The cellular mastermind(?) – Mechanotransduction and the nucleus

Science.gov (United States)

Kaminski, Ashley; Fedorchak, Gregory R.; Lammerding, Jan

2015-01-01

Cells respond to mechanical stimulation by activation of specific signaling pathways and genes that allow the cell to adapt to its dynamic physical environment. How cells sense the various mechanical inputs and translate them into biochemical signals remains an area of active investigation. Recent reports suggest that the cell nucleus may be directly implicated in this cellular mechanotransduction process. In this chapter, we discuss how forces applied to the cell surface and cytoplasm induce changes in nuclear structure and organization, which could directly affect gene expression, while also highlighting the complex interplay between nuclear structural proteins and transcriptional regulators that may further modulate mechanotransduction signaling. Taken together, these findings paint a picture of the nucleus as a central hub in cellular mechanotransduction—both structurally and biochemically—with important implications in physiology and disease. PMID:25081618

External Environment Sensing by a Module on Self-reconfiguration Robot

Science.gov (United States)

Goto, Tomotsugu; Uchida, Masafumi; Onogaki, Hitoshi

In the situation in which a robot and a human work together by collaborating with each other, a robot and a human share one working environment, and each interferes in each other. The boundary of each complex dynamic occupation area changes in the connection movement which is the component of collaborative works at this time. The main restraint condition which relates to the robustness of that connection movement is each physical charactristics, that is, the embodiment. A robot body is variability though the embodiment of a human is almost fixed. Therefore, the safe and the robust connection movement is brought when a robot has the robot body which is well suitable for the embodiment of a human. A purpose for this research is that the colaboration works between the self-reconfiguration robot and a human is realized. To achieve this purpose, sensing function of external environment on a module was examined. A module is a component of the self-reconfiguration robot. A robot body vibrates when a module actuates an arm actively. This vibration is observed by using some acceleration sensors. Measured datas reflects a difference of objects that it touches a robot body. In this paper, the sensing technique of external environment which identifies this difference by using the neural network is proposed.

Ebola virus modulates transforming growth factor β signaling and cellular markers of mesenchyme-like transition in hepatocytes.

Science.gov (United States)

Kindrachuk, Jason; Wahl-Jensen, Victoria; Safronetz, David; Trost, Brett; Hoenen, Thomas; Arsenault, Ryan; Feldmann, Friederike; Traynor, Dawn; Postnikova, Elena; Kusalik, Anthony; Napper, Scott; Blaney, Joseph E; Feldmann, Heinz; Jahrling, Peter B

2014-09-01

Ebola virus (EBOV) causes a severe hemorrhagic disease in humans and nonhuman primates, with a median case fatality rate of 78.4%. Although EBOV is considered a public health concern, there is a relative paucity of information regarding the modulation of the functional host response during infection. We employed temporal kinome analysis to investigate the relative early, intermediate, and late host kinome responses to EBOV infection in human hepatocytes. Pathway overrepresentation analysis and functional network analysis of kinome data revealed that transforming growth factor (TGF-β)-mediated signaling responses were temporally modulated in response to EBOV infection. Upregulation of TGF-β signaling in the kinome data sets correlated with the upregulation of TGF-β secretion from EBOV-infected cells. Kinase inhibitors targeting TGF-β signaling, or additional cell receptors and downstream signaling pathway intermediates identified from our kinome analysis, also inhibited EBOV replication. Further, the inhibition of select cell signaling intermediates identified from our kinome analysis provided partial protection in a lethal model of EBOV infection. To gain perspective on the cellular consequence of TGF-β signaling modulation during EBOV infection, we assessed cellular markers associated with upregulation of TGF-β signaling. We observed upregulation of matrix metalloproteinase 9, N-cadherin, and fibronectin expression with concomitant reductions in the expression of E-cadherin and claudin-1, responses that are standard characteristics of an epithelium-to-mesenchyme-like transition. Additionally, we identified phosphorylation events downstream of TGF-β that may contribute to this process. From these observations, we propose a model for a broader role of TGF-β-mediated signaling responses in the pathogenesis of Ebola virus disease. Ebola virus (EBOV), formerly Zaire ebolavirus, causes a severe hemorrhagic disease in humans and nonhuman primates and is the most

Cellularity of certain quantum endomorphism algebras

DEFF Research Database (Denmark)

Andersen, Henning Haahr; Lehrer, Gus; Zhang, Ruibin

2015-01-01

For any ring A˜ such that Z[q±1∕2]⊆A˜⊆Q(q1∕2), let ΔA˜(d) be an A˜-form of the Weyl module of highest weight d∈N of the quantised enveloping algebra UA˜ of sl2. For suitable A˜, we exhibit for all positive integers r an explicit cellular structure for EndUA˜(ΔA˜(d)⊗r). This algebra and its cellular...... structure are described in terms of certain Temperley–Lieb-like diagrams. We also prove general results that relate endomorphism algebras of specialisations to specialisations of the endomorphism algebras. When ζ is a root of unity of order bigger than d we consider the Uζ-module structure...... of the specialisation Δζ(d)⊗r at q↦ζ of ΔA˜(d)⊗r. As an application of these results, we prove that knowledge of the dimensions of the simple modules of the specialised cellular algebra above is equivalent to knowledge of the weight multiplicities of the tilting modules for Uζ(sl2). As an example, in the final section...

Cellular stress-induced up-regulation of FMRP promotes cell survival by modulating PI3K-Akt phosphorylation cascades

Directory of Open Access Journals (Sweden)

Wells David

2011-02-01

Full Text Available Abstract Background Fragile X syndrome (FXS, the most commonly inherited mental retardation and single gene cause of autistic spectrum disorder, occurs when the Fmr1 gene is mutated. The product of Fmr1, fragile X linked mental retardation protein (FMRP is widely expressed in HeLa cells, however the roles of FMRP within HeLa cells were not elucidated, yet. Interacting with a diverse range of mRNAs related to cellular survival regulatory signals, understanding the functions of FMRP in cellular context would provide better insights into the role of this interesting protein in FXS. Using HeLa cells treated with etoposide as a model, we tried to determine whether FMRP could play a role in cell survival. Methods Apoptotic cell death was induced by etoposide treatment on Hela cells. After we transiently modulated FMRP expression (silencing or enhancing by using molecular biotechnological methods such as small hairpin RNA virus-induced knock down and overexpression using transfection with FMRP expression vectors, cellular viability was measured using propidium iodide staining, TUNEL staining, and FACS analysis along with the level of activation of PI3K-Akt pathway by Western blot. Expression level of FMRP and apoptotic regulator BcL-xL was analyzed by Western blot, RT-PCR and immunocytochemistry. Results An increased FMRP expression was measured in etoposide-treated HeLa cells, which was induced by PI3K-Akt activation. Without FMRP expression, cellular defence mechanism via PI3K-Akt-Bcl-xL was weakened and resulted in an augmented cell death by etoposide. In addition, FMRP over-expression lead to the activation of PI3K-Akt signalling pathway as well as increased FMRP and BcL-xL expression, which culminates with the increased cell survival in etoposide-treated HeLa cells. Conclusions Taken together, these results suggest that FMRP expression is an essential part of cellular survival mechanisms through the modulation of PI3K, Akt, and Bcl-xL signal

Next-Generation Environment-Aware Cellular Networks: Modern Green Techniques and Implementation Challenges

KAUST Repository

Ghazzai, Hakim

2016-09-16

Over the last decade, mobile communications have been witnessing a noteworthy increase of data traffic demand that is causing an enormous energy consumption in cellular networks. The reduction of their fossil fuel consumption in addition to the huge energy bills paid by mobile operators is considered as the most important challenges for the next-generation cellular networks. Although most of the proposed studies were focusing on individual physical layer power optimizations, there is a growing necessity to meet the green objective of fifth-generation cellular networks while respecting the user\\'s quality of service. This paper investigates four important techniques that could be exploited separately or together in order to enable wireless operators achieve significant economic benefits and environmental savings: 1) the base station sleeping strategy; 2) the optimized energy procurement from the smart grid; 3) the base station energy sharing; and 4) the green networking collaboration between competitive mobile operators. The presented simulation results measure the gain that could be obtained using these techniques compared with that of traditional scenarios. Finally, this paper discusses the issues and challenges related to the implementations of these techniques in real environments. © 2016 IEEE.

Internal Disequilibria and Phenotypic Diversification during Replication of Hepatitis C Virus in a Noncoevolving Cellular Environment.

Science.gov (United States)

Moreno, Elena; Gallego, Isabel; Gregori, Josep; Lucía-Sanz, Adriana; Soria, María Eugenia; Castro, Victoria; Beach, Nathan M; Manrubia, Susanna; Quer, Josep; Esteban, Juan Ignacio; Rice, Charles M; Gómez, Jordi; Gastaminza, Pablo; Domingo, Esteban; Perales, Celia

2017-05-15

Viral quasispecies evolution upon long-term virus replication in a noncoevolving cellular environment raises relevant general issues, such as the attainment of population equilibrium, compliance with the molecular-clock hypothesis, or stability of the phenotypic profile. Here, we evaluate the adaptation, mutant spectrum dynamics, and phenotypic diversification of hepatitis C virus (HCV) in the course of 200 passages in human hepatoma cells in an experimental design that precluded coevolution of the cells with the virus. Adaptation to the cells was evidenced by increase in progeny production. The rate of accumulation of mutations in the genomic consensus sequence deviated slightly from linearity, and mutant spectrum analyses revealed a complex dynamic of mutational waves, which was sustained beyond passage 100. The virus underwent several phenotypic changes, some of which impacted the virus-host relationship, such as enhanced cell killing, a shift toward higher virion density, and increased shutoff of host cell protein synthesis. Fluctuations in progeny production and failure to reach population equilibrium at the genomic level suggest internal instabilities that anticipate an unpredictable HCV evolution in the complex liver environment. IMPORTANCE Long-term virus evolution in an unperturbed cellular environment can reveal features of virus evolution that cannot be explained by comparing natural viral isolates. In the present study, we investigate genetic and phenotypic changes that occur upon prolonged passage of hepatitis C virus (HCV) in human hepatoma cells in an experimental design in which host cell evolutionary change is prevented. Despite replication in a noncoevolving cellular environment, the virus exhibited internal population disequilibria that did not decline with increased adaptation to the host cells. The diversification of phenotypic traits suggests that disequilibria inherent to viral populations may provide a selective advantage to viruses that can

Development and application of visual support module for remote operator in 3D virtual environment

International Nuclear Information System (INIS)

Choi, Kyung Hyun; Cho, Soo Jeong; Yang, Kyung Boo; Bae, Chang Hyun

2006-02-01

In this research, the 3D graphic environment was developed for remote operation, and included the visual support module. The real operation environment was built by employing a experiment robot, and also the identical virtual model was developed. The well-designed virtual models can be used to retrieve the necessary conditions for developing the devices and processes. The integration of 3D virtual models, the experimental operation environment, and the visual support module was used for evaluating the operation efficiency and accuracy by applying different methods such as only monitor image and with visual support module

Development and application of visual support module for remote operator in 3D virtual environment

Energy Technology Data Exchange (ETDEWEB)

Choi, Kyung Hyun; Cho, Soo Jeong; Yang, Kyung Boo [Cheju Nat. Univ., Jeju (Korea, Republic of); Bae, Chang Hyun [Pusan Nat. Univ., Busan (Korea, Republic of)

2006-02-15

In this research, the 3D graphic environment was developed for remote operation, and included the visual support module. The real operation environment was built by employing a experiment robot, and also the identical virtual model was developed. The well-designed virtual models can be used to retrieve the necessary conditions for developing the devices and processes. The integration of 3D virtual models, the experimental operation environment, and the visual support module was used for evaluating the operation efficiency and accuracy by applying different methods such as only monitor image and with visual support module.

Novel approach to the diagnosis of fractures in an austere environment using a stethoscope and a cellular phone.

Science.gov (United States)

Matzek, Brett A; Fivecoat, Phillip T; Ritz, Reis B

2014-03-01

Fracture diagnosis in the austere environment where radiographic tests are not available can be a challenge. In the past, a diagnostic technique has been described using a tuning fork and stethoscope to assess decreased sound conduction in the fractured extremity. In this study, we evaluate the use of a cellular phone's vibrate function and a stethoscope to limit equipment carried by expeditionary practitioners. The purpose of this study was to evaluate the accuracy of fracture diagnosis using a cellular phone and stethoscope. This is a pilot study to assess the usefulness of the above technique before clinical implementation. In 3 cadavers, we created fractures of the humerus and femur. Twenty-seven emergency medicine residents and an attending physician performed the diagnostic technique. Overall, the use of the cellular phone and stethoscope resulted in a sensitivity of 73% (95% confidence interval [CI]: 0.64 to 0.81) and a specificity of 83% (95% CI: 0.77 to 0.88), with a positive predicted value of 68% (95% CI: 0.59 to 0.77) and a negative predicted value of 86% (95% CI: 0.81 to 0.90). Positive likelihood ratio was 4.3, and negative likelihood ratio was 0.32. The use of a cellular phone and stethoscope may be a useful tool for the diagnosis of fractures in the austere environment. However, further study is needed to validate these findings in the clinical environment. Published by Wilderness Medical Society on behalf of Wilderness Medical Society.

Behind the curtain: cellular mechanisms for allosteric modulation of calcium-sensing receptors

Science.gov (United States)

Cavanaugh, Alice; Huang, Ying; Breitwieser, Gerda E

2012-01-01

Calcium-sensing receptors (CaSR) are integral to regulation of systemic Ca2+ homeostasis. Altered expression levels or mutations in CaSR cause Ca2+ handling diseases. CaSR is regulated by both endogenous allosteric modulators and allosteric drugs, including the first Food and Drug Administration-approved allosteric agonist, Cinacalcet HCl (Sensipar®). Recent studies suggest that allosteric modulators not only alter function of plasma membrane-localized CaSR, but regulate CaSR stability at the endoplasmic reticulum. This brief review summarizes our current understanding of the role of membrane-permeant allosteric agonists in cotranslational stabilization of CaSR, and highlights additional, indirect, signalling-dependent role(s) for membrane-impermeant allosteric drugs. Overall, these studies suggest that allosteric drugs act at multiple cellular organelles to control receptor abundance and hence function, and that drug hydrophobicity can bias the relative contributions of plasma membrane and intracellular organelles to CaSR abundance and signalling. LINKED ARTICLES This article is part of a themed section on the Molecular Pharmacology of G Protein-Coupled Receptors (GPCRs). To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-6. To view the 2010 themed section on the same topic visit http://onlinelibrary.wiley.com/doi/10.1111/bph.2010.159.issue-5/issuetoc PMID:21470201

Sub-cellular mRNA localization modulates the regulation of gene expression by small RNAs in bacteria

Science.gov (United States)

Teimouri, Hamid; Korkmazhan, Elgin; Stavans, Joel; Levine, Erel

2017-10-01

Small non-coding RNAs can exert significant regulatory activity on gene expression in bacteria. In recent years, substantial progress has been made in understanding bacterial gene expression by sRNAs. However, recent findings that demonstrate that families of mRNAs show non-trivial sub-cellular distributions raise the question of how localization may affect the regulatory activity of sRNAs. Here we address this question within a simple mathematical model. We show that the non-uniform spatial distributions of mRNA can alter the threshold-linear response that characterizes sRNAs that act stoichiometrically, and modulate the hierarchy among targets co-regulated by the same sRNA. We also identify conditions where the sub-cellular organization of cofactors in the sRNA pathway can induce spatial heterogeneity on sRNA targets. Our results suggest that under certain conditions, interpretation and modeling of natural and synthetic gene regulatory circuits need to take into account the spatial organization of the transcripts of participating genes.

Using Cellular Automata for Parking Recommendations in Smart Environments

Science.gov (United States)

Horng, Gwo-Jiun

2014-01-01

In this work, we propose an innovative adaptive recommendation mechanism for smart parking. The cognitive RF module will transmit the vehicle location information and the parking space requirements to the parking congestion computing center (PCCC) when the driver must find a parking space. Moreover, for the parking spaces, we use a cellular automata (CA) model mechanism that can adjust to full and not full parking lot situations. Here, the PCCC can compute the nearest parking lot, the parking lot status and the current or opposite driving direction with the vehicle location information. By considering the driving direction, we can determine when the vehicles must turn around and thus reduce road congestion and speed up finding a parking space. The recommendation will be sent to the drivers through a wireless communication cognitive radio (CR) model after the computation and analysis by the PCCC. The current study evaluates the performance of this approach by conducting computer simulations. The simulation results show the strengths of the proposed smart parking mechanism in terms of avoiding increased congestion and decreasing the time to find a parking space. PMID:25153671

Performance Evaluation of Various Flat Plate Photovoltaic Modules in Hot and Arid Environment

International Nuclear Information System (INIS)

Alamoud, A. R. M.

2000-01-01

The present paper reports the results of a simplified methods for evaluating the performance of selected photovoltaic (PV?) modules in use in Saudi Arabia and makes a comparative assessment at standard reporting conditions. Experimental results, normalized to standard reporting conditions using the two-axis translation I-V model have revealed that all PV module parameters, except Isc decreased during the period the modules were exposed to outdoor environment. The degradation resulted in a decrease in the module efficiency of 0.22% to 11% depending on the make of the module. Moreover, the measured PV module parameters were found to differ from manufacturer's specified values yielding a decrease in efficiency (Author)

Induction of Osmoadaptive Mechanisms and Modulation of Cellular Physiology Help Bacillus licheniformis Strain SSA 61 Adapt to Salt Stress

Energy Technology Data Exchange (ETDEWEB)

Paul, Sangeeta; Aggarwal, Chetana; Thakur, Jyoti Kumar; Bandeppa, G. S.; Khan, Md. Aslam; Pearson, Lauren M.; Babnigg, Gyorgy; Giometti, Carol S.; Joachimiak, Andrzej

2015-01-06

Bacillus licheniformis strain SSA 61, originally isolated from Sambhar salt lake, was observed to grow even in the presence of 25 % salt stress. Osmoadaptive mechanisms of this halotolerant B. licheniformis strain SSA 61, for long-term survival and growth under salt stress, were determined. Proline was the preferentially accumulated compatible osmolyte. There was also increased accumulation of antioxidants ascorbic acid and glutathione. Among the different antioxidative enzymes assayed, superoxide dismutase played the most crucial role in defense against salt-induced stress in the organism. Adaptation to stress by the organism involved modulation of cellular physiology at various levels. There was enhanced expression of known proteins playing essential roles in stress adaptation, such as chaperones DnaK and GroEL, and general stress protein YfkM and polynucleotide phosphorylase/polyadenylase. Proteins involved in amino acid biosynthetic pathway, ribosome structure, and peptide elongation were also overexpressed. Salt stress-induced modulation of expression of enzymes involved in carbon metabolism was observed. There was up-regulation of a number of enzymes involved in generation of NADH and NADPH, indicating increased cellular demand for both energy and reducing power.

Estimating induced-activation of SCT barrel-modules in the ATLAS radiation environment.

CERN Document Server

Buttar, C M; Dawson, I; Mandic, I; Moraes, A

2002-01-01

One of the consequences of operating detector systems in the harsh radiation environments of the ATLAS inner-detector will be radioactivation of the components. If the levels of radioactivity and corresponding dose rates are significant, then there will be implications for any access or maintenance operations. Given in this note are predictions for the radioactivation of SCT barrel-modules in the expected radiation environment of the inner-detector, based on both calculations and measurements. It is shown that both neutron-capture and high-energy hadron reactions must be taken into account. The predictions show that, from a radiological point of view, the SCT barrel-modules should not pose any serious problems.

Cellular adhesome screen identifies critical modulators of focal adhesion dynamics, cellular traction forces and cell migration behaviour

Science.gov (United States)

Fokkelman, Michiel; Balcıoğlu, Hayri E.; Klip, Janna E.; Yan, Kuan; Verbeek, Fons J.; Danen, Erik H. J.; van de Water, Bob

2016-01-01

Cancer cells migrate from the primary tumour into surrounding tissue in order to form metastasis. Cell migration is a highly complex process, which requires continuous remodelling and re-organization of the cytoskeleton and cell-matrix adhesions. Here, we aimed to identify genes controlling aspects of tumour cell migration, including the dynamic organization of cell-matrix adhesions and cellular traction forces. In a siRNA screen targeting most cell adhesion-related genes we identified 200+ genes that regulate size and/or dynamics of cell-matrix adhesions in MCF7 breast cancer cells. In a subsequent secondary screen, the 64 most effective genes were evaluated for growth factor-induced cell migration and validated by tertiary RNAi pool deconvolution experiments. Four validated hits showed significantly enlarged adhesions accompanied by reduced cell migration upon siRNA-mediated knockdown. Furthermore, loss of PPP1R12B, HIPK3 or RAC2 caused cells to exert higher traction forces, as determined by traction force microscopy with elastomeric micropillar post arrays, and led to considerably reduced force turnover. Altogether, we identified genes that co-regulate cell-matrix adhesion dynamics and traction force turnover, thereby modulating overall motility behaviour. PMID:27531518

Noncoding RNAs and HIV: viral manipulation of host dark matter to shape the cellular environment

Directory of Open Access Journals (Sweden)

Samantha eBarichievy

2015-03-01

Full Text Available On October 28th 1943 Winston Churchill said we shape our buildings, and afterwards our buildings shape us (Humes, 1994. Churchill was pondering how and when to rebuild the British House of Commons, which had been destroyed by enemy bombs on May 10th 1941. The old House had been small and insufficient to hold all its members, but was restored to its original form in 1950 in order to recapture the convenience and dignity that the building had shaped into its parliamentary members. The circular loop whereby buildings or dwellings are shaped and go on to shape those that reside in them is also true of pathogens and their hosts. As obligate parasites, pathogens need to alter their cellular host environments to ensure survival. Typically pathogens modify cellular transcription profiles and in doing so, the pathogen in turn is affected, thereby closing the loop. As key orchestrators of gene expression, noncoding RNAs provide a vast and extremely precise set of tools for pathogens to target in order to shape the cellular environment. This review will focus on host noncoding RNAs that are manipulated by the infamous intracellular pathogen, the Human Immunodeficiency Virus (HIV. We will briefly describe both short and long host noncoding RNAs and discuss how HIV gains control of these factors to ensure widespread dissemination throughout the host as well as the establishment of lifelong, chronic infection.

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

Science.gov (United States)

Brattsand, R; Linden, M

1996-01-01

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.

Special Testing for Modules Deployed in Hot Use Environments - Are We Doing This in a Low-Cost Way?

Energy Technology Data Exchange (ETDEWEB)

Repins, Ingrid; Jordan, Dirk; Bosco, Nick; Flueckiger, Chris

2016-09-12

The proposed new IEC standard will address the test temperature requirements in IEC 61215 (module design), IEC 61730 (module safety), IEC 62790 (junction box safety) and IEC 62852 (connectors), and will provide guidelines to modify temperature limits in four existing standards to better describe module performance in hotter climates. This workshop includes four presentations: Special Testing for Modules Deployed in Hot Use Environments - Are We Doing This in a Low-Cost Way?, Experimental Evidence, Why the highest temperatures are the most stressful to PV modules during thermal cycling, and Safety Aspects for Modules Deployed in Hot Use Environments.

The cellular environment in computer simulations of radiation-induced damage to DNA

International Nuclear Information System (INIS)

Moiseenko, V.V.; Waker, A.J.; Prestwich, W.V.

1998-01-01

Radiation-induced DNA single- and double-strand breaks were modeled for 660 keV photon radiation and scavenger capacity mimicking the cellular environment. Atomistic representation of DNA in B form with a first hydration shell was utilized to model direct and indirect damage. Monte Carlo generated electron tracks were used to model energy deposition in matter and to derive initial spatial distributions of species which appear in the medium following radiolysis. Diffusion of species was followed with time, and their reactions with DNA and each other were modeled in an encounter-controlled manner. Three methods to account for hydroxyl radical diffusion in a cellular environment were tested: assumed exponential survival, time-limited modeling and modeling of reactions between hydroxyl radicals and scavengers in an encounter-controlled manner. Although the method based on modeling scavenging in an encounter-controlled manner is more precise, it requires substantially more computer resources than either the exponential or time-limiting method. Scavenger concentrations of 0.5 and 0.15 M were considered using exponential and encounter-controlled methods with reaction rate set at 3 x 10 9 dm 3 mol -1 s -1 . Diffusion length and strand break yields, predicted by these two methods for the same scavenger molarity, were different by 20%-30%. The method based on limiting time of chemistry follow-up to 10 -9 s leads to DNA damage and radical diffusion estimates similar to 0.5 M scavenger concentration in the other two methods. The difference observed in predictions made by the methods considered could be tolerated in computer simulations of DNA damage. (orig.)

The cellular environment in computer simulations of radiation-induced damage to DNA

International Nuclear Information System (INIS)

Moiseenko, V.V.; Hamm, R.N.; Waker, A.J.; Prestwich, W.V.

1988-01-01

Radiation-induced DNA single- and double-strand breaks were modeled for 660 keV photon radiation and scavenger capacity mimicking the cellular environment. Atomistic representation of DNA in B form with a first hydration shell was utilized to model direct and indirect damage. Monte Carlo generated electron tracks were used to model energy deposition in matter and to derive initial spatial distributions of species which appear in the medium following radiolysis. Diffusion of species was followed with time, and their reactions with DNA and each other were modeled in an encounter-controlled manner. Three methods to account for hydroxyl radical diffusion in cellular environment were tested: assumed exponential survival, time-limited modeling and modeling of reactions between hydroxyl radicals and scavengers in an encounter-controlled manner. Although the method based on modeling scavenging in an encounter-controlled manner is more precise, it requires substantially more computer resources than either the exponential or time-limiting method. Scavenger concentrations of 0.5 and 0.15 M were considered using exponential and encounter-controlled methods with reaction rate set at 3x10 9 dm 3 mol -1 s-1. Diffusion length and strand break yields, predicted by these two methods for the same scavenger molarity, were different by 20%-30%. The method based on limiting time of chemistry follow-up to 10 -9 s leads to DNA damage and radical diffusion estimates similar to 0.5 M scavenger concentration in the other two methods. The difference observed in predictions made by the methods considered could be tolerated in computer simulations of DNA damage. (author)

Modulation of hyaluronan synthase activity in cellular membrane fractions.

Science.gov (United States)

Vigetti, Davide; Genasetti, Anna; Karousou, Evgenia; Viola, Manuela; Clerici, Moira; Bartolini, Barbara; Moretto, Paola; De Luca, Giancarlo; Hascall, Vincent C; Passi, Alberto

2009-10-30

Hyaluronan (HA), the only non-sulfated glycosaminoglycan, is involved in morphogenesis, wound healing, inflammation, angiogenesis, and cancer. In mammals, HA is synthesized by three homologous HA synthases, HAS1, HAS2, and HAS3, that polymerize the HA chain using UDP-glucuronic acid and UDP-N-acetylglucosamine as precursors. Since the amount of HA is critical in several pathophysiological conditions, we developed a non-radioactive assay for measuring the activity of HA synthases (HASs) in eukaryotic cells and addressed the question of HAS activity during intracellular protein trafficking. We prepared three cellular fractions: plasma membrane, cytosol (containing membrane proteins mainly from the endoplasmic reticulum and Golgi), and nuclei. After incubation with UDP-sugar precursors, newly synthesized HA was quantified by polyacrylamide gel electrophoresis of fluorophore-labeled saccharides and high performance liquid chromatography. This new method measured HAS activity not only in the plasma membrane fraction but also in the cytosolic membranes. This new technique was used to evaluate the effects of 4-methylumbeliferone, phorbol 12-myristate 13-acetate, interleukin 1beta, platelet-derived growth factor BB, and tunicamycin on HAS activities. We found that HAS activity can be modulated by post-translational modification, such as phosphorylation and N-glycosylation. Interestingly, we detected a significant increase in HAS activity in the cytosolic membrane fraction after tunicamycin treatment. Since this compound is known to induce HA cable structures, this result links HAS activity alteration with the capability of the cell to promote HA cable formation.

A linear 180 nm SOI CMOS antenna switch module using integrated passive device filters for cellular applications

Science.gov (United States)

Jie, Cui; Lei, Chen; Peng, Zhao; Xu, Niu; Yi, Liu

2014-06-01

A broadband monolithic linear single pole, eight throw (SP8T) switch has been fabricated in 180 nm thin film silicon-on-insulator (SOI) CMOS technology with a quad-band GSM harmonic filter in integrated passive devices (IPD) technology, which is developed for cellular applications. The antenna switch module (ASM) features 1.2 dB insertion loss with filter on 2G bands and 0.4 dB insertion loss in 3G bands, less than -45 dB isolation and maximum -103 dB intermodulation distortion for mobile front ends by applying distributed architecture and adaptive supply voltage generator.

Oleuropein Prevents Neuronal Death, Mitigates Mitochondrial Superoxide Production and Modulates Autophagy in a Dopaminergic Cellular Model

Directory of Open Access Journals (Sweden)

Imène Achour

2016-08-01

Full Text Available Parkinson’s disease (PD is a progressive neurodegenerative disorder, primarily affecting dopaminergic neurons in the substantia nigra. There is currently no cure for PD and present medications aim to alleviate clinical symptoms, thus prevention remains the ideal strategy to reduce the prevalence of this disease. The goal of this study was to investigate whether oleuropein (OLE, the major phenolic compound in olive derivatives, may prevent neuronal degeneration in a cellular dopaminergic model of PD, differentiated PC12 cells exposed to the potent parkinsonian toxin 6-hydroxydopamine (6-OHDA. We also investigated OLE’s ability to mitigate mitochondrial oxidative stress and modulate the autophagic flux. Our results obtained by measuring cytotoxicity and apoptotic events demonstrate that OLE significantly decreases neuronal death. OLE could also reduce mitochondrial production of reactive oxygen species resulting from blocking superoxide dismutase activity. Moreover, quantification of autophagic and acidic vesicles in the cytoplasm alongside expression of specific autophagic markers uncovered a regulatory role for OLE against autophagic flux impairment induced by bafilomycin A1. Altogether, our results define OLE as a neuroprotective, anti-oxidative and autophagy-regulating molecule, in a neuronal dopaminergic cellular model.

Standard Test Method for Saltwater Pressure Immersion and Temperature Testing of Photovoltaic Modules for Marine Environments

CERN Document Server

American Society for Testing and Materials. Philadelphia

2010-01-01

1.1 This test method provides a procedure for determining the ability of photovoltaic modules to withstand repeated immersion or splash exposure by seawater as might be encountered when installed in a marine environment, such as a floating aid-to-navigation. A combined environmental cycling exposure with modules repeatedly submerged in simulated saltwater at varying temperatures and under repetitive pressurization provides an accelerated basis for evaluation of aging effects of a marine environment on module materials and construction. 1.2 This test method defines photovoltaic module test specimens and requirements for positioning modules for test, references suitable methods for determining changes in electrical performance and characteristics, and specifies parameters which must be recorded and reported. 1.3 This test method does not establish pass or fail levels. The determination of acceptable or unacceptable results is beyond the scope of this test method. 1.4 The values stated in SI units are to be ...

Sub-cellular distribution and translocation of TRP channels.

Science.gov (United States)

Toro, Carlos A; Arias, Luis A; Brauchi, Sebastian

2011-01-01

Cellular electrical activity is the result of a highly complex processes that involve the activation of ion channel proteins. Ion channels make pores on cell membranes that rapidly transit between conductive and non-conductive states, allowing different ions to flow down their electrochemical gradients across cell membranes. In the case of neuronal cells, ion channel activity orchestrates action potentials traveling through axons, enabling electrical communication between cells in distant parts of the body. Somatic sensation -our ability to feel touch, temperature and noxious stimuli- require ion channels able to sense and respond to our peripheral environment. Sensory integration involves the summing of various environmental cues and their conversion into electrical signals. Members of the Transient Receptor Potential (TRP) family of ion channels have emerged as important mediators of both cellular sensing and sensory integration. The regulation of the spatial and temporal distribution of membrane receptors is recognized as an important mechanism for controlling the magnitude of the cellular response and the time scale on which cellular signaling occurs. Several studies have shown that this mechanism is also used by TRP channels to modulate cellular response and ultimately fulfill their physiological function as sensors. However, the inner-working of this mode of control for TRP channels remains poorly understood. The question of whether TRPs intrinsically regulate their own vesicular trafficking or weather the dynamic regulation of TRP channel residence on the cell surface is caused by extrinsic changes in the rates of vesicle insertion or retrieval remain open. This review will examine the evidence that sub-cellular redistribution of TRP channels plays an important role in regulating their activity and explore the mechanisms that control the trafficking of vesicles containing TRP channels.

Cell-Nonautonomous Mechanisms Underlying Cellular and Organismal Aging.

Science.gov (United States)

Medkour, Younes; Svistkova, Veronika; Titorenko, Vladimir I

2016-01-01

Cell-autonomous mechanisms underlying cellular and organismal aging in evolutionarily distant eukaryotes have been established; these mechanisms regulate longevity-defining processes within a single eukaryotic cell. Recent findings have provided valuable insight into cell-nonautonomous mechanisms modulating cellular and organismal aging in eukaryotes across phyla; these mechanisms involve a transmission of various longevity factors between different cells, tissues, and organisms. Herein, we review such cell-nonautonomous mechanisms of aging in eukaryotes. We discuss the following: (1) how low molecular weight transmissible longevity factors modulate aging and define longevity of cells in yeast populations cultured in liquid media or on solid surfaces, (2) how communications between proteostasis stress networks operating in neurons and nonneuronal somatic tissues define longevity of the nematode Caenorhabditis elegans by modulating the rates of aging in different tissues, and (3) how different bacterial species colonizing the gut lumen of C. elegans define nematode longevity by modulating the rate of organismal aging. Copyright © 2016. Published by Elsevier Inc.

A linear 180 nm SOI CMOS antenna switch module using integrated passive device filters for cellular applications

International Nuclear Information System (INIS)

Cui Jie; Chen Lei; Liu Yi; Zhao Peng; Niu Xu

2014-01-01

A broadband monolithic linear single pole, eight throw (SP8T) switch has been fabricated in 180 nm thin film silicon-on-insulator (SOI) CMOS technology with a quad-band GSM harmonic filter in integrated passive devices (IPD) technology, which is developed for cellular applications. The antenna switch module (ASM) features 1.2 dB insertion loss with filter on 2G bands and 0.4 dB insertion loss in 3G bands, less than −45 dB isolation and maximum −103 dB intermodulation distortion for mobile front ends by applying distributed architecture and adaptive supply voltage generator. (semiconductor integrated circuits)

Method for Signal Processing of Electric Field Modulation Sensor in a Conductive Environment

Directory of Open Access Journals (Sweden)

O. I. Miseyk

2015-01-01

Full Text Available In investigating the large waters and deep oceans the most promising are modulation sensors for measuring electric field in a conducting environment in a very low frequency range in devices of autonomous or non-autonomous vertical sounding. When using sensors of this type it is necessary to solve the problem of enhancement and measurement of the modulated signal from the baseband noise.The work analyses hydrodynamic and electromagnetic noise at the input of transducer with "rotating" sensitive axis. By virtue of matching the measuring electrodes with the signal processing circuit a conclusion has been drawn that the proposed basic model of a transducer with "rotating” sensitive axis is the most efficient in terms of enhancement and measurement of modulated signal from the baseband noise. It has been shown that it is undesirable for transducers to have the rotation of electrodes resulting, in this case, in arising noise to be synchronously changed with transducer rotation frequency (modulation frequency. This will complicate the further signal-noise enhancement later in their processing.The paper justifies the choice of demodulation output signal, called synchronous demodulation using a low-pass filter with a cutoff frequency much lower than the carrier frequency to provide an output signal in the range of very low frequency and dc electric fields.The paper offers an original circuit to process the signals taken from the modulation sensor with "rotating" measurement base. This circuit has advantages over the earlier known circuits for measuring electric fields in a conducting (marine environment in the ultralow frequency range of these fields in terms of sensitivity and measuring accuracy of modulation sensors.

Matrix rigidity regulates cancer cell growth by modulating cellular metabolism and protein synthesis.

Directory of Open Access Journals (Sweden)

Robert W Tilghman

Full Text Available Tumor cells in vivo encounter diverse types of microenvironments both at the site of the primary tumor and at sites of distant metastases. Understanding how the various mechanical properties of these microenvironments affect the biology of tumor cells during disease progression is critical in identifying molecular targets for cancer therapy.This study uses flexible polyacrylamide gels as substrates for cell growth in conjunction with a novel proteomic approach to identify the properties of rigidity-dependent cancer cell lines that contribute to their differential growth on soft and rigid substrates. Compared to cells growing on more rigid/stiff substrates (>10,000 Pa, cells on soft substrates (150-300 Pa exhibited a longer cell cycle, due predominantly to an extension of the G1 phase of the cell cycle, and were metabolically less active, showing decreased levels of intracellular ATP and a marked reduction in protein synthesis. Using stable isotope labeling of amino acids in culture (SILAC and mass spectrometry, we measured the rates of protein synthesis of over 1200 cellular proteins under growth conditions on soft and rigid/stiff substrates. We identified cellular proteins whose syntheses were either preferentially inhibited or preserved on soft matrices. The former category included proteins that regulate cytoskeletal structures (e.g., tubulins and glycolysis (e.g., phosphofructokinase-1, whereas the latter category included proteins that regulate key metabolic pathways required for survival, e.g., nicotinamide phosphoribosyltransferase, a regulator of the NAD salvage pathway.The cellular properties of rigidity-dependent cancer cells growing on soft matrices are reminiscent of the properties of dormant cancer cells, e.g., slow growth rate and reduced metabolism. We suggest that the use of relatively soft gels as cell culture substrates would allow molecular pathways to be studied under conditions that reflect the different mechanical

Frequency modulation detection atomic force microscopy in the liquid environment

Science.gov (United States)

Jarvis, S. P.; Ishida, T.; Uchihashi, T.; Nakayama, Y.; Tokumoto, H.

True atomic resolution imaging using frequency modulation detection is already well established in ultra-high vacuum. In this paper we demonstrate that it also has great potential in the liquid environment. Using a combination of magnetic activation and high-aspect-ratio carbon nanotube probes, we show that imaging can be readily combined with point spectroscopy, revealing both the tip-sample interaction and the structure of the intermediate liquid.

Standard Test Methods for Photovoltaic Modules in Cyclic Temperature and Humidity Environments

CERN Document Server

American Society for Testing and Materials. Philadelphia

2009-01-01

1.1 These test methods provide procedures for stressing photovoltaic modules in simulated temperature and humidity environments. Environmental testing is used to simulate aging of module materials on an accelerated basis. 1.2 Three individual environmental test procedures are defined by these test methods: a thermal cycling procedure, a humidity-freeze cycling procedure, and an extended duration damp heat procedure. Electrical biasing is utilized during the thermal cycling procedure to simulate stresses that are known to occur in field-deployed modules. 1.3 These test methods define mounting methods for modules undergoing environmental testing, and specify parameters that must be recorded and reported. 1.4 These test methods do not establish pass or fail levels. The determination of acceptable or unacceptable results is beyond the scope of these test methods. 1.5 Any of the individual environmental tests may be performed singly, or may be combined into a test sequence with other environmental or non-envir...

Cellular oncogene expression following exposure of mice to γ-rays

International Nuclear Information System (INIS)

Anderson, A.; Woloschak, G.E.

1991-01-01

We examined the effects of total body exposure of BCF1 mice to γ-rays (300 cGy) in modulating expression of cellular oncogenes in both gut and liver tissues. We selected specific cellular oncogenes (c-fos, c-myc, c-src, and c-H-ras), based on their normal expression in liver and gut tissues from untreated mice. As early as 5 min. following whole body exposure of BCF1 mice to γ-rays we detected induction of mRNA specific for c-src and c-H-ras in both liver and gut tissues. c-fos RNA was slightly decreased in accumulation in gut but was unaffected in liver tissue from irradiated mice relative to untreated controls. c-myc mRNA accumulation was unaffected in all tissues examined. These experiments document that modulation of cellular oncogene expression can occur as an early event in tissues following irradiation and suggest that this modulation may play a role in radiation-induced carcinogenesis

Network monitoring module of BES III system environment

International Nuclear Information System (INIS)

Song Liwen; Zhao Jingwei; Zhang Bingyun

2002-01-01

In order to meet the needs of the complicated network architecture of BES III (Beijing Spectrometer III) and make sure normal online running in the future, it is necessary to develop a multi-platforms Network Monitoring Tool which can help system administrator monitor and manage BES III network. The author provides a module that can monitor not only the traffic of switch-router's ports but also the performance status of key devices in the network environment, meanwhile it can also give warning to manager and submit the related reports. the great sense, the theory basis, the implementing method and the graph in formation of this tool will be discussed

Multiuser Diversity with Adaptive Modulation in Non-Identically Distributed Nakagami Fading Environments

KAUST Repository

Rao, Anlei

2012-09-08

In this paper, we analyze the performance of adaptive modulation with single-cell multiuser scheduling over independent but not identical distributed (i.n.i.d.) Nakagami fading channels. Closed-form expressions are derived for the average channel capacity, spectral efficiency, and bit-error-rate (BER) for both constant-power variable-rate and variable-power variable-rate uncoded/coded M-ary quadrature amplitude modulation (M-QAM) schemes. We also study the impact of time delay on the average BER of adaptive M-QAM. Selected numerical results show that the multiuser diversity brings a considerably better performance even over i.n.i.d. fading environments.

Surface topography and chemistry shape cellular behavior on wide band-gap semiconductors.

Science.gov (United States)

Bain, Lauren E; Collazo, Ramon; Hsu, Shu-Han; Latham, Nicole Pfiester; Manfra, Michael J; Ivanisevic, Albena

2014-06-01

The chemical stability and electrical properties of gallium nitride make it a promising material for the development of biocompatible electronics, a range of devices including biosensors as well as interfaces for probing and controlling cellular growth and signaling. To improve the interface formed between the probe material and the cell or biosystem, surface topography and chemistry can be applied to modify the ways in which the device interacts with its environment. PC12 cells are cultured on as-grown planar, unidirectionally polished, etched nanoporous and nanowire GaN surfaces with and without a physisorbed peptide sequence that promotes cell adhesion. While cells demonstrate preferential adhesion to roughened surfaces over as-grown flat surfaces, the topography of that roughness also influences the morphology of cellular adhesion and differentiation in neurotypic cells. Addition of the peptide sequence generally contributes further to cellular adhesion and promotes development of stereotypic long, thin neurite outgrowths over alternate morphologies. The dependence of cell behavior on both the topographic morphology and surface chemistry is thus demonstrated, providing further evidence for the importance of surface modification for modulating bio-inorganic interfaces. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Modulation of Immune Response by Organophosphorus Pesticides: Fishes as a Potential Model in Immunotoxicology

Science.gov (United States)

Díaz-Resendiz, K. J. G.; Toledo-Ibarra, G. A.; Girón-Pérez, M. I.

2015-01-01

Immune response is modulated by different substances that are present in the environment. Nevertheless, some of these may cause an immunotoxic effect. In this paper, the effect of organophosphorus pesticides (frequent substances spilled in aquatic ecosystems) on the immune system of fishes and in immunotoxicology is reviewed. Furthermore, some cellular and molecular mechanisms that might be involved in immunoregulation mechanisms of organophosphorus pesticides are discussed. PMID:25973431

The effects of zinc nanooxide on cellular stress responses of the freshwater mussels Unio tumidus are modulated by elevated temperature and organic pollutants

International Nuclear Information System (INIS)

Falfushynska, Halina; Gnatyshyna, Lesya; Yurchak, Irina; Sokolova, Inna; Stoliar, Oksana

2015-01-01

Highlights: • Effects of nano-ZnO (n-ZnO) in combination with other stressors were studied. • At 18 °C, exposures to n-ZnO caused up-regulation of lysosomal cathepsin D. • Cellular responses to n-ZnO and Zn 2+ were distinct. • Warming to 25 °C activated caspase-3 and abolished antioxidants response to n-ZnO. • Biological effects of n-ZnO in mussels are strongly modulated by other stressors. - Abstract: Nanoparticle toxicity is a growing concern in freshwater habitats. However, understanding of the nanoparticle effects on aquatic organisms is impeded by the lack of the studies of the nanoparticles effects in the environmentally relevant context of multiple stress exposures. Zinc oxide nanoparticles (n-ZnO) are widely used metal-based nanoparticles in electronics and personal care products that accumulate in aquatic environments from multiple non-point sources. In this study, we evaluated the effects of n-ZnO in a model organism, a mussel Unio tumidus, and the potential modulation of these effects by common co-occurring environmental stressors. Male U. tumidus were exposed for 14 days to n-ZnO (3.1 μM), Zn 2+ (3.1 μM), Ca-channel blocker nifedipine (Nfd 10 μM), combinations of n-ZnO and Nfd or n-ZnO and thiocarbamate fungicide Tattoo (Ta, 91 μg L −1 ) at 18 °C, and n-ZnO at 25 °C (n-ZnO + t°). Total and metallothionein-bound Zn levels as well as levels of metallothioneins (MT), cellular stress responses and cytotoxicity biomarkers were assessed in the mussels. The key biomarkers that showed differential responses to different single and combined stressors in this study were activities of caspase-3 and lysosomal cathepsin D, as well as protein carbonyl content. At 18 °C, exposures to n-ZnO, organic pollutants and their combinations led to a prominent up-regulation of MT levels (by ∼30%) and oxidative stress response including up-regulation of superoxide dismutase activity, an increase in oxyradical production, and a 2–3-fold decrease in the

High-Voltage, Multiphasic, Nanosecond Pulses to Modulate Cellular Responses.

Science.gov (United States)

Ryan, Hollie A; Hirakawa, Shinji; Yang, Enbo; Zhou, Chunrong; Xiao, Shu

2018-04-01

Nanosecond electric pulses are an effective power source in plasma medicine and biological stimulation, in which biophysical responses are governed by peak power and not energy. While uniphasic nanosecond pulse generators are widely available, the recent discovery that biological effects can be uniquely modulated by reversing the polarity of nanosecond duration pulses calls for the development of a multimodal pulse generator. This paper describes a method to generate nanosecond multiphasic pulses for biomedical use, and specifically demonstrates its ability to cancel or enhance cell swelling and blebbing. The generator consists of a series of the fundamental module, which includes a capacitor and a MOSFET switch. A positive or a negative phase pulse module can be produced based on how the switch is connected. Stacking the modules in series can increase the voltage up to 5 kV. Multiple stacks in parallel can create multiphase outputs. As each stack is independently controlled and charged, multiphasic pulses can be created to produce flexible and versatile pulse waveforms. The circuit topology can be used for high-frequency uniphasic or biphasic nanosecond burst pulse production, creating numerous opportunities for the generator in electroporation applications, tissue ablation, wound healing, and nonthermal plasma generation.

Performance of Emcore Third Generation CPV Modules in the Low Latitude Marine Environment of Hawaii

Science.gov (United States)

Hoffman, Richard; Buie, Damien; King, David; Glesne, Thomas

2011-12-01

Emcore third generation concentrating photovoltaic (CPV) modules were evaluated in the low latitude location of Kihei, Hawaii. For comparison, the best available monocrystalline silicon flat panel modules were included in both dual-axis tracked and fixed mount configurations. The daily DC uncorrected efficiency value for the CPV modules averaged over the six-month performance period was 25.9% compared to 16% to 17% for the flat panels. Higher daily energy was obtained from CPV modules than tracked flat panels when daily direct solar insolation was greater than 5 kWh/m2 and more than fixed mount flat panel when direct insolation was greater than 3 kWh/m2. The module energy conversion performance was demonstrated to be predictable using a parametric model developed by Sandia National Laboratory. Soiling accumulation on module entrance surface was surprisingly rapid in the local environment. Measured energy loss rate due to soiling were two to six times larger for CPV compared to flat panel losses.

Identifying a compound modifying a cellular response, comprises attaching cells having a reporter system onto solid supports, releasing a library member, screening and identifying target cells

DEFF Research Database (Denmark)

2011-01-01

The present invention relates to methods for identifying compounds capable of modulating a cellular response. The methods involve attaching living cells to solid supports comprising a library of test compounds. Test compounds modulating a cellular response, for example via a cell surface molecule...... may be identified by selecting solid supports comprising cells, wherein the cellular response of interest has been modulated. The cellular response may for example be changes in signal transduction pathways modulated by a cell surface molecule....

Modulation of Immune Response by Organophosphorus Pesticides: Fishes as a Potential Model in Immunotoxicology

Directory of Open Access Journals (Sweden)

K. J. G. Díaz-Resendiz

2015-01-01

Full Text Available Immune response is modulated by different substances that are present in the environment. Nevertheless, some of these may cause an immunotoxic effect. In this paper, the effect of organophosphorus pesticides (frequent substances spilled in aquatic ecosystems on the immune system of fishes and in immunotoxicology is reviewed. Furthermore, some cellular and molecular mechanisms that might be involved in immunoregulation mechanisms of organophosphorus pesticides are discussed.

Modelling of processes occurring in deep geological repository - development of new modules in the GoldSim environment

International Nuclear Information System (INIS)

Vopalka, D.; Lukin, D.; Vokal, A.

2006-01-01

Three new modules were prepared in the environment of the GoldSim environment (using its Transport Module). The source term module includes radioactive decay and ingrowth in the canister, first order degradation of fuel matrix, solubility limitation of the concentration of the studied nuclides, and diffusive migration through the surrounding bentonite layer controlled by the output boundary condition formulated with respect to the rate of water flow in the rock. The module was successfully compared with results of similar codes (MIVCYL and Pagoda) and possibilities of the module were extended by a more realistic model of matrix degradation. A better quantification of the role of radionuclide sorption on the bentonite surface was enabled by a module that included non-linear form of the interaction isotherm. Using this module both the influence of the shape of sorption isotherm on the values of diffusion coefficients and the limits of K d -approach that dominates in most codes used in performance assessment studies was discussed. The third of the GoldSim modules presented has been worked out for the description of corrosion of canisters made of carbon steel and for the transport of corrosion products in the near-field region. This module evaluates balance equations between the dissolving species and species transported by diffusion and/or advection from the surface of a solid material. The model also includes transport of iron directly to a fracture in the surrounding rock or into a layer of granite host rock without fractures, and takes into account the reduction of the actual corrosion rate of the canister by growth of the corrosion layer thickness

An Overview and Analysis of Mobile Internet Protocols in Cellular Environments.

Science.gov (United States)

Chao, Han-Chieh

2001-01-01

Notes that cellular is the inevitable future architecture for the personal communication service system. Discusses the current cellular support based on Mobile Internet Protocol version 6 (Ipv6) and points out the shortfalls of using Mobile IP. Highlights protocols especially for mobile management schemes which can optimize a high-speed mobile…

Cellular interactions of lauric acid and dextran-coated magnetite nanoparticles

International Nuclear Information System (INIS)

Pradhan, Pallab; Giri, Jyotsnendu; Banerjee, Rinti; Bellare, Jayesh; Bahadur, Dhirendra

2007-01-01

In vitro cytocompatibility and cellular interactions of lauric acid and dextran-coated magnetite nanoparticles were evaluated with two different cell lines (mouse fibroblast and human cervical carcinoma). Lauric acid-coated magnetite nanoparticles were less cytocompatible than dextran-coated magnetite nanoparticles and cellular uptake of lauric acid-coated magnetic nanoparticles was more than that of dextran-coated magnetite nanoparticles. Lesser cytocompatibility and higher uptake of lauric acid-coated magnetite nanoparticles as compared to dextran-coated magnetic nanoparticles may be due to different cellular interactions by coating material. Thus, coating plays an important role in modulation of biocompatibility and cellular interaction of magnetic nanoparticles

Mitochondria, Energetics, Epigenetics, and Cellular Responses to Stress

Science.gov (United States)

McAllister, Kimberly; Worth, Leroy; Haugen, Astrid C.; Meyer, Joel N.; Domann, Frederick E.; Van Houten, Bennett; Mostoslavsky, Raul; Bultman, Scott J.; Baccarelli, Andrea A.; Begley, Thomas J.; Sobol, Robert W.; Hirschey, Matthew D.; Ideker, Trey; Santos, Janine H.; Copeland, William C.; Tice, Raymond R.; Balshaw, David M.; Tyson, Frederick L.

2014-01-01

Background: Cells respond to environmental stressors through several key pathways, including response to reactive oxygen species (ROS), nutrient and ATP sensing, DNA damage response (DDR), and epigenetic alterations. Mitochondria play a central role in these pathways not only through energetics and ATP production but also through metabolites generated in the tricarboxylic acid cycle, as well as mitochondria–nuclear signaling related to mitochondria morphology, biogenesis, fission/fusion, mitophagy, apoptosis, and epigenetic regulation. Objectives: We investigated the concept of bidirectional interactions between mitochondria and cellular pathways in response to environmental stress with a focus on epigenetic regulation, and we examined DNA repair and DDR pathways as examples of biological processes that respond to exogenous insults through changes in homeostasis and altered mitochondrial function. Methods: The National Institute of Environmental Health Sciences sponsored the Workshop on Mitochondria, Energetics, Epigenetics, Environment, and DNA Damage Response on 25–26 March 2013. Here, we summarize key points and ideas emerging from this meeting. Discussion: A more comprehensive understanding of signaling mechanisms (cross-talk) between the mitochondria and nucleus is central to elucidating the integration of mitochondrial functions with other cellular response pathways in modulating the effects of environmental agents. Recent studies have highlighted the importance of mitochondrial functions in epigenetic regulation and DDR with environmental stress. Development and application of novel technologies, enhanced experimental models, and a systems-type research approach will help to discern how environmentally induced mitochondrial dysfunction affects key mechanistic pathways. Conclusions: Understanding mitochondria–cell signaling will provide insight into individual responses to environmental hazards, improving prediction of hazard and susceptibility to

Cellular senescence and organismal aging.

Science.gov (United States)

Jeyapalan, Jessie C; Sedivy, John M

2008-01-01

Cellular senescence, first observed and defined using in vitro cell culture studies, is an irreversible cell cycle arrest which can be triggered by a variety of factors. Emerging evidence suggests that cellular senescence acts as an in vivo tumor suppression mechanism by limiting aberrant proliferation. It has also been postulated that cellular senescence can occur independently of cancer and contribute to the physiological processes of normal organismal aging. Recent data have demonstrated the in vivo accumulation of senescent cells with advancing age. Some characteristics of senescent cells, such as the ability to modify their extracellular environment, could play a role in aging and age-related pathology. In this review, we examine current evidence that links cellular senescence and organismal aging.

VUV spectroscopy of water under cellular conditions

International Nuclear Information System (INIS)

Mota, R.; Parafita, R.; Maneira, M. J. P.; Mason, N. J.; Garcia, G.; Ribeiro, P. A.; Raposo, M.; Limao-Vieira, P.

2006-01-01

The understanding of radiation damage within cells, and thence mutagenesis, depends upon a detailed knowledge of the spectroscopy and dissociation dynamics of water. Results of a new study of the electronic state spectroscopy of water, using synchrotron radiation are reported. In order to gain some insight into how the spectroscopy and dissociation dynamics of water is influenced by its environment we also report photo-absorption spectra of water within thin films of poly(o-methoxyaniline) which have been suggested as a good mimic for biological membranes in the cellular environment. Comparison of these spectra with those of gaseous water and condensed amorphous water ice suggest that water in such films is similar to gaseous water and does not show the blue shift suggested in some cellular models. The lowest energy of OH production from dissociation of water in the cellular environment may therefore be around 6.7 eV (185 nm). (authors)

The effects of zinc nanooxide on cellular stress responses of the freshwater mussels Unio tumidus are modulated by elevated temperature and organic pollutants

Energy Technology Data Exchange (ETDEWEB)

Falfushynska, Halina; Gnatyshyna, Lesya; Yurchak, Irina [Research Laboratory of Comparative Biochemistry and Molecular Biology, Ternopil National Pedagogical University, 46027, Kryvonosa Str. 2, Ternopil (Ukraine); Sokolova, Inna, E-mail: isokolov@uncc.edu [Department of Biological Sciences, University of North Carolina at Charlotte, 9201 University City Blvd., Charlotte, NC 28223 (United States); Stoliar, Oksana [Research Laboratory of Comparative Biochemistry and Molecular Biology, Ternopil National Pedagogical University, 46027, Kryvonosa Str. 2, Ternopil (Ukraine)

2015-05-15

Highlights: • Effects of nano-ZnO (n-ZnO) in combination with other stressors were studied. • At 18 °C, exposures to n-ZnO caused up-regulation of lysosomal cathepsin D. • Cellular responses to n-ZnO and Zn{sup 2+} were distinct. • Warming to 25 °C activated caspase-3 and abolished antioxidants response to n-ZnO. • Biological effects of n-ZnO in mussels are strongly modulated by other stressors. - Abstract: Nanoparticle toxicity is a growing concern in freshwater habitats. However, understanding of the nanoparticle effects on aquatic organisms is impeded by the lack of the studies of the nanoparticles effects in the environmentally relevant context of multiple stress exposures. Zinc oxide nanoparticles (n-ZnO) are widely used metal-based nanoparticles in electronics and personal care products that accumulate in aquatic environments from multiple non-point sources. In this study, we evaluated the effects of n-ZnO in a model organism, a mussel Unio tumidus, and the potential modulation of these effects by common co-occurring environmental stressors. Male U. tumidus were exposed for 14 days to n-ZnO (3.1 μM), Zn{sup 2+} (3.1 μM), Ca-channel blocker nifedipine (Nfd 10 μM), combinations of n-ZnO and Nfd or n-ZnO and thiocarbamate fungicide Tattoo (Ta, 91 μg L{sup −1}) at 18 °C, and n-ZnO at 25 °C (n-ZnO + t°). Total and metallothionein-bound Zn levels as well as levels of metallothioneins (MT), cellular stress responses and cytotoxicity biomarkers were assessed in the mussels. The key biomarkers that showed differential responses to different single and combined stressors in this study were activities of caspase-3 and lysosomal cathepsin D, as well as protein carbonyl content. At 18 °C, exposures to n-ZnO, organic pollutants and their combinations led to a prominent up-regulation of MT levels (by ∼30%) and oxidative stress response including up-regulation of superoxide dismutase activity, an increase in oxyradical production, and a 2–3-fold

Cell Adhesions: Actin-Based Modules that Mediate Cell-Extracellular Matrix and Cell-Cell Interactions

Science.gov (United States)

Bachir, Alexia; Horwitz, Alan Rick; Nelson, W. James; Bianchini, Julie M.

2018-01-01

Cell adhesions link cells to the extracellular matrix (ECM) and to each other, and depend on interactions with the actin cytoskeleton. Both cell-ECM and cell-cell adhesion sites contain discrete, yet overlapping functional modules. These modules establish physical association with the actin cytoskeleton, locally modulate actin organization and dynamics, and trigger intracellular signaling pathways. Interplay between these modules generates distinct actin architectures that underlie different stages, types, and functions of cell-ECM and cell-cell adhesions. Actomyosin contractility is required to generate mature, stable adhesions, as well as sense and translate the mechanical properties of the cellular environment to changes in cell organization and behavior. In this chapter we discuss the organization and function of different adhesion modules and how they interact with the actin cytoskeleton. We highlight the molecular mechanisms of mechanotransduction in adhesions, and how adhesion molecules mediate crosstalk between cell-ECM and cell-cell adhesion sites. PMID:28679638

Stress-induced ECM alteration modulates cellular microRNAs that feedback to readjust the extracellular environment and cell behaviour

Directory of Open Access Journals (Sweden)

Halyna R Shcherbata

2013-12-01

Full Text Available The extracellular environment is a complex entity comprising of the extracellular matrix (ECM and regulatory molecules. It is highly dynamic and under cell-extrinsic stress, transmits the stressed organism’s state to each individual ECM-connected cell. microRNAs (miRNAs are regulatory molecules involved in virtually all the processes in the cell, especially under stress. In this review, we analyse how microRNA expression is regulated downstream of various signal transduction pathways induced by changes in the extracellular environment. In particular, we focus on the muscular dystrophy-associated cell adhesion molecule dystroglycan capable of signal transduction. Then we show how exactly the same miRNAs feedback to regulate the extracellular environment. The ultimate goal of this bi-directional signal transduction process is to change cell behaviour under cell-extrinsic stress in order to respond to it accordingly.

Their function on angiogenesis and cellular signalling

Indian Academy of Sciences (India)

Copper, although known as a micronutrient, has a pivotal role in modulating the cellular metabolism. Many studieshave reported the role of copper in angiogenesis. Copper chaperones are intracellular proteins that mediate coppertrafficking to various cell organelles. However, the role and function of copper chaperones in ...

Cucurbitacin IIb exhibits anti-inflammatory activity through modulating multiple cellular behaviors of mouse lymphocytes.

Directory of Open Access Journals (Sweden)

Yao Wang

Full Text Available Cucurbitacin IIb (CuIIb is one of the major active compounds in Hemsleyadine tablets which have been used for clinical treatment of bacillary dysentery, enteritis and acute tonsilitis. However, its action mechanism has not been completely understood. This study aimed to explore the anti-inflammatory activity of CuIIb and its underlying mechanism in mitogen-activated lymphocytes isolated from mouse mesenteric lymph nodes. The results showed that CuIIb inhibited the proliferation of concanavalin A (Con A-activated lymphocytes in a time- and dose-dependent manner. CuIIb treatment arrested their cell cycle in S and G2/M phases probably due to the disruption of the actin cytoskeleton and the modulation of p27(Kip1 and cyclin levels. Moreover, the surface expression of activation markers CD69 and CD25 on Con A-activated CD3(+ T lymphocytes was suppressed by CuIIb treatment. Both Con A- and phorbol ester plus ionomycin-induced expression of TNF-α, IFN-γ and IL-6 proteins was attenuated upon exposure to CuIIb. Mechanistically, CuIIb treatment suppressed the phosphorylation of JNK and Erk1/2 but not p38 in Con A-activated lymphocytes. Although CuIIb unexpectedly enhanced the phosphorylation of IκB and NF-κB (p65, it blocked the nuclear translocation of NF-κB (p65. In support of this, CuIIb significantly decreased the mRNA levels of IκBα and TNF-α, two target genes of NF-κB, in Con A-activated lymphocytes. In addition, CuIIb downregulated Con A-induced STAT3 phosphorylation and increased cell apoptosis. Collectively, these results suggest that CuIIb exhibits its anti-inflammatory activity through modulating multiple cellular behaviors and signaling pathways, leading to the suppression of the adaptive immune response.

Receptor Oligomerization as a Process Modulating Cellular Semiotics

DEFF Research Database (Denmark)

Giorgi, Franco; Bruni, Luis Emilio; Maggio, Roberto

2010-01-01

be another level of quality control that may help maintaining GPCRs rather stable throughout evolution. We propose here receptor oligomerization to be a basic molecular mechanism controlling GPCRs redundancy in many different cell types, and the plasma membrane as the first hierarchical cell structure...... at which selective categorical sensing may occur. Categorical sensing can be seen as the cellular capacity for identifying and ordering complex patterns of mixed signals out of a contextual matrix, i.e., the recognition of meaningful patterns out of ubiquitous signals. In this context, redundancy...

Tetraspanin CD9 modulates human lymphoma cellular proliferation via histone deacetylase activity

Energy Technology Data Exchange (ETDEWEB)

Herr, Michael J. [Vascular Biology Center of Excellence, The University of Tennessee Health Science Center, Memphis, TN 38163 (United States); Department of Medicine, The University of Tennessee Health Science Center, Memphis, TN 38163 (United States); Department of Molecular Sciences, The University of Tennessee Health Science Center, Memphis, TN 38163 (United States); Department of Surgery, The University of Tennessee Health Science Center, Memphis, TN 38163 (United States); Longhurst, Celia M.; Baker, Benjamin [Vascular Biology Center of Excellence, The University of Tennessee Health Science Center, Memphis, TN 38163 (United States); Homayouni, Ramin [Department of Biology, Bioinformatics Program, University of Memphis, Memphis, TN 38152 (United States); Speich, Henry E.; Kotha, Jayaprakash [Vascular Biology Center of Excellence, The University of Tennessee Health Science Center, Memphis, TN 38163 (United States); Jennings, Lisa K., E-mail: ljennings@uthsc.edu [Vascular Biology Center of Excellence, The University of Tennessee Health Science Center, Memphis, TN 38163 (United States); Department of Medicine, The University of Tennessee Health Science Center, Memphis, TN 38163 (United States); Department of Molecular Sciences, The University of Tennessee Health Science Center, Memphis, TN 38163 (United States); Department of Surgery, The University of Tennessee Health Science Center, Memphis, TN 38163 (United States); Department of Biology, Bioinformatics Program, University of Memphis, Memphis, TN 38152 (United States)

2014-05-16

Highlights: • CD9 is differentially expressed in human Burkitt’s lymphoma cells. • We found that CD9 expression promotes these cells proliferation. • CD9 expression also increases HDAC activity. • HDAC inhibition decreased both cell proliferation and importantly CD9 expression. • CD9 may dictate HDAC efficacy and play a role in HDAC regulation. - Abstract: Non-Hodgkin Lymphoma (NHL) is a type of hematological malignancy that affects two percent of the overall population in the United States. Tetraspanin CD9 is a cell surface protein that has been thoroughly demonstrated to be a molecular facilitator of cellular phenotype. CD9 expression varies in two human lymphoma cell lines, Raji and BJAB. In this report, we investigated the functional relationship between CD9 and cell proliferation regulated by histone deacetylase (HDAC) activity in these two cell lines. Introduction of CD9 expression in Raji cells resulted in significantly increased cell proliferation and HDAC activity compared to Mock transfected Raji cells. The increase in CD9–Raji cell proliferation was significantly inhibited by HDAC inhibitor (HDACi) treatment. Pretreatment of BJAB cells with HDAC inhibitors resulted in a significant decrease in endogenous CD9 mRNA and cell surface expression. BJAB cells also displayed decreased cell proliferation after HDACi treatment. These results suggest a significant relationship between CD9 expression and cell proliferation in human lymphoma cells that may be modulated by HDAC activity.

