However, one must not neglect the other areas, be it the project summary through which one catches the eyes of the reviewer of the proposal, or the background and the literature review, or the aims and objectives of the study. Two critical areas in the “methods” section that cannot be emphasized more are the sampling strategy and a formal estimation of sample size. Without a legitimate sample size, none of the conclusions based on the statistical analysis would be valid. Finally, the ethical parameters of the study should be well understood by the researchers, and that should get reflected in the proposal. PMID:28979004

Testing FSO WDM communication system in simulation software optiwave OptiSystem in different atmospheric environments

NASA Astrophysics Data System (ADS)

Vanderka, Ales; Hajek, Lukas; Bednarek, Lukas; Latal, Jan; Vitasek, Jan; Hejduk, Stanislav; Vasinek, Vladimir

2016-09-01

In this article the author's team deals with using Wavelength Division Multiplexing (WDM) for Free Space Optical (FSO) Communications. In FSO communication occurs due to the influence of atmospheric effect (attenuation, and fluctuation of the received power signal, influence turbulence) and the WDM channel suffers from interchannel crosstalk. There is considered only the one direction. The behavior FSO link was tested for one or eight channels. Here we will be dealing with modulation schemes OOK (On-Off keying), QAM (Quadrature Amplitude Modulation) and Subcarrier Intensity Modulation (SIM) based on a BPSK (Binary Phase Shift Keying). Simulation software OptiSystem 14 was used for tasting. For simulation some parameters were set according to real FSO link such as the datarate 1.25 Gbps, link range 1.4 km. Simulated FSO link used wavelength of 1550 nm with 0.8 nm spacing. There is obtained the influence of crosstalk and modulation format for the BER, depending on the amount of turbulence in the propagation medium.

Four-amplitude shift keying-single sideband millimeter-wave signal generation with frequency sextupling based on optical phase modulation

NASA Astrophysics Data System (ADS)

Wu, Peng; Ma, Jianxin

2017-03-01

We have proposed and demonstrated a scheme to generate a frequency-sextupling amplitude shift keying (ASK)-single sideband optical millimeter (mm)-wave signal with high dispersion tolerance based on an optical phase modulator (PM) by ably using the-4th-order and +2nd-order sidebands of the optical modulation. The ASK radio frequency signal, superposed by a local oscillator with the same frequency, modulates the lightwave via an optical PM with proper voltage amplitudes, the +2nd-order sideband carries the ASK signal with a constant slope while the -4th-order sideband maintains constant amplitude. These two sidebands can be abstracted by a wavelength selective switch to form a dual-tone optical mm-wave with only one tone carrying the ASK signal. As only one tone bears the ASK signal while the other tone is unmodulated, the generated dual-tone optical mm-wave signal has high dispersion tolerance.

Research on the system performance evaluation of minimum-shift keying in uplink ground-to-satellite with gamma-gamma distribution

NASA Astrophysics Data System (ADS)

Wang, Yi; Zhang, Ao; Ma, Jing

2017-07-01

Minimum-shift keying (MSK) has the advantages of constant envelope, continuous phase, and high spectral efficiency, and it is applied in radio communication and optical fiber communication. MSK modulation of coherent detection is proposed in the ground-to-satellite laser communication system; in addition, considering the inherent noise of uplink, such as intensity scintillation and beam wander, the communication performance of the MSK modulation system with coherent detection is studied in the uplink ground-to-satellite laser. Based on the gamma-gamma channel model, the closed form of bit error rate (BER) of MSK modulation with coherent detection is derived. In weak, medium, and strong turbulence, the BER performance of the MSK modulation system is simulated and analyzed. To meet the requirements of the ground-to-satellite coherent MSK system to optimize the parameters and configuration of the transmitter and receiver, the influence of the beam divergence angle, the zenith angle, the transmitter beam radius, and the receiver diameter are studied.

Module 3: Text Versions | State, Local, and Tribal Governments | NREL

Science.gov Websites

walk through the key considerations and activities that should be performed when evaluating a site for speak about larger systems. So generally when you start thinking about site evaluation and kinda moving some of the key considerations, key things that should be considered when you're doing a site

Socio-economic and psychological correlates of suicidality among Hong Kong working-age adults: results from a population-based survey.

PubMed

Liu, Ka Y; Chen, Eric Y H; Chan, Cecilia L W; Lee, Dominic T S; Law, Y W; Conwell, Yeates; Yip, Paul S F

2006-12-01

The global toll of suicide is estimated to be one million lives per year, which exceeded the number of deaths by homicide and war combined. A key step to suicide prevention is to prevent less serious suicidal behaviour to preclude more lethal outcomes. Although 61% of the world's suicides take place in Asia and the suicide rates among middle age groups have been increasing since the economic crisis in many Asian countries, population-based studies of suicidal behaviour among working-age adults in non-western communities are scarce. Data from a population-based survey with 2015 participants were used to estimate the prevalence of suicidal ideation and behaviour among the working-age population in Hong Kong, and to study the associated socio-economic and psychological correlates. We focused particularly on potential modulating factors between life-event-related factors and suicidal ideation. Six per cent of the Hong Kong population aged 20-59 years considered suicide in the past year, while 1.4% attempted suicide. Hopelessness, reasons for living, and reluctance to seek help from family and friends had direct association with past-year suicidal ideation. Reasons for living were found to moderate the effect of perceived stress on suicidal ideation. Suicidality is a multi-faceted problem that calls for a multi-sectored, multi-layered approach to prevention. Prevention programmes can work on modulating factors such as reasons for living to reduce suicidal risk in working-age adults.

Lifestyle Shapes the Dialogue between Environment, Microglia, and Adult Neurogenesis.

PubMed

Valero, Jorge; Paris, Iñaki; Sierra, Amanda

2016-04-20

Lifestyle modulates brain function. Diet, stress levels, and physical exercise among other factors influence the "brain cognitive reserve", that is, the capacity of the brain to maintain a normal function when confronting neurodegenerative diseases, injury, and/or aging. This cognitive reserve relays on several cellular and molecular elements that contribute to brain plasticity allowing adaptive responses to cognitive demands, and one of its key components is the hippocampal neurogenic reserve. Hippocampal neural stem cells give rise to new neurons that integrate into the local circuitry and contribute to hippocampal functions such as memory and learning. Importantly, adult hippocampal neurogenesis is well-known to be modulated by the demands of the environment and lifestyle factors. Diet, stress, and physical exercise directly act on neural stem cells and/or their progeny, but, in addition, they may also indirectly affect neurogenesis by acting on microglia. Microglia, the guardians of the brain, rapidly sense changes in the brain milieu, and it has been recently shown that their function is affected by lifestyle factors. However, few studies have analyzed the modulatory effect of microglia on adult neurogenesis in these conditions. Here, we review the current knowledge about the dialogue maintained between microglia and the hippocampal neurogenic cascade. Understanding how the communication between microglia and hippocampal neurogenesis is affected by lifestyle choices is crucial to maintain the brain cognitive reserve and prevent the maladaptive responses that emerge during disease or injury through adulthood and aging.

Role of promoter DNA sequence variations on the binding of EGR1 transcription factor.

PubMed

Mikles, David C; Schuchardt, Brett J; Bhat, Vikas; McDonald, Caleb B; Farooq, Amjad

2014-05-01

In response to a wide variety of stimuli such as growth factors and hormones, EGR1 transcription factor is rapidly induced and immediately exerts downstream effects central to the maintenance of cellular homeostasis. Herein, our biophysical analysis reveals that DNA sequence variations within the target gene promoters tightly modulate the energetics of binding of EGR1 and that nucleotide substitutions at certain positions are much more detrimental to EGR1-DNA interaction than others. Importantly, the reduction in binding affinity poorly correlates with the loss of enthalpy and gain of entropy-a trend indicative of a complex interplay between underlying thermodynamic factors due to the differential role of water solvent upon nucleotide substitution. We also provide a rationale for the physical basis of the effect of nucleotide substitutions on the EGR1-DNA interaction at atomic level. Taken together, our study bears important implications on understanding the molecular determinants of a key protein-DNA interaction at the cross-roads of human health and disease. Copyright © 2014 Elsevier Inc. All rights reserved.

Macrophage migration inhibitory factor deficiency is associated with impaired killing of gram-negative bacteria by macrophages and increased susceptibility to Klebsiella pneumoniae sepsis.