Decision framework of photovoltaic module selection under interval-valued intuitionistic fuzzy environment

International Nuclear Information System (INIS)

Long, Shengping; Geng, Shuai

2015-01-01

Highlights: • The evaluation index system is set by the engineering and supply chain perspectives. • The interval-valued intuitionistic fuzzy set (IVIFS) to express the performances. • The IVIFS entropy weight method is applied to improve the objectivity of weights. - Abstract: The selection of appropriate photovoltaic module is of extremely high importance for the solar power station project; however the comprehensive problem of evaluation index system, the information loss problem and the lack-objectivity problem in the selection process will decrease the reasonability of the selection result. The innovation points of this paper are as follows: first, the comprehensive evaluation index system of photovoltaic module is established from the engineering management and supply chain management perspectives to solve the comprehensive problem; second, the interval-valued intuitionistic fuzzy set (IVIFS) are introduced into the photovoltaic modules selection process to express the alternatives’ performances to solve the information loss problem; third, the IVIFS entropy weight method is applied to improve the objectivity of the criteria’s weights. According to the aforementioned solutions, the decision framework of photovoltaic module selection under interval-valued intuitionistic fuzzy environment are established and used in a case study to demonstrate its effectiveness. Therefore, from the theoretical modeling and empirical demonstration, the decision framework proposed in this paper can effectively handle such a complicated problem and lead to an outstanding result.

Protein Modification with Amphiphilic Block Copoly(2-oxazoline)s as a New Platform for Enhanced Cellular Delivery

KAUST Repository

Tong, Jing; Luxenhofer, Robert; Yi, Xiang; Jordan, Rainer; Kabanov, Alexander V.

2010-01-01

Several homopolymers, random copolymers and block copolymers based on poly(2-oxazoline)s (POx) were synthesized and conjugated to horseradish peroxidase (HRP) using biodegradable and nonbiodegradable linkers. These conjugates were characterized by amino group titration, polyacrylamide gel electrophoresis (PAGE), isoelectric focusing, enzymatic activity assay and conformation analysis. The conjugates contained on average from about one to two polymer chains per enzyme. From 70% to 90% of enzymatic activity was retained in most cases. Circular dichroism (CD) analysis revealed that HRP modification affected the secondary structure of the apoprotein but did not affect the tertiary structure and heme environment. Enhanced cellular uptake was found in the conjugates of two block copolymers using both MDCK cells and Caco-2 cells, but not in the conjugates of random copolymer and homopolymer. Conjugation with a block copolymer of 2-methyl-2-oxazoline and 2-butyl-2-oxazoline led to the highest cellular uptake as compared to other conjugates. Our data indicates that modification with amphiphilic POx has the potential to modulate and enhance cellular delivery of proteins.

Protein Modification with Amphiphilic Block Copoly(2-oxazoline)s as a New Platform for Enhanced Cellular Delivery

KAUST Repository

Tong, Jing

2010-08-02

Several homopolymers, random copolymers and block copolymers based on poly(2-oxazoline)s (POx) were synthesized and conjugated to horseradish peroxidase (HRP) using biodegradable and nonbiodegradable linkers. These conjugates were characterized by amino group titration, polyacrylamide gel electrophoresis (PAGE), isoelectric focusing, enzymatic activity assay and conformation analysis. The conjugates contained on average from about one to two polymer chains per enzyme. From 70% to 90% of enzymatic activity was retained in most cases. Circular dichroism (CD) analysis revealed that HRP modification affected the secondary structure of the apoprotein but did not affect the tertiary structure and heme environment. Enhanced cellular uptake was found in the conjugates of two block copolymers using both MDCK cells and Caco-2 cells, but not in the conjugates of random copolymer and homopolymer. Conjugation with a block copolymer of 2-methyl-2-oxazoline and 2-butyl-2-oxazoline led to the highest cellular uptake as compared to other conjugates. Our data indicates that modification with amphiphilic POx has the potential to modulate and enhance cellular delivery of proteins.

Do Inner Planets Modulate the Space Environment of the Earth?

Directory of Open Access Journals (Sweden)

Jung-Hee Kim

2014-03-01

Full Text Available Variabilities in the solar wind cause disturbances throughout the heliosphere on all temporal and spatial scales, which leads to changeable space weather. As a view of space weather forecasting, in particular, it is important to know direct and indirect causes modulating the space environment near the Earth in advance. Recently, there are discussions on a role of the interaction of the solar wind with Mercury in affecting the solar wind velocity in the Earth’s neighborhood during its inferior conjunctions. In this study we investigate a question of whether other parameters describing the space environment near the Earth are modulated by the inner planets’ wake, by examining whether the interplanetary magnetic field and the proton density in the solar wind observed by the Advanced Composition Explorer (ACE spacecraft, and the geomagnetic field via the Dst index and Auroral Electrojet index (AE index are dependent upon the relative position of the inner planets. We find there are indeed apparent variations. For example, the mean variations of the geomagnetic fields measured in the Earth’s neighborhood apparently have varied with a timescale of about 10 to 25 days. Those variations in the parameters we have studied, however, turn out to be a part of random fluctuations and have nothing to do with the relative position of inner planets. Moreover, it is found that variations of the proton density in the solar wind, the Dst index, and the AE index are distributed with the Gaussian distribution. Finally, we point out that some of properties in the behavior of the random fluctuation are to be studied.

Intermolecular masking of the HIV-1 Rev NLS by the cellular protein HIC: novel insights into the regulation of Rev nuclear import.

LENUS (Irish Health Repository)

Gu, Lili

2011-01-01

The HIV-1 regulatory protein Rev, which is essential for viral replication, mediates the nuclear export of unspliced viral transcripts. Rev nuclear function requires active nucleocytoplasmic shuttling, and Rev nuclear import is mediated by the recognition of its Nuclear Localisation Signal (NLS) by multiple import factors, which include transportin and importin β. However, it remains unclear which nuclear import pathway(s) predominate in vivo, and the cellular environment that modulates Rev nucleocytoplasmic shuttling remains to be characterised.

Radioactivation of silicon tracker modules in high-luminosity hadron collider radiation environments

CERN Document Server

Dawson, I; Buttar, C; Cindro, V; Mandic, I

2003-01-01

One of the consequences of operating detector systems in harsh radiation environments will be radioactivation of the components. This will certainly be true in experiments such as ATLAS and CMS, which are currently being built to exploit the physics potential at CERN's Large Hadron Collider. If the levels of radioactivity and corresponding dose rates are significant, then there will be implications for any access or maintenance operations. This paper presents predictions for the radioactivation of ATLAS's Semi- Conductor Tracker (SCT) barrel system, based on both calculations and measurements. It is shown that both neutron capture and high-energy hadron reactions must be taken into account. The predictions also show that the SCT barrel-module should not pose any serious radiological problems after operation in high radiation environments.

Hybrid cellular automaton modeling of nutrient modulated cell growth in tissue engineering constructs.

Science.gov (United States)

Chung, C A; Lin, Tze-Hung; Chen, Shih-Di; Huang, Hsing-I

2010-01-21

Mathematic models help interpret experimental results and accelerate tissue engineering developments. We develop in this paper a hybrid cellular automata model that combines the differential nutrient transport equation to investigate the nutrient limited cell construct development for cartilage tissue engineering. Individual cell behaviors of migration, contact inhibition and cell collision, coupled with the cell proliferation regulated by oxygen concentration were carefully studied. Simplified two-dimensional simulations were performed. Using this model, we investigated the influence of cell migration speed on the overall cell growth within in vitro cell scaffolds. It was found that intense cell motility can enhance initial cell growth rates. However, since cell growth is also significantly modulated by the nutrient contents, intense cell motility with conventional uniform cell seeding method may lead to declined cell growth in the final time because concentrated cell population has been growing around the scaffold periphery to block the nutrient transport from outside culture media. Therefore, homogeneous cell seeding may not be a good way of gaining large and uniform cell densities for the final results. We then compared cell growth in scaffolds with various seeding modes, and proposed a seeding mode with cells initially residing in the middle area of the scaffold that may efficiently reduce the nutrient blockage and result in a better cell amount and uniform cell distribution for tissue engineering construct developments.

Modeling the mechanics of cancer: effect of changes in cellular and extra-cellular mechanical properties.

Science.gov (United States)

Katira, Parag; Bonnecaze, Roger T; Zaman, Muhammad H

2013-01-01

Malignant transformation, though primarily driven by genetic mutations in cells, is also accompanied by specific changes in cellular and extra-cellular mechanical properties such as stiffness and adhesivity. As the transformed cells grow into tumors, they interact with their surroundings via physical contacts and the application of forces. These forces can lead to changes in the mechanical regulation of cell fate based on the mechanical properties of the cells and their surrounding environment. A comprehensive understanding of cancer progression requires the study of how specific changes in mechanical properties influences collective cell behavior during tumor growth and metastasis. Here we review some key results from computational models describing the effect of changes in cellular and extra-cellular mechanical properties and identify mechanistic pathways for cancer progression that can be targeted for the prediction, treatment, and prevention of cancer.

Modelling of processes occurring in deep geological repository - development of new modules in the GoldSim environment

International Nuclear Information System (INIS)

Vopalka, D.; Lukin, D.; Vokal, A.

2006-01-01

Three new modules modelling the processes that occur in a deep geological repository have been prepared in the GoldSim computer code environment (using its Transport Module). These modules help to understand the role of selected parameters in the near-field region of the final repository and to prepare an own complex model of the repository behaviour. The source term module includes radioactive decay and ingrowth in the canister, first order degradation of fuel matrix, solubility limitation of the concentration of the studied nuclides, and diffusive migration through the surrounding bentonite layer controlled by the output boundary condition formulated with respect to the rate of water flow in the rock. The corrosion module describes corrosion of canisters made of carbon steel and transport of corrosion products in the near-field region. This module computes balance equations between dissolving species and species transported by diffusion and/or advection from the surface of a solid material. The diffusion module that includes also non-linear form of the interaction isotherm can be used for an evaluation of small-scale diffusion experiments. (author)

Modelling of processes occurring in deep geological repository - Development of new modules in the GoldSim environment

Science.gov (United States)

Vopálka, D.; Lukin, D.; Vokál, A.

2006-01-01

Three new modules modelling the processes that occur in a deep geological repository have been prepared in the GoldSim computer code environment (using its Transport Module). These modules help to understand the role of selected parameters in the near-field region of the final repository and to prepare an own complex model of the repository behaviour. The source term module includes radioactive decay and ingrowth in the canister, first order degradation of fuel matrix, solubility limitation of the concentration of the studied nuclides, and diffusive migration through the surrounding bentonite layer controlled by the output boundary condition formulated with respect to the rate of water flow in the rock. The corrosion module describes corrosion of canisters made of carbon steel and transport of corrosion products in the near-field region. This module computes balance equations between dissolving species and species transported by diffusion and/or advection from the surface of a solid material. The diffusion module that includes also non-linear form of the interaction isotherm can be used for an evaluation of small-scale diffusion experiments.

Targeting Cellular Calcium Homeostasis to Prevent Cytokine-Mediated Beta Cell Death.

Science.gov (United States)

Clark, Amy L; Kanekura, Kohsuke; Lavagnino, Zeno; Spears, Larry D; Abreu, Damien; Mahadevan, Jana; Yagi, Takuya; Semenkovich, Clay F; Piston, David W; Urano, Fumihiko

2017-07-17

Pro-inflammatory cytokines are important mediators of islet inflammation, leading to beta cell death in type 1 diabetes. Although alterations in both endoplasmic reticulum (ER) and cytosolic free calcium levels are known to play a role in cytokine-mediated beta cell death, there are currently no treatments targeting cellular calcium homeostasis to combat type 1 diabetes. Here we show that modulation of cellular calcium homeostasis can mitigate cytokine- and ER stress-mediated beta cell death. The calcium modulating compounds, dantrolene and sitagliptin, both prevent cytokine and ER stress-induced activation of the pro-apoptotic calcium-dependent enzyme, calpain, and partly suppress beta cell death in INS1E cells and human primary islets. These agents are also able to restore cytokine-mediated suppression of functional ER calcium release. In addition, sitagliptin preserves function of the ER calcium pump, sarco-endoplasmic reticulum Ca 2+ -ATPase (SERCA), and decreases levels of the pro-apoptotic protein thioredoxin-interacting protein (TXNIP). Supporting the role of TXNIP in cytokine-mediated cell death, knock down of TXNIP in INS1-E cells prevents cytokine-mediated beta cell death. Our findings demonstrate that modulation of dynamic cellular calcium homeostasis and TXNIP suppression present viable pharmacologic targets to prevent cytokine-mediated beta cell loss in diabetes.

Modular design of artificial tissue homeostasis: robust control through synthetic cellular heterogeneity.

Directory of Open Access Journals (Sweden)

Miles Miller

Full Text Available Synthetic biology efforts have largely focused on small engineered gene networks, yet understanding how to integrate multiple synthetic modules and interface them with endogenous pathways remains a challenge. Here we present the design, system integration, and analysis of several large scale synthetic gene circuits for artificial tissue homeostasis. Diabetes therapy represents a possible application for engineered homeostasis, where genetically programmed stem cells maintain a steady population of β-cells despite continuous turnover. We develop a new iterative process that incorporates modular design principles with hierarchical performance optimization targeted for environments with uncertainty and incomplete information. We employ theoretical analysis and computational simulations of multicellular reaction/diffusion models to design and understand system behavior, and find that certain features often associated with robustness (e.g., multicellular synchronization and noise attenuation are actually detrimental for tissue homeostasis. We overcome these problems by engineering a new class of genetic modules for 'synthetic cellular heterogeneity' that function to generate beneficial population diversity. We design two such modules (an asynchronous genetic oscillator and a signaling throttle mechanism, demonstrate their capacity for enhancing robust control, and provide guidance for experimental implementation with various computational techniques. We found that designing modules for synthetic heterogeneity can be complex, and in general requires a framework for non-linear and multifactorial analysis. Consequently, we adapt a 'phenotypic sensitivity analysis' method to determine how functional module behaviors combine to achieve optimal system performance. We ultimately combine this analysis with Bayesian network inference to extract critical, causal relationships between a module's biochemical rate-constants, its high level functional behavior in

Modular design of artificial tissue homeostasis: robust control through synthetic cellular heterogeneity.

Science.gov (United States)

Miller, Miles; Hafner, Marc; Sontag, Eduardo; Davidsohn, Noah; Subramanian, Sairam; Purnick, Priscilla E M; Lauffenburger, Douglas; Weiss, Ron

2012-01-01

Synthetic biology efforts have largely focused on small engineered gene networks, yet understanding how to integrate multiple synthetic modules and interface them with endogenous pathways remains a challenge. Here we present the design, system integration, and analysis of several large scale synthetic gene circuits for artificial tissue homeostasis. Diabetes therapy represents a possible application for engineered homeostasis, where genetically programmed stem cells maintain a steady population of β-cells despite continuous turnover. We develop a new iterative process that incorporates modular design principles with hierarchical performance optimization targeted for environments with uncertainty and incomplete information. We employ theoretical analysis and computational simulations of multicellular reaction/diffusion models to design and understand system behavior, and find that certain features often associated with robustness (e.g., multicellular synchronization and noise attenuation) are actually detrimental for tissue homeostasis. We overcome these problems by engineering a new class of genetic modules for 'synthetic cellular heterogeneity' that function to generate beneficial population diversity. We design two such modules (an asynchronous genetic oscillator and a signaling throttle mechanism), demonstrate their capacity for enhancing robust control, and provide guidance for experimental implementation with various computational techniques. We found that designing modules for synthetic heterogeneity can be complex, and in general requires a framework for non-linear and multifactorial analysis. Consequently, we adapt a 'phenotypic sensitivity analysis' method to determine how functional module behaviors combine to achieve optimal system performance. We ultimately combine this analysis with Bayesian network inference to extract critical, causal relationships between a module's biochemical rate-constants, its high level functional behavior in isolation, and

Identify Dynamic Network Modules with Temporal and Spatial Constraints

Energy Technology Data Exchange (ETDEWEB)

Jin, R; McCallen, S; Liu, C; Almaas, E; Zhou, X J

2007-09-24

Despite the rapid accumulation of systems-level biological data, understanding the dynamic nature of cellular activity remains a difficult task. The reason is that most biological data are static, or only correspond to snapshots of cellular activity. In this study, we explicitly attempt to detangle the temporal complexity of biological networks by using compilations of time-series gene expression profiling data.We define a dynamic network module to be a set of proteins satisfying two conditions: (1) they form a connected component in the protein-protein interaction (PPI) network; and (2) their expression profiles form certain structures in the temporal domain. We develop the first efficient mining algorithm to discover dynamic modules in a temporal network, as well as frequently occurring dynamic modules across many temporal networks. Using yeast as a model system, we demonstrate that the majority of the identified dynamic modules are functionally homogeneous. Additionally, many of them provide insight into the sequential ordering of molecular events in cellular systems. We further demonstrate that identifying frequent dynamic network modules can significantly increase the signal to noise separation, despite the fact that most dynamic network modules are highly condition-specific. Finally, we note that the applicability of our algorithm is not limited to the study of PPI systems, instead it is generally applicable to the combination of any type of network and time-series data.

Reduced labor and condensed schedules with cellular concrete solutions

Energy Technology Data Exchange (ETDEWEB)

Lavis, D. [CEMATRIX Inc., Calgary, AB (Canada)

2008-07-01

This paper discussed the use of cellular concrete materials in oil sands tank base foundation systems, shallow buried utility insulation systems, roadways, slabs, and buried modules. The concrete is formed from Portland cement, water, specialized pre-formed foaming agents, and air mixed in controlled proportions. Fly ash and polypropylene or glass fibers can also be used as additions. Cellular concrete can often be used to speed up construction and minimize labour requirements. Cellular concrete can be cast-in-place, and has soil-stabilizing and self-compacting features. The concrete can be produced and placed on-site at rates exceeding 120 cubic meters per hour. Cellular concrete can be pumped into place over long distances through flexible hoses. A case study comparing the cellular concrete to traditional plastic foam insulation was used to demonstrate the equivalency and adequacy of insulation, structural properties and installation costs. The study showed that although the cellular concrete had a high installation cost, greater compressive strength was gained. The concrete was self-levelling and did not require compaction or vibration. The use of the cellular concrete resulted in an accelerated construction schedule. 6 refs., 2 tabs., 6 figs.

Performances of Hybrid Amplitude Shape Modulation for UWB Communications Systems over AWGN Channel in a Single and Multi-User Environment

Directory of Open Access Journals (Sweden)

M. Herceg

2009-09-01

Full Text Available This paper analyzes the performance of the hybrid Amplitude Shape Modulation (h-ASM scheme for the time-hopping ultra-wideband (TH-UWB communication systems in the single and multi-user environment. h-ASM is the combination of Pulse Amplitude Modulation (PAM and Pulse Shape Modulation (PSM based on modified Hermite pulses (MHP. This scheme is suitable for high rate data transmission applications because b = log2(MN bits can be mapped with one waveform. The channel capacity and error probability over AWGN channel are derived and compared with other modulation schemes.

Biomimetic approaches to modulate cellular adhesion in biomaterials: A review.

Science.gov (United States)

Rahmany, Maria B; Van Dyke, Mark

2013-03-01

Natural extracellular matrix (ECM) proteins possess critical biological characteristics that provide a platform for cellular adhesion and activation of highly regulated signaling pathways. However, ECM-based biomaterials can have several limitations, including poor mechanical properties and risk of immunogenicity. Synthetic biomaterials alleviate the risks associated with natural biomaterials but often lack the robust biological activity necessary to direct cell function beyond initial adhesion. A thorough understanding of receptor-mediated cellular adhesion to the ECM and subsequent signaling activation has facilitated development of techniques that functionalize inert biomaterials to provide a biologically active surface. Here we review a range of approaches used to modify biomaterial surfaces for optimal receptor-mediated cell interactions, as well as provide insights into specific mechanisms of downstream signaling activation. In addition to a brief overview of integrin receptor-mediated cell function, so-called "biomimetic" techniques reviewed here include (i) surface modification of biomaterials with bioadhesive ECM macromolecules or specific binding motifs, (ii) nanoscale patterning of the materials and (iii) the use of "natural-like" biomaterials. Copyright © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Towards developing high-fidelity simulated learning environment training modules in audiology.

Science.gov (United States)

Dzulkarnain, A A; Rahmat, S; Mohd Puzi, N A F; Badzis, M

2017-02-01

This discussion paper reviews and synthesises the literature on simulated learning environment (SLE) from allied health sciences, medical and nursing in general and audiology specifically. The focus of the paper is on discussing the use of high-fidelity (HF) SLE and describing the challenges for developing a HF SLE for clinical audiology training. Through the review of the literature, this paper discusses seven questions, (i) What is SLE? (ii) What are the types of SLEs? (iii) How is SLE classified? (iv) What is HF SLE? (v) What types of SLEs are available in audiology and their level of fidelity? (vi) What are the components needed for developing HF SLE? (vii) What are the possible types of HF SLEs that are suitable for audiology training? Publications were identified by structured searches from three major databases PubMed, Web of Knowledge and PsychInfo and from the reference lists of relevant articles. The authors discussed and mapped the levels of fidelity of SLE audiology training modules from the literature and the learning domains involved in the clinical audiology courses. The discussion paper has highlighted that most of the existing SLE audiology training modules consist of either low- or medium-fidelity types of simulators. Those components needed to achieve a HF SLE for audiology training are also highlighted. Overall, this review recommends that the combined approach of different levels and types of SLE could be used to obtain a HF SLE training module in audiology training.

Effects of Redox Modulation on Cell Proliferation, Viability, and Migration in Cultured Rat and Human Tendon Progenitor Cells

Directory of Open Access Journals (Sweden)

Yuk Wa Lee

2017-01-01

Full Text Available Tendon healing is slow and usually results in inferior fibrotic tissue formation. Recently, application of tendon derived stem cells (TDSCs improved tendon healing in animal studies. In a chicken model, local injection of antioxidants reduced tendon adhesion after tendon injury. An in vitro study demonstrated that supplementation of H2O2 reduced tenogenic marker expression in TDSCs. These findings suggested that the possibility of TDSCs is involved in tendon healing and the cellular activities of TDSCs might be affected by oxidative stress of the local environment. After tendon injury, oxidative stress is increased. Redox modulation might affect healing outcomes via affecting cellular activities in TDSCs. To study the effect of oxidative stress on TDSCs, the cellular activities of rat/human TDSCs were measured under different dosages of vitamin C or H2O2 in this study. Lower dose of vitamin C increased cell proliferation, viability and migration; H2O2 affected colony formation and suppressed cell migration, cell viability, apoptosis, and proliferation. Consistent with previous studies, oxidative stresses (H2O2 affect both recruitment and survival of TDSCs, while the antioxidant vitamin C may exert beneficial effects at low doses. In conclusion, redox modulation affected cellular activities of TDSCs and might be a potential strategy for tendon healing treatment.

Nitric Oxide Synthase and Cyclooxygenase Pathways: A Complex Interplay in Cellular Signaling.

Science.gov (United States)

Sorokin, Andrey

2016-01-01

The cellular reaction to external challenges is a tightly regulated process consisting of integrated processes mediated by a variety of signaling molecules, generated as a result of modulation of corresponding biosynthetic systems. Both, nitric oxide synthase (NOS) and cyclooxygenase (COX) systems, consist of constitutive forms (NOS1, NOS3 and COX-1), which are mostly involved in housekeeping tasks, and inducible forms (NOS2 and COX-2), which shape the cellular response to stress and variety of bioactive agents. The complex interplay between NOS and COX pathways can be observed at least at three levels. Firstly, products of NOS and Cox systems can mediate the regulation and the expression of inducible forms (NOS2 and COX-2) in response of similar and dissimilar stimulus. Secondly, the reciprocal modulation of cyclooxygenase activity by nitric oxide and NOS activity by prostaglandins at the posttranslational level has been shown to occur. Mechanisms by which nitric oxide can modulate prostaglandin synthesis include direct S-nitrosylation of COX and inactivation of prostaglandin I synthase by peroxynitrite, product of superoxide reaction with nitric oxide. Prostaglandins, conversely, can promote an increased association of dynein light chain (DLC) (also known as protein inhibitor of neuronal nitric oxide synthase) with NOS1, thereby reducing its activity. The third level of interplay is provided by intracellular crosstalk of signaling pathways stimulated by products of NOS and COX which contributes significantly to the complexity of cellular signaling. Since modulation of COX and NOS pathways was shown to be principally involved in a variety of pathological conditions, the dissection of their complex relationship is needed for better understanding of possible therapeutic strategies. This review focuses on implications of interplay between NOS and COX for cellular function and signal integration.

Performance Evaluation Of Mobile Cellular Networks In Nigeria

OpenAIRE

Shoewu, O.O

2018-01-01

The aim of this paper is to evaluate the performance of mobile networks such as MTN, GLO, and ETISALAT in Nigeria and suggest ways the performance of digital cellular networks can improve to minimize some of its present short comings or limitations. This paper discusses the performance improvement of digital cellular networks. A non- CDMA cellular network is use in an overall wireless environment for the purpose of this paper. This paper also discusses the performance assessment of three mobi...

Modeling cellular networks in fading environments with dominant specular components

KAUST Repository

Alammouri, Ahmad; Elsawy, Hesham; Salem, Ahmed Sultan; Di Renzo, Marco; Alouini, Mohamed-Slim

2016-01-01

to the Nakagami-m fading in some special cases. However, neither the Rayleigh nor the Nakagami-m accounts for dominant specular components (DSCs) which may appear in realistic fading channels. In this paper, we present a tractable model for cellular networks

Fluoxetine effects on molecular, cellular and behavioral endophenotypes of depression are driven by the living environment.

Science.gov (United States)

Alboni, S; van Dijk, R M; Poggini, S; Milior, G; Perrotta, M; Drenth, T; Brunello, N; Wolfer, D P; Limatola, C; Amrein, I; Cirulli, F; Maggi, L; Branchi, I

2017-04-01

Selective serotonin reuptake inhibitors (SSRIs) represent the most common treatment for major depression. However, their efficacy is variable and incomplete. In order to elucidate the cause of such incomplete efficacy, we explored the hypothesis positing that SSRIs may not affect mood per se but, by enhancing neural plasticity, render the individual more susceptible to the influence of the environment. Consequently, SSRI administration in a favorable environment promotes a reduction of symptoms, whereas in a stressful environment leads to a worse prognosis. To test such hypothesis, we exposed C57BL/6 mice to chronic stress in order to induce a depression-like phenotype and, subsequently, to fluoxetine treatment (21 days), while being exposed to either an enriched or a stressful condition. We measured the most commonly investigated molecular, cellular and behavioral endophenotypes of depression and SSRI outcome, including depression-like behavior, neurogenesis, brain-derived neurotrophic factor levels, hypothalamic-pituitary-adrenal axis activity and long-term potentiation. Results showed that, in line with our hypothesis, the endophenotypes investigated were affected by the treatment according to the quality of the living environment. In particular, mice treated with fluoxetine in an enriched condition overall improved their depression-like phenotype compared with controls, whereas those treated in a stressful condition showed a distinct worsening. Our findings suggest that the effects of SSRI on the depression- like phenotype is not determined by the drug per se but is induced by the drug and driven by the environment. These findings may be helpful to explain variable effects of SSRI found in clinical practice and to device strategies aimed at enhancing their efficacy by means of controlling environmental conditions.

Modeling cellular networks in fading environments with dominant specular components

KAUST Repository

AlAmmouri, Ahmad

2016-07-26

Stochastic geometry (SG) has been widely accepted as a fundamental tool for modeling and analyzing cellular networks. However, the fading models used with SG analysis are mainly confined to the simplistic Rayleigh fading, which is extended to the Nakagami-m fading in some special cases. However, neither the Rayleigh nor the Nakagami-m accounts for dominant specular components (DSCs) which may appear in realistic fading channels. In this paper, we present a tractable model for cellular networks with generalized two-ray (GTR) fading channel. The GTR fading explicitly accounts for two DSCs in addition to the diffuse components and offers high flexibility to capture diverse fading channels that appear in realistic outdoor/indoor wireless communication scenarios. It also encompasses the famous Rayleigh and Rician fading as special cases. To this end, the prominent effect of DSCs is highlighted in terms of average spectral efficiency. © 2016 IEEE.

Frequency modulation atomic force microscopy in ambient environments utilizing robust feedback tuning

Science.gov (United States)

Kilpatrick, J. I.; Gannepalli, A.; Cleveland, J. P.; Jarvis, S. P.

2009-02-01

Frequency modulation atomic force microscopy (FM-AFM) is rapidly evolving as the technique of choice in the pursuit of high resolution imaging of biological samples in ambient environments. The enhanced stability afforded by this dynamic AFM mode combined with quantitative analysis enables the study of complex biological systems, at the nanoscale, in their native physiological environment. The operational bandwidth and accuracy of constant amplitude FM-AFM in low Q environments is heavily dependent on the cantilever dynamics and the performance of the demodulation and feedback loops employed to oscillate the cantilever at its resonant frequency with a constant amplitude. Often researchers use ad hoc feedback gains or instrument default values that can result in an inability to quantify experimental data. Poor choice of gains or exceeding the operational bandwidth can result in imaging artifacts and damage to the tip and/or sample. To alleviate this situation we present here a methodology to determine feedback gains for the amplitude and frequency loops that are specific to the cantilever and its environment, which can serve as a reasonable "first guess," thus making quantitative FM-AFM in low Q environments more accessible to the nonexpert. This technique is successfully demonstrated for the low Q systems of air (Q ˜40) and water (Q ˜1). In addition, we present FM-AFM images of MC3T3-E1 preosteoblast cells acquired using the gains calculated by this methodology demonstrating the effectiveness of this technique.

Modulation in vitro and in vivo of cytotoxicity but not cellular levels of doxorubicin by the calmodulin inhibitor trifluoperazine is dependent on the level of resistance.

Science.gov (United States)

Ganapathi, R.; Schmidt, H.; Grabowski, D.; Melia, M.; Ratliff, N.

1988-01-01

The role of the calmodulin inhibitor trifluoperazine (TFP) in modulating the cellular levels and cytotoxicity in vitro and antitumour effects in vivo of doxorubicin (DOX), was evaluated in progressively DOX-resistant (5- to 40-fold) sublines of B16-BL6 mouse melanoma. In parental-sensitive B16-BL6 cells treated for 3 h, the IC50 of DOX was 0.1 microgram ml-1, and a less than 2-fold enhancement in DOX cell kill in the presence of a noncytotoxic concentration of 5 microM TFP was observed. However, in the DOX-resistant sublines, the IC50 was 0.7 to 5.0 micrograms ml-1 DOX in the absence of 5 microM TFP and 0.3 to 0.7 microgram ml-1 DOX in the presence of 5 microM TFP. The 2- to 7.5-fold decrease in the IC50 of DOX in the presence of 5 microM TFP, was dependent on the level of DOX-resistance in the various sublines. Compared to parental-sensitive cells, a 2-fold decrease in DOX-accumulation was evident only in the 40-fold DOX-resistant subline. Further, maximal enhancement (50%) of cellular DOX accumulation in the presence of 5 microM TFP was observed only in the 40-fold resistant cells treated with 5.0 micrograms ml-1 DOX. Retention of DOX in the 40-fold resistant subline was only 20% lower than similarly treated sensitive cells, and the inclusion of TFP increased DOX retention less than 10-15%. Antitumour studies in mice with experimental pulmonary metastases revealed that although DOX and DOX plus TFP had similar antitumour activity with the parental sensitive B16-BL6 cells, the combination of DOX plus TFP was significantly more effective than DOX alone with the DOX-resistant sublines. No overt toxicity was observed in normal mice treated with doses of TFP, DOX or DOX plus TFP used for in vivo chemotherapy studies. Results from this study suggest that gross cellular DOX levels do not appear to correlate with the magnitude of resistance, and the effects of TFP in modulating DOX resistance is possibly due to mechanisms other than mere alterations in cellular drug

Modulation of the mechanical properties of ventricular extracellular matrix hydrogels with a carbodiimide crosslinker and investigation of their cellular compatibility

Directory of Open Access Journals (Sweden)

Kyohei Fujita

2018-01-01

Full Text Available Hydrogels made from the cardiac extracellular matrix (ECM as two-dimensional (2D or 3D cell-culture substrates have beneficial biochemical effects on the differentiation of stem cells into cardiomyocytes. The mechanical properties of the substrates that match those of the host tissues have been identified as critical biophysical cues for coaxing the tissue-specific differentiation of stem cells. The objectives of the present study are (1 to fabricate hydrogels comprising pure ventricular ECM (vECM, (2 to make the gels possess mechanical properties similar to those of the decellularized ventricular tissue, and (3 to evaluate the cellular compatibility of the hydrogels. In order to achieve these aims, (1 a simplified protocol was developed to produce vECM solution easily and rapidly, (2 N-(3-Dimethylaminopropyl-N’-ethylcarbodiimide hydrochloride (EDAC was chosen to crosslink the hydrogels made from the vECM solution to enhance their mechanical properties and stabilize the microstructure of the gels, (3 rat embryonic fibroblasts or cardiomyocytes were cultured on these gels to determine the cellular compatibility of the gels. In particular, the nonlinearity and viscoelasticity of the gels were characterized quantitatively using a newly proposed nonlinear Kelvin model. The results showed that EDAC treatment allowed modulation of the mechanical properties of the gels to the same level as those of decellularized ventricular tissue in terms of the equilibrium elasticity and relaxation coefficient. Cell culture confirmed the cellular compatibility of the gels. Furthermore, an empirical relationship between the equilibrium elastic modulus of the gels and the vECM and EDAC concentrations was derived, which is important to tailor the mechanical properties of the gels. Finally, the influence of the mechanical properties of the gels on the behavior of cultured fibroblasts and cardiomyocytes was discussed.

Winding through the WNT pathway during cellular development and demise.

Science.gov (United States)

Li, F; Chong, Z Z; Maiese, K

2006-01-01

In slightly over a period of twenty years, our comprehension of the cellular and molecular mechanisms that govern the Wnt signaling pathway continue to unfold. The Wnt proteins were initially implicated in viral carcinogenesis experiments associated with mammary tumors, but since this period investigations focusing on the Wnt pathways and their transmembrane receptors termed Frizzled have been advanced to demonstrate the critical nature of Wnt for the development of a variety of cell populations as well as the potential of the Wnt pathway to avert apoptotic injury. In particular, Wnt signaling plays a significant role in both the cardiovascular and nervous systems during embryonic cell patterning, proliferation, differentiation, and orientation. Furthermore, modulation of Wnt signaling under specific cellular influences can either promote or prevent the early and late stages of apoptotic cellular injury in neurons, endothelial cells, vascular smooth muscle cells, and cardiomyocytes. A number of downstream signal transduction pathways can mediate the biological response of the Wnt proteins that include Dishevelled, beta-catenin, intracellular calcium, protein kinase C, Akt, and glycogen synthase kinase-3beta. Interestingly, these cellular cascades of the Wnt-Frizzled pathways can participate in several neurodegenerative, vascular, and cardiac disorders and may be closely integrated with the function of trophic factors. Identification of the critical elements that modulate the Wnt-Frizzled signaling pathway should continue to unlock the potential of Wnt pathway for the development of new therapeutic options against neurodegenerative and vascular diseases.

The cellular environment of cancerous human tissue. Interfacial and dangling water as a "hydration fingerprint".

Science.gov (United States)

Abramczyk, Halina; Brozek-Pluska, Beata; Krzesniak, Marta; Kopec, Monika; Morawiec-Sztandera, Alina

2014-08-14

Despite a large number of publications, the role of water in the cellular environment of biological tissue has not been clarified. Characterizing the biological interface is a key challenge in understanding the interactions of water in the tissue. Although we often assume that the properties of the bulk water can be translated to the crowded biological environment, this approach must be considerably revised when considering the biological interface. To our knowledge, few studies have directly monitored the interactions and accumulation of water in the restricted environments of the biological tissue upon realistic crowding conditions. The present study focuses on a molecular picture of water molecules at the biological interface, or specifically, water molecules adjacent to the hydrophobic and hydrophilic surfaces of normal and cancerous tissues. We recorded and analyzed the IR and Raman spectra of the νs(OH) stretching modes of water at the biological interfaces of the human breast and neck tissues. The results revealed dramatic changes in the water content in the tissue and are potentially relevant to both the fundamental problems of interfacial water modeling and the molecular diagnostics of cancer as a 'hydration fingerprint'. Herein, we will discuss the origin of the vibrational substructures observed for the νs(OH) stretching modes of water, showing that the interfacial water interacting via H-bond with other water molecules and biomolecules at the biological surface and free OH vibration of the dangling water are sensitive indicators of the pathology between the normal (noncancerous) and cancerous tissue and cancer types. Copyright © 2014 Elsevier B.V. All rights reserved.

MNK1 expression increases during cellular senescence and modulates the subcellular localization of hnRNP A1

International Nuclear Information System (INIS)

Ziaei, Samira; Shimada, Naoko; Kucharavy, Herman; Hubbard, Karen

2012-01-01

Heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is an RNA-binding protein that modulates splice site usage, polyadenylation, and cleavage efficiency. This protein has also been implicated in mRNA stability and transport from the nucleus. We have previously demonstrated that hnRNP A1 had diminished protein levels and showed cytoplasmic accumulation in senescent human diploid fibroblasts. Furthermore, we have shown that inhibition of p38 MAPK, a key regulator of cellular senescence, elevated hnRNP A1 protein levels and inhibited hnRNP A1 cytoplasmic localization. In this study, we have explored the possible involvement of MNK1, one of the downstream effector of p38 MAPK, in the regulation of hnRNP A1. We have demonstrated that pharmacological inhibition of MNK1 by CGP 57380 decreased the phosphorylation levels of hnRNP A1 in young and senescent fibroblast cells and blocked the cytoplasmic accumulation of hnRNP A1 in senescent cells. In addition, MNK1 formed a complex with hnRNP A1 in vivo. The expression levels of MNK1, phospho-MNK1, and phospho-eIF4E proteins were found to be elevated in senescent cells. These data suggest that MNK1 regulates the phosphorylation and the subcellular distribution of hnRNP A1 and that MNK1 may play a role in the induction of senescence. -- Highlights: ► MNK1 and not MAPKAPK2 phosphorylates hnRNP A1. ► MNK1 has elevated levels in senescent cells, this has not been reported previously. ► MNK1 activity induces cytoplasmic accumulation of hnRNP A1 in senescent cells. ► Altered cytoplasmic localization of hnRNP A1 may alter gene expression patterns. ► Our studies may increase our understanding of RNA metabolism during cellular aging.

Matrix remodeling between cells and cellular interactions with collagen bundle

Science.gov (United States)

Kim, Jihan; Sun, Bo

When cells are surrounded by complex environment, they continuously probe and interact with it by applying cellular traction forces. As cells apply traction forces, they can sense rigidity of their local environment and remodel the matrix microstructure simultaneously. Previous study shows that single human carcinoma cell (MDA-MB-231) remodeled its surrounding extracellular matrix (ECM) and the matrix remodeling was reversible. In this study we examined the matrix microstructure between cells and cellular interaction between them using quantitative confocal microscopy. The result shows that the matrix microstructure is the most significantly remodeled between cells consisting of aligned, and densified collagen fibers (collagen bundle)., the result shows that collagen bundle is irreversible and significantly change micromechanics of ECM around the bundle. We further examined cellular interaction with collagen bundle by analyzing dynamics of actin and talin formation along with the direction of bundle. Lastly, we analyzed dynamics of cellular protrusion and migrating direction of cells along the bundle.

Application of Digital Cellular Radio for Mobile Location Estimation

Directory of Open Access Journals (Sweden)

Farhat Anwar

2012-08-01

Full Text Available The capability to locate the position of mobiles is a prerequisite to implement a wide range of evolving ITS services. Radiolocation has the potential to serve a wide geographical area. This paper reports an investigation regarding the feasibility of utilizing cellular radio for the purpose of mobile location estimation. Basic strategies to be utilized for location estimation are elaborated. Two possible approaches for cellular based location estimation are investigated with the help of computer simulation. Their effectiveness and relative merits and demerits are identified. An algorithm specifically adapted for cellular environment is reported with specific features where mobiles, irrespective of their numbers, can locate their position without adversely loading the cellular system.Key Words: ITS, GSM, Cellular Radio, DRGS, GPS.

Cellular volume regulation and substrate stiffness modulate the detachment dynamics of adherent cells

Science.gov (United States)

Yang, Yuehua; Jiang, Hongyuan

2018-03-01

Quantitative characterizations of cell detachment are vital for understanding the fundamental mechanisms of cell adhesion. Experiments have found that cell detachment shows strong rate dependence, which is mostly attributed to the binding-unbinding kinetics of receptor-ligand bond. However, our recent study showed that the cellular volume regulation can significantly regulate the dynamics of adherent cell and cell detachment. How this cellular volume regulation contributes to the rate dependence of cell detachment remains elusive. Here, we systematically study the role of cellular volume regulation in the rate dependence of cell detachment by investigating the cell detachments of nonspecific adhesion and specific adhesion. We find that the cellular volume regulation and the bond kinetics dominate the rate dependence of cell detachment at different time scales. We further test the validity of the traditional Johnson-Kendall-Roberts (JKR) contact model and the detachment model developed by Wyart and Gennes et al (W-G model). When the cell volume is changeable, the JKR model is not appropriate for both the detachments of convex cells and concave cells. The W-G model is valid for the detachment of convex cells but is no longer applicable for the detachment of concave cells. Finally, we show that the rupture force of adherent cells is also highly sensitive to substrate stiffness, since an increase in substrate stiffness will lead to more associated bonds. These findings can provide insight into the critical role of cell volume in cell detachment and might have profound implications for other adhesion-related physiological processes.

Cellular telephone-based radiation detection instrument

Science.gov (United States)

Craig, William W [Pittsburg, CA; Labov, Simon E [Berkeley, CA

2011-06-14

A network of radiation detection instruments, each having a small solid state radiation sensor module integrated into a cellular phone for providing radiation detection data and analysis directly to a user. The sensor module includes a solid-state crystal bonded to an ASIC readout providing a low cost, low power, light weight compact instrument to detect and measure radiation energies in the local ambient radiation field. In particular, the photon energy, time of event, and location of the detection instrument at the time of detection is recorded for real time transmission to a central data collection/analysis system. The collected data from the entire network of radiation detection instruments are combined by intelligent correlation/analysis algorithms which map the background radiation and detect, identify and track radiation anomalies in the region.

Analogy-Integrated e-Learning Module: Facilitating Students' Conceptual Understanding

Science.gov (United States)

Florida, Jennifer

2012-01-01

The study deals with the development of an analogy-integrated e-learning module on Cellular Respiration, which is intended to facilitate conceptual understanding of students with different brain hemisphere dominance and learning styles. The module includes eight analogies originally conceptualized following the specific steps used to prepare…

Phase-Modulation Laser Interference Microscopy

DEFF Research Database (Denmark)

Brazhe, Alexey; Brazhe, Nadezda; Maximov, G. V.

2008-01-01

We describe how phase-modulation laser interference microscopy and wavelet analysis can be applied to noninvasive nonstained visualization and study of the structural and dynamical properties of living cells. We show how phase images of erythrocytes can reveal the difference between various...... erythrocyte forms and stages of hemolysis and how phase images of neurons reveal their complex intracellular structure. Temporal variations of the refractive index are analyzed to detect cellular rhythmic activity on different time scales as well as to uncover interactions between the cellular processes....

Liquid rocket propulsion dynamic flow modeling using the ROCETS engineering modules in the EASY5x environment

Science.gov (United States)

Follett, Randolph F.; Taylor, Robert P.; Nunez, Stephen C.

1993-01-01

A report on the progress of porting the ROCETS (ROCket Engine Transient Simulator) into the EASY5x simulation environment is presented. Brief descriptions of each of the software systems, information regarding the actual port process, and examples comparing the results of the two systems are given. It is shown that EASY5x is a suitable environment for utilization of the ROCETS engineering modules, and that, for the example systems shown, EASY5x actually seems to give more accurate solutions than the straight ROCETS code.

A novel flow cytometric HTS assay reveals functional modulators of ATP binding cassette transporter ABCB6.

Science.gov (United States)

Polireddy, Kishore; Khan, Mohiuddin Md Taimur; Chavan, Hemantkumar; Young, Susan; Ma, Xiaochao; Waller, Anna; Garcia, Matthew; Perez, Dominique; Chavez, Stephanie; Strouse, Jacob J; Haynes, Mark K; Bologa, Cristian G; Oprea, Tudor I; Tegos, George P; Sklar, Larry A; Krishnamurthy, Partha

2012-01-01

ABCB6 is a member of the adenosine triphosphate (ATP)-binding cassette family of transporter proteins that is increasingly recognized as a relevant physiological and therapeutic target. Evaluation of modulators of ABCB6 activity would pave the way toward a more complete understanding of the significance of this transport process in tumor cell growth, proliferation and therapy-related drug resistance. In addition, this effort would improve our understanding of the function of ABCB6 in normal physiology with respect to heme biosynthesis, and cellular adaptation to metabolic demand and stress responses. To search for modulators of ABCB6, we developed a novel cell-based approach that, in combination with flow cytometric high-throughput screening (HTS), can be used to identify functional modulators of ABCB6. Accumulation of protoporphyrin, a fluorescent molecule, in wild-type ABCB6 expressing K562 cells, forms the basis of the HTS assay. Screening the Prestwick Chemical Library employing the HTS assay identified four compounds, benzethonium chloride, verteporfin, tomatine hydrochloride and piperlongumine, that reduced ABCB6 mediated cellular porphyrin levels. Validation of the identified compounds employing the hemin-agarose affinity chromatography and mitochondrial transport assays demonstrated that three out of the four compounds were capable of inhibiting ABCB6 mediated hemin transport into isolated mitochondria. However, only verteporfin and tomatine hydrochloride inhibited ABCB6's ability to compete with hemin as an ABCB6 substrate. This assay is therefore sensitive, robust, and suitable for automation in a high-throughput environment as demonstrated by our identification of selective functional modulators of ABCB6. Application of this assay to other libraries of synthetic compounds and natural products is expected to identify novel modulators of ABCB6 activity.

Modulation of aerial respiratory behaviour in a pond snail.

Science.gov (United States)

Lukowiak, Ken; Martens, Kara; Orr, Mike; Parvez, Kashif; Rosenegger, David; Sangha, Susan

2006-11-01

Aerial respiratory in Lymnaea is driven by a three-neuron CPG whose sufficiency and necessity has been directly demonstrated. While this CPG is 'hard-wired' it displays a tremendous amount of plasticity. That is, it is possible by employing specific training procedures to alter how it functions in a specific hypoxic environment. Thus, it is possible to study directly the causal mechanisms of long-term memory formation, forgetting, and modulation of the memory at a single cell level. Thus, it is possible to use a relatively simple three-neuron CPG to study not only important questions concerning regulation of important homeostatic mechanisms but to also use it to study how learning and non-declarative memory are mediated at a cellular level.

Molecular and cellular mechanisms of cadmium carcinogenesis

International Nuclear Information System (INIS)

Waisberg, Michael; Joseph, Pius; Hale, Beverley; Beyersmann, Detmar

2003-01-01

Cadmium is a heavy metal, which is widely used in industry, affecting human health through occupational and environmental exposure. In mammals, it exerts multiple toxic effects and has been classified as a human carcinogen by the International Agency for Research on Cancer. Cadmium affects cell proliferation, differentiation, apoptosis and other cellular activities. Cd 2+ does not catalyze Fenton-type reactions because it does not accept or donate electrons under physiological conditions, and it is only weakly genotoxic. Hence, indirect mechanisms are implicated in the carcinogenicity of cadmium. In this review multiple mechanisms are discussed, such as modulation of gene expression and signal transduction, interference with enzymes of the cellular antioxidant system and generation of reactive oxygen species (ROS), inhibition of DNA repair and DNA methylation, role in apoptosis and disruption of E-cadherin-mediated cell-cell adhesion. Cadmium affects both gene transcription and translation. The major mechanisms of gene induction by cadmium known so far are modulation of cellular signal transduction pathways by enhancement of protein phosphorylation and activation of transcription and translation factors. Cadmium interferes with antioxidant defense mechanisms and stimulates the production of reactive oxygen species, which may act as signaling molecules in the induction of gene expression and apoptosis. The inhibition of DNA repair processes by cadmium represents a mechanism by which cadmium enhances the genotoxicity of other agents and may contribute to the tumor initiation by this metal. The disruption of E-cadherin-mediated cell-cell adhesion by cadmium probably further stimulates the development of tumors. It becomes clear that there exist multiple mechanisms which contribute to the carcinogenicity of cadmium, although the relative weights of these contributions are difficult to estimate

An automation of design and modelling tasks in NX Siemens environment with original software - cost module

Science.gov (United States)

Zbiciak, R.; Grabowik, C.; Janik, W.

2015-11-01

The design-constructional process is a creation activity which strives to fulfil, as well as it possible at the certain moment of time, all demands and needs formulated by a user taking into account social, technical and technological advances. Engineer knowledge and skills and their inborn abilities have the greatest influence on the final product quality and cost. They have also deciding influence on product technical and economic value. Taking into account above it seems to be advisable to make software tools that support an engineer in the process of manufacturing cost estimation. The Cost module is built with analytical procedures which are used for relative manufacturing cost estimation. As in the case of the Generator module the Cost module was written in object programming language C# in Visual Studio environment. During the research the following eight factors, that have the greatest influence on overall manufacturing cost, were distinguished and defined: (i) a gear wheel teeth type it is straight or helicoidal, (ii) a gear wheel design shape A, B with or without wheel hub, (iii) a gear tooth module, (iv) teeth number, (v) gear rim width, (vi) gear wheel material, (vii) heat treatment or thermochemical treatment, (viii) accuracy class. Knowledge of parameters (i) to (v) is indispensable for proper modelling of 3D gear wheels models in CAD system environment. These parameters are also processed in the Cost module. The last three parameters it is (vi) to (viii) are exclusively used in the Cost module. The estimation of manufacturing relative cost is based on indexes calculated for each particular parameter. Estimated in this way the manufacturing relative cost gives an overview of design parameters influence on the final gear wheel manufacturing cost. This relative manufacturing cost takes values from 0.00 to 1,00 range. The bigger index value the higher relative manufacturing cost is. Verification whether the proposed algorithm of relative manufacturing

Enhancing the cellular uptake of Py–Im polyamides through next-generation aryl turns

OpenAIRE

Meier, Jordan L.; Montgomery, David C.; Dervan, Peter B.

2012-01-01

Pyrrole–imidazole (Py–Im) hairpin polyamides are a class of programmable, sequence-specific DNA binding oligomers capable of disrupting protein–DNA interactions and modulating gene expression in living cells. Methods to control the cellular uptake and nuclear localization of these compounds are essential to their application as molecular probes or therapeutic agents. Here, we explore modifications of the hairpin γ-aminobutyric acid turn unit as a means to enhance cellular uptake and biologica...

The cyto- and genotoxicity of organotin compounds is dependent on the cellular uptake capability

International Nuclear Information System (INIS)

Dopp, E.; Hartmann, L.M.; Recklinghausen, U. von; Florea, A.M.; Rabieh, S.; Shokouhi, B.; Hirner, A.V.; Obe, G.; Rettenmeier, A.W.

2007-01-01

Organotin compounds have been widely used as stabilizers and anti-fouling agents with the result that they are ubiquitously distributed in the environment. Organotins accumulate in the food chain and potential effects on human health are disquieting. It is not known as yet whether cell surface adsorption or accumulation within the cell, or indeed both is a prerequisite for the toxicity of organotin compounds. In this study, the alkylated tin derivatives monomethyltin trichloride (MMT), dimethyltin dichloride (DMT), trimethyltin chloride (TMT) and tetramethyltin (TetraMT) were investigated for cyto- and genotoxic effects in CHO-9 cells in relation to the cellular uptake. To identify genotoxic effects, induction of micronuclei (MN), chromosome aberrations (CA) and sister chromatid exchanges (SCE) were analyzed and the nuclear division index (NDI) was calculated. The cellular uptake was assessed using ICP-MS analysis. The toxicity of the tin compounds was also evaluated after forced uptake by electroporation. Our results show that uptake of the organotin compounds was generally low but dose-dependent. Only weak genotoxic effects were observed after exposure of cells to DMT and TMT. MMT and TetraMT were negative in the test systems. After forced uptake by electroporation MMT, DMT and TMT induced significant DNA damage at non-cytotoxic concentrations. The results presented here indicate a considerable toxicological potential of some organotin species but demonstrate clearly that the toxicity is modulated by the cellular uptake capability

Super-Resolution Microscopy: Shedding Light on the Cellular Plasma Membrane.

Science.gov (United States)

Stone, Matthew B; Shelby, Sarah A; Veatch, Sarah L

2017-06-14

Lipids and the membranes they form are fundamental building blocks of cellular life, and their geometry and chemical properties distinguish membranes from other cellular environments. Collective processes occurring within membranes strongly impact cellular behavior and biochemistry, and understanding these processes presents unique challenges due to the often complex and myriad interactions between membrane components. Super-resolution microscopy offers a significant gain in resolution over traditional optical microscopy, enabling the localization of individual molecules even in densely labeled samples and in cellular and tissue environments. These microscopy techniques have been used to examine the organization and dynamics of plasma membrane components, providing insight into the fundamental interactions that determine membrane functions. Here, we broadly introduce the structure and organization of the mammalian plasma membrane and review recent applications of super-resolution microscopy to the study of membranes. We then highlight some inherent challenges faced when using super-resolution microscopy to study membranes, and we discuss recent technical advancements that promise further improvements to super-resolution microscopy and its application to the plasma membrane.

Cellular phone interference with the operation of mechanical ventilators.

Science.gov (United States)

Shaw, Cheryl I; Kacmarek, Robert M; Hampton, Rickey L; Riggi, Vincent; El Masry, Ashraf; Cooper, Jeffrey B; Hurford, William E

2004-04-01

To determine whether a cellular phone would interfere with the operation of mechanical ventilators. Laboratory study. University medical center. Fourteen mechanical ventilators. We evaluated change in operation and malfunction of the mechanical ventilators. The cellular phone (Nokia 6120i) was computer controlled, operating at 828.750 MHz analog modulation. It was operated at 16, 40, 100, 250, and 600 mW, 30 cm from the floor and 30, 15, and ventilator. Six of the 14 ventilators tested malfunctioned when a cellular phone at maximum power output was placed ventilating when the cellular phone at maximum power output was placed ventilator. One ventilator doubled the ventilatory rate and another increased the displayed tidal volume from 350 to 1033 mL. In one of the infant ventilators, displayed tidal volume increased from 21 to 100 mL. In another ventilator, the high respiratory rate alarm sounded but the rate had not changed. In a controlled laboratory setting, cellular phones placed in close proximity to some commercially available intensive care ventilators can cause malfunctions, including irrecoverable cessation of ventilation. This is most likely to occur if the cellular phone is or =3 feet from all medical devices. The current electromagnetic compatibility standards for mechanical ventilators are inadequate to prevent malfunction. Manufacturers should ensure that their products are not affected by wireless technology even when placed immediately next to the device.

Modeling and Analysis of Cellular CDMA Forward Channel

National Research Council Canada - National Science Library

Tighe, Jan

2001-01-01

In this thesis, we develop the forward channel model for a DS-CDMA cellular system operating in a slow-flat Rayleigh fading and log normal shadowing environment, which incorporates the extended Hata...

Modulation of microRNA-mRNA Target Pairs by Human Papillomavirus 16 Oncoproteins

Directory of Open Access Journals (Sweden)

Mallory E. Harden

2017-01-01

Full Text Available The E6 and E7 proteins are the major oncogenic drivers encoded by high-risk human papillomaviruses (HPVs. While many aspects of the transforming activities of these proteins have been extensively studied, there are fewer studies that have investigated how HPV E6/E7 expression affects the expression of cellular noncoding RNAs. The goal of our study was to investigate HPV16 E6/E7 modulation of cellular microRNA (miR levels and to determine the potential consequences for cellular gene expression. We performed deep sequencing of small and large cellular RNAs in primary undifferentiated cultures of human foreskin keratinocytes (HFKs with stable expression of HPV16 E6/E7 or a control vector. After integration of the two data sets, we identified 51 differentially expressed cellular miRs associated with the modulation of 1,456 potential target mRNAs in HPV16 E6/E7-expressing HFKs. We discovered that the degree of differential miR expression in HFKs expressing HPV16 E6/E7 was not necessarily predictive of the number of corresponding mRNA targets or the potential impact on gene expression. Additional analyses of the identified miR-mRNA pairs suggest modulation of specific biological activities and biochemical pathways. Overall, our study supports the model that perturbation of cellular miR expression by HPV16 E6/E7 importantly contributes to the rewiring of cellular regulatory circuits by the high-risk HPV E6 and E7 proteins that contribute to oncogenic transformation.

Cellular potts models multiscale extensions and biological applications

CERN Document Server

Scianna, Marco

2013-01-01

A flexible, cell-level, and lattice-based technique, the cellular Potts model accurately describes the phenomenological mechanisms involved in many biological processes. Cellular Potts Models: Multiscale Extensions and Biological Applications gives an interdisciplinary, accessible treatment of these models, from the original methodologies to the latest developments. The book first explains the biophysical bases, main merits, and limitations of the cellular Potts model. It then proposes several innovative extensions, focusing on ways to integrate and interface the basic cellular Potts model at the mesoscopic scale with approaches that accurately model microscopic dynamics. These extensions are designed to create a nested and hybrid environment, where the evolution of a biological system is realistically driven by the constant interplay and flux of information between the different levels of description. Through several biological examples, the authors demonstrate a qualitative and quantitative agreement with t...

Error performance analysis in downlink cellular networks with interference management

KAUST Repository

Afify, Laila H.

2015-05-01

Modeling aggregate network interference in cellular networks has recently gained immense attention both in academia and industry. While stochastic geometry based models have succeeded to account for the cellular network geometry, they mostly abstract many important wireless communication system aspects (e.g., modulation techniques, signal recovery techniques). Recently, a novel stochastic geometry model, based on the Equivalent-in-Distribution (EiD) approach, succeeded to capture the aforementioned communication system aspects and extend the analysis to averaged error performance, however, on the expense of increasing the modeling complexity. Inspired by the EiD approach, the analysis developed in [1] takes into consideration the key system parameters, while providing a simple tractable analysis. In this paper, we extend this framework to study the effect of different interference management techniques in downlink cellular network. The accuracy of the proposed analysis is verified via Monte Carlo simulations.

A novel flow cytometric HTS assay reveals functional modulators of ATP binding cassette transporter ABCB6.

Directory of Open Access Journals (Sweden)

Kishore Polireddy

Full Text Available ABCB6 is a member of the adenosine triphosphate (ATP-binding cassette family of transporter proteins that is increasingly recognized as a relevant physiological and therapeutic target. Evaluation of modulators of ABCB6 activity would pave the way toward a more complete understanding of the significance of this transport process in tumor cell growth, proliferation and therapy-related drug resistance. In addition, this effort would improve our understanding of the function of ABCB6 in normal physiology with respect to heme biosynthesis, and cellular adaptation to metabolic demand and stress responses. To search for modulators of ABCB6, we developed a novel cell-based approach that, in combination with flow cytometric high-throughput screening (HTS, can be used to identify functional modulators of ABCB6. Accumulation of protoporphyrin, a fluorescent molecule, in wild-type ABCB6 expressing K562 cells, forms the basis of the HTS assay. Screening the Prestwick Chemical Library employing the HTS assay identified four compounds, benzethonium chloride, verteporfin, tomatine hydrochloride and piperlongumine, that reduced ABCB6 mediated cellular porphyrin levels. Validation of the identified compounds employing the hemin-agarose affinity chromatography and mitochondrial transport assays demonstrated that three out of the four compounds were capable of inhibiting ABCB6 mediated hemin transport into isolated mitochondria. However, only verteporfin and tomatine hydrochloride inhibited ABCB6's ability to compete with hemin as an ABCB6 substrate. This assay is therefore sensitive, robust, and suitable for automation in a high-throughput environment as demonstrated by our identification of selective functional modulators of ABCB6. Application of this assay to other libraries of synthetic compounds and natural products is expected to identify novel modulators of ABCB6 activity.

Evaluation of Different Parameters of Humoral and Cellular Immune Responses in HIV Serodiscordant Heterosexual Couples: Humoral Response Potentially Implicated in Modulating Transmission Rates

Directory of Open Access Journals (Sweden)

María Julia Ruiz

2017-12-01

Full Text Available As the HIV/AIDS pandemic still progresses, understanding the mechanisms governing viral transmission as well as protection from HIV acquisition is fundamental. In this context, cohorts of HIV serodiscordant heterosexual couples (SDC represent a unique tool. The present study was aimed to evaluate specific parameters of innate, cellular and humoral immune responses in SDC. Specifically, plasma levels of cytokines and chemokines, HIV-specific T-cell responses, gp120-specific IgG and IgA antibodies, and HIV-specific antibody-dependent cellular cytotoxicity (ADCC activity were assessed in nine HIV-exposed seronegative individuals (ESN and their corresponding HIV seropositive partners (HIV+-P, in eighteen chronically infected HIV subjects (C, nine chronically infected subjects known to be HIV transmitters (CT and ten healthy HIV− donors (HD. Very low magnitude HIV-specific cellular responses were found in two out of six ESN. Interestingly, HIV+-P had the highest ADCC magnitude, the lowest IgA levels and the highest IgG/IgA ratio, all compared to CT. Positive correlations between CD4+ T-cell counts and both IgG/IgA ratios and %ADCC killing uniquely distinguished HIV+-P. Additionally, evidence of IgA interference with ADCC responses from HIV+-P and CT is provided. These data suggest for the first time a potential role of ADCC and/or gp120-specific IgG/IgA balance in modulating heterosexual transmission. In sum, this study provides key information to understand the host factors that influence viral transmission, which should be considered in both the development of prophylactic vaccines and novel immunotherapies for HIV-1 infection.

Tension and robustness in multitasking cellular networks.

Directory of Open Access Journals (Sweden)

Jeffrey V Wong

Full Text Available Cellular networks multitask by exhibiting distinct, context-dependent dynamics. However, network states (parameters that generate a particular dynamic are often sub-optimal for others, defining a source of "tension" between them. Though multitasking is pervasive, it is not clear where tension arises, what consequences it has, and how it is resolved. We developed a generic computational framework to examine the source and consequences of tension between pairs of dynamics exhibited by the well-studied RB-E2F switch regulating cell cycle entry. We found that tension arose from task-dependent shifts in parameters associated with network modules. Although parameter sets common to distinct dynamics did exist, tension reduced both their accessibility and resilience to perturbation, indicating a trade-off between "one-size-fits-all" solutions and robustness. With high tension, robustness can be preserved by dynamic shifting of modules, enabling the network to toggle between tasks, and by increasing network complexity, in this case by gene duplication. We propose that tension is a general constraint on the architecture and operation of multitasking biological networks. To this end, our work provides a framework to quantify the extent of tension between any network dynamics and how it affects network robustness. Such analysis would suggest new ways to interfere with network elements to elucidate the design principles of cellular networks.

Molecular imaging of drug-modulated protein-protein interactions in living subjects.

Science.gov (United States)

Paulmurugan, Ramasamy; Massoud, Tarik F; Huang, Jing; Gambhir, Sanjiv S

2004-03-15

Networks of protein interactions mediate cellular responses to environmental stimuli and direct the execution of many different cellular functional pathways. Small molecules synthesized within cells or recruited from the external environment mediate many protein interactions. The study of small molecule-mediated interactions of proteins is important to understand abnormal signal transduction pathways in cancer and in drug development and validation. In this study, we used split synthetic renilla luciferase (hRLUC) protein fragment-assisted complementation to evaluate heterodimerization of the human proteins FRB and FKBP12 mediated by the small molecule rapamycin. The concentration of rapamycin required for efficient dimerization and that of its competitive binder ascomycin required for dimerization inhibition were studied in cell lines. The system was dually modulated in cell culture at the transcription level, by controlling nuclear factor kappaB promoter/enhancer elements using tumor necrosis factor alpha, and at the interaction level, by controlling the concentration of the dimerizer rapamycin. The rapamycin-mediated dimerization of FRB and FKBP12 also was studied in living mice by locating, quantifying, and timing the hRLUC complementation-based bioluminescence imaging signal using a cooled charged coupled device camera. This split reporter system can be used to efficiently screen small molecule drugs that modulate protein-protein interactions and also to assess drugs in living animals. Both are essential steps in the preclinical evaluation of candidate pharmaceutical agents targeting protein-protein interactions, including signaling pathways in cancer cells.

Characteristics of Middle School Students Learning Actions in Outdoor Mathematical Activities with the Cellular Phone

Science.gov (United States)

Daher, Wajeeh; Baya'a, Nimer

2012-01-01

Learning in the cellular phone environment enables utilizing the multiple functions of the cellular phone, such as mobility, availability, interactivity, verbal and voice communication, taking pictures or recording audio and video, measuring time and transferring information. These functions together with mathematics-designated cellular phone…

Immune modulation in the blue mussel Mytilus edulis exposed to North Sea produced water

Energy Technology Data Exchange (ETDEWEB)

Hannam, M.L., E-mail: marie.hannam@plymouth.ac.u [Ecotoxicology and Stress Biology Research Centre, School of Biological Sciences, University of Plymouth, Drake Circus, Plymouth, Devon, PL4 8AA (United Kingdom); Bamber, S.D.; Sundt, R.C. [IRIS - Biomiljo, Mekjarvik 12, 4070 Randaberg (Norway); Galloway, T.S. [School of Biosciences, University of Exeter, Hatherly Laboratories, Prince of Wales Road, Exeter, EX4 4PS (United Kingdom)

2009-06-15

The discharge of oil well produced water (PW) provides a constant source of contaminants to the marine environment including polycyclic aromatic hydrocarbons, alkylated phenols, metals and production chemicals. High concentrations of PW cause adverse effects to exposed biota, including reduced survival, growth and reproduction. Here we explore the effects of PW on immune function in the blue mussel, Mytilus edulis. Mussels were exposed for 21 days to sublethal PW concentrations (0.125-0.5%) and cellular parameters were measured. Cell viability, phagocytosis and cytotoxicity were inhibited after exposure to 0.25% and 0.5% PW, whilst the 0.125% PW treatment produced significant increases in these biomarker responses. This biphasic response was only observed after 7 days exposure; longer exposure periods led to a reduction in immune parameters. Results indicate that PW concentrations close to the discharge point cause modulation to cellular immunity. The implications for longer-term disease resistance are discussed. - Exposure to produced water alters immune function in the sentinel species Mytilus edulis.

Immune modulation in the blue mussel Mytilus edulis exposed to North Sea produced water

International Nuclear Information System (INIS)

Hannam, M.L.; Bamber, S.D.; Sundt, R.C.; Galloway, T.S.

2009-01-01

The discharge of oil well produced water (PW) provides a constant source of contaminants to the marine environment including polycyclic aromatic hydrocarbons, alkylated phenols, metals and production chemicals. High concentrations of PW cause adverse effects to exposed biota, including reduced survival, growth and reproduction. Here we explore the effects of PW on immune function in the blue mussel, Mytilus edulis. Mussels were exposed for 21 days to sublethal PW concentrations (0.125-0.5%) and cellular parameters were measured. Cell viability, phagocytosis and cytotoxicity were inhibited after exposure to 0.25% and 0.5% PW, whilst the 0.125% PW treatment produced significant increases in these biomarker responses. This biphasic response was only observed after 7 days exposure; longer exposure periods led to a reduction in immune parameters. Results indicate that PW concentrations close to the discharge point cause modulation to cellular immunity. The implications for longer-term disease resistance are discussed. - Exposure to produced water alters immune function in the sentinel species Mytilus edulis.

Mir-513a-3p contributes to the controlling of cellular migration processes in the A549 lung tumor cells by modulating integrin β-8 expression.

Science.gov (United States)

da Silveira, Marina Bonfogo; Lima, Kelvin Furtado; da Silva, Andrea Renata; Dos Santos, Robson Augusto Souza; Moraes, Karen C M

2017-12-04

Lung tumors are a frequent type of cancer in humans and a leading cause of death, and the late diagnostic contributes to high mortality rates. New therapeutic strategies are needed, and the heptapeptide angiotensin-(1-7) [ang-(1-7)] demonstrated the ability to control cancer growth rates and migration in vitro and in vivo. However, the possible use of the heptapeptide in clinical trials demands deeper analyses to elucidate molecular mechanisms of its effect in the target cells. In this study, we investigated relevant elements that control pro-inflammatory environment and cellular migration, focusing in the post-transcription mechanism using lung tumor cell line. In our cellular model, the microRNA-513a-3p was identified as a novel element targeting ITG-β8, thereby controlling the protein level and its molecular function in the controlling of migration and pro-inflammatory environment. These findings provide useful information for future studies, using miR-513a-3p as an innovative molecular tool to control lung tumor cell migration, which will support more effective clinical treatment of the patients with the widely used chemotherapeutic agents, increasing survival rates.

Role of Neuroinflammation in Amyotrophic Lateral Sclerosis: Cellular Mechanisms and Therapeutic Implications

Directory of Open Access Journals (Sweden)

Jia Liu

2017-08-01

Full Text Available Amyotrophic lateral sclerosis (ALS is a progressive neurodegenerative disease that affects upper motor neurons (MNs comprising the corticospinal tract and lower MNs arising from the brain stem nuclei and ventral roots of the spinal cord, leading to fatal paralysis. Currently, there are no effective therapies for ALS. Increasing evidence indicates that neuroinflammation plays an important role in ALS pathogenesis. The neuroinflammation in ALS is characterized by infiltration of lymphocytes and macrophages, activation of microglia and reactive astrocytes, as well as the involvement of complement. In this review, we focus on the key cellular players of neuroinflammation during the pathogenesis of ALS by discussing not only their detrimental roles but also their immunomodulatory actions. We will summarize the pharmacological therapies for ALS that target neuroinflammation, as well as recent advances in the field of stem cell therapy aimed at modulating the inflammatory environment to preserve the remaining MNs in ALS patients and animal models of the disease.

Multichip module technology for automotive application

Science.gov (United States)

Johnson, R. Wayne; Evans, John L.; Bosley, Larry

1995-01-01

Advancements in multichip module technology are creating design freedoms previously unavailable to design engineers. These advancements are opening new markets for laminate based multichip module products. In particular, material improvements in laminate printed wiring boards are allowing multichip module technology to meet more stringent environmental conditions. In addition, improvements in encapsulants and adhesives are enhancing the capabilities of multichip module technology to meet harsh environment. Furthermore, improvements in manufacturing techniques are providing the reliability improvements necessary for use in high quality electronic systems. These advances are making multichip module technology viable for high volume, harsh environment applications like under-the-hood automotive electronics. This paper will provide a brief review of multichip module technology, a discussion of specific research activities with Chrysler for use of multichip modules in automotive engine controllers and finally a discussion of prototype multichip modules fabricated and tested.

Cellular immobilization within microfluidic microenvironments: dielectrophoresis with polyelectrolyte multilayers.

Science.gov (United States)

Forry, Samuel P; Reyes, Darwin R; Gaitan, Michael; Locascio, Laurie E

2006-10-25

The development of biomimetic microenvironments will improve cell culture techniques by enabling in vitro cell cultures that mimic in vivo behavior; however, experimental control over attachment, cellular position, or intercellular distances within such microenvironments remains challenging. We report here the rapid and controllable immobilization of suspended mammalian cells within microfabricated environments using a combination of electronic (dielectrophoresis, DEP) and chemical (polyelectrolyte multilayers, PEMS) forces. While cellular position within the microsystem is rapidly patterned via intermittent DEP trapping, persistent adhesion after removal of electronic forces is enabled by surface treatment with PEMS that are amenable to cellular attachment. In contrast to DEP trapping alone, persistent adhesion enables the soluble microenvironment to be systematically varied, facilitating the use of soluble probes of cell state and enabling cellular characterization in response to various soluble stimuli.

Glutathione modulation in cancer treatment: will it work

International Nuclear Information System (INIS)

Mitchell, J.B.; Cook, J.A.; DeGraff, W.; Glatstein, E.; Russo, A.

1989-01-01

Glutathione (GSH) assumes a pivotal role in numerous cellular functions including bioreductive reactions, maintenance of enzyme activity, amino acid transport, protection from harmful oxidative species, and detoxification of xenobiotics. The importance of GSH in modifying the cellular response to several anti-cancer treatment modalities has become better appreciated with the introduction of agents which can either decrease or elevate GSH levels in cells and tissues. In general, GSH depletion has been demonstrated to further enhance the cytotoxicity of several chemotherapy drugs and nitroimidazole hypoxic cell radiosensitizers. Conversely, GSH elevation affords varying degrees of protection. Whether or not GSH modulating agents will be useful as an adjuvant to selected cancer treatment modalities will depend on whether differential levels of GSH can be achieved in tumor versus normal tissues. Accurate GSH measurements in tumor and normal tissues will be required to adequately use and interpret the results of clinical studies where GSH modulating agents are employed. Precise tumor GSH measurements pose a considerable challenge due to the complicated cellular makeup of tumors.44 references

Modulation of human IAPP fibrillation: cosolutes, crowders and chaperones.

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Gao, Mimi; Estel, Kathrin; Seeliger, Janine; Friedrich, Ralf P; Dogan, Susanne; Wanker, Erich E; Winter, Roland; Ebbinghaus, Simon

2015-04-07

The cellular environment determines the structure and function of proteins. Marginal changes of the environment can severely affect the energy landscape of protein folding. However, despite the important role of chaperones on protein folding, less is known about chaperonal modulation of protein aggregation and fibrillation considering different classes of chaperones. We find that the pharmacological chaperone O4, the chemical chaperone proline as well as the protein chaperone serum amyloid P component (SAP) are inhibitors of the type 2 diabetes mellitus-related aggregation process of islet amyloid polypeptide (IAPP). By applying biophysical methods such as thioflavin T fluorescence spectroscopy, fluorescence anisotropy, total reflection Fourier-transform infrared spectroscopy, circular dichroism spectroscopy and atomic force microscopy we analyse and compare their inhibition mechanism. We demonstrate that the fibrillation reaction of human IAPP is strongly inhibited by formation of globular, amorphous assemblies by both, the pharmacological and the protein chaperones. We studied the inhibition mechanism under cell-like conditions by using the artificial crowding agents Ficoll 70 and sucrose. Under such conditions the suppressive effect of proline was decreased, whereas the pharmacological chaperone remains active.

TNF and TNF Receptor Superfamily Members in HIV infection: New Cellular Targets for Therapy?

Directory of Open Access Journals (Sweden)

Amit Kumar

2013-01-01

Full Text Available Tumor necrosis factor (TNF and TNF receptors (TNFR superfamily members are engaged in diverse cellular phenomena such as cellular proliferation, morphogenesis, apoptosis, inflammation, and immune regulation. Their role in regulating viral infections has been well documented. Viruses have evolved with numerous strategies to interfere with TNF-mediated signaling indicating the importance of TNF and TNFR superfamily in viral pathogenesis. Recent research reports suggest that TNF and TNFRs play an important role in the pathogenesis of HIV. TNFR signaling modulates HIV replication and HIV proteins interfere with TNF/TNFR pathways. Since immune activation and inflammation are the hallmark of HIV infection, the use of TNF inhibitors can have significant impact on HIV disease progression. In this review, we will describe how HIV infection is modulated by signaling mediated through members of TNF and TNFR superfamily and in turn how these latter could be targeted by HIV proteins. Finally, we will discuss the emerging therapeutics options based on modulation of TNF activity that could ultimately lead to the cure of HIV-infected patients.

Modulation of DNA methylation by human papillomavirus E6 and E7 oncoproteins in cervical cancer

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Sen, Prakriti; Ganguly, Pooja; Ganguly, Niladri

2018-01-01

Human papillomaviruses (HPVs) are double stranded circular DNA viruses that infect cutaneous and mucosal epithelial cells. Almost 99% of cervical cancer has a HPV infection. The early oncoproteins E6 and E7 are important in this cellular transformation process. Epigenetic mechanisms have long been known to result in decisive alterations in DNA, leading to alterations in DNA-protein interactions, alterations in chromatin structure and compaction and significant alterations in gene expression. The enzymes responsible for these epigenetic modifications are DNA methyl transferases (DNMTs), histone acetylases and deacetylases. Epigenetics has an important role in cancer development by modifying the cellular micro environment. In this review, the authors discuss the role of HPV oncoproteins E6 and E7 in modulating the epigenetic mechanisms inside the host cell. The oncoproteins induce the expression of DNMTs which lead to aberrant DNA methylations and disruption of the normal epigenetic processes. The E7 oncoprotein may additionally directly bind and induce methyl transferase activity of the enzyme. These modulations lead to altered gene expression levels, particularly the genes involved in apoptosis, cell cycle and cell adhesion. In addition, the present review discusses how epigenetic mechanisms may be targeted for possible therapeutic interventions for HPV mediated cervical cancer. PMID:29285184

Load-aware modeling for uplink cellular networks in a multi-channel environment

KAUST Repository

Alammouri, Ahmad; Elsawy, Hesham; Alouini, Mohamed-Slim

2014-01-01

We exploit tools from stochastic geometry to develop a tractable analytical approach for modeling uplink cellular networks. The developed model is load aware and accounts for per-user power control as well as the limited transmit power constraint

Two conserved modules of Schizosaccharomyces pombe Mediator regulate distinct cellular pathways

DEFF Research Database (Denmark)

Linder, Tomas; Rasmussen, Nina; Samuelsen, Camilla O

2008-01-01

Mediator is an evolutionary conserved coregulator complex required for transcription of almost all RNA polymerase II-dependent genes. The Schizosaccharomyces pombe Mediator consists of two dissociable components-a core complex organized into a head and middle domain as well as the Cdk8 regulatory...... subcomplex. In this work we describe a functional characterization of the S. pombe Mediator. We report the identification of the S. pombe Med20 head subunit and the isolation of ts alleles of the core head subunit encoding med17+. Biochemical analysis of med8(ts), med17(ts), Deltamed18, Deltamed20...... and Deltamed27 alleles revealed a stepwise head domain molecular architecture. Phenotypical analysis of Cdk8 and head module alleles including expression profiling classified the Mediator mutant alleles into one of two groups. Cdk8 module mutants flocculate due to overexpression of adhesive cell...

Homotopy theory of modules over diagrams of rings

Directory of Open Access Journals (Sweden)

J. P. C. Greenlees

2014-09-01

Full Text Available Given a diagram of rings, one may consider the category of modules over them. We are interested in the homotopy theory of categories of this type: given a suitable diagram of model categories ℳ( (as runs through the diagram, we consider the category of diagrams where the object ( at comes from ℳ(. We develop model structures on such categories of diagrams and Quillen adjunctions that relate categories based on different diagram shapes. Under certain conditions, cellularizations (or right Bousfield localizations of these adjunctions induce Quillen equivalences. As an application we show that a cellularization of a category of modules over a diagram of ring spectra (or differential graded rings is Quillen equivalent to modules over the associated inverse limit of the rings. Another application of the general machinery here is given in work by the authors on algebraic models of rational equivariant spectra. Some of this material originally appeared in the preprint “An algebraic model for rational torus-equivariant stable homotopy theory”, arXiv:1101.2511, but has been generalized here.

Development of second generation peptides modulating cellular adiponectin receptor responses

Directory of Open Access Journals (Sweden)

Laszlo eOtvos

2014-10-01

Full Text Available The adipose tissue participates in the regulation of energy homeostasis as an important endocrine organ that secretes a number of biologically active adipokines, including adiponectin. Recently we developed and characterized a first-in-class peptide-based adiponectin receptor agonist by using in vitro and in vivo models of glioblastoma and breast cancer (BC. In the current study, we further explored the effects of peptide ADP355 in additional cellular models and found that ADP355 inhibited chronic myeloid leukemia (CML cell proliferation and renal myofibroblast differentiation with mid-nanomolar IC50 values. According to molecular modeling calculations, ADP355 was remarkably flexible in the global minimum with a turn present in the middle of the peptide. Considering these structural features of ADP355 and the fact that adiponectin normally circulates as multimeric complexes, we developed and tested the activity of a linear branched dimer (ADP399. The dimer exhibited approximately 20-fold improved cellular activity inhibiting K562 CML and MCF-7 cell growth with high pM - low nM relative IC50 values. Biodistribution studies suggested superior tissue dissemination of both peptides after subcutaneous administration relative to intraperitoneal inoculation. After screening of a 397-member adiponectin active site library, a novel octapeptide (ADP400 was designed that counteracted 10-1000 nM ADP355- and ADP399-mediated effects on CML and BC cell growth at nanomolar concentrations. ADP400 induced mitogenic effects in MCF-7 BC cells perhaps due to antagonizing endogenous adiponectin actions or acting as an inverse agonist. While the linear dimer agonist ADP399 meets pharmacological criteria of a contemporary peptide drug lead, the peptide showing antagonist activity (ADP400 at similar concentrations will be an important target validation tool to study adiponectin functions.

Development of second generation peptides modulating cellular adiponectin receptor responses

Science.gov (United States)

Otvos, Laszlo; Knappe, Daniel; Hoffmann, Ralf; Kovalszky, Ilona; Olah, Julia; Hewitson, Tim; Stawikowska, Roma; Stawikowski, Maciej; Cudic, Predrag; Lin, Feng; Wade, John; Surmacz, Eva; Lovas, Sandor

2014-10-01

The adipose tissue participates in the regulation of energy homeostasis as an important endocrine organ that secretes a number of biologically active adipokines, including adiponectin. Recently we developed and characterized a first-in-class peptide-based adiponectin receptor agonist by using in vitro and in vivo models of glioblastoma and breast cancer (BC). In the current study, we further explored the effects of peptide ADP355 in additional cellular models and found that ADP355 inhibited chronic myeloid leukemia (CML) cell proliferation and renal myofibroblast differentiation with mid-nanomolar IC50 values. According to molecular modeling calculations, ADP355 was remarkably flexible in the global minimum with a turn present in the middle of the peptide. Considering these structural features of ADP355 and the fact that adiponectin normally circulates as multimeric complexes, we developed and tested the activity of a linear branched dimer (ADP399). The dimer exhibited approximately 20-fold improved cellular activity inhibiting K562 CML and MCF-7 cell growth with high pM - low nM relative IC50 values. Biodistribution studies suggested superior tissue dissemination of both peptides after subcutaneous administration relative to intraperitoneal inoculation. After screening of a 397-member adiponectin active site library, a novel octapeptide (ADP400) was designed that counteracted 10-1000 nM ADP355- and ADP399-mediated effects on CML and BC cell growth at nanomolar concentrations. ADP400 induced mitogenic effects in MCF-7 BC cells perhaps due to antagonizing endogenous adiponectin actions or acting as an inverse agonist. While the linear dimer agonist ADP399 meets pharmacological criteria of a contemporary peptide drug lead, the peptide showing antagonist activity (ADP400) at similar concentrations will be an important target validation tool to study adiponectin functions.

Physical Property Control on the Cellular Uptake Pathway and Spatial Distribution of Nanoparticles in Cells.

Science.gov (United States)

Ahn, Sungsook; Seo, Eunseok; Kim, Ki Hean; Lee, Sang Joon

2015-06-01

Nanoparticles have been developed in broad biomedical research in terms of effective cellular interactions to treat and visualize diseased cells. Considering the charge and polar functional groups of proteins that are embedded in cellular membranes, charged nanoparticles have been strategically developed to enhance electrostatic cellular interactions. In this study, we show that cellular uptake efficiency, pathway, and spatial distribution of gold nanoparticles in a cell are significantly modulated based on the surface condition of gold nanoparticles and human cancer cells that were tuned by controlling the pH of the medium and by introducing an electron beam. Cellular uptake efficiency is increased when electrostatic attraction is induced between the cells and the gold nanoparticles. Cell surface modification changes the cellular uptake pathways of the gold nanoparticles and concentrates the gold nanoparticles at the membrane region. Surface modification of the gold nanoparticles also contributes to deep penetration and homogeneous spatial distributions in a cell.

Intermolecular masking of the HIV-1 Rev NLS by the cellular protein HIC: Novel insights into the regulation of Rev nuclear import.

LENUS (Irish Health Repository)

Gu, Lili

2011-03-14

Abstract Background The HIV-1 regulatory protein Rev, which is essential for viral replication, mediates the nuclear export of unspliced viral transcripts. Rev nuclear function requires active nucleocytoplasmic shuttling, and Rev nuclear import is mediated by the recognition of its Nuclear Localisation Signal (NLS) by multiple import factors, which include transportin and importin β. However, it remains unclear which nuclear import pathway(s) predominate in vivo, and the cellular environment that modulates Rev nucleocytoplasmic shuttling remains to be characterised. Results In our study, we have identified the cellular protein HIC (Human I-mfa domain-Containing protein) as a novel interactor of HIV-1 Rev. We demonstrate that HIC selectively interferes with Rev NLS interaction with importin β and impedes its nuclear import and function, but does not affect Rev nuclear import mediated by transportin. Hence, the molecular determinants mediating Rev-NLS recognition by importin β and transportin appear to be distinct. Furthermore, we have employed HIC and M9 M, a peptide specifically designed to inhibit the transportin-mediated nuclear import pathway, to characterise Rev nuclear import pathways within different cellular environments. Remarkably, we could show that in 293T, HeLa, COS7, Jurkat, U937, THP-1 and CEM cells, Rev nuclear import is cell type specific and alternatively mediated by transportin or importin β, in a mutually exclusive fashion. Conclusions Rev cytoplasmic sequestration by HIC may represent a novel mechanism for the control of Rev function. These studies highlight that the multivalent nature of the Rev NLS for different import receptors enables Rev to adapt its nuclear trafficking strategy.

Cellular telephone-based wide-area radiation detection network

Science.gov (United States)

Craig, William W [Pittsburg, CA; Labov, Simon E [Berkeley, CA

2009-06-09

A network of radiation detection instruments, each having a small solid state radiation sensor module integrated into a cellular phone for providing radiation detection data and analysis directly to a user. The sensor module includes a solid-state crystal bonded to an ASIC readout providing a low cost, low power, light weight compact instrument to detect and measure radiation energies in the local ambient radiation field. In particular, the photon energy, time of event, and location of the detection instrument at the time of detection is recorded for real time transmission to a central data collection/analysis system. The collected data from the entire network of radiation detection instruments are combined by intelligent correlation/analysis algorithms which map the background radiation and detect, identify and track radiation anomalies in the region.

Building mathematics cellular phone learning communities

Directory of Open Access Journals (Sweden)

Wajeeh M. Daher

2011-04-01

Full Text Available Researchers emphasize the importance of maintaining learning communities and environments. This article describes the building and nourishment of a learning community, one comprised of middle school students who learned mathematics out-of-class using the cellular phone. The building of the learning community was led by three third year pre-service teachers majoring in mathematics and computers. The pre-service teachers selected thirty 8th grade students to learn mathematics with the cellular phone and be part of a learning community experimenting with this learning. To analyze the building and development stages of the cellular phone learning community, two models of community building stages were used; first the team development model developed by Tuckman (1965, second the life cycle model of a virtual learning community developed by Garber (2004. The research findings indicate that a learning community which is centered on a new technology has five 'life' phases of development: Pre-birth, birth, formation, performing, and maturity. Further, the research finding indicate that the norms that were encouraged by the preservice teachers who initiated the cellular phone learning community resulted in a community which developed, nourished and matured to be similar to a community of experienced applied mathematicians who use mathematical formulae to study everyday phenomena.

Toxicology and cellular effect of manufactured nanomaterials

Science.gov (United States)

Chen, Fanqing

2014-07-22

The increasing use of nanotechnology in consumer products and medical applications underlies the importance of understanding its potential toxic effects to people and the environment. Herein are described methods and assays to predict and evaluate the cellular effects of nanomaterial exposure. Exposing cells to nanomaterials at cytotoxic doses induces cell cycle arrest and increases apoptosis/necrosis, activates genes involved in cellular transport, metabolism, cell cycle regulation, and stress response. Certain nanomaterials induce genes indicative of a strong immune and inflammatory response within skin fibroblasts. Furthermore, the described multiwall carbon nanoonions (MWCNOs) can be used as a therapeutic in the treatment of cancer due to its cytotoxicity.

HDACi: cellular effects, opportunities for restorative dentistry.

LENUS (Irish Health Repository)

Duncan, H F

2011-12-01

Acetylation of histone and non-histone proteins alters gene expression and induces a host of cellular effects. The acetylation process is homeostatically balanced by two groups of cellular enzymes, histone acetyltransferases (HATs) and histone deacetylases (HDACs). HAT activity relaxes the structure of the human chromatin, rendering it transcriptionally active, thereby increasing gene expression. In contrast, HDAC activity leads to gene silencing. The enzymatic balance can be \\'tipped\\' by histone deacetylase inhibitors (HDACi), leading to an accumulation of acetylated proteins, which subsequently modify cellular processes including stem cell differentiation, cell cycle, apoptosis, gene expression, and angiogenesis. There is a variety of natural and synthetic HDACi available, and their pleiotropic effects have contributed to diverse clinical applications, not only in cancer but also in non-cancer areas, such as chronic inflammatory disease, bone engineering, and neurodegenerative disease. Indeed, it appears that HDACi-modulated effects may differ between \\'normal\\' and transformed cells, particularly with regard to reactive oxygen species accumulation, apoptosis, proliferation, and cell cycle arrest. The potential beneficial effects of HDACi for health, resulting from their ability to regulate global gene expression by epigenetic modification of DNA-associated proteins, also offer potential for application within restorative dentistry, where they may promote dental tissue regeneration following pulpal damage.

A comparative study on fluorescent cholesterol analogs as versatile cellular reporters

DEFF Research Database (Denmark)

Sezgin, Erdinc; Betul Can, Fatma; Schneider, Falk

2016-01-01

Cholesterol is a crucial component of cellular membranes, but knowledge of its intracellular dynamics is scarce. Thus, it is of utmost interest to develop tools for visualization of cholesterol organization and dynamics in cells and tissues. For this purpose, many studies make use of fluorescently...... for their performance in cellular assays: 1) plasma membrane incorporation, specifically the preference for more ordered membrane environments in phase separated giant unilamellar vesicles (GUVs) and giant plasma membrane vesicles (GPMVs); 2) cellular trafficking, specifically subcellular localization in Niemann-Pick C...... in the intracellular trafficking assay. However, none showed positive performance in all assays. Our results constitute a concise guide for the careful use of fluorescent cholesterol analogs in visualizing cellular cholesterol dynamics....

Cellular energy allocation in zebra mussels exposed along a pollution gradient: linking cellular effects to higher levels of biological organization.

Science.gov (United States)

Smolders, R; Bervoets, L; De Coen, W; Blust, R

2004-05-01

Organisms exposed to suboptimal environments incur a cost of dealing with stress in terms of metabolic resources. The total amount of energy available for maintenance, growth and reproduction, based on the biochemical analysis of the energy budget, may provide a sensitive measure of stress in an organism. While the concept is clear, linking cellular or biochemical responses to the individual and population or community level remains difficult. The aim of this study was to validate, under field conditions, using cellular energy budgets [i.e. changes in glycogen-, lipid- and protein-content and mitochondrial electron transport system (ETS)] as an ecologically relevant measurement of stress by comparing these responses to physiological and organismal endpoints. Therefore, a 28-day in situ bioassay with zebra mussels (Dreissena polymorpha) was performed in an effluent-dominated stream. Five locations were selected along the pollution gradient and compared with a nearby (reference) site. Cellular Energy Allocation (CEA) served as a biomarker of cellular energetics, while Scope for Growth (SFG) indicated effects on a physiological level and Tissue Condition Index and wet tissue weight/dry tissue weight ratio were used as endpoints of organismal effects. Results indicated that energy budgets at a cellular level of biological organization provided the fastest and most sensitive response and energy budgets are a relevant currency to extrapolate cellular effects to higher levels of biological organization within the exposed mussels.

Unlike physical exercise, modified environment increases the lifespan of SOD1G93A mice however both conditions induce cellular changes.

Directory of Open Access Journals (Sweden)

Yannick N Gerber

Full Text Available Amyotrophic lateral sclerosis (ALS is characterized by a gradual muscular paralysis resulting from progressive motoneurons death. ALS etiology remains unknown although it has been demonstrated to be a multifactorial disease involving several cellular partners. There is currently no effective treatment. Even if the effect of exercise is under investigation for many years, whether physical exercise is beneficial or harmful is still under debate.We investigated the effect of three different intensities of running exercises on the survival of SOD1(G93A mice. At the early-symptomatic stage (P60, males were isolated and randomly assigned to 5 conditions: 2 sedentary groups ("sedentary" and "sedentary treadmill" placed on the inert treadmill, and 3 different training intensity groups (5 cm/s, 10 cm/s and 21 cm/s; 15 min/day, 5days/week. We first demonstrated that an appropriate "control" of the environment is of the utmost importance since comparison of the two sedentary groups evidenced an 11.6% increase in survival in the "sedentary treadmill" group. Moreover, we showed by immunohistochemistry that this increased lifespan is accompanied with motoneurons survival and increased glial reactivity in the spinal cord. In a second step, we showed that when compared with the proper control, all three running-based training did not modify lifespan of the animals, but result in motoneurons preservation and changes in glial cells activation.We demonstrate that increase in survival induced by a slight daily modification of the environment is associated with motoneurons preservation and strong glial modifications in the lumbar spinal cord of SOD1(G93A. Using the appropriate control, we then demonstrate that all running intensities have no effect on the survival of ALS mice but induce cellular modifications. Our results highlight the critical importance of the control of the environment in ALS studies and may explain discrepancy in the literature regarding the

Modulated Raman Spectroscopy for Enhanced Cancer Diagnosis at the Cellular Level

Science.gov (United States)

De Luca, Anna Chiara; Dholakia, Kishan; Mazilu, Michael

2015-01-01

Raman spectroscopy is emerging as a promising and novel biophotonics tool for non-invasive, real-time diagnosis of tissue and cell abnormalities. However, the presence of a strong fluorescence background is a key issue that can detract from the use of Raman spectroscopy in routine clinical care. The review summarizes the state-of-the-art methods to remove the fluorescence background and explores recent achievements to address this issue obtained with modulated Raman spectroscopy. This innovative approach can be used to extract the Raman spectral component from the fluorescence background and improve the quality of the Raman signal. We describe the potential of modulated Raman spectroscopy as a rapid, inexpensive and accurate clinical tool to detect the presence of bladder cancer cells. Finally, in a broader context, we show how this approach can greatly enhance the sensitivity of integrated Raman spectroscopy and microfluidic systems, opening new prospects for portable higher throughput Raman cell sorting. PMID:26110401

Model Development of Degradation of PV Modules Backsheet with Locating Place of Module

Energy Technology Data Exchange (ETDEWEB)

Kempe, Michael D [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Wang, Yu [Case Western Reserve University; Fairbrother, Andrew [National Institute of Standards and Technology (NIST); Merzlic, Sebastien [Arkema; Julien, Scott [Northeastern University; Fridman, Lucas S. [Case Western Reserve University; Loyer, Camille [Arkema; Lefebvre, Amy L. [Arkema; O' Brien, Gregory [Arkema; Gu, Xiaohong [National Institute of Standards and Technology (NIST); Ji, Liang [Underwriters Laboratories; Boyce, Kenneth P. [Underwriters Laboratories; Wan, Kai-tak [Northeastern University; French, Roger H. [Case Western Reserve University; Bruckman, Laura S. [Case Western Reserve University

2017-08-23

Performance of a photovoltaic (PV) module is related to the micro-environment around the module. The position of photovoltaic modules in an array row have a large effect on the yellowing and gloss of PV module backsheet exposed in Dfa climatic zone (Gaithersburg, MD) with a polyethylene naphthalate (PEN) outer layer. Stress/Response models of yellowing and gloss-losing as function of location parameters of module, including the shed, row, measurement position in a same module and the distance of module location to the row center, are under development. The module installation height had the greatest influence on degradation of PEN PV backsheet in the Dfa climatic zone. The module backsheets at the end of an array have higher degradation rate (edge effect). The edge effect decreases with increasing of module installation heights.

Spinal cellular and network properties modulate pain perception

Directory of Open Access Journals (Sweden)

Darbon Pascal

2016-01-01

Previously, it has been shown that high levels of plasma glucocorticoids give rise to analgesia. However to our knowledge nothing has been reported regarding a direct non genomic modulation of neuronal spinal activity by peripheral CORT. In the present study, we used combined in vivo and in vitro electrophysiology approaches, associated with the measure of nociceptive mechanical sensitivity and plasma corticosterone level measurement to assess the impact of circulating CORT on rat nociception. We showed that CORT plasma level elevation produced analgesia via the reduction of nociceptive fiber mediated spinal responses. CORT is spinally reduced in the neuroactive metabolite THDOC that specifically enhances lamina II GABAergic synaptic transmission. The main consequence is a reduction of lamina II network excitability reflecting a selective decrease in processing of nociceptive inputs. The depressed neuronal activity at the spinal level then in turn leads to a weaker nociceptive message transmission to supraspinal structures and hence to an alleviation of pain.

Glucose stimulates intestinal epithelial crypt proliferation by modulating cellular energy metabolism.

Science.gov (United States)

Zhou, Weinan; Ramachandran, Deepti; Mansouri, Abdelhak; Dailey, Megan J

2018-04-01

The intestinal epithelium plays an essential role in nutrient absorption, hormone release, and barrier function. Maintenance of the epithelium is driven by continuous cell renewal by stem cells located in the intestinal crypts. The amount and type of diet influence this process and result in changes in the size and cellular make-up of the tissue. The mechanism underlying the nutrient-driven changes in proliferation is not known, but may involve a shift in intracellular metabolism that allows for more nutrients to be used to manufacture new cells. We hypothesized that nutrient availability drives changes in cellular energy metabolism of small intestinal epithelial crypts that could contribute to increases in crypt proliferation. We utilized primary small intestinal epithelial crypts from C57BL/6J mice to study (1) the effect of glucose on crypt proliferation and (2) the effect of glucose on crypt metabolism using an extracellular flux analyzer for real-time metabolic measurements. We found that glucose increased both crypt proliferation and glycolysis, and the glycolytic pathway inhibitor 2-deoxy-d-glucose (2-DG) attenuated glucose-induced crypt proliferation. Glucose did not enhance glucose oxidation, but did increase the maximum mitochondrial respiratory capacity, which may contribute to glucose-induced increases in proliferation. Glucose activated Akt/HIF-1α signaling pathway, which might be at least in part responsible for glucose-induced glycolysis and cell proliferation. These results suggest that high glucose availability induces an increase in crypt proliferation by inducing an increase in glycolysis with no change in glucose oxidation. © 2017 Wiley Periodicals, Inc.

Increasing cellular coverage within integrated terrestrial/satellite mobile networks

Science.gov (United States)

Castro, Jonathan P.

1995-01-01

When applying the hierarchical cellular concept, the satellite acts as giant umbrella cell covering a region with some terrestrial cells. If a mobile terminal traversing the region arrives to the border-line or limits of a regular cellular ground service, network transition occurs and the satellite system continues the mobile coverage. To adequately assess the boundaries of service of a mobile satellite system an a cellular network within an integrated environment, this paper provides an optimized scheme to predict when a network transition may be necessary. Under the assumption of a classified propagation phenomenon and Lognormal shadowing, the study applies an analytical approach to estimate the location of a mobile terminal based on a reception of the signal strength emitted by a base station.

Cellular energy allocation in zebra mussels exposed along a pollution gradient: linking cellular effects to higher levels of biological organization

International Nuclear Information System (INIS)

Smolders, R.; Bervoets, L.; Coen, W. de; Blust, R.

2004-01-01

Organisms exposed to suboptimal environments incur a cost of dealing with stress in terms of metabolic resources. The total amount of energy available for maintenance, growth and reproduction, based on the biochemical analysis of the energy budget, may provide a sensitive measure of stress in an organism. While the concept is clear, linking cellular or biochemical responses to the individual and population or community level remains difficult. The aim of this study was to validate, under field conditions, using cellular energy budgets [i.e. changes in glycogen-, lipid- and protein-content and mitochondrial electron transport system (ETS)] as an ecologically relevant measurement of stress by comparing these responses to physiological and organismal endpoints. Therefore, a 28-day in situ bioassay with zebra mussels (Dreissena polymorpha) was performed in an effluent-dominated stream. Five locations were selected along the pollution gradient and compared with a nearby (reference) site. Cellular Energy Allocation (CEA) served as a biomarker of cellular energetics, while Scope for Growth (SFG) indicated effects on a physiological level and Tissue Condition Index and wet tissue weight/dry tissue weight ratio were used as endpoints of organismal effects. Results indicated that energy budgets at a cellular level of biological organization provided the fastest and most sensitive response and energy budgets are a relevant currency to extrapolate cellular effects to higher levels of biological organization within the exposed mussels. - Exposure of zebra mussels along a pollution gradient has adverse effects on the cellular energy allocation, and results can be linked with higher levels of biological organization

Cellular energy allocation in zebra mussels exposed along a pollution gradient: linking cellular effects to higher levels of biological organization

Energy Technology Data Exchange (ETDEWEB)

Smolders, R.; Bervoets, L.; Coen, W. de; Blust, R

2004-05-01

Organisms exposed to suboptimal environments incur a cost of dealing with stress in terms of metabolic resources. The total amount of energy available for maintenance, growth and reproduction, based on the biochemical analysis of the energy budget, may provide a sensitive measure of stress in an organism. While the concept is clear, linking cellular or biochemical responses to the individual and population or community level remains difficult. The aim of this study was to validate, under field conditions, using cellular energy budgets [i.e. changes in glycogen-, lipid- and protein-content and mitochondrial electron transport system (ETS)] as an ecologically relevant measurement of stress by comparing these responses to physiological and organismal endpoints. Therefore, a 28-day in situ bioassay with zebra mussels (Dreissena polymorpha) was performed in an effluent-dominated stream. Five locations were selected along the pollution gradient and compared with a nearby (reference) site. Cellular Energy Allocation (CEA) served as a biomarker of cellular energetics, while Scope for Growth (SFG) indicated effects on a physiological level and Tissue Condition Index and wet tissue weight/dry tissue weight ratio were used as endpoints of organismal effects. Results indicated that energy budgets at a cellular level of biological organization provided the fastest and most sensitive response and energy budgets are a relevant currency to extrapolate cellular effects to higher levels of biological organization within the exposed mussels. - Exposure of zebra mussels along a pollution gradient has adverse effects on the cellular energy allocation, and results can be linked with higher levels of biological organization.

Using Primary Literature in an Undergraduate Assignment: Demonstrating Connections among Cellular Processes

Science.gov (United States)

Yeong, Foong May

2015-01-01

Learning basic cell biology in an essential module can be daunting to second-year undergraduates, given the depth of information that is provided in major molecular and cell biology textbooks. Moreover, lectures on cellular pathways are organised into sections, such that at the end of lectures, students might not see how various processes are…

Identification of unstable network modules reveals disease modules associated with the progression of Alzheimer's disease.

Directory of Open Access Journals (Sweden)

Masataka Kikuchi

Full Text Available Alzheimer's disease (AD, the most common cause of dementia, is associated with aging, and it leads to neuron death. Deposits of amyloid β and aberrantly phosphorylated tau protein are known as pathological hallmarks of AD, but the underlying mechanisms have not yet been revealed. A high-throughput gene expression analysis previously showed that differentially expressed genes accompanying the progression of AD were more down-regulated than up-regulated in the later stages of AD. This suggested that the molecular networks and their constituent modules collapsed along with AD progression. In this study, by using gene expression profiles and protein interaction networks (PINs, we identified the PINs expressed in three brain regions: the entorhinal cortex (EC, hippocampus (HIP and superior frontal gyrus (SFG. Dividing the expressed PINs into modules, we examined the stability of the modules with AD progression and with normal aging. We found that in the AD modules, the constituent proteins, interactions and cellular functions were not maintained between consecutive stages through all brain regions. Interestingly, the modules were collapsed with AD progression, specifically in the EC region. By identifying the modules that were affected by AD pathology, we found the transcriptional regulation-associated modules that interact with the proteasome-associated module via UCHL5 hub protein, which is a deubiquitinating enzyme. Considering PINs as a system made of network modules, we found that the modules relevant to the transcriptional regulation are disrupted in the EC region, which affects the ubiquitin-proteasome system.

hybrid modulation scheme fo rid modulation scheme fo dulation

African Journals Online (AJOL)

eobe

control technique is done through simulations and ex control technique .... HYBRID MODULATION SCHEME FOR CASCADED H-BRIDGE INVERTER CELLS. C. I. Odeh ..... and OR operations. Referring to ... MATLAB/SIMULINK environment.

Analysis and evaluation of the impact of climatic conditions on the photovoltaic modules performance in the desert environment

International Nuclear Information System (INIS)

Bouraiou, Ahmed; Hamouda, Messaoud; Chaker, Abdelkader; Mostefaoui, Mohammed; Lachtar, Salah; Sadok, Mohammed; Boutasseta, Nadir; Othmani, Mourad; Issam, Attoui

2015-01-01

Highlights: • Modeling and simulation of PV Module based on one and two diode model. • Power loss due to partial shading and dust accumulation were investigated. • Effect of variation of irradiation and temperature on PV performance parameters was examined. • Performance degradation of PV modules was evaluated using I–V and P–V curves. • Mean annual maximum power degradation rate due to delamination and discoloration equal to 1.89%/year. - Abstract: The main objective of this study is to investigate the impact of climatic conditions on the performance of photovoltaic modules installed in the desert region in south of Algeria. Firstly, the performance of ISOFOTON 100 module under daily weather conditions is evaluated. Next, the effects of partial shading and accumulation of sand dust for a period of two months on power loss and the current–voltage characteristics of photovoltaic modules are examined. Finally, the visual inspection of the degradation of the UDTS 50 modules such as discoloration of encapsulant and delamination show the influence of high temperature and the other climatic factors in the Saharan environment after a long time exposure of more than 10 years observed in the field at the Unit of Research in Renewable energy URERMS Adrar. The performance degradation is also assessed using (I–V and P–V) curves normalized at STC condition compared with the nominal STC data given by the manufacturer. The experimental results show that the performance parameters such as maximum output current (I_m_a_x), maximum output voltage (V_m_a_x), maximum power output (P_m_a_x), open-circuit voltage (V_o_c), short-circuit current (I_s_c) and fill factor (FF) of UDTS 50 modules are degraded after these years of exposition.

RESEARCH INTO PHOTOVOLTAIC MODULES EFFICIENCY IN THE ŻYWIEC BESKIDS ENVIRONMENT

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Danuta Hilse

2014-10-01

Full Text Available Research into photovoltaic modules in the highlands, based on the example of the Żywiec Beskids, was conducted in 2009 in the town of Stryszawa on the border between the regions of Lesser Poland and Silesia. It involved measurements of the quantity of the produced electric power in three different systems of diverse power (570 Wp, 360 Wp oraz 200 Wp and different technical solutions (rotary modules tracing the Sun rotation and stationary modules. Efficiency of the photovoltaic modules was compared to the intensity of the solar radiation in the city of Żywiec. This way the efficiency of the solar energy processing was determined. The conducted research indicates that with the intensity of the solar radiation amounting to 890 kWh/ m2·year it is possible to produce electric power in the quantity of over 150 kWh/m2·year (rotary modules or about 110 kWh/ m2·year (stationary modules. The highest efficiency of the solar energy processing into the electric energy has been observed in the winter season (ca. 26%.

MicroRNA-31 controls phenotypic modulation of human vascular smooth muscle cells by regulating its target gene cellular repressor of E1A-stimulated genes

International Nuclear Information System (INIS)

Wang, Jie; Yan, Cheng-Hui; Li, Yang; Xu, Kai; Tian, Xiao-Xiang; Peng, Cheng-Fei; Tao, Jie; Sun, Ming-Yu; Han, Ya-Ling

2013-01-01

Phenotypic modulation of vascular smooth muscle cells (VSMCs) plays a critical role in the pathogenesis of a variety of proliferative vascular diseases. The cellular repressor of E1A-stimulated genes (CREG) has been shown to play an important role in phenotypic modulation of VSMCs. However, the mechanism regulating CREG upstream signaling remains unclear. MicroRNAs (miRNAs) have recently been found to play a critical role in cell differentiation via target-gene regulation. This study aimed to identify a miRNA that binds directly to CREG, and may thus be involved in CREG-mediated VSMC phenotypic modulation. Computational analysis indicated that miR-31 bound to the CREG mRNA 3′ untranslated region (3′-UTR). miR-31 was upregulated in quiescent differentiated VSMCs and downregulated in proliferative cells stimulated by platelet-derived growth factor and serum starvation, demonstrating a negative relationship with the VSMC differentiation marker genes, smooth muscle α-actin, calponin and CREG. Using gain-of-function and loss-of-function approaches, CREG and VSMC differentiation marker gene expression levels were shown to be suppressed by a miR-31 mimic, but increased by a miR-31 inhibitor at both protein and mRNA levels. Notably, miR-31 overexpression or inhibition affected luciferase expression driven by the CREG 3′-UTR containing the miR-31 binding site. Furthermore, miR-31-mediated VSMC phenotypic modulation was inhibited in CREG-knockdown human VSMCs. We also determined miR-31 levels in the serum of patients with coronary artery disease (CAD), with or without in stent restenosis and in healthy controls. miR-31 levels were higher in the serum of CAD patients with restenosis compared to CAD patients without restenosis and in healthy controls. In summary, these data demonstrate that miR-31 not only directly binds to its target gene CREG and modulates the VSMC phenotype through this interaction, but also can be an important biomarker in diseases involving VSMC

A Method of Extracting Ontology Module Using Concept Relations for Sharing Knowledge in Mobile Cloud Computing Environment

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Keonsoo Lee

2014-01-01

Full Text Available In mobile cloud computing environment, the cooperation of distributed computing objects is one of the most important requirements for providing successful cloud services. To satisfy this requirement, all the members, who are employed in the cooperation group, need to share the knowledge for mutual understanding. Even if ontology can be the right tool for this goal, there are several issues to make a right ontology. As the cost and complexity of managing knowledge increase according to the scale of the knowledge, reducing the size of ontology is one of the critical issues. In this paper, we propose a method of extracting ontology module to increase the utility of knowledge. For the given signature, this method extracts the ontology module, which is semantically self-contained to fulfill the needs of the service, by considering the syntactic structure and semantic relation of concepts. By employing this module, instead of the original ontology, the cooperation of computing objects can be performed with less computing load and complexity. In particular, when multiple external ontologies need to be combined for more complex services, this method can be used to optimize the size of shared knowledge.

A method of extracting ontology module using concept relations for sharing knowledge in mobile cloud computing environment.

Science.gov (United States)

Lee, Keonsoo; Rho, Seungmin; Lee, Seok-Won

2014-01-01

In mobile cloud computing environment, the cooperation of distributed computing objects is one of the most important requirements for providing successful cloud services. To satisfy this requirement, all the members, who are employed in the cooperation group, need to share the knowledge for mutual understanding. Even if ontology can be the right tool for this goal, there are several issues to make a right ontology. As the cost and complexity of managing knowledge increase according to the scale of the knowledge, reducing the size of ontology is one of the critical issues. In this paper, we propose a method of extracting ontology module to increase the utility of knowledge. For the given signature, this method extracts the ontology module, which is semantically self-contained to fulfill the needs of the service, by considering the syntactic structure and semantic relation of concepts. By employing this module, instead of the original ontology, the cooperation of computing objects can be performed with less computing load and complexity. In particular, when multiple external ontologies need to be combined for more complex services, this method can be used to optimize the size of shared knowledge.

Structural, biochemical, cellular, and functional changes in skeletal muscle extracellular matrix with aging

DEFF Research Database (Denmark)

Kragstrup, Tue Wenzel; Kjaer, M; Mackey, A L

2011-01-01

The extracellular matrix (ECM) of skeletal muscle is critical for force transmission and for the passive elastic response of skeletal muscle. Structural, biochemical, cellular, and functional changes in skeletal muscle ECM contribute to the deterioration in muscle mechanical properties with aging......-links and a buildup of advanced glycation end-product cross-links. Altered mechanotransduction, poorer activation of satellite cells, poorer chemotactic and delayed inflammatory responses, and a change in modulators of the ECM are important cellular changes. It is possible that the structural and biochemical changes...... in skeletal muscle ECM contribute to the increased stiffness and impairment in force generated by the contracting muscle fibers seen with aging. The cellular interactions provide and potentially coordinate an adaptation to mechanical loading and ensure successful regeneration after muscle injury. Some...

AFM studies of environmental effects on nanomechanical properties and cellular structure of human hair

International Nuclear Information System (INIS)

Bhushan, Bharat; Chen, Nianhuan

2006-01-01

Characterization of cellular structure and physical and mechanical properties of hair are essential to develop better cosmetic products and advance biological and cosmetic science. Although the morphology of the cellular structure of human hair has been traditionally investigated using scanning electron microscopy and transmission electron microscopy, these techniques provide limited capability to in situ study of the physical and mechanical properties of human hair in various environments. Atomic force microscopy (AFM) overcomes these problems and can be used for characterization in ambient conditions without requiring specific sample preparations and surface treatment. In this study, film thickness, adhesive forces and effective Young's modulus of various hair surfaces were measured at different environments (humidity and temperature) using force calibration plot technique with an AFM. Torsional resonance mode phase contrast images were also taken in order to characterize the morphology and cellular structure changes of human hair at different humidity. The correlation between the nanomechanical properties and the cellular structure of hair is discussed

Antioxidant allocation modulates sperm quality across changing social environments.

Science.gov (United States)

Rojas Mora, Alfonso; Meniri, Magali; Gning, Ophélie; Glauser, Gaëtan; Vallat, Armelle; Helfenstein, Fabrice

2017-01-01

In promiscuous species, male reproductive success depends on their ability to mate with fertile females and on the fertilizing ability of their sperm. In such species, theory predicts that, owing to a trade-off between pre- and post-copulatory reproductive traits, males with lesser access to females should increase resource investment into those sperm traits that enhance fertilization success-usually referred to as ejaculate quality. This prediction has been validated in several taxa, yet studies on the physiological mechanisms modulating ejaculate quality are lacking. Sperm cells are highly vulnerable to oxidative stress, which impairs male fertility. Therefore, males that better protect their sperm from oxidative stress are expected to achieve higher ejaculate quality. Based on theoretical expectations, and since social dominance is a major determinant of mating opportunity, we predicted that subordinate males should invest more into the antioxidant protection of their sperm in order to achieve higher ejaculate quality. We maintained 60 male and 60 female wild-caught house sparrows Passer domesticus in outdoor aviaries, where we experimentally manipulated male social status to test our predictions. We measured cellular oxidative stress and enzymatic antioxidant activity in blood and sperm both before and after manipulating social ranks. Before manipulating the social status, we found that ejaculate viability correlated with oxidative stress level in sperm, with dominant males producing more oxidized and less viable ejaculates. Further, males at the lower end of the hierarchy produced ejaculates of similar quality to those of dominant males, suggesting that restricted access to resources might limit male reproductive strategies. After experimentally manipulating the social status, males matched their ejaculate quality to their new rank, while increases in antioxidant investment into ejaculates paralleled increases in ejaculate viability. Oxidative stress has been

NAD(H) and NADP(H) Redox Couples and Cellular Energy Metabolism.

Science.gov (United States)

Xiao, Wusheng; Wang, Rui-Sheng; Handy, Diane E; Loscalzo, Joseph

2018-01-20

The nicotinamide adenine dinucleotide (NAD + )/reduced NAD + (NADH) and NADP + /reduced NADP + (NADPH) redox couples are essential for maintaining cellular redox homeostasis and for modulating numerous biological events, including cellular metabolism. Deficiency or imbalance of these two redox couples has been associated with many pathological disorders. Recent Advances: Newly identified biosynthetic enzymes and newly developed genetically encoded biosensors enable us to understand better how cells maintain compartmentalized NAD(H) and NADP(H) pools. The concept of redox stress (oxidative and reductive stress) reflected by changes in NAD(H)/NADP(H) has increasingly gained attention. The emerging roles of NAD + -consuming proteins in regulating cellular redox and metabolic homeostasis are active research topics. The biosynthesis and distribution of cellular NAD(H) and NADP(H) are highly compartmentalized. It is critical to understand how cells maintain the steady levels of these redox couple pools to ensure their normal functions and simultaneously avoid inducing redox stress. In addition, it is essential to understand how NAD(H)- and NADP(H)-utilizing enzymes interact with other signaling pathways, such as those regulated by hypoxia-inducible factor, to maintain cellular redox homeostasis and energy metabolism. Additional studies are needed to investigate the inter-relationships among compartmentalized NAD(H)/NADP(H) pools and how these two dinucleotide redox couples collaboratively regulate cellular redox states and cellular metabolism under normal and pathological conditions. Furthermore, recent studies suggest the utility of using pharmacological interventions or nutrient-based bioactive NAD + precursors as therapeutic interventions for metabolic diseases. Thus, a better understanding of the cellular functions of NAD(H) and NADP(H) may facilitate efforts to address a host of pathological disorders effectively. Antioxid. Redox Signal. 28, 251-272.

Modulation of the Genome and Epigenome of Individuals Susceptible to Autism by Environmental Risk Factors

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Costas Koufaris

2015-04-01

Full Text Available Diverse environmental factors have been implicated with the development of autism spectrum disorders (ASD. Genetic factors also underlie the differential vulnerability to environmental risk factors of susceptible individuals. Currently the way in which environmental risk factors interact with genetic factors to increase the incidence of ASD is not well understood. A greater understanding of the metabolic, cellular, and biochemical events involved in gene x environment interactions in ASD would have important implications for the prevention and possible treatment of the disorder. In this review we discuss various established and more alternative processes through which environmental factors implicated in ASD can modulate the genome and epigenome of genetically-susceptible individuals.

Considering Maternal Dietary Modulators for Epigenetic Regulation and Programming of the Fetal Epigenome

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Abalo Chango

2015-04-01

Full Text Available Fetal life is characterized by a tremendous plasticity and ability to respond to various environmental and lifestyle factors, including maternal nutrition. Identification of the role of dietary factors that can modulate and reshape the cellular epigenome during development, including methyl group donors (e.g., folate, choline and bioactive compounds (e.g., polyphenols is of great importance; however, there is insufficient knowledge of a particular effect of each type of modulator and/or their combination on fetal life. To enhance the quality and safety of food products for proper fetal health and disease prevention in later life, a better understanding of the underlying mechanisms of dietary epigenetic modulators during the critical prenatal period is necessary. This review focuses on the influence of maternal dietary components on DNA methylation, histone modification, and microRNAs, and summarizes current knowledge of the effect and importance of dietary components on epigenetic mechanisms that control the proper expression of genetic information. Evidence reveals that some components in the maternal diet can directly or indirectly affect epigenetic mechanisms. Understanding the underlying mechanisms of how early-life nutritional environment affects the epigenome during development is of great importance for the successful prevention of adult chronic diseases through optimal maternal nutrition.

Considering maternal dietary modulators for epigenetic regulation and programming of the fetal epigenome.

Science.gov (United States)

Chango, Abalo; Pogribny, Igor P

2015-04-14

Fetal life is characterized by a tremendous plasticity and ability to respond to various environmental and lifestyle factors, including maternal nutrition. Identification of the role of dietary factors that can modulate and reshape the cellular epigenome during development, including methyl group donors (e.g., folate, choline) and bioactive compounds (e.g., polyphenols) is of great importance; however, there is insufficient knowledge of a particular effect of each type of modulator and/or their combination on fetal life. To enhance the quality and safety of food products for proper fetal health and disease prevention in later life, a better understanding of the underlying mechanisms of dietary epigenetic modulators during the critical prenatal period is necessary. This review focuses on the influence of maternal dietary components on DNA methylation, histone modification, and microRNAs, and summarizes current knowledge of the effect and importance of dietary components on epigenetic mechanisms that control the proper expression of genetic information. Evidence reveals that some components in the maternal diet can directly or indirectly affect epigenetic mechanisms. Understanding the underlying mechanisms of how early-life nutritional environment affects the epigenome during development is of great importance for the successful prevention of adult chronic diseases through optimal maternal nutrition.

Intermolecular masking of the HIV-1 Rev NLS by the cellular protein HIC: Novel insights into the regulation of Rev nuclear import

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Sheehy Noreen

2011-03-01

Full Text Available Abstract Background The HIV-1 regulatory protein Rev, which is essential for viral replication, mediates the nuclear export of unspliced viral transcripts. Rev nuclear function requires active nucleocytoplasmic shuttling, and Rev nuclear import is mediated by the recognition of its Nuclear Localisation Signal (NLS by multiple import factors, which include transportin and importin β. However, it remains unclear which nuclear import pathway(s predominate in vivo, and the cellular environment that modulates Rev nucleocytoplasmic shuttling remains to be characterised. Results In our study, we have identified the cellular protein HIC (Human I-mfa domain-Containing protein as a novel interactor of HIV-1 Rev. We demonstrate that HIC selectively interferes with Rev NLS interaction with importin β and impedes its nuclear import and function, but does not affect Rev nuclear import mediated by transportin. Hence, the molecular determinants mediating Rev-NLS recognition by importin β and transportin appear to be distinct. Furthermore, we have employed HIC and M9 M, a peptide specifically designed to inhibit the transportin-mediated nuclear import pathway, to characterise Rev nuclear import pathways within different cellular environments. Remarkably, we could show that in 293T, HeLa, COS7, Jurkat, U937, THP-1 and CEM cells, Rev nuclear import is cell type specific and alternatively mediated by transportin or importin β, in a mutually exclusive fashion. Conclusions Rev cytoplasmic sequestration by HIC may represent a novel mechanism for the control of Rev function. These studies highlight that the multivalent nature of the Rev NLS for different import receptors enables Rev to adapt its nuclear trafficking strategy.

Cellular entry of G3.5 poly (amido amine) dendrimers by clathrin- and dynamin-dependent endocytosis promotes tight junctional opening in intestinal epithelia.

Science.gov (United States)

Goldberg, Deborah S; Ghandehari, Hamidreza; Swaan, Peter W

2010-08-01

This study investigates the mechanisms of G3.5 poly (amido amine) dendrimer cellular uptake, intracellular trafficking, transepithelial transport and tight junction modulation in Caco-2 cells in the context of oral drug delivery. Chemical inhibitors blocking clathrin-, caveolin- and dynamin-dependent endocytosis pathways were used to investigate the mechanisms of dendrimer cellular uptake and transport across Caco-2 cells using flow cytometry and confocal microscopy. Dendrimer cellular uptake was found to be dynamin-dependent and was reduced by both clathrin and caveolin endocytosis inhibitors, while transepithelial transport was only dependent on dynamin- and clathrin-mediated endocytosis. Dendrimers were quickly trafficked to the lysosomes after 15 min of incubation and showed increased endosomal accumulation at later time points, suggesting saturation of this pathway. Dendrimers were unable to open tight junctions in cell monolayers treated with dynasore, a selective inhibitor of dynamin, confirming that dendrimer internalization promotes tight junction modulation. G3.5 PAMAM dendrimers take advantage of several receptor-mediated endocytosis pathways for cellular entry in Caco-2 cells. Dendrimer internalization by dynamin-dependent mechanisms promotes tight junction opening, suggesting that dendrimers act on intracellular cytoskeletal proteins to modulate tight junctions, thus catalyzing their own transport via the paracellular route.

Cellular mechanisms of estradiol-mediated sexual differentiation of the brain.

Science.gov (United States)

Wright, Christopher L; Schwarz, Jaclyn S; Dean, Shannon L; McCarthy, Margaret M

2010-09-01

Gonadal steroids organize the developing brain during a perinatal sensitive period and have enduring consequences for adult behavior. In male rodents testicular androgens are aromatized in neurons to estrogens and initiate multiple distinct cellular processes that ultimately determine the masculine phenotype. Within specific brain regions, overall cell number and dendritic morphology are the principal targets for hormonal organization. Recent advances have been made in elucidating the cellular mechanisms by which the neurological underpinnings of sexually dimorphic physiology and behavior are determined. These include estradiol-mediated prostaglandin synthesis, presynaptic release of glutamate, postsynaptic changes in glutamate receptors and changes in cell adhesion molecules. Sex differences in cell death are mediated by hormonal modulation of survival and death factors such as TNFalpha and Bcl-2/BAX. Copyright 2010 Elsevier Ltd. All rights reserved.

Phase-Modulated Optical Communication Systems

CERN Document Server

Ho, Keang-Po

2005-01-01

Fiber-optic communication systems have revolutionized our telecommunication infrastructures – currently, almost all telephone land-line, cellular, and internet communications must travel via some form of optical fibers. In these transmission systems, neither the phase nor frequency of the optical signal carries information – only the intensity of the signal is used. To transmit more information in a single optical carrier, the phase of the optical carrier must be explored. As a result, there is renewed interest in phase-modulated optical communications, mainly in direct-detection DPSK signals for long-haul optical communication systems. When optical amplifiers are used to maintain certain signal level among the fiber link, the system is limited by amplifier noises and fiber nonlinearities. Phase-Modulated Optical Communication Systems surveys this newly popular area, covering the following topics: The transmitter and receiver for phase-modulated coherent lightwave systems Method for performance analysis o...

Salinity and temperature variations reflecting on cellular PCNA, IGF-I and II expressions, body growth and muscle cellularity of a freshwater fish larvae.

Science.gov (United States)

Martins, Y S; Melo, R M C; Campos-Junior, P H A; Santos, J C E; Luz, R K; Rizzo, E; Bazzoli, N

2014-06-01

The present study assessed the influence of salinity and temperature on body growth and on muscle cellularity of Lophiosilurus alexaxdri vitelinic larvae. Slightly salted environments negatively influenced body growth of freshwater fish larvae and we observed that those conditions notably act as an environmental influencer on muscle growth and on local expression of hypertrophia and hypeplasia markers (IGFs and PCNA). Furthermore, we could see that salinity tolerance for NaCl 4gl(-)(1) diminishes with increasing temperature, evidenced by variation in body and muscle growth, and by irregular morphology of the lateral skeletal muscle of larvae. We saw that an increase of both PCNA and autocrine IGF-II are correlated to an increase in fibre numbers and fibre diameter as the temperature increases and salinity diminishes. On the other hand, autocrine IGF-I follows the opposite way to the other biological parameters assessed, increasing as salinity increases and temperature diminishes, showing that this protein did not participate in muscle cellularity, but participating in molecular/cellular repair. Therefore, slightly salted environments may provide adverse conditions that cause some obstacles to somatic growth of this species, suggesting some osmotic expenditure with a salinity increment. Copyright © 2014 Elsevier Inc. All rights reserved.

The impact of technological innovations on work design in a cellular manufacturing environment

NARCIS (Netherlands)

Molleman, E.; Slomp, J.

2001-01-01

The impact of developments in market and technology on grouping machinery and work design is analysed. Over time a cellular design changed into a functional system with fewer cells, fewer workers and fewer but more advanced machines. This encourages high utilisation, specialised workers and the

The impact of technological innovations on work design in a cellular manufacturing environment

NARCIS (Netherlands)

Molleman, E.; Slomp, J.