PubMed

Roger, Thierry; Delaloye, Julie; Chanson, Anne-Laure; Giddey, Marlyse; Le Roy, Didier; Calandra, Thierry

2013-01-15

The cytokine macrophage migration inhibitory factor (MIF) is an important component of the early proinflammatory response of the innate immune system. However, the antimicrobial defense mechanisms mediated by MIF remain fairly mysterious. In the present study, we examined whether MIF controls bacterial uptake and clearance by professional phagocytes, using wild-type and MIF-deficient macrophages. MIF deficiency did not affect bacterial phagocytosis, but it strongly impaired the killing of gram-negative bacteria by macrophages and host defenses against gram-negative bacterial infection, as shown by increased mortality in a Klebsiella pneumonia model. Consistent with MIF's regulatory role of Toll-like 4 expression in macrophages, MIF-deficient cells stimulated with lipopolysaccharide or Escherichia coli exhibited reduced nuclear factor κB activity and tumor necrosis factor (TNF) production. Addition of recombinant MIF or TNF corrected the killing defect of MIF-deficient macrophages. Together, these data show that MIF is a key mediator of host responses against gram-negative bacteria, acting in part via a modulation of bacterial killing by macrophages.

Encoding of frequency-modulation (FM) rates in human auditory cortex.

PubMed

Okamoto, Hidehiko; Kakigi, Ryusuke

2015-12-14

Frequency-modulated sounds play an important role in our daily social life. However, it currently remains unclear whether frequency modulation rates affect neural activity in the human auditory cortex. In the present study, using magnetoencephalography, we investigated the auditory evoked N1m and sustained field responses elicited by temporally repeated and superimposed frequency-modulated sweeps that were matched in the spectral domain, but differed in frequency modulation rates (1, 4, 16, and 64 octaves per sec). The results obtained demonstrated that the higher rate frequency-modulated sweeps elicited the smaller N1m and the larger sustained field responses. Frequency modulation rate had a significant impact on the human brain responses, thereby providing a key for disentangling a series of natural frequency-modulated sounds such as speech and music.

Bidirectional private key exchange using delay-coupled semiconductor lasers.

PubMed

Porte, Xavier; Soriano, Miguel C; Brunner, Daniel; Fischer, Ingo

2016-06-15

We experimentally demonstrate a key exchange cryptosystem based on the phenomenon of identical chaos synchronization. In our protocol, the private key is symmetrically generated by the two communicating partners. It is built up from the synchronized bits occurring between two current-modulated bidirectionally coupled semiconductor lasers with additional self-feedback. We analyze the security of the exchanged key and discuss the amplification of its privacy. We demonstrate private key generation rates up to 11  Mbit/s over a public channel.

Rescue Manual. Module 2.

ERIC Educational Resources Information Center

Ohio State Univ., Columbus. Instructional Materials Lab.

This learner manual for rescuers covers the current techniques or practices required in the rescue service. The second of 10 modules contains 5 chapters: (1) patient care and handling techniques; (2) rescue carries and drags; (3) emergency vehicle operations; (4) self-contained breathing apparatus; and (5) protective clothing. Key points, an…

Rescue Manual. Module 6.

ERIC Educational Resources Information Center

Ohio State Univ., Columbus. Instructional Materials Lab.

This learner manual for rescuers covers the current techniques or practices required in the rescue service. The sixth of 10 modules contains 4 chapters: (1) industrial rescue; (2) rescue from a confined space; (3) extrication from heavy equipment; and (4) rescue operations involving elevators. Key points, an introduction, and conclusion accompany…

Rescue Manual. Module 8.

ERIC Educational Resources Information Center

Ohio State Univ., Columbus. Instructional Materials Lab.

This learner manual for rescuers covers the current techniques or practices required in the rescue service. The eighth of 10 modules contains 6 chapters: (1) trench rescue; (2) shoring and tunneling techniques; (3) farm accident rescue; (4) wilderness search and rescue; (5) aircraft rescue; and (6) helicopter information. Key points, an…

Welding. Student Learning Guide.

ERIC Educational Resources Information Center

Palm Beach County Board of Public Instruction, West Palm Beach, FL.

This student learning guide contains 30 modules for completing a course in welding. It is designed especially for use in secondary schools in Palm Beach County, Florida. Each module covers one task, and consists of a purpose, performance objective, enabling objectives, learning activities keyed to resources, information sheets, student self-check…

Chirp-free optical return-to-zero modulation based on a single microring resonator.