The impact of developments in market and technology on grouping machinery and work design is analysed. Over time a cellular design changed into a functional system with fewer cells, fewer workers and fewer but more advanced machines. This encourages high utilisation, specialised workers and the

The role of the cytoskeleton in cellular force generation in 2D and 3D environments

International Nuclear Information System (INIS)

Kraning-Rush, Casey M; Carey, Shawn P; Califano, Joseph P; Smith, Brooke N; Reinhart-King, Cynthia A

2011-01-01

To adhere and migrate, cells generate forces through the cytoskeleton that are transmitted to the surrounding matrix. While cellular force generation has been studied on 2D substrates, less is known about cytoskeletal-mediated traction forces of cells embedded in more in vivo-like 3D matrices. Recent studies have revealed important differences between the cytoskeletal structure, adhesion, and migration of cells in 2D and 3D. Because the cytoskeleton mediates force, we sought to directly compare the role of the cytoskeleton in modulating cell force in 2D and 3D. MDA-MB-231 cells were treated with agents that perturbed actin, microtubules, or myosin, and analyzed for changes in cytoskeletal organization and force generation in both 2D and 3D. To quantify traction stresses in 2D, traction force microscopy was used; in 3D, force was assessed based on single cell-mediated collagen fibril reorganization imaged using confocal reflectance microscopy. Interestingly, even though previous studies have observed differences in cell behaviors like migration in 2D and 3D, our data indicate that forces generated on 2D substrates correlate with forces within 3D matrices. Disruption of actin, myosin or microtubules in either 2D or 3D microenvironments disrupts cell-generated force. These data suggest that despite differences in cytoskeletal organization in 2D and 3D, actin, microtubules and myosin contribute to contractility and matrix reorganization similarly in both microenvironments

Design of small-molecule epigenetic modulators

Science.gov (United States)

Pachaiyappan, Boobalan

2013-01-01

The field of epigenetics has expanded rapidly to reveal multiple new targets for drug discovery. The functional elements of the epigenomic machinery can be catagorized as writers, erasers and readers, and together these elements control cellular gene expression and homeostasis. It is increasingly clear that aberrations in the epigenome can underly a variety of diseases, and thus discovery of small molecules that modulate the epigenome in a specific manner is a viable approach to the discovery of new therapeutic agents. In this Digest, the components of epigenetic control of gene expression will be briefly summarized, and efforts to identify small molecules that modulate epigenetic processes will be described. PMID:24300735

Postnatal odorant exposure induces peripheral olfactory plasticity at the cellular level

OpenAIRE

CADIOU , Hervé; AOUDE , Imad; Tazir , Bassim; Molinas , Adrien; Forbes Fenech , Claire; Meunier , Nicolas; Grosmaitre , Xavier

2014-01-01

Mammalian olfactory sensory neurons (OSNs) form the primary elements of the olfactory system. Inserted in the olfactory mucosa lining of the nasal cavity, they are exposed to the environment and their lifespan is brief. Several reports say that OSNs are regularly regenerated during the entire life and that odorant environment affects the olfactory epithelium. However, little is known about the impact of the odorant environment on OSNs at the cellular level and more precisely in the context of...

Asymmetrical Modulation for Uplink Communication in Cooperative Networks

DEFF Research Database (Denmark)

Zhang, Qi; Fitzek, Frank H.P.; Iversen, Villy Bæk

2008-01-01

-range links with neighboring mobile devices to form cooperative clusters. So far the physical communication over cellular links and over short-range links are separated in time or in frequency. Beyond this state of the art, we exploit a method, referred to as asymmetrical modulation, where a mobile device...

Structural basis for the ATP-independent proteolytic activity of LonB proteases and reclassification of their AAA+ modules.

Science.gov (United States)

An, Young Jun; Na, Jung-Hyun; Kim, Myung-Il; Cha, Sun-Shin

2015-10-01

Lon proteases degrade defective or denature proteins as well as some folded proteins for the control of cellular protein quality. There are two types of Lon proteases, LonA and LonB. Each consists of two functional components: a protease component and an ATPase associated with various cellular activities (AAA+ module). Here, we report the 2.03 -resolution crystal structure of the isolated AAA+ module (iAAA+ module) of LonB from Thermococcus onnurineus NA1 (TonLonB). The iAAA+ module, having no bound nucleotide, adopts a conformation virtually identical to the ADP-bound conformation of AAA+ modules in the hexameric structure of TonLonB; this provides insights into the ATP-independent proteolytic activity observed in a LonB protease. Structural comparison of AAA+ modules between LonA and LonB revealed that the AAA+ modules of Lon proteases are separated into two distinct clades depending on their structural features. The AAA+ module of LonB belongs to the -H2 & Ins1 insert clade (HINS clade)- defined for the first time in this study, while the AAA+ module of LonA is a member of the HCLR clade.

From "Cellular" RNA to "Smart" RNA: Multiple Roles of RNA in Genome Stability and Beyond.

Science.gov (United States)

Michelini, Flavia; Jalihal, Ameya P; Francia, Sofia; Meers, Chance; Neeb, Zachary T; Rossiello, Francesca; Gioia, Ubaldo; Aguado, Julio; Jones-Weinert, Corey; Luke, Brian; Biamonti, Giuseppe; Nowacki, Mariusz; Storici, Francesca; Carninci, Piero; Walter, Nils G; Fagagna, Fabrizio d'Adda di

2018-03-30

Coding for proteins has been considered the main function of RNA since the "central dogma" of biology was proposed. The discovery of noncoding transcripts shed light on additional roles of RNA, ranging from the support of polypeptide synthesis, to the assembly of subnuclear structures, to gene expression modulation. Cellular RNA has therefore been recognized as a central player in often unanticipated biological processes, including genomic stability. This ever-expanding list of functions inspired us to think of RNA as a "smart" phone, which has replaced the older obsolete "cellular" phone. In this review, we summarize the last two decades of advances in research on the interface between RNA biology and genome stability. We start with an account of the emergence of noncoding RNA, and then we discuss the involvement of RNA in DNA damage signaling and repair, telomere maintenance, and genomic rearrangements. We continue with the depiction of single-molecule RNA detection techniques, and we conclude by illustrating the possibilities of RNA modulation in hopes of creating or improving new therapies. The widespread biological functions of RNA have made this molecule a reoccurring theme in basic and translational research, warranting it the transcendence from classically studied "cellular" RNA to "smart" RNA.

Therapeutic intervention at cellular quality control systems in Alzheimer's and Parkinson's diseases.

Science.gov (United States)

Arduino, Daniela M; Esteves, A Raquel; Silva, Diana F F; Martins-Branco, Diogo; Santos, Daniel; Pimentel, Diana F Gomes; Cardoso, Sandra M

2011-01-01

Cellular homeostasis relies on quality control systems so that damaged biologic structures are either repaired or degraded and entirely replaced by newly formed proteins or even organelles. The clearance of dysfunctional cellular structures in long-lived postmitotic cells, like neurons, is essential to eliminate, per example, defective mitochondria, lipofuscin-loaded lysosomes and oxidized proteins. Short-lived proteins are degraded mainly by proteases and proteasomes whether most long-lived proteins and all organelles are digested by autophagy in the lysosomes. Recently, it an interplay was established between the ubiquitin-proteasome system and macroautophagy, so that both degradative mechanisms compensate for each other. In this article we describe each of these clearance systems and their contribution to neuronal quality control. We will highlight some of the findings that provide evidence for the dysfunction of these systems in Alzheimer's and Parkinson's diseases. Ultimately, we provide an outline on potential therapeutic interventions based on the modulation of cellular degradative systems.

Cellular stress induces a protective sleep-like state in C. elegans.

Science.gov (United States)

Hill, Andrew J; Mansfield, Richard; Lopez, Jessie M N G; Raizen, David M; Van Buskirk, Cheryl

2014-10-20

Sleep is recognized to be ancient in origin, with vertebrates and invertebrates experiencing behaviorally quiescent states that are regulated by conserved genetic mechanisms. Despite its conservation throughout phylogeny, the function of sleep remains debated. Hypotheses for the purpose of sleep include nervous-system-specific functions such as modulation of synaptic strength and clearance of metabolites from the brain, as well as more generalized cellular functions such as energy conservation and macromolecule biosynthesis. These models are supported by the identification of synaptic and metabolic processes that are perturbed during prolonged wakefulness. It remains to be seen whether perturbations of cellular homeostasis in turn drive sleep. Here we show that under conditions of cellular stress, including noxious heat, cold, hypertonicity, and tissue damage, the nematode Caenorhabditis elegans engages a behavioral quiescence program. The stress-induced quiescent state displays properties of sleep and is dependent on the ALA neuron, which mediates the conserved soporific effect of epidermal growth factor (EGF) ligand overexpression. We characterize heat-induced quiescence in detail and show that it is indeed dependent on components of EGF signaling, providing physiological relevance to the behavioral effects of EGF family ligands. We find that after noxious heat exposure, quiescence-defective animals show elevated expression of cellular stress reporter genes and are impaired for survival, demonstrating the benefit of stress-induced behavioral quiescence. These data provide evidence that cellular stress can induce a protective sleep-like state in C. elegans and suggest that a deeply conserved function of sleep is to mitigate disruptions of cellular homeostasis. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cellular automata and integrodifferential equation models for cell renewal in mosaic tissues

Science.gov (United States)

Bloomfield, J. M.; Sherratt, J. A.; Painter, K. J.; Landini, G.

2010-01-01

Mosaic tissues are composed of two or more genetically distinct cell types. They occur naturally, and are also a useful experimental method for exploring tissue growth and maintenance. By marking the different cell types, one can study the patterns formed by proliferation, renewal and migration. Here, we present mathematical modelling suggesting that small changes in the type of interaction that cells have with their local cellular environment can lead to very different outcomes for the composition of mosaics. In cell renewal, proliferation of each cell type may depend linearly or nonlinearly on the local proportion of cells of that type, and these two possibilities produce very different patterns. We study two variations of a cellular automaton model based on simple rules for renewal. We then propose an integrodifferential equation model, and again consider two different forms of cellular interaction. The results of the continuous and cellular automata models are qualitatively the same, and we observe that changes in local environment interaction affect the dynamics for both. Furthermore, we demonstrate that the models reproduce some of the patterns seen in actual mosaic tissues. In particular, our results suggest that the differing patterns seen in organ parenchymas may be driven purely by the process of cell replacement under different interaction scenarios. PMID:20375040

Manipulation of colony environment modulates honey bee aggression and brain gene expression.

Science.gov (United States)

Rittschof, C C; Robinson, G E

2013-11-01

The social environment plays an essential role in shaping behavior for most animals. Social effects on behavior are often linked to changes in brain gene expression. In the honey bee (Apis mellifera L.), social modulation of individual aggression allows colonies to adjust the intensity with which they defend their hive in response to predation threat. Previous research has showed social effects on both aggression and aggression-related brain gene expression in honey bees, caused by alarm pheromone and unknown factors related to colony genotype. For example, some bees from less aggressive genetic stock reared in colonies with genetic predispositions toward increased aggression show both increased aggression and more aggressive-like brain gene expression profiles. We tested the hypothesis that exposure to a colony environment influenced by high levels of predation threat results in increased aggression and aggressive-like gene expression patterns in individual bees. We assessed gene expression using four marker genes. Experimentally induced predation threats modified behavior, but the effect was opposite of our predictions: disturbed colonies showed decreased aggression. Disturbed colonies also decreased foraging activity, suggesting that they did not habituate to threats; other explanations for this finding are discussed. Bees in disturbed colonies also showed changes in brain gene expression, some of which paralleled behavioral findings. These results show that bee aggression and associated molecular processes are subject to complex social influences. © 2013 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Does Branched-Chain Amino Acids Supplementation Modulate Skeletal Muscle Remodeling through Inflammation Modulation? Possible Mechanisms of Action

Directory of Open Access Journals (Sweden)

Humberto Nicastro

2012-01-01

Full Text Available Skeletal muscle protein turnover is modulated by intracellular signaling pathways involved in protein synthesis, degradation, and inflammation. The proinflammatory status of muscle cells, observed in pathological conditions such as cancer, aging, and sepsis, can directly modulate protein translation initiation and muscle proteolysis, contributing to negative protein turnover. In this context, branched-chain amino acids (BCAAs, especially leucine, have been described as a strong nutritional stimulus able to enhance protein translation initiation and attenuate proteolysis. Furthermore, under inflammatory conditions, BCAA can be transaminated to glutamate in order to increase glutamine synthesis, which is a substrate highly consumed by inflammatory cells such as macrophages. The present paper describes the role of inflammation on muscle remodeling and the possible metabolic and cellular effects of BCAA supplementation in the modulation of inflammatory status of skeletal muscle and the consequences on protein synthesis and degradation.

The CORVET complex: compositions, function, and impact on cellular behaviour

NARCIS (Netherlands)

Jonker, CTH

2016-01-01

The endolysosomal system is positioned on the crossroad of the intracellular and extracellular environment and is therefore crucial to regulate many cellular processes. Proper function of the endolysosomal system greatly depends on the concept of membrane identity; the controlled protein and lipid

Kinetic theory approach to modeling of cellular repair mechanisms under genome stress.

Directory of Open Access Journals (Sweden)

Jinpeng Qi

Full Text Available Under acute perturbations from outer environment, a normal cell can trigger cellular self-defense mechanism in response to genome stress. To investigate the kinetics of cellular self-repair process at single cell level further, a model of DNA damage generating and repair is proposed under acute Ion Radiation (IR by using mathematical framework of kinetic theory of active particles (KTAP. Firstly, we focus on illustrating the profile of Cellular Repair System (CRS instituted by two sub-populations, each of which is made up of the active particles with different discrete states. Then, we implement the mathematical framework of cellular self-repair mechanism, and illustrate the dynamic processes of Double Strand Breaks (DSBs and Repair Protein (RP generating, DSB-protein complexes (DSBCs synthesizing, and toxins accumulating. Finally, we roughly analyze the capability of cellular self-repair mechanism, cellular activity of transferring DNA damage, and genome stability, especially the different fates of a certain cell before and after the time thresholds of IR perturbations that a cell can tolerate maximally under different IR perturbation circumstances.

Kinetic theory approach to modeling of cellular repair mechanisms under genome stress.

Science.gov (United States)

Qi, Jinpeng; Ding, Yongsheng; Zhu, Ying; Wu, Yizhi

2011-01-01

Under acute perturbations from outer environment, a normal cell can trigger cellular self-defense mechanism in response to genome stress. To investigate the kinetics of cellular self-repair process at single cell level further, a model of DNA damage generating and repair is proposed under acute Ion Radiation (IR) by using mathematical framework of kinetic theory of active particles (KTAP). Firstly, we focus on illustrating the profile of Cellular Repair System (CRS) instituted by two sub-populations, each of which is made up of the active particles with different discrete states. Then, we implement the mathematical framework of cellular self-repair mechanism, and illustrate the dynamic processes of Double Strand Breaks (DSBs) and Repair Protein (RP) generating, DSB-protein complexes (DSBCs) synthesizing, and toxins accumulating. Finally, we roughly analyze the capability of cellular self-repair mechanism, cellular activity of transferring DNA damage, and genome stability, especially the different fates of a certain cell before and after the time thresholds of IR perturbations that a cell can tolerate maximally under different IR perturbation circumstances.

A global interaction network maps a wiring diagram of cellular function

Science.gov (United States)

Costanzo, Michael; VanderSluis, Benjamin; Koch, Elizabeth N.; Baryshnikova, Anastasia; Pons, Carles; Tan, Guihong; Wang, Wen; Usaj, Matej; Hanchard, Julia; Lee, Susan D.; Pelechano, Vicent; Styles, Erin B.; Billmann, Maximilian; van Leeuwen, Jolanda; van Dyk, Nydia; Lin, Zhen-Yuan; Kuzmin, Elena; Nelson, Justin; Piotrowski, Jeff S.; Srikumar, Tharan; Bahr, Sondra; Chen, Yiqun; Deshpande, Raamesh; Kurat, Christoph F.; Li, Sheena C.; Li, Zhijian; Usaj, Mojca Mattiazzi; Okada, Hiroki; Pascoe, Natasha; Luis, Bryan-Joseph San; Sharifpoor, Sara; Shuteriqi, Emira; Simpkins, Scott W.; Snider, Jamie; Suresh, Harsha Garadi; Tan, Yizhao; Zhu, Hongwei; Malod-Dognin, Noel; Janjic, Vuk; Przulj, Natasa; Troyanskaya, Olga G.; Stagljar, Igor; Xia, Tian; Ohya, Yoshikazu; Gingras, Anne-Claude; Raught, Brian; Boutros, Michael; Steinmetz, Lars M.; Moore, Claire L.; Rosebrock, Adam P.; Caudy, Amy A.; Myers, Chad L.; Andrews, Brenda; Boone, Charles

2017-01-01

We generated a global genetic interaction network for Saccharomyces cerevisiae, constructing over 23 million double mutants, identifying ~550,000 negative and ~350,000 positive genetic interactions. This comprehensive network maps genetic interactions for essential gene pairs, highlighting essential genes as densely connected hubs. Genetic interaction profiles enabled assembly of a hierarchical model of cell function, including modules corresponding to protein complexes and pathways, biological processes, and cellular compartments. Negative interactions connected functionally related genes, mapped core bioprocesses, and identified pleiotropic genes, whereas positive interactions often mapped general regulatory connections among gene pairs, rather than shared functionality. The global network illustrates how coherent sets of genetic interactions connect protein complex and pathway modules to map a functional wiring diagram of the cell. PMID:27708008

Quantum fluctuations of a fullerene cage modulate its internal magnetic environment.

Science.gov (United States)

Kawatsu, Tsutomu; Tachikawa, Masanori

2018-01-17

To investigate the effect of quantum fluctuations on the magnetic environment inside a C 60 fullerene cage, we have calculated the nuclear magnetic shielding constant of protons in H 2 @C 60 and HD@C 60 systems by on-the-fly ab initio path integral simulation, including both thermal and nuclear quantum effects. The most dominant upfield from an isolated hydrogen molecule occurs due to the diamagnetic current of the C 60 cage, which is partly cancelled by the paramagnetic current, where the paramagnetic contribution is enlarged by the zero-point vibrational fluctuation of the C 60 carbon backbone structure via a widely distributed HOMO-LUMO gap. This quantum modulation mechanism of the nuclear magnetic shielding constant is newly proposed. Because this quantum effect is independent of the difference between H 2 and HD, the H 2 /HD isotope shift occurs in spite of the C 60 cage. The nuclear magnetic constants computed for H 2 @C 60 and HD@C 60 are 32.047 and 32.081 ppm, respectively, which are in reasonable agreement with the corresponding values of 32.19 and 32.23 ppm estimated from the experimental values of the chemical shifts.

Modulation of cellular radiation responses by 2-deoxy-D-glucose and other glycolytic inhibitors: Implications for cancer therapy

OpenAIRE

Kalia Vijay; Prabhakara S; Narayanan Vidya

2009-01-01

Background: 2-Deoxy-D-glucose (2-DG), a glycolytic inhibitor, was observed earlier to increase DNA, chromosomal, and cellular damage in tumor cells, by inhibiting energy-dependent repair processes. Lonidamine (LND) selectively inhibits glycolysis in cancer cells. It damages the condensed mitochondria in these cells, impairing thereby the activity of hexokinase (predominantly attached to the outer mitochondrial membranes). It inhibits repair of radiation-induced potentially lethal cellular da...

Advances and Perspectives in Chemical Imaging in Cellular Environments Using Electrochemical Methods

Directory of Open Access Journals (Sweden)

Robert A. Lazenby

2018-05-01

Full Text Available This review discusses a broad range of recent advances (2013–2017 in chemical imaging using electrochemical methods, with a particular focus on techniques that have been applied to study cellular processes, or techniques that show promise for use in this field in the future. Non-scanning techniques such as microelectrode arrays (MEAs offer high time-resolution (<10 ms imaging; however, at reduced spatial resolution. In contrast, scanning electrochemical probe microscopies (SEPMs offer higher spatial resolution (as low as a few nm per pixel imaging, with images collected typically over many minutes. Recent significant research efforts to improve the spatial resolution of SEPMs using nanoscale probes and to improve the temporal resolution using fast scanning have resulted in movie (multiple frame imaging with frame rates as low as a few seconds per image. Many SEPM techniques lack chemical specificity or have poor selectivity (defined by the choice of applied potential for redox-active species. This can be improved using multifunctional probes, ion-selective electrodes and tip-integrated biosensors, although additional effort may be required to preserve sensor performance after miniaturization of these probes. We discuss advances to the field of electrochemical imaging, and technological developments which are anticipated to extend the range of processes that can be studied. This includes imaging cellular processes with increased sensor selectivity and at much improved spatiotemporal resolution than has been previously customary.

Predicting cellular growth from gene expression signatures.

Directory of Open Access Journals (Sweden)

Edoardo M Airoldi

2009-01-01

Full Text Available Maintaining balanced growth in a changing environment is a fundamental systems-level challenge for cellular physiology, particularly in microorganisms. While the complete set of regulatory and functional pathways supporting growth and cellular proliferation are not yet known, portions of them are well understood. In particular, cellular proliferation is governed by mechanisms that are highly conserved from unicellular to multicellular organisms, and the disruption of these processes in metazoans is a major factor in the development of cancer. In this paper, we develop statistical methodology to identify quantitative aspects of the regulatory mechanisms underlying cellular proliferation in Saccharomyces cerevisiae. We find that the expression levels of a small set of genes can be exploited to predict the instantaneous growth rate of any cellular culture with high accuracy. The predictions obtained in this fashion are robust to changing biological conditions, experimental methods, and technological platforms. The proposed model is also effective in predicting growth rates for the related yeast Saccharomyces bayanus and the highly diverged yeast Schizosaccharomyces pombe, suggesting that the underlying regulatory signature is conserved across a wide range of unicellular evolution. We investigate the biological significance of the gene expression signature that the predictions are based upon from multiple perspectives: by perturbing the regulatory network through the Ras/PKA pathway, observing strong upregulation of growth rate even in the absence of appropriate nutrients, and discovering putative transcription factor binding sites, observing enrichment in growth-correlated genes. More broadly, the proposed methodology enables biological insights about growth at an instantaneous time scale, inaccessible by direct experimental methods. Data and tools enabling others to apply our methods are available at http://function.princeton.edu/growthrate.

Multi-cellular logistics of collective cell migration.

Directory of Open Access Journals (Sweden)

Masataka Yamao

Full Text Available During development, the formation of biological networks (such as organs and neuronal networks is controlled by multicellular transportation phenomena based on cell migration. In multi-cellular systems, cellular locomotion is restricted by physical interactions with other cells in a crowded space, similar to passengers pushing others out of their way on a packed train. The motion of individual cells is intrinsically stochastic and may be viewed as a type of random walk. However, this walk takes place in a noisy environment because the cell interacts with its randomly moving neighbors. Despite this randomness and complexity, development is highly orchestrated and precisely regulated, following genetic (and even epigenetic blueprints. Although individual cell migration has long been studied, the manner in which stochasticity affects multi-cellular transportation within the precisely controlled process of development remains largely unknown. To explore the general principles underlying multicellular migration, we focus on the migration of neural crest cells, which migrate collectively and form streams. We introduce a mechanical model of multi-cellular migration. Simulations based on the model show that the migration mode depends on the relative strengths of the noise from migratory and non-migratory cells. Strong noise from migratory cells and weak noise from surrounding cells causes "collective migration," whereas strong noise from non-migratory cells causes "dispersive migration." Moreover, our theoretical analyses reveal that migratory cells attract each other over long distances, even without direct mechanical contacts. This effective interaction depends on the stochasticity of the migratory and non-migratory cells. On the basis of these findings, we propose that stochastic behavior at the single-cell level works effectively and precisely to achieve collective migration in multi-cellular systems.

Force control for mechanoinduction of impedance variation in cellular organisms

International Nuclear Information System (INIS)

Nam, Joo Hoo; Chen, Peter C Y; Lu, Zhe; Luo, Hong; Lin, Wei; Ge, Ruowen

2010-01-01

Constantly exposed to various forms of mechanical forces inherent in their physical environment (such as gravity, stress induced by fluid flow or cell–cell interactions, etc), cellular organisms sense such forces and convert them into biochemical signals through the processes of mechanosensing and mechanotransduction that eventually lead to biological changes. The effect of external forces on the internal structures and activities in a cellular organism may manifest in changes its physical properties, such as impedance. Studying variation in the impedance of a cellular organism induced by the application of an external mechanical force represents a meaningful endeavor (from a biosystems perspective) in exploring the complex mechanosensing and mechanotransduction mechanisms that govern the behavior of a cellular organism under the influence of external mechanical stimuli. In this paper we describe the development of an explicit force-feedback control system for exerting an indentation force on a cellular organism while simultaneously measuring its impedance. To demonstrate the effectiveness of this force-control system, we have conducted experiments using zebrafish embryos as a test model of a cellular organism. We report experimental results demonstrating that the application of a properly controlled external force leads to a significant change in the impedance of a zebrafish embryo. These results offer support for a plausible explanation that activities of pore canals in the chorion are responsible for the observed change in impedance.

Selfish cellular networks and the evolution of complex organisms.

Science.gov (United States)

Kourilsky, Philippe

2012-03-01

Human gametogenesis takes years and involves many cellular divisions, particularly in males. Consequently, gametogenesis provides the opportunity to acquire multiple de novo mutations. A significant portion of these is likely to impact the cellular networks linking genes, proteins, RNA and metabolites, which constitute the functional units of cells. A wealth of literature shows that these individual cellular networks are complex, robust and evolvable. To some extent, they are able to monitor their own performance, and display sufficient autonomy to be termed "selfish". Their robustness is linked to quality control mechanisms which are embedded in and act upon the individual networks, thereby providing a basis for selection during gametogenesis. These selective processes are equally likely to affect cellular functions that are not gamete-specific, and the evolution of the most complex organisms, including man, is therefore likely to occur via two pathways: essential housekeeping functions would be regulated and evolve during gametogenesis within the parents before being transmitted to their progeny, while classical selection would operate on other traits of the organisms that shape their fitness with respect to the environment. Copyright © 2012 Académie des sciences. Published by Elsevier SAS. All rights reserved.

Computer Modeling of the Earliest Cellular Structures and Functions

Science.gov (United States)

Pohorille, Andrew; Chipot, Christophe; Schweighofer, Karl

2000-01-01

In the absence of extinct or extant record of protocells (the earliest ancestors of contemporary cells). the most direct way to test our understanding of the origin of cellular life is to construct laboratory models of protocells. Such efforts are currently underway in the NASA Astrobiology Program. They are accompanied by computational studies aimed at explaining self-organization of simple molecules into ordered structures and developing designs for molecules that perform proto-cellular functions. Many of these functions, such as import of nutrients, capture and storage of energy. and response to changes in the environment are carried out by proteins bound to membranestructures at water-membrane interfaces and insert into membranes, (b) how these peptides aggregate to form membrane-spanning structures (eg. channels), and (c) by what mechanisms such aggregates perform essential proto-cellular functions, such as proton transport of protons across cell walls, a key step in cellular bioenergetics. The simulations were performed using the molecular dynamics method, in which Newton's equations of motion for each item in the system are solved iteratively. The problems of interest required simulations on multi-nanosecond time scales, which corresponded to 10(exp 6)-10(exp 8) time steps.

Inducing repetitive action potential firing in neurons via synthesized photoresponsive nanoscale cellular prostheses.

Science.gov (United States)

Lu, Siyuan; Madhukar, Anupam

2013-02-01

Recently we reported an analysis that examined the potential of synthesized photovoltaic functional abiotic nanosystems (PVFANs) to modulate membrane potential and activate action potential firing in neurons. Here we extend the analysis to delineate the requirements on the electronic energy levels and the attendant photophysical properties of the PVFANs to induce repetitive action potential under continuous light, a capability essential for the proposed potential application of PVFANs as retinal cellular prostheses to compensate for loss of photoreceptors. We find that repetitive action potential firing demands two basic characteristics in the electronic response of the PVFANs: an exponential dependence of the PVFAN excited state decay rate on the membrane potential and a three-state system such that, following photon absorption, the electron decay from the excited state to the ground state is via intermediate state(s) whose lifetime is comparable to the refractory time following an action potential. In this study, the potential of synthetic photovoltaic functional abiotic nanosystems (PVFANs) is examined under continuous light to modulate membrane potential and activate action potential firing in neurons with the proposed potential application of PVFANs as retinal cellular prostheses. Copyright © 2013 Elsevier Inc. All rights reserved.

Tissue Engineering Strategies for Myocardial Regeneration: Acellular Versus Cellular Scaffolds?

Science.gov (United States)

Domenech, Maribella; Polo-Corrales, Lilliana; Ramirez-Vick, Jaime E; Freytes, Donald O

2016-12-01

Heart disease remains one of the leading causes of death in industrialized nations with myocardial infarction (MI) contributing to at least one fifth of the reported deaths. The hypoxic environment eventually leads to cellular death and scar tissue formation. The scar tissue that forms is not mechanically functional and often leads to myocardial remodeling and eventual heart failure. Tissue engineering and regenerative medicine principles provide an alternative approach to restoring myocardial function by designing constructs that will restore the mechanical function of the heart. In this review, we will describe the cellular events that take place after an MI and describe current treatments. We will also describe how biomaterials, alone or in combination with a cellular component, have been used to engineer suitable myocardium replacement constructs and how new advanced culture systems will be required to achieve clinical success.

Intracellular calcium modulates basolateral K(+)-permeability in frog skin epithelium

DEFF Research Database (Denmark)

Brodin, Birger; Rytved, K A; Nielsen, R

1994-01-01

Cytosolic calcium ([Ca2+]i) has been suggested as a key modulator in the regulation of active sodium transport across electrically "tight" (high resistance) epithelia. In this study we investigated the effects of calcium on cellular electrophysiological parameters in a classical model tissue, the...

SU-E-P-04: Transport Theory Learning Module in the Maple Environment

Energy Technology Data Exchange (ETDEWEB)

Both, J [University of Miami, Miller School of Medicine, Department of Radiation Oncology (United States)

2014-06-01

Purpose: The medical physics graduate program at the University of Miami is developing a computerized instructional module which provides an interactive mechanism for students to learn transport theory. While not essential in the medical physics curriculum, transport theory should be taught because the conceptual level of transport theory is fundamental, a substantial literature exists and ought to be accessible, and students should understand commercial software which solves the Boltzmann equation.But conventional teaching and learning of transport theory is challenging. Students may be under prepared to appreciate its methods, results, and relevance, and it is not substantially addressed in textbooks for the medical physicists. Other resources an instructor might reasonably use, while excellent, may be too briskly paced for beginning students. The purpose of this work is to render teaching of transport theory more tractable by making learning highly interactive. Methods: The module is being developed in the Maple mathematics environment by instructors and graduate students. It will refresh the students' knowledge of vector calculus and differential equations, and will develop users' intuition for phase space concepts. Scattering concepts will be developed with animated simulations using tunable parameters characterizing interactions, so that students may develop a “feel” for cross section. Transport equations for one and multiple types of radiation will be illustrated with phase space animations. Numerical methods of solution will be illustrated. Results: Attempts to teach rudiments of transport theory in radiation physics and dosimetry courses using conventional classroom techniques at the University of Miami have had small success, because classroom time is limited and the material has been hard for our students to appreciate intuitively. Conclusion: A joint effort of instructor and students to teach and learn transport theory by building an

SU-E-P-04: Transport Theory Learning Module in the Maple Environment

International Nuclear Information System (INIS)

Both, J

2014-01-01

Purpose: The medical physics graduate program at the University of Miami is developing a computerized instructional module which provides an interactive mechanism for students to learn transport theory. While not essential in the medical physics curriculum, transport theory should be taught because the conceptual level of transport theory is fundamental, a substantial literature exists and ought to be accessible, and students should understand commercial software which solves the Boltzmann equation.But conventional teaching and learning of transport theory is challenging. Students may be under prepared to appreciate its methods, results, and relevance, and it is not substantially addressed in textbooks for the medical physicists. Other resources an instructor might reasonably use, while excellent, may be too briskly paced for beginning students. The purpose of this work is to render teaching of transport theory more tractable by making learning highly interactive. Methods: The module is being developed in the Maple mathematics environment by instructors and graduate students. It will refresh the students' knowledge of vector calculus and differential equations, and will develop users' intuition for phase space concepts. Scattering concepts will be developed with animated simulations using tunable parameters characterizing interactions, so that students may develop a “feel” for cross section. Transport equations for one and multiple types of radiation will be illustrated with phase space animations. Numerical methods of solution will be illustrated. Results: Attempts to teach rudiments of transport theory in radiation physics and dosimetry courses using conventional classroom techniques at the University of Miami have had small success, because classroom time is limited and the material has been hard for our students to appreciate intuitively. Conclusion: A joint effort of instructor and students to teach and learn transport theory by building an interactive

Adult mouse epicardium modulates myocardial injury by secreting paracrine factors

Science.gov (United States)

Zhou, Bin; Honor, Leah B.; He, Huamei; Ma, Qing; Oh, Jin-Hee; Butterfield, Catherine; Lin, Ruei-Zeng; Melero-Martin, Juan M.; Dolmatova, Elena; Duffy, Heather S.; von Gise, Alexander; Zhou, Pingzhu; Hu, Yong Wu; Wang, Gang; Zhang, Bing; Wang, Lianchun; Hall, Jennifer L.; Moses, Marsha A.; McGowan, Francis X.; Pu, William T.

2011-01-01

The epicardium makes essential cellular and paracrine contributions to the growth of the fetal myocardium and the formation of the coronary vasculature. However, whether the epicardium has similar roles postnatally in the normal and injured heart remains enigmatic. Here, we have investigated this question using genetic fate-mapping approaches in mice. In uninjured postnatal heart, epicardial cells were quiescent. Myocardial infarction increased epicardial cell proliferation and stimulated formation of epicardium-derived cells (EPDCs), which remained in a thickened layer on the surface of the heart. EPDCs did not adopt cardiomyocyte or coronary EC fates, but rather differentiated into mesenchymal cells expressing fibroblast and smooth muscle cell markers. In vitro and in vivo assays demonstrated that EPDCs secreted paracrine factors that strongly promoted angiogenesis. In a myocardial infarction model, EPDC-conditioned medium reduced infarct size and improved heart function. Our findings indicate that epicardium modulates the cardiac injury response by conditioning the subepicardial environment, potentially offering a new therapeutic strategy for cardiac protection. PMID:21505261

Balancing Uplink and Downlink under Asymmetric Traffic Environments Using Distributed Receive Antennas

Science.gov (United States)

Sohn, Illsoo; Lee, Byong Ok; Lee, Kwang Bok

Recently, multimedia services are increasing with the widespread use of various wireless applications such as web browsers, real-time video, and interactive games, which results in traffic asymmetry between the uplink and downlink. Hence, time division duplex (TDD) systems which provide advantages in efficient bandwidth utilization under asymmetric traffic environments have become one of the most important issues in future mobile cellular systems. It is known that two types of intercell interference, referred to as crossed-slot interference, additionally arise in TDD systems; the performances of the uplink and downlink transmissions are degraded by BS-to-BS crossed-slot interference and MS-to-MS crossed-slot interference, respectively. The resulting performance unbalance between the uplink and downlink makes network deployment severely inefficient. Previous works have proposed intelligent time slot allocation algorithms to mitigate the crossed-slot interference problem. However, they require centralized control, which causes large signaling overhead in the network. In this paper, we propose to change the shape of the cellular structure itself. The conventional cellular structure is easily transformed into the proposed cellular structure with distributed receive antennas (DRAs). We set up statistical Markov chain traffic model and analyze the bit error performances of the conventional cellular structure and proposed cellular structure under asymmetric traffic environments. Numerical results show that the uplink and downlink performances of the proposed cellular structure become balanced with the proper number of DRAs and thus the proposed cellular structure is notably cost-effective in network deployment compared to the conventional cellular structure. As a result, extending the conventional cellular structure into the proposed cellular structure with DRAs is a remarkably cost-effective solution to support asymmetric traffic environments in future mobile cellular

Effects of motexafin gadolinium on tumor oxygenation and cellular oxygen consumption

International Nuclear Information System (INIS)

Donnelly, E.T.; Liu, Y.; Rockwell, S.; Magda, D.

2003-01-01

Full text: Recent work in our laboratory showed that motexafin gadolinium (MGd, Xcytrin), a drug currently in Phase III clinical trials as an adjuvant to radiation therapy, modulates the oxygen tensions in EMT6 tumors. The median pO 2 increased from the control value of 1.5±0.4 mmHg to 7.4 ± 3.8 mmHg six hours after treatment with 40 μmol/kg MGd and the percentage of severely hypoxic readings in the tumors ( 7 plateau phase EMT6 cells in 3 mL Dulbecco's Modified Eagle's Medium supplemented with 10% dialyzed fetal bovine serum, which contains no ascorbic acid. In the absence of ascorbic acid, 100 μM MGd did not alter the cellular oxygen consumption rate for EMT6 cells significantly. Marked inhibition of cellular oxygen consumption was observed when cells were incubated with 100 μM MGd in medium supplemented with equimolar ascorbic acid (a 31.5% decrease in consumption was observed after 6 hours of treatment). The 5% mannitol vehicle solution with equimolar ascorbic acid had no discernible effect on cellular oxygen consumption. Ascorbic acid may facilitate cellular uptake of MGd via the intermediate formation of a MGd-oxalate complex. These studies suggest that changes in cellular oxygen consumption could contribute to the changes in tumor oxygenation seen after administration of MGd. These experiments were supported by Pharmacyclics and training grant T32CA09085 from the NIH (E.T.D.). We thank Dr. Raymond Russell for allowing us to use his oxygen electrode apparatus

Design of small molecule epigenetic modulators.

Science.gov (United States)

Pachaiyappan, Boobalan; Woster, Patrick M

2014-01-01

The field of epigenetics has expanded rapidly to reveal multiple new targets for drug discovery. The functional elements of the epigenomic machinery can be categorized as writers, erasers and readers, and together these elements control cellular gene expression and homeostasis. It is increasingly clear that aberrations in the epigenome can underly a variety of diseases, and thus discovery of small molecules that modulate the epigenome in a specific manner is a viable approach to the discovery of new therapeutic agents. In this Digest, the components of epigenetic control of gene expression will be briefly summarized, and efforts to identify small molecules that modulate epigenetic processes will be described. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

[Danger of cellular telephones and their relay stations].

Science.gov (United States)

Santini, R; Seigne, M; Bonhomme-Faivre, L

2000-07-01

Cellular phones and their base stations emit pulsed microwaves in the environment. Cellular phone users are exposed in the near field and, under this condition, a large part of the electromagnetic energy is absorbed by the head, leading to an increased brain temperature. The general population is exposed under far field conditions to an electromagnetic intensity depending on the distance from the base station, passive re-emitters, the number of communications maintained by the base station and their position in relation to antennae (in front of the antenna or behind). Biological effects have been reported, such as radiofrequency sickness, electroencephalographic and blood pressure changes and also cancer risks in humans and animals exposed to microwave irradiation. Some European countries (Italy, France, Belgium, etc.) have taken measures to protect their populations.

The emergence of extracellular matrix mechanics and cell traction forces as important regulators of cellular self-organization.

Science.gov (United States)

Checa, Sara; Rausch, Manuel K; Petersen, Ansgar; Kuhl, Ellen; Duda, Georg N

2015-01-01

Physical cues play a fundamental role in a wide range of biological processes, such as embryogenesis, wound healing, tumour invasion and connective tissue morphogenesis. Although it is well known that during these processes, cells continuously interact with the local extracellular matrix (ECM) through cell traction forces, the role of these mechanical interactions on large scale cellular and matrix organization remains largely unknown. In this study, we use a simple theoretical model to investigate cellular and matrix organization as a result of mechanical feedback signals between cells and the surrounding ECM. The model includes bi-directional coupling through cellular traction forces to deform the ECM and through matrix deformation to trigger cellular migration. In addition, we incorporate the mechanical contribution of matrix fibres and their reorganization by the cells. We show that a group of contractile cells will self-polarize at a large scale, even in homogeneous environments. In addition, our simulations mimic the experimentally observed alignment of cells in the direction of maximum stiffness and the building up of tension as a consequence of cell and fibre reorganization. Moreover, we demonstrate that cellular organization is tightly linked to the mechanical feedback loop between cells and matrix. Cells with a preference for stiff environments have a tendency to form chains, while cells with a tendency for soft environments tend to form clusters. The model presented here illustrates the potential of simple physical cues and their impact on cellular self-organization. It can be used in applications where cell-matrix interactions play a key role, such as in the design of tissue engineering scaffolds and to gain a basic understanding of pattern formation in organogenesis or tissue regeneration.

Cellular regulation of the structure and function of aortic valves

Directory of Open Access Journals (Sweden)

Ismail El-Hamamsy

2010-01-01

Full Text Available The aortic valve was long considered a passive structure that opens and closes in response to changes in transvalvular pressure. Recent evidence suggests that the aortic valve performs highly sophisticated functions as a result of its unique microscopic structure. These functions allow it to adapt to its hemodynamic and mechanical environment. Understanding the cellular and molecular mechanisms involved in normal valve physiology is essential to elucidate the mechanisms behind valve disease. We here review the structure and developmental biology of aortic valves; we examine the role of its cellular parts in regulating its function and describe potential pathophysiological and clinical implications.

Unified Stochastic Geometry Model for MIMO Cellular Networks with Retransmissions

KAUST Repository

Afify, Laila H.

2016-10-11

This paper presents a unified mathematical paradigm, based on stochastic geometry, for downlink cellular networks with multiple-input-multiple-output (MIMO) base stations (BSs). The developed paradigm accounts for signal retransmission upon decoding errors, in which the temporal correlation among the signal-to-interference-plus-noise-ratio (SINR) of the original and retransmitted signals is captured. In addition to modeling the effect of retransmission on the network performance, the developed mathematical model presents twofold analysis unification for MIMO cellular networks literature. First, it integrates the tangible decoding error probability and the abstracted (i.e., modulation scheme and receiver type agnostic) outage probability analysis, which are largely disjoint in the literature. Second, it unifies the analysis for different MIMO configurations. The unified MIMO analysis is achieved by abstracting unnecessary information conveyed within the interfering signals by Gaussian signaling approximation along with an equivalent SISO representation for the per-data stream SINR in MIMO cellular networks. We show that the proposed unification simplifies the analysis without sacrificing the model accuracy. To this end, we discuss the diversity-multiplexing tradeoff imposed by different MIMO schemes and shed light on the diversity loss due to the temporal correlation among the SINRs of the original and retransmitted signals. Finally, several design insights are highlighted.

Unified Stochastic Geometry Model for MIMO Cellular Networks with Retransmissions

KAUST Repository

Afify, Laila H.; Elsawy, Hesham; Al-Naffouri, Tareq Y.; Alouini, Mohamed-Slim

2016-01-01

This paper presents a unified mathematical paradigm, based on stochastic geometry, for downlink cellular networks with multiple-input-multiple-output (MIMO) base stations (BSs). The developed paradigm accounts for signal retransmission upon decoding errors, in which the temporal correlation among the signal-to-interference-plus-noise-ratio (SINR) of the original and retransmitted signals is captured. In addition to modeling the effect of retransmission on the network performance, the developed mathematical model presents twofold analysis unification for MIMO cellular networks literature. First, it integrates the tangible decoding error probability and the abstracted (i.e., modulation scheme and receiver type agnostic) outage probability analysis, which are largely disjoint in the literature. Second, it unifies the analysis for different MIMO configurations. The unified MIMO analysis is achieved by abstracting unnecessary information conveyed within the interfering signals by Gaussian signaling approximation along with an equivalent SISO representation for the per-data stream SINR in MIMO cellular networks. We show that the proposed unification simplifies the analysis without sacrificing the model accuracy. To this end, we discuss the diversity-multiplexing tradeoff imposed by different MIMO schemes and shed light on the diversity loss due to the temporal correlation among the SINRs of the original and retransmitted signals. Finally, several design insights are highlighted.

Redox modulation of cellular stress response and lipoxin A4 expression by Hericium Erinaceus in rat brain: relevance to Alzheimer's disease pathogenesis.

Science.gov (United States)

Trovato, A; Siracusa, R; Di Paola, R; Scuto, M; Ontario, M L; Bua, Ornella; Di Mauro, Paola; Toscano, M A; Petralia, C C T; Maiolino, L; Serra, A; Cuzzocrea, S; Calabrese, Vittorio

2016-01-01

There has been a recent upsurge of interest in complementary medicine, especially dietary supplements and foods functional in delaying the onset of age-associated neurodegenerative diseases. Mushrooms have long been used in traditional medicine for thousands of years, being now increasingly recognized as antitumor, antioxidant, antiviral, antibacterial and hepatoprotective agent also capable to stimulate host immune responses. Here we provide evidence of neuroprotective action of Hericium Herinaceus when administered orally to rat. Expression of Lipoxin A4 (LXA4) was measured in different brain regions after oral administration of a biomass Hericium preparation, given for 3 month. LXA4 up-regulation was associated with an increased content of redox sensitive proteins involved in cellular stress response, such as Hsp72, Heme oxygenase -1 and Thioredoxin. In the brain of rats receiving Hericium, maximum induction of LXA4 was observed in cortex, and hippocampus followed by substantia Nigra, striatum and cerebellum. Increasing evidence supports the notion that oxidative stress-driven neuroinflammation is a fundamental cause in neurodegenerative diseases. As prominent intracellular redox system involved in neuroprotection, the vitagene system is emerging as a neurohormetic potential target for novel cytoprotective interventions. Vitagenes encode for cytoprotective heat shock proteins 70, heme oxygenase-1, thioredoxin and Lipoxin A4. Emerging interest is now focussing on molecules capable of activating the vitagene system as novel therapeutic target to minimize deleterious consequences associated with free radical-induced cell damage, such as in neurodegeneration. LXA4 is an emerging endogenous eicosanoid able to promote resolution of inflammation, acting as an endogenous "braking signal" in the inflammatory process. In addition, Hsp system is emerging as key pathway for modulation to prevent neuronal dysfunction, caused by protein misfolding. Conceivably, activation of

Tribological behavior of Ti6Al4V cellular structures produced by Selective Laser Melting.

Science.gov (United States)

Bartolomeu, F; Sampaio, M; Carvalho, O; Pinto, E; Alves, N; Gomes, J R; Silva, F S; Miranda, G

2017-05-01

Additive manufacturing (AM) technologies enable the fabrication of innovative structures with complex geometries not easily manufactured by traditional processes. Regarding metallic cellular structures with tailored/customized mechanical and wear performance aiming to biomedical applications, Selective Laser Melting (SLM) is a remarkable solution for their production. Focusing on prosthesis and implants, in addition to a suitable Young's modulus it is important to assess the friction response and wear resistance of these cellular structures in a natural environment. In this sense, five cellular Ti6Al4V structures with different open-cell sizes (100-500µm) were designed and produced by SLM. These structures were tribologicaly tested against alumina using a reciprocating sliding ball-on-plate tribometer. Samples were submerged in Phosphate Buffered Saline (PBS) fluid at 37°C, in order to mimic in some extent the human body environment. The results showed that friction and wear performance of Ti6Al4V cellular structures is influenced by the structure open-cell size. The higher wear resistance was obtained for structures with 100µm designed open-cell size due to the higher apparent area of contact to support tribological loading. Copyright © 2017 Elsevier Ltd. All rights reserved.

Interplay between cellular activity and three-dimensional scaffold-cell constructs with different foam structure processed by electron beam melting.

Science.gov (United States)

Nune, Krishna C; Misra, R Devesh K; Gaytan, Sara M; Murr, Lawrence E

2015-05-01

The cellular activity, biological response, and consequent integration of scaffold-cell construct in the physiological system are governed by the ability of cells to adhere, proliferate, and biomineralize. In this regard, we combine cellular biology and materials science and engineering to fundamentally elucidate the interplay between cellular activity and interconnected three-dimensional foamed architecture obtained by a novel process of electron beam melting and computational tools. Furthermore, the organization of key proteins, notably, actin, vinclulin, and fibronectin, involved in cellular activity and biological functions and relationship with the structure was explored. The interconnected foamed structure with ligaments was favorable to cellular activity that includes cell attachment, proliferation, and differentiation. The primary rationale for favorable modulation of cellular functions is that the foamed structure provided a channel for migration and communication between cells leading to highly mineralized extracellular matrix (ECM) by the differentiating osteoblasts. The filopodial interaction amongst cells on the ligaments was a governing factor in the secretion of ECM, with consequent influence on maturation and mineralization. © 2014 Wiley Periodicals, Inc.

[Drug vectorization or how to modulate tissular and cellular distribution of biologically active compounds].

Science.gov (United States)

Couvreur, P

2001-07-01

Drug vectorization has undergone considerable development over the last few years. This review focuses on the intravenous route of administration. Colloid formulations allow a modulation of drug tissue distribution. Using liposomes and nanoparticles with unmodified surfaces, drugs can be targeted to macrophages of the reticulum endothelium system. When the liposomes or nanoparticles are covered with hydrophilic or flexible polymers, the vascular phase can be favored in order, for example, to facilitate selective extravasation at a tumor site. Therapeutic applications of these systems are presented. The development of "intelligent" vectors capable of modulating intracellular distribution of an active compounds is an equally interesting approach, for example pH-sensitive liposomes or nanoparticles decorated with folic acid capable of targeting intracellular cytoplasm.

Nitric Oxide and ERK mediates regulation of cellular processes by Ecdysterone

Energy Technology Data Exchange (ETDEWEB)

Omanakuttan, Athira; Bose, Chinchu; Pandurangan, Nanjan; Kumar, Geetha B.; Banerji, Asoke; Nair, Bipin G., E-mail: bipin@amrita.edu

2016-08-15

The complex process of wound healing is a major problem associated with diabetes, venous or arterial disease, old age and infection. A wide range of pharmacological effects including anabolic, anti-diabetic and hepato-protective activities have been attributed to Ecdysterone. In earlier studies, Ecdysterone has been shown to modulate eNOS and iNOS expression in diabetic animals and activate osteogenic differentiation through the Extracellular-signal-Regulated Kinase (ERK) pathway in periodontal ligament stem cells. However, in the wound healing process, Ecdysterone has only been shown to enhance granulation tissue formation in rabbits. There have been no studies to date, which elucidate the molecular mechanism underlying the complex cellular process involved in wound healing. The present study, demonstrates a novel interaction between the phytosteroid Ecdysterone and Nitric Oxide Synthase (NOS), in an Epidermal Growth Factor Receptor (EGFR)-dependent manner, thereby promoting cell proliferation, cell spreading and cell migration. These observations were further supported by the 4-amino-5-methylamino- 2′ ,7′ -difluorofluorescein diacetate (DAF FM) fluorescence assay which indicated that Ecdysterone activates NOS resulting in increased Nitric Oxide (NO) production. Additionally, studies with inhibitors of both the EGFR and ERK, demonstrated that Ecdysterone activates NOS through modulation of EGFR and ERK. These results clearly demonstrate, for the first time, that Ecdysterone enhances Nitric Oxide production and modulates complex cellular processes by activating ERK1/2 through the EGF pathway. - Highlights: • Ecdysterone significantly enhances cell migration in a dose dependent manner. • Ecdysterone augments cell spreading during the initial phase of cell migration through actin cytoskeletal rearrangement. • Ecdysterone enhances cell proliferation in a nitric oxide dependent manner. • Ecdysterone enhances nitric oxide production via activation of EGFR

Nitric Oxide and ERK mediates regulation of cellular processes by Ecdysterone

International Nuclear Information System (INIS)

Omanakuttan, Athira; Bose, Chinchu; Pandurangan, Nanjan; Kumar, Geetha B.; Banerji, Asoke; Nair, Bipin G.

2016-01-01

The complex process of wound healing is a major problem associated with diabetes, venous or arterial disease, old age and infection. A wide range of pharmacological effects including anabolic, anti-diabetic and hepato-protective activities have been attributed to Ecdysterone. In earlier studies, Ecdysterone has been shown to modulate eNOS and iNOS expression in diabetic animals and activate osteogenic differentiation through the Extracellular-signal-Regulated Kinase (ERK) pathway in periodontal ligament stem cells. However, in the wound healing process, Ecdysterone has only been shown to enhance granulation tissue formation in rabbits. There have been no studies to date, which elucidate the molecular mechanism underlying the complex cellular process involved in wound healing. The present study, demonstrates a novel interaction between the phytosteroid Ecdysterone and Nitric Oxide Synthase (NOS), in an Epidermal Growth Factor Receptor (EGFR)-dependent manner, thereby promoting cell proliferation, cell spreading and cell migration. These observations were further supported by the 4-amino-5-methylamino- 2′ ,7′ -difluorofluorescein diacetate (DAF FM) fluorescence assay which indicated that Ecdysterone activates NOS resulting in increased Nitric Oxide (NO) production. Additionally, studies with inhibitors of both the EGFR and ERK, demonstrated that Ecdysterone activates NOS through modulation of EGFR and ERK. These results clearly demonstrate, for the first time, that Ecdysterone enhances Nitric Oxide production and modulates complex cellular processes by activating ERK1/2 through the EGF pathway. - Highlights: • Ecdysterone significantly enhances cell migration in a dose dependent manner. • Ecdysterone augments cell spreading during the initial phase of cell migration through actin cytoskeletal rearrangement. • Ecdysterone enhances cell proliferation in a nitric oxide dependent manner. • Ecdysterone enhances nitric oxide production via activation of EGFR

Testing flat plate photovoltaic modules for terrestrial environment

Science.gov (United States)

Hoffman, A. R.; Arnett, J. C.; Ross, R. G., Jr.

1979-01-01

New qualification tests have been developed for flat plate photovoltaic modules. Temperature cycling, cyclic pressure load, and humidity exposure are especially useful for detecting design and fabrication deficiencies. There is positive correlation between many of the observed field effects, such as power loss, and qualification test induced degradation. The status of research efforts for the development of test methodology for field-related problems is reviewed.

Photovoltaic module and laminate

Science.gov (United States)

Bunea, Gabriela E.; Kim, Sung Dug; Kavulak, David F.J.

2018-04-10

A photovoltaic module is disclosed. The photovoltaic module has a first side directed toward the sun during normal operation and a second, lower side. The photovoltaic module comprises a perimeter frame and a photovoltaic laminate at least partially enclosed by and supported by the perimeter frame. The photovoltaic laminate comprises a transparent cover layer positioned toward the first side of the photovoltaic module, an upper encapsulant layer beneath and adhering to the cover layer, a plurality of photovoltaic solar cells beneath the upper encapsulant layer, the photovoltaic solar cells electrically interconnected, a lower encapsulant layer beneath the plurality of photovoltaic solar cells, the upper and lower encapsulant layers enclosing the plurality of photovoltaic solar cells, and a homogenous rear environmental protection layer, the rear environmental protection layer adhering to the lower encapsulant layer, the rear environmental protection layer exposed to the ambient environment on the second side of the photovoltaic module.

Fisetin and hesperetin induced apoptosis and cell cycle arrest in chronic myeloid leukemia cells accompanied by modulation of cellular signaling.

Science.gov (United States)

Adan, Aysun; Baran, Yusuf

2016-05-01

Fisetin and hesperetin, naturally occurring flavonoids, have been reported as novel antioxidants with chemopreventive/chemotherapeutic potential against various types of cancer. However, their mechanism of action in CML is still unknown. This particular study aims to evaluate the therapeutic potentials of fisetin and hesperetin and their effects on cell proliferation, apoptosis, and cell cycle progression in human K562 CML cells. The results indicated that fisetin and hesperetin inhibited cell proliferation and triggered programmed cell death in these cells. The latter was confırmed by mitochondrial membrane depolarization and an increase in caspase-3 activation. In addition to that, we have detected S and G2/M cell cycle arrests and G0/G1 arrest upon fisetin and hesperetin treatment, respectively. To identify the altered genes and genetic networks in response to fisetin and hesperetin, whole-genome microarray analysis was performed. The microarray gene profiling analysis revealed some important signaling pathways including JAK/STAT pathway, KIT receptor signaling, and growth hormone receptor signaling that were altered upon fisetin and hesperetin treatment. Moreover, microarray data suggested potential candidate genes for targeted CML therapy. Fisetin and hesperetin significantly modulated the expression of genes involved in cell proliferation and division, apoptosis, cell cycle regulation, and other significant cellular processes such as replication, transcription, and translation. In conclusion, our results suggest that fisetin and hesperetin as potential natural agents for CML therapy.

Development of a High-Throughput Gene Expression Screen for Modulators of RAS-MAPK Signaling in a Mutant RAS Cellular Context.

Science.gov (United States)

Severyn, Bryan; Nguyen, Thi; Altman, Michael D; Li, Lixia; Nagashima, Kumiko; Naumov, George N; Sathyanarayanan, Sriram; Cook, Erica; Morris, Erick; Ferrer, Marc; Arthur, Bill; Benita, Yair; Watters, Jim; Loboda, Andrey; Hermes, Jeff; Gilliland, D Gary; Cleary, Michelle A; Carroll, Pamela M; Strack, Peter; Tudor, Matt; Andersen, Jannik N

2016-10-01

The RAS-MAPK pathway controls many cellular programs, including cell proliferation, differentiation, and apoptosis. In colorectal cancers, recurrent mutations in this pathway often lead to increased cell signaling that may contribute to the development of neoplasms, thereby making this pathway attractive for therapeutic intervention. To this end, we developed a 26-member gene signature of RAS-MAPK pathway activity utilizing the Affymetrix QuantiGene Plex 2.0 reagent system and performed both primary and confirmatory gene expression-based high-throughput screens (GE-HTSs) using KRAS mutant colon cancer cells (SW837) and leveraging a highly annotated chemical library. The screen achieved a hit rate of 1.4% and was able to enrich for hit compounds that target RAS-MAPK pathway members such as MEK and EGFR. Sensitivity and selectivity performance measurements were 0.84 and 1.00, respectively, indicating high true-positive and true-negative rates. Active compounds from the primary screen were confirmed in a dose-response GE-HTS assay, a GE-HTS assay using 14 additional cancer cell lines, and an in vitro colony formation assay. Altogether, our data suggest that this GE-HTS assay will be useful for larger unbiased chemical screens to identify novel compounds and mechanisms that may modulate the RAS-MAPK pathway. © 2016 Society for Laboratory Automation and Screening.

Polymeric nanocarriers for transport modulation across the pulmonary epithelium: dendrimers, polymeric nanoparticles, and their nanoblends.

Science.gov (United States)

Bharatwaj, Balaji; Dimovski, Radovan; Conti, Denise S; da Rocha, Sandro R P

2014-05-01

The purpose of this study was to (a) Determine the cellular transport and uptake of amine-terminated generation 3 (G3) poly(amido amine) (PAMAM) dendrimers across an in vitro model of the pulmonary epithelium, and the ability to modulate their transport by forming nanoblends of the dendrimers with biodegradable solid polymeric nanoparticles (NPs) and (b) to formulate dendrimer nanocarriers in portable oral inhalation devices and evaluate their aerosol characteristics. To that end, fluorescein isothiocyanate (FITC)-labeled G3 PAMAM dendrimer nanocarriers (DNCs) were synthesized, and also encapsulated within poly lactide-co-glycolide nanoparticles (NPs). Transport and uptake of both DNCs encapsulated within NPs (nanoblends) and unencapsulated DNCs were tracked across polarized monolayers of airway epithelial cells, Calu-3. DNCs were also formulated as core-shell microparticles in pressurized metered-dose inhalers (pMDIs) and their aerodynamic properties evaluated by Andersen cascade impaction. The apparent permeability of DNCs across the airway epithelial model was similar to that of a paracellular marker of comparable molar mass--order of 10(-7) cm s(-1). The transport and cellular internalization of the DNCs can be modulated by formulating them as nanoblends. The transport of the DNCs across the lung epithelium was completely suppressed within the time of the experiment (5 h) when formulated as blends. The encapsulation also prevents saturation of the cellular internalization profile. Nanoblending may be a potential strategy to modulate the rate of transport and cellular uptake of DNCs, and thus be used as a design strategy to achieve enhanced local or systemic drug delivery.

Prediction Based Energy Balancing Forwarding in Cellular Networks

Directory of Open Access Journals (Sweden)

Yang Jian-Jun

2017-01-01

Full Text Available In the recent cellular network technologies, relay stations extend cell coverage and enhance signal strength for mobile users. However, busy traffic makes the relay stations in hot area run out of energy quickly. Energy is a very important factor in the forwarding of cellular network since mobile users(cell phones in hot cells often suffer from low throughput due to energy lack problems. In many situations, the energy lack problems take place because the energy loading is not balanced. In this paper, we present a prediction based forwarding algorithm to let a mobile node dynamically select the next relay station with highest potential energy capacity to resume communication. Key to this strategy is that a relay station only maintains three past status, and then it is able to predict the potential energy capacity. Then, the node selects the next hop with potential maximal energy. Moreover, a location based algorithm is developed to let the mobile node figure out the target region in order to avoid flooding. Simulations demonstrate that our approach significantly increase the aggregate throughput and decrease the delay in cellular network environment.

Cellular gravity

NARCIS (Netherlands)

F.C. Gruau; J.T. Tromp (John)

1999-01-01

textabstractWe consider the problem of establishing gravity in cellular automata. In particular, when cellular automata states can be partitioned into empty, particle, and wall types, with the latter enclosing rectangular areas, we desire rules that will make the particles fall down and pile up on

Cellular automata model for traffic flow at intersections in internet of vehicles

Science.gov (United States)

Zhao, Han-Tao; Liu, Xin-Ru; Chen, Xiao-Xu; Lu, Jian-Cheng

2018-03-01

Considering the effect of the front vehicle's speed, the influence of the brake light and the conflict of the traffic flow, we established a cellular automata model called CE-NS for traffic flow at the intersection in the non-vehicle networking environment. According to the information interaction of Internet of Vehicles (IoV), introducing parameters describing the congestion and the accurate speed of the front vehicle into the CE-NS model, we improved the rules of acceleration, deceleration and conflict, and finally established a cellular automata model for traffic flow at intersections of IoV. The relationship between traffic parameters such as vehicle speed, flow and average travel time is obtained by numerical simulation of two models. Based on this, we compared the traffic situation of the non-vehicle networking environment with conditions of IoV environment, and analyzed the influence of the different degree of IoV on the traffic flow. The results show that the traffic speed is increased, the travel time is reduced, the flux of intersections is increased and the traffic flow is more smoothly under IoV environment. After the vehicle which achieves IoV reaches a certain proportion, the operation effect of the traffic flow begins to improve obviously.

Cellular reprogramming through mitogen-activated protein kinases

Directory of Open Access Journals (Sweden)

Justin eLee

2015-10-01

Full Text Available Mitogen-activated protein kinase (MAPK cascades are conserved eukaryote signaling modules where MAPKs, as the final kinases in the cascade, phosphorylate protein substrates to regulate cellular processes. While some progress in the identification of MAPK substrates has been made in plants, the knowledge on the spectrum of substrates and their mechanistic action is still fragmentary. In this focused review, we discuss the biological implications of the data in our original paper (Sustained mitogen-activated protein kinase activation reprograms defense metabolism and phosphoprotein profile in Arabidopsis thaliana; Frontiers in Plant Science 5: 554 in the context of related research. In our work, we mimicked in vivo activation of two stress-activated MAPKs, MPK3 and MPK6, through transgenic manipulation of Arabidopsis thaliana and used phosphoproteomics analysis to identify potential novel MAPK substrates. Here, we plotted the identified putative MAPK substrates (and downstream phosphoproteins as a global protein clustering network. Based on a highly stringent selection confidence level, the core networks highlighted a MAPK-induced cellular reprogramming at multiple levels of gene and protein expression – including transcriptional, post-transcriptional, translational, post-translational (such as protein modification, folding and degradation steps, and also protein re-compartmentalization. Additionally, the increase in putative substrates/phosphoproteins of energy metabolism and various secondary metabolite biosynthesis pathways coincides with the observed accumulation of defense antimicrobial substances as detected by metabolome analysis. Furthermore, detection of protein networks in phospholipid or redox elements suggests activation of downstream signaling events. Taken in context with other studies, MAPKs are key regulators that reprogram cellular events to orchestrate defense signaling in eukaryotes.

Digital Cellular Solid Pressure Vessels: A Novel Approach for Human Habitation in Space

Science.gov (United States)

Cellucci, Daniel; Jenett, Benjamin; Cheung, Kenneth C.

2017-01-01

It is widely assumed that human exploration beyond Earth's orbit will require vehicles capable of providing long duration habitats that simulate an Earth-like environment - consistent artificial gravity, breathable atmosphere, and sufficient living space- while requiring the minimum possible launch mass. This paper examines how the qualities of digital cellular solids - high-performance, repairability, reconfigurability, tunable mechanical response - allow the accomplishment of long-duration habitat objectives at a fraction of the mass required for traditional structural technologies. To illustrate the impact digital cellular solids could make as a replacement to conventional habitat subsystems, we compare recent proposed deep space habitat structural systems with a digital cellular solids pressure vessel design that consists of a carbon fiber reinforced polymer (CFRP) digital cellular solid cylindrical framework that is lined with an ultra-high molecular weight polyethylene (UHMWPE) skin. We use the analytical treatment of a linear specific modulus scaling cellular solid to find the minimum mass pressure vessel for a structure and find that, for equivalent habitable volume and appropriate safety factors, the use of digital cellular solids provides clear methods for producing structures that are not only repairable and reconfigurable, but also higher performance than their conventionally manufactured counterparts.

Self-organized perturbations enhance class IV behavior and 1/f power spectrum in elementary cellular automata.