PubMed

Sun, Lili; Ye, Tong; Wang, Xiaowen; Zhou, Linjie; Chen, Jianping

2012-03-26

This paper proposes a chirp-free optical return-to-zero (RZ) modulator using a double coupled microring resonator. Optical RZ modulation is achieved by applying a clock (CLK) driving signal to the input coupling region and a non-return-to-zero (NRZ) driving signal to the output coupling region. Static and time-domain coupled-mode theory (CMT) based dynamic analyse are performed to theoretically investigate its performance in RZ modulation. The criteria to realize RZ modulation are deduced. Various RZ modulation formats, including RZ phase-shift-keying (RZ-PSK), carrier-suppressed RZ (CSRZ), and RZ intensity modulation formats, can be implemented by using CLK and NRZ signals with different combinations of polarities. Numerical simulations are performed and the feasibility of our modulator at 10 Gbit/s for the multiple RZ modulation formats is verified.

Cellular and molecular mechanisms for the bone response to mechanical loading

NASA Technical Reports Server (NTRS)

Bloomfield, S. A.

2001-01-01

To define the cellular and molecular mechanisms for the osteogenic response of bone to increased loading, several key steps must be defined: sensing of the mechanical signal by cells in bone, transduction of the mechanical signal to a biochemical one, and transmission of that biochemical signal to effector cells. Osteocytes are likely to serve as sensors of loading, probably via interstitial fluid flow produced during loading. Evidence is presented for the role of integrins, the cell's actin cytoskeleton, G proteins, and various intracellular signaling pathways in transducing that mechanical signal to a biochemical one. Nitric oxide, prostaglandins, and insulin-like growth factors all play important roles in these pathways. There is growing evidence for modulation of these mechanotransduction steps by endocrine factors, particularly parathyroid hormone and estrogen. The efficiency of this process is also impaired in the aged animal, yet what remains undefined is at what step mechanotransduction is affected.

Cryptochrome 1 interacts with PIF4 to regulate high temperature-mediated hypocotyl elongation in response to blue light.

PubMed

Ma, Dingbang; Li, Xu; Guo, Yongxia; Chu, Jingfang; Fang, Shuang; Yan, Cunyu; Noel, Joseph P; Liu, Hongtao

2016-01-05

Cryptochrome 1 (CRY1) is a blue light receptor that mediates primarily blue-light inhibition of hypocotyl elongation. Very little is known of the mechanisms by which CRY1 affects growth. Blue light and temperature are two key environmental signals that profoundly affect plant growth and development, but how these two abiotic factors integrate remains largely unknown. Here, we show that blue light represses high temperature-mediated hypocotyl elongation via CRY1. Furthermore, CRY1 interacts directly with PHYTOCHROME-INTERACTING FACTOR 4 (PIF4) in a blue light-dependent manner to repress the transcription activity of PIF4. CRY1 represses auxin biosynthesis in response to elevated temperature through PIF4. Our results indicate that CRY1 signal by modulating PIF4 activity, and that multiple plant photoreceptors [CRY1 and PHYTOCHROME B (PHYB)] and ambient temperature can mediate morphological responses through the same signaling component-PIF4.

The intersection between growth factors, autophagy and ER stress: A new target to treat neurodegenerative diseases?

PubMed

Garcia-Huerta, Paula; Troncoso-Escudero, Paulina; Jerez, Carolina; Hetz, Claudio; Vidal, Rene L

2016-10-15

One of the salient features of most neurodegenerative diseases is the aggregation of specific proteins in the brain. This proteostasis imbalance is proposed as a key event triggering the neurodegenerative cascade. The unfolded protein response (UPR) and autophagy pathways are emerging as critical processes implicated in handling disease-related misfolded proteins. However, in some conditions, perturbations in the buffering capacity of the proteostasis network may be part of the etiology of the disease. Thus, pharmacological or gene therapy strategies to enhance autophagy or UPR responses are becoming an attractive target for disease intervention. Here, we discuss current evidence depicting the complex involvement of autophagy and ER stress in brain diseases. Novel pathways to modulate protein misfolding are discussed including the relation between aging and growth factor signaling. This article is part of a Special Issue entitled SI:Autophagy. Copyright © 2016 Elsevier B.V. All rights reserved.