Science.gov (United States)

Nakajima, Kohei; Haruna, Taichi

2011-09-01

In this paper, we propose a new class of cellular automata based on the modification of its state space. It is introduced to model a computation which is exposed to an environment. We formalized the computation as extension and projection processes of its state space and resulting misidentifications of the state. This is motivated to embed the role of an environment into the system itself, which naturally induces self-organized internal perturbations rather than the usual external perturbations. Implementing this structure into the elementary cellular automata, we characterized its effect by means of input entropy and power spectral analysis. As a result, the cellular automata with this structure showed robust class IV behavior and a 1/f power spectrum in a wide range of rule space comparative to the notion of the edge of chaos. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Synthetic Biology: Tools to Design, Build, and Optimize Cellular Processes

Science.gov (United States)

Young, Eric; Alper, Hal

2010-01-01

The general central dogma frames the emergent properties of life, which make biology both necessary and difficult to engineer. In a process engineering paradigm, each biological process stream and process unit is heavily influenced by regulatory interactions and interactions with the surrounding environment. Synthetic biology is developing the tools and methods that will increase control over these interactions, eventually resulting in an integrative synthetic biology that will allow ground-up cellular optimization. In this review, we attempt to contextualize the areas of synthetic biology into three tiers: (1) the process units and associated streams of the central dogma, (2) the intrinsic regulatory mechanisms, and (3) the extrinsic physical and chemical environment. Efforts at each of these three tiers attempt to control cellular systems and take advantage of emerging tools and approaches. Ultimately, it will be possible to integrate these approaches and realize the vision of integrative synthetic biology when cells are completely rewired for biotechnological goals. This review will highlight progress towards this goal as well as areas requiring further research. PMID:20150964

Synthetic Biology: Tools to Design, Build, and Optimize Cellular Processes

Directory of Open Access Journals (Sweden)

Eric Young

2010-01-01

Full Text Available The general central dogma frames the emergent properties of life, which make biology both necessary and difficult to engineer. In a process engineering paradigm, each biological process stream and process unit is heavily influenced by regulatory interactions and interactions with the surrounding environment. Synthetic biology is developing the tools and methods that will increase control over these interactions, eventually resulting in an integrative synthetic biology that will allow ground-up cellular optimization. In this review, we attempt to contextualize the areas of synthetic biology into three tiers: (1 the process units and associated streams of the central dogma, (2 the intrinsic regulatory mechanisms, and (3 the extrinsic physical and chemical environment. Efforts at each of these three tiers attempt to control cellular systems and take advantage of emerging tools and approaches. Ultimately, it will be possible to integrate these approaches and realize the vision of integrative synthetic biology when cells are completely rewired for biotechnological goals. This review will highlight progress towards this goal as well as areas requiring further research.

Synthetic biology: tools to design, build, and optimize cellular processes.

Science.gov (United States)

Young, Eric; Alper, Hal

2010-01-01

The general central dogma frames the emergent properties of life, which make biology both necessary and difficult to engineer. In a process engineering paradigm, each biological process stream and process unit is heavily influenced by regulatory interactions and interactions with the surrounding environment. Synthetic biology is developing the tools and methods that will increase control over these interactions, eventually resulting in an integrative synthetic biology that will allow ground-up cellular optimization. In this review, we attempt to contextualize the areas of synthetic biology into three tiers: (1) the process units and associated streams of the central dogma, (2) the intrinsic regulatory mechanisms, and (3) the extrinsic physical and chemical environment. Efforts at each of these three tiers attempt to control cellular systems and take advantage of emerging tools and approaches. Ultimately, it will be possible to integrate these approaches and realize the vision of integrative synthetic biology when cells are completely rewired for biotechnological goals. This review will highlight progress towards this goal as well as areas requiring further research.

HSV-I and the cellular DNA damage response.

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Smith, Samantha; Weller, Sandra K

2015-04-01

Peter Wildy first observed genetic recombination between strains of HSV in 1955. At the time, knowledge of DNA repair mechanisms was limited, and it has only been in the last decade that particular DNA damage response (DDR) pathways have been examined in the context of viral infections. One of the first reports addressing the interaction between a cellular DDR protein and HSV-1 was the observation by Lees-Miller et al . that DNA-dependent protein kinase catalytic subunit levels were depleted in an ICP0-dependent manner during Herpes simplex virus 1 infection. Since then, there have been numerous reports describing the interactions between HSV infection and cellular DDR pathways. Due to space limitations, this review will focus predominantly on the most recent observations regarding how HSV navigates a potentially hostile environment to replicate its genome.

PV-Powered CoMP-Based Green Cellular Networks with a Standby Grid Supply

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Abu Jahid

2017-01-01

Full Text Available This paper proposes a novel framework for PV-powered cellular networks with a standby grid supply and an essential energy management technique for achieving envisaged green networks. The proposal considers an emerging cellular network architecture employing two types of coordinated multipoint (CoMP transmission techniques for serving the subscribers. Under the proposed framework, each base station (BS is powered by an individual PV solar energy module having an independent storage device. BSs are also connected to the conventional grid supply for meeting additional energy demand. We also propose a dynamic inter-BS solar energy sharing policy through a transmission line for further greening the proposed network by minimizing the consumption from the grid supply. An extensive simulation-based study in the downlink of a Long-Term Evolution (LTE cellular system is carried out for evaluating the energy efficiency performance of the proposed framework. System performance is also investigated for identifying the impact of various system parameters including storage factor, storage capacity, solar generation capacity, transmission line loss, and different CoMP techniques.

Cellular neural networks for the stereo matching problem

International Nuclear Information System (INIS)

Taraglio, S.; Zanela, A.

1997-03-01

The applicability of the Cellular Neural Network (CNN) paradigm to the problem of recovering information on the tridimensional structure of the environment is investigated. The approach proposed is the stereo matching of video images. The starting point of this work is the Zhou-Chellappa neural network implementation for the same problem. The CNN based system we present here yields the same results as the previous approach, but without the many existing drawbacks

A global genetic interaction network maps a wiring diagram of cellular function.

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Costanzo, Michael; VanderSluis, Benjamin; Koch, Elizabeth N; Baryshnikova, Anastasia; Pons, Carles; Tan, Guihong; Wang, Wen; Usaj, Matej; Hanchard, Julia; Lee, Susan D; Pelechano, Vicent; Styles, Erin B; Billmann, Maximilian; van Leeuwen, Jolanda; van Dyk, Nydia; Lin, Zhen-Yuan; Kuzmin, Elena; Nelson, Justin; Piotrowski, Jeff S; Srikumar, Tharan; Bahr, Sondra; Chen, Yiqun; Deshpande, Raamesh; Kurat, Christoph F; Li, Sheena C; Li, Zhijian; Usaj, Mojca Mattiazzi; Okada, Hiroki; Pascoe, Natasha; San Luis, Bryan-Joseph; Sharifpoor, Sara; Shuteriqi, Emira; Simpkins, Scott W; Snider, Jamie; Suresh, Harsha Garadi; Tan, Yizhao; Zhu, Hongwei; Malod-Dognin, Noel; Janjic, Vuk; Przulj, Natasa; Troyanskaya, Olga G; Stagljar, Igor; Xia, Tian; Ohya, Yoshikazu; Gingras, Anne-Claude; Raught, Brian; Boutros, Michael; Steinmetz, Lars M; Moore, Claire L; Rosebrock, Adam P; Caudy, Amy A; Myers, Chad L; Andrews, Brenda; Boone, Charles

2016-09-23

We generated a global genetic interaction network for Saccharomyces cerevisiae, constructing more than 23 million double mutants, identifying about 550,000 negative and about 350,000 positive genetic interactions. This comprehensive network maps genetic interactions for essential gene pairs, highlighting essential genes as densely connected hubs. Genetic interaction profiles enabled assembly of a hierarchical model of cell function, including modules corresponding to protein complexes and pathways, biological processes, and cellular compartments. Negative interactions connected functionally related genes, mapped core bioprocesses, and identified pleiotropic genes, whereas positive interactions often mapped general regulatory connections among gene pairs, rather than shared functionality. The global network illustrates how coherent sets of genetic interactions connect protein complex and pathway modules to map a functional wiring diagram of the cell. Copyright © 2016, American Association for the Advancement of Science.

Dendritic cells modulate burn wound healing by enhancing early proliferation.

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Vinish, Monika; Cui, Weihua; Stafford, Eboni; Bae, Leon; Hawkins, Hal; Cox, Robert; Toliver-Kinsky, Tracy

2016-01-01

Adequate wound healing is vital for burn patients to reduce the risk of infections and prolonged hospitalization. Dendritic cells (DCs) are antigen presenting cells that release cytokines and are central for the activation of innate and acquired immune responses. Studies have showed their presence in human burn wounds; however, their role in burn wound healing remains to be determined. This study investigated the role of DCs in modulating healing responses within the burn wound. A murine model of full-thickness contact burns was used to study wound healing in the absence of DCs (CD11c promoter-driven diphtheria toxin receptor transgenic mice) and in a DC-rich environment (using fms-like tyrosine kinase-3 ligand, FL- a DC growth factor). Wound closure was significantly delayed in DC-deficient mice and was associated with significant suppression of early cellular proliferation, granulation tissue formation, wound levels of TGFβ1 and formation of CD31+ vessels in healing wounds. In contrast, DC enhancement significantly accelerated early wound closure, associated with increased and accelerated cellular proliferation, granulation tissue formation, and increased TGFβ1 levels and CD31+ vessels in healing wounds. We conclude that DCs play an important role in the acceleration of early wound healing events, likely by secreting factors that trigger the proliferation of cells that mediate wound healing. Therefore, pharmacological enhancement of DCs may provide a therapeutic intervention to facilitate healing of burn wounds. © 2016 by the Wound Healing Society.

Module-based analysis of robustness tradeoffs in the heat shock response system.

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Hiroyuki Kurata

2006-07-01

Full Text Available Biological systems have evolved complex regulatory mechanisms, even in situations where much simpler designs seem to be sufficient for generating nominal functionality. Using module-based analysis coupled with rigorous mathematical comparisons, we propose that in analogy to control engineering architectures, the complexity of cellular systems and the presence of hierarchical modular structures can be attributed to the necessity of achieving robustness. We employ the Escherichia coli heat shock response system, a strongly conserved cellular mechanism, as an example to explore the design principles of such modular architectures. In the heat shock response system, the sigma-factor sigma32 is a central regulator that integrates multiple feedforward and feedback modules. Each of these modules provides a different type of robustness with its inherent tradeoffs in terms of transient response and efficiency. We demonstrate how the overall architecture of the system balances such tradeoffs. An extensive mathematical exploration nevertheless points to the existence of an array of alternative strategies for the existing heat shock response that could exhibit similar behavior. We therefore deduce that the evolutionary constraints facing the system might have steered its architecture toward one of many robustly functional solutions.

Multi-Omics Studies towards Novel Modulators of Influenza A Virus–Host Interaction

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Sandra Söderholm

2016-09-01

Full Text Available Human influenza A viruses (IAVs cause global pandemics and epidemics. These viruses evolve rapidly, making current treatment options ineffective. To identify novel modulators of IAV–host interactions, we re-analyzed our recent transcriptomics, metabolomics, proteomics, phosphoproteomics, and genomics/virtual ligand screening data. We identified 713 potential modulators targeting 199 cellular and two viral proteins. Anti-influenza activity for 48 of them has been reported previously, whereas the antiviral efficacy of the 665 remains unknown. Studying anti-influenza efficacy and immuno/neuro-modulating properties of these compounds and their combinations as well as potential viral and host resistance to them may lead to the discovery of novel modulators of IAV–host interactions, which might be more effective than the currently available anti-influenza therapeutics.

Bringing the light to high throughput screening: use of optogenetic tools for the development of recombinant cellular assays

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Agus, Viviana; Di Silvio, Alberto; Rolland, Jean Francois; Mondini, Anna; Tremolada, Sara; Montag, Katharina; Scarabottolo, Lia; Redaelli, Loredana; Lohmer, Stefan

2015-03-01

The use of light-activated proteins represents a powerful tool to control biological processes with high spatial and temporal precision. These so called "optogenetic" technologies have been successfully validated in many recombinant systems, and have been widely applied to the study of cellular mechanisms in intact tissues or behaving animals; to do that, complex, high-intensity, often home-made instrumentations were developed to achieve the optimal power and precision of light stimulation. In our study we sought to determine if this optical modulation can be obtained also in a miniaturized format, such as a 384-well plate, using the instrumentations normally dedicated to fluorescence analysis in High Throughput Screening (HTS) activities, such as for example the FLIPR (Fluorometric Imaging Plate Reader) instrument. We successfully generated optogenetic assays for the study of different ion channel targets: the CaV1.3 calcium channel was modulated by the light-activated Channelrhodopsin-2, the HCN2 cyclic nucleotide gated (CNG) channel was modulated by the light activated bPAC adenylyl cyclase, and finally the genetically encoded voltage indicator ArcLight was efficiently used to measure potassium, sodium or chloride channel activity. Our results showed that stable, robust and miniaturized cellular assays can be developed using different optogenetic tools, and efficiently modulated by the FLIPR instrument LEDs in a 384-well format. The spatial and temporal resolution delivered by this technology might enormously advantage the early stages of drug discovery, leading to the identification of more physiological and effective drug molecules.

HIV-1 Replication and the Cellular Eukaryotic Translation Apparatus

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Santiago Guerrero

2015-01-01

Full Text Available Eukaryotic translation is a complex process composed of three main steps: initiation, elongation, and termination. During infections by RNA- and DNA-viruses, the eukaryotic translation machinery is used to assure optimal viral protein synthesis. Human immunodeficiency virus type I (HIV-1 uses several non-canonical pathways to translate its own proteins, such as leaky scanning, frameshifting, shunt, and cap-independent mechanisms. Moreover, HIV-1 modulates the host translation machinery by targeting key translation factors and overcomes different cellular obstacles that affect protein translation. In this review, we describe how HIV-1 proteins target several components of the eukaryotic translation machinery, which consequently improves viral translation and replication.

New approach to modulate retinal cellular toxic effects of high glucose using marine epa and dha

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Fagon Roxane

2011-06-01

Full Text Available Abstract Background Protective effects of omega-3 fatty acids against cellular damages of high glucose were studied on retinal pigmented epithelial (RPE cells. Methods Retinal epithelial cells were incubated with omega-3 marine oils rich in EPA and DHA and then with high glucose (25 mM for 48 hours. Cellular responses were compared to normal glucose (5 mM: intracellular redox status, reactive oxygen species (ROS, mitochondrial succinate deshydrogenase activity, inflammatory cytokines release and caveolin-1 expression were evaluated using microplate cytometry, ELISA and flow cytometry techniques. Fatty acids incorporation in retinal cell membranes was analysed using chromatography. Results Preincubation of the cells with fish oil decreased ROS overproduction, mitochondrial alterations and TNFα release. These protective effects could be attributed to an increase in caveolin-1 expression induced by marine oil. Conclusion Marine formulations rich in omega-3 fatty acids represent a promising therapeutic approach for diabetic retinopathy.

Functions of NQO1 in Cellular Protection and CoQ10 Metabolism and its Potential Role as a Redox Sensitive Molecular Switch

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David Ross

2017-08-01

Full Text Available NQO1 is one of the two major quinone reductases in mammalian systems. It is highly inducible and plays multiple roles in cellular adaptation to stress. A prevalent polymorphic form of NQO1 results in an absence of NQO1 protein and activity so it is important to elucidate the specific cellular functions of NQO1. Established roles of NQO1 include its ability to prevent certain quinones from one electron redox cycling but its role in quinone detoxification is dependent on the redox stability of the hydroquinone generated by two-electron reduction. Other documented roles of NQO1 include its ability to function as a component of the plasma membrane redox system generating antioxidant forms of ubiquinone and vitamin E and at high levels, as a direct superoxide reductase. Emerging roles of NQO1 include its function as an efficient intracellular generator of NAD+ for enzymes including PARP and sirtuins which has gained particular attention with respect to metabolic syndrome. NQO1 interacts with a growing list of proteins, including intrinsically disordered proteins, protecting them from 20S proteasomal degradation. The interactions of NQO1 also extend to mRNA. Recent identification of NQO1 as a mRNA binding protein have been investigated in more detail using SERPIN1A1 (which encodes the serine protease inhibitor α-1-antitrypsin as a target mRNA and indicate a role of NQO1 in control of translation of α-1-antitrypsin, an important modulator of COPD and obesity related metabolic syndrome. NQO1 undergoes structural changes and alterations in its ability to bind other proteins as a result of the cellular reduced/oxidized pyridine nucleotide ratio. This suggests NQO1 may act as a cellular redox switch potentially altering its interactions with other proteins and mRNA as a result of the prevailing redox environment.

Cellular MR Imaging

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Michel Modo

2005-07-01

Full Text Available Cellular MR imaging is a young field that aims to visualize targeted cells in living organisms. In order to provide a different signal intensity of the targeted cell, they are either labeled with MR contrast agents in vivo or prelabeled in vitro. Either (ultrasmall superparamagnetic iron oxide [(USPIO] particles or (polymeric paramagnetic chelates can be used for this purpose. For in vivo cellular labeling, Gd3+- and Mn2+- chelates have mainly been used for targeted hepatobiliary imaging, and (USPIO-based cellular imaging has been focused on imaging of macrophage activity. Several of these magneto-pharmaceuticals have been FDA-approved or are in late-phase clinical trials. As for prelabeling of cells in vitro, a challenge has been to induce a sufficient uptake of contrast agents into nonphagocytic cells, without affecting normal cellular function. It appears that this issue has now largely been resolved, leading to an active research on monitoring the cellular biodistribution in vivo following transplantation or transfusion of these cells, including cell migration and trafficking. New applications of cellular MR imaging will be directed, for instance, towards our understanding of hematopoietic (immune cell trafficking and of novel guided (stem cell-based therapies aimed to be translated to the clinic in the future.

Zizyphin modulates calcium signalling in human taste bud cells and fat taste perception in the mouse.

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Murtaza, Babar; Berrichi, Meryem; Bennamar, Chahid; Tordjmann, Thierry; Djeziri, Fatima Z; Hichami, Aziz; Leemput, Julia; Belarbi, Meriem; Ozdener, Hakan; Khan, Naim A

2017-10-01

Zizyphin, isolated from Zizyphus sps. leaf extracts, has been shown to modulate sugar taste perception, and the palatability of a sweet solution is increased by the addition of fatty acids. We, therefore, studied whether zizyphin also modulates fat taste perception. Zizyphin was purified from edible fruit of Zizyphus lotus L. Zizyphin-induced increases in [Ca 2+ ]i in human taste bud cells (hTBC). Zizyphin shared the endoplasmic reticulum Ca 2+ pool and also recruited, in part, Ca 2+ from extracellular environment via the opening of store-operated Ca 2+ channels. Zizyphin exerted additive actions on linoleic acid (LA)-induced increases in [Ca 2+ ]i in these cells, indicating that zizyphin does not exert its action via fatty acid receptors. However, zizyphin seemed to exert, at least in part, its action via bile acid receptor Takeda-G-protein-receptor-5 in hTBC. In behavioural tests, mice exhibited preference for both LA and zizyphin. Interestingly, zizyphin increased the preference for a solution containing-LA. This study is the first evidence of the modulation of fat taste perception by zizyphin at the cellular level in hTBC. Our study might be helpful for considering the synthesis of zizyphin analogues as 'taste modifiers' with a potential in the management of obesity and lipid-mediated disorders. © 2017 Société Française de Pharmacologie et de Thérapeutique.

Contribution of cellular autolysis to tissular functions during plant development.

Science.gov (United States)

Escamez, Sacha; Tuominen, Hannele

2017-02-01

Plant development requires specific cells to be eliminated in a predictable and genetically regulated manner referred to as programmed cell death (PCD). However, the target cells do not merely die but they also undergo autolysis to degrade their cellular corpses. Recent progress in understanding developmental cell elimination suggests that distinct proteins execute PCD sensu stricto and autolysis. In addition, cell death alone and cell dismantlement can fulfill different functions. Hence, it appears biologically meaningful to distinguish between the modules of PCD and autolysis during plant development. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

An automation of design and modelling tasks in NX Siemens environment with original software - generator module

Science.gov (United States)

Zbiciak, M.; Grabowik, C.; Janik, W.

2015-11-01

Nowadays the design constructional process is almost exclusively aided with CAD/CAE/CAM systems. It is evaluated that nearly 80% of design activities have a routine nature. These design routine tasks are highly susceptible to automation. Design automation is usually made with API tools which allow building original software responsible for adding different engineering activities. In this paper the original software worked out in order to automate engineering tasks at the stage of a product geometrical shape design is presented. The elaborated software works exclusively in NX Siemens CAD/CAM/CAE environment and was prepared in Microsoft Visual Studio with application of the .NET technology and NX SNAP library. The software functionality allows designing and modelling of spur and helicoidal involute gears. Moreover, it is possible to estimate relative manufacturing costs. With the Generator module it is possible to design and model both standard and non-standard gear wheels. The main advantage of the model generated in such a way is its better representation of an involute curve in comparison to those which are drawn in specialized standard CAD systems tools. It comes from fact that usually in CAD systems an involute curve is drawn by 3 points that respond to points located on the addendum circle, the reference diameter of a gear and the base circle respectively. In the Generator module the involute curve is drawn by 11 involute points which are located on and upper the base and the addendum circles therefore 3D gear wheels models are highly accurate. Application of the Generator module makes the modelling process very rapid so that the gear wheel modelling time is reduced to several seconds. During the conducted research the analysis of differences between standard 3 points and 11 points involutes was made. The results and conclusions drawn upon analysis are shown in details.

Activation of the hypothalamic-pituitary-adrenal stress axis induces cellular oxidative stress

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Jereme G. Spiers

2015-01-01

Full Text Available Glucocorticoids released from the adrenal gland in response to stress-induced activation of the hypothalamic-pituitary-adrenal (HPA axis induce activity in the cellular reduction-oxidation (redox system. The redox system is a ubiquitous chemical mechanism allowing the transfer of electrons between donor/acceptors and target molecules during oxidative phosphorylation while simultaneously maintaining the overall cellular environment in a reduced state. The objective of this review is to present an overview of the current literature discussing the link between HPA axis-derived glucocorticoids and increased oxidative stress, particularly focussing on the redox changes observed in the hippocampus following glucocorticoid exposure.

Perturbation of cellular signaling cascades modulated by ionizing radiation and environmental stress

International Nuclear Information System (INIS)

Ugolini, M.

2014-01-01

Cellular signaling plays a central role in the regulation of several cell functions, which can be perturbed by different external stimuli, including environmental stress and ionizing radiation. The dysregulation of intra- and extracellular mechanisms may alter the correct behaviour of cells. The aim of this work was to investigate the activation of strongly interlaced intracellular signaling pathways, following the exposure to low- and medium-doses of X-rays, with a focus on the mechanisms involved in the inflammatory- and apoptotic-related responses. In particular, the temporal dynamics of the ERK1/2 and PKB/AKT pathways and their possible dose dependences were investigated. The presented results indicate a clear dose dependence of such pathways only at early time points, suggesting a fast response of the system to X-rays and the need for further studies at shorter times after exposures.

Programmable cellular arrays. Faults testing and correcting in cellular arrays

International Nuclear Information System (INIS)

Cercel, L.

1978-03-01

A review of some recent researches about programmable cellular arrays in computing and digital processing of information systems is presented, and includes both combinational and sequential arrays, with full arbitrary behaviour, or which can realize better implementations of specialized blocks as: arithmetic units, counters, comparators, control systems, memory blocks, etc. Also, the paper presents applications of cellular arrays in microprogramming, in implementing of a specialized computer for matrix operations, in modeling of universal computing systems. The last section deals with problems of fault testing and correcting in cellular arrays. (author)

Cannabinoids Modulate Neuronal Activity and Cancer by CB1 and CB2 Receptor-Independent Mechanisms

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Ken Soderstrom

2017-10-01

Full Text Available Cannabinoids include the active constituents of Cannabis or are molecules that mimic the structure and/or function of these Cannabis-derived molecules. Cannabinoids produce many of their cellular and organ system effects by interacting with the well-characterized CB1 and CB2 receptors. However, it has become clear that not all effects of cannabinoid drugs are attributable to their interaction with CB1 and CB2 receptors. Evidence now demonstrates that cannabinoid agents produce effects by modulating activity of the entire array of cellular macromolecules targeted by other drug classes, including: other receptor types; ion channels; transporters; enzymes, and protein- and non-protein cellular structures. This review summarizes evidence for these interactions in the CNS and in cancer, and is organized according to the cellular targets involved. The CNS represents a well-studied area and cancer is emerging in terms of understanding mechanisms by which cannabinoids modulate their activity. Considering the CNS and cancer together allow identification of non-cannabinoid receptor targets that are shared and divergent in both systems. This comparative approach allows the identified targets to be compared and contrasted, suggesting potential new areas of investigation. It also provides insight into the diverse sources of efficacy employed by this interesting class of drugs. Obtaining a comprehensive understanding of the diverse mechanisms of cannabinoid action may lead to the design and development of therapeutic agents with greater efficacy and specificity for their cellular targets.

Cellular mechanics and motility

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Hénon, Sylvie; Sykes, Cécile

2015-10-01

The term motility defines the movement of a living organism. One widely known example is the motility of sperm cells, or the one of flagellar bacteria. The propulsive element of such organisms is a cilium(or flagellum) that beats. Although cells in our tissues do not have a flagellum in general, they are still able to move, as we will discover in this chapter. In fact, in both cases of movement, with or without a flagellum, cell motility is due to a dynamic re-arrangement of polymers inside the cell. Let us first have a closer look at the propulsion mechanism in the case of a flagellum or a cilium, which is the best known, but also the simplest, and which will help us to define the hydrodynamic general conditions of cell movement. A flagellum is sustained by cellular polymers arranged in semi-flexible bundles and flagellar beating generates cell displacement. These polymers or filaments are part of the cellular skeleton, or "cytoskeleton", which is, in this case, external to the cellular main body of the organism. In fact, bacteria move in a hydrodynamic regime in which viscosity dominates over inertia. The system is thus in a hydrodynamic regime of low Reynolds number (Box 5.1), which is nearly exclusively the case in all cell movements. Bacteria and their propulsion mode by flagella beating are our unicellular ancestors 3.5 billion years ago. Since then, we have evolved to form pluricellular organisms. However, to keep the ability of displacement, to heal our wounds for example, our cells lost their flagellum, since it was not optimal in a dense cell environment: cells are too close to each other to leave enough space for the flagella to accomplish propulsion. The cytoskeleton thus developed inside the cell body to ensure cell shape changes and movement, and also mechanical strength within a tissue. The cytoskeleton of our cells, like the polymers or filaments that sustain the flagellum, is also composed of semi-flexible filaments arranged in bundles, and also in

47 CFR 22.970 - Unacceptable interference to part 90 non-cellular 800 MHz licensees from cellular radiotelephone...

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2010-10-01

...-cellular 800 MHz licensees from cellular radiotelephone or part 90-800 MHz cellular systems. 22.970 Section... MOBILE SERVICES Cellular Radiotelephone Service § 22.970 Unacceptable interference to part 90 non-cellular 800 MHz licensees from cellular radiotelephone or part 90-800 MHz cellular systems. (a) Definition...

Using Mouse Mammary Tumor Cells to Teach Core Biology Concepts: A Simple Lab Module.

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McIlrath, Victoria; Trye, Alice; Aguanno, Ann

2015-06-18

Undergraduate biology students are required to learn, understand and apply a variety of cellular and molecular biology concepts and techniques in preparation for biomedical, graduate and professional programs or careers in science. To address this, a simple laboratory module was devised to teach the concepts of cell division, cellular communication and cancer through the application of animal cell culture techniques. Here the mouse mammary tumor (MMT) cell line is used to model for breast cancer. Students learn to grow and characterize these animal cells in culture and test the effects of traditional and non-traditional chemotherapy agents on cell proliferation. Specifically, students determine the optimal cell concentration for plating and growing cells, learn how to prepare and dilute drug solutions, identify the best dosage and treatment time course of the antiproliferative agents, and ascertain the rate of cell death in response to various treatments. The module employs both a standard cell counting technique using a hemocytometer and a novel cell counting method using microscopy software. The experimental procedure lends to open-ended inquiry as students can modify critical steps of the protocol, including testing homeopathic agents and over-the-counter drugs. In short, this lab module requires students to use the scientific process to apply their knowledge of the cell cycle, cellular signaling pathways, cancer and modes of treatment, all while developing an array of laboratory skills including cell culture and analysis of experimental data not routinely taught in the undergraduate classroom.

Manned Mission Space Exploration Utilizing a Flexible Universal Module

Science.gov (United States)

Humphries, P.; Barez, F.; Gowda, A.

2018-02-01

The proposed ASMS, Inc. "Flexible Universal Module" is in support of NASA's Deep Space Gateway project. The Flexible Universal Module provides a possible habitation or manufacturing environment in support of Manned Mission for Space Exploration.

Health effects of a subway environment in healthy volunteers.

Science.gov (United States)

Klepczyńska Nyström, A; Svartengren, M; Grunewald, J; Pousette, C; Rödin, I; Lundin, A; Sköld, C M; Eklund, A; Larsson, B-M

2010-08-01

Environmental particle exposure, often estimated as the particulate mass of particles with a diameter subway environment. 20 healthy volunteers were exposed to a subway and a control environment for 2 h, followed by measurements of lung function and the inflammatory response in the lower airways (bronchoscopy) and in the peripheral blood. No cellular response was found in the airways after exposure to the subway environment. In the blood, we found a statistically significant increase in fibrinogen and regulatory T-cells expressing CD4/CD25/FOXP3. Subway and road tunnel environments have similar levels of PM(10) and PM(2.5), whilst the concentrations of ultrafine particles, nitrogen monoxide and dioxide are lower in the subway. Although no cellular response was detected, the findings indicate a biological response to the subway environment. Our studies show that using gravimetric estimates of ambient particulate air pollution alone may have clear limitations in health-risk assessment.

AV nodal function during atrial fibrillation: the role of electrotonic modulation of propagation

NARCIS (Netherlands)

Meijler, F.L.; Jalife, J.; Beaumont, J.; Vaidya, D.

1996-01-01

The irregular ventricular rhythm that accompanies atrial fibrillation (AF) has been explained in terms of concealed conduction within the AV node (AVN). However, the cellular basis of concealed conduction in AF remains poorly understood. Our hypothesis is that electrotonic modulation of AVN

Cellular and molecular response to irradiation in ataxia telangiectasia and in Fanconi's anemia

International Nuclear Information System (INIS)

Ridet, A.; Guillouf, C.; Duchaud, E.; Moustacchi, E.; Rosselli, F.

1997-01-01

Ataxia telangiectasia (AT) and Fanconi anemia (FA) are recessive genetic diseases featuring chromosomal instability, increased predisposition to cancer and in vitro hypersensitivity to ionizing radiation (AT) or DNA cross-linking agents (FA). Moreover, an in vivo hypersensitivity to γ-rays exposure was reported in both syndromes. Cellular response to irradiation includes growth arrest (cell cycle modification) and cell death (by apoptosis or necrosis). Since it is generally accepted that apoptosis modulates cellular sensitivity to genotoxic stress, it was of interest to investigate the contribution of apoptosis in determining FA and AT responses to DNA Damaging Agents. The results support the contention that the in vivo hypersensitivity to radiation in these syndromes is not related to a higher rate of apoptotic cells but could be to a higher necrotic response triggering inflammatory reactions in the patients affected by this syndromes. (authors)

Heterogeneous cellular networks

CERN Document Server

Hu, Rose Qingyang

2013-01-01

A timely publication providing coverage of radio resource management, mobility management and standardization in heterogeneous cellular networks The topic of heterogeneous cellular networks has gained momentum in industry and the research community, attracting the attention of standardization bodies such as 3GPP LTE and IEEE 802.16j, whose objectives are looking into increasing the capacity and coverage of the cellular networks. This book focuses on recent progresses,  covering the related topics including scenarios of heterogeneous network deployment, interference management i

Acanthamoeba and Dictyostelium as Cellular Models for Legionella Infection

Science.gov (United States)

Swart, A. Leoni; Harrison, Christopher F.; Eichinger, Ludwig; Steinert, Michael; Hilbi, Hubert

2018-01-01

Environmental bacteria of the genus Legionella naturally parasitize free-living amoebae. Upon inhalation of bacteria-laden aerosols, the opportunistic pathogens grow intracellularly in alveolar macrophages and can cause a life-threatening pneumonia termed Legionnaires' disease. Intracellular replication in amoebae and macrophages takes place in a unique membrane-bound compartment, the Legionella-containing vacuole (LCV). LCV formation requires the bacterial Icm/Dot type IV secretion system, which translocates literally hundreds of “effector” proteins into host cells, where they modulate crucial cellular processes for the pathogen's benefit. The mechanism of LCV formation appears to be evolutionarily conserved, and therefore, amoebae are not only ecologically significant niches for Legionella spp., but also useful cellular models for eukaryotic phagocytes. In particular, Acanthamoeba castellanii and Dictyostelium discoideum emerged over the last years as versatile and powerful models. Using genetic, biochemical and cell biological approaches, molecular interactions between amoebae and Legionella pneumophila have recently been investigated in detail with a focus on the role of phosphoinositide lipids, small and large GTPases, autophagy components and the retromer complex, as well as on bacterial effectors targeting these host factors. PMID:29552544

Acanthamoeba and Dictyostelium as Cellular Models for Legionella Infection

Directory of Open Access Journals (Sweden)

A. Leoni Swart

2018-03-01

Full Text Available Environmental bacteria of the genus Legionella naturally parasitize free-living amoebae. Upon inhalation of bacteria-laden aerosols, the opportunistic pathogens grow intracellularly in alveolar macrophages and can cause a life-threatening pneumonia termed Legionnaires' disease. Intracellular replication in amoebae and macrophages takes place in a unique membrane-bound compartment, the Legionella-containing vacuole (LCV. LCV formation requires the bacterial Icm/Dot type IV secretion system, which translocates literally hundreds of “effector” proteins into host cells, where they modulate crucial cellular processes for the pathogen's benefit. The mechanism of LCV formation appears to be evolutionarily conserved, and therefore, amoebae are not only ecologically significant niches for Legionella spp., but also useful cellular models for eukaryotic phagocytes. In particular, Acanthamoeba castellanii and Dictyostelium discoideum emerged over the last years as versatile and powerful models. Using genetic, biochemical and cell biological approaches, molecular interactions between amoebae and Legionella pneumophila have recently been investigated in detail with a focus on the role of phosphoinositide lipids, small and large GTPases, autophagy components and the retromer complex, as well as on bacterial effectors targeting these host factors.

Random-Access Technique for Self-Organization of 5G Millimeter-Wave Cellular Communications

Directory of Open Access Journals (Sweden)

Jasper Meynard Arana

2016-01-01

Full Text Available The random-access (RA technique is a key procedure in cellular networks and self-organizing networks (SONs, but the overall processing time of this technique in millimeter-wave (mm-wave cellular systems with directional beams is very long because RA preambles (RAPs should be transmitted in all directions of Tx and Rx beams. In this paper, two different types of preambles (RAP-1 and RAP-2 are proposed to reduce the processing time in the RA stage. After analyzing the correlation property, false-alarm probability, and detection probability of the proposed RAPs, we perform simulations to show that the RAP-2 is suitable for RA in mm-wave cellular systems with directional beams because of the smaller processing time and high detection probability in multiuser environments.

A versatile cis-acting inverter module for synthetic translational switches.

Science.gov (United States)

Endo, Kei; Hayashi, Karin; Inoue, Tan; Saito, Hirohide

2013-01-01

Artificial genetic switches have been designed and tuned individually in living cells. A method to directly invert an existing OFF switch to an ON switch should be highly convenient to construct complex circuits from well-characterized modules, but developing such a technique has remained a challenge. Here we present a cis-acting RNA module to invert the function of a synthetic translational OFF switch to an ON switch in mammalian cells. This inversion maintains the property of the parental switch in response to a particular input signal. In addition, we demonstrate simultaneous and specific expression control of both the OFF and ON switches. The module fits the criteria of universality and expands the versatility of mRNA-based information processing systems developed for artificially controlling mammalian cellular behaviour.

47 CFR 22.909 - Cellular markets.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 2 2010-10-01 2010-10-01 false Cellular markets. 22.909 Section 22.909... Cellular Radiotelephone Service § 22.909 Cellular markets. Cellular markets are standard geographic areas used by the FCC for administrative convenience in the licensing of cellular systems. Cellular markets...

Multiscale evaluation of cellular adhesion alteration and cytoskeleton remodeling by magnetic bead twisting.

Science.gov (United States)

Isabey, Daniel; Pelle, Gabriel; André Dias, Sofia; Bottier, Mathieu; Nguyen, Ngoc-Minh; Filoche, Marcel; Louis, Bruno

2016-08-01

Cellular adhesion forces depend on local biological conditions meaning that adhesion characterization must be performed while preserving cellular integrity. We presently postulate that magnetic bead twisting provides an appropriate stress, i.e., basically a clamp, for assessment in living cells of both cellular adhesion and mechanical properties of the cytoskeleton. A global dissociation rate obeying a Bell-type model was used to determine the natural dissociation rate ([Formula: see text]) and a reference stress ([Formula: see text]). These adhesion parameters were determined in parallel to the mechanical properties for a variety of biological conditions in which either adhesion or cytoskeleton was selectively weakened or strengthened by changing successively ligand concentration, actin polymerization level (by treating with cytochalasin D), level of exerted stress (by increasing magnetic torque), and cell environment (by using rigid and soft 3D matrices). On the whole, this multiscale evaluation of the cellular and molecular responses to a controlled stress reveals an evolution which is consistent with stochastic multiple bond theories and with literature results obtained with other molecular techniques. Present results confirm the validity of the proposed bead-twisting approach for its capability to probe cellular and molecular responses in a variety of biological conditions.

Nanomaterials and the Environment

International Nuclear Information System (INIS)

Manzo, Sonia; Rametta, Gabriella; Miglietta Maria Lucia; Di Francia, Girolamo

2015-01-01

Nanotechnology intend to engineer the material using the special properties that it exhibits in the nanoscale to create new products. These properties imply a greater chemical reactivity, a higher strength and electrical conductivity and, potentially, a more pronounced biological activity. This can have not only positive valence (antioxidant activity, penetration of cellular barriers to the release of drugs), but also negative (eg. Toxicity, induction of oxidative stress or cellular dysfunction). Therefore, in addition to the great practical interest, nanotechnology has attracted the attention of the scientific community and the legislative authority for the specific interactions that may occur with living beings and the environment [it

Contextual modulation of pain sensitivity utilising virtual environments.

Science.gov (United States)

Smith, Ashley; Carlow, Klancy; Biddulph, Tara; Murray, Brooke; Paton, Melissa; Harvie, Daniel S

2017-05-01

Investigating psychological mechanisms that modulate pain, such as those that might be accessed by manipulation of context, is of great interest to researchers seeking to better understand and treat pain. The aim of this study was to better understand the interaction between pain sensitivity, and contexts with inherent emotional and social salience - by exploiting modern immersive virtual reality (VR) technology. A within-subjects, randomised, double-blinded, repeated measures (RM) design was used. In total, 25 healthy participants were exposed to neutral, pleasant, threatening, socially positive and socially negative contexts, using an Oculus Rift DK2. Pressure pain thresholds (PPTs) were recorded in each context, as well as prior to and following the procedure. We also investigated whether trait anxiety and pain catastrophisation interacted with the relationship between the different contexts and pain. Pressure pain sensitivity was not modulated by context ( p  = 0.48). Anxiety and pain catastrophisation were not significantly associated with PPTs, nor did they interact with the relationship between context and PPTs. Contrary to our hypothesis, socially and emotionally salient contexts did not influence pain thresholds. In light of other research, we suggest that pain outcomes might only be tenable to manipulation by contextual cues if they specifically manipulate the meaning of the pain-eliciting stimulus, rather than manipulate psychological state generally - as per the current study. Future research might exploit immersive VR technology to better explore the link between noxious stimuli and contexts that directly alter its threat value.

Auditory object formation affects modulation perception

DEFF Research Database (Denmark)

Piechowiak, Tobias

2005-01-01

Most sounds in our environment, including speech, music, animal vocalizations and environmental noise, have fluctuations in intensity that are often highly correlated across different frequency regions. Because across-frequency modulation is so common, the ability to process such information...... is thought to be a powerful survival strategy in the natural world (Klump, 1996; Nelken et al., 1999). Coherent modulations in one sound can aid in the detection of another sound (Hall et al., 1984; Durlach, 1963). On the other hand, modulation in one frequency region can also impede the detection...... or discrimination of modulation in other frequency regions (Yost et al., 1989). Although the neural substrates for across-frequency modulation processing remain unclear, recent studies have concentrated on brainstem structures (Pressnitzer et al., 2001). In this study it is shown that sounds occurring after...

MARS Code in Linux Environment

Energy Technology Data Exchange (ETDEWEB)

Hwang, Moon Kyu; Bae, Sung Won; Jung, Jae Joon; Chung, Bub Dong [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

2005-07-01

The two-phase system analysis code MARS has been incorporated into Linux system. The MARS code was originally developed based on the RELAP5/MOD3.2 and COBRA-TF. The 1-D module which evolved from RELAP5 alone could be applied for the whole NSSS system analysis. The 3-D module developed based on the COBRA-TF, however, could be applied for the analysis of the reactor core region where 3-D phenomena would be better treated. The MARS code also has several other code units that could be incorporated for more detailed analysis. The separate code units include containment analysis modules and 3-D kinetics module. These code modules could be optionally invoked to be coupled with the main MARS code. The containment code modules (CONTAIN and CONTEMPT), for example, could be utilized for the analysis of the plant containment phenomena in a coupled manner with the nuclear reactor system. The mass and energy interaction during the hypothetical coolant leakage accident could, thereby, be analyzed in a more realistic manner. In a similar way, 3-D kinetics could be incorporated for simulating the three dimensional reactor kinetic behavior, instead of using the built-in point kinetics model. The MARS code system, developed initially for the MS Windows environment, however, would not be adequate enough for the PC cluster system where multiple CPUs are available. When parallelism is to be eventually incorporated into the MARS code, MS Windows environment is not considered as an optimum platform. Linux environment, on the other hand, is generally being adopted as a preferred platform for the multiple codes executions as well as for the parallel application. In this study, MARS code has been modified for the adaptation of Linux platform. For the initial code modification, the Windows system specific features have been removed from the code. Since the coupling code module CONTAIN is originally in a form of dynamic load library (DLL) in the Windows system, a similar adaptation method

MARS Code in Linux Environment

International Nuclear Information System (INIS)

Hwang, Moon Kyu; Bae, Sung Won; Jung, Jae Joon; Chung, Bub Dong

2005-01-01

The two-phase system analysis code MARS has been incorporated into Linux system. The MARS code was originally developed based on the RELAP5/MOD3.2 and COBRA-TF. The 1-D module which evolved from RELAP5 alone could be applied for the whole NSSS system analysis. The 3-D module developed based on the COBRA-TF, however, could be applied for the analysis of the reactor core region where 3-D phenomena would be better treated. The MARS code also has several other code units that could be incorporated for more detailed analysis. The separate code units include containment analysis modules and 3-D kinetics module. These code modules could be optionally invoked to be coupled with the main MARS code. The containment code modules (CONTAIN and CONTEMPT), for example, could be utilized for the analysis of the plant containment phenomena in a coupled manner with the nuclear reactor system. The mass and energy interaction during the hypothetical coolant leakage accident could, thereby, be analyzed in a more realistic manner. In a similar way, 3-D kinetics could be incorporated for simulating the three dimensional reactor kinetic behavior, instead of using the built-in point kinetics model. The MARS code system, developed initially for the MS Windows environment, however, would not be adequate enough for the PC cluster system where multiple CPUs are available. When parallelism is to be eventually incorporated into the MARS code, MS Windows environment is not considered as an optimum platform. Linux environment, on the other hand, is generally being adopted as a preferred platform for the multiple codes executions as well as for the parallel application. In this study, MARS code has been modified for the adaptation of Linux platform. For the initial code modification, the Windows system specific features have been removed from the code. Since the coupling code module CONTAIN is originally in a form of dynamic load library (DLL) in the Windows system, a similar adaptation method

Temporal organization of cellular self-replication

Science.gov (United States)

Alexandrov, Victor; Pugatch, Rami

Recent experiments demonstrate that single cells grow exponentially in time. A coarse grained model of cellular self-replication is presented based on a novel concept - the cell is viewed as a self-replicating queue. This allows to have a more fundamental look into various temporal organizations and, importantly, the inherent non-Markovianity of noise distributions. As an example, the distribution of doubling times can be inferred and compared to single cell experiments in bacteria. We observe data collapse upon scaling by the average doubling time for different environments and present an inherent task allocation trade-off. Support from the Simons Center for Systems Biology, IAS, Princeon.

Dunnione ameliorates cisplatin-induced small intestinal damage by modulating NAD{sup +} metabolism

Energy Technology Data Exchange (ETDEWEB)

Pandit, Arpana; Kim, Hyung-Jin; Oh, Gi-Su; Shen, AiHua; Lee, Su-Bin; Khadka, Dipendra; Lee, SeungHoon [Center for Metabolic Function Regulation & Department of Microbiology, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Shim, Hyeok; Yang, Sei-Hoon; Cho, Eun-Young [Department of Internal Medicine, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Kwon, Kang-Beom [Department of Oriental Medical Physiology, School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Kwak, Tae Hwan [PAEAN Biotechnology, 160 Techno-2 Street, Yuseong-gu, Daejeon 305-500 (Korea, Republic of); Choe, Seong-Kyu; Park, Raekil [Center for Metabolic Function Regulation & Department of Microbiology, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); So, Hong-Seob, E-mail: jeanso@wku.ac.kr [Center for Metabolic Function Regulation & Department of Microbiology, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of)

2015-11-27

Although cisplatin is a widely used anticancer drug for the treatment of a variety of tumors, its use is critically limited because of adverse effects such as ototoxicity, nephrotoxicity, neuropathy, and gastrointestinal damage. Cisplatin treatment increases oxidative stress biomarkers in the small intestine, which may induce apoptosis of epithelial cells and thereby elicit damage to the small intestine. Nicotinamide adenine dinucleotide (NAD{sup +}) is a cofactor for various enzymes associated with cellular homeostasis. In the present study, we demonstrated that the hyper-activation of poly(ADP-ribose) polymerase-1 (PARP-1) is closely associated with the depletion of NAD{sup +} in the small intestine after cisplatin treatment, which results in downregulation of sirtuin1 (SIRT1) activity. Furthermore, a decrease in SIRT1 activity was found to play an important role in cisplatin-mediated small intestinal damage through nuclear factor (NF)-κB p65 activation, facilitated by its acetylation increase. However, use of dunnione as a strong substrate for the NADH:quinone oxidoreductase 1 (NQO1) enzyme led to an increase in intracellular NAD{sup +} levels and prevented the cisplatin-induced small intestinal damage correlating with the modulation of PARP-1, SIRT1, and NF-κB. These results suggest that direct modulation of cellular NAD{sup +} levels by pharmacological NQO1 substrates could be a promising therapeutic approach for protecting against cisplatin-induced small intestinal damage. - Highlights: • NAD{sup +} acts as a cofactor for numerous enzymes including Sirtuins and PARP. • Up-regulation of SIRT1 could attenuate the cisplatin-induced intestinal damage. • Modulation of the cellular NAD{sup +} could be a promising therapeutic approach.

Modulation of transcription factors by curcumin.

Science.gov (United States)

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.

Prospects for cellular mutational assays in human populations

International Nuclear Information System (INIS)

Mendelsohn, M.L.

1985-01-01

Practical, sensitive, effective, human cellular assays for detecting somatic and germinal mutations would have great value in environmental mutagenesis and carcinogenesis. When available, such assays should allow us to fill the void between human mutagenicity and the data that exist from short-term tests and from mutagenicity in other species. We will be able to validate the role of somatic mutations in carcinogenesis, to identify environmental factors that affect human germ cells, to integrate the effects of complex mixtures and the environment in the human subject, and to identify people who are hypersusceptible to genetic injury. Human cellular mutational assays, particularly when combined with cytogenetic and heritable mutational tests, promise to play pivotal roles in estimating the risk from low-dose radiation and chemical exposures. These combined methods avoid extrapolations of dose and from species to species, and may be sensitive enough and credible enough to permit politically, socially and scientifically acceptable risk management. 16 references

Forensic Tools for Mobile Phone Subscriber Identity Modules

Directory of Open Access Journals (Sweden)

Wayne Jansen

2006-06-01

Full Text Available Mobile phones and other handheld devices incorporating cellular capabilities, such as Personal Digital Assistants, are ubiquitous.  Besides placing calls, these devices allow users to perform other useful tasks, including text messaging and phonebook entry management.  When cell phones and cellular devices are involved in a crime or other incident, forensic specialists require tools that allow the proper retrieval and speedy examination of data present on the device.  For devices conforming to the Global System for Mobile Communications (GSM standards, certain data such as dialed numbers, text messages, and phonebook entries are maintained on a Subscriber Identity Module (SIM.  This paper gives a snapshot of the state of the art of forensic software tools for SIMs and an explanation of the types of digital evidence they can recover.

Preliminary Investigation of the Role of Cellular Immunity in Estrous Cycle Modulation of Post-Resection Breast Cancer Spread

National Research Council Canada - National Science Library

Hrushesky, William

2002-01-01

It is hypothesized that the short term objectives of doing this proposal are to better understand which sex steroids and which cellular immune functions control post resection metastatic cancer spread...

MRF Family Genes Are Involved in Translation Control, Especially under Energy-Deficient Conditions, and Their Expression and Functions Are Modulated by the TOR Signaling Pathway[OPEN

Science.gov (United States)

Lee, Du-Hwa; Park, Seung Jun; Ahn, Chang Sook

2017-01-01

Dynamic control of protein translation in response to the environment is essential for the survival of plant cells. Target of rapamycin (TOR) coordinates protein synthesis with cellular energy/nutrient availability through transcriptional modulation and phosphorylation of the translation machinery. However, mechanisms of TOR-mediated translation control are poorly understood in plants. Here, we report that Arabidopsis thaliana MRF (MA3 DOMAIN-CONTAINING TRANSLATION REGULATORY FACTOR) family genes encode translation regulatory factors under TOR control, and their functions are particularly important in energy-deficient conditions. Four MRF family genes (MRF1-MRF4) are transcriptionally induced by dark and starvation (DS). Silencing of multiple MRFs increases susceptibility to DS and treatment with a TOR inhibitor, while MRF1 overexpression decreases susceptibility. MRF proteins interact with eIF4A and cofractionate with ribosomes. MRF silencing decreases translation activity, while MRF1 overexpression increases it, accompanied by altered ribosome patterns, particularly in DS. Furthermore, MRF deficiency in DS causes altered distribution of mRNAs in sucrose gradient fractions and accelerates rRNA degradation. MRF1 is phosphorylated in vivo and phosphorylated by S6 kinases in vitro. MRF expression and MRF1 ribosome association and phosphorylation are modulated by cellular energy status and TOR activity. We discuss possible mechanisms of the function of MRF family proteins under normal and energy-deficient conditions and their functional link with the TOR pathway. PMID:29084871

Literature Review on Dynamic Cellular Manufacturing System

Science.gov (United States)

Nouri Houshyar, A.; Leman, Z.; Pakzad Moghadam, H.; Ariffin, M. K. A. M.; Ismail, N.; Iranmanesh, H.

2014-06-01

In previous decades, manufacturers faced a lot of challenges because of globalization and high competition in markets. These problems arise from shortening product life cycle, rapid variation in demand of products, and also rapid changes in manufcaturing technologies. Nowadays most manufacturing companies expend considerable attention for improving flexibility and responsiveness in order to overcome these kinds of problems and also meet customer's needs. By considering the trend toward the shorter product life cycle, the manufacturing environment is towards manufacturing a wide variety of parts in small batches [1]. One of the major techniques which are applied for improving manufacturing competitiveness is Cellular Manufacturing System (CMS). CMS is type of manufacturing system which tries to combine flexibility of job shop and also productivity of flow shop. In addition, Dynamic cellular manufacturing system which considers different time periods for the manufacturing system becomes an important topic and attracts a lot of attention to itself. Therefore, this paper made attempt to have a brief review on this issue and focused on all published paper on this subject. Although, this topic gains a lot of attention to itself during these years, none of previous researchers focused on reviewing the literature of that which can be helpful and useful for other researchers who intend to do the research on this topic. Therefore, this paper is the first study which has focused and reviewed the literature of dynamic cellular manufacturing system.

Complement factor H family proteins in their non-canonical role as modulators of cellular functions.

Science.gov (United States)

Józsi, Mihály; Schneider, Andrea E; Kárpáti, Éva; Sándor, Noémi

2018-01-04

Complement factor H is a major regulator of the alternative pathway of the complement system. The factor H-related proteins are less characterized, but recent data indicate that they rather promote complement activation. These proteins have some common ligands with factor H and have both overlapping and distinct functions depending on domain composition and the degree of conservation of amino acid sequence. Factor H and some of the factor H-related proteins also appear in a non-canonical function that is beyond their role in the modulation of complement activation. This review covers our current understanding on this emerging role of factor H family proteins in modulating the activation and function of various cells by binding to receptors or receptor ligands. Copyright © 2018 Elsevier Ltd. All rights reserved.

Modeling and Experimental Study of Soft Error Propagation Based on Cellular Automaton

Directory of Open Access Journals (Sweden)

Wei He

2016-01-01

Full Text Available Aiming to estimate SEE soft error performance of complex electronic systems, a soft error propagation model based on cellular automaton is proposed and an estimation methodology based on circuit partitioning and error propagation is presented. Simulations indicate that different fault grade jamming and different coupling factors between cells are the main parameters influencing the vulnerability of the system. Accelerated radiation experiments have been developed to determine the main parameters for raw soft error vulnerability of the module and coupling factors. Results indicate that the proposed method is feasible.

Human equilibrative nucleoside transporter-1 knockdown tunes cellular mechanics through epithelial-mesenchymal transition in pancreatic cancer cells.

Directory of Open Access Journals (Sweden)

Yeonju Lee

Full Text Available We report cell mechanical changes in response to alteration of expression of the human equilibrative nucleoside transporter-1 (hENT1, a most abundant and widely distributed plasma membrane nucleoside transporter in human cells and/or tissues. Modulation of hENT1 expression level altered the stiffness of pancreatic cancer Capan-1 and Panc 03.27 cells, which was analyzed by atomic force microscopy (AFM and correlated to microfluidic platform. The hENT1 knockdown induced reduction of cellular stiffness in both of cells up to 70%. In addition, cellular phenotypic changes such as cell morphology, migration, and expression level of epithelial-mesenchymal transition (EMT markers were observed after hENT1 knockdown. Cells with suppressed hENT1 became elongated, migrated faster, and had reduced E-cadherin and elevated N-cadherin compared to parental cells which are consistent with epithelial-mesenchymal transition (EMT. Those cellular phenotypic changes closely correlated with changes in cellular stiffness. This study suggests that hENT1 expression level affects cellular phenotype and cell elastic behavior can be a physical biomarker for quantify hENT1 expression and detect phenotypic shift. Furthermore, cell mechanics can be a critical tool in detecting disease progression and response to therapy.

Biomechanics of cellular solids.

Science.gov (United States)

Gibson, Lorna J

2005-03-01

Materials with a cellular structure are widespread in nature and include wood, cork, plant parenchyma and trabecular bone. Natural cellular materials are often mechanically efficient: the honeycomb-like microstructure of wood, for instance, gives it an exceptionally high performance index for resisting bending and buckling. Here we review the mechanics of a wide range of natural cellular materials and examine their role in lightweight natural sandwich structures (e.g. iris leaves) and natural tubular structures (e.g. plant stems or animal quills). We also describe two examples of engineered biomaterials with a cellular structure, designed to replace or regenerate tissue in the body.

Influence of the membrane environment on cholesterol transfer.

Science.gov (United States)

Breidigan, Jeffrey Michael; Krzyzanowski, Natalie; Liu, Yangmingyue; Porcar, Lionel; Perez-Salas, Ursula

2017-12-01

Cholesterol, an essential component in biological membranes, is highly unevenly distributed within the cell, with most localized in the plasma membrane while only a small fraction is found in the endoplasmic reticulum, where it is synthesized. Cellular membranes differ in lipid composition and protein content, and these differences can exist across their leaflets too. This thermodynamic landscape that cellular membranes impose on cholesterol is expected to modulate its transport. To uncover the role the membrane environment has on cholesterol inter- and intra-membrane movement, we used time-resolved small angle neutron scattering to study the passive movement of cholesterol between and within membranes with varying degrees of saturation content. We found that cholesterol moves systematically slower as the degree of saturation in the membranes increases, from a palmitoyl oleyl phosphotidylcholine membrane, which is unsaturated, to a dipalmitoylphosphatidylcholine (DPPC) membrane, which is fully saturated. Additionally, we found that the energetic barrier to move cholesterol in these phosphatidylcholine membranes is independent of their relative lipid composition and remains constant for both flip-flop and exchange at ∼100 kJ/mol. Further, by replacing DPPC with the saturated lipid palmitoylsphingomyelin, an abundant saturated lipid of the outer leaflet of the plasma membrane, we found the rates decreased by a factor of two. This finding is in stark contrast with recent molecular dynamic simulations that predict a dramatic slow-down of seven orders of magnitude for cholesterol flipping in membranes with a similar phosphocholine and SM lipid composition. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

Defining the cellular environment in the organ of Corti following extensive hair cell loss: a basis for future sensory cell replacement in the Cochlea.

Directory of Open Access Journals (Sweden)

Ruth R Taylor

Full Text Available BACKGROUND: Following the loss of hair cells from the mammalian cochlea, the sensory epithelium repairs to close the lesions but no new hair cells arise and hearing impairment ensues. For any cell replacement strategy to be successful, the cellular environment of the injured tissue has to be able to nurture new hair cells. This study defines characteristics of the auditory sensory epithelium after hair cell loss. METHODOLOGY/PRINCIPAL FINDINGS: Studies were conducted in C57BL/6 and CBA/Ca mice. Treatment with an aminoglycoside-diuretic combination produced loss of all outer hair cells within 48 hours in both strains. The subsequent progressive tissue re-organisation was examined using immunohistochemistry and electron microscopy. There was no evidence of significant de-differentiation of the specialised columnar supporting cells. Kir4.1 was down regulated but KCC4, GLAST, microtubule bundles, connexin expression patterns and pathways of intercellular communication were retained. The columnar supporting cells became covered with non-specialised cells migrating from the outermost region of the organ of Corti. Eventually non-specialised, flat cells replaced the columnar epithelium. Flat epithelium developed in distributed patches interrupting regions of columnar epithelium formed of differentiated supporting cells. Formation of the flat epithelium was initiated within a few weeks post-treatment in C57BL/6 mice but not for several months in CBA/Ca's, suggesting genetic background influences the rate of re-organisation. CONCLUSIONS/SIGNIFICANCE: The lack of dedifferentiation amongst supporting cells and their replacement by cells from the outer side of the organ of Corti are factors that may need to be considered in any attempt to promote endogenous hair cell regeneration. The variability of the cellular environment along an individual cochlea arising from patch-like generation of flat epithelium, and the possible variability between individuals

Cellular Reflectarray Antenna

Science.gov (United States)

Romanofsky, Robert R.

2010-01-01

The cellular reflectarray antenna is intended to replace conventional parabolic reflectors that must be physically aligned with a particular satellite in geostationary orbit. These arrays are designed for specified geographical locations, defined by latitude and longitude, each called a "cell." A particular cell occupies nominally 1,500 square miles (3,885 sq. km), but this varies according to latitude and longitude. The cellular reflectarray antenna designed for a particular cell is simply positioned to align with magnetic North, and the antenna surface is level (parallel to the ground). A given cellular reflectarray antenna will not operate in any other cell.

The Neurona at Home project: Simulating a large-scale cellular automata brain in a distributed computing environment

Science.gov (United States)

Acedo, L.; Villanueva-Oller, J.; Moraño, J. A.; Villanueva, R.-J.

2013-01-01

The Berkeley Open Infrastructure for Network Computing (BOINC) has become the standard open source solution for grid computing in the Internet. Volunteers use their computers to complete an small part of the task assigned by a dedicated server. We have developed a BOINC project called Neurona@Home whose objective is to simulate a cellular automata random network with, at least, one million neurons. We consider a cellular automata version of the integrate-and-fire model in which excitatory and inhibitory nodes can activate or deactivate neighbor nodes according to a set of probabilistic rules. Our aim is to determine the phase diagram of the model and its behaviour and to compare it with the electroencephalographic signals measured in real brains.

The software environment of RODOS

International Nuclear Information System (INIS)

Schuele, O.; Rafat, M.; Kossykh, V.

1996-01-01

The Software Environment of RODOS provides tools for processing and managing a large variety of different types of information, including those which are categorized in terms of meteorology, radiology, economy, emergency actions and countermeasures, rules, preferences, facts, maps, statistics, catalogues, models and methods. The main tasks of the Operating Subsystem OSY, which is based on the Client-Server Model, are the control of system operation, data management, and the exchange of information among various modules as well as the interaction with users in distributed computer systems. The paper describes the software environment of RODOS, in particular, the individual modules of its Operating Subsystem OSY, its distributed database, the geographical information system RoGIS, the on-line connections to radiological and meteorological networks and the software environment for the integration of external programs into the RODOS system

The software environment of RODOS

International Nuclear Information System (INIS)

Schuele, O.; Rafat, M.

1998-01-01

The Software Environment of RODOS provides tools for processing and managing a large variety of different types of information, including those which are categorised in terms of meteorology, radiology, economy, emergency actions and countermeasures, rules, preferences, facts, maps, statistics, catalogues, models and methods. The main tasks of the Operating Subsystem OSY, which is based on the Client-Server Model, are the control of system operation, data management, and the exchange of information among various modules as well as the interaction with users in distributed computer systems. The paper describes the software environment of RODOS, in particular, the individual modules of its Operating Subsystem OSY, its distributed database, the geographical information system RoGIS, the on-line connections to radiological and meteorological networks and the software environment for the integration of external programs into the RODOS system. (orig.)

The software environment of RODOS

Energy Technology Data Exchange (ETDEWEB)

Schuele, O; Rafat, M [Forschungszentrum Karlsruhe, Institut fuer Neutronenphysik und Reaktortechnik, Karlsruhe (Germany); Kossykh, V [Scientific Production Association ' TYPHOON' , Emergency Centre, Obninsk (Russian Federation)

1996-07-01

The Software Environment of RODOS provides tools for processing and managing a large variety of different types of information, including those which are categorized in terms of meteorology, radiology, economy, emergency actions and countermeasures, rules, preferences, facts, maps, statistics, catalogues, models and methods. The main tasks of the Operating Subsystem OSY, which is based on the Client-Server Model, are the control of system operation, data management, and the exchange of information among various modules as well as the interaction with users in distributed computer systems. The paper describes the software environment of RODOS, in particular, the individual modules of its Operating Subsystem OSY, its distributed database, the geographical information system RoGIS, the on-line connections to radiological and meteorological networks and the software environment for the integration of external programs into the RODOS system.

Linearizable cellular automata

International Nuclear Information System (INIS)

Nobe, Atsushi; Yura, Fumitaka

2007-01-01

The initial value problem for a class of reversible elementary cellular automata with periodic boundaries is reduced to an initial-boundary value problem for a class of linear systems on a finite commutative ring Z 2 . Moreover, a family of such linearizable cellular automata is given

Cellular and molecular response to irradiation in ataxia telangiectasia and in Fanconi`s anemia

Energy Technology Data Exchange (ETDEWEB)

Ridet, A.; Guillouf, C.; Duchaud, E.; Moustacchi, E.; Rosselli, F. [Institut Curie-Recherche, UMR 218, CNRS, 75 - Paris (France)

1997-03-01

Ataxia telangiectasia (AT) and Fanconi anemia (FA) are recessive genetic diseases featuring chromosomal instability, increased predisposition to cancer and in vitro hypersensitivity to ionizing radiation (AT) or DNA cross-linking agents (FA). Moreover, an in vivo hypersensitivity to {gamma}-rays exposure was reported in both syndromes. Cellular response to irradiation includes growth arrest (cell cycle modification) and cell death (by apoptosis or necrosis). Since it is generally accepted that apoptosis modulates cellular sensitivity to genotoxic stress, it was of interest to investigate the contribution of apoptosis in determining FA and AT responses to DNA Damaging Agents. The results support the contention that the in vivo hypersensitivity to radiation in these syndromes is not related to a higher rate of apoptotic cells but could be to a higher necrotic response triggering inflammatory reactions in the patients affected by this syndromes. (authors)

Electromagnetic cellular interactions.

Science.gov (United States)

Cifra, Michal; Fields, Jeremy Z; Farhadi, Ashkan

2011-05-01

Chemical and electrical interaction within and between cells is well established. Just the opposite is true about cellular interactions via other physical fields. The most probable candidate for an other form of cellular interaction is the electromagnetic field. We review theories and experiments on how cells can generate and detect electromagnetic fields generally, and if the cell-generated electromagnetic field can mediate cellular interactions. We do not limit here ourselves to specialized electro-excitable cells. Rather we describe physical processes that are of a more general nature and probably present in almost every type of living cell. The spectral range included is broad; from kHz to the visible part of the electromagnetic spectrum. We show that there is a rather large number of theories on how cells can generate and detect electromagnetic fields and discuss experimental evidence on electromagnetic cellular interactions in the modern scientific literature. Although small, it is continuously accumulating. Copyright © 2010 Elsevier Ltd. All rights reserved.

Active cellular sensing with quantum dots: Transitioning from research tool to reality; a review

International Nuclear Information System (INIS)

Delehanty, James B.; Susumu, Kimihiro; Manthe, Rachel L.; Algar, W. Russ; Medintz, Igor L.

2012-01-01

Highlights: ► Quantum dots (QDs) have evolved beyond mere cellular labeling reagents. ► Significant advances have been made in QD materials, surface coatings and bioconjugation. ► Cellular targeting/delivery has been achieved using polymers, peptides, proteins. ► Numerous QD-based sensing applications: extracellular, membrane, intracellular. - Abstract: The application of luminescent semiconductor quantum dots (QDs) within a wide range of biological imaging and sensing formats is now approaching its 15th year. The unique photophysical properties of these nanomaterials have long been envisioned as having the potential to revolutionize biosensing within cellular studies that rely on fluorescence. However, it is only now that these materials are making the transition towards accomplishing this goal. With the idea of understanding how to actively incorporate QDs into different types of cellular biosensing, we review the progress in many of the areas relevant to achieving this goal. This includes the synthesis of the QDs themselves, with an emphasis on minimizing potential toxicity, along with the general methods for making these nanocrystalline structures stable in aqueous media. We next survey some methods for conjugating QDs to biomolecules to allow them to participate in active biosensing. Lastly, we extensively review many of the applications where QDs have been demonstrated in an active role in cellular biosensing. These formats cover a wide range of possibilities including where the QDs have contributed to: monitoring the cell's interaction with its extracellular environment; elucidating the complex molecular interplay that characterizes the plasma membrane; understanding how cells continuously endocytose and exocytose materials across the cellular membrane; visualizing organelle trafficking; and, perhaps most importantly, monitoring the intracellular presence of target molecules such as nucleic acids, nutrients, cofactors, and ions or, alternatively

High performance cellular level agent-based simulation with FLAME for the GPU.

Science.gov (United States)

Richmond, Paul; Walker, Dawn; Coakley, Simon; Romano, Daniela

2010-05-01

Driven by the availability of experimental data and ability to simulate a biological scale which is of immediate interest, the cellular scale is fast emerging as an ideal candidate for middle-out modelling. As with 'bottom-up' simulation approaches, cellular level simulations demand a high degree of computational power, which in large-scale simulations can only be achieved through parallel computing. The flexible large-scale agent modelling environment (FLAME) is a template driven framework for agent-based modelling (ABM) on parallel architectures ideally suited to the simulation of cellular systems. It is available for both high performance computing clusters (www.flame.ac.uk) and GPU hardware (www.flamegpu.com) and uses a formal specification technique that acts as a universal modelling format. This not only creates an abstraction from the underlying hardware architectures, but avoids the steep learning curve associated with programming them. In benchmarking tests and simulations of advanced cellular systems, FLAME GPU has reported massive improvement in performance over more traditional ABM frameworks. This allows the time spent in the development and testing stages of modelling to be drastically reduced and creates the possibility of real-time visualisation for simple visual face-validation.

Cellular chromophores and signaling in low level light therapy

Science.gov (United States)

Hamblin, Michael R.; Demidova-Rice, Tatiana N.

2007-02-01

The use of low levels of visible or near infrared light (LLLT) for reducing pain, inflammation and edema, promoting healing of wounds, deeper tissues and nerves, and preventing tissue damage by reducing cellular apoptosis has been known for almost forty years since the invention of lasers. Originally thought to be a peculiar property of laser light (soft or cold lasers), the subject has now broadened to include photobiomodulation and photobiostimulation using non-coherent light. Despite many reports of positive findings from experiments conducted in vitro, in animal models and in randomized controlled clinical trials, LLLT remains controversial. This likely is due to two main reasons; firstly the biochemical mechanisms underlying the positive effects are incompletely understood, and secondly the complexity of rationally choosing amongst a large number of illumination parameters such as wavelength, fluence, power density, pulse structure and treatment timing has led to the publication of a number of negative studies as well as many positive ones. In recent years major advances have been made in understanding the mechanisms that operate at the cellular and tissue levels during LLLT. Mitochondria are thought to be the main site for the initial effects of light and specifically cytochrome c oxidase that has absorption peaks in the red and near infrared regions of the electromagnetic spectrum matches the action spectra of LLLT effects. The discovery that cells employ nitric oxide (NO) synthesized in the mitochondria by neuronal nitric oxide synthase, to regulate respiration by competitive binding to the oxygen binding of cytochrome c oxidase, now suggests how LLLT can affect cell metabolism. If LLLT photodissociates inhibitory NO from cytochrome c oxidase, this would explain increased ATP production, modulation of reactive oxygen species, reduction and prevention of apoptosis, stimulation of angiogenesis, increase of blood flow and induction of transcription factors. In

Monoaminergic Control of Cellular Glucose Utilization by Glycogenolysis in Neocortex and Hippocampus.

Science.gov (United States)

DiNuzzo, Mauro; Giove, Federico; Maraviglia, Bruno; Mangia, Silvia

2015-12-01

Brainstem nuclei are the principal sites of monoamine (MA) innervation to major forebrain structures. In the cortical grey matter, increased secretion of MA neuromodulators occurs in response to a wealth of environmental and homeostatic challenges, whose onset is associated with rapid, preparatory changes in neural activity as well as with increases in energy metabolism. Blood-borne glucose is the main substrate for energy production in the brain. Once entered the tissue, interstitial glucose is equally accessible to neurons and astrocytes, the two cell types accounting for most of cellular volume and energy metabolism in neocortex and hippocampus. Astrocytes also store substantial amounts of glycogen, but non-stimulated glycogen turnover is very small. The rate of cellular glucose utilization in the brain is largely determined by hexokinase, which under basal conditions is more than 90 % inhibited by its product glucose-6-phosphate (Glc-6-P). During rapid increases in energy demand, glycogen is a primary candidate in modulating the intracellular level of Glc-6-P, which can occur only in astrocytes. Glycogenolysis can produce Glc-6-P at a rate higher than uptake and phosphorylation of glucose. MA neurotransmitter are released extrasinaptically by brainstem neurons projecting to neocortex and hippocampus, thus activating MA receptors located on both neuronal and astrocytic plasma membrane. Importantly, MAs are glycogenolytic agents and thus they are exquisitely suitable for regulation of astrocytic Glc-6-P concentration, upstream substrate flow through hexokinase and hence cellular glucose uptake. Conforming to such mechanism, Gerald A. Dienel and Nancy F. Cruz recently suggested that activation of noradrenergic locus coeruleus might reversibly block astrocytic glucose uptake by stimulating glycogenolysis in these cells, thereby anticipating the rise in glucose need by active neurons. In this paper, we further develop the idea that the whole monoaminergic system

Magnitude and duration of stretch modulate fibroblast remodeling.

Science.gov (United States)

Balestrini, Jenna L; Billiar, Kristen L

2009-05-01

Mechanical cues modulate fibroblast tractional forces and remodeling of extracellular matrix in healthy tissue, healing wounds, and engineered matrices. The goal of the present study is to establish dose-response relationships between stretch parameters (magnitude and duration per day) and matrix remodeling metrics (compaction, strength, extensibility, collagen content, contraction, and cellularity). Cyclic equibiaxial stretch of 2-16% was applied to fibroblast-populated fibrin gels for either 6 h or 24 h/day for 8 days. Trends in matrix remodeling metrics as a function of stretch magnitude and duration were analyzed using regression analysis. The compaction and ultimate tensile strength of the tissues increased in a dose-dependent manner with increasing stretch magnitude, yet remained unaffected by the duration in which they were cycled (6 h/day versus 24 h/day). Collagen density increased exponentially as a function of both the magnitude and duration of stretch, with samples stretched for the reduced duration per day having the highest levels of collagen accumulation. Cell number and failure tension were also dependent on both the magnitude and duration of stretch, although stretch-induced increases in these metrics were only present in the samples loaded for 6 h/day. Our results indicate that both the magnitude and the duration per day of stretch are critical parameters in modulating fibroblast remodeling of the extracellular matrix, and that these two factors regulate different aspects of this remodeling. These findings move us one step closer to fully characterizing culture conditions for tissue equivalents, developing improved wound healing treatments and understanding tissue responses to changes in mechanical environments during growth, repair, and disease states.

Incorporating Geodectic Processing Modules into a Real-Time Earthworm Environment to Enhance NOAA's Tsunami Warning Capability

Science.gov (United States)

Macpherson, K. A.

2017-12-01

, Berkeley, and a module for a Static Offset Estimator algorithm that was developed by the NASA Jet Propulsion Laboratory. In this presentation we will discuss module architecture and show output computed by replaying both synthetic and historical scenarios in a simulated real-time Earthworm environment.

Solar PV powered mobile cellular base station: Models and use cases in South Africa

CSIR Research Space (South Africa)

Aderemi, BA

2017-09-01

Full Text Available The huge costs of operating a mobile cellular base station, and the negative impact of greenhouse gasses on the environment have made the solar PV renewable energy source a sought after. In addition to cost and environmental factor, abundant supply...

Feasibility of Ecological Momentary Assessment Using Cellular Telephones in Methamphetamine Dependent Subjects

Directory of Open Access Journals (Sweden)

John Mendelson

2008-01-01

Full Text Available Background: Predictors of relapse to methamphetamine use are poorly understood. State variables may play an important role in relapse, but they have been difficult to measure at frequent intervals in outpatients.Methods: We conducted a feasibility study of the use of cellular telephones to collect state variable data from outpatients. Six subjects in treatment for methamphetamine dependence were called three times per weekday for approximately seven weeks. Seven questionnaires were administered that assessed craving, stress, affect and current type of location and social environment.Results: 395/606 (65% of calls attempted were completed. The mean time to complete each call was 4.9 (s.d. 1.8 minutes and the mean time to complete each item was 8.4 (s.d. 4.8 seconds. Subjects rated the acceptability of the procedures as good. All six cellular phones and battery chargers were returned undamaged.Conclusion: Cellular telephones are a feasible method for collecting state data from methamphetamine dependent outpatients.

Interactive instruction of cellular physiology for remote learning.

Science.gov (United States)

Huang, C; Huang, H K

2003-12-01

The biomedical sciences are a rapidly changing discipline that have adapted to innovative technological advances. Despite these many advances, we face two major challenges: a) the number of experts in the field is vastly outnumbered by the number of students, many of whom are separated geographically or temporally and b) the teaching methods used to instruct students and learners have not changed. Today's students have adapted to technology--they use the web as a source of information and communicate via email and chat rooms. Teaching in the biomedical sciences should adopt these new information technologies (IT), but has thus far failed to capitalize on technological opportunity. Creating a "digital textbook" of the traditional learning material is not sufficient for dynamic processes such as cellular physiology. This paper describes innovative teaching techniques that incorporate familiar IT and high-quality interactive learning content with user-centric instruction design models. The Virtual Labs Project from Stanford University has created effective interactive online teaching modules in physiology (simPHYSIO) and delivered them over broadband networks to their undergraduate and medical students. Evaluation results of the modules are given as a measure of success of such innovative teaching method. This learning media strategically merges IT innovations with pedagogy to produce user-driven animations of processes and engaging interactive simulations.

Plasticity Regulators Modulate Specific Root Traits in Discrete Nitrogen Environments

Science.gov (United States)

Gifford, Miriam L.; Banta, Joshua A.; Katari, Manpreet S.; Hulsmans, Jo; Chen, Lisa; Ristova, Daniela; Tranchina, Daniel; Purugganan, Michael D.; Coruzzi, Gloria M.; Birnbaum, Kenneth D.

2013-01-01

Plant development is remarkably plastic but how precisely can the plant customize its form to specific environments? When the plant adjusts its development to different environments, related traits can change in a coordinated fashion, such that two traits co-vary across many genotypes. Alternatively, traits can vary independently, such that a change in one trait has little predictive value for the change in a second trait. To characterize such “tunability” in developmental plasticity, we carried out a detailed phenotypic characterization of complex root traits among 96 accessions of the model Arabidopsis thaliana in two nitrogen environments. The results revealed a surprising level of independence in the control of traits to environment – a highly tunable form of plasticity. We mapped genetic architecture of plasticity using genome-wide association studies and further used gene expression analysis to narrow down gene candidates in mapped regions. Mutants in genes implicated by association and expression analysis showed precise defects in the predicted traits in the predicted environment, corroborating the independent control of plasticity traits. The overall results suggest that there is a pool of genetic variability in plants that controls traits in specific environments, with opportunity to tune crop plants to a given environment. PMID:24039603

Use of Ion-Channel Modulating Agents to Study Cyanobacterial Na+ - K+ Fluxes

Directory of Open Access Journals (Sweden)

Pomati Francesco

2004-01-01

Full Text Available Here we describe an experimental design aimed to investigate changes in total cellular levels of Na+ and K+ ions in cultures of freshwater filamentous cyanobacteria. Ion concentrations were measured in whole cells by flame photometry. Cellular Na+ levels increased exponentially with rising alkalinity, with K+ levels being maximal for optimal growth pH (~8. At standardized pH conditions, the increase in cellular Na+, as induced by NaCl at 10 mM, was coupled by the two sodium channel-modulating agents lidocaine hydrochloride at 1 &mgr;M and veratridine at 100 &mgr;M. Both the channel-blockers amiloride (1 mM and saxitoxin (1 &mgr;M, decreased cell-bound Na+ and K+ levels. Results presented demonstrate the robustness of well-defined channel blockers and channel-activators in the study of cyanobacterial Na+- K+ fluxes.

Steviol Glycosides Modulate Glucose Transport in Different Cell Types

Science.gov (United States)

Rizzo, Benedetta; Zambonin, Laura; Leoncini, Emanuela; Vieceli Dalla Sega, Francesco; Prata, Cecilia; Fiorentini, Diana; Hrelia, Silvana

2013-01-01

Extracts from Stevia rebaudiana Bertoni, a plant native to Central and South America, have been used as a sweetener since ancient times. Currently, Stevia extracts are largely used as a noncaloric high-potency biosweetener alternative to sugar, due to the growing incidence of type 2 diabetes mellitus, obesity, and metabolic disorders worldwide. Despite the large number of studies on Stevia and steviol glycosides in vivo, little is reported concerning the cellular and molecular mechanisms underpinning the beneficial effects on human health. The effect of four commercial Stevia extracts on glucose transport activity was evaluated in HL-60 human leukaemia and in SH-SY5Y human neuroblastoma cells. The extracts were able to enhance glucose uptake in both cellular lines, as efficiently as insulin. Our data suggest that steviol glycosides could act by modulating GLUT translocation through the PI3K/Akt pathway since treatments with both insulin and Stevia extracts increased the phosphorylation of PI3K and Akt. Furthermore, Stevia extracts were able to revert the effect of the reduction of glucose uptake caused by methylglyoxal, an inhibitor of the insulin receptor/PI3K/Akt pathway. These results corroborate the hypothesis that Stevia extracts could mimic insulin effects modulating PI3K/Akt pathway. PMID:24327825

Cellular characterization of compression induced-damage in live biological samples

Science.gov (United States)

Bo, Chiara; Balzer, Jens; Hahnel, Mark; Rankin, Sara M.; Brown, Katherine A.; Proud, William G.

2011-06-01

Understanding the dysfunctions that high-intensity compression waves induce in human tissues is critical to impact on acute-phase treatments and requires the development of experimental models of traumatic damage in biological samples. In this study we have developed an experimental system to directly assess the impact of dynamic loading conditions on cellular function at the molecular level. Here we present a confinement chamber designed to subject live cell cultures in liquid environment to compression waves in the range of tens of MPa using a split Hopkinson pressure bars system. Recording the loading history and collecting the samples post-impact without external contamination allow the definition of parameters such as pressure and duration of the stimulus that can be related to the cellular damage. The compression experiments are conducted on Mesenchymal Stem Cells from BALB/c mice and the damage analysis are compared to two control groups. Changes in Stem cell viability, phenotype and function are assessed flow cytometry and with in vitro bioassays at two different time points. Identifying the cellular and molecular mechanisms underlying the damage caused by dynamic loading in live biological samples could enable the development of new treatments for traumatic injuries.

Malignant monoblasts can function as effector cells in natural killer cell and antibody-dependent cellular cytotoxicity assays

DEFF Research Database (Denmark)

Hokland, P; Hokland, M; Ellegaard, J

1981-01-01

This is the first report describing natural killer (NK) and antibody-dependent cellular cytotoxicity (ADCC) of malignant monoblasts. Pure acute monoblastic leukemia was diagnosed in bone marrow aspirations from two patients by use of conventional cytochemical methods as well as multiple immunolog...... no modulation was seen in ADCC. These findings are discussed in the light of our present knowledge of lymphoid NK cells. Udgivelsesdato: 1981-May...

Sparx PCA Module

Energy Technology Data Exchange (ETDEWEB)

2017-04-25

Sparx, a new environment for Cryo-EM image processing; Cryo-EM, Single particle reconstruction, principal component analysis; Hardware Req.: PC, MAC, Supercomputer, Mainframe, Multiplatform, Workstation. Software Req.: operating system is Unix; Compiler C++; type of files: source code, object library, executable modules, compilation instructions; sample problem input data. Location/transmission: http://sparx-em.org; User manual & paper: http://sparx-em.org;

Modulators of Stomatal Lineage Signal Transduction Alter Membrane Contact Sites and Reveal Specialization among ERECTA Kinases.

Science.gov (United States)

Ho, Chin-Min Kimmy; Paciorek, Tomasz; Abrash, Emily; Bergmann, Dominique C

2016-08-22

Signal transduction from a cell's surface to its interior requires dedicated signaling elements and a cellular environment conducive to signal propagation. Plant development, defense, and homeostasis rely on plasma membrane receptor-like kinases to perceive endogenous and environmental signals, but little is known about their immediate downstream targets and signaling modifiers. Using genetics, biochemistry, and live-cell imaging, we show that the VAP-RELATED SUPPRESSOR OF TMM (VST) family is required for ERECTA-mediated signaling in growth and cell-fate determination and reveal a role for ERECTA-LIKE2 in modulating signaling by its sister kinases. We show that VSTs are peripheral plasma membrane proteins that can form complexes with integral ER-membrane proteins, thereby potentially influencing the organization of the membrane milieu to promote efficient and differential signaling from the ERECTA-family members to their downstream intracellular targets. Copyright © 2016 Elsevier Inc. All rights reserved.

Cellular characterization of human dermal fibroblasts, focus on mitochondria and maple syrup urine disease

DEFF Research Database (Denmark)

Fernandez-Guerra, Paula

and functions are expressed in HDFs’ culture environment. Studies of molecular disease mechanisms often point to the involvement of mitochondria. Mitochondria are involved in the regulation of cell cycle and programmed cell death as well as cellular stress responses because they are the main producers...

An Asynchronous Cellular Automata-Based Adaptive Illumination Facility

Science.gov (United States)

Bandini, Stefania; Bonomi, Andrea; Vizzari, Giuseppe; Acconci, Vito

The term Ambient Intelligence refers to electronic environments that are sensitive and responsive to the presence of people; in the described scenario the environment itself is endowed with a set of sensors (to perceive humans or other physical entities such as dogs, bicycles, etc.), interacting with a set of actuators (lights) that choose their actions (i.e. state of illumination) in an attempt improve the overall experience of these users. The model for the interaction and action of sensors and actuators is an asynchronous Cellular Automata (CA) with memory, supporting a self-organization of the system as a response to the presence and movements of people inside it. The paper will introduce the model, as well as an ad hoc user interface for the specification of the relevant parameters of the CA transition rule that determines the overall system behaviour.

Leading research report for fiscal 1998. Research and study of 3-dimensional cell structure module engineering; 1998 nendo sendo chosa kenkyu hokokusho. Sanjigen saibo soshiki module kogaku chosa kenkyu

Energy Technology Data Exchange (ETDEWEB)

NONE

1999-03-01

For the formation of cellular tissues to replace bionic tissues, researches were conducted about technologies of forming bionic tissue modules by culturing various kinds of cells. As for the materials and methods for constructing cellular tissues, researches were conducted about the trends of research and development of 3-dimensional tissue culturing matrices and materials for micromanipulation. As for the development of technologies for the functionalization of 3-dimensionally structured cells, research and study were conducted about the technology of 3-dimensional cell structure organization through application of physical stimulation, the biochemical technology of differentiation inducing, and the differentiation inducing technology for hetero tissue culturing. As for the development of technologies for evaluation using 3-dimensionally structured cells, light CT (computer tomography), analysis and evaluation using spectroscopy and the like, feasibility of the biochemical analysis of the cell state using biosensors, technologies for measuring the secretion of carcinogenic and toxic substances, etc., were studied. In addition, the development of organic models to replace test animals, industrial evolution of 3-dimensional tissue module engineering, etc., were investigated. (NEDO)

Cellular Particle Dynamics simulation of biomechanical relaxation processes of multi-cellular systems

Science.gov (United States)

McCune, Matthew; Kosztin, Ioan

2013-03-01

Cellular Particle Dynamics (CPD) is a theoretical-computational-experimental framework for describing and predicting the time evolution of biomechanical relaxation processes of multi-cellular systems, such as fusion, sorting and compression. In CPD, cells are modeled as an ensemble of cellular particles (CPs) that interact via short range contact interactions, characterized by an attractive (adhesive interaction) and a repulsive (excluded volume interaction) component. The time evolution of the spatial conformation of the multicellular system is determined by following the trajectories of all CPs through numerical integration of their equations of motion. Here we present CPD simulation results for the fusion of both spherical and cylindrical multi-cellular aggregates. First, we calibrate the relevant CPD model parameters for a given cell type by comparing the CPD simulation results for the fusion of two spherical aggregates to the corresponding experimental results. Next, CPD simulations are used to predict the time evolution of the fusion of cylindrical aggregates. The latter is relevant for the formation of tubular multi-cellular structures (i.e., primitive blood vessels) created by the novel bioprinting technology. Work supported by NSF [PHY-0957914]. Computer time provided by the University of Missouri Bioinformatics Consortium.

Modulation of cellular phosphoprotein profiles in transformation and redifferentiation of murine and embryonic fibroblastic cells

International Nuclear Information System (INIS)

Chakrabarty, Subhas; Brattain, M.G.

1985-01-01

Cellular phosphoprotein profiles from normal mouse embryonic fibroblast AKR-2B cells were compared to those of their permanently, chemically transformed malignant counterparts AKR-MCA cells, and AKR-2B cells reversibly transformed by transforming growth factor (AKR-TGF). Similar 32 P-phosphorylation profiles were observed for both the AKR-TGF and AKR-MCA cells which were distinct from that of the normal AKR-2B cells. Dimethylformamide (DMF)-induced differentiation of the AKR-MCA cells resulted in restoration of the normal AKR-2B phosphorylation profile to the malignant AKR-MCA cells. (author)

Modulation of pathogen recognition by autophagy

Directory of Open Access Journals (Sweden)

Ji Eun eOh

2012-03-01

Full Text Available Autophagy is an ancient biological process for maintaining cellular homeostasis by degradation of long-lived cytosolic proteins and organelles. Recent studies demonstrated that autophagy is availed by immune cells to regulate innate immunity. On the one hand, cells exert direct effector function by degrading intracellular pathogens; on the other hand, autophagy modulates pathogen recognition and downstream signaling for innate immune responses. Pathogen recognition via pattern recognition receptors induces autophagy. The function of phagocytic cells is enhanced by recruitment of autophagy-related proteins. Moreover, autophagy acts as a delivery system for viral replication complexes to migrate to the endosomal compartments where virus sensing occurs. In another case, key molecules of the autophagic pathway have been found to negatively regulate immune signaling, thus preventing aberrant activation of cytokine production and consequent immune responses. In this review, we focus on the recent advances in the role of autophagy in pathogen recognition and modulation of innate immune responses.

Excitant and depressant drugs modulate effects of environment on brain weight and cholinesterases

Energy Technology Data Exchange (ETDEWEB)

Bennett, E.L.; Rosenzweig, M.R.; Wu, S.Y.C.

1973-01-01

Certain excitant drugs can enhance the effects of enriched experience on weights of brain sections and on the activities of acetylcholinesterase and cholinesterase in the brain, and certain depressants can lessen the brain weight effects. Most experiments were performed with prepubertal male rats. Some rats were exposed in groups of 12 to an enriched environmental condition (EC), usually for 2 h per day and over a 30-day period; others remained in their individual home cages (HC) throughout. Some received a drug injection and others received a saline injection before the daily EC period; HC controls received similar injections. The drug injections had no significant effects on brain values of HC rats, but they altered effects of EC, probably by influencing the animals' reactions to the environment. Methamphetamine and d-amphetamine enhanced the EC effects; metrazol had small positive effects; and strychnine was without effects. Phenobarbital depressed the brain weight effects but increased the enzymatic effects. Use of methamphetamine made it possible to find EC effects with short daily periods (30 min) or with a shortened experimental duration (15 days). In experiments with adult rats, methamphetamine did not modulate the brain weight effects. The results of this study may bear on the use of stimulants to promote recovery from brain damage.

SH2 domains: modulators of nonreceptor tyrosine kinase activity

OpenAIRE

Filippakopoulos, Panagis; Müller, Susanne; Knapp, Stefan

2009-01-01

The Src homology 2 (SH2) domain is a sequence-specific phosphotyrosine-binding module present in many signaling molecules. In cytoplasmic tyrosine kinases, the SH2 domain is located N-terminally to the catalytic kinase domain (SH1) where it mediates cellular localization, substrate recruitment, and regulation of kinase activity. Initially, structural studies established a role of the SH2 domain stabilizing the inactive state of Src family members. However, biochemical characterization showed ...

Acquisition system for the CLIC Module

CERN Document Server

Vilalte, Sebastien

2011-01-01

The status of R&D activities for CLIC module acquisition are discussed [1]. LAPP is involved in the design of the local CLIC module acquisition crate, described in the document Study of the CLIC Module Front-End Acquisition and Evaluation Electronics [2]. This acquisition system is a project based on a local crate, assigned to the CLIC module, including several mother boards. These motherboards are foreseen to hold mezzanines dedicated to the different subsystems. This system has to work in radiation environment. LAPP is involved in the development of Drive Beam stripline position monitors read-out, described in the document Drive Beam Stripline BPM Electronics and Acquisition [3]. LAPP also develops a generic acquisition mezzanine that allows to perform all-around acquisition and components tests for drive beam stripline BPM read-out.

Study of bypass diodes configuration on PV modules

Energy Technology Data Exchange (ETDEWEB)

Silvestre, S.; Boronat, A.; Chouder, A. [Electronics Engineering Department - UPC., C/Jordi Girona 1-3, Modul C4 Campus Nord UPC., 08034 Barcelona (Spain)

2009-09-15

A procedure of simulation and modelling solar cells and PV modules, working partially shadowed in Pspice environment, is presented. Simulation results have been contrasted with real measured data from a commercial PV module of 209 Wp from Siliken. Some cases of study are presented as application examples of this simulation methodology, showing its potential on the design of bypass diodes configuration to include in a PV module and also on the study of PV generators working in partial shading conditions. (author)

Cellular and molecular mechanisms of immunomodulation in the brain through environmental enrichment

Science.gov (United States)

Singhal, Gaurav; Jaehne, Emily J.; Corrigan, Frances; Baune, Bernhard T.

2014-01-01

Recent studies on environmental enrichment (EE) have shown cytokines, cellular immune components [e.g., T lymphocytes, natural killer (NK) cells], and glial cells in causal relationship to EE in bringing out changes to neurobiology and behavior. The purpose of this review is to evaluate these neuroimmune mechanisms associated with neurobiological and behavioral changes in response to different EE methods. We systematically reviewed common research databases. After applying all inclusion and exclusion criteria, 328 articles remained for this review. Physical exercise (PE), a form of EE, elicits anti-inflammatory and neuromodulatory effects through interaction with several immune pathways including interleukin (IL)-6 secretion from muscle fibers, reduced expression of Toll-like receptors on monocytes and macrophages, reduced secretion of adipokines, modulation of hippocampal T cells, priming of microglia, and upregulation of mitogen-activated protein kinase phosphatase-1 in central nervous system. In contrast, immunomodulatory roles of other enrichment methods are not studied extensively. Nonetheless, studies showing reduction in the expression of IL-1β and tumor necrosis factor-α in response to enrichment with novel objects and accessories suggest anti-inflammatory effects of novel environment. Likewise, social enrichment, though considered a necessity for healthy behavior, results in immunosuppression in socially defeated animals. This has been attributed to reduction in T lymphocytes, NK cells and IL-10 in subordinate animals. EE through sensory stimuli has been investigated to a lesser extent and the effect on immune factors has not been evaluated yet. Discovery of this multidimensional relationship between immune system, brain functioning, and EE has paved a way toward formulating environ-immuno therapies for treating psychiatric illnesses with minimal use of pharmacotherapy. While the immunomodulatory role of PE has been evaluated extensively, more research

Biomolecule delivery to engineer the cellular microenvironment for regenerative medicine.

Science.gov (United States)

Bishop, Corey J; Kim, Jayoung; Green, Jordan J

2014-07-01

To realize the potential of regenerative medicine, controlling the delivery of biomolecules in the cellular microenvironment is important as these factors control cell fate. Controlled delivery for tissue engineering and regenerative medicine often requires bioengineered materials and cells capable of spatiotemporal modulation of biomolecule release and presentation. This review discusses biomolecule delivery from the outside of the cell inwards through the delivery of soluble and insoluble biomolecules as well as from the inside of the cell outwards through gene transfer. Ex vivo and in vivo therapeutic strategies are discussed, as well as combination delivery of biomolecules, scaffolds, and cells. Various applications in regenerative medicine are highlighted including bone tissue engineering and wound healing.

Noradrenergic Modulation of Cognition in Health and Disease

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Olga Borodovitsyna

2017-01-01

Full Text Available Norepinephrine released by the locus coeruleus modulates cellular processes and synaptic transmission in the central nervous system through its actions at a number of pre- and postsynaptic receptors. This transmitter system facilitates sensory signal detection and promotes waking and arousal, processes which are necessary for navigating a complex and dynamic sensory environment. In addition to its effects on sensory processing and waking behavior, norepinephrine is now recognized as a contributor to various aspects of cognition, including attention, behavioral flexibility, working memory, and long-term mnemonic processes. Two areas of dense noradrenergic innervation, the prefrontal cortex and the hippocampus, are particularly important with regard to these functions. Due to its role in mediating normal cognitive function, it is reasonable to expect that noradrenergic transmission becomes dysfunctional in a number of neuropsychiatric and neurodegenerative diseases characterized by cognitive deficits. In this review, we summarize the unique role that norepinephrine plays in prefrontal cortical and hippocampal function and how its interaction with its various receptors contributes to cognitive behaviors. We further assess the changes that occur in the noradrenergic system in Alzheimer’s disease, Parkinson’s disease, attention-deficit/hyperactivity disorder, and schizophrenia and how these changes contribute to cognitive decline in these pathologies.

Radio Frequency Identification (RFID) in medical environment: Gaussian Derivative Frequency Modulation (GDFM) as a novel modulation technique with minimal interference properties.

Science.gov (United States)

Rieche, Marie; Komenský, Tomás; Husar, Peter

2011-01-01

Radio Frequency Identification (RFID) systems in healthcare facilitate the possibility of contact-free identification and tracking of patients, medical equipment and medication. Thereby, patient safety will be improved and costs as well as medication errors will be reduced considerably. However, the application of RFID and other wireless communication systems has the potential to cause harmful electromagnetic disturbances on sensitive medical devices. This risk mainly depends on the transmission power and the method of data communication. In this contribution we point out the reasons for such incidents and give proposals to overcome these problems. Therefore a novel modulation and transmission technique called Gaussian Derivative Frequency Modulation (GDFM) is developed. Moreover, we carry out measurements to show the inteference properties of different modulation schemes in comparison to our GDFM.

Dynamic behavior of cellular materials and cellular structures: Experiments and modeling

Science.gov (United States)

Gao, Ziyang

Cellular solids, including cellular materials and cellular structures (CMS), have attracted people's great interests because of their low densities and novel physical, mechanical, thermal, electrical and acoustic properties. They offer potential for lightweight structures, energy absorption, thermal management, etc. Therefore, the studies of cellular solids have become one of the hottest research fields nowadays. From energy absorption point of view, any plastically deformed structures can be divided into two types (called type I and type II), and the basic cells of the CMS may take the configurations of these two types of structures. Accordingly, separated discussions are presented in this thesis. First, a modified 1-D model is proposed and numerically solved for a typical type II structure. Good agreement is achieved with the previous experimental data, hence is used to simulate the dynamic behavior of a type II chain. Resulted from different load speeds, interesting collapse modes are observed, and the parameters which govern the cell's post-collapse behavior are identified through a comprehensive non-dimensional analysis on general cellular chains. Secondly, the MHS specimens are chosen as an example of type I foam materials because of their good uniformity of the cell geometry. An extensive experimental study was carried out, where more attention was paid to their responses to dynamic loadings. Great enhancement of the stress-strain curve was observed in dynamic cases, and the energy absorption capacity is found to be several times higher than that of the commercial metal foams. Based on the experimental study, finite elemental simulations and theoretical modeling are also conducted, achieving good agreements and demonstrating the validities of those models. It is believed that the experimental, numerical and analytical results obtained in the present study will certainly deepen the understanding of the unsolved fundamental issues on the mechanical behavior of

How does a neuron know to modulate its epigenetic machinery in response to early-life environment/experience?

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Carley A Karsten

2013-08-01

Full Text Available Exciting information is emerging about epigenetic mechanisms and their role in long-lasting changes of neuronal gene expression. Whereas these mechanisms are active throughout life, recent findings point to a critical window of early postnatal development during which neuronal gene expression may be persistently re-programmed via epigenetic modifications. However, it remains unclear how the epigenetic machinery is modulated. Here we focus on an important example of early-life programming: the effect of sensory input from the mother on expression patterns of key stress-related genes in the developing brain. We focus on the lasting effects of this early life experience on corticotropin releasing hormone (CRH gene expression in the hypothalamus, and describe recent work that integrates organism-wide signals with cellular signals that in turn impact epigenetic regulation. We describe the operational brain networks that convey sensory input to CRH-expressing cells, and highlight the resulting re-wiring of synaptic connectivity to these neurons. We then move from intercellular to intracellular mechanisms, speculating about the induction and maintenance of lifelong CRH repression provoked by early-life experience. Elucidating such pathways is critical for understanding the enduring links between experience and gene expression. In the context of responses to stress, such mechanisms should contribute to vulnerability or resilience to post-traumatic stress disorder (PTSD and other stress-related disorders.

MRF Family Genes Are Involved in Translation Control, Especially under Energy-Deficient Conditions, and Their Expression and Functions Are Modulated by the TOR Signaling Pathway.

Science.gov (United States)

Lee, Du-Hwa; Park, Seung Jun; Ahn, Chang Sook; Pai, Hyun-Sook

2017-11-01

Dynamic control of protein translation in response to the environment is essential for the survival of plant cells. Target of rapamycin (TOR) coordinates protein synthesis with cellular energy/nutrient availability through transcriptional modulation and phosphorylation of the translation machinery. However, mechanisms of TOR-mediated translation control are poorly understood in plants. Here, we report that Arabidopsis thaliana MRF (MA3 DOMAIN-CONTAINING TRANSLATION REGULATORY FACTOR) family genes encode translation regulatory factors under TOR control, and their functions are particularly important in energy-deficient conditions. Four MRF family genes ( MRF1 - MRF4 ) are transcriptionally induced by dark and starvation (DS). Silencing of multiple MRFs increases susceptibility to DS and treatment with a TOR inhibitor, while MRF1 overexpression decreases susceptibility. MRF proteins interact with eIF4A and cofractionate with ribosomes. MRF silencing decreases translation activity, while MRF1 overexpression increases it, accompanied by altered ribosome patterns, particularly in DS. Furthermore, MRF deficiency in DS causes altered distribution of mRNAs in sucrose gradient fractions and accelerates rRNA degradation. MRF1 is phosphorylated in vivo and phosphorylated by S6 kinases in vitro. MRF expression and MRF1 ribosome association and phosphorylation are modulated by cellular energy status and TOR activity. We discuss possible mechanisms of the function of MRF family proteins under normal and energy-deficient conditions and their functional link with the TOR pathway. © 2017 American Society of Plant Biologists. All rights reserved.

Degradation-mediated cellular traction directs stem cell fate in covalently crosslinked three-dimensional hydrogels

Science.gov (United States)

Khetan, Sudhir; Guvendiren, Murat; Legant, Wesley R.; Cohen, Daniel M.; Chen, Christopher S.; Burdick, Jason A.

2013-05-01

Although cell-matrix adhesive interactions are known to regulate stem cell differentiation, the underlying mechanisms, in particular for direct three-dimensional encapsulation within hydrogels, are poorly understood. Here, we demonstrate that in covalently crosslinked hyaluronic acid (HA) hydrogels, the differentiation of human mesenchymal stem cells (hMSCs) is directed by the generation of degradation-mediated cellular traction, independently of cell morphology or matrix mechanics. hMSCs within HA hydrogels of equivalent elastic moduli that permit (restrict) cell-mediated degradation exhibited high (low) degrees of cell spreading and high (low) tractions, and favoured osteogenesis (adipogenesis). Moreover, switching the permissive hydrogel to a restrictive state through delayed secondary crosslinking reduced further hydrogel degradation, suppressed traction, and caused a switch from osteogenesis to adipogenesis in the absence of changes to the extended cellular morphology. Furthermore, inhibiting tension-mediated signalling in the permissive environment mirrored the effects of delayed secondary crosslinking, whereas upregulating tension induced osteogenesis even in the restrictive environment.

Network analysis of oyster transcriptome revealed a cascade of cellular responses during recovery after heat shock.

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Lingling Zhang

Full Text Available Oysters, as a major group of marine bivalves, can tolerate a wide range of natural and anthropogenic stressors including heat stress. Recent studies have shown that oysters pretreated with heat shock can result in induced heat tolerance. A systematic study of cellular recovery from heat shock may provide insights into the mechanism of acquired thermal tolerance. In this study, we performed the first network analysis of oyster transcriptome by reanalyzing microarray data from a previous study. Network analysis revealed a cascade of cellular responses during oyster recovery after heat shock and identified responsive gene modules and key genes. Our study demonstrates the power of network analysis in a non-model organism with poor gene annotations, which can lead to new discoveries that go beyond the focus on individual genes.

The calculating methods of the release of airborne radionuclides to environment during the normal operation of a module high temperature gas-cooled reactor

International Nuclear Information System (INIS)

Liu Yuanzhong

1993-01-01

The calculations of the release of radionuclides to environment are the basis of environmental impact assessment during the normal operation of a module high temperature gas-cooled reactor of the Institute of Nuclear Energy Technology, Tsinghua University, China. According to the features of the reactor it is pointed out that only five sources of the airborne radioactive materials released to environment are important. They are: (1) the activation of the air in the reactor cavity; (2) the escape from the primary coolant systems; (3) the release of radioactively contaminated helium from storage tanks; (4) the release of radioactively contaminated helium from the gas evacuation system of fuel load and unload system; (5) the leakage of the vapour from water-steam loop. In accordance with five release sources the calculating methods of radionuclides released to environment are worked out respectively and the respective calculating formulas are derived for the normal operation of the reactor

X-ray micro-modulated luminescence tomography (XMLT)

Science.gov (United States)

Cong, Wenxiang; Liu, Fenglin; Wang, Chao; Wang, Ge

2014-01-01

Imaging depth of optical microscopy has been fundamentally limited to millimeter or sub-millimeter due to strong scattering of light in a biological sample. X-ray microscopy can resolve spatial details of few microns deep inside a sample but contrast resolution is inadequate to depict heterogeneous features at cellular or sub-cellular levels. To enhance and enrich biological contrast at large imaging depth, various nanoparticles are introduced and become essential to basic research and molecular medicine. Nanoparticles can be functionalized as imaging probes, similar to fluorescent and bioluminescent proteins. LiGa5O8:Cr3+ nanoparticles were recently synthesized to facilitate luminescence energy storage with x-ray pre-excitation and subsequently stimulated luminescence emission by visible/near-infrared (NIR) light. In this paper, we propose an x-ray micro-modulated luminescence tomography (XMLT, or MLT to be more general) approach to quantify a nanophosphor distribution in a thick biological sample with high resolution. Our numerical simulation studies demonstrate the feasibility of the proposed approach. PMID:24663898

Statistical mechanics of cellular automata

International Nuclear Information System (INIS)

Wolfram, S.

1983-01-01

Cellular automata are used as simple mathematical models to investigate self-organization in statistical mechanics. A detailed analysis is given of ''elementary'' cellular automata consisting of a sequence of sites with values 0 or 1 on a line, with each site evolving deterministically in discrete time steps according to p definite rules involving the values of its nearest neighbors. With simple initial configurations, the cellular automata either tend to homogeneous states, or generate self-similar patterns with fractal dimensions approx. =1.59 or approx. =1.69. With ''random'' initial configurations, the irreversible character of the cellular automaton evolution leads to several self-organization phenomena. Statistical properties of the structures generated are found to lie in two universality classes, independent of the details of the initial state or the cellular automaton rules. More complicated cellular automata are briefly considered, and connections with dynamical systems theory and the formal theory of computation are discussed

Macrophage migration inhibitory factor (MIF) modulates trophic signaling through interaction with serine protease HTRA1

DEFF Research Database (Denmark)

Fex Svenningsen, Åsa; Loering, Svenja; Sørensen, Anna Lahn

2017-01-01

Macrophage migration inhibitory factor (MIF), a small conserved protein, is abundant in the immune- and central nervous system (CNS). MIF has several receptors and binding partners that can modulate its action on a cel-lular level. It is upregulated in neurodegenerative diseases and cancer although...

Human T lymphotropic virus type-1 p30II alters cellular gene expression to selectively enhance signaling pathways that activate T lymphocytes

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Feuer Gerold

2004-11-01

Full Text Available Abstract Background Human T-lymphotropic virus type-1 (HTLV-1 is a deltaretrovirus that causes adult T-cell leukemia/lymphoma and is implicated in a variety of lymphocyte-mediated disorders. HTLV-1 contains both regulatory and accessory genes in four pX open reading frames. pX ORF-II encodes two proteins, p13II and p30II, which are incompletely defined in the virus life cycle or HTLV-1 pathogenesis. Proviral clones of the virus with pX ORF-II mutations diminish the ability of the virus to maintain viral loads in vivo. Exogenous expression of p30II differentially modulates CREB and Tax-responsive element-mediated transcription through its interaction with CREB-binding protein/p300 and represses tax/rex RNA nuclear export. Results Herein, we further characterized the role of p30II in regulation of cellular gene expression, using stable p30II expression system employing lentiviral vectors to test cellular gene expression with Affymetrix U133A arrays, representing ~33,000 human genes. Reporter assays in Jurkat T cells and RT-PCR in Jurkat and primary CD4+ T-lymphocytes were used to confirm selected gene expression patterns. Our data reveals alterations of interrelated pathways of cell proliferation, T-cell signaling, apoptosis and cell cycle in p30II expressing Jurkat T cells. In all categories, p30II appeared to be an overall repressor of cellular gene expression, while selectively increasing the expression of certain key regulatory genes. Conclusions We are the first to demonstrate that p30II, while repressing the expression of many genes, selectively activates key gene pathways involved in T-cell signaling/activation. Collectively, our data suggests that this complex retrovirus, associated with lymphoproliferative diseases, relies upon accessory gene products to modify cellular environment to promote clonal expansion of the virus genome and thus maintain proviral loads in vivo.

Emotional Modulation of Learning and Memory: Pharmacological Implications.

Science.gov (United States)

LaLumiere, Ryan T; McGaugh, James L; McIntyre, Christa K

2017-07-01

Memory consolidation involves the process by which newly acquired information becomes stored in a long-lasting fashion. Evidence acquired over the past several decades, especially from studies using post-training drug administration, indicates that emotional arousal during the consolidation period influences and enhances the strength of the memory and that multiple different chemical signaling systems participate in this process. The mechanisms underlying the emotional influences on memory involve the release of stress hormones and activation of the basolateral amygdala, which work together to modulate memory consolidation. Moreover, work suggests that this amygdala-based memory modulation occurs with numerous types of learning and involves interactions with many different brain regions to alter consolidation. Additionally, studies suggest that emotional arousal and amygdala activity in particular influence synaptic plasticity and associated proteins in downstream brain regions. This review considers the historical understanding for memory modulation and cellular consolidation processes and examines several research areas currently using this foundational knowledge to develop therapeutic treatments. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Modulation of NADP(+)-dependent isocitrate dehydrogenase in aging.

Science.gov (United States)

Kil, In Sup; Lee, Young Sup; Bae, Young Seuk; Huh, Tae Lin; Park, Jeen-Woo

2004-01-01

NADPH is an important cofactor in many biosynthesis pathways and the regeneration of reduced glutathione, critically important in cellular defense against oxidative damage. It is mainly produced by glucose-6-phosphate dehydrogenase, malic enzyme, and NADP(+)-specific isocitrate dehydrogenases (ICDHs). Here, we investigated age-related changes in ICDH activity and protein expression in IMR-90 human diploid fibroblast cells and tissues from Fischer 344 rats. We found that in IMR-90 cells the activity of cytosolic ICDH (IDPc) gradually increased with age up to the 46-48 population doubling level (PDL) and then gradually decreased at later PDL. 2',7'-Dichloro-fluorescein fluorescence which reflects intracellular ROS generation was increased with aging in IMR-90 cells. In ad libitum-fed rats, we noted age-related, tissue-specific modulations of IDPc and mitochondrial ICDH (IDPm) activities and protein expression in the liver, kidney and testes. In contrast, ICDH activities and protein expression were not significantly modulated in diet-restricted rats. These data suggest that modulation of ICDH is an age-dependent and a tissue-specific phenomenon.

Wireless Cellular Mobile Communications

OpenAIRE

Zalud, V.

2002-01-01

In this article is briefly reviewed the history of wireless cellular mobile communications, examined the progress in current second generation (2G) cellular standards and discussed their migration to the third generation (3G). The European 2G cellular standard GSM and its evolution phases GPRS and EDGE are described somewhat in detail. The third generation standard UMTS taking up on GSM/GPRS core network and equipped with a new advanced access network on the basis of code division multiple ac...

Error performance analysis in K-tier uplink cellular networks using a stochastic geometric approach

KAUST Repository

Afify, Laila H.

2015-09-14

In this work, we develop an analytical paradigm to analyze the average symbol error probability (ASEP) performance of uplink traffic in a multi-tier cellular network. The analysis is based on the recently developed Equivalent-in-Distribution approach that utilizes stochastic geometric tools to account for the network geometry in the performance characterization. Different from the other stochastic geometry models adopted in the literature, the developed analysis accounts for important communication system parameters and goes beyond signal-to-interference-plus-noise ratio characterization. That is, the presented model accounts for the modulation scheme, constellation type, and signal recovery techniques to model the ASEP. To this end, we derive single integral expressions for the ASEP for different modulation schemes due to aggregate network interference. Finally, all theoretical findings of the paper are verified via Monte Carlo simulations.

Hierarchical structure and modules in the Escherichia coli transcriptional regulatory network revealed by a new top-down approach

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Buer Jan

2004-12-01

Full Text Available Abstract Background Cellular functions are coordinately carried out by groups of genes forming functional modules. Identifying such modules in the transcriptional regulatory network (TRN of organisms is important for understanding the structure and function of these fundamental cellular networks and essential for the emerging modular biology. So far, the global connectivity structure of TRN has not been well studied and consequently not applied for the identification of functional modules. Moreover, network motifs such as feed forward loop are recently proposed to be basic building blocks of TRN. However, their relationship to functional modules is not clear. Results In this work we proposed a top-down approach to identify modules in the TRN of E. coli. By studying the global connectivity structure of the regulatory network, we first revealed a five-layer hierarchical structure in which all the regulatory relationships are downward. Based on this regulatory hierarchy, we developed a new method to decompose the regulatory network into functional modules and to identify global regulators governing multiple modules. As a result, 10 global regulators and 39 modules were identified and shown to have well defined functions. We then investigated the distribution and composition of the two basic network motifs (feed forward loop and bi-fan motif in the hierarchical structure of TRN. We found that most of these network motifs include global regulators, indicating that these motifs are not basic building blocks of modules since modules should not contain global regulators. Conclusion The transcriptional regulatory network of E. coli possesses a multi-layer hierarchical modular structure without feedback regulation at transcription level. This hierarchical structure builds the basis for a new and simple decomposition method which is suitable for the identification of functional modules and global regulators in the transcriptional regulatory network of E

MSAT and cellular hybrid networking

Science.gov (United States)

Baranowsky, Patrick W., II

Westinghouse Electric Corporation is developing both the Communications Ground Segment and the Series 1000 Mobile Phone for American Mobile Satellite Corporation's (AMSC's) Mobile Satellite (MSAT) system. The success of the voice services portion of this system depends, to some extent, upon the interoperability of the cellular network and the satellite communication circuit switched communication channels. This paper will describe the set of user-selectable cellular interoperable modes (cellular first/satellite second, etc.) provided by the Mobile Phone and described how they are implemented with the ground segment. Topics including roaming registration and cellular-to-satellite 'seamless' call handoff will be discussed, along with the relevant Interim Standard IS-41 Revision B Cellular Radiotelecommunications Intersystem Operations and IOS-553 Mobile Station - Land Station Compatibility Specification.

Teaching Experimental Methods: A Framework for Hands-On Modules

Science.gov (United States)

Doherty, David

2011-01-01

Experiments provide a simple and engaging framework for familiarizing students with the process of quantitative social research. In this article, I illustrate how experiments can be used in the classroom environment by describing a module that was implemented in four high school classrooms. The module familiarized students with how the scientific…

CORPORATE REPUTATION INFLUENCES CONSUMER SATISFACTION AND LOYALTY: EVIDENCE FROM CELLULAR INDUSTRY OF PAKISTAN

Directory of Open Access Journals (Sweden)

IMRAN ALI

2011-04-01

Full Text Available Research suggests that it takes five times more expenses to attract new customer than to retain existing consumer. The growing concern of corporations in today’s competitive environment is to retain consumers. As a result, plenty of researches have been conducted to identify the approaches to satisfy and retain consumers. The current study examines the affects of corporate reputation on consumer satisfaction and consumer loyalty. The primary data has been collected from the consumers of cellular industry in Pakistan. The rationale behind selecting respondents from cellular industry is the intense competition, which is enduring in the cellular companies of Pakistan. The study used SPSS and AMOS to analyze the data. The correlation analysis, regression analysis, reliability analysis and model fit index analysis has been used to test hypotheses and interpret some interesting results. The study found significantly positive associations of corporate reputation on consumer satisfaction and consumer loyalty. The study also found strongly positive affects of consumer satisfaction on consumer loyalty for the case of cellular industry of Pakistan. The study proposes some useful recommendations for policy makers in the area.

LHCb VErtex LOcator module characterisation and long term quality assurance tests

CERN Document Server

Bates, A; Doherty, F; Dumps, R; Dwyer, L; Gersabeck, M; Marinho, 1, F; Melone, J; Parkes, C; Saavedra, A; Tobin, M; Viret, S

2009-01-01

LHCb is the dedicated b-physics experiment of the LHC. Its vertex detector, the VErtex LOcator (VELO), will operate in a harsh radiation environment with limited access due to its proximity to the LHC beam. To ensure the long term operation and performance, every module was required to pass a set of quality assurance tests. These were specifically developed for the VELO modules to take into account their operational environment and assembly steps. Each VELO module was rigorously inspected, tested and thermally cycled in the Glasgow module burn-in procedures. This paper provides details of the burn-in procedures and summarises the main results that were found. Some of the major results presented in this paper are: the full characterisation of the leakage currents; identification of bad channels; and signal to noise measurements. A few minor problems were identified through visual inspections of the modules and the feedback into the production process proved critical. As a result of the electrical and thermal t...

Designing a Growing Functional Modules “Artificial Brain”

Directory of Open Access Journals (Sweden)

Jérôme Leboeuf-Pasquier

2012-05-01

Full Text Available

The present paper illustrates the design process for the Growing Functional Modules (GFM learning based controller. GFM controllers are elaborated interconnecting four kinds of components: Global Goals, Acting Modules, Sensations and Sensing Modules. Global Goals trigger intrinsic motivations, Acting and Sensing Modules develop specific functionalities and Sensations provide the controlled system's feedback. GFM controllers learn to satisfy some predefined goals while interacting with the environment and thus should be considered as artificial brains. An example of the design process of a simple controller is provided herein to explain the inherent methodology, to exhibit the components' interconnections and to demonstrate the control process.

Top-down cellular pyramids

Energy Technology Data Exchange (ETDEWEB)

Wu, A Y; Rosenfeld, A

1983-10-01

A cellular pyramid is an exponentially tapering stack of arrays of processors (cells), where each cell is connected to its neighbors (siblings) on its own level, to a parent on the level above, and to its children on the level below. It is shown that in some situations, if information flows top-down only, from fathers to sons, then a cellular pyramid may be no faster than a one-level cellular array; but it may be possible to use simpler cells in the pyramid case. 23 references.

Cellular decomposition in vikalloys

International Nuclear Information System (INIS)

Belyatskaya, I.S.; Vintajkin, E.Z.; Georgieva, I.Ya.; Golikov, V.A.; Udovenko, V.A.

1981-01-01

Austenite decomposition in Fe-Co-V and Fe-Co-V-Ni alloys at 475-600 deg C is investigated. The cellular decomposition in ternary alloys results in the formation of bcc (ordered) and fcc structures, and in quaternary alloys - bcc (ordered) and 12R structures. The cellular 12R structure results from the emergence of stacking faults in the fcc lattice with irregular spacing in four layers. The cellular decomposition results in a high-dispersion structure and magnetic properties approaching the level of well-known vikalloys [ru

High-performance, polymer-based direct cellular interfaces for electrical stimulation and recording

Science.gov (United States)

Kim, Seong-Min; Kim, Nara; Kim, Youngseok; Baik, Min-Seo; Yoo, Minsu; Kim, Dongyoon; Lee, Won-June; Kang, Dong-Hee; Kim, Sohee; Lee, Kwanghee; Yoon, Myung-Han

2018-04-01

Due to the trade-off between their electrical/electrochemical performance and underwater stability, realizing polymer-based, high-performance direct cellular interfaces for electrical stimulation and recording has been very challenging. Herein, we developed transparent and conductive direct cellular interfaces based on a water-stable, high-performance poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) film via solvent-assisted crystallization. The crystallized PEDOT:PSS on a polyethylene terephthalate (PET) substrate exhibited excellent electrical/electrochemical/optical characteristics, long-term underwater stability without film dissolution/delamination, and good viability for primarily cultured cardiomyocytes and neurons over several weeks. Furthermore, the highly crystallized, nanofibrillar PEDOT:PSS networks enabled dramatically enlarged surface areas and electrochemical activities, which were successfully employed to modulate cardiomyocyte beating via direct electrical stimulation. Finally, the high-performance PEDOT:PSS layer was seamlessly incorporated into transparent microelectrode arrays for efficient, real-time recording of cardiomyocyte action potentials with a high signal fidelity. All these results demonstrate the strong potential of crystallized PEDOT:PSS as a crucial component for a variety of versatile bioelectronic interfaces.

Enhancing isoprenoid production through systematically assembling and modulating efflux pumps in Escherichia coli.

Science.gov (United States)

Wang, Jian-Feng; Xiong, Zhi-Qiang; Li, Shi-Yuan; Wang, Yong

2013-09-01

Enhancement of the cellular exportation of heterologous compounds is an important aspect to improve the product yield in microbial cell factory. Efflux pumps can expel various intra- or extra-cellular substances out of microbial hosts and increase the cellular tolerance. Thus in this study, by using the hydrophobic sesquiterpene (amorphadiene) and diterpene (kaurene) as two model compounds, we attempted to improve isoprenoid production through systematically engineering the efflux pumps in Escherichia coli BL21(DE3). The pleiotropic resistant pumps, AcrAB-TolC, MdtEF-TolC from E. coli and heterologous MexAB-OprM pump from Pseudomonas aeruginosa, were overexpressed, assembled, and finely modulated. We found that overexpression of AcrB and TolC components can effectively enhance the specific yield of amorphadiene and kaurene, e.g., 31 and 37 % improvement for amorphadiene compared with control, respectively. The heterologous MexB component can enhance kaurene production with 70 % improvement which is more effective than TolC and AcrB. The results suggest that the three components of tripartite efflux pumps play varied effect to enhance isoprenoid production. Considering the highly organized structure of efflux pumps and importance of components interaction, various component combinations were constructed and the copy number of key components AcrB and TolC was finely modulated as well. The results exhibit that the combination TolC and TolC and AcrB improved the specific yield of amorphadiene with 118 %, and AcrA and TolC and AcrB improved that of kaurene with 104 %. This study indicates that assembling and finely modulating efflux pumps is an effective strategy to improve the production of heterologous compounds in E. coli.

Mass spectrometry reveals thioredoxin-1 as a new partner of ADAM17 that can modulate its sheddase activity

International Nuclear Information System (INIS)

Aragao, A.Z.B.; Simabuco, F.M.; Smetana, J.H.C.; Yokoo, S.; Paes Leme, A.F.; Rodrigues, E.; Mercadante, A.Z.

2012-01-01

Full text: ADAMs are a family of membrane-associated metalloproteinases with a complex multi-domain structure: a metalloproteinase domain, a disintegrin domain, a cysteine-rich region, an epidermal growth factor-like repeat, a transmembrane domain and a cytoplasmic tail. These proteases are responsible for shedding the ectodomains of cell surface proteins, modulating regulatory mechanisms. Many ADAMs are highly associated with tumorigenesis and tumor progression. The aim of this study is identify novel binding partners that can modulate ADAM17 activation via cytoplasmatic domain. We performed the cloning and overexpression of the ADAM17 cytoplasmic tail in HEK-293 cell line and the ligands were determined by LC-MS/MS after proteins immunoprecipitation (IP) with anti-FLAG M2 Affinity Gel (Sigma). Thioredoxin-1 (Trx-1) and others ligands were identified at least in two independent experiments, and this binding is independent of phosphorylation. The IP of Trx-1 was confirmed by Western blot, furthermore Trx-1 immunolocalized with full length ADAM17-HA and cytoplasmic tail-FLAG recombinant proteins in HEK293 and HeLa cells. Trx-1 is part of the system peroxiredoxin/thioredoxin/thioredoxin reductase, one of the mechanisms by which cells maintain the reduced cellular environment, inactivating the reactive oxygen species (ROS). We investigate whether ADAM17 activity is modulate by Trx-1 on AP reporter assay that was performed using HEK293 and SCC-9 cells transfected stably with HB-EGF-AP in co-transfection with transient recombinant Trx-1-HA. The results indicate that Trx-1 can modulate negatively the activity or maturation of ADAM17 in presence of PMA, which is known to increase ROS. In summary, this study identifies Trx-1 and suggest that this protein can modulate ADAM17 activity in normal and tumorigenic cells lines. (author)

Mass spectrometry reveals thioredoxin-1 as a new partner of ADAM17 that can modulate its sheddase activity

Energy Technology Data Exchange (ETDEWEB)

Aragao, A.Z.B.; Simabuco, F.M.; Smetana, J.H.C. [Laboratorio Nacional de Biociencias - LNBIO, Campinas, SP (Brazil); Yokoo, S.; Paes Leme, A.F. [Laboratorio Nacional de Luz Sincrotron (LNLS), Campinas, SP (Brazil); Rodrigues, E.; Mercadante, A.Z. [Universidade Estadual de Campinas (UNICAMP), SP (Brazil)

2012-07-01

Full text: ADAMs are a family of membrane-associated metalloproteinases with a complex multi-domain structure: a metalloproteinase domain, a disintegrin domain, a cysteine-rich region, an epidermal growth factor-like repeat, a transmembrane domain and a cytoplasmic tail. These proteases are responsible for shedding the ectodomains of cell surface proteins, modulating regulatory mechanisms. Many ADAMs are highly associated with tumorigenesis and tumor progression. The aim of this study is identify novel binding partners that can modulate ADAM17 activation via cytoplasmatic domain. We performed the cloning and overexpression of the ADAM17 cytoplasmic tail in HEK-293 cell line and the ligands were determined by LC-MS/MS after proteins immunoprecipitation (IP) with anti-FLAG M2 Affinity Gel (Sigma). Thioredoxin-1 (Trx-1) and others ligands were identified at least in two independent experiments, and this binding is independent of phosphorylation. The IP of Trx-1 was confirmed by Western blot, furthermore Trx-1 immunolocalized with full length ADAM17-HA and cytoplasmic tail-FLAG recombinant proteins in HEK293 and HeLa cells. Trx-1 is part of the system peroxiredoxin/thioredoxin/thioredoxin reductase, one of the mechanisms by which cells maintain the reduced cellular environment, inactivating the reactive oxygen species (ROS). We investigate whether ADAM17 activity is modulate by Trx-1 on AP reporter assay that was performed using HEK293 and SCC-9 cells transfected stably with HB-EGF-AP in co-transfection with transient recombinant Trx-1-HA. The results indicate that Trx-1 can modulate negatively the activity or maturation of ADAM17 in presence of PMA, which is known to increase ROS. In summary, this study identifies Trx-1 and suggest that this protein can modulate ADAM17 activity in normal and tumorigenic cells lines. (author)

Cellular and Molecular Anesthesia: from Bench to Bedside

Directory of Open Access Journals (Sweden)

Ali Dabbagh

2015-12-01

Full Text Available Cellular and Molecular Anesthesia: from Bench to BedsideIn the current practice of anesthesia, each day, anesthesiologists deal with a great work: they use the cellular mechanisms of drug molecules to induce their desired effects for induction and maintenance of anesthesia to achieve appropriate tolerance of surgery and its pain, modulation of stress response, sedation needed for performing a variety of procedures, emergency anesthesia care, acute and chronic pain management or other everyday jobs of anesthesiologists during perioperative period.As a matter of fact, molecular anesthesia has been cited for more than 6 decades though in avery limited scale. In 1956, the molecular mechanisms of morphine and pethidine are described (1. Pauling in 1961 published an article in Science describing a molecular theorey for general anesthesia (2.In its report “the World in 2025”, Thomson Reuters has predicted clinical medicine would be the most active research front; while molecular biology has the 9th rank (3. But are we still practicing in clinic the same as today?In fact, the future trend of anesthesia is highly dependent on finding the novel cellular and molecular mechanisms and the possible interactions of the newly discovered molecules and inreraction mechanisms with organ systems. Today, we emphasize on the role of pharmacologists, physiologists, immunologists, anatomists, embryologists, geneticians, cellular medicine specialists, physicists and other basic science specialists; some very interesting examples are published in this volume of the Journal (4-7.However, changes that have well started now would “revolutionize” our daily practice during the next decade in such a way that it will change the basis of medicine: presumably we will have a new model medicine known as “personalized medicine” or “precision medicine”. In this approach, the content of each patient’s genes accompanied with his/her cellular and molecular analysis is

Outreach Education Modules on Space Sciences in Taiwan

Science.gov (United States)

Lee, I.-Te; Tiger Liu, Jann-Yeng; Chen, Chao-Yen

2013-04-01

The Ionospheric Radio Science Laboratory (IRSL) at Institute of Space Science, National Central University in Taiwan has been conducting a program for public outreach educations on space science by giving lectures, organizing camps, touring exhibits, and experiencing hand-on experiments to elementary school, high school, and college students as well as general public since 1991. The program began with a topic of traveling/living in space, and was followed by space environment, space mission, and space weather monitoring, etc. and a series of course module and experiment (i.e. experiencing activity) module was carried out. For past decadal, the course modules have been developed to cover the space environment of the Sun, interplanetary space, and geospace, as well as the space technology of the rocket, satellite, space shuttle (plane), space station, living in space, observing the Earth from space, and weather observation. Each course module highlights the current status and latest new finding as well as discusses 1-3 key/core issues/concepts and equip with 2-3 activity/experiment modules to make students more easily to understand the topics/issues. Meanwhile, scientific camps are given to lead students a better understanding and interesting on space science. Currently, a visualized image projecting system, Dagik Earth, is developed to demonstrate the scientific results on a sphere together with the course modules. This system will dramatically improve the educational skill and increase interests of participators.

Social constructivist learning environment in an online professional practice course.

Science.gov (United States)

Sthapornnanon, Nunthaluxna; Sakulbumrungsil, Rungpetch; Theeraroungchaisri, Anuchai; Watcharadamrongkun, Suntaree

2009-02-19

To assess the online social constructivist learning environment (SCLE) and student perceptions of the outcomes of the online introductory module of pharmacy professional practice that was designed based on social constructivism theory. The online introductory module of pharmacy professional practice in pharmaceutical marketing and business was carefully designed by organizing various activities, which were intended to encourage social interaction among students. The Constructivist Online Learning Environment Survey (COLLES) was applied to assess the SCLE. Course evaluation questionnaires were administered to assess student perceptions of this online module. The result from the COLLES illustrated the development of SCLE in the course. The students reported positive perceptions of the course. An online introductory module of pharmacy professional practice in pharmaceutical marketing and business was effective in promoting SCLE.

Exosomes and their role in the micro-/macro-environment: a comprehensive review.

Science.gov (United States)

Javeed, Naureen; Mukhopadhyay, Debabrata

2017-09-26

The importance of extracellular vesicles (EVs) in cell-cell communication has long been recognized due to their ability to transfer important cellular cargoes such as DNA, mRNA, miRNAs, and proteins to target cells. Compelling evidence supports the role of EVs in the horizontal transfer of cellular material which has the potential to influence normal cellular physiology and promote various disease states. Of the different types of EVs, exosomes have garnered much attention in the past decade due to their abundance in various biological fluids and ability to affect multiple organ systems. The main focus of this review will be on cancer and how cancer-derived exosomes are important mediators of metastasis, angiogenesis, immune modulation, and the tumor macro-/microenvironment. We will also discuss exosomes as potential biomarkers for cancers due to their abundance in biological fluids, ease of uptake, and cellular content. Exosome use in diagnosis, prognosis, and in establishing treatment regimens has enormous potential to revolutionize patient care.

Active cellular sensing with quantum dots: Transitioning from research tool to reality; a review

Energy Technology Data Exchange (ETDEWEB)

Delehanty, James B., E-mail: james.delehanty@nrl.navy.mil [Center for Bio/Molecular Science and Engineering, Code 6900, U.S. Naval Research Laboratory, Washington, DC 20375 (United States); Susumu, Kimihiro, E-mail: susumu@ccs.nrl.navy.mil [Optical Sciences Division, Code 5611, U.S. Naval Research Laboratory, Washington, DC 20375 (United States); Manthe, Rachel L., E-mail: rmanthe@umd.edu [Center for Bio/Molecular Science and Engineering, Code 6900, U.S. Naval Research Laboratory, Washington, DC 20375 (United States); Fischell Department of Bioengineering, School of Engineering, University of Maryland College Park, College Park, MD 20742 (United States); Algar, W. Russ, E-mail: russ.algar.ctr.ca@nrl.navy.mil [Center for Bio/Molecular Science and Engineering, Code 6900, U.S. Naval Research Laboratory, Washington, DC 20375 (United States); College of Science, George Mason University, Fairfax, VA 22030 (United States); Medintz, Igor L., E-mail: igor.medintz@nrl.navy.mil [Center for Bio/Molecular Science and Engineering, Code 6900, U.S. Naval Research Laboratory, Washington, DC 20375 (United States)

2012-10-31

Highlights: Black-Right-Pointing-Pointer Quantum dots (QDs) have evolved beyond mere cellular labeling reagents. Black-Right-Pointing-Pointer Significant advances have been made in QD materials, surface coatings and bioconjugation. Black-Right-Pointing-Pointer Cellular targeting/delivery has been achieved using polymers, peptides, proteins. Black-Right-Pointing-Pointer Numerous QD-based sensing applications: extracellular, membrane, intracellular. - Abstract: The application of luminescent semiconductor quantum dots (QDs) within a wide range of biological imaging and sensing formats is now approaching its 15th year. The unique photophysical properties of these nanomaterials have long been envisioned as having the potential to revolutionize biosensing within cellular studies that rely on fluorescence. However, it is only now that these materials are making the transition towards accomplishing this goal. With the idea of understanding how to actively incorporate QDs into different types of cellular biosensing, we review the progress in many of the areas relevant to achieving this goal. This includes the synthesis of the QDs themselves, with an emphasis on minimizing potential toxicity, along with the general methods for making these nanocrystalline structures stable in aqueous media. We next survey some methods for conjugating QDs to biomolecules to allow them to participate in active biosensing. Lastly, we extensively review many of the applications where QDs have been demonstrated in an active role in cellular biosensing. These formats cover a wide range of possibilities including where the QDs have contributed to: monitoring the cell's interaction with its extracellular environment; elucidating the complex molecular interplay that characterizes the plasma membrane; understanding how cells continuously endocytose and exocytose materials across the cellular membrane; visualizing organelle trafficking; and, perhaps most importantly, monitoring the intracellular

Performance evaluation of CPPM modulation in multi-path environments

International Nuclear Information System (INIS)

Tasev, Zarko; Kocarev, Ljupco

2003-01-01

Chaotic pulse position modulation (CPPM) is a novel technique to communicate with chaotic signals based upon pulse trains in which the intervals between two pulses are determined by chaotic dynamics of a pulse generator. Using numerical simulations we show that CPPM offers excellent multi-path performance. We simulated the CPPM radio system, which is designed for a WLAN application and operates in the 2.4 GHz ISM frequency band with IEEE 802.11 compliant channel spacing. In this case, the average performance loss due the multi-path for CPPM is less than 5 dB

Performance evaluation of CPPM modulation in multi-path environments

Energy Technology Data Exchange (ETDEWEB)

Tasev, Zarko E-mail: ztasev@ucsd.edu; Kocarev, Ljupco E-mail: lkocarev@ucsd.edu

2003-01-01

Chaotic pulse position modulation (CPPM) is a novel technique to communicate with chaotic signals based upon pulse trains in which the intervals between two pulses are determined by chaotic dynamics of a pulse generator. Using numerical simulations we show that CPPM offers excellent multi-path performance. We simulated the CPPM radio system, which is designed for a WLAN application and operates in the 2.4 GHz ISM frequency band with IEEE 802.11 compliant channel spacing. In this case, the average performance loss due the multi-path for CPPM is less than 5 dB.

The mechanical environment modulates intracellular calcium oscillation activities of myofibroblasts.

Directory of Open Access Journals (Sweden)

Charles Godbout

Full Text Available Myofibroblast contraction is fundamental in the excessive tissue remodeling that is characteristic of fibrotic tissue contractures. Tissue remodeling during development of fibrosis leads to gradually increasing stiffness of the extracellular matrix. We propose that this increased stiffness positively feeds back on the contractile activities of myofibroblasts. We have previously shown that cycles of contraction directly correlate with periodic intracellular calcium oscillations in cultured myofibroblasts. We analyze cytosolic calcium dynamics using fluorescent calcium indicators to evaluate the possible impact of mechanical stress on myofibroblast contractile activity. To modulate extracellular mechanics, we seeded primary rat subcutaneous myofibroblasts on silicone substrates and into collagen gels of different elastic modulus. We modulated cell stress by cell growth on differently adhesive culture substrates, by restricting cell spreading area on micro-printed adhesive islands, and depolymerizing actin with Cytochalasin D. In general, calcium oscillation frequencies in myofibroblasts increased with increasing mechanical challenge. These results provide new insight on how changing mechanical conditions for myofibroblasts are encoded in calcium oscillations and possibly explain how reparative cells adapt their contractile behavior to the stresses occurring in normal and pathological tissue repair.

Cellular automata analysis and applications

CERN Document Server

Hadeler, Karl-Peter

2017-01-01

This book focuses on a coherent representation of the main approaches to analyze the dynamics of cellular automata. Cellular automata are an inevitable tool in mathematical modeling. In contrast to classical modeling approaches as partial differential equations, cellular automata are straightforward to simulate but hard to analyze. In this book we present a review of approaches and theories that allow the reader to understand the behavior of cellular automata beyond simulations. The first part consists of an introduction of cellular automata on Cayley graphs, and their characterization via the fundamental Cutis-Hedlund-Lyndon theorems in the context of different topological concepts (Cantor, Besicovitch and Weyl topology). The second part focuses on classification results: What classification follows from topological concepts (Hurley classification), Lyapunov stability (Gilman classification), and the theory of formal languages and grammars (Kůrka classification). These classifications suggest to cluster cel...

Rigid two-axis MEMS force plate for measuring cellular traction force

International Nuclear Information System (INIS)

Takahashi, Hidetoshi; Jung, Uijin G; Shimoyama, Isao; Kan, Tetsuo; Tsukagoshi, Takuya; Matsumoto, Kiyoshi

2016-01-01

Cellular traction force is one of the important factors for understanding cell behaviors, such as spreading, migration and differentiation. Cells are known to change their behavior according to the mechanical stiffness of the environment. However, the measurement of cell traction forces on a rigid environment has remained difficult. This paper reports a micro-electromechanical systems (MEMS) force plate that provides a cellular traction force measurement on a rigid substrate. Both the high force sensitivity and high stiffness of the substrate were obtained using piezoresistive sensing elements. The proposed force plate consists of a 70 µ m  ×  15 µ m  ×  5 µ m base as the substrate for cultivating a bovine aortic smooth muscle cell, and the supporting beams with piezoresistors on the sidewall and the surface were used to measure the forces in both the horizontal and vertical directions. The spring constant and force resolution of the fabricated force plate in the horizontal direction were 0.2 N m −1 and less than 0.05 µ N, respectively. The cell traction force was measured, and the traction force increased by approximately 1 µ N over 30 min. These results demonstrate that the proposed force plate is applicable as an effective traction force measurement. (paper)

Investigating Youth Sport Coach Perspectives of an Asthma Education Module

Directory of Open Access Journals (Sweden)

Francesca S. Cardwell

2018-01-01

Full Text Available Physical activity can reduce symptoms and improve wellbeing in people who have asthma, and organized sport is one way for children and youth with asthma to engage in exercise. While asthmatic youth may experience a number of barriers to sport participation, healthy physical and social sport environments supported by coaches can help asthmatic youth athletes maintain long-term engagement in activity. This paper reports results of an assessment of an online coach education tool related to air quality, physical activity, and allergic disease (e.g., asthma. Focus groups with youth team sport coaches in southern Ontario (n=12 participants were conducted to explore how users experience the module and short- and medium-term outcomes of implementation. Although coaches perceive the module as relevant, it is considered less valuable in certain contexts (e.g., indoor environments or when compared with other coach education (e.g., tactical. Although broad asthma management behaviours (e.g., athlete medical forms were recognized, specific module-identified prevention and management techniques (e.g., the Air Quality Health Index were less frequently described. Ensuring environment and health coach education emphasizes athlete performance while reducing risk is critical to promoting module application and providing safe and enjoyable youth team sport spaces.

Cellular and molecular mechanisms in malignant transformation of diploid rodent and human cells by radiation

International Nuclear Information System (INIS)

Borek, C.

1985-01-01

The development of cell culture systems has made it possible to probe into the effects of radiation at a cellular and molecular level, under defined conditions where homeostatic mechanisms do not prevail. Using in vitro systems free of host-medicated influences, one can assess qualitatively and quantitatively dose-related and time-dependent interactions of radiation with single cells and to evaluate the influences of agents that may enhance or inhibit the oncogenic potential of radiation. These systems are useful in pragmatic studies where dose response relationships and cancer risk estimates are assessed with particular focus on the low dose range of radiation where epidemiological and animal studies are limiting. The in vitro systems serve well also in mechanistic studies where cellular and molecular processes underlying transformation can be elucidated and where the role of modulating factors which determine the frequency and quality of these events can be investigated

MIMO Communication for Cellular Networks

CERN Document Server

Huang, Howard; Venkatesan, Sivarama

2012-01-01

As the theoretical foundations of multiple-antenna techniques evolve and as these multiple-input multiple-output (MIMO) techniques become essential for providing high data rates in wireless systems, there is a growing need to understand the performance limits of MIMO in practical networks. To address this need, MIMO Communication for Cellular Networks presents a systematic description of MIMO technology classes and a framework for MIMO system design that takes into account the essential physical-layer features of practical cellular networks. In contrast to works that focus on the theoretical performance of abstract MIMO channels, MIMO Communication for Cellular Networks emphasizes the practical performance of realistic MIMO systems. A unified set of system simulation results highlights relative performance gains of different MIMO techniques and provides insights into how best to use multiple antennas in cellular networks under various conditions. MIMO Communication for Cellular Networks describes single-user,...

[Pulse-modulated Electromagnetic Radiation of Extremely High Frequencies Protects Cellular DNA against Damaging Effect of Physico-Chemical Factors in vitro].

Science.gov (United States)

Gapeyev, A B; Lukyanova, N A

2015-01-01

Using a comet assay technique, we investigated protective effects of. extremely high frequency electromagnetic radiation in combination with the damaging effect of X-ray irradiation, the effect of damaging agents hydrogen peroxide and methyl methanesulfonate on DNA in mouse whole blood leukocytes. It was shown that the preliminary exposure of the cells to low intensity pulse-modulated electromagnetic radiation (42.2 GHz, 0.1 mW/cm2, 20-min exposure, modulation frequencies of 1 and 16 Hz) caused protective effects decreasing the DNA damage by 20-45%. The efficacy of pulse-modulated electromagnetic radiation depended on the type of genotoxic agent and increased in a row methyl methanesulfonate--X-rays--hydrogen peroxide. Continuous electromagnetic radiation was ineffective. The mechanisms of protective effects may be connected with an induction of the adaptive response by nanomolar concentrations of reactive oxygen species formed by pulse-modulated electromagnetic radiation.

Hypertension module: an interactive learning tool in physiology.

Science.gov (United States)

Işman, C A; Gülpinar, M A; Kurtel, H; Alican, I; Yeğen, B C

2003-12-01

The aim of the present study was to evaluate the strong or weak aspects of an interactive study module introduced during the "Cardiovascular and Respiratory Systems Subject Committee" in the second year of the medical program. Five study groups consisting of 25 students attended two-hour module sessions for six weeks with the same tutor. According to the module assessment questionnaire, the majority of the students assessed the module as excellent or good. The students reported that they had gained not only in knowledge but also in skills development. The general opinion of the students was that both the organization and the implementation of the module met their expectations. Nearly one-half of the students reported that their expectations with regard to the educational environment and the participation of students were fully met. The major weakness in this new educational trial appears to be assessment of the module.

Dunnione ameliorates cisplatin ototoxicity through modulation of NAD(+) metabolism.

Science.gov (United States)

Kim, Hyung-Jin; Pandit, Arpana; Oh, Gi-Su; Shen, AiHua; Lee, Su-Bin; Khadka, Dipendra; Lee, SeungHoon; Shim, Hyeok; Yang, Sei-Hoon; Cho, Eun-Young; Kwak, Tae Hwan; Choe, Seong-Kyu; Park, Raekil; So, Hong-Seob

2016-03-01

Ototoxicity is an important issue in patients receiving cisplatin chemotherapy. Numerous studies have demonstrated that cisplatin-induced ototoxicity is related to oxidative stress and DNA damage. However, the precise mechanism underlying cisplatin-associated ototoxicity is still unclear. The cofactor nicotinamide adenine dinucleotide (NAD(+)) has emerged as an important regulator of energy metabolism and cellular homeostasis. Here, we demonstrate that the levels and activities of sirtuin-1 (SIRT1) are suppressed by the reduction of intracellular NAD(+) levels in cisplatin-mediated ototoxicity. We provide evidence that the decreases in SIRT1 activity and expression facilitated by increasing poly(ADP-ribose) polymerase-1 (PARP-1) activation and microRNA-34a levels through cisplatin-mediated p53 activation aggravate the associated ototoxicity. Furthermore, we show that the induction of cellular NAD(+) levels using dunnione, which targets intracellular NQO1, prevents the toxic effects of cisplatin through the regulation of PARP-1 and SIRT1 activity. These results suggest that direct modulation of cellular NAD(+) levels by pharmacological agents could be a promising therapeutic approach for protection from cisplatin-induced ototoxicity. Copyright © 2015 Elsevier B.V. All rights reserved.

Social Constructivist Learning Environment in an Online Professional Practice Course

Science.gov (United States)

Sakulbumrungsil, Rungpetch; Theeraroungchaisri, Anuchai; Watcharadamrongkun, Suntaree

2009-01-01

Objective To assess the online social constructivist learning environment (SCLE) and student perceptions of the outcomes of the online introductory module of pharmacy professional practice that was designed based on social constructivism theory. Design The online introductory module of pharmacy professional practice in pharmaceutical marketing and business was carefully designed by organizing various activities, which were intended to encourage social interaction among students. The Constructivist Online Learning Environment Survey (COLLES) was applied to assess the SCLE. Course evaluation questionnaires were administered to assess student perceptions of this online module. Assessment The result from the COLLES illustrated the development of SCLE in the course. The students reported positive perceptions of the course. Conclusion An online introductory module of pharmacy professional practice in pharmaceutical marketing and business was effective in promoting SCLE. PMID:19513147

Lrp4: a novel modulator of extracellular signaling in craniofacial organogenesis

OpenAIRE

Ohazama, Atsushi; Porntaveetus, Thantrira; Ota, Masato S.; Herz, Joachim; Sharpe, Paul T.

2010-01-01

The low-density lipoprotein (LDL) receptor family is a large evolutionarily conserved group of transmembrane proteins. It has been shown that LDL receptor family members can also function as direct signal transducers or modulators for a broad range of cellular signalling pathways. We have identified a novel mode of signalling pathway integration/coordination that occurs outside cells during development that involves an LDL family member. Physical interaction between an extracellular protein (...

Sleep and the price of plasticity: from synaptic and cellular homeostasis to memory consolidation and integration.

Science.gov (United States)

Tononi, Giulio; Cirelli, Chiara

2014-01-08

Sleep is universal, tightly regulated, and its loss impairs cognition. But why does the brain need to disconnect from the environment for hours every day? The synaptic homeostasis hypothesis (SHY) proposes that sleep is the price the brain pays for plasticity. During a waking episode, learning statistical regularities about the current environment requires strengthening connections throughout the brain. This increases cellular needs for energy and supplies, decreases signal-to-noise ratios, and saturates learning. During sleep, spontaneous activity renormalizes net synaptic strength and restores cellular homeostasis. Activity-dependent down-selection of synapses can also explain the benefits of sleep on memory acquisition, consolidation, and integration. This happens through the offline, comprehensive sampling of statistical regularities incorporated in neuronal circuits over a lifetime. This Perspective considers the rationale and evidence for SHY and points to open issues related to sleep and plasticity. Copyright © 2014 Elsevier Inc. All rights reserved.

Modulation and interactions of charged biomimetic membranes with bivalent ions

Science.gov (United States)

Kazadi Badiambile, Adolphe

biomolecules in a dynamic environment and the lack of appropriate physical and biochemical tools. In contrast, biomimetic membrane models that rely on the amphiphilic properties of phospholipids are powerful tools that enable the study of these molecules in vitro. By having control over the different experimental parameters such as temperature and pH, reliable and repeatable experimental conditions can be created. One of the key questions I investigated in this thesis is related to the clustering mechanism of PtdIns(4, 5)P2 into pools or aggregates that enable independent cellular control of this species by geometric separation. The lateral aggregation of PtdIns(4, 5)P2 and its underlying physical causes is still a matter of debate. In the first part of this thesis I introduce the general information on lipid membranes with a special focus on the PtdIns family and their associated signaling events. In addition, I explain the Langmuir-Blodgett film balance (LB) system as tool to study lipid membranes and lipid interactions. In the second chapter, I describe my work on the lateral compressibility of PtdIns(4, 5)P2, PtdIns and DOPG monolayers and its modulation by bivalent ions using Langmuir monolayers. In addition, a theoretical framework of compressibility that depends on a surface potential induced by a planar layer of charged molecules and ions in the bulk was provided. In the third part, I present my work on the excess Gibbs free energy of the lipid systems PtdIns(4, 5)P2 --POPC, PtdIns(4, 5)P2, and POPC as they are modulated by bivalent ions. In the fourth part, I report on my foray in engineering a light-based system that relies on different dye properties to simulate calcium induced calcium release (CICR) that occurs in many cell types. In the final chapter, I provide a general conclusion and present directions for future research that would build on my findings.

Can complex cellular processes be governed by simple linear rules?

Science.gov (United States)

Selvarajoo, Kumar; Tomita, Masaru; Tsuchiya, Masa

2009-02-01

Complex living systems have shown remarkably well-orchestrated, self-organized, robust, and stable behavior under a wide range of perturbations. However, despite the recent generation of high-throughput experimental datasets, basic cellular processes such as division, differentiation, and apoptosis still remain elusive. One of the key reasons is the lack of understanding of the governing principles of complex living systems. Here, we have reviewed the success of perturbation-response approaches, where without the requirement of detailed in vivo physiological parameters, the analysis of temporal concentration or activation response unravels biological network features such as causal relationships of reactant species, regulatory motifs, etc. Our review shows that simple linear rules govern the response behavior of biological networks in an ensemble of cells. It is daunting to know why such simplicity could hold in a complex heterogeneous environment. Provided physical reasons can be explained for these phenomena, major advancement in the understanding of basic cellular processes could be achieved.

Signaling beyond Punching Holes: Modulation of Cellular Responses by Vibrio cholerae Cytolysin

Directory of Open Access Journals (Sweden)

Barkha Khilwani

2015-08-01

Full Text Available Pore-forming toxins (PFTs are a distinct class of membrane-damaging cytolytic proteins that contribute significantly towards the virulence processes employed by various pathogenic bacteria. Vibrio cholerae cytolysin (VCC is a prominent member of the beta-barrel PFT (beta-PFT family. It is secreted by most of the pathogenic strains of the intestinal pathogen V. cholerae. Owing to its potent membrane-damaging cell-killing activity, VCC is believed to play critical roles in V. cholerae pathogenesis, particularly in those strains that lack the cholera toxin. Large numbers of studies have explored the mechanistic basis of the cell-killing activity of VCC. Consistent with the beta-PFT mode of action, VCC has been shown to act on the target cells by forming transmembrane oligomeric beta-barrel pores, thereby leading to permeabilization of the target cell membranes. Apart from the pore-formation-induced direct cell-killing action, VCC exhibits the potential to initiate a plethora of signal transduction pathways that may lead to apoptosis, or may act to enhance the cell survival/activation responses, depending on the type of target cells. In this review, we will present a concise view of our current understanding regarding the multiple aspects of these cellular responses, and their underlying signaling mechanisms, evoked by VCC.

Cellular communications a comprehensive and practical guide

CERN Document Server

Tripathi, Nishith

2014-01-01

Even as newer cellular technologies and standards emerge, many of the fundamental principles and the components of the cellular network remain the same. Presenting a simple yet comprehensive view of cellular communications technologies, Cellular Communications provides an end-to-end perspective of cellular operations, ranging from physical layer details to call set-up and from the radio network to the core network. This self-contained source forpractitioners and students represents a comprehensive survey of the fundamentals of cellular communications and the landscape of commercially deployed

Detection of silent cells, synchronization and modulatory activity in developing cellular networks.

Science.gov (United States)

Hjorth, Johannes J J; Dawitz, Julia; Kroon, Tim; Pires, Johny; Dassen, Valerie J; Berkhout, Janna A; Emperador Melero, Javier; Nadadhur, Aish G; Alevra, Mihai; Toonen, Ruud F; Heine, Vivi M; Mansvelder, Huibert D; Meredith, Rhiannon M

2016-04-01

Developing networks in the immature nervous system and in cellular cultures are characterized by waves of synchronous activity in restricted clusters of cells. Synchronized activity in immature networks is proposed to regulate many different developmental processes, from neuron growth and cell migration, to the refinement of synapses, topographic maps, and the mature composition of ion channels. These emergent activity patterns are not present in all cells simultaneously within the network and more immature "silent" cells, potentially correlated with the presence of silent synapses, are prominent in different networks during early developmental periods. Many current network analyses for detection of synchronous cellular activity utilize activity-based pixel correlations to identify cellular-based regions of interest (ROIs) and coincident cell activity. However, using activity-based correlations, these methods first underestimate or ignore the inactive silent cells within the developing network and second, are difficult to apply within cell-dense regions commonly found in developing brain networks. In addition, previous methods may ignore ROIs within a network that shows transient activity patterns comprising both inactive and active periods. We developed analysis software to semi-automatically detect cells within developing neuronal networks that were imaged using calcium-sensitive reporter dyes. Using an iterative threshold, modulation of activity was tracked within individual cells across the network. The distribution pattern of both inactive and active, including synchronous cells, could be determined based on distance measures to neighboring cells and according to different anatomical layers. © 2015 Wiley Periodicals, Inc.

Extracellular pH Modulates Neuroendocrine Prostate Cancer Cell Metabolism and Susceptibility to the Mitochondrial Inhibitor Niclosamide

Science.gov (United States)

Ippolito, Joseph E.; Brandenburg, Matthew W.; Ge, Xia; Crowley, Jan R.; Kirmess, Kristopher M.; Som, Avik; D’Avignon, D. Andre; Arbeit, Jeffrey M.; Achilefu, Samuel; Yarasheski, Kevin E.; Milbrandt, Jeffrey

2016-01-01

Neuroendocrine prostate cancer is a lethal variant of prostate cancer that is associated with castrate-resistant growth, metastasis, and mortality. The tumor environment of neuroendocrine prostate cancer is heterogeneous and characterized by hypoxia, necrosis, and numerous mitoses. Although acidic extracellular pH has been implicated in aggressive cancer features including metastasis and therapeutic resistance, its role in neuroendocrine prostate cancer physiology and metabolism has not yet been explored. We used the well-characterized PNEC cell line as a model to establish the effects of extracellular pH (pH 6.5, 7.4, and 8.5) on neuroendocrine prostate cancer cell metabolism. We discovered that alkalinization of extracellular pH converted cellular metabolism to a nutrient consumption-dependent state that was susceptible to glucose deprivation, glutamine deprivation, and 2-deoxyglucose (2-DG) mediated inhibition of glycolysis. Conversely, acidic pH shifted cellular metabolism toward an oxidative phosphorylation (OXPHOS)-dependent state that was susceptible to OXPHOS inhibition. Based upon this mechanistic knowledge of pH-dependent metabolism, we identified that the FDA-approved anti-helminthic niclosamide depolarized mitochondrial potential and depleted ATP levels in PNEC cells whose effects were enhanced in acidic pH. To further establish relevance of these findings, we tested the effects of extracellular pH on susceptibility to nutrient deprivation and OXPHOS inhibition in a cohort of castrate-resistant prostate cancer cell lines C4-2B, PC-3, and PC-3M. We discovered similar pH-dependent toxicity profiles among all cell lines with these treatments. These findings underscore a potential importance to acidic extracellular pH in the modulation of cell metabolism in tumors and development of an emerging paradigm that exploits the synergy of environment and therapeutic efficacy in cancer. PMID:27438712

Magnetohydrodynamics cellular automata

International Nuclear Information System (INIS)

Hatori, Tadatsugu.

1990-02-01

There has been a renewal of interest in cellular automata, partly because they give an architecture for a special purpose computer with parallel processing optimized to solve a particular problem. The lattice gas cellular automata are briefly surveyed, which are recently developed to solve partial differential equations such as hydrodynamics or magnetohydrodynamics. A new model is given in the present paper to implement the magnetic Lorentz force in a more deterministic and local procedure than the previous one. (author)

Magnetohydrodynamic cellular automata

Energy Technology Data Exchange (ETDEWEB)

Hatori, Tadatsugu [National Inst. for Fusion Science, Nagoya (Japan)

1990-03-01

There has been a renewal of interest in cellular automata, partly because they give an architecture for a special purpose computer with parallel processing optimized to solve a particular problem. The lattice gas cellular automata are briefly surveyed, which are recently developed to solve partial differential equations such as hydrodynamics or magnetohydrodynamics. A new model is given in the present paper to implement the magnetic Lorentz force in a more deterministic and local procedure than the previous one. (author).

Magnetohydrodynamic cellular automata

International Nuclear Information System (INIS)

Hatori, Tadatsugu

1990-01-01

There has been a renewal of interest in cellular automata, partly because they give an architecture for a special purpose computer with parallel processing optimized to solve a particular problem. The lattice gas cellular automata are briefly surveyed, which are recently developed to solve partial differential equations such as hydrodynamics or magnetohydrodynamics. A new model is given in the present paper to implement the magnetic Lorentz force in a more deterministic and local procedure than the previous one. (author)

Modeling cellular systems

CERN Document Server

Matthäus, Franziska; Pahle, Jürgen

2017-01-01

This contributed volume comprises research articles and reviews on topics connected to the mathematical modeling of cellular systems. These contributions cover signaling pathways, stochastic effects, cell motility and mechanics, pattern formation processes, as well as multi-scale approaches. All authors attended the workshop on "Modeling Cellular Systems" which took place in Heidelberg in October 2014. The target audience primarily comprises researchers and experts in the field, but the book may also be beneficial for graduate students.

Stress Response and Cognitive Performance Modulation in Classroom versus Natural Environments

DEFF Research Database (Denmark)

Mygind, Lærke; Stevenson, Matt P; Liebst, Lasse S

2018-01-01

explores the impact of natural environments on stress response during rest and mental load and cognitive performance in 47 children aged 10⁻12 years in a school context. Heart rate variability measures indexing tonic, event, and phasic vagal tone and attention scores were compared across classroom...... and natural environments. Tonic vagal tone was higher in the natural environment than the classrooms, but no differences were found in event or phasic vagal tone or cognitive performance measures. These findings suggest a situational aspect of the conditions under which natural environments may give rise...

Dynamics and mechanisms of quantum dot nanoparticle cellular uptake

Directory of Open Access Journals (Sweden)

Telford William G

2010-06-01

Full Text Available Abstract Background The rapid growth of the nanotechnology industry and the wide application of various nanomaterials have raised concerns over their impact on the environment and human health. Yet little is known about the mechanism of cellular uptake and cytotoxicity of nanoparticles. An array of nanomaterials has recently been introduced into cancer research promising for remarkable improvements in diagnosis and treatment of the disease. Among them, quantum dots (QDs distinguish themselves in offering many intrinsic photophysical properties that are desirable for targeted imaging and drug delivery. Results We explored the kinetics and mechanism of cellular uptake of QDs with different surface coatings in two human mammary cells. Using fluorescence microscopy and laser scanning cytometry (LSC, we found that both MCF-7 and MCF-10A cells internalized large amount of QD655-COOH, but the percentage of endocytosing cells is slightly higher in MCF-7 cell line than in MCF-10A cell line. Live cell fluorescent imaging showed that QD cellular uptake increases with time over 40 h of incubation. Staining cells with dyes specific to various intracellular organelles indicated that QDs were localized in lysosomes. Transmission electron microscopy (TEM images suggested a potential pathway for QD cellular uptake mechanism involving three major stages: endocytosis, sequestration in early endosomes, and translocation to later endosomes or lysosomes. No cytotoxicity was observed in cells incubated with 0.8 nM of QDs for a period of 72 h. Conclusions The findings presented here provide information on the mechanism of QD endocytosis that could be exploited to reduce non-specific targeting, thereby improving specific targeting of QDs in cancer diagnosis and treatment applications. These findings are also important in understanding the cytotoxicity of nanomaterials and in emphasizing the importance of strict environmental control of nanoparticles.

Cellular Angiofibroma of the Nasopharynx.

Science.gov (United States)

Erdur, Zülküf Burak; Yener, Haydar Murat; Yilmaz, Mehmet; Karaaltin, Ayşegül Batioğlu; Inan, Hakki Caner; Alaskarov, Elvin; Gozen, Emine Deniz

2017-11-01

Angiofibroma is a common tumor of the nasopharynx region but cellular type is extremely rare in head and neck. A 13-year-old boy presented with frequent epistaxis and nasal obstruction persisting for 6 months. According to the clinical symptoms and imaging studies juvenile angiofibroma was suspected. Following angiographic embolization total excision of the lesion by midfacial degloving approach was performed. Histological examination revealed that the tumor consisted of staghorn blood vessels and irregular fibrous stroma. Stellate fibroblasts with small pyknotic to large vesicular nuclei were seen in a highly cellular stroma. These findings identified cellular angiofibroma mimicking juvenile angiofibroma. This article is about a very rare patient of cellular angiofibroma of nasopharynx.

Referent 3D tumor model at cellular level in radionuclide therapy

International Nuclear Information System (INIS)

Spaic, R.; Ilic, R.D.; Petrovic, B.J.

2002-01-01

Aim Conventional internal dosimetry has a lot of limitations because of tumor dose nonuniformity. The best approach for absorbed dose at cellular level for different tumors in radionuclide therapy calculation is Monte Carlo method. The purpose of this study is to introduce referent tumor 3D model at cellular level for Monte Carlo simulation study in radionuclide therapy. Material and Methods The moment when tumor is detectable and when same therapy can start is time period in which referent 3D tumor model at cellular level was defined. In accordance with tumor growth rate at that moment he was a sphere with same radius (10 000 μm). In that tumor there are cells or cluster of cells, which are randomly distributed spheres. Distribution of cells/cluster of cells can be calculated from histology data but it was assumed that this distribution is normal with the same mean value and standard deviation (100±50 mm). Second parameter, which was selected to define referent tumor, is volume density of cells (30%). In this referent tumor there are no necroses. Stroma is defined as space between spheres with same concentration of materials as in spheres. Results: Referent tumor defined on this way have about 2,2 10 5 cells or cluster of cells random distributed. Using this referent 3D tumor model and for same concentration of radionuclides (1:100) and energy of beta emitters (1000 keV) which are homogeneously distributed in labeled cells absorbed dose for all cells was calculated. Simulations are done using FOTELP Monte Carlo code, which is modified for this purposes. Results of absorbed dose in cells are given in numerical values (1D distribution) and as the images (2D or 3D distributions). Conclusion Geometrical module for Monte Carlo simulation study can be standardized by introducing referent 3D tumor model at cellular level. This referent 3D tumor model gives most realistic presentation of different tumors at the moment of their detectability. Referent 3D tumor model at

Detector Modules for the CMS Pixel Phase 1 Upgrade

CERN Document Server

Zhu, De Hua; Berger, Pirmin; Meinhard, Maren Tabea; Starodumov, Andrey; Tavolaro, Vittorio Raoul

2017-01-01

The CMS Pixel phase 1 upgrade detector consists of 1184 modules with new design. An important part of the production is the module qualification and calibration, ensuring their proper functionality within the detector. This paper summarizes the qualification and calibration results of modules used in the innermost two detector layers with focus on methods using module-internal calibration signals. Extended characterizations on pixel level such as electronic noise and bump bond connectivity, optimization of operational parameters, sensor quality and thermal stress resistance were performed using a customized setup with controlled environment. It could be shown that the selected modules have on average $0.55 \\mathrm{ {}^{0\\!}\\!/\\!_{00} }\\, \\pm \\, 0.01 \\mathrm{ {}^{0\\!}\\!/\\!_{00} }\\,$ defective pixels and that all performance parameters stay within their specifications.

FPGA remote update for nuclear environments

Energy Technology Data Exchange (ETDEWEB)

Fernandes, Ana; Pereira, Rita C.; Sousa, Jorge; Carvalho, Paulo F.; Correia, Miguel; Rodrigues, Antonio P.; Carvalho, Bernardo B.; Goncalves, Bruno [Instituto de Plasmasbe Fusao Nuclear, Instituto Superior Tecnico, Universidade de Lisboa, 1049-001 Lisboa, (Portugal); Correia, Carlos M.B.A. [Centro de Instrumentacao, Dept. de Fisica, Universidade de Coimbra, 3004-516 Coimbra, (Portugal)

2015-07-01

The Instituto de Plasmas e Fusao Nuclear (IPFN) has developed dedicated re-configurable modules based on field programmable gate array (FPGA) devices for several nuclear fusion machines worldwide. Moreover, new Advanced Telecommunication Computing Architecture (ATCA) based modules developed by IPFN are already included in the ITER catalogue. One of the requirements for re-configurable modules operating in future nuclear environments including ITER is the remote update capability. Accordingly, this work presents an alternative method for FPGA remote programing to be implemented in new ATCA based re-configurable modules. FPGAs are volatile devices and their programming code is usually stored in dedicated flash memories for properly configuration during module power-on. The presented method is capable to store new FPGA codes in Serial Peripheral Interface (SPI) flash memories using the PCIexpress (PCIe) network established on the ATCA back-plane, linking data acquisition endpoints and the data switch blades. The method is based on the Xilinx Quick Boot application note, adapted to PCIe protocol and ATCA based modules. (authors)

Microarray analysis identifies a common set of cellular genes modulated by different HCV replicon clones

Directory of Open Access Journals (Sweden)

Gerosolimo Germano

2008-06-01

Full Text Available Abstract Background Hepatitis C virus (HCV RNA synthesis and protein expression affect cell homeostasis by modulation of gene expression. The impact of HCV replication on global cell transcription has not been fully evaluated. Thus, we analysed the expression profiles of different clones of human hepatoma-derived Huh-7 cells carrying a self-replicating HCV RNA which express all viral proteins (HCV replicon system. Results First, we compared the expression profile of HCV replicon clone 21-5 with both the Huh-7 parental cells and the 21-5 cured (21-5c cells. In these latter, the HCV RNA has been eliminated by IFN-α treatment. To confirm data, we also analyzed microarray results from both the 21-5 and two other HCV replicon clones, 22-6 and 21-7, compared to the Huh-7 cells. The study was carried out by using the Applied Biosystems (AB Human Genome Survey Microarray v1.0 which provides 31,700 probes that correspond to 27,868 human genes. Microarray analysis revealed a specific transcriptional program induced by HCV in replicon cells respect to both IFN-α-cured and Huh-7 cells. From the original datasets of differentially expressed genes, we selected by Venn diagrams a final list of 38 genes modulated by HCV in all clones. Most of the 38 genes have never been described before and showed high fold-change associated with significant p-value, strongly supporting data reliability. Classification of the 38 genes by Panther System identified functional categories that were significantly enriched in this gene set, such as histones and ribosomal proteins as well as extracellular matrix and intracellular protein traffic. The dataset also included new genes involved in lipid metabolism, extracellular matrix and cytoskeletal network, which may be critical for HCV replication and pathogenesis. Conclusion Our data provide a comprehensive analysis of alterations in gene expression induced by HCV replication and reveal modulation of new genes potentially useful

47 CFR 22.923 - Cellular system configuration.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 2 2010-10-01 2010-10-01 false Cellular system configuration. 22.923 Section... MOBILE SERVICES Cellular Radiotelephone Service § 22.923 Cellular system configuration. Mobile stations... directly or through cellular repeaters. Auxiliary test stations may communicate with base or mobile...

Penetration of sulfur hexafluoride into cellular polypropylene films and its effect on the electric charging and electromechanical response of ferroelectrets

International Nuclear Information System (INIS)

Qiu Xunlin; Wegener, Michael; Wirges, Werner; Zhang Xiaoqing; Hillenbrand, Joachim; Xia Zhongfu; Gerhard-Multhaupt, Reimund; Sessler, Gerhard M

2005-01-01

Cellular polypropylene (PP) films were treated with sulfur hexafluoride (SF 6 ) gas in order to study the SF 6 penetration behaviour and optimize the electric charging conditions. There were differences in the penetration of SF 6 for different cellular PP materials, depending on the microscopic properties, which manifest themselves in the voided structure as well as in the mechanical stiffnesses of the cellular films. The penetration of SF 6 after long-term pressure treatment is confirmed in strongly inflated cellular PP films with a low mechanical stiffness of about 1 MPa. No SF 6 penetration occurs for slightly inflated cellular PP films with smaller void sizes and higher mechanical stiffnesses of around 5.8 MPa. The observed thickness variations, the higher charging fields during corona charging because of SF 6 penetration and the SF 6 environment, as well as the resulting electromechanical properties are discussed

Copper-free click reactions with polar bicyclononyne derivatives for modulation of cellular imaging.

Science.gov (United States)

Leunissen, E H P; Meuleners, M H L; Verkade, J M M; Dommerholt, J; Hoenderop, J G J; van Delft, F L

2014-07-07

The ability of cells to incorporate azidosugars metabolically is a useful tool for extracellular glycan labelling. The exposed azide moiety can covalently react with alkynes, such as bicyclo[6.1.0]nonyne (BCN), by strain-promoted alkyne-azide cycloaddition (SPAAC). However, the use of SPAAC can be hampered by low specificity of the cycloalkyne. In this article we describe the synthesis of more polar BCN derivatives and their properties for selective cellular glycan labelling. The new polar derivatives [amino-BCN, glutarylamino-BCN and bis(hydroxymethyl)-BCN] display reaction rates similar to those of BCN and are less cell-permeable. The labelling specificity in HEK293 cells is greater than that of BCN, as determined by confocal microscopy and flow cytometry. Interestingly, amino-BCN appears to be highly specific for the Golgi apparatus. In addition, the polar BCN derivatives label the N-glycan of the membrane calcium channel TRPV5 in HEK293 cells with significantly enhanced signal-to-noise ratios. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Kinetic and Thermodynamic Aspects of Cellular Thiol-Disulfide Redox Regulation

DEFF Research Database (Denmark)

Jensen, Kristine Steen; Hansen, Rosa Erritzøe; Winther, Jakob R

2009-01-01

. In the cytosol regulatory disulfide bonds are typically formed in spite of the prevailing reducing conditions and may thereby function as redox switches. Such disulfide bonds are protected from enzymatic reduction by kinetic barriers and are thus allowed to exist long enough to elicit the signal. Factors......Regulation of intracellular thiol-disulfide redox status is an essential part of cellular homeostasis. This involves the regulation of both oxidative and reductive pathways, production of oxidant scavengers and, importantly, the ability of cells to respond to changes in the redox environment...... that affect the rate of thiol-disulfide exchange and stability of disulfide bonds are discussed within the framework of the underlying chemical foundations. This includes the effect of thiol acidity (pKa), the local electrostatic environment, molecular strain and entropy. Even though a thiol-disulfide...

APRON: A Cellular Processor Array Simulation and Hardware Design Tool

Science.gov (United States)

Barr, David R. W.; Dudek, Piotr

2009-12-01

We present a software environment for the efficient simulation of cellular processor arrays (CPAs). This software (APRON) is used to explore algorithms that are designed for massively parallel fine-grained processor arrays, topographic multilayer neural networks, vision chips with SIMD processor arrays, and related architectures. The software uses a highly optimised core combined with a flexible compiler to provide the user with tools for the design of new processor array hardware architectures and the emulation of existing devices. We present performance benchmarks for the software processor array implemented on standard commodity microprocessors. APRON can be configured to use additional processing hardware if necessary and can be used as a complete graphical user interface and development environment for new or existing CPA systems, allowing more users to develop algorithms for CPA systems.

APRON: A Cellular Processor Array Simulation and Hardware Design Tool

Directory of Open Access Journals (Sweden)

David R. W. Barr

2009-01-01

Full Text Available We present a software environment for the efficient simulation of cellular processor arrays (CPAs. This software (APRON is used to explore algorithms that are designed for massively parallel fine-grained processor arrays, topographic multilayer neural networks, vision chips with SIMD processor arrays, and related architectures. The software uses a highly optimised core combined with a flexible compiler to provide the user with tools for the design of new processor array hardware architectures and the emulation of existing devices. We present performance benchmarks for the software processor array implemented on standard commodity microprocessors. APRON can be configured to use additional processing hardware if necessary and can be used as a complete graphical user interface and development environment for new or existing CPA systems, allowing more users to develop algorithms for CPA systems.

BRD4 regulates cellular senescence in gastric cancer cells via E2F/miR-106b/p21 axis.

Science.gov (United States)

Dong, Xingchen; Hu, Xiangming; Chen, Jinjing; Hu, Dan; Chen, Lin-Feng

2018-02-12

Small molecules targeting bromodomains of BET proteins possess strong anti-tumor activities and have emerged as potential therapeutics for cancer. However, the underlying mechanisms for the anti-proliferative activity of these inhibitors are still not fully characterized. In this study, we demonstrated that BET inhibitor JQ1 suppressed the proliferation and invasiveness of gastric cancer cells by inducing cellular senescence. Depletion of BRD4, which was overexpressed in gastric cancer tissues, but not other BET proteins recapitulated JQ1-induced cellular senescence with increased cellular SA-β-Gal activity and elevated p21 levels. In addition, we showed that the levels of p21 were regulated at the post-transcriptional level by BRD4-dependent expression of miR-106b-5p, which targets the 3'-UTR of p21 mRNA. Overexpression of miR-106b-5p prevented JQ1-induced p21 expression and BRD4 inhibition-associated cellular senescence, whereas miR-106b-5p inhibitor up-regulated p21 and induced cellular senescence. Finally, we demonstrated that inhibition of E2F suppressed the binding of BRD4 to the promoter of miR-106b-5p and inhibited its transcription, leading to the increased p21 levels and cellular senescence in gastric cancer cells. Our results reveal a novel mechanism by which BRD4 regulates cancer cell proliferation by modulating the cellular senescence through E2F/miR-106b-5p/p21 axis and provide new insights into using BET inhibitors as potential anticancer drugs.

Recursive definition of global cellular-automata mappings

International Nuclear Information System (INIS)

Feldberg, R.; Knudsen, C.; Rasmussen, S.

1994-01-01

A method for a recursive definition of global cellular-automata mappings is presented. The method is based on a graphical representation of global cellular-automata mappings. For a given cellular-automaton rule the recursive algorithm defines the change of the global cellular-automaton mapping as the number of lattice sites is incremented. A proof of lattice size invariance of global cellular-automata mappings is derived from an approximation to the exact recursive definition. The recursive definitions are applied to calculate the fractal dimension of the set of reachable states and of the set of fixed points of cellular automata on an infinite lattice

The Effects of Chronological Age on the Cellular Mechanics of Human Dermal Fibroblasts

Science.gov (United States)

Pan, Z.; Hung, V.; Kambhampati, S.; Ge, S. R.; Rafailovich, M.; Ghosh, K.; Clark, R.; Liu, Y. J.; Nakamura, T.; Shu, X. Z.; Prestwich, G.

2006-03-01

It is often observed that older people display diminished wound healing abilities. Understanding of this phenomenon is important for many in vivo applications of tissue engineering. In this study, the cell mechanics of dermal fibroblasts from 25, 40 and 84 years old female subjects were compared. These cells were cultured on functionalized hyaluronic acid hydrogel substrates which emulated physiological conditions in dermal tissue. The deformation of the substrate caused by cellular traction forces was detected by tracing the displacement of fluorescent beads embedded in the substrate using Digital Image Speckle Correlation. Then cellular traction forces were quantitatively determined by Finite Element Method in a linear elastic model with a high spatial resolution. These results were correlated with auxiliary measurements of substrate modulus, cell modulus and migration. We found that with increasing age, the magnitude of the cellular traction forces diminished. Similarly, the ability of the cells to adapt to changes in the mechanical properties of their environment and migrate was also impaired. The interrelationship between these factors and wound healing will be discussed. This work is supported by NSF- MRSEC program.

Testing the precision optical calibration module for PINGU

Energy Technology Data Exchange (ETDEWEB)

Jurkovic, Martin; Holzapfel, Kilian [TU Muenchen, Physik-Department, Excellence Cluster Universe, Boltzmannstr. 2, 85748 Garching (Germany); Collaboration: IceCube-Collaboration

2015-07-01

The Precision IceCube Next Generation Upgrade (PINGU) is primarily designed to determine the neutrino mass hierarchy. This measurement requires an accurate calibration of the detector in order to reduce systematic uncertainties. The Precision Optical Calibration Modules (POCAM) will be placed in the detector as a well calibrated artificial light source in the ice. The POCAM will be enclosed in a glass sphere identical to those used for the detector modules. To construct and simulate a prototype of the POCAM, every component needs to be analyzed by their optical characteristics and by the behavior in temperatures down to -50 C. Therefore a highly shielded an isolated environment has to be build up. We report the status of the testing environment and the hardware selected.

Zeno's paradox in quantum cellular automata

Energy Technology Data Exchange (ETDEWEB)

Groessing, G [Atominst. der Oesterreichischen Universitaeten, Vienna (Austria); Zeilinger, A [Inst. fuer Experimentalphysik, Univ. Innsbruck (Austria)

1991-07-01

The effect of Zeno's paradox in quantum theory is demonstrated with the aid of quantum mechanical cellular automata. It is shown that the degree of non-unitarity of the cellular automaton evolution and the frequency of consecutive measurements of cellular automaton states are operationally indistinguishable. (orig.).

Zeno's paradox in quantum cellular automata

International Nuclear Information System (INIS)

Groessing, G.; Zeilinger, A.

1991-01-01

The effect of Zeno's paradox in quantum theory is demonstrated with the aid of quantum mechanical cellular automata. It is shown that the degree of non-unitarity of the cellular automaton evolution and the frequency of consecutive measurements of cellular automaton states are operationally indistinguishable. (orig.)

Efficiency of cellular information processing

International Nuclear Information System (INIS)

Barato, Andre C; Hartich, David; Seifert, Udo

2014-01-01

We show that a rate of conditional Shannon entropy reduction, characterizing the learning of an internal process about an external process, is bounded by the thermodynamic entropy production. This approach allows for the definition of an informational efficiency that can be used to study cellular information processing. We analyze three models of increasing complexity inspired by the Escherichia coli sensory network, where the external process is an external ligand concentration jumping between two values. We start with a simple model for which ATP must be consumed so that a protein inside the cell can learn about the external concentration. With a second model for a single receptor we show that the rate at which the receptor learns about the external environment can be nonzero even without any dissipation inside the cell since chemical work done by the external process compensates for this learning rate. The third model is more complete, also containing adaptation. For this model we show inter alia that a bacterium in an environment that changes at a very slow time-scale is quite inefficient, dissipating much more than it learns. Using the concept of a coarse-grained learning rate, we show for the model with adaptation that while the activity learns about the external signal the option of changing the methylation level increases the concentration range for which the learning rate is substantial. (paper)

Semantic integration to identify overlapping functional modules in protein interaction networks

Directory of Open Access Journals (Sweden)

Ramanathan Murali

2007-07-01

Full Text Available Abstract Background The systematic analysis of protein-protein interactions can enable a better understanding of cellular organization, processes and functions. Functional modules can be identified from the protein interaction networks derived from experimental data sets. However, these analyses are challenging because of the presence of unreliable interactions and the complex connectivity of the network. The integration of protein-protein interactions with the data from other sources can be leveraged for improving the effectiveness of functional module detection algorithms. Results We have developed novel metrics, called semantic similarity and semantic interactivity, which use Gene Ontology (GO annotations to measure the reliability of protein-protein interactions. The protein interaction networks can be converted into a weighted graph representation by assigning the reliability values to each interaction as a weight. We presented a flow-based modularization algorithm to efficiently identify overlapping modules in the weighted interaction networks. The experimental results show that the semantic similarity and semantic interactivity of interacting pairs were positively correlated with functional co-occurrence. The effectiveness of the algorithm for identifying modules was evaluated using functional categories from the MIPS database. We demonstrated that our algorithm had higher accuracy compared to other competing approaches. Conclusion The integration of protein interaction networks with GO annotation data and the capability of detecting overlapping modules substantially improve the accuracy of module identification.

In vivo cellular imaging with microscopes enabled by MEMS scanners

Science.gov (United States)

Ra, Hyejun

High-resolution optical imaging plays an important role in medical diagnosis and biomedical research. Confocal microscopy is a widely used imaging method for obtaining cellular and sub-cellular images of biological tissue in reflectance and fluorescence modes. Its characteristic optical sectioning capability also enables three-dimensional (3-D) image reconstruction. However, its use has mostly been limited to excised tissues due to the requirement of high numerical aperture (NA) lenses for cellular resolution. Microscope miniaturization can enable in vivo imaging to make possible early cancer diagnosis and biological studies in the innate environment. In this dissertation, microscope miniaturization for in vivo cellular imaging is presented. The dual-axes confocal (DAC) architecture overcomes limitations of the conventional single-axis confocal (SAC) architecture to allow for miniaturization with high resolution. A microelectromechanical systems (MEMS) scanner is the central imaging component that is key in miniaturization of the DAC architecture. The design, fabrication, and characterization of the two-dimensional (2-D) MEMS scanner are presented. The gimbaled MEMS scanner is fabricated on a double silicon-on-insulator (SOI) wafer and is actuated by self-aligned vertical electrostatic combdrives. The imaging performance of the MEMS scanner in a DAC configuration is shown in a breadboard microscope setup, where reflectance and fluorescence imaging is demonstrated. Then, the MEMS scanner is integrated into a miniature DAC microscope. The whole imaging system is integrated into a portable unit for research in small animal models of human biology and disease. In vivo 3-D imaging is demonstrated on mouse skin models showing gene transfer and siRNA silencing. The siRNA silencing process is sequentially imaged in one mouse over time.

Module-based complexity formation: periodic patterning in feathers and hairs.

Science.gov (United States)

Chuong, Cheng-Ming; Yeh, Chao-Yuan; Jiang, Ting-Xin; Widelitz, Randall

2013-01-01

Patterns describe order which emerges from homogeneity. Complex patterns on the integument are striking because of their visibility throughout an organism’s lifespan. Periodic patterning is an effective design because the ensemble of hair or feather follicles (modules) allows the generation of complexity, including regional variations and cyclic regeneration, giving the skin appendages a new lease on life. Spatial patterns include the arrangements of feathers and hairs in specific number, size, and spacing.We explorehowa field of equivalent progenitor cells can generate periodically arranged modules based on genetic information, physical–chemical rules and developmental timing. Reconstitution experiments suggest a competitive equilibrium regulated by activators/inhibitors involving Turing reaction-diffusion. Temporal patterns result from oscillating stem cell activities within each module (microenvironment regulation), reflected as growth (anagen) and resting (telogen) phases during the cycling of feather and hair follicles. Stimulating modules with activators initiates the spread of regenerative hair waves, while global inhibitors outside each module (macroenvironment) prevent this. Different wave patterns can be simulated by cellular automata principles. Hormonal status and seasonal changes can modulate appendage phenotypes, leading to ‘organ metamorphosis’, with multiple ectodermal organ phenotypes generated from the same precursors. We discuss potential novel evolutionary steps using this module-based complexity in several amniote integument organs, exemplified by the spectacular peacock feather pattern. We thus explore the application of the acquired knowledge of patterning in tissue engineering. New hair follicles can be generated after wounding. Hairs and feathers can be reconstituted through self-organization of dissociated progenitor cells. © 2012 Wiley Periodicals, Inc.

Validation of self-reported cellular phone use

DEFF Research Database (Denmark)

Samkange-Zeeb, Florence; Berg, Gabriele; Blettner, Maria

2004-01-01

BACKGROUND: In recent years, concern has been raised over possible adverse health effects of cellular telephone use. In epidemiological studies of cancer risk associated with the use of cellular telephones, the validity of self-reported cellular phone use has been problematic. Up to now there is ......BACKGROUND: In recent years, concern has been raised over possible adverse health effects of cellular telephone use. In epidemiological studies of cancer risk associated with the use of cellular telephones, the validity of self-reported cellular phone use has been problematic. Up to now...... there is very little information published on this subject. METHODS: We conducted a study to validate the questionnaire used in an ongoing international case-control study on cellular phone use, the "Interphone study". Self-reported cellular phone use from 68 of 104 participants who took part in our study...... was compared with information derived from the network providers over a period of 3 months (taken as the gold standard). RESULTS: Using Spearman's rank correlation, the correlation between self-reported phone use and information from the network providers for cellular phone use in terms of the number of calls...

47 CFR 90.672 - Unacceptable interference to non-cellular 800 MHz licensees from 800 MHz cellular systems or part...

Science.gov (United States)

2010-10-01

... 47 Telecommunication 5 2010-10-01 2010-10-01 false Unacceptable interference to non-cellular 800 MHz licensees from 800 MHz cellular systems or part 22 Cellular Radiotelephone systems, and within the... Procedures and Process-Unacceptable Interference § 90.672 Unacceptable interference to non-cellular 800 MHz...

Flat-plate solar array project. Volume 7: Module encapsulation

Science.gov (United States)

Cuddihy, E.; Coulbert, C.; Gupta, A.; Liang, R.

1986-01-01

The objective of the Encapsulation Task was to develop, demonstrate, and qualify photovoltaic (PV) module encapsulation systems that would provide 20 year (later decreased to 30 year) life expectancies in terrestrial environments, and which would be compatible with the cost and performance goals of the Flat-Plate Solar Array (FSA) Project. The scope of the Encapsulation Task included the identification, development, and evaluation of material systems and configurations required to support and protect the optically and electrically active solar cell circuit components in the PV module operating environment. Encapsulation material technologies summarized include the development of low cost ultraviolet protection techniques, stable low cost pottants, soiling resistant coatings, electrical isolation criteria, processes for optimum interface bonding, and analytical and experimental tools for evaluating the long term durability and structural adequacy of encapsulated modules. Field testing, accelerated stress testing, and design studies have demonstrated that encapsulation materials, processes, and configurations are available that meet the FSA cost and performance goals.

Alterations in cellular metabolism modulate CD1d-mediated NKT-cell responses.

Science.gov (United States)

Webb, Tonya J; Carey, Gregory B; East, James E; Sun, Wenji; Bollino, Dominique R; Kimball, Amy S; Brutkiewicz, Randy R

2016-08-01

Natural killer T (NKT) cells play a critical role in the host's innate immune response. CD1d-mediated presentation of glycolipid antigens to NKT cells has been established; however, the mechanisms by which NKT cells recognize infected or cancerous cells remain unclear. 5(')-AMP activated protein kinase (AMPK) is a master regulator of lipogenic pathways. We hypothesized that activation of AMPK during infection and malignancy could alter the repertoire of antigens presented by CD1d and serve as a danger signal to NKT cells. In this study, we examined the effect of alterations in metabolism on CD1d-mediated antigen presentation to NKT cells and found that an infection with lymphocytic choriomeningitis virus rapidly increased CD1d-mediated antigen presentation. Hypoxia inducible factors (HIF) enhance T-cell effector functions during infection, therefore antigen presenting cells pretreated with pharmacological agents that inhibit glycolysis, induce HIF and activate AMPK were assessed for their ability to induce NKT-cell responses. Pretreatment with 2-deoxyglucose, cobalt chloride, AICAR and metformin significantly enhanced CD1d-mediated NKT-cell activation. In addition, NKT cells preferentially respond to malignant B cells and B-cell lymphomas express HIF-1α. These data suggest that targeting cellular metabolism may serve as a novel means of inducing innate immune responses. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

A Knowledge-based Environment for Software Process Performance Analysis

Directory of Open Access Journals (Sweden)

Natália Chaves Lessa Schots

2015-08-01

Full Text Available Background: Process performance analysis is a key step for implementing continuous improvement in software organizations. However, the knowledge to execute such analysis is not trivial and the person responsible to executing it must be provided with appropriate support. Aim: This paper presents a knowledge-based environment, named SPEAKER, proposed for supporting software organizations during the execution of process performance analysis. SPEAKER comprises a body of knowledge and a set of activities and tasks for software process performance analysis along with supporting tools to executing these activities and tasks. Method: We conducted an informal literature reviews and a systematic mapping study, which provided basic requirements for the proposed environment. We implemented the SPEAKER environment integrating supporting tools for the execution of activities and tasks of performance analysis and the knowledge necessary to execute them, in order to meet the variability presented by the characteristics of these activities. Results: In this paper, we describe each SPEAKER module and the individual evaluations of these modules, and also present an example of use comprising how the environment can guide the user through a specific performance analysis activity. Conclusion: Although we only conducted individual evaluations of SPEAKER’s modules, the example of use indicates the feasibility of the proposed environment. Therefore, the environment as a whole will be further evaluated to verify if it attains its goal of assisting in the execution of process performance analysis by non-specialist people.

Thermal equilibrium control by frequent bang-bang modulation.

Science.gov (United States)

Yang, Cheng-Xi; Wang, Xiang-Bin

2010-05-01

In this paper, we investigate the non-Markovian heat transfer between a weakly damped harmonic oscillator (system) and a thermal bath. When the system is initially in a thermal state and not correlated with the environment, the mean energy of the system always first increases, then oscillates, and finally reaches equilibrium with the bath, no matter what the initial temperature of the system is. Moreover, the heat transfer between the system and the bath can be controlled by fast bang-bang modulation. This modulation does work on the system, and temporarily inverts the direction of heat flow. In this case, the common sense that heat always transfers from hot to cold does not hold any more. At the long time scale, a new dynamic equilibrium is established between the system and the bath. At this equilibrium, the energy of the system can be either higher or lower than its normal equilibrium value. A comprehensive analysis of the relationship between the dynamic equilibrium and the parameters of the modulation as well as the environment is presented.

Origami interleaved tube cellular materials

International Nuclear Information System (INIS)

Cheung, Kenneth C; Tachi, Tomohiro; Calisch, Sam; Miura, Koryo

2014-01-01

A novel origami cellular material based on a deployable cellular origami structure is described. The structure is bi-directionally flat-foldable in two orthogonal (x and y) directions and is relatively stiff in the third orthogonal (z) direction. While such mechanical orthotropicity is well known in cellular materials with extruded two dimensional geometry, the interleaved tube geometry presented here consists of two orthogonal axes of interleaved tubes with high interfacial surface area and relative volume that changes with fold-state. In addition, the foldability still allows for fabrication by a flat lamination process, similar to methods used for conventional expanded two dimensional cellular materials. This article presents the geometric characteristics of the structure together with corresponding kinematic and mechanical modeling, explaining the orthotropic elastic behavior of the structure with classical dimensional scaling analysis. (paper)

Origami interleaved tube cellular materials

Science.gov (United States)

Cheung, Kenneth C.; Tachi, Tomohiro; Calisch, Sam; Miura, Koryo

2014-09-01

A novel origami cellular material based on a deployable cellular origami structure is described. The structure is bi-directionally flat-foldable in two orthogonal (x and y) directions and is relatively stiff in the third orthogonal (z) direction. While such mechanical orthotropicity is well known in cellular materials with extruded two dimensional geometry, the interleaved tube geometry presented here consists of two orthogonal axes of interleaved tubes with high interfacial surface area and relative volume that changes with fold-state. In addition, the foldability still allows for fabrication by a flat lamination process, similar to methods used for conventional expanded two dimensional cellular materials. This article presents the geometric characteristics of the structure together with corresponding kinematic and mechanical modeling, explaining the orthotropic elastic behavior of the structure with classical dimensional scaling analysis.

Multiuser Diversity with Adaptive Modulation in Non-Identically Distributed Nakagami Fading Environments

KAUST Repository

Rao, Anlei; Alouini, Mohamed-Slim

2012-01-01

In this paper, we analyze the performance of adaptive modulation with single-cell multiuser scheduling over independent but not identical distributed (i.n.i.d.) Nakagami fading channels. Closed-form expressions are derived for the average channel

Estimating cellular network performance during hurricanes

International Nuclear Information System (INIS)

Booker, Graham; Torres, Jacob; Guikema, Seth; Sprintson, Alex; Brumbelow, Kelly

2010-01-01

Cellular networks serve a critical role during and immediately after a hurricane, allowing citizens to contact emergency services when land-line communication is lost and serving as a backup communication channel for emergency responders. However, due to their ubiquitous deployment and limited design for extreme loading events, basic network elements, such as cellular towers and antennas are prone to failures during adverse weather conditions such as hurricanes. Accordingly, a systematic and computationally feasible approach is required for assessing and improving the reliability of cellular networks during hurricanes. In this paper we develop a new multi-disciplinary approach to efficiently and accurately assess cellular network reliability during hurricanes. We show how the performance of a cellular network during and immediately after future hurricanes can be estimated based on a combination of hurricane wind field models, structural reliability analysis, Monte Carlo simulation, and cellular network models and simulation tools. We then demonstrate the use of this approach for assessing the improvement in system reliability that can be achieved with discrete topological changes in the system. Our results suggest that adding redundancy, particularly through a mesh topology or through the addition of an optical fiber ring around the perimeter of the system can be an effective way to significantly increase the reliability of some cellular systems during hurricanes.

Arginine vasopressin increases cellular free calcium concentration and adenosine 3',5'-monophosphate production in rat renal papillary collecting tubule cells in culture

International Nuclear Information System (INIS)

Ishikawa, S.; Okada, K.; Saito, T.

1988-01-01

The role of calcium (Ca) in the cellular action of arginine vasopressin (AVP) was examined in rat renal papillary collecting tubule cells in culture. AVP increased both the cellular free Ca concentration ([Ca2+]i) using fura-2, and cAMP production in a dose-dependent manner. AVP-induced cellular Ca mobilization was totally blocked by the antagonist to the antidiuretic action of AVP, and somewhat weakened by the antagonist to the vascular action of AVP. 1-Deamino-8-D-AVP (dDAVP). an antidiuretic analog of AVP, also increased [Ca2+] significantly. Cellular Ca mobilization was not obtained with cAMP, forskolin (a diterpene activator of adenylate cyclase), or phorbol-12-myristate-13-acetate. The early phase of [Ca2+]i depended on the intracellular Ca pool, since an AVP-induced rise in [Ca2+]i was obtained in cells pretreated with Ca-free medium containing 1 mM EGTA, verapamil, or cobalt, which blocked cellular Ca uptake. Also, AVP increased 45 Ca2+ influx during the initial 10 min, which initiated the sustained phase of cellular Ca mobilization. However, cellular cAMP production induced by AVP during the 10-min observation period was diminished in the cells pretreated with Ca-free medium, verapamil, or cobalt, but was still significantly higher than the basal level. This was also diminished by a high Ca concentration in medium. These results indicate that 1) AVP concomitantly regulates cellular free Ca as well as its second messenger cAMP production; 2) AVP-induced elevation of cellular free Ca is dependent on both the cellular Ca pool and extracellular Ca; and 3) there is an optimal level of extracellular Ca to modulate the AVP action in renal papillary collecting tubule cells

The cellular memory disc of reprogrammed cells.

Science.gov (United States)

Anjamrooz, Seyed Hadi

2013-04-01

The crucial facts underlying the low efficiency of cellular reprogramming are poorly understood. Cellular reprogramming occurs in nuclear transfer, induced pluripotent stem cell (iPSC) formation, cell fusion, and lineage-switching experiments. Despite these advances, there are three fundamental problems to be addressed: (1) the majority of cells cannot be reprogrammed, (2) the efficiency of reprogramming cells is usually low, and (3) the reprogrammed cells developed from a patient's own cells activate immune responses. These shortcomings present major obstacles for using reprogramming approaches in customised cell therapy. In this Perspective, the author synthesises past and present observations in the field of cellular reprogramming to propose a theoretical picture of the cellular memory disc. The current hypothesis is that all cells undergo an endogenous and exogenous holographic memorisation such that parts of the cellular memory dramatically decrease the efficiency of reprogramming cells, act like a barrier against reprogramming in the majority of cells, and activate immune responses. Accordingly, the focus of this review is mainly to describe the cellular memory disc (CMD). Based on the present theory, cellular memory includes three parts: a reprogramming-resistance memory (RRM), a switch-promoting memory (SPM) and a culture-induced memory (CIM). The cellular memory arises genetically, epigenetically and non-genetically and affects cellular behaviours. [corrected].

Research on the water environment capacity of Qingyi River (Xuchang Section with GIS technology

Directory of Open Access Journals (Sweden)

Wang Li

2017-01-01

Full Text Available Water environment capacity calculation is the foundation of basin environment management. Due to lack of basic materials and data, the water environment capacity in small basin was not massively researched with appropriate calculating method. This paper mentioned a water capacity calculating method suitable for environment management. The method was based on the study of Xuchang Section of Qingyi River and described with details as follows: Xuchang Section was divided into four control units with GIS technology. The river pollution loads of non-point source pollutants from farmland runoff, rural life, livestock and poultry were calculated with the in-site and statistical data of pollution resource. Meanwhile the calculated river pollution loads of non-point / point source pollutants were statistically analyzed on the basis of control units. Then a water quality module was tested and verified, in which the predicted value tallied with the measured value. The parameter of this water quality module corresponds to the in-site data within relative error ±14%. This module was used to estimate and calculate water environment capacity. With this module the available water environment capacity of each control unit and pollutant reduction amount can be earned through deducting the river pollutant load of point pollutant. The results showed that the utilized method in this paper can satisfy the requirement for the calculating accuracy of small basin water environment capacity.

Prisoner's Dilemma in One-Dimensional Cellular Automata: Visualization of Evolutionary Patterns

OpenAIRE

Pereira, Marcelo Alves; Martinez, Alexandre Souto; Espindola, Aquino Lauri

2007-01-01

The spatial Prisoner's Dilemma is a prototype model to show the emergence of cooperation in very competitive environments. It considers players, at site of lattices, that can either cooperate or defect when playing the Prisoner's Dilemma with other z players. This model presents a rich phase diagram. Here we consider players in cells of one-dimensional cellular automata. Each player interacts with other z players. This geometry allows us to vary, in a simple manner, the number of neighbors ra...

Cosserat modeling of cellular solids

NARCIS (Netherlands)

Onck, P.R.

Cellular solids inherit their macroscopic mechanical properties directly from the cellular microstructure. However, the characteristic material length scale is often not small compared to macroscopic dimensions, which limits the applicability of classical continuum-type constitutive models. Cosserat

Recursive expectation-maximization clustering: A method for identifying buffering mechanisms composed of phenomic modules

Science.gov (United States)

Guo, Jingyu; Tian, Dehua; McKinney, Brett A.; Hartman, John L.

2010-06-01

Interactions between genetic and/or environmental factors are ubiquitous, affecting the phenotypes of organisms in complex ways. Knowledge about such interactions is becoming rate-limiting for our understanding of human disease and other biological phenomena. Phenomics refers to the integrative analysis of how all genes contribute to phenotype variation, entailing genome and organism level information. A systems biology view of gene interactions is critical for phenomics. Unfortunately the problem is intractable in humans; however, it can be addressed in simpler genetic model systems. Our research group has focused on the concept of genetic buffering of phenotypic variation, in studies employing the single-cell eukaryotic organism, S. cerevisiae. We have developed a methodology, quantitative high throughput cellular phenotyping (Q-HTCP), for high-resolution measurements of gene-gene and gene-environment interactions on a genome-wide scale. Q-HTCP is being applied to the complete set of S. cerevisiae gene deletion strains, a unique resource for systematically mapping gene interactions. Genetic buffering is the idea that comprehensive and quantitative knowledge about how genes interact with respect to phenotypes will lead to an appreciation of how genes and pathways are functionally connected at a systems level to maintain homeostasis. However, extracting biologically useful information from Q-HTCP data is challenging, due to the multidimensional and nonlinear nature of gene interactions, together with a relative lack of prior biological information. Here we describe a new approach for mining quantitative genetic interaction data called recursive expectation-maximization clustering (REMc). We developed REMc to help discover phenomic modules, defined as sets of genes with similar patterns of interaction across a series of genetic or environmental perturbations. Such modules are reflective of buffering mechanisms, i.e., genes that play a related role in the maintenance

Silymarin Suppresses Cellular Inflammation By Inducing Reparative Stress Signaling

Energy Technology Data Exchange (ETDEWEB)

Lovelace, Erica S.; Wagoner, Jessica; MacDonald, James; Bammler, Theo; Bruckner, Jacob; Brownell, Jessica; Beyer, Richard; Zink, Erika M.; Kim, Young-Mo; Kyle, Jennifer E.; Webb-Robertson, Bobbie-Jo M.; Waters, Katrina M.; Metz, Thomas O.; Farin, Federico; Oberlies, Nicholas H.; Polyak, Steve

2015-08-28

Silymarin (SM), a natural product, is touted as a liver protectant and preventer of both chronic inflammation and diseases. To define how SM elicits these effects at a systems level, we performed transcriptional profiling, metabolomics, and signaling studies in human liver and T cell lines. Multiple pathways associated with cellular stress and metabolism were modulated by SM treatment within 0.5 to four hours: activation of Activating Transcription Factor 4 (ATF-4) and adenosine monophosphate protein kinase (AMPK) and inhibition of mammalian target of rapamycin (mTOR) signaling, the latter being associated with induction of DNA-damage-inducible transcript 4 (DDIT4). Metabolomics analyses revealed suppression of glycolytic, TCA cycle, and amino acid metabolism by SM treatment. Antiinflammatory effects arose with prolonged (i.e. 24 hours) SM exposure, with suppression of multiple proinflammatory mRNAs and nuclear factor kappa B (NF-κB) and forkhead box O (FOXO) signaling. Studies with murine knock out cells revealed that SM inhibition of both mTOR and NF-κB was partially AMPK dependent, while SM inhibition of the mTOR pathway in part required DDIT4. Thus, SM activates stress and repair responses that culminate in an anti-inflammatory phenotype. Other natural products induced similar stress responses, which correlated with their ability to suppress inflammation. Therefore, natural products like SM may be useful as tools to define how metabolic, stress, and repair pathways regulate cellular inflammation.

Common Genetic Variation In Cellular Transport Genes and Epithelial Ovarian Cancer (EOC) Risk

DEFF Research Database (Denmark)

Chornokur, Ganna; Lin, Hui-Yi; Tyrer, Jonathan P

2015-01-01

. As DNA damage and uncontrolled proliferation are hallmarks of cancer, including epithelial ovarian cancer (EOC), we hypothesized that inherited variation in the cellular transport genes contributes to EOC risk. METHODS: In total, DNA samples were obtained from 14,525 case subjects with invasive EOC......BACKGROUND: Defective cellular transport processes can lead to aberrant accumulation of trace elements, iron, small molecules and hormones in the cell, which in turn may promote the formation of reactive oxygen species, promoting DNA damage and aberrant expression of key regulatory cancer genes...... and from 23,447 controls from 43 sites in the Ovarian Cancer Association Consortium (OCAC). Two hundred seventy nine SNPs, representing 131 genes, were genotyped using an Illumina Infinium iSelect BeadChip as part of the Collaborative Oncological Gene-environment Study (COGS). SNP analyses were conducted...

Recursive definition of global cellular-automata mappings

DEFF Research Database (Denmark)

Feldberg, Rasmus; Knudsen, Carsten; Rasmussen, Steen

1994-01-01

A method for a recursive definition of global cellular-automata mappings is presented. The method is based on a graphical representation of global cellular-automata mappings. For a given cellular-automaton rule the recursive algorithm defines the change of the global cellular-automaton mapping...... as the number of lattice sites is incremented. A proof of lattice size invariance of global cellular-automata mappings is derived from an approximation to the exact recursive definition. The recursive definitions are applied to calculate the fractal dimension of the set of reachable states and of the set...

Cytokines and cytokine networks target neurons to modulate long-term potentiation.

Science.gov (United States)

Prieto, G Aleph; Cotman, Carl W

2017-04-01

Cytokines play crucial roles in the communication between brain cells including neurons and glia, as well as in the brain-periphery interactions. In the brain, cytokines modulate long-term potentiation (LTP), a cellular correlate of memory. Whether cytokines regulate LTP by direct effects on neurons or by indirect mechanisms mediated by non-neuronal cells is poorly understood. Elucidating neuron-specific effects of cytokines has been challenging because most brain cells express cytokine receptors. Moreover, cytokines commonly increase the expression of multiple cytokines in their target cells, thus increasing the complexity of brain cytokine networks even after single-cytokine challenges. Here, we review evidence on both direct and indirect-mediated modulation of LTP by cytokines. We also describe novel approaches based on neuron- and synaptosome-enriched systems to identify cytokines able to directly modulate LTP, by targeting neurons and synapses. These approaches can test multiple samples in parallel, thus allowing the study of multiple cytokines simultaneously. Hence, a cytokine networks perspective coupled with neuron-specific analysis may contribute to delineation of maps of the modulation of LTP by cytokines. Copyright © 2017 Elsevier Ltd. All rights reserved.

Targeting brain cells with glutathione-modulated nanoliposomes: in vitro and in vivo study

Directory of Open Access Journals (Sweden)

Salem HF

2015-07-01

Full Text Available Heba F Salem,1 Sayed M Ahmed,2 Ashraf E Hassaballah,3 Mahmoud M Omar1,4 1Department of Pharmaceutics and Industrial Pharmacy, Beni-suef University, 2Department of Industrial Pharmacy, Assiut University, 3Department of Clinical Pathology, Faculty of Medicine, Assiut University, Assuit, 4Department of Pharmaceutics and Industrial Pharmacy, Deraya University, Egypt Background: The blood–brain barrier prevents many drug moieties from reaching the central nervous system. Therefore, glutathione-modulated nanoliposomes have been engineered to enhance the targeting of flucytosine to the brain. Methods: Glutathione-modulated nanoliposomes were prepared by thin-film hydration technique and evaluated in the primary brain cells of rats. Lecithin, cholesterol, and span 65 were mixed at 1:1:1 molar ratio. The molar percentage of PEGylated glutathione varied from 0 mol% to 0.75 mol%. The cellular binding and the uptake of the targeted liposomes were both monitored by epifluorescent microscope and flow cytometry techniques. A biodistribution and a pharmacokinetic study of flucytosine and flucytosine-loaded glutathione–modulated liposomes was carried out to evaluate the in vivo brain-targeting efficiency. Results: The size of glutathione-modulated nanoliposomes was <100 nm and the zeta potential was more than -65 mV. The cumulative release reached 70% for certain formulations. The cellular uptake increased as molar percent of glutathione increased to reach the maximum at 0.75 mol%. The uptake of the targeted liposomes by brain cells of the rats was three times greater than that of the nontargeted liposomes. An in vivo study showed that the relative efficiency was 2.632±0.089 and the concentration efficiency was 1.590±0.049, and also, the drug-targeting index was 3.670±0.824. Conclusion: Overall, these results revealed that glutathione-PEGylated nanoliposomes enhance the effective delivery of flucytosine to brain and could become a promising new

Load-aware modeling for uplink cellular networks in a multi-channel environment

KAUST Repository

AlAmmouri, Ahmad

2014-09-01

We exploit tools from stochastic geometry to develop a tractable analytical approach for modeling uplink cellular networks. The developed model is load aware and accounts for per-user power control as well as the limited transmit power constraint for the users\\' equipment (UEs). The proposed analytical paradigm is based on a simple per-user power control scheme in which each user inverts his path-loss such that the signal is received at his serving base station (BS) with a certain power threshold ρ Due to the limited transmit power of the UEs, users that cannot invert their path-loss to their serving BSs are allowed to transmit with their maximum transmit power. We show that the proposed power control scheme not only provides a balanced cell center and cell edge user performance, it also facilitates the analysis when compared to the state-of-the-art approaches in the literature. To this end, we discuss how to manipulate the design variable ρ in response to the network parameters to optimize one or more of the performance metrics such as the outage probability, the network capacity, and the energy efficiency.

Evaluation of Structural Cellular Glass

Science.gov (United States)

Adams, M. A.; Zwissler, J. G.

1984-01-01

Preliminary design information presented. First report discusses state of structural-cellular-glass programs as of June 1979. Second report gives further details of program to develop improved cellular glasses and to characterize properties of glasses and commercially available materials.

Uniform and localized corrosion modelling by means of probabilistic cellular automata

International Nuclear Information System (INIS)

Perez-Brokate, Cristian

2016-01-01

Numerical modelling is complementary tool for corrosion prediction. The objective of this work is to develop a corrosion model by means of a probabilistic cellular automata approach at a mesoscopic scale. In this work, we study the morphological evolution and kinetics of corrosion. This model couples electrochemical oxidation and reduction reactions. Regarding kinetics, cellular automata models are able to describe current as a function of the applied potential for a redox reaction on an inert electrode. The inclusion of probabilities allows the description of the stochastic nature of anodic and cathodic reactions. Corrosion morphology has been studied in different context: generalised corrosion, pitting corrosion and corrosion in an occluded environment. a general tendency of two regimes is found. a first regime of uniform corrosion where the anodic and cathodic reactions occur homogeneously over the surface. a second regime of localized corrosion when there is a spatial separation of anodic and cathodic zones, with an increase of anodic reaction rate. (author) [fr

Epigenetics and Cellular Metabolism

OpenAIRE

Wenyi Xu; Fengzhong Wang; Zhongsheng Yu; Fengjiao Xin

2016-01-01

Living eukaryotic systems evolve delicate cellular mechanisms for responding to various environmental signals. Among them, epigenetic machinery (DNA methylation, histone modifications, microRNAs, etc.) is the hub in transducing external stimuli into transcriptional response. Emerging evidence reveals the concept that epigenetic signatures are essential for the proper maintenance of cellular metabolism. On the other hand, the metabolite, a main environmental input, can also influence the proce...

Implementation of the Air Program Information Management System (APIMS) Inspection Module

Science.gov (United States)

2009-05-01

7 5 T H A I R B A S E W I N G Implementation of the Air Program Information Management System (APIMS) Inspection Module 2009 Environment...Implementation of the Air Program Information Management System (APIMS) Inspection Module 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER

Within-host spatiotemporal dynamics of plant virus infection at the cellular level.

Directory of Open Access Journals (Sweden)

Nicolas Tromas

2014-02-01

Full Text Available A multicellular organism is not a monolayer of cells in a flask; it is a complex, spatially structured environment, offering both challenges and opportunities for viruses to thrive. Whereas virus infection dynamics at the host and within-cell levels have been documented, the intermediate between-cell level remains poorly understood. Here, we used flow cytometry to measure the infection status of thousands of individual cells in virus-infected plants. This approach allowed us to determine accurately the number of cells infected by two virus variants in the same host, over space and time as the virus colonizes the host. We found a low overall frequency of cellular infection (<0.3, and few cells were coinfected by both virus variants (<0.1. We then estimated the cellular contagion rate (R, the number of secondary infections per infected cell per day. R ranged from 2.43 to values not significantly different from zero, and generally decreased over time. Estimates of the cellular multiplicity of infection (MOI, the number of virions infecting a cell, were low (<1.5. Variance of virus-genotype frequencies increased strongly from leaf to cell levels, in agreement with a low MOI. Finally, there were leaf-dependent differences in the ease with which a leaf could be colonized, and the number of virions effectively colonizing a leaf. The modeling of infection patterns suggests that the aggregation of virus-infected cells plays a key role in limiting spread; matching the observation that cell-to-cell movement of plant viruses can result in patches of infection. Our results show that virus expansion at the between-cell level is restricted, probably due to the host environment and virus infection itself.

Depth-resolved cellular microrheology using HiLo microscopy.

Science.gov (United States)

Michaelson, Jarett; Choi, Heejin; So, Peter; Huang, Hayden

2012-06-01

It is increasingly important to measure cell mechanical properties in three-dimensional environments. Particle tracking microrheology (PTM) can measure cellular viscoelastic properties; however, out-of-plane data can introduce artifacts into these measurements. We developed a technique that employs HiLo microscopy to reduce out-of-plane contributions. This method eliminated signals from 90% of probes 0.5 μm or further from the focal plane, while retaining all in-plane probes. We used this technique to characterize live-cell bilayers and found that there were significant, frequency-dependent changes to the extracted cell moduli when compared to conventional analysis. Our results indicate that removal of out-of-plane information is vital for accurate assessments of cell mechanical properties.

Only small fractions of soluble ß-glucan modulate the mucosal immune system in carp (Cyprinus carpio L.)

DEFF Research Database (Denmark)

Przybylska, Dominika Alicja; Nielsen, Michael Engelbrecht

For decades the ability of β-glucans to modulate immunity through activation of innate cellular components has been observed. However, toxicological effects associated with the systemic administration and dose-related immune-suppression has also been described. The superior aim of this study...... is to understand the effect of β-glucan induced modulation in carp in relation to tissue regeneration, mucosal immunity and host-pathogen interactions. Expression profiles of immune related genes will be measured in fresh water specie – common carp (Cyprinus carpio L.). The methodology of the project involves...

Non-classical Correlations and Quantum Coherence in Mixed Environments

Science.gov (United States)

Hu, Zheng-Da; Wei, Mei-Song; Wang, Jicheng; Zhang, Yixin; He, Qi-Liang

2018-05-01

We investigate non-classical correlations (entanglement and quantum discord) and quantum coherence for an open two-qubit system each independently coupled to a bosonic environment and a spin environment, respectively. The modulating effects of spin environment and bosonic environment are respectively explored. A relation among the quantum coherence, quantum discord and classical correlation is found during the sudden transition phenomenon. We also compare the case of mixed environments with that of the same environments, showing that the dynamics is dramatically changed.

Real-Time Molecular Monitoring of Chemical Environment in ObligateAnaerobes during Oxygen Adaptive Response

Energy Technology Data Exchange (ETDEWEB)

Holman, Hoi-Ying N.; Wozei, Eleanor; Lin, Zhang; Comolli, Luis R.; Ball, David. A.; Borglin, Sharon; Fields, Matthew W.; Hazen, Terry C.; Downing, Kenneth H.

2009-02-25

Determining the transient chemical properties of the intracellular environment canelucidate the paths through which a biological system adapts to changes in its environment, for example, the mechanisms which enable some obligate anaerobic bacteria to survive a sudden exposure to oxygen. Here we used high-resolution Fourier Transform Infrared (FTIR) spectromicroscopy to continuously follow cellular chemistry within living obligate anaerobes by monitoring hydrogen bonding in their cellular water. We observed a sequence of wellorchestrated molecular events that correspond to changes in cellular processes in those cells that survive, but only accumulation of radicals in those that do not. We thereby can interpret the adaptive response in terms of transient intracellular chemistry and link it to oxygen stress and survival. This ability to monitor chemical changes at the molecular level can yield important insights into a wide range of adaptive responses.

Cellular observations enabled by microculture: paracrine signaling and population demographics†

Science.gov (United States)

Domenech, Maribella; Yu, Hongmei; Warrick, Jay; Badders, Nisha M.; Meyvantsson, Ivar; Alexander, Caroline M.; Beebe, David J.

2009-01-01

The cellular microenvironment plays a critical role in shaping and directing the process of communication between the cells. Soluble signals are responsible for many cellular behaviors such as cell survival, proliferation and differentiation. Despite the importance of soluble signals, canonical methods are not well suited to the study of soluble factor interactions between multiple cell types. Macro-scale technology often puts cells into a convective environment that can wash away and dilute soluble signals from their targets, minimizing local concentrations of important factors. In addition, current methods such as transwells, require large numbers of cells and are limited to studying just two cell types. Here, we present data supporting the use of microchannels to study soluble factor signaling providing improved sensitivity as well as the ability to move beyond existing co-culture and conditioned medium paradigms. In addition, we present data suggesting that microculture can be used to unmask effects of population demographics. In this example the data support the hypothesis that a growth promoting subpopulation of cells exists in the mouse mammary gland. PMID:20011455

Cellular observations enabled by microculture: paracrine signaling and population demographics.

Science.gov (United States)

Domenech, Maribella; Yu, Hongmei; Warrick, Jay; Badders, Nisha M; Meyvantsson, Ivar; Alexander, Caroline M; Beebe, David J

2009-03-01

The cellular microenvironment plays a critical role in shaping and directing the process of communication between the cells. Soluble signals are responsible for many cellular behaviors such as cell survival, proliferation and differentiation. Despite the importance of soluble signals, canonical methods are not well suited to the study of soluble factor interactions between multiple cell types. Macro-scale technology often puts cells into a convective environment that can wash away and dilute soluble signals from their targets, minimizing local concentrations of important factors. In addition, current methods such as transwells, require large numbers of cells and are limited to studying just two cell types. Here, we present data supporting the use of microchannels to study soluble factor signaling providing improved sensitivity as well as the ability to move beyond existing co-culture and conditioned medium paradigms. In addition, we present data suggesting that microculture can be used to unmask effects of population demographics. In this example the data support the hypothesis that a growth promoting subpopulation of cells exists in the mouse mammary gland.

Physiological actions of corticosterone and its modulation by an immune challenge in reptiles.

Science.gov (United States)

Meylan, Sandrine; Haussy, Claudy; Voituron, Yann

2010-11-01

Hormones are an important interface between genome and environment, because of their ability to modulate the animal's phenotype. In particular, corticosterone, the stress hormone in lizards, is known to reallocate energy from non-essential functions to affect morphological, physiological and behavioral traits that help the organism to deal with acute or chronic stressors. However, the effects of corticosterone on life history stages are still unclear primarily because of the dependence of life history stages on both internal and external factors. Using a cross-design, we tested the effect of elevated levels of exogenous corticosterone on the physiology of pregnant females in different immune contexts in a wild population of common lizards (Lacerta vivipara). Immune challenge was induced by the injection of sheep red blood cells (SRBC) and corticosterone levels were increased using a transdermal administration of corticosterone. Thereafter, reproductive traits, metabolism and cellular immune responses were measured. The elevation of corticosterone in pregnant females significantly altered reproductive and physiological performance. The corticosterone treatment decreased clutch success, juvenile size and body condition, but enhanced measures of physiological performance, such as metabolism and catalase activity. These first results reinforce the understanding of the physiological actions of corticosterone in reptiles. The data also demonstrated different direct impacts of immune challenge by SRBC on inflammatory response and antioxidant activity. The injection of SRBC stimulated the SOD activity in larger females. Finally, we demonstrated experimentally the modulation of the corticosterone action by the immune challenge on stamina and hatching date. Copyright © 2010 Elsevier Inc. All rights reserved.

Quality Assurance Tests of the LHCb VELO Modules

CERN Document Server

Marinho, Franciole

2007-01-01

The LHCb experiment has a dedicated vertex detector (VELO) to measure the particle’s tracks close to the interaction point. This paper describes the main steps of the quality assurance tests performed during assembly, reception and installation of the LHCb VELO modules. Visual inspection, electrical tests, thermal tests and metrology measurements were made. A burn-in test of the modules was performed in a vacuum environment similar to that of the LHCb experiment. The signal to noise of the sensors was estimated to be 20.4 3.0 for R sensors and 22.4 3 0 for Φ sensors. The modules were tested up to 350 V and the leakage current of the modules did not exceed 20µA at any stage of the testing. Only 0.6% of channels were found to be noisy or not fully functional. The acceptable operating pressures of the modules in vacuum was also evaluated.

Applications of thermoelectric modules on heat flow detection.

Science.gov (United States)

Leephakpreeda, Thananchai

2012-03-01

This paper presents quantitative analysis and practical scenarios of implementation of the thermoelectric module for heat flow detection. Mathematical models of the thermoelectric effects are derived to describe the heat flow from/to the detected media. It is observed that the amount of the heat flow through the thermoelectric module proportionally induces the conduction heat owing to the temperature difference between the hot side and the cold side of the thermoelectric module. In turn, the Seebeck effect takes place in the thermoelectric module where the temperature difference is converted to the electric voltage. Hence, the heat flow from/to the detected media can be observed from both the amount and the polarity of the voltage across the thermoelectric module. Two experiments are demonstrated for viability of the proposed technique by the measurements of the heat flux through the building wall and thermal radiation from the outdoor environment during daytime. Copyright © 2011 ISA. Published by Elsevier Ltd. All rights reserved.

Genome-wide identification of key modulators of gene-gene interaction networks in breast cancer.

Science.gov (United States)

Chiu, Yu-Chiao; Wang, Li-Ju; Hsiao, Tzu-Hung; Chuang, Eric Y; Chen, Yidong

2017-10-03

With the advances in high-throughput gene profiling technologies, a large volume of gene interaction maps has been constructed. A higher-level layer of gene-gene interaction, namely modulate gene interaction, is composed of gene pairs of which interaction strengths are modulated by (i.e., dependent on) the expression level of a key modulator gene. Systematic investigations into the modulation by estrogen receptor (ER), the best-known modulator gene, have revealed the functional and prognostic significance in breast cancer. However, a genome-wide identification of key modulator genes that may further unveil the landscape of modulated gene interaction is still lacking. We proposed a systematic workflow to screen for key modulators based on genome-wide gene expression profiles. We designed four modularity parameters to measure the ability of a putative modulator to perturb gene interaction networks. Applying the method to a dataset of 286 breast tumors, we comprehensively characterized the modularity parameters and identified a total of 973 key modulator genes. The modularity of these modulators was verified in three independent breast cancer datasets. ESR1, the encoding gene of ER, appeared in the list, and abundant novel modulators were illuminated. For instance, a prognostic predictor of breast cancer, SFRP1, was found the second modulator. Functional annotation analysis of the 973 modulators revealed involvements in ER-related cellular processes as well as immune- and tumor-associated functions. Here we present, as far as we know, the first comprehensive analysis of key modulator genes on a genome-wide scale. The validity of filtering parameters as well as the conservativity of modulators among cohorts were corroborated. Our data bring new insights into the modulated layer of gene-gene interaction and provide candidates for further biological investigations.

Protein-protein interaction networks identify targets which rescue the MPP+ cellular model of Parkinson’s disease

Science.gov (United States)

Keane, Harriet; Ryan, Brent J.; Jackson, Brendan; Whitmore, Alan; Wade-Martins, Richard

2015-11-01

Neurodegenerative diseases are complex multifactorial disorders characterised by the interplay of many dysregulated physiological processes. As an exemplar, Parkinson’s disease (PD) involves multiple perturbed cellular functions, including mitochondrial dysfunction and autophagic dysregulation in preferentially-sensitive dopamine neurons, a selective pathophysiology recapitulated in vitro using the neurotoxin MPP+. Here we explore a network science approach for the selection of therapeutic protein targets in the cellular MPP+ model. We hypothesised that analysis of protein-protein interaction networks modelling MPP+ toxicity could identify proteins critical for mediating MPP+ toxicity. Analysis of protein-protein interaction networks constructed to model the interplay of mitochondrial dysfunction and autophagic dysregulation (key aspects of MPP+ toxicity) enabled us to identify four proteins predicted to be key for MPP+ toxicity (P62, GABARAP, GBRL1 and GBRL2). Combined, but not individual, knockdown of these proteins increased cellular susceptibility to MPP+ toxicity. Conversely, combined, but not individual, over-expression of the network targets provided rescue of MPP+ toxicity associated with the formation of autophagosome-like structures. We also found that modulation of two distinct proteins in the protein-protein interaction network was necessary and sufficient to mitigate neurotoxicity. Together, these findings validate our network science approach to multi-target identification in complex neurological diseases.

Three-dimensional immersive virtual reality for studying cellular compartments in 3D models from EM preparations of neural tissues

KAUST Repository

Cali, Corrado

2015-07-14

Advances for application of electron microscopy to serial imaging are opening doors to new ways of analyzing cellular structure. New and improved algorithms and workflows for manual and semiautomated segmentation allow to observe the spatial arrangement of the smallest cellular features with unprecedented detail in full three-dimensions (3D). From larger samples, higher complexity models can be generated; however, they pose new challenges to data management and analysis. Here, we review some currently available solutions and present our approach in detail. We use the fully immersive virtual reality (VR) environment CAVE (cave automatic virtual environment), a room where we are able to project a cellular reconstruction and visualize in 3D, to step into a world created with Blender, a free, fully customizable 3D modeling software with NeuroMorph plug-ins for visualization and analysis of electron microscopy (EM) preparations of brain tissue. Our workflow allows for full and fast reconstructions of volumes of brain neuropil using ilastik, a software tool for semiautomated segmentation of EM stacks. With this visualization environment, we can walk into the model containing neuronal and astrocytic processes to study the spatial distribution of glycogen granules, a major energy source that is selectively stored in astrocytes. The use of CAVE was key to observe a nonrandom distribution of glycogen, and led us to develop tools to quantitatively analyze glycogen clustering and proximity to other subcellular features. This article is protected by copyright. All rights reserved.

Cellular Stress Response to Engineered Nanoparticles: Effect of Size, Surface Coating, and Cellular Uptake

Science.gov (United States)

CELLULAR STRESS RESPONSE TO ENGINEERED NANOPARTICLES: EFFECT OF SIZE, SURFACE COATING, AND CELLULAR UPTAKE RY Prasad 1, JK McGee2, MG Killius1 D Ackerman2, CF Blackman2 DM DeMarini2 , SO Simmons2 1 Student Services Contractor, US EPA, RTP, NC 2 US EPA, RTP, NC The num...

A two-Transputer VME module for data acquisition and on-line event selection in ZEUS

International Nuclear Information System (INIS)

Boterenbrood, H.; Goble, S.; Jong, S.J. de; Kieft, G.; Lugt, H.J. van der; Uijterwaal, H.A.J.R.; Vermeulen, J.C.; Waard, A. de; Wiggers, L.W.

1993-01-01

For the ZEUS experiment at the HERA e-p collider in Hamburg a versatile and fast VME-based processor module has been developed at NIKHEF-H. The single-slot wide VME module contains two INMOS T800 Transputers, each with private memory, and a triple-port memory (TPM), accessible to both Transputers. Both Transputers have access to the VME bus, while an external master can also access the TPM directly. The VME accesses proceed typically with 10 Mbyte/s. Three application-specific integrated circuits (ASICs) handle the internal and external Transputer interfacing. The module combines the VME environment with the parallel processing and link-oriented environment of the Transputer. Over 200 modules are used in the data acquisition and event selection systems of ZEUS. (orig.)

The research of nuclear experiment radiation environment wireless alarm device

International Nuclear Information System (INIS)

Wang Xiaoqiong; Wang Pan; Fang Fang

2009-01-01

This article introduces based on monolithic integrated circuit's nuclear experiment radiation environment wireless alarm device's software and hardware design. The system by G-M tube, high-pressured module, signal conditioning circuit, power source module, monolithic integrated circuit and wireless transmission module is composed. The device has low power consumption, high performance, high accuracy detection, easy maintenance, small size, simple operation, and other features, and has a broad application prospects. (authors)

Eukaryotic Cell Cycle as a Test Case for Modeling Cellular Regulation in a Collaborative Problem-Solving Environment

Science.gov (United States)

2007-03-01

computer models of cell cycle regulation in a variety of organisms, including yeast cells, amphibian embryos, bacterial cells and human cells. These...and meiosis ), but they do not nullify the central role played by irreversible, alternating START and FINISH transitions in the cell cycle. 32...AFRL-IF-RS-TR-2007-69 Final Technical Report March 2007 EUKARYOTIC CELL CYCLE AS A TEST CASE FOR MODELING CELLULAR REGULATION IN A

Thermal and optical performance of encapsulation systems for flat-plate photovoltaic modules

Science.gov (United States)

Minning, C. P.; Coakley, J. F.; Perrygo, C. M.; Garcia, A., III; Cuddihy, E. F.

1981-01-01

The electrical power output from a photovoltaic module is strongly influenced by the thermal and optical characteristics of the module encapsulation system. Described are the methodology and computer model for performing fast and accurate thermal and optical evaluations of different encapsulation systems. The computer model is used to evaluate cell temperature, solar energy transmittance through the encapsulation system, and electric power output for operation in a terrestrial environment. Extensive results are presented for both superstrate-module and substrate-module design schemes which include different types of silicon cell materials, pottants, and antireflection coatings.

Creep Burst Testing of a Woven Inflatable Module

Science.gov (United States)

Selig, Molly M.; Valle, Gerard D.; James, George H.; Oliveras, Ovidio M.; Jones, Thomas C.; Doggett, William R.

2015-01-01

A woven Vectran inflatable module 88 inches in diameter and 10 feet long was tested at the NASA Johnson Space Center until failure from creep. The module was pressurized pneumatically to an internal pressure of 145 psig, and was held at pressure until burst. The external environment remained at standard atmospheric temperature and pressure. The module burst occurred after 49 minutes at the target pressure. The test article pressure and temperature were monitored, and video footage of the burst was captured at 60 FPS. Photogrammetry was used to obtain strain measurements of some of the webbing. Accelerometers on the test article measured the dynamic response. This paper discusses the test article, test setup, predictions, observations, photogrammetry technique and strain results, structural dynamics methods and quick-look results, and a comparison of the module level creep behavior to the strap level creep behavior.

Oral Probiotic VSL#3 Prevents Autoimmune Diabetes by Modulating Microbiota and Promoting Indoleamine 2,3-Dioxygenase-Enriched Tolerogenic Intestinal Environment

Directory of Open Access Journals (Sweden)

Jayashree Dolpady

2016-01-01

Full Text Available The gut microbiota modulates the autoimmune pathogenesis of type 1 diabetes (T1D via mechanisms that remain largely unknown. The inflammasome components are innate immune sensors that are highly influenced by the gut environment and play pivotal roles in maintaining intestinal immune homeostasis. In this study we show that modifications of the gut microbiota induced by oral treatment with Lactobacillaceae-enriched probiotic VSL#3, alone or in combination with retinoic acid (RA, protect NOD mice from T1D by affecting inflammasome at the intestinal level. In particular, we show that VSL#3 treatment inhibits IL-1β expression while enhancing release of protolerogenic components of the inflammasome, such as indoleamine 2,3-dioxygenase (IDO and IL-33. Those modifications of the intestinal microenvironment in VSL#3-treated NOD mice modulate gut immunity by promoting differentiation of tolerogenic CD103+ DCs and reducing differentiation/expansion of Th1 and Th17 cells in the intestinal mucosa and at the sites of autoimmunity, that is, within the pancreatic lymph nodes (PLN of VSL#3-treated NOD mice. Our data provide a link between dietary factors, microbiota composition, intestinal inflammation, and immune homeostasis in autoimmune diabetes and could pave the way for new therapeutic approaches aimed at changing the intestinal microenvironment with probiotics to counterregulate autoimmunity and prevent T1D.

Epigenetics and Cellular Metabolism

Directory of Open Access Journals (Sweden)

Wenyi Xu

2016-01-01

Full Text Available Living eukaryotic systems evolve delicate cellular mechanisms for responding to various environmental signals. Among them, epigenetic machinery (DNA methylation, histone modifications, microRNAs, etc. is the hub in transducing external stimuli into transcriptional response. Emerging evidence reveals the concept that epigenetic signatures are essential for the proper maintenance of cellular metabolism. On the other hand, the metabolite, a main environmental input, can also influence the processing of epigenetic memory. Here, we summarize the recent research progress in the epigenetic regulation of cellular metabolism and discuss how the dysfunction of epigenetic machineries influences the development of metabolic disorders such as diabetes and obesity; then, we focus on discussing the notion that manipulating metabolites, the fuel of cell metabolism, can function as a strategy for interfering epigenetic machinery and its related disease progression as well.

Cellular-based preemption system

Science.gov (United States)

Bachelder, Aaron D. (Inventor)

2011-01-01

A cellular-based preemption system that uses existing cellular infrastructure to transmit preemption related data to allow safe passage of emergency vehicles through one or more intersections. A cellular unit in an emergency vehicle is used to generate position reports that are transmitted to the one or more intersections during an emergency response. Based on this position data, the one or more intersections calculate an estimated time of arrival (ETA) of the emergency vehicle, and transmit preemption commands to traffic signals at the intersections based on the calculated ETA. Additional techniques may be used for refining the position reports, ETA calculations, and the like. Such techniques include, without limitation, statistical preemption, map-matching, dead-reckoning, augmented navigation, and/or preemption optimization techniques, all of which are described in further detail in the above-referenced patent applications.

Measurements of Electromagnetic Fields Emitted from Cellular Base Stations in

Directory of Open Access Journals (Sweden)

K. J. Ali

2013-05-01

Full Text Available With increasing the usage of mobile communication devices and internet network information, the entry of private telecommunications companies in Iraq has been started since 2003. These companies began to build up cellular towers to accomplish the telecommunication works but they ignore the safety conditions imposed for the health and environment that are considered in random way. These negative health effects which may cause a health risk for life beings and environment pollution. The aim of this work is to determine the safe and unsafe ranges and discuss damage caused by radiation emitted from Asia cell base stations in Shirqat city and discuses the best ways in which can be minimize its exposure level to avoid its negative health effects. Practical measurements of power density around base stations has been accomplished by using a radiation survey meter type (Radio frequency EMF Strength Meter 480846 in two ways. The first way of measurements has been accomplished at a height of 2 meters above ground for different distances from (0-300 meters .The second way is at a distance of 150 meters for different levels from (2-15 meters above ground level. The maximum measured power density is about (3 mW/m2. Results indicate that the levels of power density are far below the RF radiation exposure of USSR safety standards levels. And that means these cellular base station don't cause negative the health effect for life being if the exposure is within the acceptable international standard levels.

Gait modulation in C. elegans: An integrated neuromechanical model

Directory of Open Access Journals (Sweden)

Jordan Hylke Boyle

2012-03-01

Full Text Available Equipped with its 302-cell nervous system, the nematode Caenorhabditis elegans adapts its locomotion in different environments, exhibiting so-called swimming in liquids and crawling on dense gels. Recent experiments have demonstrated that the worm displays the full range of intermediate behaviors when placed in intermediate environments. The continuous nature of this transition strongly suggests that these behaviors all stem from modulation of a single underlying mechanism. Wepresent a model of C. elegans forward locomotion that includes a neuromuscular control system that relies on a sensory feedback mechanism to generate undulations and is integrated with a physical model of the body and environment. We find that the model reproduces the entire swim-crawl transition, as well as locomotion in complex and heterogeneous environments. This is achieved with no modulatory mechanism, except via the proprioceptive response to the physical environment. Manipulations of the model are used to dissect the proposed pattern generation mechanism and its modulation. The model suggests a possible role for GABAergic D-class neurons in forward locomotion and makes a number of experimentalpredictions, in particular with respect to nonlinearities in the model and to symmetry breaking between the neuromuscular systems on the ventral and dorsal sides of the body.

DOOCS environment for FPGA-based cavity control system and control algorithms development

International Nuclear Information System (INIS)

Pucyk, P.; Koprek, W.; Kaleta, P.; Szewinski, J.; Pozniak, K.T.; Czarski, T.; Romaniuk, R.S.

2005-01-01

The paper describes the concept and realization of the DOOCS control software for FPGAbased TESLA cavity controller and simulator (SIMCON). It bases on universal software components, created for laboratory purposes and used in MATLAB based control environment. These modules have been recently adapted to the DOOCS environment to ensure a unified software to hardware communication model. The presented solution can be also used as a general platform for control algorithms development. The proposed interfaces between MATLAB and DOOCS modules allow to check the developed algorithm in the operation environment before implementation in the FPGA. As the examples two systems have been presented. (orig.)

Module theory, extending modules and generalizations

CERN Document Server

Tercan, Adnan

2016-01-01

The main focus of this monograph is to offer a comprehensive presentation of known and new results on various generalizations of CS-modules and CS-rings. Extending (or CS) modules are generalizations of injective (and also semisimple or uniform) modules. While the theory of CS-modules is well documented in monographs and textbooks, results on generalized forms of the CS property as well as dual notions are far less present in the literature. With their work the authors provide a solid background to module theory, accessible to anyone familiar with basic abstract algebra. The focus of the book is on direct sums of CS-modules and classes of modules related to CS-modules, such as relative (injective) ejective modules, (quasi) continuous modules, and lifting modules. In particular, matrix CS-rings are studied and clear proofs of fundamental decomposition results on CS-modules over commutative domains are given, thus complementing existing monographs in this area. Open problems round out the work and establish the...

Risk perception and public concerns of electromagnetic waves from cellular phones in Korea.

Science.gov (United States)

Kim, Kyunghee; Kim, Hae-Joon; Song, Dae Jong; Cho, Yong Min; Choi, Jae Wook

2014-05-01

In this study, the difference between the risk perception of electromagnetic waves from cellular phones and the risk perception of other factors such as environment and food was analyzed. The cause of the difference in the psychological and social factors that affect the group with high risk perception of electromagnetic waves was also analyzed. A questionnaire survey on the risk perception of electromagnetic waves from cellular phones was carried out on 1001 subjects (men and women) over the age of 20. In the group with high risk perception of electromagnetic waves from cellular phones, women had higher risk perception than men. Logistic regression analysis, where the group with high risk perception of electromagnetic waves and the group with low risk perception were used as dependent variables, indicated that the risk perception of electromagnetic waves in women was 1.815 times statistically significantly higher than the risk perception of men (95% CI: 1.340-2.457). Also, high risk perception of electromagnetic waves from cellular phones was observed when the subjects considered that they had more personal knowledge (OR: 1.416, 95% CI: 1.216-1.648), that the seriousness of the risk to future generations was high (OR: 1.410, 95% CI: 1.234-1.611), and their outrage for the occurrence of accidents related to electromagnetic waves was high (OR: 1.460, 95% CI: 1.264-1.686). The results of this study need to be sufficiently considered and reflected in designing the risk communication strategies and communication methods for the preventive measures and advice on electromagnetic waves from cellular phones. © 2014 Wiley Periodicals, Inc.

The crystal zero degree detector at BESIII as a realistic high rate environment for evaluating PANDA data acquisition modules

International Nuclear Information System (INIS)

Werner, Marcel

2015-03-01

The BESIII experiment located in Beijing, China, is investigating physics in the energy region of the charm-quark via electron positron annihilation reactions. A small detector to be placed in the very forward/backward region around θ=0 at BESIII is foreseen to measure photons from the initial state. This is especially interesting, because it opens the door for various physics measurements over a wide range of energies, even below the experiment's designated energy threshold, which is fixed by the accelerator. This thesis is investigating the capabilities of a crystal zero degree detector (cZDD) consisting of PbWO 4 crystals placed in that region of BESIII. Detailed Geant4-based simulations have been performed, and the energy resolution of the detector has been determined to be σ/μ=0.06+0.025/√(E[GeV]). The determination of the center-of-mass energy √(s) isr after the emission of the photon is of great importance for the study of such events. Preliminary simulations estimated the resolution of the reconstructed √(s) isr using the cZDD information to be significantly better than 10 % for appropriate photon impacts on the detector. Such events can only be investigated, when data from the cZDD and other detectors of BESIII can be correlated. A fast and powerful Data Acquisition (DAQ) capable of performing event correlation in real time is needed. DAQ modules capable of performing real time event correlation are being developed for the PANDA experiment at the future FAIR facility in Darmstadt, Germany. Investigating these modules in a realistic high-rate environment such as provided at BESIII, offers a great opportunity to gain experience in real time event correlation before the start of PANDA. Developments for the cZDD's DAQ using prototype PANDA DAQ modules have been done and successfully tested in experiments with radioactive sources and a beamtest with 210 MeV electrons at the Mainz Microtron.

Modulation of sociotechnical change as climate change challenge

International Nuclear Information System (INIS)

Arentsen, M.J.; Eberg, J.W.

2001-01-01

Results of the MATRIC (Management of Technology Responses to the Climate Change Challenge) project are summarized. The project empirically studied technological change and innovation to learn more about the contingencies conditioning and influencing these processes with the aim to recommend national technology oriented climate change policies. The first chapter explains the background, the central research question, the structure and the methodology of Matric. The central research question was how to modulate the ongoing dynamics of socio-technical change to the climate change needs. Chapter two summarizes the core of the analytical framework of Matric. The fundamental idea of social embedding of technology has been the analytical point of departure of the Matric project. It says that innovations emerge and technology changes in close interaction with its social environment. The social environment turns out to be a strong conditioner of technological change and development and therefore, technology and its embedding social environment tend to co-evolve in the course of time. Co-evolution of technology and its social environment theoretically draws on evolutionary oriented economics and sociology. Both theoretical traditions are in turn inspired by biologically oriented. Chapter three summarizes the empirical findings of the analysis of socio-technical change patterns in three cases: electricity generation and use, car-based transport and mobility and eco-efficiency in industrial production. The cases have been selected for their climate change impact and for their social and economic significance. Chapter four comparatively analyzes the significance of the analytical and empirical findings of Matric for the central research question of the project. The chapter comparatively analysis the general pattern of the development, the change and development of the socio-technical regimes, the socio-technical governance arrangements and processes and the public policy

Novel cellular targets of AhR underlie alterations in neutrophilic inflammation and iNOS expression during influenza virus infection

Science.gov (United States)

Head Wheeler, Jennifer L.; Martin, Kyle C.; Lawrence, B. Paige

2012-01-01

The underlying reasons for variable clinical outcomes from respiratory viral infections remain uncertain. Several studies suggest that environmental factors contribute to this variation, but limited knowledge of cellular and molecular targets of these agents hampers our ability to quantify or modify their contribution to disease and improve public health. The aryl hydrocarbon receptor (AhR) is an environment sensing transcription factor that binds many anthropogenic and natural chemicals. The immunomodulatory properties of AhR ligands are best characterized with extensive studies of changes in CD4+ T cell responses. Yet, AhR modulates other aspects of immune function. We previously showed that during influenza virus infection, AhR activation modulates neutrophil accumulation in the lung, and this contributes to increased mortality in mice. Enhanced levels of inducible nitric oxide synthase (iNOS) in infected lungs are observed during the same timeframe as AhR-mediated increased pulmonary neutrophilia. In this study, we evaluated whether these two consequences of AhR activation are causally linked. Reciprocal inhibition of AhR-mediated elevations in iNOS and pulmonary neutrophilia reveal that, although they are contemporaneous, they are not causally related. We show using Cre/loxP technology that elevated iNOS levels and neutrophil number in the infected lung result from separate, AhR-dependent signaling in endothelial and respiratory epithelial cells, respectively. Studies using mutant mice further reveal that AhR-mediated alterations in these innate responses to infection require a functional nuclear localization signal and DNA binding domain. Thus, gene targets of AhR in non-hematopoietic cells are important new considerations for understanding AhR-mediated changes in innate anti-viral immunity. PMID:23233726

Probabilistic cellular automata.

Science.gov (United States)

Agapie, Alexandru; Andreica, Anca; Giuclea, Marius

2014-09-01

Cellular automata are binary lattices used for modeling complex dynamical systems. The automaton evolves iteratively from one configuration to another, using some local transition rule based on the number of ones in the neighborhood of each cell. With respect to the number of cells allowed to change per iteration, we speak of either synchronous or asynchronous automata. If randomness is involved to some degree in the transition rule, we speak of probabilistic automata, otherwise they are called deterministic. With either type of cellular automaton we are dealing with, the main theoretical challenge stays the same: starting from an arbitrary initial configuration, predict (with highest accuracy) the end configuration. If the automaton is deterministic, the outcome simplifies to one of two configurations, all zeros or all ones. If the automaton is probabilistic, the whole process is modeled by a finite homogeneous Markov chain, and the outcome is the corresponding stationary distribution. Based on our previous results for the asynchronous case-connecting the probability of a configuration in the stationary distribution to its number of zero-one borders-the article offers both numerical and theoretical insight into the long-term behavior of synchronous cellular automata.

A biphasic endothelial stress-survival mechanism regulates the cellular response to vascular endothelial growth factor A

International Nuclear Information System (INIS)

Latham, Antony M.; Odell, Adam F.; Mughal, Nadeem A.; Issitt, Theo; Ulyatt, Clare; Walker, John H.; Homer-Vanniasinkam, Shervanthi; Ponnambalam, Sreenivasan

2012-01-01

Vascular endothelial growth factor A (VEGF-A) is an essential cytokine that regulates endothelial function and angiogenesis. VEGF-A binding to endothelial receptor tyrosine kinases such as VEGFR1 and VEGFR2 triggers cellular responses including survival, proliferation and new blood vessel sprouting. Increased levels of a soluble VEGFR1 splice variant (sFlt-1) correlate with endothelial dysfunction in pathologies such as pre-eclampsia; however the cellular mechanism(s) underlying the regulation and function of sFlt-1 are unclear. Here, we demonstrate the existence of a biphasic stress response in endothelial cells, using serum deprivation as a model of endothelial dysfunction. The early phase is characterized by a high VEGFR2:sFlt-1 ratio, which is reversed in the late phase. A functional consequence is a short-term increase in VEGF-A-stimulated intracellular signaling. In the late phase, sFlt-1 is secreted and deposited at the extracellular matrix. We hypothesized that under stress, increased endothelial sFlt-1 levels reduce VEGF-A bioavailability: VEGF-A treatment induces sFlt-1 expression at the cell surface and VEGF-A silencing inhibits sFlt-1 anchorage to the extracellular matrix. Treatment with recombinant sFlt-1 inhibits VEGF-A-stimulated in vitro angiogenesis and sFlt-1 silencing enhances this process. In this response, increased VEGFR2 levels are regulated by the phosphatidylinositol-3-kinase and PKB/Akt signaling pathways and increased sFlt-1 levels by the ERK1/2 signaling pathway. We conclude that during serum withdrawal, cellular sensing of environmental stress modulates sFlt-1 and VEGFR2 levels, regulating VEGF-A bioavailability and ensuring cell survival takes precedence over cell proliferation and migration. These findings may underpin an important mechanism contributing to endothelial dysfunction in pathological states. -- Highlights: ► Endothelial cells mount a stress response under conditions of low serum. ► Endothelial VEGFR levels are

47 CFR 32.5003 - Cellular mobile revenue.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 2 2010-10-01 2010-10-01 false Cellular mobile revenue. 32.5003 Section 32... SYSTEM OF ACCOUNTS FOR TELECOMMUNICATIONS COMPANIES Instructions For Revenue Accounts § 32.5003 Cellular mobile revenue. This account shall include message revenue derived from cellular mobile...

Modulating presence and impulsiveness by external stimulation of the brain

Directory of Open Access Journals (Sweden)

Baumgartner Thomas

2008-08-01

Full Text Available Abstract Background "The feeling of being there" is one possible way to describe the phenomenon of feeling present in a virtual environment and to act as if this environment is real. One brain area, which is hypothesized to be critically involved in modulating this feeling (also called presence is the dorso-lateral prefrontal cortex (dlPFC, an area also associated with the control of impulsive behavior. Methods In our experiment we applied transcranial direct current stimulation (tDCS to the right dlPFC in order to modulate the experience of presence while watching a virtual roller coaster ride. During the ride we also registered electro-dermal activity. Subjects also performed a test measuring impulsiveness and answered a questionnaire about their presence feeling while they were exposed to the virtual roller coaster scenario. Results Application of cathodal tDCS to the right dlPFC while subjects were exposed to a virtual roller coaster scenario modulates the electrodermal response to the virtual reality stimulus. In addition, measures reflecting impulsiveness were also modulated by application of cathodal tDCS to the right dlPFC. Conclusion Modulating the activation with the right dlPFC results in substantial changes in responses of the vegetative nervous system and changed impulsiveness. The effects can be explained by theories discussing the top-down influence of the right dlPFC on the "impulsive system".

Resveratrol induces cellular senescence with attenuated mono-ubiquitination of histone H2B in glioma cells

International Nuclear Information System (INIS)

Gao, Zhen; Xu, Michael S.; Barnett, Tamara L.; Xu, C. Wilson

2011-01-01

Research highlights: → Resveratrol induces cellular senescence in glioma cell. → Resveratrol inhibits mono-ubiquitination of histone H2B at K120. → Depletion of RNF20, phenocopies the inhibitory effects of resveratrol. → Mono-ubiquitination of histone H2B at K120 is a novel target of resveratrol. → RNF20 inhibits cellular senescence in proliferating glioma cells. -- Abstract: Resveratrol (3,4',5-trihydroxy-trans-stilbene), a polyphenol naturally occurring in grapes and other plants, has cancer chemo-preventive effects and therapeutic potential. Although resveratrol modulates multiple pathways in tumor cells, how resveratrol or its affected pathways converge on chromatin to mediate its effects is not known. Using glioma cells as a model, we showed here that resveratrol inhibited cell proliferation and induced cellular hypertrophy by transforming spindle-shaped cells to enlarged, irregular and flatten-shaped ones. We further showed that resveratrol-induced hypertrophic cells expressed senescence-associated-β-galactosidase, suggesting that resveratrol-induced cellular senescence in glioma cells. Consistent with these observations, we demonstrated that resveratrol inhibited clonogenic efficiencies in vitro and tumor growth in a xenograft model. Furthermore, we found that acute treatment of resveratrol inhibited mono-ubiquitination of histone H2B at K120 (uH2B) in breast, prostate, pancreatic, lung, brain tumor cells as well as primary human cells. Chronic treatment with low doses of resveratrol also inhibited uH2B in the resveratrol-induced senescent glioma cells. Moreover, we showed that depletion of RNF20, a ubiquitin ligase of histone H2B, inhibited uH2B and induced cellular senescence in glioma cells in vitro, thereby recapitulated the effects of resveratrol. Taken together, our results suggest that uH2B is a novel direct or indirect chromatin target of resveratrol and RNF20 plays an important role in inhibiting cellular senescence programs that are

Resveratrol induces cellular senescence with attenuated mono-ubiquitination of histone H2B in glioma cells

Energy Technology Data Exchange (ETDEWEB)

Gao, Zhen; Xu, Michael S.; Barnett, Tamara L. [Nevada Cancer Institute, Las Vegas, NV 89135 (United States); Xu, C. Wilson, E-mail: wxu@nvcancer.org [Nevada Cancer Institute, Las Vegas, NV 89135 (United States)

2011-04-08

Research highlights: {yields} Resveratrol induces cellular senescence in glioma cell. {yields} Resveratrol inhibits mono-ubiquitination of histone H2B at K120. {yields} Depletion of RNF20, phenocopies the inhibitory effects of resveratrol. {yields} Mono-ubiquitination of histone H2B at K120 is a novel target of resveratrol. {yields} RNF20 inhibits cellular senescence in proliferating glioma cells. -- Abstract: Resveratrol (3,4',5-trihydroxy-trans-stilbene), a polyphenol naturally occurring in grapes and other plants, has cancer chemo-preventive effects and therapeutic potential. Although resveratrol modulates multiple pathways in tumor cells, how resveratrol or its affected pathways converge on chromatin to mediate its effects is not known. Using glioma cells as a model, we showed here that resveratrol inhibited cell proliferation and induced cellular hypertrophy by transforming spindle-shaped cells to enlarged, irregular and flatten-shaped ones. We further showed that resveratrol-induced hypertrophic cells expressed senescence-associated-{beta}-galactosidase, suggesting that resveratrol-induced cellular senescence in glioma cells. Consistent with these observations, we demonstrated that resveratrol inhibited clonogenic efficiencies in vitro and tumor growth in a xenograft model. Furthermore, we found that acute treatment of resveratrol inhibited mono-ubiquitination of histone H2B at K120 (uH2B) in breast, prostate, pancreatic, lung, brain tumor cells as well as primary human cells. Chronic treatment with low doses of resveratrol also inhibited uH2B in the resveratrol-induced senescent glioma cells. Moreover, we showed that depletion of RNF20, a ubiquitin ligase of histone H2B, inhibited uH2B and induced cellular senescence in glioma cells in vitro, thereby recapitulated the effects of resveratrol. Taken together, our results suggest that uH2B is a novel direct or indirect chromatin target of resveratrol and RNF20 plays an important role in inhibiting cellular

M19 modulates skeletal muscle differentiation and insulin secretion in pancreatic β-cells through modulation of respiratory chain activity.

Directory of Open Access Journals (Sweden)

Linda Cambier

Full Text Available Mitochondrial dysfunction due to nuclear or mitochondrial DNA alterations contributes to multiple diseases such as metabolic myopathies, neurodegenerative disorders, diabetes and cancer. Nevertheless, to date, only half of the estimated 1,500 mitochondrial proteins has been identified, and the function of most of these proteins remains to be determined. Here, we characterize the function of M19, a novel mitochondrial nucleoid protein, in muscle and pancreatic β-cells. We have identified a 13-long amino acid sequence located at the N-terminus of M19 that targets the protein to mitochondria. Furthermore, using RNA interference and over-expression strategies, we demonstrate that M19 modulates mitochondrial oxygen consumption and ATP production, and could therefore regulate the respiratory chain activity. In an effort to determine whether M19 could play a role in the regulation of various cell activities, we show that this nucleoid protein, probably through its modulation of mitochondrial ATP production, acts on late muscle differentiation in myogenic C2C12 cells, and plays a permissive role on insulin secretion under basal glucose conditions in INS-1 pancreatic β-cells. Our results are therefore establishing a functional link between a mitochondrial nucleoid protein and the modulation of respiratory chain activities leading to the regulation of major cellular processes such as myogenesis and insulin secretion.

47 CFR 22.905 - Channels for cellular service.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 2 2010-10-01 2010-10-01 false Channels for cellular service. 22.905 Section... MOBILE SERVICES Cellular Radiotelephone Service § 22.905 Channels for cellular service. The following frequency bands are allocated for assignment to service providers in the Cellular Radiotelephone Service. (a...

Cholesterol modulates the cellular localization of Orai1 channels and its disposition among membrane domains.

Science.gov (United States)

Bohórquez-Hernández, A; Gratton, Enrico; Pacheco, Jonathan; Asanov, Alexander; Vaca, Luis

2017-12-01

Store Operated Calcium Entry (SOCE) is one of the most important mechanisms for calcium mobilization in to the cell. Two main proteins sustain SOCE: STIM1 that acts as the calcium sensor in the endoplasmic reticulum (ER) and Orai1 responsible for calcium influx upon depletion of ER. There are many studies indicating that SOCE is modulated by the cholesterol content of the plasma membrane (PM). However, a myriad of questions remain unanswered concerning the precise molecular mechanism by which cholesterol modulates SOCE. In the present study we found that reducing PM cholesterol results in the internalization of Orai1 channels, which can be prevented by overexpressing caveolin 1 (Cav1). Furthermore, Cav1 and Orai1 associate upon SOCE activation as revealed by FRET and coimmunoprecipitation assays. The effects of reducing cholesterol were not limited to an increased rate of Orai1 internalization, but also, affects the lateral movement of Orai1, inducing movement in a linear pattern (unobstructed diffusion) opposite to basal cholesterol conditions were most of Orai1 channels moves in a confined space, as assessed by Fluorescence Correlation Spectroscopy, Cav1 overexpression inhibited these alterations maintaining Orai1 into a confined and partially confined movement. These results not only highlight the complex effect of cholesterol regulation on SOCE, but also indicate a direct regulatory effect on Orai1 localization and compartmentalization by this lipid. Copyright © 2017 Elsevier B.V. All rights reserved.

Cellular metabolic rate is influenced by life-history traits in tropical and temperate birds.

Science.gov (United States)

Jimenez, Ana Gabriela; Van Brocklyn, James; Wortman, Matthew; Williams, Joseph B

2014-01-01

In general, tropical birds have a "slow pace of life," lower rates of whole-animal metabolism and higher survival rates, than temperate species. A fundamental challenge facing physiological ecologists is the understanding of how variation in life-history at the whole-organism level might be linked to cellular function. Because tropical birds have lower rates of whole-animal metabolism, we hypothesized that cells from tropical species would also have lower rates of cellular metabolism than cells from temperate species of similar body size and common phylogenetic history. We cultured primary dermal fibroblasts from 17 tropical and 17 temperate phylogenetically-paired species of birds in a common nutritive and thermal environment and then examined basal, uncoupled, and non-mitochondrial cellular O2 consumption (OCR), proton leak, and anaerobic glycolysis (extracellular acidification rates [ECAR]), using an XF24 Seahorse Analyzer. We found that multiple measures of metabolism in cells from tropical birds were significantly lower than their temperate counterparts. Basal and uncoupled cellular metabolism were 29% and 35% lower in cells from tropical birds, respectively, a decrease closely aligned with differences in whole-animal metabolism between tropical and temperate birds. Proton leak was significantly lower in cells from tropical birds compared with cells from temperate birds. Our results offer compelling evidence that whole-animal metabolism is linked to cellular respiration as a function of an animal's life-history evolution. These findings are consistent with the idea that natural selection has uniquely fashioned cells of long-lived tropical bird species to have lower rates of metabolism than cells from shorter-lived temperate species.

Cellular metabolic rate is influenced by life-history traits in tropical and temperate birds.

Directory of Open Access Journals (Sweden)

Ana Gabriela Jimenez

Full Text Available In general, tropical birds have a "slow pace of life," lower rates of whole-animal metabolism and higher survival rates, than temperate species. A fundamental challenge facing physiological ecologists is the understanding of how variation in life-history at the whole-organism level might be linked to cellular function. Because tropical birds have lower rates of whole-animal metabolism, we hypothesized that cells from tropical species would also have lower rates of cellular metabolism than cells from temperate species of similar body size and common phylogenetic history. We cultured primary dermal fibroblasts from 17 tropical and 17 temperate phylogenetically-paired species of birds in a common nutritive and thermal environment and then examined basal, uncoupled, and non-mitochondrial cellular O2 consumption (OCR, proton leak, and anaerobic glycolysis (extracellular acidification rates [ECAR], using an XF24 Seahorse Analyzer. We found that multiple measures of metabolism in cells from tropical birds were significantly lower than their temperate counterparts. Basal and uncoupled cellular metabolism were 29% and 35% lower in cells from tropical birds, respectively, a decrease closely aligned with differences in whole-animal metabolism between tropical and temperate birds. Proton leak was significantly lower in cells from tropical birds compared with cells from temperate birds. Our results offer compelling evidence that whole-animal metabolism is linked to cellular respiration as a function of an animal's life-history evolution. These findings are consistent with the idea that natural selection has uniquely fashioned cells of long-lived tropical bird species to have lower rates of metabolism than cells from shorter-lived temperate species.

Fiscal 1999 leading research report. Research on 3-D cell tissue module technology; 1999 nendo sanjigen saibo soshiki module kogaku chosa kenkyu hokokusho

Energy Technology Data Exchange (ETDEWEB)

NONE

2000-03-01

For forming cell tissues alternative to bio-tissues, this research targets the technology for forming bio-tissue modules by cultivating 3-D cell tissues from various kinds of cells. In fiscal 1999, research was made on various issues of element technologies necessary for forming module structure of bio-tissues, and study was also made on the application of 3-D cell tissue module engineering to industrial fields. Survey was made on element technologies and solutions supporting such engineering, and in addition, on progressive conditions of cell cultivation techniques, and concrete techniques for expressing cell functions. Research was made on a cell behavior under physicochemical stimulus environment to study the optimum environment for cell multiplication and function expression. Further research was made on state analysis of cells, in particular, fast precise measurement techniques of activation or malignant of cells and secretion of toxic substances by physical/optical analytical evaluation techniques such as photo-CT and spectroscopic analysis, and biochemical analysis techniques using bio-sensors. Study was also made on successful development and application cases of practical bio-artificial organs in western countries. (NEDO)